C Noel Bairey Merz MD FACC FAHA FESCProfessor and Endowed ChairDirector Barbra Streisand Womenrsquos Heart CetnerDirector Preventive Cardiac CenterCedars-Sinai Smidt Heart InstituteLos Angeles California USAmerzcshsorg

Ischemic Heart Disease in Women Monet vs Manet (why women have more adverse outcomes)

2

Financial conflicts of interests

bull The following relationships exist related to this presentation (paid to Cedars-Sinai Medical Center)

bull Grant support NHLBI Louis B Mayer Foundation NIH-CTSI CMDRP-DoD NIH-Caladrius California Institute for Precision Medicine (CIAPM) Sanofi-Vascular

bull Consulting Medscape Sanofi-Vascular NIH CSR and NIH ORWHAB iRhythm

bull Honorarium Abbott Diagnostics bull Stocks Nonepaid to CSMC

Monet or Manet

Monet or Manet

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

New femalemajority Yentl and

Yentl Syndrome

WISENHLBIAHABegin

1984-1996 12 years to recognize take action

1615PC Bairey-MerzSlide

8

Bugiardini and Bairey Merz JAMA 2005293477-84

Paradox Women have a two-fold increase in ldquonormalrdquo Coronary arteries in the setting of ACS NSTEMI and STEMI

9

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Monet vs ManetMore womendie

More men receive treatment

Bairey Merz EHJ 2011

GuidelineImplementation ACS and the Sex Survival Gap

Novak et al Am J Medicine 2008121602

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

2

Financial conflicts of interests

bull The following relationships exist related to this presentation (paid to Cedars-Sinai Medical Center)

bull Grant support NHLBI Louis B Mayer Foundation NIH-CTSI CMDRP-DoD NIH-Caladrius California Institute for Precision Medicine (CIAPM) Sanofi-Vascular

bull Consulting Medscape Sanofi-Vascular NIH CSR and NIH ORWHAB iRhythm

bull Honorarium Abbott Diagnostics bull Stocks Nonepaid to CSMC

Monet or Manet

Monet or Manet

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

New femalemajority Yentl and

Yentl Syndrome

WISENHLBIAHABegin

1984-1996 12 years to recognize take action

1615PC Bairey-MerzSlide

8

Bugiardini and Bairey Merz JAMA 2005293477-84

Paradox Women have a two-fold increase in ldquonormalrdquo Coronary arteries in the setting of ACS NSTEMI and STEMI

9

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Monet vs ManetMore womendie

More men receive treatment

Bairey Merz EHJ 2011

GuidelineImplementation ACS and the Sex Survival Gap

Novak et al Am J Medicine 2008121602

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

Monet or Manet

Monet or Manet

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

New femalemajority Yentl and

Yentl Syndrome

WISENHLBIAHABegin

1984-1996 12 years to recognize take action

1615PC Bairey-MerzSlide

8

Bugiardini and Bairey Merz JAMA 2005293477-84

Paradox Women have a two-fold increase in ldquonormalrdquo Coronary arteries in the setting of ACS NSTEMI and STEMI

9

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Monet vs ManetMore womendie

More men receive treatment

Bairey Merz EHJ 2011

GuidelineImplementation ACS and the Sex Survival Gap

Novak et al Am J Medicine 2008121602

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

Monet or Manet

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

New femalemajority Yentl and

Yentl Syndrome

WISENHLBIAHABegin

1984-1996 12 years to recognize take action

1615PC Bairey-MerzSlide

8

Bugiardini and Bairey Merz JAMA 2005293477-84

Paradox Women have a two-fold increase in ldquonormalrdquo Coronary arteries in the setting of ACS NSTEMI and STEMI

9

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Monet vs ManetMore womendie

More men receive treatment

Bairey Merz EHJ 2011

GuidelineImplementation ACS and the Sex Survival Gap

Novak et al Am J Medicine 2008121602

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

New femalemajority Yentl and

Yentl Syndrome

WISENHLBIAHABegin

1984-1996 12 years to recognize take action

1615PC Bairey-MerzSlide

8

Bugiardini and Bairey Merz JAMA 2005293477-84

Paradox Women have a two-fold increase in ldquonormalrdquo Coronary arteries in the setting of ACS NSTEMI and STEMI

9

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Monet vs ManetMore womendie

More men receive treatment

Bairey Merz EHJ 2011

GuidelineImplementation ACS and the Sex Survival Gap

Novak et al Am J Medicine 2008121602

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

New femalemajority Yentl and

Yentl Syndrome

WISENHLBIAHABegin

1984-1996 12 years to recognize take action

1615PC Bairey-MerzSlide

8

Bugiardini and Bairey Merz JAMA 2005293477-84

Paradox Women have a two-fold increase in ldquonormalrdquo Coronary arteries in the setting of ACS NSTEMI and STEMI

9

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Monet vs ManetMore womendie

More men receive treatment

Bairey Merz EHJ 2011

GuidelineImplementation ACS and the Sex Survival Gap

Novak et al Am J Medicine 2008121602

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

1615PC Bairey-MerzSlide

8

Bugiardini and Bairey Merz JAMA 2005293477-84

Paradox Women have a two-fold increase in ldquonormalrdquo Coronary arteries in the setting of ACS NSTEMI and STEMI

9

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Monet vs ManetMore womendie

More men receive treatment

Bairey Merz EHJ 2011

GuidelineImplementation ACS and the Sex Survival Gap

Novak et al Am J Medicine 2008121602

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

9

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Monet vs ManetMore womendie

More men receive treatment

Bairey Merz EHJ 2011

GuidelineImplementation ACS and the Sex Survival Gap

Novak et al Am J Medicine 2008121602

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

Monet vs ManetMore womendie

More men receive treatment

Bairey Merz EHJ 2011

GuidelineImplementation ACS and the Sex Survival Gap

Novak et al Am J Medicine 2008121602

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

GuidelineImplementation ACS and the Sex Survival Gap

Novak et al Am J Medicine 2008121602

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrows(RED)

Novak et al Am J Medicine 2008121602

+

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

GuidelineImplementationACS and the Sex Survival GapFollowing guidelineimplementation mortality for womenimproves andthe sex gap narrow (RED)

Persistent sex gap (BLUE)suggests more workstill neededto understand sex-specific pathophysiologyto improve outcomesfor women and men

Novak et al Am J Medicine 2008121602

+

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

14

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

Anderson RD et al Circulation 2007115823-826

Prevalence of normal or non-obstructive coronary arteriescommon in women

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

Normal Coronaries

22

1V Non-Obstructive

CAD14

2V Non-Obstructive

CAD8

3V Non-Obstructive

CAD3

1V Obstructive CAD23

2V Obstructive CAD14

3VLM Obstructive

CAD16

VA CART 37674 male patients ndash47 non-obstructive or normal coronary arteries

Now common in men

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

17Crea Filippo Paolo G Camici and Cathleen Noel Bairey Merz Coronary microvascular dysfunction an update European heart journal (2013) eht513

Mechanisms of Myocardial Ischemia (including INOCA)

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

Coronary Vascular Resistance

bullEpicardial arteries normally

contribute lt10 of the

coronary vascular resistance

ndashhemodynamic significance when

gt70 of the lumen is obstructed

bullCoronary microvasculature

is responsible for gt70 of

the coronary resistance

under physiological

circumstances Gould KL et al Am J Cardiol 19743387ndash94 Camici P et al Heart Lung and Circ 20091819-27

wwwvhlabumnedu

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

Coronary Microvascular Dysfunction

Crea F et al Nature Reviews Cardiology 20151248ndash62

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

20

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

DES in Stable Angina ORBITA Trial

21

Change from Baseline PCI Sham P ValueExercise time (sec) 284 118 0200Peak oxygen uptake (mlmin) -20 109 0741SAQ Physical Limitation 74 50 0420SAQ Angina Frequency 140 96 0260SAQ Angina Stability -42 -51 0851Quality of Life 003 003 0994Duke Treadmill Score 122 010 0104Complete Freedom from Angina 495 315 lt005

Compared with placebo PCI improved stress echo by 107 segment units (plt000001) with larger improvements in stress echo with lower levels of FFR and iFR (pinteraction lt000001)

Al-Lamee R et al Lancet 2018 391 31ndash40

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

22

Mechanisms WISE-IVUS gt80 INOCA Subjects have Coronary Atherosclerosis

80

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

23

Chan

ge in

PCr

ATP

dur

ing

stre

ss p

erce

nt

-50

-40

-30

-20

-10

0

10

20

30

gt70 StenosisWomen with Chest Pain

but normal Angio

ReferencePopulation

p lt 0025compared to normals

2 sd

Myocardial ischemia is frequent in subjects with signs and symptoms but no obstructive coronary diseaseThese are not ldquofalse positiverdquo stress tests

Mechanisms WISE-Magnetic Resonance Spectroscopy confirms Myocardial Ischemia over 70 of INOCA subjects

Buchal et al NEJM 2001

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

24

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

WISE CMD Randomized Pharmacologic PROBE TrialsTrial (n) Intervention Results

QWISE1 (n=78) quinipril CFR angina

FemHRT-WISE 2(n=35) ethinyl estradiol and norethindrone acetate

MRS angina

EWISE3 (n=41) eplenerone CFR angina

SWISE4 (n=23) sildenafil CFR angina

RWISE Pilot5 (n=20) ranolazine MPRI angina

RWISE6 (n=128) ranolazine MPRI angina

CFR = coronary flow reserve MRS = magnetic resonance spectrosopy myocardial perfusion reserve index WISE = Womenrsquos Ischemia Syndrome Evaluation 1 Pauley AHJ 2011 2 Bairey Merz AHJ 2010 3 BavryAHJ 2014 Denardo Clin Card 2011 5 Mehta JACC Imaging 6 Bairey Merz EHJ 2015

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

Randomized CRT Protocol Improves Angina Outcomes

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Carl Pepine MDNoel Bairey Merz MDEileen Handberg PhD

Rhonda Cooper-DeHoff PharmDJanet Wei MD

John Spertus MDBernard Chaitman MDWilliam Weintraub MD

4422 subjects with angina no obstructive CAD randomized to IMT (intensive statin and ACEARB) vs GMT (guideline directed risk factor management) for reduction of MACE (all-cause death non-fatal-MI -stroke or hospitalization for angina or HF)

Womenrsquos IschemiaSyndrome Evaluation

WISE

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

WARRIOR Womenrsquos IschemiA TReatment Reduces Events In Non-ObstRuctive CAD Trial

Womenrsquos IschemiaSyndrome Evaluation

WISE

Intensive Medical therapy (IMT)

Guideline Medical Therapy (GMT)

Lipid Lowering Lowering

AtorvastatinIntolerant

Randomize

ACE InhibitorIntolerant

Maximally tolerated RAS Blockade

Lisinopril 10mg20mg40mg

PO QD 90Refills 3

Losartan25mg50mg100mg

PO QD 90Refills 3

Intensive Statin

Atorvastatin10mg20mg40mg80mg

PO QD 90Refills 3

Rosuvastatin 5mg10mg20mg40mg

PO QD 90Refills 3

Yes NoYes No

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart Truth and AHA Go Red Awarenessand Guidelines Campaigns

1997-2007

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

Total

Males

Females

Per 100000 Population

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

ampA

Page ampP

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Death

s i

n T

ho

usan

ds

Males Females

0

NHLBI Heart TruthAHA WISE andGuideline Campaigns

1997-2007 43

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

Chart1

Males

Females

Years

Deaths in Thousands

496676

466361

506154

487194

487453

495286

444763

475482

452452

503139

440175

505661

410365

461152

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

79		79
80		80
49657		481104
491564		480988
494841		491291
487461		49071
85		85
477968		494949
472445		495989
473119		50085
453057		4831
90		90
443673		476809
441233		476675
454352		497858
4491		495675
95		95
450761		503646
447687		500725
443221		501741
445871		512904
00		00
432245		498863
433827		49369
427891		483372
04		04

USCVTREND

ampA

Page ampP

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

	CVD		CVD			Cardiovascular Disease Mortality Trends for Males and Females											CVD		CVD				CVD		CVD
	Males		Females			United States 1979-2004											Males		Females				Males		Females
79		500		469												79		497		466			79		497		466
80		510		490												80		506		487			80		506		487
81		500		484													497		481			85		487		495
82		495		484													492		481			90		445		475
83		498		494													495		491			95		452		503
84		491		493													487		491			00		439		505		adjusted
85		491		498												85		487		495			04		410		460		adjusted
86		481		498													478		495
87		475		499													472		496
88		476		504													473		501
89		456		486													453		483
90		448		478												90		445		475
91		447		479													444		477
92		444		479													441		477
93		457		500													454		498
94		452		498													449		496
95		455		505												95		452		503
96		453		506													451		504
97		450		503													448		501
98		446		504				Actual Mortality					Adjusted Mortality						443		502
99		446		513			adjusted by 9-10 comparability ratio (09981)						445024		511929					446		513
00		440		506				440175		505661				439339		504700				00		440		506
01		432		499				432245		498863				431424		497915					432		499
Source Final mortality data NCHS						433827		493690			02		433003		492752					434		494
Numbers are in thousands						427891		483372			03		427078		482454					428		483
CVD including congenital CV disease						410365		461152			04		409585		460276				04		410		461
	CVD		CVD		CVD		CVD
	White Males		White Females		Black Males		Black Females				- Since comparability ratio is so close to 100
79		445		418		48		46				it is not necessary to adjust As per TT 92606
80		452		435
81		444		430
82		439		430
83		441		438
84		434		437
85		433		440
86		423		440		50		52
87		417		440		50		52
88		417		443		50		54					White Males		White Females		Black Males		Black Females
89		398		425		49		53				90		391		420		48		51
90		391		420		48		51				91		389		420		48		52
91		389		420		48		52				92		387		420		47		52
92		387		420		47		52				93		398		438		49		54
93		398		438		49		54				94		394		436		48		54
94		394		436		48		54				95		395		442		50		55
95		395		442		50		55				96		394		442		48		55
96		394		442		48		55				97		391		440		48		54
97		391		440		48		54				98		386		439		49		55
98		386		439		49		55				99		386		447		49		56
99		386		447		49		56				00		381		439		48		57
0		381		439		48		57
							Cardiovascular Disease Mortality Trends by Sex and Race
							United States 1990-2000

USCVTREND

ampA

Page ampP

Males

Females

Years

Deaths in Thousands

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

drwomencvcan

Males

Females

Years

Deaths in Thousands

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

chdstrhypmor

White Males

White Females

Black Males

Black Females

Year

Deaths in Thousands

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

ampA

Page ampP

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

	DR FOR WOMEN CV AND CANCER 1996(1940)										DR FOR WOMEN CV AND CANCER 2004										CVD AND CANCER 2001
			Whites		Blacks									White Females		Black Females								Total		Males		Females
Coronary Heart Disease				589		800						Coronary Heart Disease				1154		1486						CVD			3296		3914		2817
Stroke				229		392						Stroke				474		649						Cancer			1960		2437		1647
Breast Cancer				198		265						Lung Cancer				416		390
Lung Cancer				280		276						Breast Cancer				237		319
Age-Adjusted Death Rates for Coronary Heart Disease Stroke Breast										Age-Adjusted Death Rates for Coronary Heart Disease Stroke and Lung										Age-Adjusted Death Rates for Cardiovascular Disease and Cancer
and Lung Cancer for White and Black Females(1940)										and Breast Cancer for White and Black Females										United States 2001
United States 1996 Final Mortality										United States 2004

ampA

Page ampP

Whites

Blacks

Per 100000 Population

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

White Females

Black Females

Per 100000 Population

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

Total

Males

Females

Per 100000 Population

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

ampA

Page ampP

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

OF HEART ATTACK amp STROKE DEATHS US 1979-91										of stroke deaths			OF CHD DEATHS				of hyp deaths
	M CHD		F CHD			M STROKE		F STROKE					M STROKE		F STROKE			M CHD		F CHD		m		f
79		307286		244079		551365		70439		9949				79		70439		9949		79		307286		244079		13786		1813
80		310774		254981		565755		69973		100252				80		69973		100252		80		310774		254981		13943		1869
81		303929		251229		555158		66429		97075				81		66429		97075		81		303929		251229		13822		17905
82		300820		251966		552786		63855		93855				82		63855		93855		82		30082		251966		1355		17828
83		297522		254970		552492		62847		92751				83		62847		92751		83		297522		25497		13803		17993
84		289461		251827		541288		61697		9263				84		61697		9263		84		289461		251827		13478		17863
85		286181		250624		536805		6078		9227				85		6078		9227		85		286181		250624		13507		17926
86		274184		246545		520729		59164		90479				86		59164		90479		86		274184		246545		13034		17955
87		267757		244381		512138		59061		90774				87		59061		90774		87		267757		244381		13382		17956
88		264505		245087		509592		59759		90758				88		59759		90758		88		264505		245087		13399		18295
89		257524		240497		498021		57321		8823				89		57321		8823		89		257524		240497		13648		18466
90		252597		236574		489171		56697		87391				90		56697		87391		90		252597		236574		13614		19004
91		249736		235702		485438		56714		86767				91		56714		86767		91		249736		235702		13947		19387
92		246913		233138		480051						92		56645		87124		92		246913		233138		1452		2009
93		250362		239701		490063						93		59048		9106		93		250362		239701		15306		21438
94		245350		236108		481458						94		60225		93081		94		24535		236108		15915		22287
95		244819		236468		481287						95		61563		96428		95		244819		236468		1666		23321
96		242036		234088		476124
97		237332		228769		466101

1 An epidemic of death in

women

2 Low hanging fruit - gender

3 Critical investigation - sex

4 Results of our labor

5 Policy and our future

Female-pattern Ischemic Heart Disease(or why women have more adverse IHD outcomes)

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

Is this optimal for women

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

bull This slide set was adapted from the following 2004-6 ACCAHA guidelines

bull Cardiovascular Disease Prevention in Women 2004 2007 2010bull Management of Patients With ST-Elevation Myocardial Infarctionbull Management of Patients with Unstable Angina and Non-ST-Segment

Elevation Myocardial Infarctionbull Preventing Heart Attack and Death in Patients with Atherosclerotic

Cardiovascular Diseasebull Management of Patients with Chronic Stable Anginabull Update for Coronary Artery Bypass Graft Surgerybull Evaluation and Management of Chronic Heart Failure in the Adult

bull The full-text guidelines and executive summaries are also available on the

bull ACC and AHA websites at wwwaccorg and wwwamericanheartorg

Clinical Practice Guidelines

ACC=American College of Cardiology AHA=American Heart Association

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

Under-representation of Women in Cardiovascular Clinical Trials

Melloni et al Circ Cardiovasc Qual Outcomes 2010

Remains low compared to disease prevalence and death rates - Largest gaps in CAD and HF due to phenotype inclusion criteria (eg obstructive CAD troponin and reduced ejection fraction)

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

Monet or Manet

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680

DoD WARRIOR Trial

For more information subject referral or site participationmerzcshsorg310 423 9680