Coronary Heart Disease in Women

1
Coronary Heart DiseaseinWomen

• David Putnam, MD
• Albany Medical College

2
Introduction

• Cardiovascular disease is the leading cause of
  death in U.S. women
• Over 250,000 deaths annually
• Historically CHD has been viewed as a problem of
  middle-aged men

3
Leading Causes of Death in Women
4
Introduction

• Treatment of CHD in older women has been
  traditionally based on a male model
• U.S. women do not perceive heart disease as a
  priority health problem

5
Age-Related Issues

• CHD is more age-dependent in women than in men
• Women are about 10 years older than men at
  initial manifestation of CHD
• Women are about 20 years older than men at
  occurrence of first MI

6
Incidence of CHD in Women
7
Incidence of CHD in Women
8
Age-Related Issues

• Women will spend more than 1/3 of their lives in
  the post-menopausal state
• Burden of CHD among women will increase

9
Angina in Women

• Women presenting with angina are older than men
• Risk for subsequent MI and cardiac death is
  lower
• Advancing age associated with increasing risk for
  death
• JAMA 19932692392-7.

10
Long-term Survival of Women with Angina
11
Angina in Women

• Atypical pain is more common in women than in men
• Vasospastic and microvascular angina are more
  common in women
• Syndromes of nonischemic chest pain, such as
  mitral-valve prolapse are more common in women

12

• In women, especially those under the age of 50,
  coronary artery disease is unusual in the absence
  of diabetes or hypertension. Yet precordial pain
  stimulating angina is a common symptom.
• Levy and Boas, Mt. Sinai Hosp, NY 1936

13
Angina in Women

• Unlikely that the natural history of angina in
  women with documented CAD by cath will ever be
  known

14
MI in WomenFramingham Data

• Initial MI was more often fatal during the first
  year
• Mortality in the initial weeks following MI was
  greater
• Prevelance of silent MI was higher

15
MI in WomenMILIS Trial ( 1987 )

• 555 men, 228 women
• Greater hospital and post-hospital mortality in
  women
• More post-infarction angina in women

16
MI in WomenThrombolytic Therapy

• Equal gender benefit in restoring arterial
  patency and improving outcome
• Women had an excess of bleeding complications
• Women more often inelgible for thrombolytic
  therapy

17
CABG in WomenDifferences in Men/Women

• Women are older
• Women have more severe and unstable angina
• Women more likely to have urgent/emergency
  procedures

18
CABG in WomenDifferences in Men/Women

• Operative mortality higher in women
• Women have less extensive multivessel disease,
  less left main coronary disease, less prior MI,
  and less abnormal ventricular function
• Long-term survival rates are similar

19
PTCA in Women

• In the early years of this procedure (1977-1981)
  women had a lower success rate
• More recently gender related differences in
  outcome have been eliminated

20
MI in WomenPharmacologic Therapy

• Beta-blockers reduce fatal/non-fatal reinfarction
  
• Aspirin reduces MI/stroke
• No other drugs have been compared for gender
  efficacy and safety in adequate-sized clinical
  trials

21
Cardiac Risk Factors in Women

• Both women and men share traditional coronary
  risk factors
• Potential risk factors unique to women
• A. Oral contraceptive use
• B. Hysterectomy
• C. Menopause
• D. Post-menopausal hormone replacement

22
CHD in WomenMajor Determinants

• Typical angina pectoris
• Postmenopausal status without hormone replacement
• Diabetes mellitus
• Peripheral vascular disease

23
CHD in WomenAngina

• A pattern of non-ischemic pain is associated with
  a very low risk of CHD, although definite angina
  is strongly suggestive of disease

24
Evaluation of Chest Pain in Women
25
CHD in WomenMenopausal Status

• Premenopausal women have a low risk of CHD
• Postmenopausal women have a higher risk of CHD
• Postmenopausal women with hormonal-replacement
  therapy have an intermediate risk of CHD

26
Estrogen TherapyTraditional Teaching

• Reduces risk for CHD by 35
• Reduces cardiovascular mortality by 50
• Improves symptoms of vascular instability
• Given without progesterin increases the risk of
  endometrial cancer and may increase the risk of
  breast cancer
• ANN INT MED 19921171016-37.

27
Hormonal Replacement TherapyPossible Mechanisms
of Effect

• Increased HDL cholesterol
• Lower LDL cholesterol
• Decreased lipid uptake into the vascular wall
• Coronary vasodilation

28
HERS Trial

• 2763 women ( average age 67 )
• Estrogen/medroxyprogesterone vs. placebo
• Average follow-up 4.1 years
• Primary endpoint CHD death, nonfatal MI
• JAMA 1998280605-613.

29
HERS Trial

• No difference in endpoints between groups at end
  of study
• Increase in cardiovascular events in treatment
  arm after 1 year
• Decrease in cardiovascular events in treatment
  arm after 4 years
• Early pro-coagulant effect?
• JAMA 1998280605-613

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HERS Trial

• Does not support initiation of ERT in older
  postmenopausal women with confirmed coronary
  disease
• For women with CHD already on ERT for 1year, may
  be reasonable to continue therapy
• What to do with postmenopausal women free of
  vascular disease?
• JAMA 1998280605-613.

31
Estrogen Therapy

• The use of estrogen replacement therapy to
  prevent CHD is a difficult health decision for
  postmenopausal women
• Potential benefits of therapy must be weighed
  against the possible risks

32
CHD in WomenDiabetes

• More powerful predictor of CHD and its prognosis
  in women than in men
• Associated with fivefold increase in risk of
  heart disease
• Asympotmatic hyperglycemia has been shown to
  increase risk in women

33
CHD in WomenPeripheral Vascular Disease

• Few data are available that specifically assess
  the likelihood of CHD in women with PVD
• In general the association between the two is
  strong

34
CHD in WomenIntermediate Determinants

• Hypertension
• Smoking
• Lipoprotein abnormalities, especially low HDL
  cholesterol levels

35
CHD in WomenHypertension

• HTN is a major risk factor for heart disease in
  women
• Prevalence of HTN reaches 80 in women 75 years
  of age

36
CHD in WomenHypertension

• Definitive data that antihypertensive treatment
  in women is associated with similar benefical
  cardiovascular effects as compared to men is
  lacking
• Women have been excluded from several major
  hypertensive treatment trials

37
Treatment of Hypertensionin Women

• More women then men eventually develop
  hypertension
• Women suffer less cardiovascular damage
• Women receive less benefit from therapy
• Estrogen for postmenapausal replacement therapy
  almost never raises BP
• ARCH INT MED 1995155563-7.

38
CHD in WomenSmoking

• Several large studies have clearly established
  that smoking is an important risk factor for CAD
  in women
• The number of young women beginning to smoke
  exceeds men
• Decline of smoking in women is substantially less
  than that of men ( 6 vs 21 )

39
CHD in WomenSmoking

• Average number of cigarettes that women smoke has
  doubled since 1965
• Smoking has been associated with half of all
  coronary events in women

40
CHD in WomenSmoking

• Risk of MI conferred by smoking is largely
  dissipated after 2 to 3 years
• Switching to low nicotine yield cigarettes is not
  an effective substitute for abstinance
• Reducing consumption to a few cigarettes per day
  is not an acceptable alternative

41
CHD in WomenLipids

• Abnormal lipid levels increase the risk of CAD in
  women
• A low level of HDL is a better predictor of the
  risk of CHD in pre-menopausal women than is a
  high LDL

42
Triglycerides and Coronary Risk

• Casually related to the progress of atherogenesis
• Significant risk factor for CAD in women, more so
  than in men
• Predictor of coronary risk in both men and women
  older than 65 years
• ARCH INT MED 1997157961-968

43
CHD in Women4S Trial

• Secondary prevention trial
• Involved 827 women
• 34 reduction in fatal and non-fatal MI
• 49 reduction in the need for PTCA and CABG

44
CHD in WomenCARE Trial

• Secondary prevention trial
• Involved 576 women
• 43 reduction in coronary death and MI
• 50 reduction in stroke

45
CHD in WomenAFCCAPS/TexCAPS Trial

• Primary prevention trial
• Included 997 women
• 57 relative risk reduction for coronary events
  at 5 years

46
Cardiac Risk Factors in Women

• Risk factors for CHD in women are well documented
• Compelling data from epidemiological studies and
  randomized clinical trials show that CHD is
  largely preventable

47
CHD in WomenMinor Determinants

• Age 65 years
• Obesity, especially central obesity
• Sedentary lifestyle
• Family history of coronary heart disease
• Other risk factors for CHD ( e.g., psychosocial
  or hemostatic )

48
CHD in WomenObesity

• Nurses Health Study
• Higher levels of adiposity within normal range
  associated with higher risk
• 11 to 19 kg weight gain associated with relative
  risk of 1.9
• JAMA 1995273461-5.

49
CHD in WomenAlcohol Consumption

• Nurses Health Study
• Women who consumed light to moderate amounts of
  alcohol had reduced risks for death from CHD
• 10 to 20 decrease in overall mortality rates
• NEJM 19953221245-50.

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CHD in WomenAlcohol Consumption

• Moderate to heavy alcohol consumption increases
  the risk for breast cancer
• Women with the highest alcohol consumption had
  increased risk for death from all causes.
• NEJM 19953221245-50

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Cardiac Risk Factors in WomenAlarming Trends

• Smoking rates are declining less for women than
  men
• Prevalence of obesity is increasing
• 25 of women report no regular, sustained
  physical exercise
• 52 of women 45 years old have hypertension
• 40 of women 55 years old have increased
  cholesterol

52
CHD in WomenMissed Opportunities

• Initial perception of angina as begign has been
  associated with a number of missed opportunities
• Lack of emphasis on preventive strategies

53
CHD in WomenMissed Opportunities

• Lack of inclusion of women in clinical trials
• Inadequate attention to the need for and
  methodology of risk stratification of women with
  chest pain