Cardiovascular Risk Assessment —Guidelines for Women, Putting it all Together

Suma H. Konety, M.D., M.S. Assistant Professor of Medicine Cardiovascular Division Objectives • Identify 2007 ACC/AHA guidelines for primary prevention of heart disease in women. • Understand the benefits and limitations of current cardiovascular risk scores. • Recognize and evaluate independent risk factors otherwise unaccounted for. The Gender Gap in CVD Mortality

Evidence-based guidelines for prevention in women: 2007 Update

Circulation 2007;115;1481-1501 What changed in the 2007 guidelines? • 2004 guidelines focused on classifying women as being high, intermediate, lower and optimal risk. • In 2007, the revised guidelines recommend a scheme to risk stratify the female patient. • Current guidelines place a greater emphasis on lifetime risk than on short-term absolute risk. • Current guidelines also incorporate more definitive data on hormone therapy, therapy and folic acid therapy. Why is this important? • The average lifetime risk for CVD in women is very high, approaching 1 in 2, so prevention is important in all women. • Women comprise of 52% of US population and are living longer. • Post menopausal women are at greater risk of CAD and today 33 M women are over 55 years of age

Cardiovascular Risk Scores Framingham Risk Score

Optimal risk: <10% Intermediate risk: 10 to 20% High risk: >20% Framingham Risk Score: Advantages

• By assessment of a few readily available clinical and laboratory variables (age, sex, total cholesterol level, HDL-c level, status, and SBP), the 10-year risk of a cardiovascular event can be rapidly and conveniently calculated with a discriminant accuracy of approximately 75%. • It is inexpensive to assess and provides an opportunity to intervene in cases of cigarette smoking and abnormalities in blood pressure and lipid level. Framingham Risk Score: Limitations • Underestimates individual patient risk. – Presence of a single risk factor at 50 years of age is associated with a substantially increased lifetime absolute risk for CVD and shorter survival, but considered low Framingham risk – Lack of inclusion of family history, exercise tolerance, unhealthy lifestyle – Women with subclinical disease (abnormal CAC, cIMT) could be classified as being low risk. Reynolds Risk Score Reynolds Risk Score • Gender-specific tool • Cohort of 25,000 healthy women prospectively followed for 10 years for incident CVD events. • Model was derived from 2/3rds of the cohort and validated on the remaining 1/3rd of the cohort. • Use of the Reynolds's score resulted in risk reclassification in 40% of intermediate FRS women (10-yr risk of 10-20%) Reynolds Risk Score • The outcomes measured to calculate RRS was broader CVD events (, MI, death) compared to the ATP III model (hard CHD end points of MI or coronary death), which could translate into larger 10-year absolute risks and enhanced reclassification. Performance of Reynolds Risk Score in Women • No women were reclassified from low risk (<10%) to high risk (≥20%), which, although difficult to achieve, would provide the greatest clinical value. • Most of the women who were reclassified move to a lower-risk category, a shift that is unlikely to warrant a change in medical therapy. • 54 women reclassified from the 10% to <20% category to the 5% to <10% category, had an event rate of 20.8% (high-risk range). Was the reclassification correct? AHA Guidelines for Screening • Guidelines from the AHA recommend a 10-year risk assessment beginning at age 40 years and repeat assessment every 5 years (or more frequently if risk factors change). • Although no specific risk score is mandated, the general consensus supports the Framingham 10-year CHD score, while acknowledging its limitations in some race and ethnic groups. USPSTF on Adding CRP to Risk Score • A new risk factor should, when added to traditional FRS, reclassify a substantial proportion of originally intermediate-risk persons as high-risk. • In addition, such reclassification should change clinical management that is different than it would otherwise have been, and be effective in reducing the risk for incident CHD. • Although promising evidence indicates that CRP level can be used to correctly reclassify intermediate-risk persons, evidence that changes in CRP level reduce the risk for incident CHD events is insufficient. Multiple biomarkers? An Assessment of Incremental Coronary Risk Prediction Using C-Reactive Protein and Other Novel Risk Markers The Risk in Communities Study Folsom et al. Arch Intern Med. 2006 • Model including the traditional risk factors (age, race, sex, total and HDL-c, SBP, antihypertensive medication use, smoking status and DM) predicted CHD well (AUC=0.8). • CRP level did not significantly add to the AUC (increase in AUC of 0.003). Assessment of Claims of Improved Prediction

Beyond the FRS Tzoulaki I, et al. JAMA, 2009:302 • Most studies examining the additive predictive value of a risk factor with the FRS did so by presenting statistically significant associations with the outcome after the FRS or its components were included in multivariable regression models. • However, a P value alone usually offers weak support for credibility and provides no information on model calibration (ability to predict absolute risk) & discrimination (c statistic, ability to separate those who do and do not experience an outcome) Lifetime CVD Risk

The lifetime risk of atherosclerotic CVD for persons at age 50 years, on average, is estimated to be 52% for men and 39% for women, with a wide variation depending on risk factor burden Cumulative incidence of CVD according to risk factor burden at 50 years of age Which end point should we evaluate? CVD versus CHD? Although many studies are designed using “hard end points” (MI, stroke, and death), the inclusion of “softer” or more subjective end points (such as , claudication, , and revascularizations) are important from a patient’s perspective and policy standpoint. Detrano et al. NEJM 2008:358. Arch Intern Med 2007 Novel Risk Factors Worth Exploring.. • Maternal placental syndromes may be an early indicator of CVD risk. • Obesity, metabolic syndrome may be additive in defining CVD risk in women • Polycystic ovary syndrome - prevalent in 8-10% of women and is associated with cardiometabolic syndrome, DM-type 2 and increased cardiovascular events. • Inflammatory conditions – RA, SLE. Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening? Satta N, et al. BMJ 2002;325 Gestational : a neglected CVD Robbins CL et al. Am J Obstet risk marker Gynecol 2010. Guidelines for Prevention of CVD in Women: Clinical Recommendations Guidelines for Prevention of CVD in Women • Lifestyle interventions: – Cigarette smoking – Physical activity (30 mn of moderate intensity daily exercise) – Rehabilitation (women with recent ACS or PCI, angina, recent CVA, PAD, or current/prior symptoms of heart failure and an LVEF 40%) – Dietary intake (whole-grain, high-fiber foods; consume fish, especially oily fish,* at least twice a week)

– Weight (BMI between 18.5 - 24.9 kg/m2 and a waist circumference 35 in) – Omega-3 fatty acids (as an adjunct to diet, 850 - 1000 mg of EPA and DHA) may be considered in women with CHD, and higher doses (2 to 4 g) may be used for treatment of high triglyceride) – Depression Guidelines for Prevention of CVD in Women • Major risk factor interventions: – Blood pressure • Optimal <120/80 mm Hg • Pharmacotherapy when >140/90 mm Hg and > 130/80 mm Hg in DM and CKD. – Lipids • Optimal - LDL-c <100 mg/dL, HDL-c >50 mg/dL, triglycerides <150 mg/dL, and non–HDL-C (total cholesterol - HDL cholesterol) <130 mg/dL • Pharmacotherapy to achieve LDL-c < 70 mg/dl in women with CHD and high risk, <130 in those with multiple RF. • Consider niacin or fibrate to increase HDL-c after LDL-c is at goal. – • HbA1c <7% Gender and Aspirin Prophylaxis

• Women are at higher risk for stroke earlier in life, whereas men are at higher risk for MI. • Primary prevention trials have demonstrated that aspirin has been effective in the reduction of stroke for women and MI in men. Preventive Drug Interventions – Aspirin, for high risk women • Aspirin 75 to 325 mg/d should be used unless contraindicated. If a high-risk woman is intolerant of aspirin therapy, clopidogrel should be substituted. – Aspirin, for other at-risk or healthy women • In women >65 years of age, (ASA 81 mg daily or 100 mg every other day) if blood pressure is controlled and benefit for ischemic stroke and MI prevention is likely to outweigh risk of gastrointestinal bleeding and hemorrhagic stroke (Class IIa, Level B) • In women <65 years of age when benefit for ischemic stroke prevention is likely to outweigh adverse effects of therapy (Class IIb, Level B). Drug Interventions to Avoid Algorithm for CVD preventive care in women