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Women and Coronary Artery Disease (CAD)

Women and Coronary Artery Disease (CAD). What do we need to know ? Dr. R.V.S.N.Sarma, M.D., M.Sc., (Canada) Consultant Physician and Chest Specialist Thiruvallur, Chennai. Myths vs Facts. Women’s Perceptions of Heart Disease.

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Women and Coronary Artery Disease (CAD)

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  1. Women and Coronary Artery Disease (CAD) What do we need to know ? Dr. R.V.S.N.Sarma, M.D., M.Sc., (Canada) Consultant Physician and Chest Specialist Thiruvallur, Chennai

  2. Myths vs Facts

  3. Women’s Perceptions of Heart Disease • 72% of young women (ages 25-40) still consider cancer to be the greatest threat to women’s health • Some women know about the risks of heart disease but do not hear it from their own doctors and do not “personalize” it • 65% of women recognize that symptoms may be “atypical” but do not know classic symptoms • Most women learn about coronary artery disease (CAD) from magazines and the Web—not from their own physicians! Robinson A. Circulation. 2001

  4. Gender Bias in the Treatment of Women “… The community has viewed women’s health almost with a ‘bikini’ approach, looking essentially at the breast and reproductive system, and almost ignoring the rest of the woman as part of women’s health ….”Nanette Wenger, MD Chief of Cardiology, Grady Hospital Professor of Medicine, Emory University Atlanta, Georgia

  5. Magnitude of the Problem • 2.5 million women per year in the US are hospitalized with cardiovascular disease (CVD) • Deaths from CVD = 500,000/yr • Leading cause of death in US women: CAD • >230,000 women die from CAD each year • 1990: US Congress directed the National Institutes of Health that women be included in clinical trials and that gender differences be evaluated

  6. Women in Clinical Trials • Women are underrepresented in cardiovascular (CV) trials • Evidence-based CV medicine biased toward men • Food and Drug Administration/National Institutes of Health mandate: 50% enrollment of women • Women need to be empowered to enroll in clinical trials for heart disease • Breast-cancer awareness is a good example

  7. Publication Bias: Gender Representation and Negative Studies • 1966-1994 noninvasive testing literature • 8% to 27% women • Lower diagnostic accuracy in women • High false-positive rates • Inability to perform maximal stress

  8. CVD Mortality Trends (1979-1999) Deaths in Thousands American Heart Association. 2002 Heart and Stroke Statistical Update. 2001

  9. Prevalence of CVD in the US American Heart Association. 2002 Heart and Stroke Statistical Update. 2001

  10. Deaths From CVD and Cancer by Age and Sex Anderson RN. National Vital Statistics Reports. 2002

  11. Deaths From CVD (1999) American Heart Association. 2002 Heart and Stroke Statistical Update. 2001

  12. Health Threats to Women: Perception vs Reality 1 2 • 1. Gallup survey. 1995 2. American Heart Association. Heart & Stroke Facts. 1996 Statistical Supplement

  13. Death From Breast Cancer or Heart Disease in Women in the US • US Vital Statistics, 1990

  14. Statistics for Women • 503,927 died of CVD in 1998 • 226,467 from heart attack or other cardiac events • 97,303 from stroke • 1 in 5 women has some form of CVD • 38% of women who have a heart attack die within 1 year • 40% of coronary events in women are fatal • Most occur without prior warning

  15. Women and Coronary Artery Disease (CAD) Risk Factors and Gender Differences

  16. Warning Signs and Symptoms of CAD

  17. Typical in both sexes Pain, pressure, squeezing, or stabbing pain in the chest Pain radiating to neck, shoulder, back, arm, or jaw Pounding heart, change in rhythm Difficulty breathing Heartburn, nausea, vomiting, abdominal pain Cold sweats or clammy skin Dizziness Typical in women Milder symptoms (without chest pain) Sudden onset of weakness, shortness of breath, fatigue, body aches, or overall feeling of illness (without chest pain) Unusual feeling or mild discomfort in the back, chest, arm, neck, or jaw (without chest pain) Gender Differences in Heart Attack Symptoms

  18. Less Common Heart Attack Symptoms in Women • Milder symptoms without accompanying chest pain • Sudden onset of weakness, shortness of breath, fatigue, body aches, overall feeling of illness • Burning sensation in the chest, may be mistaken as heartburn • An “unusual” feeling or mild discomfort in the back, chest, arm, neck, or jaw

  19. Major Risk Factorsfor Heart Disease Grundy SM, et al. Circulation. 1998; Grundy SM. Circulation. 1999 Braunwald E. N Engl J Med. 1997; Grundy SM, et al. J Am Coll Cardiol. 1999

  20. Emerging Risk Factors • Lipoprotein (a) • Homocysteine • Prothrombotic factors • Proinflammatory factors • Impaired fasting glucose • Subclinical atherosclerosis • Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) • Abnormal internal or common carotid CIT, ankle-arm index <0.9, coronary Ca2+

  21. Diabetes Creates Higher Risks for Women With CAD • 65% of diabetics die from heart disease or stroke • 4.2 million American women have diabetes • Diabetes increases CAD risk 3-fold to 7-fold in women vs 2-fold to 3-fold in men • Diabetes doubles the risk of second heart attack in women but not in men • Every year, heart disease kills 50,000 more American women than men • Statistics are particularly high among African American women American Heart Association Centers for Disease Control and Prevention Manson JE, et al. Prevention of Myocardial Infarction. 1996

  22. Lowest Survival Rates for Diabetic Women • CAD mortality rates in diabetics, especially women, have not decreased to the same extent as those in the general population • In a large cohort referred for coronary disease, diabetic women had the highest mortality rates • Estimate of ischemic burden with stress myocardial perfusion imaging significantly improved risk stratification in diabetic women compared with clinical risk alone • Stratification by the number of ischemic vessels demonstrated a significant linear increase in cardiac events with escalating ischemic burden (sex-diabetes interaction, P = .016) Gu K, et al. JAMA. 1999 Giri S, et al. Circulation. 2002

  23. Diabetes: Powerful Risk Factor for CAD in Women • Framingham Heart Study • Women with diabetes mellitus had relative risk of 5.4% for CAD vs women without diabetes • Men with diabetes had relative risk of 2.4% • Nurses’ Health Study • Relative risk of 6.3% for total cardiovascular (CV) mortality • Even if women had diabetes for <4 years, their risk of CAD was significantly elevated Kannel W. Am Heart J. 1987 Manson J, et al. Arch Intern Med. 1991

  24. Clinical Identification of the Metabolic Syndrome • Abdominal obesity • Men >88 cm (>40 in) • Women >80 cm (>35 in) • Triglycerides (TG) >150 mg/dL • HDL cholesterol • Women <50 mg/dL • Men <40 mg/dL • Blood pressure >130/>85 mm Hg • Fasting glucose >100 mg/dL National Heart, Lung, and Blood Institute

  25. Impact of Triglyceride Levels on Relative Risk of CAD Castelli WP. Can J Cardiol. 1988

  26. Women and CAD Risk Factors • Higher prevalence of avoidable risk factors1 • ↑ blood cholesterol, ↑ TG • ↑ physical inactivity • ↑ overweight (body mass index, 25.0-29.9) • Diabetes is a more powerful risk factor for CAD2 • 3- to 7-fold in women vs 2- to 3-fold in men • ↓ HDL cholesterol levels more predictive of CAD2 • Women counseled less about nutrition, exercise, and weight control2 1. American Heart Association. 1999 Heart and Stroke Statistical Update. 1998 2. Mosca L, et al. Circulation. 1999

  27. MI or Death Often First Sign of CAD Levy D, et al. Textbook of Cardiovascular Medicine. 1998

  28. Smoking • Single most preventable cause of death in US • Smoking by women causes 150% more deaths from heart disease than lung cancer • Women who smoke are 2-6 times more likely to suffer a heart attack • Use of birth control pills in smokers compounds cardiac risk

  29. Overweight American Heart Association. 2002 Heart and Stroke Statistical Update. 2001

  30. Physical Inactivity • Lack of exercise is a proven risk factor for heart disease • A lack of regular physical exercise is a growing epidemic all over the world. “We seem to eat much more than what we burn” • Heart disease is twice as likely to develop in inactive people than in those who are more active • Physical activity helps maintain weight, blood pressure, and diabetes • Women should exercise to increase heart rate for 20-30 minutes a day, 3-5 times per week

  31. Hormonal Effects on Ischemia and Disease Prevalence • Premenopause • Estrogen has digoxin-like effect:  ST  • Post-menopause effect on HRT •  ST  - vasodilatory effects of HRT • Increase exercise duration/decrease chest pain • Women with intact uterus take progestin to protect against uterine malignancies • Estrogen and medroxyprogesterone attenuate this effect Lloyd GW, et al. Heart. 2000; Webb CM, et al. Lancet. 1998; Morise AP, et al. Am J Cardiol. 1993; Rosano GM, et al. J Am Coll Cardiol. 2000

  32. Hormonal Effects on Ischemia and Disease Prevalence • Estrogen modulates chest pain syndromes • Premenopausal CAD: angina/ischemia variation by menstrual cycle • Early follicular phase estradiol and progesterone levels - low < time to ischemia onset • Mid-cycle estrogen levels - highest > time to ischemia onset Lloyd GW, et al. Heart. 2000; Webb CM, et al. Lancet. 1998; Morise AP, et al. Am J Cardiol. 1993; Rosano GM, et al. J Am Coll Cardiol. 2000

  33. Postmenopausal Hormone Therapy and Cardioprotection • First randomized trial • HERS trial (Heart and Estrogen/Progestin Replacement Study) • Secondary CAD prevention trial • Randomized trial of placebo vs estrogen and medroxyprogesterone • Follow-up = 4 years • N = 2,763 women with an intact uterus • Outcome measures • Primary: nonfatal MI or cardiac death • Secondary: unstable angina, coronary revascularization, congestive heart failure HERS trial. JAMA. 1998.

  34. Is There a Role for HRT? • Secondary prevention • 1998: HERS • 4 years of treatment with conjugated estrogen plus medroxyprogesterone acetate • No reduction in the risk of MI and coronary death in women with established CAD HERS trial. JAMA. 1998.

  35. Is There a Role for HRT? • Secondary prevention • 3/2000: Estrogen Replacement and Atherosclerosis trial (ERA) • 309 postmenopausal women with CAD • Placebo vs conjugated estrogen (.625 mg/day) vs conjugated estrogen (.625 mg/day) with medroxyprogesterone acetate (2.5 mg/day) • Angiographic analysis of the diameter of the coronary arteries at the start of the study and 3 years later • ERA trial results at follow-up angiography • The progression of coronary atherosclerosis was unchanged in the women randomized to either of the estrogen groups ERA trial. J Am Coll Cardiol. 2001

  36. Is There A Role for HRT? • Primary prevention • Women’s Health Initiative. WHI trial • 160,000 women:1991-2005 • Initial results: no cardioprotection attributed to HRT in women on HRT • American Heart Association: HRT not recommended for primary or secondary cardioprotection

  37. Conclusions: Risk Factor Management • CVD begins in childhood and is strongly associated with major risk factors for heart disease • Multiple risk factors require more aggressive management • Aggressive risk-factor modification (often with multiple medications) is the most effective strategy for reducing the consequences of heart disease Berenson GS, et al. N Engl J Med. 1998. Neaton JD, et al. Arch Intern Med. 1992. Kannel WB. in Atherosclerosis and Coronary Artery Disease. 1996. Grundy SM, et al. Circulation. 1999

  38. Gender Differences in CAD Risk Factors • Increasing recognition that atherosclerosis is an inflammatory process • Ridker PM, et al: A prospective case-controlled study among 28,263 postmenopausal women • Among 12 markers of inflammation, C reactive protein was the strongest univariate predictor of the risk of CV events Ridker PM, et al. N Engl J Med. 2000

  39. Women andCoronary Artery Disease (CAD) Diagnosis and Prognosis

  40. Diagnosis and Management of CAD in Women • Gender differences: presentation, manifestation, and diagnosis of CAD • Gender differences in mortality • 63% of women who die suddenly from CAD had no prior warning symptoms • 42% of women vs 24% of men will die within 1 year after MI • Thus, early recognition of symptoms and accurate diagnosis of CAD is of great importance

  41. Heart Disease in Women: Lessons From the Past Decade • The importance of studying gender-specific aspects of CAD have helped in the following clinical dilemmas: • At Presentation of CAD: women are older than men • Less specific clinical manifestations of CAD in women • Greater difficulty in diagnosis: women > men • More severe consequences on MI when it occurs in women

  42. Screening for Heart Disease What Tests Should we use to identify Coronary Heart Disease?

  43. Limited Representation of Women in Studies of CAD Testing Adapted from: Shaw LJ, et al. Coronary Artery Disease in Women: What All Physicians Need to Know. 1999

  44. Are There Gender Differences in Noninvasive Diagnostic Tests? Is There a Difference in Diagnostic Accuracy of Noninvasive Tests?

  45. Noninvasive Testing Options Stress ECG Stress Echo Stress MPI EBCT PET MRI

  46. Noninvasive Testing in Symptomatic Women • Stress electrocardiography (ECG) • Stress echocardiography (ECHO) • Stress nuclear imaging (MPI)

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