Hypertension Management in Women: What’s Different?

Emma A. Meagher, MDAssociate Professor, Medicine and Pharmacology

University of Pennsylvania

Conflict of Interest Disclosure

Emma A. Meagher, MD has no conflicts to disclose

Death

s, t

housa

nds

520

500

480

460

440

420

400

Years

1979

1985 1990 1995 2000 2005

Females

Males

Rosamond W et al. Circulation. 2007:115.

United States: 1979–2004

CVD Mortality in Women Has NOT Decreased at the Same Rate as in Men

AHA. 2008 Heart and Stroke Statistical Update. 2010.

Hypertension: The Silent Disorder

• Prevalence– 55 million people in the United States have

hypertension• of these, 31.6% do not know they have it

• Causes– In 9 of 10 individuals with hypertension the etiology

unknown• Detection

– measuring blood pressure is the only way to detect hypertension

Control of Hypertension Low in Women

Hajjar et al. JAMA. 2003;290:199–206.

Control*Treatment

Awareness

III (Phase 1 1988–1991)

III (Phase 2 1991–1994)

1999–2000

Wom

en,

%

About Half Are Treated; About a Quarter Are Controlled

75.1 73.6 71.262.060.060.1

29.627.429.1

0

10

20

30

40

50

60

70

80

*Percentage of hypertensive patients controlled.

Lloyd-Jones DM et al. Hypertension 2000;36:594-599.

SBP and DBP levels of all 1959 subjects with hypertension, treated and untreated, are represented.

SBP is a Major Factor in the Lack of BP Control in the Community

Uncontrolled SBP/DBP

Uncontrolled DBP

140

20

40

60

80

100

120

80 100 120 140 160 180 200 220

SBP (mm Hg)

3.7%

13.4%

53.9%29.0%

DB

P

(mm

Hg)

Hypertensive Subjects Examined in the Framingham Heart Study Between 1990 and 1995

Controlled SBP/DBP

Uncontrolled SBP

Gain ≥25

Gain 20.0–24.9

Gain 1.0–19.9

Hypertension Increases With Weight Gain in Women

Nurses’ Health Study: Hypertension† According to Weight Change

Huang Z et al. Ann Intern Med. 1998;128:81–88. Ogden C et al. JAMA. 2006;295(13):1549-55.

Overweight=BMI ≥25 kg/m2; obese=BMI ≥30 kg/m2; extreme obesity=BMI ≥40 kg/m2

*Adjusted for age, BMI at age 18 years, height, family history of myocardial infarction, parity, oral contraceptive use, menopausal status, postmenopausal use of hormones, and smoking. †>140/90 mmHg.

Loss 5.0–9.9

Loss 2.1–4.9

Loss ≥10

Change ≤2.1

Gain 2.1–4.9

7

6

5

4

3

2

1

0Gain 5.0–9.9

Weight Change After 18 Years, kg

Age <45

Age 45–54

Age ≥55

Overweight: 61.8%Obese: 33.2%Extreme Obesity: 6.9%

Weight Status in WomenNHANES data: 2002–2004

Mult

ivari

ate

RR

*

BP Rises After Menopause—Risk of Hypertension Triples

Staessen JA et al. J Hum Hypertens. 1997;11:507–514.

Changes in SBP From Baseline to Follow-up (Mean 5.2 Years)

6

5

4

3

2

1

0

–1

–2

–3

–1.9

0.4 3.3

†

0.23.8

*

–0.1

*P≤0.05.†P=0.07.Baseline SBP: Pre=121.4 ± 1.3 mmHg; Peri=122.0 ± 1.8 mmHg; Post=126.5 ± 1.7 mmHg; Controls: men matched by age and BMI.

Women ControlsPremenopausal (n=166)

Δ F

rom

Base

line

SB

P,

mm

Hg

Postmenopausal (n=105)

Perimenopausal (n=44)

Menopause Increases Salt-sensitivityIncreases in Salt Intake Lead to Increases in Blood Pressure in Postmenopausal Women

Oparil S, Miller AP. J Clin Hypertens (Greenwich). 2005;7:300–309.

24-hour Mean Blood Pressure, mmHg

Salt

Inta

ke

(U N

a

V,

mm

ol/d) Follicular

LutealContraceptiveMenopause

70 80 90 100 110

250

200

150

100

50

0

Estrogen Is a Potent VasodilatorInterruption of Estrogen in Postmenopausal Hypertension

Estrogen relax vascular smooth muscle by increasing NO levels and decreasing vasoconstriction by acting as a calcium antagonist

Schwertz DW et al. Heart Lung. 2001;30:401–426.Orshal JM et al. Am J Physiol Regul Integr Comp Physiol. 2004;286:R233–R249.

vessel

Endothelial CellL-citrulline L-arginine

No NOS

↑CA2+ VSMCGTPNo

cGMPprotein kinase

acetylcholine

ContractionCatecholamineRelaxationPGI2

Impact of High-Normal BP on CV Risk

JNC 7Classification of Blood Pressure for Adults Aged 18 Years or Older

BP Classification Systolic BP Diastolic BP

Normal <120 And <80

Prehypertension 120-139 Or 80-89

Stage 1 Hypertension 140-159 Or 90-99

Stage 2 Hypertension ≥160 Or ≥100

Chobanian AV, et al. JAMA 2003;289:2560-72

Goals of Hypertensive Management

• Maintenance of normal BP (avoidance of stroke, CHF)

• Cardioprotection (primary/secondary prevention)

• Renoprotection

• Quality of life (cost, avoidance of side effects)

• Non-interference with concurrent diseases/treatments

How Low Should Blood Pressure Be Lowered?

Condition BP Target

Uncomplicated HTN <140/90 mm Hg

HTN + Diabetes <130/80 mm Hg

HTN + Chronic Renal Disease <130/80 mm Hg

JNC 71: Blood Pressure Goals

1. Chobanian AV et al. Hypertension. 2003;42:1206-1252. 2. Rosendorff C et al. Circulation. 2007;115:2761-2788.

AHA2: Blood Pressure GoalsCondition Target

Uncomplicated HTN <140/90 mm Hg

HTN + High Risk of CAD* <130/80 mm Hg

HTN + Angina <130/80 mm Hg

*Diabetes mellitus, chronic kidney disease, known CAD or CAD equivalent, or 10-year Framingham risk score ≥10%.

JNC=Joint National Committee; HTN=hypertension; AHA=American Heart Association; CAD=coronary artery disease.

Lifestyle Modifications to Prevent and Manage Hypertension

Avoid tobacco

(JNC VII)

Reduce weight Moderate consumption of:• alcohol • sodium• saturated fat• cholesterol

Increase physical activity

Maintain adequate intake of dietary:• potassium• calcium • magnesium

A DASH Towards Cardiovascular Health

• DASH* Diet is recommended by JNC 7 for all patients with, or at risk of, hypertension

• Diet adherence is low and declining

– Only about 20% of people with hypertension follow the diet;

DASH Diet Provides Greater BP ReductionsThan Control Diet

-15

-10

-5

0

mm

Hg

Chobanian AV et al. Hypertension. 2003;42:1206-1252. Mitka M. JAMA. 2007;298(2):164-5.Appel LJ et al. Hypertension. 2006;47:296-308.

.

*DASH=Dietary Approaches to Stop Hypertension, a study that showed a diet rich in fruits, vegetables, grains, low-fat dairy products, and low in fat, cholesterol, and sodium lowered systolic and diastolic blood pressures

-11.4

-5.5

Systolic

Diastolic

Limited Efficacy of Monotherapy A Reason for Poor BP Control

HCTZ, hydrochlorothiazide.*Response = DBP <90 mm Hg at the end of the titration period and <95 mm Hg at the end of 1 year of therapy.Materson BJ et al. N Engl J Med. 1993;328:914-921.

59

Diltiazem

Responserate*(%)

0

10

20

30

40

50

60

51

Atenolol

50

Clonidine

46

HCTZ

42

Captopril

42

Prazosin

Advantages of Combination Therapy• Increased efficacy

– Important as lower BP goals require more drug therapy

• Decreased toxicity – Avoid dose dependent side effects– One drug offset side effects of another drug– Improved compliance– Reduced cost of global health care costs

• Reduced cost to patient (in form of co-pays)• Target organ protection

– Reduction in proteinuria, preservation of GFR?– Regression of LVH?

Recommendations Regarding Initial Use of Combination Therapy

JNC 7 >20/10 mm Hg above goal

ISHIB >15/10 mm Hg above goal

ESH >20/10 mm Hg above goal OR high cardiovascular risk

AHA SBP ≥160 mm Hg or DBP ≥100 mm Hg irrespective of the BP goals (Stage 2 Hypertension)

ASH >20/10 mm Hg above goal pressure of <130/80 mm Hg for diabetics

NKF SBP >20 mm Hg above goal according to the stage of CKD and CVD risk

Chobanian AV, et al. Hypertension. 2003;42:1206–1252. Douglas JG, et al. Arch Intern Med. 2003;163: 525-541. American Journal of Kidney Diseases. 2004;43(Suppl 1):S55-S230. Mancia G, et al. J Hypertens. 2007;25:1105–1187. Rosendorff C, et al. Circulation. 2007;115;2761-2788. Bakris GL and Sowers JR. J Clin Hypertens. 2008;10:707-713. K/DOQI. Am J Kidney Dis. 2004;43 (Suppl1):s65-230.

JNC 7=Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; ISHIB=International Society on Hypertension in Blacks; ESH=European Society of Hypertension; AHA=American Heart Association; ASH=American Society of Hypertension; NKF =National Kidney Foundation

JNC 7

Management of Blood Pressure for Adults Without Compelling Conditions

BP Classification Initial Drug Therapy Recommendation

PrehypertensionLifestyle modification only

Stage 1 HypertensionThiazide-type diuretics for most;

ACE inhibitor, ARB, b-Blocker, CCB, or combination

Stage 2 Hypertension2-Drug combination for most (usually

thiazide-type diuretic and ACE inhibitor, ARB, b-Blocker, or CCB)

Chobanian AV, et al. JAMA 2003;289:2560-72

The 7th report of the Joint National Committee: Compelling Indications

Compelling Indications Diuretic βB ACEI ARB CCA AA

Heart Failure √ √ √ √

Post-MI √ √ √

High CAD risk √ √ √ √

Diabetes √ √ √ √

Chronic kidney disease √ √

Recurrent stroke prevention √ √

AA=Aldosterone AntagonistBB=Beta BlockerCCB=Calcium Channel Blocker

Chobanian AV, et al. JAMA. 2003;289(19):2560-2572.

BP = X

P V R R V R

S V R

S trokeV o l H R

C O

Pathophysiology of BP

Antihypertensive Drug Therapy

Directvasodilators

ACEinhibitors-blockers

ARBs Renin inhibitors

Ganglion blockers

Central 2 agonistsCCAs -non DHPs

-blockers

Thiazidesdiuretics

CCAs - DHPs

1940’s 1950 1957 1960’s 1970’s 1980’s 1990’s 2001 2007

Perceived Improvements in TolerabilityHighly effective

SBP control

ETAs*VPIs*

*Not currently available for clinical use

Rational Use of Antihypertensive DrugsIn Combination

Less effective

Diuretics Beta Blockers

ACEIs ARBs

CCAs

1-Receptor Blockers

Particularly effective

Adapted from Chalmers J. Clin Exp Hypertens. 1993;15:1299–1313.

• t-PA•Cathepsin G•Tonin

Angiotensinogen

Ang I

Renin X DRI

Ang II

CAGECathepsin GChymase

• Antiproliferation• NO Release• Differentiation• Vasodilation

• Hypertrophy/proliferation• Vasoconstriction• Aldosterone release• Antidiuretic hormone release

AT1 receptor AT2 receptorARB site of action

ACEI site of action

ACE

Renin Angiotensin System

de Gasparo M et al. Hypertension. Pathophysiology, Diagnosis, and Management. 2nd ed. New York, NY: Raven Press; 1995:1695–1720. Dzau VJ. J Hypertens. 1989;7:933-936.

Indications and contraindications for major classes of antihypertensive drugs

Drug Indications Contraindications

Diuretics Elderly Gout

Beta-blockers MI, Angina Asthma, Heart blockHeart failure Heart failure

ACE inhibitors HF, Type 1 Pregnancy,DM nephropathy Renovascular disease

Ca2+ antagonists Isolated systolic HTN Short acting in pts with IHDAngina

Alpha-blockers Prostatism Urinary incontinence

AT1 blockers ACE cough Pregnancy,Heart failure Renovascular disease

Case #1• 55 yr old African American Female with hx of HTN for 10 yrs

• CV risk factors include diabetes, obesity and fibromyalgia

• Meds: Simvastatin 40 mg for elevated cholesterol

• FHx: father CKD at 50 and died @ 67 of MI

• Exam: BP 150/92, HR 74, RR 16

• BMI 28.9, waist circumference 37 inches

• CV exam within normal limits

• ECG sinus, HR 70, LVH by volatge criteria

• eGFR 48 mL/min/1.73m2

• Glucose 128, HbA1c 6.8%

• HDL-C 44 mg/dL, LDL-C 112 mg/dL, TG 220 mg/dL

Case #2• 75 yr old Caucasian woman with 20yr history of HTN,

mild urinary incontinence, former smoker

▪ Exam:▪ BP 168/70, HR 68, RR 12, ▪ BMI 25, waist circumference 30”, weight 140 lbs▪ Lungs trace bilateral end expiratory wheezes▪ ECG WNL NSR 68, no chamber enlargement

▪ Labs▪ Urine negative for protein, blood or sediment▪ Fasting blood sugar 82 mg/dL▪ HDL-C 61mg/dL, TG 118 mg/dL, LDL-C 87 mg/dL▪ Bun/Cr 24/0.8, eGFR 66.5 mL/1.73m2

Many Providers Not Motivated to Initiate or Change Treatment

87%79%

72%

55%

0%

20%

40%

60%

80%

100%

150-159 160-169 170-179 ≥180

Percentage of Visits Without Medication Intensification1

1. Adapted from Andrade et al. Am J Manag Care. 2004;10:481-486. 2. Chobanian AV et al. Hypertension 2003;42;1206-1252.

Baseline SBP (mm Hg)

Failure to titrate or combine medications and to reinforce lifestyle modifications despite knowing that the patient is not at goal BP represents clinical inertia that must be overcome.- JNC 72

Retrospective Analysis

Retrospective Study

For your confidential information only

What Is Therapeutic Inertia?

Overestimation of care provided

Use of “soft” reasons to avoid intensifying therapy

Lack of education, training, and practice organizations on:

– The benefits of treating to therapeutic targets

– The practical complexity and need for polypharmacy in treating to target

– The need to structure routine practice to facilitate identification of therapeutic problems

The failure of health care providers to initiate or intensify

therapy when indicated

Causes:

Phillips LS et al. Ann Intern Med. 2001;135:825–834.

CVD Mortality Trends for Males and Females: US 1979–2002

American Heart Association. Heart Disease and Stroke Statistics — 2005 Update. Dallas, Tex: American Heart Association; 2005. ©2005, American Heart Association.

Years

Males Females

400

440

480

520

0

1979 81 83 85 87 89 91 93 95 97 99 01 02

Dea

ths

(tho

usan

ds)

NCEP I NCEP II NCEP III

NCEP = National Cholesterol Education Program.