Heart disease in Women

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1 Heart disease in Women Extent and risk assessment Charles McCreery MB FACC St Vincent's Hospital Dublin St Columcille s Hospital Dublin

2 Natural Progression of Atherosclerosis

3 Heart disease risk differs between Women and Men Women experience MI differently than men More women than men will have a second heart attack within 6 years of their first Diabetic women 3 4 times more likely to develop CAD Diabetes doubles the risk of a second MI Hormone therapy no longer a viable protective strategy

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

6 Deaths in Ireland Total Cancer CVD Men Women

7 Gender Differences in Atherosclerosis Women undergoing coronary angiography have more diffuse atherosclerosis measured by IVUS, more total compromised lumen adjusted for BSA throughout the arterial tree compared to men (WISE study) Women and men have similar magnitude of atherosclerosis, but it looks and functions differently, possibly for estrogen-related related reasons. A consequence of more diffuse atherosclerosis might be more microvascular disease (limited flow reserve) that is not due to obvious obstructive disease* *C. Noel Bairey-Merz. WISE study data ACC 3/2002

8 39 yo female

9 Gender Differences in Atherosclerosis Potential explanations Estrogen reduces cellular hypertrophy and enhances vessel wall elasticity, possibly contributing to less lumen intrusion for the same amount of atherosclerosis Estrogen reduces smooth muscle cell migration and lower collagen deposition in response to injury, which may lead to thinner fibrous plaque in women Estrogen and progesterone upregulate degradative collagenases and inflammatory markers (hscrp( hscrp)

12 Challenges Delay in symptom recognition and treatment Misdiagnosis Lower use of angio,, ASA, Beta blockers and ACE-I Fewer referrals to rehab and more dropouts

15 Gender Differences in Heart Attack Symptoms Typical in both sexes Pain, pressure or squeezing 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 Lightheaded Typical in women Milder symptoms (without chest pain) Sudden onset of weakness, shortness of breath, fatigue, body aches, or overall feeling of illness (without pain) Unusual feeling or mild discomfort in the back, chest, arm, neck, or jaw (without pain)

16 Gender Differences in ED Presentation for CAD Without Chest Pain Percent of patients Women (n = 90) Men (n =127) Dyspnea Nausea/vomiting Indigestion Fatigue Sweating Arm/shoulder pain Milner KA, et al. Am J Cardiol. 1999

17 Risk awareness in women with heart disease 45% had not believed they were at risk Mans disease Complete surprise Protected from family history Marcuccio et al Womens Health Issues 2003, 13;23

18 Gender and MI Mortality Vaccarino V et al. N Engl J Med 1999;341:

19 Proportions of Patients Considered Ideally Suited for Treatments and Procedures after Acute Myocardial Infarction, According to Sex and Race by Study Year Vaccarino V et al. N Engl J Med 2005;353:

20 Value of Exercise ECG in Women Men Women 10 0 Source: Kwok 1999 Sensitivity Specificity

21 Diagnostic Accuracy of Thallium-201 SPECT Myocardial Perfusion Imaging in Men and Women Diagnostic Accuracy [Area under receiver operating characteristic (ROC) curve] Men Women Men Women P < 0.05 Source: Hansen 1996

22 Value of Stress Echocardiography Compared to Stress ECG in Women % Sensitivity Specificity Accuracy * ** Echo ECG *P < vs. Echo **Old P < vs. Echo Source: Marwick 1995

23 Cardiac Catheterization Indications for Presumed/Known CAD: ACC/AHA Guidelines To determine the presence and extent of obstructive coronary artery disease (CAD) when diagnosis cannot be reasonably excluded by noninvasive testing To assess the feasibility and appropriateness of revascularization To assess treatment results progression or regression of coronary atherosclerosis Source: Scanlon 1999

24 What Test to Order When In high risk women with typical symptoms of coronary artery disease, consider referral for immediate cardiac catheterization Exertional chest pain Exertional dyspnea For new-onset symptoms, resting, or rapidly worsening symptoms, women should be referred immediately for evaluation Source: Braunwald 2002

25 What Test to Order When In intermediate risk women able to exercise, consider treadmill echocardiography or nuclear perfusion imaging Assess expertise available, body habitus of patient in deciding which test For women unable to exercise, consider stress echo or adenosine nuclear imaging or cath In lower risk women, consider stress echocardiography or nuclear perfusion imaging?msct increasingly available Source: Gibbons 2002, Cheitlan 2003, Ritchie 1995

26 Clinical Recommendations Lifestyle Interventions Major Risk Factor Interventions Preventive Drug Interventions Atrial Fibrillation/Stroke Prevention Interventions that are not useful/effective and may be harmful Source: Mosca 2004

27 Risk Stratification: CHD equivalent Diabetes mellitus = High risk Established atherosclerotic disease Includes many patients with chronic kidney disease, especially ESRD Major Risk Factors: Age > 55 years Smoking Hypertension, whether or not treated with medication HDL cholesterol < 1.2mmol/L (HDL cholesterol 1.6mmol/L is a negative risk factor) Family history of premature CVD = CVD in a female first degree relative < 65 years old, or a first degree male relative < 55 years old Source: Mosca 2004, ATP III 2002

28 Use electronic calculator for most precise estimate:

29 CHD Risk Equivalents High Risk > 20% 10-yr risk for CHD events Established coronary artery disease Carotid artery stenosis Peripheral arterial disease Abdominal aortic aneurysm Diabetes Includes many patients with chronic renal disease, especially ESRD Source: Mosca 2004

30 Risk Stratification Intermediate Risk 10-20% 10-yr risk for CHD events May include women with metabolic syndrome, especially women over the age of 60 or with individual factors that are markedly elevated or severe Often includes women with multiple risk factors, a single markedly elevated risk factor, or a 1 st degree relative with premature CVD Source: Mosca 2004

31 Risk Stratification Lower Risk <10% 10-yr risk for CHD events May include women with one or more risk factors May include women with defined metabolic syndrome, if no individual factor is severe or markedly elevated May include women with no risk factors, but non-optimal optimal lifestyle factors, such as lack of regular exercise or a high fat diet Optimal Risk <10% 10-yr risk for CHD events Optimal levels of risk factors Heart healthy lifestyle Source: Mosca 2004

Smoking Single most preventable cause of death Smoking by women causes 150% more deaths from heart disease than lung cancer Women who smoke are 2-62 times more likely to suffer a

32 Smoking Single most preventable cause of death Smoking by women causes 150% more deaths from heart disease than lung cancer Women who smoke are 2-62 times more likely to suffer a heart attack Use of birth control pills in smokers compounds cardiac risk Women face different barriers to quitting Concomitant depression Concerns about weight gain Source: Fiore 2000

33 Exercise Manson J et al. N Engl J Med 1999;341: Age-Adjusted and Multivariate Relative Risks of Coronary Events (Nonfatal Myocardial Infarction or Death from Coronary Causes) According to Walking Pace

34 Rehab Improvements similar Less referrals 20% decreased exercise Dependents Career Guilt 38% of women vs 25% men die within one year of MI

35 Diet Encourage healthy eating patterns Healthy food selections: Fruits and vegetables Whole grains Low-fat or nonfat dairy Legumes Low-fat protein Fish Saturated fats < 10% of calories, < 300mg cholesterol Limit trans fatty acid intake (main dietary sources are baked goods and fried foods made with partially hydrogenated vegetable oil) Source: Mosca 2004

36 Weight Maintenance/Reduction Goals BMI between 18.5 and 24.9 Waist circumference < 35 inches Weight loss goals 10% of body weight over six months or 1-21 pounds weight loss/week Reduce calories by 500-1,000 per day Source: Mosca 2004, ATP III 2002

37 As an adjunct to diet, omega-3 3 fatty acid supplements may be considered in high-risk women. Folic acid supplementation may be considered in high risk women (except after revascularization procedure) if a higher-than than- normal level of homocysteine has been detected Source: Mosca 2004

38 Major Risk Factor Interventions Blood Pressure Lipids Diabetes Source: Mosca 2004

39 Major Risk Factor Interventions Blood Pressure Target BP<120/80 mmhg Pharmacotherapy if BP> 140/90, or > 130/80 in diabetics or patients with renal disease Lipids Follow NCEP/ATP III guidelines Diabetes Target HbA1C<7% Source: Mosca 2004

40 Hypertension Encourage an optimal blood pressure of < 120/80 mm Hg through lifestyle approaches Pharmacologic therapy is indicated when blood pressure is > 140/90 mm Hg or an even lower blood pressure in the setting of diabetes or target-organ damage (>( 130/80 mm Hg) Source: Mosca 2004

41 Lipids Optimal levels of lipids and lipoproteins in women are as follows (these should be encouraged in all women with lifestyle approaches): LDL < 3.0mmol/L HDL > 1.4mmol/L Triglycerides < 150mg/d Source: Mosca 2004

42 Lipids Treat high risk women aggressively with pharmacotherapy LDL-lowering pharmacotherapy (preferably a statin) should be initiated simultaneously with lifestyle modification for women with LDL>100mg/dl Source: Mosca 2004

43 Lipids 4S trial Lipids 4S trial % Without major CAD event

44 Cholesterol and risk reduction CARE trial Risk reduction (%)

45 Very High Risk Women Recent heart attack or known CAD, along with one or more of the following: Multiple major risk factors, particularly in diabetics Severe or poorly controlled risk factors (i.e., continued smoking) Multiple risk factors of the metabolic syndrome, especially TG > 200 mg/dl AND HDL < 40 mg/dl LDL goal of < 2.5mmol/L Consider statin, even if LDL < 2.5mmol/L Optional LDL goal of < 2.0mmol/L per ATP III 2004 update Source: Grundy 2004

46 Diabetes Recommendation: Lifestyle and pharmacotherapy should be used to achieve near normal HbA1C (<7%) in women with diabetes Source: Grundy 2004

47 Diabetes Creates Higher Risks for Women With CAD 65% of diabetics die from heart disease or stroke Diabetes increases CAD risk 3-fold 3 to 7-7 fold in women vs 2-fold 2 to 3-fold 3 in men Diabetes doubles the risk of second heart attack in women but not in men American Heart Association Centers for Disease Control and Prevention Manson JE, et al. Prevention of Myocardial Infarction. 1996

48 Preventive Drug Interventions for Women with CHD Aspirin Beta-blockers Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Source: Mosca 2004

49 Preventive Drug Interventions Aspirin High risk women 75mg or clopidogrel if patient intolerant to aspirin; should be used in high-risk women unless contraindicated Aspirin-Intermediate risk women Consider aspirin therapy (75 mg) in intermediate-risk risk women as long as blood pressure is controlled and benefit is likely to outweigh risk of GI side effects Source: Mosca 2004

50 Cumulative Incidence Rates of Stroke, Myocardial Infarction, Ischemic Stroke, and Hemorrhagic Stroke Ridker P et al. N Engl J Med 2005;352:

51 Aspirin in the Primary Prevention of Myocardial Infarction and Stroke among Men and Women Ridker P et al. N Engl J Med 2005;352:

52 Preventive Drug Interventions Aspirin Lower risk women Many women, especially those age 65 and older, may benefit from taking low-dose aspirin every other day to prevent stroke Women over age 65 may benefit from taking low-dose aspirin to reduce major cardiovascular events The use of low dose aspirin in lower risk women should be balanced against the risk of increased internal bleeding Source: NHLBI

53 Preventive Drug Interventions Beta-Blockers Blockers Should be used indefinitely in all women who have had a myocardial infarction or who have had chronic ischemic syndromes (unless contraindicated) Angiotensin-Converting Enzyme Inhibitors Should be used (unless contraindicated) in high-risk women Angiotensin-receptor blockers Should be used in high-risk women with clinical evidence of heart failure or an ejection fraction of <40% who are intolerant of ACE inhibitors Source: Mosca 2004

54 Atrial Fibrillation/Stroke Prevention Warfarin: Among women with chronic or paroxysmal atrial fibrillation, warfarin should be used to maintain the INR at unless they are considered to be at low risk of stroke ( <1%/year). Aspirin should be used in women with chronic or paroxysmal atrial fibrillation with a contraindication to warfarin or a low risk for stroke (<1%/year). Source: Mosca 2004

55 Interventions that are not useful/effective and may be harmful for the prevention of heart disease Antioxidant supplements No cardiovascular benefit in randomized trials of primary and secondary prevention Hormone Therapy Combined estrogen and progesterone hormone therapy should not be initiated or continued to prevent CVD in post-menopausal women. Alternative forms of HT should not be used to prevent CVD, pending results of ongoing trials Source: Mosca 2004

56 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

57 Is There A Role for HRT? Primary prevention Women s Health Initiative 160,000 women: Initial results: no cardioprotection attributed to HRT in women on HRT American Heart Association: HRT not recommended for primary or secondary cardioprotection

58 Risk for major CHD according to current hormone use and timing of HRT initiation with respect to Analyses excluding women with prevalent heart disease Near menopause** Never Started estrogen alone Started estrogen+progestin onset of menopause Case s Age- adjusted model, RR Person- years Multivariate- adjusted model, RR* 1.0 (reference) (reference) *Multivariate-adjusted model includes follow-up from 1980 to 2000, includes only the 80% of women who provided dietary data, and adjusts for age, BMI, hypercholesterolemia, hypertension, parental history of premature heart disease, diabetes, smoking, husband's education, alcohol intake, physical activity, vitamin E supplementation, multivitamin supplementation, and aspirin use **Defined as within 4 years of menopause Grodstein F et al. J Womens Health 2006; 15:35-44.

59 Conclusions Risk Factor Management

60 CAD Risk Factors: Goals Risk Factor Hypertension (mm Hg) High cholesterol (mg/dl) Diabetes Cigarette smoking Minimal Goal Systolic <140 Diastolic <90 LDL-C C 3.0 Serum TC 5.0 HDL-C C 1.2 (men) HDL-C C 1.4 (women) Near-normal fasting glucose (HbA1c <7%) Complete cessation Optimal Goal Systolic <120 Diastolic <80 LDL-C C 2.5 HDL-C C >1.4, TG <1.7 Same Same

61 Advice from women with CAD Be positive Don t smoke Reduce stress Ask questions Talk to your GP Listen to your body Take personal responsibility

62 Things your patients need to know 1. Heart disease is a serious killer of Irish women 2. Cardiovascular disease kills as many women as men 3. Cardiovascular disease can be different in women 4. Signs and symptoms of heart disease can be different in women 5. Some tests are less accurate in women 6. Today treatment options exist for heart disease 7. Women can reduce their risk of heart disease 8. Know your numbers especially LDL/HDL 9. Adopt a heart healthy lifestyle 10. Every woman can take action to improve their heart health

Primary and Secondary Prevention of Cardiovascular Disease. Frank J. Green, M.D., F.A.C.C. St. Vincent Medical Group

Primary and Secondary Prevention of Cardiovascular Disease Frank J. Green, M.D., F.A.C.C. St. Vincent Medical Group AHA Diet and Lifestyle Recommendations Balance calorie intake and physical activity to