Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women

1. Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women This slide set was updated in April 2008.This slide set was updated in April 2008.

2. Objectives To present strategies to assess and stratify women into high risk, at risk, and optimal risk categories for cardiovascular disease To summarize lifestyle approaches to the prevention of cardiovascular disease in women

3. Objectives To review evidence-based approaches to cardiovascular disease prevention for patients with hypertension, lipid abnormalities, and diabetes To review an evidence-based approach to pharmacological risk intervention for women at risk for cardiovascular events

4. Objectives To summarize commonly used therapies that shouldnot be initiated for the prevention or treatment ofheart disease, because they lack benefit, or becauserisks outweigh benefits

5. Cardiovascular Disease Mortality: U.S. Males and Females 1980-2004 SLIDE INFORMATION SOURCE: Rosamond W, et al. Heart disease and stroke statistics– 2008 Update. Circulation 2008; 117: e25-e146. This slide shows mortality trends by gender. While mortality in males has been steadily declining over the past 15-20 years, cardiovascular mortality for women remained flat or increased slightly during the 1980s and 1990s. Mortality rates for women have exceeded those for men over the past 20 years.(1). (1) Rosamond W, et al. Heart disease and stroke statistics– 2008 Update. Circulation 2008; 117: e25-e146. SLIDE INFORMATION SOURCE: Rosamond W, et al. Heart disease and stroke statistics– 2008 Update. Circulation 2008; 117: e25-e146. This slide shows mortality trends by gender. While mortality in males has been steadily declining over the past 15-20 years, cardiovascular mortality for women remained flat or increased slightly during the 1980s and 1990s. Mortality rates for women have exceeded those for men over the past 20 years.(1). (1) Rosamond W, et al. Heart disease and stroke statistics– 2008 Update. Circulation 2008; 117: e25-e146.

6. 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 SLIDE INFORMATION SOURCE: Rosamond W, et al. Heart disease and stroke statistics– 2008 Update. Circulation 2008; 117: e25-e146. SLIDE INFORMATION SOURCE: Rosamond W, et al. Heart disease and stroke statistics– 2008 Update. Circulation 2008; 117: e25-e146.

7. 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 SLIDE INFORMATION SOURCES: Chandra NC, et al. Observations of the treatment of women in the United States with myocardial infarction; a report from the National Registry of Myocardial Infarction-I. Arch Intern Med 1998; 158:981-988; Nohria A, et al. Gender differences in coronary artery disease in women: gender differences in mortality after myocardial infarction: why women fare worse than men. Cardiol Clin 1998; 16:45-57. Scott LB, Allen JK. Providers perceptions of factors affecting women’s referral to outpatient cardiac rehabilitation programs: an exploratory study. J Cardiopulm Rehab 2004; 24:387-391. O’Meara JG, et al. Ethnic and sex differences in the prevalence, treatment, and control of dyslipidemia among hypertensive adults in the GENOA study. Arch Intern Med 2004; 164:1313-1318. Hendrix KH, et al. Ethnic, gender, and age-related differences in treatment and control of dyslipidemia in hypertensive patients. Ethn Dis 2005; 15:11-16, Cho L, et al. Gender differences in utilization of effective cardiovascular secondary prevention: a Cleveland Clinic Prevention Database study. J Womens Health (Larchmt) 2008; 17: 1-7, Hernandez AF, et al. Sex and racial differences in the use of implantable cardioverter-defibrillators among patients hospitalized with heart failure. JAMA 2007; 298: 1535-1532, Chou AF, et al. Gender disparities in the quality of cardiovascular disease care in private managed care plans. Womens Health Issues 2007; 17: 120-130. SLIDE INFORMATION SOURCES: Chandra NC, et al. Observations of the treatment of women in the United States with myocardial infarction; a report from the National Registry of Myocardial Infarction-I. Arch Intern Med 1998; 158:981-988; Nohria A, et al. Gender differences in coronary artery disease in women: gender differences in mortality after myocardial infarction: why women fare worse than men. Cardiol Clin 1998; 16:45-57. Scott LB, Allen JK. Providers perceptions of factors affecting women’s referral to outpatient cardiac rehabilitation programs: an exploratory study. J Cardiopulm Rehab 2004; 24:387-391. O’Meara JG, et al. Ethnic and sex differences in the prevalence, treatment, and control of dyslipidemia among hypertensive adults in the GENOA study. Arch Intern Med 2004; 164:1313-1318. Hendrix KH, et al. Ethnic, gender, and age-related differences in treatment and control of dyslipidemia in hypertensive patients. Ethn Dis 2005; 15:11-16, Cho L, et al. Gender differences in utilization of effective cardiovascular secondary prevention: a Cleveland Clinic Prevention Database study. J Womens Health (Larchmt) 2008; 17: 1-7, Hernandez AF, et al. Sex and racial differences in the use of implantable cardioverter-defibrillators among patients hospitalized with heart failure. JAMA 2007; 298: 1535-1532, Chou AF, et al. Gender disparities in the quality of cardiovascular disease care in private managed care plans. Womens Health Issues 2007; 17: 120-130.

8. Acute MI Mortality by Age and Sex SLIDE INFORMATION SOURCE: Vaccarino V. et al. Sex-based differences in early mortality after myocardial infarction. National registry of myocardial infarction 2 participants. N Engl J Med 1999; 341(4): 217-225. Based on national registry data including 155,565 women and 229,313 men enrolled between June 1994 and January 1998, overall in-hospital mortality during hospitalization for myocardial infarction is 16.7% for women, compared to 11.5% for men(1) Among persons less than 50 years of age, the rate of mortality for women is twice the rate of mortality for men (1). In contrast, for persons over the age of 74 years, there is no statistically significant difference in mortality rates between women and men(1). (1) Vaccarino V. et al. Sex-based differences in early mortality after myocardial infarction. National registry of myocardial infarction 2 participants. N Engl J Med 1999; 341(4): 217-225. SLIDE INFORMATION SOURCE: Vaccarino V. et al. Sex-based differences in early mortality after myocardial infarction. National registry of myocardial infarction 2 participants. N Engl J Med 1999; 341(4): 217-225. Based on national registry data including 155,565 women and 229,313 men enrolled between June 1994 and January 1998, overall in-hospital mortality during hospitalization for myocardial infarction is 16.7% for women, compared to 11.5% for men(1) Among persons less than 50 years of age, the rate of mortality for women is twice the rate of mortality for men (1). In contrast, for persons over the age of 74 years, there is no statistically significant difference in mortality rates between women and men(1). (1) Vaccarino V. et al. Sex-based differences in early mortality after myocardial infarction. National registry of myocardial infarction 2 participants. N Engl J Med 1999; 341(4): 217-225.

9. Evidence-based Guidelines for Cardiovascular Disease Prevention in Women: 2007 Update Mosca L, et al. Circulation 2007; 115:1481-501. http://www.circ.ahajournals.org An update to evidence-based guidelines for the prevention of cardiovascular disease in women developed in 2004 were published in Circulation in 2007. For the original 2004 guidelines, over 1270 articles were screened by the panel, and 400 articles were included for evidence tables. For the update, new topics were added, and a systematic search on previously identified topics was performed to include the time period from January 2003- June, 2006. A complete listing of references reviewed by the panel is listed at the website (1)(2). Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004; 109:672-693. (2) Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.An update to evidence-based guidelines for the prevention of cardiovascular disease in women developed in 2004 were published in Circulation in 2007. For the original 2004 guidelines, over 1270 articles were screened by the panel, and 400 articles were included for evidence tables. For the update, new topics were added, and a systematic search on previously identified topics was performed to include the time period from January 2003- June, 2006. A complete listing of references reviewed by the panel is listed at the website (1)(2). Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004; 109:672-693. (2) Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

10. Cardiovascular Disease Prevention in Women: Current Guidelines A five-step approach Assess and stratify women into high risk, at risk,  and optimal risk categories Lifestyle approaches recommended for all women Other cardiovascular disease interventions:  treatment of HTN, DM, lipid abnormalities Highest priority is for interventions in high risk patients Avoid initiating therapies that have been shown  to lack benefit, or where risks outweigh benefits SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004; 109:672-693. A five part approach was supported by currently available evidence. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004; 109:672-693. A five part approach was supported by currently available evidence.

11. 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 SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

12. 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 SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

13. 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 SLIDE INFORMATION SOURCE: Grundy SM, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 2005, accessed at www.circulationaha.org on October 25, 2005. The metabolic syndrome is characterized by a constellation of risk factors in one individual. This syndrome increases the risk for CHD at any given LDL-cholesterol level (1). The definition of metabolic syndrome remains controversial. This is the AHA/NHLBI definition. Patients are diagnosed with metabolic syndrome when three of five criteria are met. Patients receiving drug treatment for elevated triglycerides, reduced HDL, hypertension, or high glucose meet the threshhold for each criteria. A cutoff of 31 inches waist circumference for Asian American women should be used(1) (1) Grundy SM, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 2005, accessed at www.circulationaha.org on October 25, 2005. SLIDE INFORMATION SOURCE: Grundy SM, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 2005, accessed at www.circulationaha.org on October 25, 2005. The metabolic syndrome is characterized by a constellation of risk factors in one individual. This syndrome increases the risk for CHD at any given LDL-cholesterol level (1). The definition of metabolic syndrome remains controversial. This is the AHA/NHLBI definition. Patients are diagnosed with metabolic syndrome when three of five criteria are met. Patients receiving drug treatment for elevated triglycerides, reduced HDL, hypertension, or high glucose meet the threshhold for each criteria. A cutoff of 31 inches waist circumference for Asian American women should be used(1) (1) Grundy SM, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 2005, accessed at www.circulationaha.org on October 25, 2005.

14. Risk Stratification: Optimal risk: No risk factors Healthy lifestyle Framingham global risk < 10% SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

15. Risk Stratification Calculate 10 year risk for all patients with two or more risk factors that do not already meet criteria for CHD equivalent Use electronic calculator for most precise estimate: http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm SLIDE INFORMSTION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004; 109:672-693. SLIDE INFORMSTION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004; 109:672-693.

16. Lifestyle Interventions Smoking cessation Physical activity Heart healthy diet Weight reduction/maintenance Cardiac rehabilitation Omega-3 fatty acids Depression SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

17. Smoking All women should be consistently encouraged to stop smoking and avoid environmental tobacco The same treatments benefit both women and men Women face different barriers to quitting Concomitant depression Concerns about weight gain Provide counseling, nicotine replacement, and other pharmacotherapy as indicated in conjunction with a behavioral program or other formal smoking cessation program SLIDE INFORMATION SOURCE: Fiore MC, et al. Treating tobacco use and dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. June 2000, Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE INFORMATION SOURCE: Fiore MC, et al. Treating tobacco use and dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. June 2000, Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

18. Physical Activity Consistently encourage women to accumulate a minimum of 30 minutes of moderate intensity physical activity on most, or preferably all, days of the week Women who need to lose weight or sustain weight loss should accumulate a minimum of 60-90 minutes of moderate-intensity physical activity on most, and preferably all, days of the week SLIDE INFORMATION SOURCE: Mosca L et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE INFORMATION SOURCE: Mosca L et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

19. Body Weight and CHD Mortality Among Women SLIDE INFORMATION SOURCE: Manson JE, et al. Body weight and mortality among women. N Engl J Med 1995; 333:677-685. The participants in this part of the Nurses Health Study were 115,195 women free of diagnosed cardiovascular disease and cancer in 1976, who were followed until 1992 (1). This graph represents data for non-smokers in the study. Weight gain of 20 kg or more since the age of 18 confers a greater than 7 times relative risk of CHD mortality. (1) Manson JE, et al. Body weight and mortality among women. N Engl J Med 1995;. 333:677-685. SLIDE INFORMATION SOURCE: Manson JE, et al. Body weight and mortality among women. N Engl J Med 1995; 333:677-685. The participants in this part of the Nurses Health Study were 115,195 women free of diagnosed cardiovascular disease and cancer in 1976, who were followed until 1992 (1). This graph represents data for non-smokers in the study. Weight gain of 20 kg or more since the age of 18 confers a greater than 7 times relative risk of CHD mortality. (1) Manson JE, et al. Body weight and mortality among women. N Engl J Med 1995;. 333:677-685.

20. Weight Maintenance/Reduction Goals Women should maintain or lose weight through an appropriate balance of physical activity, calorie intake, and formal behavioral programs when indicated to maintain: BMI between 18.5 and 24.9 kg/m² Waist circumference < 35 inches SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

21. Low Risk Diet is Associated with Lower Risk of Myocardial Infarction in Women SLIDE INFORMATION SOURCE: Akesson A, et al. Combined effect of low-risk dietary and lifestyle behaviors in primary prevention of myocardial infarction in women. Arch Intern Med 2007; 167:2122. In this population-based prospective cohort study of 24,444 postmenpausal women in Sweden, after 6.2 years of follow-up, a low risk diet characterized by a high intake of vegetables, fruit, whole grains, fish, and legumes, as well as moderate alcohol consumption, physical activity, maintaining a healthy weight, and not smoking were associated with lower risk of myocardial infarction. A combination of all healthy behaviors was predicted to prevent 77% of myocardial infarctions in the study population. In this study, only 5% of women had all healthy behaviors. (1) (1) Akesson A, et al. Combined effect of low-risk dietary and lifestyle behaviors in primary prevention of myocardial infarction in women. Arch Intern Med 2007; 167:2122. SLIDE INFORMATION SOURCE: Akesson A, et al. Combined effect of low-risk dietary and lifestyle behaviors in primary prevention of myocardial infarction in women. Arch Intern Med 2007; 167:2122. In this population-based prospective cohort study of 24,444 postmenpausal women in Sweden, after 6.2 years of follow-up, a low risk diet characterized by a high intake of vegetables, fruit, whole grains, fish, and legumes, as well as moderate alcohol consumption, physical activity, maintaining a healthy weight, and not smoking were associated with lower risk of myocardial infarction. A combination of all healthy behaviors was predicted to prevent 77% of myocardial infarctions in the study population. In this study, only 5% of women had all healthy behaviors. (1) (1) Akesson A, et al. Combined effect of low-risk dietary and lifestyle behaviors in primary prevention of myocardial infarction in women. Arch Intern Med 2007; 167:2122.

22. Diet Consistently encourage healthy eating patterns Healthy food selections: Fruits and vegetables Whole grains, high fiber Fish, especially oily fish, at least twice per week No more than one drink of alcohol per day Less than 2.3 grams of sodium per day 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) SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. Trans fatty acids are found in hydrogenated vegetable oils and some animal fats(1). Major sources are baked foods like crackers, cookies, doughnuts, breads, and food fried in hydrogenated vegetable oil, like french fires and fried chicken(1). Based on data from randomized trials, trans fatty acids raise LDL cholesterol(1). (1) Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adults Treatment Panel III), NIH, NHLBI, 2002. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. Trans fatty acids are found in hydrogenated vegetable oils and some animal fats(1). Major sources are baked foods like crackers, cookies, doughnuts, breads, and food fried in hydrogenated vegetable oil, like french fires and fried chicken(1). Based on data from randomized trials, trans fatty acids raise LDL cholesterol(1). (1) Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adults Treatment Panel III), NIH, NHLBI, 2002.

23. 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 SLIDE INFORMATION SOURCE: Orth-Gomer K, et al. Marital stress worsens prognosis in women with coronary heart disease. JAMA 2000; 283:3008-3014. SLIDE INFORMATION SOURCE: Orth-Gomer K, et al. Marital stress worsens prognosis in women with coronary heart disease. JAMA 2000; 283:3008-3014.

24. 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 SLIDE INFORMATION SOURCE: Wassertheil-Smoller S, et al. Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI). Arch Intern Med. 2004; 164:289-98.  Recently, an arm of the Women’s Health Initiative reported findings on depression in 93,676 women with no baseline history of CHD. After an average of 4.1 years of follow-up, depression was an independent predictor of CHD death and all-cause mortality after adjustment for age, race, education, income, DM, HTN, smoking, body mass index, physical activity and increased cholesterol(1). Whether identification and treatment of depression will lower CHD risk is unknown(1). (1) Wassertheil-Smoller S, et al. Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI). Arch Intern Med. 2004; 164:289-98. SLIDE INFORMATION SOURCE: Wassertheil-Smoller S, et al. Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI). Arch Intern Med. 2004; 164:289-98. Recently, an arm of the Women’s Health Initiative reported findings on depression in 93,676 women with no baseline history of CHD. After an average of 4.1 years of follow-up, depression was an independent predictor of CHD death and all-cause mortality after adjustment for age, race, education, income, DM, HTN, smoking, body mass index, physical activity and increased cholesterol(1). Whether identification and treatment of depression will lower CHD risk is unknown(1). (1) Wassertheil-Smoller S, et al. Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI). Arch Intern Med. 2004; 164:289-98.

25. Omega-3 Fatty Acids As an adjunct to diet, omega-3 fatty acid supplements in capsule form (approximately 850-1000 mg of EPA and DHA) may be considered in women with CHD Higher doses (2 to 4 g) may be used for treatment of women with high triglyceride levels SLIDE INFORMATION SOURCE: . Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. Omega-3 polyunsaturated fatty acids are found in certain vegetable sources, as well as in fish oils (1). Clinical trials incorporating increased intake of omega-3 polyunsaturated acids as fatty fish, components of a “Mediterranean” diet, or fish oil capsules suggest that omega-3 fatty acids reduce sudden death and overall death in persons with coronary artery disease (1). High intake of omega-3 fatty acids can cause excessive bleeding. Some types of fish can contain methylmercury, dioxin, and other environmental toxins (2). EPA= eicosapentaenoic acid DHA= docosahexaenoic acid Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. Kris-Etherton PM, et al. Omega-3 fatty acids and cardiovascular disease. Aterioscler Thromb Vasc Biol 2003;23:151-152. SLIDE INFORMATION SOURCE: . Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. Omega-3 polyunsaturated fatty acids are found in certain vegetable sources, as well as in fish oils (1). Clinical trials incorporating increased intake of omega-3 polyunsaturated acids as fatty fish, components of a “Mediterranean” diet, or fish oil capsules suggest that omega-3 fatty acids reduce sudden death and overall death in persons with coronary artery disease (1). High intake of omega-3 fatty acids can cause excessive bleeding. Some types of fish can contain methylmercury, dioxin, and other environmental toxins (2). EPA= eicosapentaenoic acid DHA= docosahexaenoic acid Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. Kris-Etherton PM, et al. Omega-3 fatty acids and cardiovascular disease. Aterioscler Thromb Vasc Biol 2003;23:151-152.

26. Cardiac Rehabilitation A comprehensive risk reduction regimen should be recommended to women with recent acute coronary syndrome or coronary intervention, new-onset or chronic angina, recent cerebrovascular event, peripheral arterial disease, or current/prior symptoms of heart failure and an LVEF < 40% Risk reduction regimens may include: Cardiac or stroke rehabilitation Physician-guided home- or community-based exercise training programs SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501 SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501

27. 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%, if this can be accomplished without significant hypoglycemia SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

28. 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) Thiazide diuretics should be part of the drug regimenfor most patients unless contraindicated, or unless compelling indications exist for other agents For high risk women, initial treatment should be with a beta-blocker or angiotensin converting enzyme inhibitor or angiotensin receptor blocker SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. These guidelines were adopted from the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure, (JNC 7), published in 2004. Systolic BP is often more difficult to control, but is more of a CVD risk factor in those over age 50 (1). Both systolic and diastolic BP need to be treated to goal levels (1). (1)Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adults Treatment Panel III), NIH, NHLBI, 2002. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. These guidelines were adopted from the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure, (JNC 7), published in 2004. Systolic BP is often more difficult to control, but is more of a CVD risk factor in those over age 50 (1). Both systolic and diastolic BP need to be treated to goal levels (1). (1)Third Report of the National Cholesterol Education Program (NCEP) Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adults Treatment Panel III), NIH, NHLBI, 2002.

29. Lifestyle Approaches to Hypertension in Women SLIDE SOURCE: The Seventh Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure. U.S. Department of Health and Human Services. National Institutes of Health. National Heart, Lung, and Blood Institute, NIH Publication No. 04-5230, 2004, Sacks FM, et al. Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet. N Eng J Med 2001 344:3-10., Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE SOURCE: The Seventh Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure. U.S. Department of Health and Human Services. National Institutes of Health. National Heart, Lung, and Blood Institute, NIH Publication No. 04-5230, 2004, Sacks FM, et al. Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet. N Eng J Med 2001 344:3-10., Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

30. Lipids Optimal levels of lipids and lipoproteins in women are as follows (these should be encouraged in all women with lifestyle approaches): LDL < 100mg/dL HDL > 50m/dL Triglycerides < 150mg/d Non-HDL (total cholesterol minus HDL) < 130mg/d SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

31. 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 SLIDE INFORMATION SOURCE: Maron DJ. The epidemiology of low levels of high-density lipoprotein cholesterol in patients with and without coronary artery disease. Am J Cardiol 2000; 86:11L-14L. SLIDE INFORMATION SOURCE: Maron DJ. The epidemiology of low levels of high-density lipoprotein cholesterol in patients with and without coronary artery disease. Am J Cardiol 2000; 86:11L-14L.

32. 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 SLIDE INFORMATION SOURCES: Keil U. Coronary artery disease: the role of lipids, hypertension, and smoking. Basic Res Cardiol 2000; 95: I/52-I/58; Carr MC, et al. Changes in LDL density across the menopausal transition. J Investig Med 2000; 48: 245-250., Hokanson JE, Austin MA, Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996; 3: 213-219. SLIDE INFORMATION SOURCES: Keil U. Coronary artery disease: the role of lipids, hypertension, and smoking. Basic Res Cardiol 2000; 95: I/52-I/58; Carr MC, et al. Changes in LDL density across the menopausal transition. J Investig Med 2000; 48: 245-250., Hokanson JE, Austin MA, Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996; 3: 213-219.

33. Lipids In high-risk women or when LDL is elevated: Saturated fat < 7% of calories Cholesterol < 200mg/day Reduce trans-fatty acids Major dietary sources are foods baked and fried with partially hydrogenated vegetable oil SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115::1481-501. In all women with an elevated LDL cholesterol level, therapeutic lifestyle changes should be instituted (1) Trans-fatty acids should provide less than 1% of energy (1) (1) Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115::1481-501. In all women with an elevated LDL cholesterol level, therapeutic lifestyle changes should be instituted (1) Trans-fatty acids should provide less than 1% of energy (1) (1) Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

34. 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 SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

35. SLIDE INFORMATION SOURCE: Grundy SM, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239. In July, 2004, some elements of the Adult Treatment Panel III were revisited, based on the completion of five clinical trials of cholesterol-lowering statin treatment that have been conducted since the release of the previous guidelines (1). Lifestyle changes are still emphasized, including the adoption of a low saturated fat and low cholesterol diet, increased physical activity and weight control (1). The update offers options for more intensive lowering of cholesterol levels for people at very high risk(1). (1) Grundy SM, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239. SLIDE INFORMATION SOURCE: Grundy SM, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239. In July, 2004, some elements of the Adult Treatment Panel III were revisited, based on the completion of five clinical trials of cholesterol-lowering statin treatment that have been conducted since the release of the previous guidelines (1). Lifestyle changes are still emphasized, including the adoption of a low saturated fat and low cholesterol diet, increased physical activity and weight control (1). The update offers options for more intensive lowering of cholesterol levels for people at very high risk(1). (1) Grundy SM, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239.

36. 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 < 100mg/dL Consider statin, even if LDL < 100mg/dL Optional LDL goal of < 70mg/dL per ATP III 2004 update SLIDE INFORMATION SOURCE: Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239. A new category of “very high risk” was added in the update to ATP III in 2004(1). ATP III was updated based on the publication of five major clinical trials of statin therapy(1). For women determined to be in a this “very-high risk” category lowering the LDL cholesterol to less than 100mg/dl, and as low as 70 mg/dl, may be considered (1) (1) Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239. SLIDE INFORMATION SOURCE: Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239. A new category of “very high risk” was added in the update to ATP III in 2004(1). ATP III was updated based on the publication of five major clinical trials of statin therapy(1). For women determined to be in a this “very-high risk” category lowering the LDL cholesterol to less than 100mg/dl, and as low as 70 mg/dl, may be considered (1) (1) Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239.

37. High Risk Women > 20% 10-year risk of CHD CHD, large vessel atherosclerotic disease, DM Goal LDL < 100mg/dL, consider statin even if LDL< 100 mg/dL SLIDE INFORMATION SOURCES: Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239 SLIDE INFORMATION SOURCES: Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239

38. At-Risk Women: Multiple or Severe Risk Factors, 10-20% 10-Year CHD Risk Initiate drug therapy if LDL > 130 mg/dL after lifestyle therapy Goal LDL < 100 mg/dL, consider drug therapy if LDL = 100 mg/dL SLIDE INFORMATION SOURCES: Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239; Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501 SLIDE INFORMATION SOURCES: Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239; Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501

39. At-Risk Women: Multiple Risk Factors, 10-Year CHD Risk < 10% Initiate drug therapy if LDL > 160 mg/dL after lifestyle therapy SLIDE INFORMATION SOURCES: Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239; . Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501 SLIDE INFORMATION SOURCES: Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239; . Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501

40. At-Risk Women: No Other Risk Factors, 10-Year CHD Risk < 10% Initiate drug therapy if LDL > 190 mg/dL after lifestyle therapy Drug therapy optional for LDL 160-189 mg/dL after lifestyle therapy SLIDE INFORMATION SOURCES: Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239; . Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501 SLIDE INFORMATION SOURCES: Grundy SM, et al.NECP Report: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227-239; . Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501

41. Race/Ethnicity and Diabetes At high risk: Latinas American Indians African Americans Asian Americans Pacific Islanders SLIDE SOURCE: American Diabetes Association. Screening for Diabetes. Diabetes Care 2001; 24 Suppl 1:521-4; www.diabetes.org accessed on March 8, 2005. Women of color are at particularly high risk for type 2 diabetes(1). Recommendations for screening for type 2 diabetes can be found at the web site of the American Diabetes Association. (1) www.diabetes.org accessed on March 8, 2005 SLIDE SOURCE: American Diabetes Association. Screening for Diabetes. Diabetes Care 2001; 24 Suppl 1:521-4; www.diabetes.org accessed on March 8, 2005. Women of color are at particularly high risk for type 2 diabetes(1). Recommendations for screening for type 2 diabetes can be found at the web site of the American Diabetes Association. (1) www.diabetes.org accessed on March 8, 2005

42. Preventive Drug Interventions Aspirin – High risk women 75-325 mg/day, or clopidogrel if patient intolerant to aspirin, should be used in high-risk women unless contraindicated Aspirin- Other at-risk or healthy women Consider aspirin therapy (81 mg/day or 100 mg every other day) if blood pressure is controlled and benefit is likely to outweigh risk of GI side effects and hemorrhagic stroke Benefits include ischemic stroke and MI prevention in women aged > 65 years, and ischemic stroke prevention in women < 65 years SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

43. Interventions that are not useful/effective and may be harmful for the prevention of heart disease Postmenopausal hormone therapy and selective estrogen receptor modulators Antioxidants Folic acid supplementation SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501.

44. Interventions that are not useful/effective and may be harmful for the prevention of heart disease Hormone therapy and selective estrogen-receptor modulators (SERMs) should not be used for the primary or secondary prevention of CVD SLIDE INFORMATION SOURCE:Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. Both the American College of Obstetricians and Gynecologists (ACOG) and the United States Food and Drug Administration (FDA) have concluded that hormone therapy should not be initiated or continued to prevent CVD in post-menopausal women(1,2). The RUTH trial (Raloxifene Use for the Heart) found that raloxifene did not significantly affect the risk of CHD or stroke, but did find an association between the use of raloxifene and fatal stroke, compared to placebo (hazard ratio 1.49, confidence interval 1.00-2.24) (3). (1) American College of Obstetricians and Gynecologists Task Force for Hormone Therapy. Executive summary. Obstet Gynecol 2004; 104(4 Suppl): 1S-4S. FDA approves new labels for estrogen and estrogen plus progestin therapies for postmenopausal women following review of Women’s Health Initiative data. Rockville, Md: Food and Drug Administration, January 8, 2003. Barrett-Connor E,, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women N Engl J Med 2006; 355: 125-37. SLIDE INFORMATION SOURCE:Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481-501. Both the American College of Obstetricians and Gynecologists (ACOG) and the United States Food and Drug Administration (FDA) have concluded that hormone therapy should not be initiated or continued to prevent CVD in post-menopausal women(1,2). The RUTH trial (Raloxifene Use for the Heart) found that raloxifene did not significantly affect the risk of CHD or stroke, but did find an association between the use of raloxifene and fatal stroke, compared to placebo (hazard ratio 1.49, confidence interval 1.00-2.24) (3). (1) American College of Obstetricians and Gynecologists Task Force for Hormone Therapy. Executive summary. Obstet Gynecol 2004; 104(4 Suppl): 1S-4S. FDA approves new labels for estrogen and estrogen plus progestin therapies for postmenopausal women following review of Women’s Health Initiative data. Rockville, Md: Food and Drug Administration, January 8, 2003. Barrett-Connor E,, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women N Engl J Med 2006; 355: 125-37.

45. Menopausal Hormone Therapy, SERMs and CVD: Summary of Major Randomized Trials Use of estrogen plus progestin associated with a small but significant risk of CHD and stroke Use of estrogen without progestin associated with a small but significant risk of stroke Use of all hormone preparations should be limited to short term menopausal symptom relief Use of a selective estrogen receptor modulator (raloxifene) does not affect risk of CHD or stroke, but is associated with an increased risk of fatal stroke SLIDE INFORMATION SOURCES: Hulley S, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998; 280 :605;613.; Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 2002; 288:321-333.; Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004; 291:1701-1712.,;ACOG Task Force for Hormone Therapy. Summary of Balancing Risks and Benefits. Obstet Gynecol 2004; 104 (4 Suppl): 1S-129S; Barrett-Connor E, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women N Engl J Med 2006; 355: 125-37. SLIDE INFORMATION SOURCES: Hulley S, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998; 280 :605;613.; Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 2002; 288:321-333.; Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004; 291:1701-1712.,;ACOG Task Force for Hormone Therapy. Summary of Balancing Risks and Benefits. Obstet Gynecol 2004; 104 (4 Suppl): 1S-129S; Barrett-Connor E, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women N Engl J Med 2006; 355: 125-37.

46. Raloxifene Use for the Heart (RUTH) Trial: Primary and Secondary CVD Outcomes SLIDE INFORMATION SOURCE: Barrett-Connor E, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006; 355: 125-37. The RUTH trial randomized 10,101 postmenopausal women with a mean age of 67. 5 years to the selective estrogen receptor modulator (SERM) raloxifene 60 mg daily, or placebo. Median follow-up was 5.6 years. Raloxifene had no significant effect on primary coronary events, CHD fatality, or strokes. Raloxifene use was associated with an increase in fatal stroke and venous thromboembolism that reached statistical significance. Raloxifene reduced the risk of invasive breast cancers and vertebral fractures. (1) (1) Barrett-Connor E, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006; 355: 125-37. SLIDE INFORMATION SOURCE: Barrett-Connor E, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006; 355: 125-37. The RUTH trial randomized 10,101 postmenopausal women with a mean age of 67. 5 years to the selective estrogen receptor modulator (SERM) raloxifene 60 mg daily, or placebo. Median follow-up was 5.6 years. Raloxifene had no significant effect on primary coronary events, CHD fatality, or strokes. Raloxifene use was associated with an increase in fatal stroke and venous thromboembolism that reached statistical significance. Raloxifene reduced the risk of invasive breast cancers and vertebral fractures. (1) (1) Barrett-Connor E, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006; 355: 125-37.

47. Interventions that are not useful/effective and may be harmful for the prevention of heart disease Antioxidant vitamin supplements (eg, vitamin E, C, and beta carotene) should not be used for the primary or secondary prevention of CVD Folic acid, with or without B6 and B12 supplementation, should not be used for the primary or secondary prevention of CVD SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007:;115: 1481-501. The Women’s Health Study, a 10-year randomized double-blind, placebo controlled trial of nearly 40,000 healthy women aged 45 years and older showed no cardiovascular benefit or risk to vitamin E supplementation (600 IU every other day)(1). The HOPE and HOPE-TOO trials performed in patients with CHD equivalent risk also found no benefit(2). Multiple trials have shown no CHD benefit or a trend to harm for folic acid supplementation in patients with coronary artery disease or significant CHD risk(3)(4). (1)Lee IM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer. JAMA 2005; 294:56-65. (2) Lonn E, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer. JAMA 2005;293:1338-1347. (3) Bonaa KH et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354:1578-88. (4) Loscalzo J. Homocysteine trials – clear outcomes for complex reasons. N Engl J Med 2006; 354:1629-1632. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007:;115: 1481-501. The Women’s Health Study, a 10-year randomized double-blind, placebo controlled trial of nearly 40,000 healthy women aged 45 years and older showed no cardiovascular benefit or risk to vitamin E supplementation (600 IU every other day)(1). The HOPE and HOPE-TOO trials performed in patients with CHD equivalent risk also found no benefit(2). Multiple trials have shown no CHD benefit or a trend to harm for folic acid supplementation in patients with coronary artery disease or significant CHD risk(3)(4). (1)Lee IM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer. JAMA 2005; 294:56-65. (2) Lonn E, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer. JAMA 2005;293:1338-1347. (3) Bonaa KH et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354:1578-88. (4) Loscalzo J. Homocysteine trials – clear outcomes for complex reasons. N Engl J Med 2006; 354:1629-1632.

48. The NORVIT Trial: Homocysteine Lowering Did Not Reduce Cardiovascular Events in Women with Prior MI SLIDE INFORMATION SOURCE: Bonaa, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354:1578-88. In this study, which included 978 women, patients were randomized within 7 days of acute myocardial infarction to receive one of four daily treatments: 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6; 0.8 mg of folic acid and 0.4 mg of vitamin B12; 40 mg of vitamin B6; or placebo. Although mean total homocysteine levels were lowered by 27 percent among patients who received folic acid plus vitamin B12, there was no effect on a composite endpoint of recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease (1). (1) Bonaa, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354:1578-88. SLIDE INFORMATION SOURCE: Bonaa, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354:1578-88. In this study, which included 978 women, patients were randomized within 7 days of acute myocardial infarction to receive one of four daily treatments: 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6; 0.8 mg of folic acid and 0.4 mg of vitamin B12; 40 mg of vitamin B6; or placebo. Although mean total homocysteine levels were lowered by 27 percent among patients who received folic acid plus vitamin B12, there was no effect on a composite endpoint of recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease (1). (1) Bonaa, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354:1578-88.

49. Stratify women into high, at risk, and optimal risk categories Encourage lifestyle approaches Treat hypertension, lipid abnormalities, and diabetes Implement pharmacologic interventions for women at high and intermediate risk, pharmacologic interventions may be appropriate for some lower risk women Avoid initiating therapies without benefit, or where risks outweigh benefits SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007: 115: 1481-501. SLIDE INFORMATION SOURCE: Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007: 115: 1481-501.

50. The Heart Truth Professional Education Campaign Website Information for healthcare providers, including links to resources discussed in this presentation, are available at this site. Also included are links to web-based CME, and resources for health care professional educators, including slide sets and problem-based learning and standardized patient cases. Information for healthcare providers, including links to resources discussed in this presentation, are available at this site. Also included are links to web-based CME, and resources for health care professional educators, including slide sets and problem-based learning and standardized patient cases.