1. Hypertension Management in
Women: What’s Different?
Emma A. Meagher, MD
Associate Professor, Medicine and Pharmacology
University of Pennsylvania

2. Conflict of Interest Disclosure
Emma A. Meagher, MD has no conflicts to disclose

3. CVD Mortality in Women Has NOT Decreased at
the Same Rate as in Men
United States: 1979–2004
520 Females
500
Deaths, thousands
480
460
Males
440
420
400
1979 1985 1990 1995 2000 2005
Years
Rosamond W et al. Circulation. 2007:115.

4. 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
AHA. 2008 Heart and Stroke Statistical Update. 2010.

5. Control of Hypertension Low in Women
About Half Are Treated; About a Quarter Are Controlled
80 75.1 73.6 71.2
70 62.0
60.1 60.0
60
Women, %
50
40
29.1 27.4 29.6
30
20
10
0
III (Phase 1 III (Phase 2 1999–2000
1988–1991) 1991–1994)
Awareness Treatment Control*
*Percentage of hypertensive patients controlled.
Hajjar et al. JAMA. 2003;290:199–206.

6. SBP is a Major Factor in the Lack of BP Control
in the Community
Hypertensive Subjects Examined in the Framingham Heart Study
Between 1990 and 1995
140
Uncontrolled Uncontrolled
13.4%
DBP 120 SBP/DBP
3.7%
DBP (mm Hg)
100
80
60
40
29.0% 53.9% Uncontrolled
Controlled SBP
SBP/DBP 20
80 100 120 140 160 180 200 220
SBP (mm Hg)
SBP and DBP levels of all 1959 subjects with hypertension, treated and untreated, are represented.
Lloyd-Jones DM et al. Hypertension 2000;36:594-599.

7. Hypertension Increases With
Weight Gain in Women
Nurses’ Health Study: Hypertension† According to Weight Change
7 Weight Status in Women Age <45
6 NHANES data: 2002–2004
5 Overweight: 61.8% Age 45–54
Multivariate RR*
4 Obese: 33.2%
Age ≥55
3 Extreme Obesity: 6.9%
2
1
0
Loss Loss Loss Change Gain Gain Gain Gain Gain
≥10 5.0–9.9 2.1–4.9 ≤2.1 2.1–4.9 5.0–9.9 1.0–19.9 20.0–24.9 ≥25
Weight Change After 18 Years, kg
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.
Huang Z et al. Ann Intern Med. 1998;128:81–88.
Ogden C et al. JAMA. 2006;295(13):1549-55.

8. BP Rises After Menopause—
Risk of Hypertension Triples
Changes in SBP From Baseline to Follow-up (Mean 5.2 Years)
Women Controls
6 Premenopausal
5 (n=166)
4 † * Perimenopausal
(n=44)
3
Δ From BaselineSBP,
Postmenopausal
2 (n=105)
1
–1.9 –0.1
0
0.4 3.3 3.8 0.2
–1
mmHg
–2
–3
*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.
Staessen JA et al. J Hum Hypertens. 1997;11:507–514.

9. Menopause Increases Salt-sensitivity
Increases in Salt Intake Lead to Increases in
Blood Pressure in Postmenopausal Women
250
Follicular
200 Luteal
(U Na V, mmol/d)
Contraceptive
150
Menopause
Salt Intake
100
50
0
70 80 90 100 110
24-hour Mean Blood Pressure, mmHg
Oparil S, Miller AP. J Clin Hypertens (Greenwich). 2005;7:300–309.

10. Estrogen Is a Potent Vasodilator
Interruption of Estrogen in Postmenopausal Hypertension
vessel
L-citrulline L-arginine
Endothelial Cell
No NOS
acetylcholine
No
GTP cGMP
protein kinase ↑CA2+ VSMC
PGI2 Relaxation Contraction
Catecholamine
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.

11. Impact of High-Normal BP on CV Risk

12. JNC 7
Classification 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

13. 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

14. How Low Should Blood Pressure
Be Lowered?
JNC 71: Blood Pressure Goals
Condition BP Target
Uncomplicated HTN <140/90 mm Hg
HTN + Diabetes <130/80 mm Hg
HTN + Chronic Renal Disease <130/80 mm Hg
AHA2:Blood Pressure Goals
Condition 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.
1. Chobanian AV et al. Hypertension. 2003;42:1206-1252. 2. Rosendorff C et al. Circulation. 2007;115:2761-2788.

15. Lifestyle Modifications to
Prevent and Manage Hypertension
Reduce weight Moderate consumption of:
• alcohol
• sodium
• saturated fat
• cholesterol
Maintain adequate intake of dietary:
• potassium
• calcium
Increase
• magnesium
physical
activity
Avoid tobacco
(JNC VII)

16. A DASH Towards Cardiovascular Health
• DASH* Diet is recommended by DASH Diet Provides Greater BP
JNC 7 for all patients with, or at ReductionsThan Control Diet
risk of, hypertension
0
• Diet adherence is low and Diastolic
-5
mm Hg
declining
-5.5
– Only about 20% of people with -10 Systolic
hypertension follow the diet; -11.4
-15
*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
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.

17. Limited Efficacy of Monotherapy
A Reason for Poor BP Control
60 59
51 50
50 46
42 42
40
Response
rate* 30
(%)
20
10
0
Diltiazem Atenolol Clonidine HCTZ Captopril Prazosin
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.

18. 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?

19. 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
SBP ≥160 mm Hg or DBP ≥100 mm Hg irrespective of
AHA
the BP goals (Stage 2 Hypertension)
>20/10 mm Hg above goal pressure of <130/80 mm Hg
ASH
for diabetics
SBP >20 mm Hg above goal according to the stage of CKD and
NKF
CVD risk
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
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.

20. JNC 7
Management of Blood Pressure
for Adults Without Compelling Conditions
Initial Drug Therapy
BP Classification
Recommendation
Lifestyle modification only
Prehypertension
Thiazide-type diuretics for most;
Stage 1 Hypertension ACE inhibitor, ARB, -Blocker, CCB,
or combination
2-Drug combination for most (usually
Stage 2 Hypertension thiazide-type diuretic and ACE inhibitor,
ARB, -Blocker, or CCB)
Chobanian AV, et al. JAMA 2003;289:2560-72

21. The 7th report of the Joint National
Committee: Compelling Indications
Compelling
Diuretic βB ACEI ARB CCA AA
Indications
Heart Failure √ √ √ √
Post-MI √ √ √
High CAD risk √ √ √ √
Diabetes √ √ √ √
Chronic kidney
√ √
disease
Recurrent stroke
√ √
prevention
AA=Aldosterone Antagonist
BB=Beta Blocker
CCB=Calcium Channel Blocker
Chobanian AV, et al. JAMA. 2003;289(19):2560-2572.

22. Pathophysiology of BP
BP =X CO SVR
StrokeVol HR PVR RVR

23. Antihypertensive Drug Therapy
Highly effective
Perceived Improvements in Tolerability SBP control
1940’s 1950 1957 1960’s 1970’s 1980’s 1990’s 2001 2007
ACE ARBs Renin
Direct inhibitors
inhibitors
vasodilators
-blockers
Ganglion Thiazides ETAs*
blockers diuretics VPIs*
Central 2 agonists
CCAs -non DHPs
CCAs - DHPs
-blockers
*Not currently available for clinical use

24. Rational Use of Antihypertensive Drugs
In Combination
Diuretics Beta Blockers
ACEIs CCAs
ARBs
1-Receptor Blockers
Less effective Particularly effective
Adapted from Chalmers J. Clin Exp Hypertens. 1993;15:1299–1313.

25. Renin Angiotensin System
Angiotensinogen
• t-PA
Renin X DRI • Cathepsin G
Ang I • Tonin
CAGE
ACE Cathepsin G
Chymase
Ang II
ACEI site of action
ARB site of AT1 receptor AT2 receptor
action
• Hypertrophy/proliferation • Antiproliferation
• Vasoconstriction • NO Release
• Aldosterone release • Differentiation
• Antidiuretic hormone release • Vasodilation
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.

26. Indications and contraindications for
major classes of antihypertensive drugs
Drug Indications Contraindications
Diuretics Elderly Gout
Beta-blockers MI, Angina Asthma, Heart block
Heart failure Heart failure
ACE inhibitors HF, Type 1 Pregnancy,
DM nephropathy Renovascular disease
Ca2+ antagonists Isolated systolic HTN Short acting in pts with IHD
Angina
Alpha-blockers Prostatism Urinary incontinence
AT1 blockers ACE cough Pregnancy,
Heart failure Renovascular disease

27. 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

28. 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

29. Many Providers Not Motivated to Initiate or Change
Treatment
Retrospective Analysis
Percentage of Visits Without Medication Intensification1
100%
80% 87%
79%
60% 72%
55%
40%
20%
0%
150-159 160-169 170-179 ≥180
Retrospective Study 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
1. Adapted from Andrade et al. Am J Manag Care. 2004;10:481-486.
2. Chobanian AV et al. Hypertension 2003;42;1206-1252.
For your confidential information only

30. What Is Therapeutic Inertia?
Causes:
 Overestimation of care provided
The failure of
 Use of “soft” reasons to avoid
health care intensifying therapy
providers to  Lack of education, training, and practice
initiate or intensify organizations on:
therapy when – The benefits of treating to
therapeutic targets
indicated
– The practical complexity and need for
polypharmacy in treating to target
– The need to structure routine practice to
facilitate identification of therapeutic
problems
Phillips LS et al. Ann Intern Med. 2001;135:825–834.

31. CVD Mortality Trends for
Males and Females: US 1979–2002
520
Deaths (thousands)
480
Males Females
440
400
0 NCEP I NCEP II NCEP III
1979 81 83 85 87 89 91 93 95 97 99 01 02
Years
NCEP = National Cholesterol Education Program.
American Heart Association. Heart Disease and Stroke Statistics — 2005 Update.
Dallas, Tex: American Heart Association; 2005. ©2005, American Heart Association.