Women and Cardiovascular Disease

1. Women and Cardiovascular Disease 4th Annual Lourdes Cardiology Services Symposium: Cardiology for the Primary Care Physician Rozy Dunham, MD, FACC

2. Man’s Disease? • Heart disease is the leading cause of death for women in the U.S. • 1 in 3 women dies of heart disease, only 1 in 31 of breast cancer • 26% of women >45yo who have an initial MI die within one year compared to 19% of men • Women are more likely to describe chest pain that is sharp, burning, and more frequently have pain in the neck, jaw, throat, abdomen, or back • In 2004, <50% of women recognized heart disease as the #1 killer • In 2011, only 53% of women said they would call 911 first if they thought they were having a heart attack

4. Go Red For Women 2004

5. Objectives • Recognize the impact of cardiovascular disease in women (CHD and Stroke) • Recognize the presentation of heart disease can be different in women as compared to men • Identify risk factors unique to women for both CHD and Stroke • Recognize treatments that are NOT beneficial for CVD prevention in women

6. Guidelines • 1999- First female specific guidelines for heart disease prevention • 2004- Evidence Based Guidelines for Cardiovascular Disease Prevention in Women • 2011-Effectiveness Based Guidelines for Cardiovascular Disease Prevention in Women • 2014- Guidelines for the Prevention of Stroke in Women; a statement from the AHA and ASA

7. 2004 Guidelines • Written in the wake of the Women’s Health Initiative and HERS trial • Need for strategies to prevent heart disease in women

8. 2004 Guidelines • Assess and stratify women into high, intermediate, lower, or optimal risk categories • Lifestyle approaches to prevent CVD for all women and a top priority (smoking cessation, regular exercise, weight management, and heart healthy diet) • Other CVD risk-reducing interventions (BP management, lipid management, DM management) • Higher priority for therapy for highest risk patients • Avoid Class III interventions (not beneficial, may be harmful)

9. Spectrum of Risk • Based on the Framingham Risk Score • No such thing as NO risk • High Risk (>20%): • Established CHD • Cerebrovascular disease • Peripheral arterial disease • AAA • DM • CKD

10. Intermediate Risk (10-20%): • Subclinical CHD (coronary Ca) • Metabolic syndrome • Multiple risk factors (smoking, HTN, HPL, obesity, poor diet, physical inactivity) • Autoimmune collagen vascular disease (SLE, RA) • Family history of early onset CVD • History of preeclampsia, gestational DM, or pregnancy induced HTN)

11. Lower Risk (<10%): • Multiple risk factors, metabolic syndrome, or 1 or no risk factors

12. Optimal Risk (<10%): • Optimal levels of risk factors and heart healthy lifestyle(ideal lipids, HTN, blood glucose, BMI, non-smoker, physically activity, healthy diet)

13. Lifestyle Interventions • Recommended for ALL women • Smoking cessation • Physical activity (30 minutes of moderate-intensity exercise most days of the week) • Cardiac rehab • Heart healthy diet • Weight maintenance/reduction(BMI 18.5-24.9 kg/m2; waist circumference <35 in.) • Psychosocial Factors • Omega 3 fatty-acid supplementation in high risk patients

14. Other Interventions • Optimal BP <120/80 • Lipid Management • DM management

15. Preventive Drug Interventions • ASA for high or intermediate risk patients, or clopidogrel if intolerant of ASA • Beta Blockers in women with h/o MI • ACE in high risk women • ARB in high risk women intolerant of ACE • Warfarin/ASA for a.fib a stroke prevention

16. Class III Interventions • Hormone Therapy (combined estrogen/progestin or unopposed estrogen) should NOT be used for CVD prevention • Antioxidant supplements • ASA for lower risk patients

17. Effectiveness Based Guidelines-2011 Update • Reversing a trend over the last 40 years, CHD death rates in US women 35-54yo appear to be increasing, likely due to the obesity epidemic • Death rates higher in black vs. white women • Leading cause of death in women in every major developed country

19. 2011 Update • Did not endorse routine use of high-sensitivity CRP for screening purposes • Did discuss unique opportunities to assess a women’s risk, like at time of pregnancy • Preeclampsia may be an early indicator of CVD risk

20. Class III Interventions • Hormone therapy, including selective estrogen-receptor modulators, should not be used for primary or secondary prevention of CVD • Antioxidant supplements (vitamin E, C, and beta carotene) should not be used for primary or secondary prevention of CVD • Folic Acid with or without B6 and B12 supplementation should not be used for primary or secondary prevention of CVD • Routine use of ASA for prevention of MI in healthy women <65 yo (ASA can be useful in women >65yo if BP controlled and benefit for ischemic stroke prevention and MI prevention is likely to outweigh risk of GIB and hemmorhagic stroke)

21. Guidelines for the Prevention of Stroke in Women • February 2014 • Stroke accounts for a higher proportion of CVD events than CHD in women (opposite for men) • Lifetime risk of stroke higher in women, mostly because women live longer • 53.5% of new or recurrent strokes occur among women • In 2010, 60% of deaths related to stroke were in women • Majority are ischemic strokes vs. hemorrhagic • Risk factors unique to women

23. Stroke In Pregnancy • Preeclampsia/eclampsiaand pregnancy-induced HTN • Continue to be at high risk for stroke even after birth • ACOG recommends treatment of severe HTN in pregnancy (systolic BP >160 mmHg or diastolic BP>110 mmHg) • Labetolol is first-line therapy • AVOID atenolol, ACE, and ARB

24. Hypertension • History of preeclampsia, eclampsia, pregnancy induced HTN, gestational DM all are associated with a higher risk of CVD and stroke beyond the childbearing years • In one 2012 study, 18.2 % of women with a history of preeclampsia vs. 1.7 % of women with uncomplicated pregnancies had a CVD event in 10 years

25. Recommendations • Women with chronic primary or secondary HTN or previous pregnancy related HTN should take a low dose ASA from the 12th week of gestation until delivery • Calcium supplementation (>1g/day) should be considered for women with low dietary intake of calcium to prevent preeclampsia • Severe HTN in pregnancy should be treated • Consider treatment of moderate HTN • Atenolol, ACE, ARB contraindicated • After birth, women with chronic HTN should continue to be treated and monitored for post-partum preeclampsia • Because of increased risk of future HTN and stroke 1-30 years after delivery in women with a history of preeclampsia, it is reasonable to evaluate and treat for HTN, obesity, smoking, and dyslipidemia

26. Cerebral Venous Thrombosis • Thrombus formation in >1 of the venous sinuses • 0.5%-1% of all strokes • >70% of cases in women • 2 major risk factors include oral contraceptive use and pregnancy

27. Recomendations • Screen and test for prothrombotic conditions • Warfarin for 3-6 months in provoked CVT • 6-12 months in unprovoked CVT • Indefinite anticoagulation for recurrent CVT • In CVT with pregnancy, LMWH throughout pregnancy and >6 weeks post-partum • Future pregnancy not contraindicated • Women with a history of CVT can be treated prophylactically with LMWH during future pregnancies

28. Oral Contraceptive Use • 2.75 fold increase in ischemic stroke with any OC use • Progestogen only OCs revealed no significant increased risk • Overall slightly increased risk of hemorrhagic stroke • Increased risk with obesity, HPL, smoking, HTN, migraine headaches and OC use

29. Recommendations • OCs may be harmful in women with additional risk factors (smoking, prior thromboembolic events) • Among OC users, aggressive therapy of stroke risk factors reasonable • Routine screening for prothrombotic mutations before initiation of OC is NOT useful • Measurement of BP before initiation of OC is recommended

30. Menopause and Post Menopausal HT • Data seems to suggest increased risk of stroke with earlier onset of menopause (before age 42) although evidence is inconsistent • Studies of HT for primary and secondary prevention of stroke have been negative • HERS, WEST, and WHI • HT does not reduce stroke risk and may increase risk

31. Recommendations • HT (conjugated equine estrogen with or without medroxyprogesterone) should not be used for primary or secondary prevention of stroke in post-menopausal women • SERMs, such as raloxifene, tamoxifen, or tibolone, should not be used for prevention of stroke

32. Migraine With Aura • Women are 4 times more likely than men to have migraines • Migraine with aura is associated with double the risk for ischemic stroke • This association is higher in women than men • Risk increases even more with smoking and OC use

33. Recommendations • Treatment to reduce migraine frequency is reasonable as there is an association between higher migraine frequency and stroke risk • Evidence is lacking that treatment reduced risk of first stroke • Strongly recommend smoking cessation in women with migraine and aura

34. Obesity, metabolic syndrome, and lifestyle factors • Prevalence of obesity higher in women than in men • Recommendation are same for men and women: regular physical activity, moderate alcohol consumption, abstention from smoking, and healthy diet

35. Atrial Fibrillation • AF increases with age and women have greater life expectancy • 60% of AF patients >75yo are women • Risk stratification : CHADS2 and CHA2DS2-VASc score • Female sex is an independent predictor of stroke in AF

36. Recommendations • Risk stratify patients • Considering the increased prevalence of AF with age and the higher risk of stroke in elderly women with AF, active screening (age >75) in primary care settings is appropriate • Oral AC in women <65yo with AF alone and no other risk factors is not recommended (CHADS2=0, CHA2DS2-VASc=1). Antiplatelet therapy is a reasonable option • New oral anticoagulants are a useful alternative to warfarin in appropriate patients

37. Strategies For Prevention of Stroke in Women • Management of carotid disease (symptomatic or asymptomatic) same as for men • ASA therapy in women with DM, high-risk patients, and women >65yo if benefit is likely to outweigh the risk

38. Conclusions • Many gaps remain in our knowledge regarding sex differences in CVD and prevention • More awareness among women • Sex specific risk scores necessary • More women need to be represented in clinical trials of CVD • Until then, management remains essentially the same as for men (ASA)