TRANSFORMING CVD PREVENTION FOR WOMEN: … cvd prevention for women: time for the pygmalion construct to end ... • fourth generation ocps

TRANSFORMING CVD PREVENTION FOR WOMEN: TIME FOR THE PYGMALION

CONSTRUCT TO END

Nanette K. Wenger, MD, MACC, MACP, FAHA

Professor of Medicine (Cardiology) Emeritus

Emory University School of Medicine

Consultant, Emory Heart & Vascular Center

Atlanta, GA

1

DISCLOSURE STATEMENT Nanette Kass Wenger, M.D.

Name of Commitment Name of Organization Research Grants/Contracts/Trial Gilead Sciences, NHLBI, Pfizer, Steering Committee/ Trial Data Society for Women’s Health Research Safety and Monitoring Board Consultantship Amgen, AstraZeneca, Gilead Sciences, Merck

2

Time for the Pygmalion Construct to End

• George Bernard Shaw play “Pygmalion” (“My Fair Lady”)

• Why can’t a woman be more like a man?

• Traditional ASCVD risk factors impart differential risk women and

men

• Non-traditional ASCVD risk factors unique to or predominant in

women

• Gender-specific risk assessment and management potential to

improve ASCVD outcomes in women

Transforming CVD Prevention for Women

3

Shaw, Pygmalion, 1912

CVD Mortality Trends for Males and Females (United States 1979-2010)


4 Go, Circulation 129:e28, 2014

Magnitude of the Problem

• CVD leading cause of mortality, morbidity for U.S. women

• 1 of 4 U.S. women die from CVD

• Annual CVD mortality 2X that all forms cancer combined

• 2 of 3 U.S. women have at least 1 major coronary risk factor

(percentage ↑ with older age)

• Women ages 35-54 ↑ mortality by 1% annually

• Reversing trend of past 4 decades

• Increasing Framingham risk scores in past 2 decades

• Obesity epidemic, sedentary lifestyle

• Importance of providing preventive CVD screenings to women


5

S. Res. 454, 113th Congress, 2d Session, 2014

Ford, NEJM 356:2388, 2007

Towfighi, 169:1762, 2009

Disparities Among Women • African American women

• Almost ½ African American women have some form of CVD

• ↑ Hypertension (44% prevalence), earlier onset

• ↑ Metabolic syndrome

• ↑ CVD rates, mortality than white women

• Greatest risk factor burden at AMI hospitalization in black women

• Less receipt evidence-based therapies

• Hispanic women

• 2X ↑ diabetes vs non-Hispanic white women (12.6% vs 6.45 %)

• Health paradox – lower mortality, ↑ life expectancy vs non-

Hispanic white women


6

S. Res. 113th Congress, 2d Session, 2014

Go, Circulation , 129:e28, 2014

Leifheit-Limson, J Women’s Health 22:659, 2013

Pregnancy Complications

• Detailed pregnancy history integral component of risk assessment for women

• Pregnancy complications: preeclampsia, gestational diabetes, pregnancy-induced

hypertension, preterm delivery = early indicators ↑ CV risk

• Cardiovascular, metabolic stress of pregnancy → potential for early prediction future

CV risk

• ? Shared RF preeclampsia, CVD

• Preeclampsia, gestational hypertension →↑ CVD risk

• 3-6X ↑ subsequent hypertension

• 2x ↑ ischemic heart disease, stroke

• Residual endothelial dysfunction, association with ↑ CAC

• Gestational diabetes → 7x ↑ risk type 2 DM


7

Mosca, Circulation 123:1243, 2011

Fraser, Circulation 125:1367, 2012

Wenger, Am J Cardiol 113:406, 2014

Bellamy, BMJ 335:974, 2007

Ahmed, J Am Coll Cardiol 63:1815, 2014

Oral Contraceptive Therapy

• No ↑ CV risk in healthy women with no risk factors

• Smoking → 7x ↑ risk

• ↑ BP in hypertensive women

• 1.4-2.0 X ↑ risk stroke, ↑ with ↑ age

• Fourth generation OCPs (with drospirenone) →↓ BP, but ↑ VTE risk

• Second generation OCPs (levonorgesterol) →↑ MI risk

• Recommendation: RF control in OCP users


8

WHO Collaborative Study, Lancet 348:498, 1996

Lubianca, Contraception 67:19, 2003

Shufelt, J Am Coll Cardiol 53:221, 2009

Tanis, NEJM 345:1787, 2001

Bushnell, Ann Intern Med 160:853, 2014

Hormonal Fertility Therapy

• Canadian population cohort 1993-2010

• ↓ Risk all-cause mortality, non-fatal coronary ischemia, stroke, TIA,

thromboembolism, heart failure with successful fertility therapy

• All age, income groups

• ? Healthy cohort selection bias


9

Udell, J Am Coll Cardiol 62:1704, 2013

Menopausal Hormone Therapy

• Clinical trial data dramatically altered clinical recommendations,

clinical practice

• USPSTF 2012 Recommendations

• MHT not recommended for primary prevention of chronic

conditions

• MHT not recommended for primary or secondary prevention of

cardiovascular disease (WHI, HERS)


10

USPSTF, Ann Intern Med 158:47, 2013

Nelson, Ann Intern Med 157:104, 2012

Rossouw, JAMA 288:321, 2002

Anderson, JAMA 291:1701, 2004

Hulley, JAMA 280:605, 1998

Systemic Autoimmune Disorders

• Highly prevalent in women

• ↑ Risk CHD, CVA with systemic autoimmune collagen vascular

disorders

• CHD leading cause morbidity, mortality SLE

• 2-3 x ↑ MI, CVD mortality with rheumatoid arthritis

• Warrants ↑ screening for CVD risk factors


11

Salmon, Am J Med 121 (10 suppl 1):S3, 2008


Zhang, Ann Rheum Dis 73:1301, 2014

Hypertension

• Leading cause CVD worldwide

• ↑ Population-adjusted risk CVD mortality women vs men: 29.0% vs 14.9%

• Men > women ↑ BP until age 45, women > men after age 65

• Impressive correlation BMI and ↑ SBP in women

• 80% U.S. women age 75 have hypertension

• ↑ BP with age not present in non-industrialized societies

• 29% elderly women have adequate BP control vs 41% men


12


Chobanian, JAMA 289:2560, 2003

Yusuf, Lancet 364:937, 2004

Hajjar, Annu Rev Public Health 27:465, 2006

Wolf, J Hum Hypertension 11:733, 1997

Cigarette Smoking

• 16.7% U.S. women smoke

• Smoking in younger women > younger men

• 25% ↑ CVD risk women vs men smokers

• Cigarette smoking triples MI risk for women

• Smoking cessation most cost-effective CVD risk modification in U.S.


13

Go, Circulation 129:e28, 2014

Huxley, Lancet 378:1297, 2011

Diabetes Mellitus • Diabetes confers CVD risk women > men, 19.1% vs 10.1%

• 40% ↑ risk incident CHD

• 25% ↑ risk sroke

• Women > men diabetes at first MI, 25.5% vs 16.2%

• Correlation CVD mortality with diabetes women > men

• ? Related to ↑ adiposity, ↑ abdominal adiposity, insulin resistance in diabetic women

• More adverse CV risk profiles diabetic women vs diabetic men

• Diabetic women sole group without mortality improvement 1971-75 and 1982-84

• ↓ Mortality men with and without diabetes and women without diabetes (13%, 36%, 27.1%

respectively)

• ↑ Mortality diabetic women, 23%

• Diabetic women < men treatment, control of CV risk factors


14

Kalyani, Diabetes Care 37:830, 2014


Wannamethee, Diabetologia 55:80, 2012

Wexler, Diabetes Care 28:514, 2005

Peters, Diabetologia, doi:10.1007/s00125-014-3260-6

Peters, Lancet, doi:10.1016/S0140-6736(14)60040-4

Cholesterol Management • ↑ Cholesterol highest population-adjusted CVD risk for women, 47%

• Similar statin benefit women and men

• 2013 ACC/AHA guidelines: Significant change in management of dyslipidemia

• New Pooled Cohort risk equations

• Lifestyle guidelines (dietary and physical activity for LDL-C lowering)

• Fixed-dose statin therapy for women based on risk categorization; no target LDL-C

levels

• Moderate-dose statins > 75 years

• Non-statin therapies not recommended

• Likely will ↑ statin use in women, ↓ inappropriate use, ↓ non-statin use, ↓ laboratory

testing


15

Goff, http://circ.ahajournals.org/content/early/2013/11/11/01.cir.000043774

1.48606.98.full.pdf+html?sid=53af8168-4e81-45f3-81dc-7771aff9d486

Go, http://hyper.ahajournals.org/content/early/2013/11/14/HYP.

0000000000000003.Citation

Eckel, http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437740

.48606.d1.full.pdf+html?sid=cd51c796-e2cf-479c-bba7-4f460a178bf6


Kostis, J Am Coll Cardiol 59:572, 2012

http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437741.48606.98.full.pdf+html?sid=53af8168-4e81-45f3-81dc-7771aff9d486












http://hyper.ahajournals.org/content/early/2013/11/14/HYP.0000000000000003.citation




http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437740.48606.d1.full.pdf+html?sid=cd51c796-e2cf-479c-bba7-4f460a178bf6













Obesity

• 2 of 3 U.S. women obese or overweight (2010)

• Obesity associated with ↑ BP, dyslipidemia, physical inactivity,

insulin resistance

• Obesity →↑ CAD risk = 64% in women vs 46% in men

• Obesity double in women vs men in low- middle income nations

• Obesity equivalent women, men in high-income nations


16

Apovian, http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437739.71477.ee


Global Status Report, www.who..int/nmh/publications/ncd_report2010/en/

http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437739.71477.ee

Physical Inactivity

• 32% adults physically inactive, 33.2% women vs 29.9% men

• INTERHEART: protective effects exercise women > men

• Most prevalent risk factor for women

• ¼ U.S. women report no regular physical activity

• ¾ report less than recommended amount of activity

• ↓ Development diabetes in women who exercised regularly (Nurses’ Health Study)

• Physical activity ↓ risk CV events in diabetic women (Nurses’ Health Study)

• Secondary prevention

• Exercise-based cardiac rehabilitation – women 55% less likely to participate than men


17

Eckel, http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437740

.48606.d1.full.pdf+html?sid=cd51c796-e2cf-479c-bba7-4f460a178bf6



Manson, Lancet 338:774, 1991

Hu, Ann Intern Med 134:96, 2001












Depression • Psychosocial issues, particularly depression, preferentially disadvantage women

• Psychosocial factors → CVD mortality women > men, 45.2% vs 28.8% (INTERHEART)

• Stress at work, home

• Financial stress

• Major life events

• Depression → 1.64 ↑ CVD mortality

• Independent of depression severity

• ? Due to high-risk behaviors, nonadherence to therapies

• ↑ Mortality in depressed young women (< 55) with established CAD

• Depression a risk factor for adverse outcomes with acute coronary syndromes (ACS)

• ↑ Stress with ↑ global violence, current global financial instability

• Cultural taboos in access to care


18

Shah, J Am Heart Assoc 2014;3:e000741doi:10.1161/JAHA.113.000741

Lichtman, Circulation 129:1350, 2014


Rosengren, Lancet 364:953, 2004

Rutledge, J Womens Health 21:133, 2012

Aspirin for CVD Prevention

• Aspirin routinely recommended for primary prevention CVD in men but NOT women

• Women’s Health Study

• 38,876 healthy low-risk women > age 45

• Prevents stroke (not MI or CV death) < age 65

• Potential for GI bleeding

• Prevents stroke, MI, CV death > age 65 but ↑ risk GI bleeding

• Individualize

• Physicians’ Health Study - Men

• Benefit MI, not stroke

• Comparable gender recommendations aspirin use for secondary prevention


1/9

Berger, JAMA 295:306, 2006

Ridker, NEJM 352:1293, 2009

CVD Awareness in Women

• Only 54% women recognize heart disease as their leading cause of death

• 15 years of educational/awareness campaigns (NHLBI “Heart Truth”

Campaign, AHA “Go Red for Women”)

• 30%→56% ↑ awareness, recent plateau

• Lack of awareness greatest in highest-risk populations – women of racial,

ethnic minorities

• Lack of healthcare provider awareness translated →

• Suboptimal application preventive interventions

• Less appropriate diagnostic testing

• Less adherence to evidence-based guidelines

• Poorer outcomes for women

• Underrepresentation in CVD clinical trials and longitudinal studies, lack of

gender-specific analysis → limited scientific database for women

• First step to personalized medicine is incorporating information about sex/gender

differences


20 Mosca, Circ Cardiovasc Qual Outcomes 3:120, 2010


UN Summit on Noncommunicable Diseases September 2011

• Gender disparity in risk, access to diagnosis, treatment

• Linkages with empowerment of women, education of girls

• 9,127,416 cardiovascular deaths in women worldwide (2008)

• 33.2% of all deaths in women • Adversely impacts women’s contribution to society

• Productive and reproductive roles • Consumers and providers of healthcare

• Vulnerability of women

• 60% world’s poor are women • 2/3 of illiterate adults are women


21

http://www.who.int.nmh/events/un_ncd_summit2011/en/

Framework Convention NCD Alliance – NCDs: A Priority for Women’s Health and

Development

Global Status Report on Noncommunicable Diseases, 2010. World Health

Organization

The Problem: Challenges and Opportunities

• CVD → 48% NCD deaths

• 80% in low- and middle-income countries

• 15-20% ↑ global CVD prevalence 2010→2020 • Unfavorable change in CV lifestyle in developing nations

• Urbanization, Western diets, processed foods • ↑ Obesity, hypertension, dyslipidemia, diabetes

• 120% ↑ CVD mortality women in developing countries,

1990→2020 • vs 29% women in developed countries

• INTERHEART: Modifiable RF → 94% population-adjusted CV mortality in women

Yusuf, Circulation 104:2746, 2001

Gupta/Wenger, Expert Rev Cardiovasc Ther 10:379, 2012



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Key Global Issues

• Educate population, women in particular, re CVD risk factors

• Modifiable, behavioral risk factors

• Inform re basic lifestyle modifications → ↓ hypertension, dyslipidemia,

obesity, diabetes, and CVD risk in women

• Smoking cessation

• Diet with ↓ sodium and saturated fats, ↑ fruits and vegetables

• ↑ Exercise

• Messages targeted to women, especially in low- and middle-income

nations

• Organizations directed toward women’s heart health → engage

women on community level

• ↓ Risk CVD, MI, sudden death

• Programs, policies, national plans for CVD prevention targeting women


Chiuve, JAMA 306:62, 2011

Gupta/Wenger, Expert Rev Cardiovasc Ther 10:379, 2012


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TRANSFORMING CVD PREVENTION FOR WOMEN: … cvd prevention for women: time for the pygmalion construct to end ... • fourth generation ocps