Cardiovascular Disease in Women Joel Niznick MD FRCPC

Cardiovascular Disease in Women Joel Niznick MD FRCPC © Continuing Medical Implementation …. . . bridging the care gap

Attribution: Some slides adapted from © Continuing Medical Implementation …. . . bridging the care gap

The Heart and Stroke Foundation Fact Sheet –Women • Prevalence – In 2000, 1 in 5 women aged 70 and over were told by a physician that they had heart problems. • Mortality (1999 data) – Coronary artery disease accounted for almost half of all CVD deaths among women. – 9, 038 women died of stroke (8. 5% of all deaths) among women. – More men than women died from coronary artery disease (23, 617 vs. 19, 002) and heart attack (11, 948 vs. 8, 978) – More women than men died from congestive heart failure (CHF) (2, 646 vs. 1, 845). – More women than men died from stroke (9, 038 vs. 6, 371). © Continuing Medical Implementation …. . . bridging the care gap

Risk Factors in Women The Heart and Stroke Foundation Fact Sheet –Women Tobacco Smoking – In 2001, 15% of young women (15 -17 yrs) smoked daily. – In 2001, 16% of women aged 15+ years smoked daily. Physical Inactivity – In 2000, 6 in 10 women were physically inactive. Obesity – In 2000, 14. 2% of women were obese. High Blood Pressure – In 2000, 15. 7% of women aged 20+ reported having high blood pressure. Nutrition: Inadequate Consumption of Vegetables and Fruit – Almost 6 in 10 women consumed less than the recommended amount of vegetables and fruit. © Continuing Medical Implementation …. . . bridging the care gap

© Continuing Medical Implementation …. . . bridging the care gap

© Continuing Medical Implementation …. . . bridging the care gap

Mortality Rates for CVD Declining Faster in Men than Women © Continuing Medical Implementation …. . . bridging the care gap

Mortality Rates in Women Expected to Increase in Next 20 years © Continuing Medical Implementation …. . . bridging the care gap

CAD in Women • Women develop angina about 10 years later and a first MI about 20 years later than men • Women are more likely to have angina than MI as their initial presentation of CAD • Women presenting with acute MI tend to be older and have more co-morbidity • Women are less likely than men to attribute their symptoms to cardiac disease, even in the setting of acute MI © Continuing Medical Implementation …. . . bridging the care gap

Risk Factors in Women -1 Diabetes Mellitus • Diabetes mellitus is a more powerful predictor of CHD risk and prognosis in women than in men • Diabetes is commonly accompanied by other cardiovascular risk factors in women • Diabetes was found to be the only risk factor that distinguished between those with and without angiographic CHD • A history of IDDM is also a strong risk factor in women for death after MI © Continuing Medical Implementation …. . . bridging the care gap

Risk Factors in Women - 2 Hypertension • The prevalence of hypertension reaches 70 to 80 % in women above age of 70 • Hypertension in women is both a strong predictor of coronary risk and more commonly seen in those with CHD • This increase in risk is also seen in premenopausal women in whom the presence of hypertension is associated with up to 10 fold increase in coronary mortality © Continuing Medical Implementation …. . . bridging the care gap

Risk Factors in Women - 3 Smoking • Smoking has been associated with one-half of all coronary events in women • Coronary risk is elevated even in women with minimal use - RR 2. 4 for 1. 4 cigarettes/day ( Douglas and Ginsburg, 1996 ) • Smoking has a more harmful impact on women than on men and that risk increases in direct proportion to the number of cigarettes smoked daily • Smoking carries a particularly high risk in younger women, a population likely to contribute substantially to future burden of CHD © Continuing Medical Implementation …. . . bridging the care gap

Risk Factors in Women – 3 cont’d • Compared with nonsmokers, the incidence of MI was increased 6 -fold in women and 3 -fold in men who smoked at least 20 cigarettes per day • The risk particularly high in younger women – the antiestrogenic effect of cigarette smoking may be one possible explanation for the increased risk of young female smokers (Njolstad et al, 1996) • Smoking is also a powerful risk factor for MI in middleaged women than men • Most of the increased risk induced by smoking dissipates within 2 to 3 years of cessation of smoking © Continuing Medical Implementation …. . . bridging the care gap

Risk Factors in Women – 4 Dyslipidemia • Low HDL, rather than high LDL cholesterol, is more predictive of coronary risk in women • Lipoprotein (a) is a determinant of CHD ( manifested as angina or MI) in pre-menopausal women and postmenopausal women under age 66 (OR 5. 1 and 2. 4, respectively ) • The total cholesterol concentration appears to be associated with CHD only in pre-menopausal women or at high levels • Triglycerides appear to uniquely influence coronary risk in older women, especially at levels above 400 mg/dl (4. 5 mmol/L) © Continuing Medical Implementation …. . . bridging the care gap

Influence of Hormonal Status • CHD is unusual in pre-menopausal women, particularly in absence of other risk factors • If pre-menopausal women develop CHD, the disease tends to be more extensive and diffuse than in men of the same age • Surgical menopause, with or without hormone replacement, carries an added risk of CHD, in excess of that noted for natural menopause • The loss of estrogen causes increase in LDL cholesterol, total cholesterol, TGs and decrease in HDL cholesterol © Continuing Medical Implementation …. . . bridging the care gap

Estrogen Replacement Therapy (ERT): Benefits and Risks - 1 • Normal menopause ~age 51(95% age 45 -55) • ERT best therapy for peri-menopausal symptoms – Duration 6 months to 4 -5 years • Observational studies suggested benefit of ERT or combined estrogen-progestin (HRT) on risk of CHD and development of osteoporosis • Women’s Health Initiative (WHI) July 2002 discounted benefit of HRT for cardiac prevention © Continuing Implementation ERT and. Medical CV Risk I in Up. To. Date, Rose. BD …. . . bridging the 2004 care gap (ed), Wellesley, MA

Estrogen Replacement Therapy (ERT): Benefits and Risks - 2 WHI Studies • Combined estrogen/progestin replacement 1 – > 16, 000 post menopausal women age 50 -79 – Terminated early with average f/u 5. 2 years – Increased risk breast cancer, stroke, CHD (HR 1. 24) and VTE • Unopposed estrogen trial 1 – > 11, 000 women with prior hysterectomy – Received unopposed estrogen – Study discontinued early due to increased risk of stroke and no projected overall benefit NEJM 2003 Aug 9; 349(6): 523 -341. © Continuing Implementation ERT and. Medical CV Risk I in Up. To. Date, Rose. BD …. . . bridging the 2004 care gap (ed), Wellesley, MA

Estrogen Replacement Therapy (ERT): Benefits and Risks - 3 • HERS I (Heart and Estrogen/Progestin Replacement Study) – 2763 post-menopausal women < 80 with CAD – CEE/progesterone vs placebo – followed for 4 years – No difference in CHD events overall – More CHD events in HRT group in year onetrend to benefit in years 4 -5 © Continuing Implementation ERT and. Medical CV Risk I in Up. To. Date, Rose. BD …. . . bridging the 2004 care gap (ed), Wellesley, MA

Estrogen Replacement Therapy (ERT): Benefits and Risks - 4 • HERS II – Un-blinded follow-up of 93% patients in HERS I for 2. 7 years – No ongoing HRT benefit beyond years 4 -5 – Over 6. 8 years in HERS I & II no benefit of HRT © Continuing Implementation ERT and. Medical CV Risk I in Up. To. Date, Rose. BD …. . . bridging the 2004 care gap (ed), Wellesley, MA

Estrogen Replacement Therapy (ERT): Recommendations • Estrogen-progestin therapy should not be prescribed for primary prevention of CHD. • Estrogen-progestin therapy should be discontinued if an acute CHD event occurs, and should not be resumed as a secondary prevention strategy. • Unopposed estrogen, although it does not appear to increase CHD risk, should not be prescribed for primary prevention because no reduction in CHD risk was observed in the WHI trial. • Estrogen or estrogen-progestin therapy should be reserved for peri-menopausal women with moderate to severe menopausal symptoms. The lowest estrogen dose that relieves symptoms should be used for the shortest duration possible. © Continuing Implementation ERT and. Medical CV Risk I in Up. To. Date, Rose. BD …. . . bridging the 2004 care gap (ed), Wellesley, MA

Women Have An Atypical Clinical Presentation • Typical retrosternal chest pain less common • Atypical symptoms and location – Resting, nocturnal or stress induced chest pain – Jaw, arm, shoulder, back, epigastric discomfort – Dyspnea, palpitations, presyncope – Fatigue, diaphoresis, nausea © Continuing Medical Implementation …. . . bridging the care gap

Gender Bias or Clinical Conundrum? • Women who present to the emergency room with new onset chest pain are approached and diagnosed less aggressively than men • Compared to men women are less likely to: – undergo an EKG, cardiac monitoring or cardiac enzyme measurement – to receive a cardiology consult; be admitted to a coronary care or step down unit • Women are more likely to receive controlled substances and anxiolytics in the ER © Continuing Medical Implementation …. . . bridging the care gap

Comparison of Men and Women in Presentation and Outcome Presentation Comparison Outcome Comparison Angina W>M MI morbidity W > M Atypical CP W>M MI Mortality W > or = M Silent MI W>M CABG Mort. W > or = M Death from MI Sudden death W>M PCI Mortality W > or = M False + TMT W>M AP MI W<M W>M © Continuing Medical Implementation …. . . bridging the care gap

Approach to diagnosis CAD in Women • • Classify the type of pain Assess determinants of likelihood of CAD Select test based on pre-test probability of CAD Confirm or deny presence of CAD with TMT, stress perfusion study or stress echo • High false positive rate TMT rate in premenopausal females (up to 50%) or low pre-test likelihood CAD © Continuing Medical Implementation …. . . bridging the care gap

Classification of Chest Pain Typical angina 1. Steady retrosternal component 2. Provoked by exertion or stress 3. Relieved by rest or NTG Atypical angina – 2 of 3 criteria Non-anginal chest pain – 1 of 3 criteria © Continuing Medical Implementation …. . . bridging the care gap

Prevalence of CAD (%) in Symptomatic Patients According to Age and Sex Typical angina Atypical angina Non anginal chest pain AGE Men Women 30 -39 69. 7 25. 8 21. 8 4. 2 5. 2 0. 8 40 -49 87. 3 55. 2 46. 1 13. 3 14. 1 2. 8 50 -59 92. 0 79. 4 58. 9 32. 4 21. 5 8. 4 60 -69 94. 3 90. 6 54. 6 28. 1 18. 6 3 of 3 criteria 2 of 3 criteria 1) Retrosternal discomfort. 2) Provoked by exercise or stress. 3) Relieved by rest or NTG © Continuing Medical Implementation …. . . bridging the care gap

Determinants of the Likelihood of CAD in Women MAJOR - Post menopausal status / age >65 years - Diabetes - Peripheral Vascular Disease INTERMEDIATE - Hypertension - Smoking - Lipid abnormalities © Continuing Medical Implementation MINOR - Obesity - Sedentary lifestyle - Family history of CAD - Other risks factors of CAD …. . . bridging the care gap

Algorithm for Chest Pain Evaluation in Women Low Probability of CAD (< 20 %) – Consider no test – High likelihood false + result Intermediate Probability of CAD (20 -80%) – Perfusion imaging or stress echo High Risk Probability of CAD (> 80%) – Perfusion imaging or stress echo – Consider direct angiography © Continuing Medical Implementation …. . . bridging the care gap

Comparison of Non-invasive Modalities in the Diagnosis of CAD in Women Sensitivity % Specificity % TMT 61 70 Stress Thallium 78 64 SPECT MIBI 86 80 Stress Echo 86 70 80 (SVD) 91 (MVD) 79 91 90 Dobutamine Echo Rubidium PET Meta-analysis of exercise testing to detect coronary artery disease in women Kwok Y. Kim C. et al Am J Cardiol 1999. Mar 1: 83(5); 660 -6. © Continuing Medical Implementation …. . . bridging the care gap

Indications for Coronary Angiography • High risk stress test – ECG – Hemodynamic • High risk perfusion study – Multiple defects – Severe perfusion defects – TID © Continuing Medical Implementation • • • Ongoing symptoms Unstable angina Post MI angina CHF Vocational indication – Pilots – Truck/bus drivers • Diagnostic uncertainty …. . . bridging the care gap

See Diagnostic Testing 2004 Slideshow © Continuing Medical Implementation …. . . bridging the care gap