1. Women and Coronary Artery Disease (CAD) Prof. Roland KASSAB Head of Division of Cardiology, HDF Metropolitan Palace Hotel, Beirut 1st May 2010

7. Women and CAD • Epidemiology • Cardiovascular risk factors • Risk stratification • Diagnosis • Prognosis and treatment outcome • JUPITER: meta-analysis of Women • PCI and CABG • Hormone replacement therapy • Concluions

8. PROGNOSTIC VALUE : BNP

9. Epidemiology Statistics on Women and Cardiovascular Disease Comparisons to Men Age Differences Among Women Racial and Ethnic Group Differences

10. CVD and Other Major Causes of Death for Women in the United States: 2004 Source: Adapted fromAmerican Heart Association 2008

11. Congestive Heart Failure: Gender Differences Compared to men, women with heart failure are: Older More likely to have hypertension More likely to have diabetes More likely to have diastolic dysfunction Knowledge of diastolic dysfunction prognosis and treatment is limited Trials of congestive heart failure treatments have included mainly men Source: Stromberg 2003

12. Cardiovascular Disease Mortality: U.S. Males and Females 1980-2004 Source: Adapted fromAmerican Heart Association 2008

13. Annual Numbers of U.S. Adults Diagnosed with Myocardial Infarction and Fatal CHD by Age and Sex Categories: 1987-2004 Age in Years Source: Adapted fromAmerican Heart Association 2008

14. Acute MI Mortality by Age and Sex Source: Adapted from Vaccarino 1999

15. Racial and Ethnic Groups Cardiovascular disease is the leading cause of death for African Americans, Latinos, Asian Americans, Pacific Islanders, and American Indians African American women are at the highest risk for death from heart disease among all racial, ethnic, and gender groups Source: American Heart Association 2004

16. Age-adjusted Death Rates for Leading Causes of Death in White and Black/African American Women: U.S. 2004 Per 100,000 Population Source: Adapted fromAmerican Heart Association 2008

17. Summary 1 Among U.S. women, cardiovascular disease is the leading cause of death Among U.S. women, cardiovascular disease is the leading cause of death for whites, African Americans, Latinas, Asian Americans, Pacific Islanders, and American Indians Source: American Heart Association 2008

18. Summary 2 Mortality from CVD has decreased more for men in the past 20 years than for women Over 10,000 women under age 45 suffer an acute myocardial infarction every year Source: American Heart Association 2008

19. Are All Statins Born Alike ?

20. Cardiovascular Risk Factors in Women Unmodifiable Age Family History Modifiable Diabetes Dysplipidemia Hypertension Obesity Poor Diet Sedentary Lifestyle Cigarette Smoking Source: ATP III 2002, Mosca 2007

21. Approximate and Cumulative LDL Cholesterol Reduction Achievable By Dietary Modification Dietary ComponentDietary ChangeApproximate LDL Reduction Major Saturated fat <7% of calories 8-10% Dietary cholesterol <200 mg/day 3-5% Weight reduction Lose 10 lbs 5-8% Other LDL-lowering options Viscous fiber 5-10 g/day 3-5% Plant/sterol 2g/day 6-15% stanol esters Cumulative estimate 20-30% Source: Adapted from ATP III 2002

22. Treatable Risk Factors: The Epidemiology of Cholesterol Levels and Subfractions Low HDL more important in women than men For every 1 mg/dL increase in HDL 3% decrease in CHD risk for women and 2% decrease in CHD risk for men Total cholesterol/HDL ratio very predictive of CHD risk in women Triglyceride elevation associated with greater atherogenic significance in women than in men Source: Maron 2000

23. Treatable Risk Factors: Cholesterol Level and Subfractions LDL>160 mg/dL associated with 3.3-fold elevation in risk for women less than 65 years old LDL pattern of small, dense particles (more atherogenic) present in 25% of population, but less frequently seen in women Menopausal transition associated with increasing proportion of this subfraction Source: Keil 2000, Carr 2000, Hokanson 1996

24. Relative Risk of Various Factors for CHD for Women and Men 2.4 2.5 1.9 2 1.8 Relative Risk 1.6 1.5 1.5 1.4 1.4 1.5 1.3 Men 1.1 Women 1 0.5 0 HTN CHOL DM Obesity Smoking Source: MMWR 1992

25. Relative Risk of Cardiovascular Events According to Baseline Levels of hs-CRP in Healthy Postmenopausal Women P for trend < 0.001 Source: Ridker 2000

26. Fibrinogen Levels and CHD Risk in Women P for trend <0.0001 >3.6 >3.1,  3.6 >2.8,  3.1  2.8 *Adjusted for age, smoking, BMI, systolic blood pressure, total cholesterol, HDL, triglycerides, and educational level Source: Eriksson 1999

27. Relative Risk of Cardiovascular Events According to Baseline Levels of Homocysteine in Healthy Postmenopausal Women P for trend = 0.02 (not significant) μ μ μ μ Source: Ridker 2000

28. Psychosocial Stressors in Women with CHD: The Stockholm Female Coronary Risk Study Among women who were married or cohabitating with a male partner, marital stress was associated with nearly 3-fold increased risk of recurrent CHD events Living alone and work stress did not significantly increase recurrent CHD events Source: Orth-Gomer 2000

29. Depression and CHD: Results from the Women’s Health Initiative Study Depression is an independent predictor of CHD death among women with no history of CHD Source: Wassertheil-Smoller 2004

31. Risk Stratification: High Risk Diabetes mellitus Documented atherosclerotic disease Established coronary heart disease Peripheral arterial disease Cerebrovascular disease Abdominal aortic aneurysm Includes many patients with chronic kidney disease, especially ESRD 10-year Framingham global risk > 20%, or high risk based on another population-adapted global risk assessment tool Source: Mosca 2007

32. Risk Stratification: At Risk: > 1 major risk factors for CVD, including: Cigarette smoking Hypertension Dyslipidemia Family history of premature CVD (CVD at < 55 years in a male relative, or < 65 years in a female relative) Obesity, especially central obesity Physical inactivity Poor diet Metabolic syndrome Evidence of subclinical coronary artery disease (eg coronary calcification), or poor exercise capacity on treadmill test or abnormal heart rate recovery after stopping exercise Source: Mosca 2007

33. Definition of Metabolic Syndrome in Women Abdominal obesity - waist circumference > 35 in. High triglycerides ≥ 150mg/dL Low HDL cholesterol < 50mg/dL Elevated BP ≥ 130/85mm Hg Fasting glucose ≥ 100mg/dL Source: AHA/NHLBI 2005

34. Source: http://www.nhlbi.nih.gov/about/framingham/riskabs.htm

35. Source: http://www.nhlbi.nih.gov/about/framingham/riskabs.htm

37. Diagnosis of Coronary Artery Disease in Women Chest pain is experienced by most women with CHD, but non-chest pain presentations are more common in women than men Other Presenting Symptoms Upper abdominal pain, fullness, burning sensation Shortness of breath Nausea Neck, back, jaw pain Associations Precipitated by exertion Precipitated by emotional distress Source: Charney 2002, Goldberg 1998

38. Testing for Ischemic Heart Diseasein Women and Factors to Consider Source: Charney 2002, Greenland 2007

39. Drawbacks of Diagnostic Imaging in Women Low exercise capacity – likelihood of reaching adequate pressure rate product Solution: Pharmacologic stress testing Breast attenuation artifact – higher false positive imaging studies Solution: Gated acquisition; attenuation correction for nuclear imaging Solution: Echocardiography Lower pretest probability of CAD – higher false positive rate Solution: Integrate clinical variables, risk factors, into decision-making process Source: Duvernoy, personal communication

40. Value of the Exercise ECG in Women 77 80 70 68 70 61 60 50 Men 40 Women 30 20 10 0 Sensitivity Specificity Source: Kwok 1999

41. Value of Stress Echocardiography Compared to Stress ECG in Women ** * *P < 0.004 vs. Echo **Old P < 0.005 vs. Echo Source: Marwick 1995

42. CHD: Differences in Presentation and Findings in Women Compared to Men Lower prevalence of MI More severe CHF More severe angina Less angiographic CAD More ostial lesions More microvascular dysfunction? Abnormal vasomotor tone? More endothelial dysfunction? Source: Jacobs 2003

43. Women and CHD: What Test to Order When For women at high or intermediate risk of coronary artery disease, consider treadmill echocardiogarphy or nuclear perfusion imaging For women unable to exercise, consider dobutamine stress echocardiography or adenosine or dipyridamole nuclear imaging In high risk women with typical symptoms of coronary artery disease, consider coronary angiography For high risk women, consider cardiac catheterizationif symptoms persist despite negative non-invasive imaging Source: Anderson 2007, Klocke 2003, Douglas 2008, Duvernoy 2005

44. Women and CHD: What Test to Order When A stepwise approach beginning with conventional exercise testing may be considered for women who: Are at low or intermediate risk for coronary artery disease Are able to exercise Have an electrocardiogram that can be interpreted during stress testing An image-enhanced test may be more predictive in women than conventional electrocardiogram stress testing, and may also be more cost effective in women at intermediate risk for CHD Source: Anderson 2007, Klocke 2003, Douglas 2008,Mieres 2005

45. PROGNOSTIC VALUE : pro-BNP

46. Cardiovascular Disease in Women : Prognosis and Treatment Outcomes

47. Women Received Less Interventions to Prevent and Treat Heart Disease Less cholesterol screening Less lipid-lowering therapies Less use of heparin, beta-blockers and aspirin during myocardial infarction Less antiplatelet therapy for secondary prevention Fewer referrals to cardiac rehabilitation Fewer implantable cardioverter-defibrillators compared to men with the same recognized indications Sources: Chandra 1998, Nohria 1998, Scott 2004, O’Meara 2004, Hendrix 2005, Chou 2007, Hernandez 2007, Cho 2008

48. Prognosis After MI • 38% of women die within first year • Compared to 25% of men • 35% of women will have second MI within 6 years • Compared to 18% of men Source: Wenger 2004

49. Prognosis Women < 65 yrs have 2 X mortality rate after MI compared to men of same age After MI, women have significantly higher rates of: Depression Physical disability After CABG, women have significantly higher rates of: Hospital readmission Reduced mental health and physical functioning Source: Vaccarino 1999, Ades 2002, Lauzon 2003, Vaccarino 2003

50. Undertreatment of MI in Women Compared with men: Less emergent thrombolysis Less acute catheterization and angioplasty Less acute surgical revascularization Less use of heparin, beta-blockers, and aspirin Source: Chandra 1998, Nohria 1998