9/24/2019 Overview • Women and Heart Disease Cardiovascular Health 101 – Facts – Sex-specific risk factors – What is the impact of menopause on CVD risk • CVD Prevention and Menopause, when to recommend: Chrisandra Shufelt MD, MS – Statins Associate Director, Barbra Streisand Women’s Heart Center & Preventive and Rehabilitative Cardiac Center – Aspirin Director, Women’s Hormone and Menopause Program – Blood pressure Associate Professor, Cedars‐Sinai Medical Center Alarming Facts: Cardiovascular Disease in Women Disclosures • No disclosures related to this topic. • CVD remains the leading killer of women in US – Only half of women know CVD is their #1 killer • Funding: NIH/ NHLBI • Nearly every 80 seconds, a woman dies from heart disease – 1 in 8 prior to menopause – 1 in 3 after menopause • Heart disease and stroke kill more women each year than all cancers combined CDC.gov – Heart Disease Facts Benjamin et al. Circulation 2017;135(10):e146‐e603 1
9/24/2019 Incidence of CVD: Relation to Menopause Status Go Red awareness campaign Education, Women’s CVD trials The Framingham Study 7 6.5 Premenopausal 6 (per 1000 women) Postmenopausal 5 Incidence 4.0 4 3.6 3.6 3 2.2 Is this optimal for women? 2.0 ? 2 1 0.6 0.6 0 <40 40–44 45–49 50–54 Age (years) Kannel WB, et al. Ann Intern Med. 1976;85:447-52. Symptoms – Heart Disease Typical in Women Typical in both sexes • Milder symptoms • Pain, pressure, squeezing, or stabbing pain in the chest (without chest pain) • Pain radiating to neck, shoulder, back, arm, or • Sudden onset of weakness, shortness of breath, nausea/ vomiting, indigestion, fatigue, jaw body aches, or overall feeling • Pounding heart, change in rhythm of illness (without chest pain) • Difficulty breathing • Unusual feeling or mild discomfort in the back, • Heartburn, nausea, vomiting, abdominal pain chest, arm, neck, or jaw (without chest pain) • Cold sweats or clammy skin • Dizziness 2
9/24/2019 Gender Differences in Heart Attack Symptoms 60 Men n=127 P =0.032 50 Women n=90 P =0.012 Patients (%) 40 P =0.040 P =0.581 30 P =0.071 P =0.235 P =0.085 20 10 0 Dyspnea Nausea/ Indigestion Dizziness/ Fatigue Sweating Arm/shoulder vomiting fainting pain Women have more symptoms overall Women also have more atypical symptoms Aggarwal et al. Circ Cardiovasc Qual Outcomes; Feb 2018. Milner KA et al. Am J Cardiol . 1999;84:396-399. Who should take a statin for CVD Traditional CVD Risk Factors & Women prevention? Aggarwal, NR et al. Circ Cardiovasc Qual Outcomes. 2018;11:e004437. 3
9/24/2019 Use the new AHA/ACC Blood Cholesterol Guideline Algorithm for Primary Prevention to guide management Prevalence of High Serum Cholesterol ACC Risk Calculator Plus to Assess Risk Category 2005-2006 * * Population (%) Total 20- 39y/o > 40-59 y/o > 60 and older High serum total cholesterol = serum total cholesterol > 240mg/dl * Significant difference from men American Heart Association. Heart Disease and Stroke Statistics 2018 Update . Change in Lipids After Menopause ACC/AHA Guidelines: Risk-Enhancers for ASCVD Total-C HDL-C Menopause Menopause % of Mean Level 110 110 • Family history of premature ASCVD Premenopause During • Persistently elevated LDL-C ≥160 mg/dL 100 100 • Chronic kidney disease 90 90 • Metabolic syndrome -24 -18 -12 -6 0 6 -18 -24 -12 -6 0 6 • Conditions specific to women (e.g., gestational diabetes, preeclampsia, LDL-C Triglycerides premature menopause, post-menopausal state) % of Mean Level 110 110 Premenopause • Inflammatory disease (generally more common in women ) During 100 100 • Ethnicity (e.g., South-Asian ancestry) 90 90 -24 -18 -12 -6 0 6 -24 -18 -12 -6 0 6 Months Months Jensen et al. Maturitas. 1990;12:321‐331. 4
9/24/2019 2018 AHA/ACC Guideline on the Management of Available Statins Blood Cholesterol: Primary Prevention High-Intensity Statin Moderate-Intensity Low-Intensity Statin Therapy Statin Therapy Therapy Daily dose lowers LDL- Daily dose lowers Daily dose lowers LDL- LDL-C 190 mg/dL Primary Prevention: C by approximately LDL-C by approximately C by <30% No risk assessment; High-intensity statin Assess ASCVD Risk in Each Age Group ≥50% 30% to <50% Emphasize Adherence to Health Lifestyle Diabetes mellitus and age 40-75 y Atorvastatin 40-80 mg Atorvastatin 10 (20) mg Simvastatin 10 mg Moderate-intensity statin Rosuvastatin (5) 10 mg Pravastatin 10-20 mg Rosuvastatin 20(40) mg Simvastatin 20-40 mg Lovastatin 20 mg Age 0–19 y Age 20–39 y Age 40–75 y & • Lifestyle to prevent or • Estimate lifetime LDL-C 70 to <190 Diabetes mellitus and age 40-75 y Simvastatin 80 mg* Fluvastatin 20-40 mg reduce ASCVD risk risk to encourage mg/dL without Risk assessment to consider high-intensity • Diagnosis of Familial lifestyle to reduce diabetes mellitus Pravastatin 40(80) mg Pitavastatin 1 mg statin Hyper-cholesterolemia ASCVD risk • 10-year ASCVD risk → statin • Consider statin if percent begins risk Lovastatin 40 mg family history discussion Age >75 y premature ASCVD Fluvastatin XL 80 mg Clinical assessment, Risk discussion and LDL-C ≥160 mg/dL Fluvastatin 40 mg bid Class I (Strong). Benefit >>> Risk. Continued on next slide Pitavastatin 2-4 mg Class IIa (Moderate). Benefit >> Risk. Class IIb (Weak). Benefit Risk. Although high TG was noted as a CVD risk factor, treatment of Stone NJ, et al. ACC/AHA 2013 Blood Cholesterol Guidelines. HTG was covered only briefly and prescription omega-3 was not mentioned. (Published simultaneously with REDUCE-IT.) Grundy SM et al. Circulation. 2019;139:e1082-e1143. J Am Cardiol Coll. 2014;63(25):2889-2934. Who should take an Aspirin for 2018 AHA/ACC Guideline on the Management of CVD prevention? Blood Cholesterol: Primary Prevention (con’t) Class I (Strong). Benefit >>> Risk. Class IIa (Moderate). Benefit >> Risk. Class IIb (Weak). Benefit Risk. <5% 5% to <7.5% ≥7.5% to <20% ≥20% “Low Risk” “Borderline Risk” “Intermediate Risk” “High Risk” Risk discussion: Risk discussion: Risk discussion: If risk estimate + risk Risk discussion: If risk enhancers present enhancers favor statin, Emphasize lifestyle to Initiate statin to reduce then risk discussion initiate moderate-intensity reduce risk factors regarding moderate- LDL-C ≥50% statin to reduce LDL-C by intensity statin therapy 30% – 49% If risk decision is uncertain: Consider measuring CAC in selected adults: •CAC = zero (lower risk; consider no statin, unless diabetes, family history of premature CHD, or cigarette smoking are present) •CAC = 1–99 favors statin (especially after age 55) •CAC = 100+ and/or ≥75 th percentile, initiate statin therapy Grundy SM et al. Circulation. 2019;139:e1082-e1143. 5
9/24/2019 Aspirin: Mechanism of Action Women’s Health Study Membrane Phospholipids 39,876 healthy women 100 mg/d aspirin on Arachadonic Acid alternate days or placebo Irreversibly inhibits platelet average age at 55 yrs for 10 yrs Aspirin COX-1 function Aspirin did not lower the risk of MI or cardiovascular death but instead, significantly Prostaglandin H 2 lowered the risk of total stroke by 17% and risk of ischemic stroke by 24% Thromboxane A 2 Prostacyclin women 65+ years had a significant benefit from Platelet Aggregation Platelet Aggregation aspirin with reductions in major CVD events by Vasoconstriction Vasodilation 25%, MI by 35%, and ischemic stroke by 30% Husain S, et al. Circulation. 1998;97:716‐20. Vane JR. Nature. 1971;231:235‐5. Patrono C. NEJM 1994;330:1287‐94. Ridker PM, Cook NR, Lee IM, et al. N Engl J Med. 2005;352:1293‐1304. Aspirin Evidence: Primary Prevention But then came 2018… Physician’s Health Study (PHS) 22,071 male participants randomized to aspirin (325 mg every ARRIVE ASCENT ASPREE other day) followed for an average of 5 years Aspirin + omega 3 or Aspirin vs placebo, Aspirin vs placebo, placebo, n=15,480 n=19,114, one or more n=12,546, diabetes but no CVD, CVD risk factor, 70yrs Moderate risk of CVD age 40 yrs and older and older, • men >55 yrs with >2 No to minimal benefits seen for CVD, with increased risk for major bleeding CVD risk factors • 40% women • 56% women • women>60 yrs with >3 CVD risk factors Aspirin reduces the risk of myocardial Infarction among men Gaziano et al. Lancet. 2018 Aug. //doi.org/10.1016/S0140-6736(18)31924-X CI=Confidence interval, CV=Cardiovascular McNeil JJ, et al. NEJM. 2018;379(16):1509-1518. Source: Steering Committee of the Physicians’ Health Zheng SL, et al. JAMA. 2019;321(3):277-287. Study Research Group. NEJM 1989;321:129-135 6
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