Primary Care Congress for Cardiometabolic Health 213 Coronary Artery Disease in : Clinical Perspectives JoAnn E. anson, D, DrPH, AHA Chief, Division of Preventive edicine Brigham and 's Hospital Professor of edicine and the ichael and Lee Bell Professor of 's Health Harvard edical School Conflict of Interest Disclosure JoAnn E. anson, D, DrPH, has no real or apparent conflicts of interest to report. Cardiometabolic Congress Boston, assachusetts April 24, 213 Objectives To describe the major risk factors for CVD in women. To review key gender differences in risk factors. To summarize changes in risk factors during the life cycle, especially at the menopause transition. To review (briefly) clinical trial findings on menopausal hormone therapy, aspirin, and calcium/vitamin D. Cardiovascular Disease: The Leading Cause of Death in US (26 data) Heart disease Cerebrovascular disease Lung cancer COPD Unintentional Injuries Breast Cancer Diabetes Influenza/Pneumonia otor vehicle Accidents 25.5 23.5 2.1 15.5 8.8 42.6 4. 35.9 162.2 25 5 75 1 125 15 175 2 Deaths (1,) National Center for Health Statistics. Health, United States, 29: With Special eature on edical Technology. Hyattsville, D. 21. Prevalence of CVD by Age and Sex ale emale Percent of Population 8 7 6 5 4 3 2 1 18-19 2-29 3-39 4-49 5-59 6-69 7-79 8+ NHANES III 1988-1991 Copyright 213 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any 1
Primary Care Congress for Cardiometabolic Health 213 Nurses' Health Study: Preventability of Heart Disease, Stroke, and Type 2 Diabetes Percentage of US Adults Classified as Obese (BI >3) in Health Surveys from 1963-21 With lifestyle modifications*: 4 CHD Stroke Diabetes 35 3 en Risk Reduction (%) -2-4 -6-8 -1 NEJ 2; 343:16-22; NEJ 21; 345:79-7. -83% -81% -9% * Physical activity, not smoking, weight control, healthy diet (high in whole grains, fiber, fruit/veg, fish, low in saturated fat) 25 2 15 1 5 NHES I NHANES I NHANES II NHANES III NHANES NHANES NHANES NHANES (1963-7) (1971-74) (1976-8) (1988-94) (1999-22) (23-4) (27-8) (29-1) NHES indicates National Health Examination Survey; NHANES, National Health and Nutrition Examination Survey. Sources: legal K, et al. JAA 22; 288:1723-7; JAA 26; 295:1549-55; JAA 21; 33:235-41; JAA 212; 37:491-7. Percent of U.S. adults Engaging in Regular Leisure-time Physical Activity,* by Gender and Age 5 4 en 3 2 1 18-24 25-44 45-64 65-74 75+ * Regular activity = light-to-moderate activity >5 times/week for 3 minutes each time, or vigorous activity >3 times/week for >2 minutes each time. Reference: Schoenborn CA, Barnes P. Leisure-time physical activity among adults: United States, 1997-98. NCHS, 22. Percentage of the Decrease in U.S. Deaths from CHD Attributed to Treatments and Risk-actor Changes The Interheart Study Treatment Risk actors Unexplained 43 5 7 Case-control study of 15, patients with first I compared to 15, age, sex matched healthy controls. 2 4 6 8 1 Source: ord ES et al. N Engl J ed 27; 356:2388-2398. Source: Yusuf. Lancet 24. Copyright 213 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any 2
Primary Care Congress for Cardiometabolic Health 213 INTERHEART: Association of Risk actors with Acute I in And en Lifetime Risk for CVD by Risk actors at Age 5 Risk actor Gender Odds Ratio (99% CI) Current smoking Diabetes Hypertension Abdominal obesity Psychosocial index ruits/vegetables Exercise Alcohol ApoB-ApoA1 ratio Adjusted for age, sex, geographic region Note: odds ratio plotted on a doubling scale.25.5 1 2 4 8 Source: Yusuf S et al. Lancet. 24;364:937-52. Adjusted Cumulative Incidence en.7.6.5.4.3.2.1 5 6 7 8 9 Source: Lloyd-Jones, Circulation 26. 69% 5%.7.6 5% 5%.5 46%.4 39% 36%.3 27%.2.1 Attained Age 2 ajor Rs 1 ajor R 1 Elevated R 1 Not Optimal R Optimal Rs 5 6 7 8 9 8% SWAN Allows Us to Anchor Our Observations to the inal enstrual Period (P). A Steep Rise In LDL Occurs within One Year of the P Source: atthews JACC 29; 54:2366. % of ean Level During Premenopause % of ean Level During Premenopause 11 1 9 11 1 9 Total-C -24-18 -12-6 6 LDL-C enopause Source: Jensen et al. aturitas 199; 12:321-331. Change in Lipids After enopause -24-18 -12-6 6 N=1 onths 11 1 9 1 9 HDL-C enopause -24-18 -12-6 6 Triglycerides 11-24 -18-12 -6 6 onths SWAN Shows A Rise In at ass With The P SWAN: Progression of Subclinical CVD During Late Perimenopause Annual Rates of Change in Carotid IT in Pre, Early peri, Late peri, and Postmenopausal stages*.25 a,b.2 IT progression rate (mm/year).15.1.5 Premenopause Early perimenopause Late perimenopause Postmenopause * Adjusted for age at baseline and race a Rate of change in late peri significantly differs from that in premenopausal stage, P<.5 b Rate of change in late peri significantly differs from that in early peri menopausal stage, P.5 Source: Sowers et al. JCE 27; 92: 895 91. El Khoudary SR, Wildman RP, atthews KA, Thurston RC, Bromberger JT, Sutton Tyrrell K. enopause In Press Copyright 213 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any 3
Primary Care Congress for Cardiometabolic Health 213 8 7 6 5 4 3 2 1 Diabetes and Risk of CHD ortality en Diabetic en - 2-3 fold risk Diabetic - 3-7 fold risk Lipid Lowering and CHD Risk Reduction in Diabetes Scandinavian Simvastatin Survival Study (4S): 54% reduction in CHD events in D subjects randomized to simvastatin vs. controls (32% risk reduction in nondiabetic subjects). All cause mortality: reduction of 43% for D subjects and 28% for non-d. CARE Study (Pravastatin after I in subjects with average cholesterol levels): 25% reduction in CHD among D subjects and 23% reduction in non-d. Helsinki Heart Study (Gemfibrozil) Similar risk reductions in } ACAPS/TexCAPS (Lovastatin) D and non-d United Kingdom Prospective Diabetes Study (UKPDS) Predictors of irst Coronary Events 1) LDL cholesterol <.1 2) HDL cholesterol <.1 3) HbA1c.2 4) Systolic BP.6 5) Smoking.56 Pregnancy: A Stress Test for the Cardiovascular System Pregnancy: metabolic syndrome-like state. predisposed to etsyn develop gestational hypertension or gestational diabetes. Pregnancy induced risk factors often re-emerge later in life. ortality from CVD in later life is increased by these conditions. 2.71-fold higher mortality in women who had a preterm delivery and pre-eclampsia. Source: Stratton et al. BJ 2; 321:45-12 Current Opinion in Obstetrics and Gynecology 23, 15:465 471. Lipids and Coronary Heat Disease (CHD): Gender Differences Effects on major Vascular Events per 1. mmol/l Reduction in LDL Cholesterol at Different Levels of Risk, by Gender 5-year VE Risk Events (% per annum) Trend at Baseline Statin/more Control/less Test RR (CI) per 1. mmol/l reduction in LDL cholesterol LDL cholesterol: HDL cholesterol: Triglycerides: Stronger predictor of CHD risk in men than women Stronger predictor of CHD risk in women than men Stronger predictor of CHD risk in women than men Source: Cholesterol Treatment Trialists Collaborators. Lancet 212; 38(9841) supplementary appendix. Copyright 213 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any 4
Primary Care Congress for Cardiometabolic Health 213 Risk of Heart Attack: Smokers vs Ex-smokers Relative Risk Estimate* AHA Guidelines 4 3 2 Current Smokers ales emales Ex-smokers Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in 211 Update: A guideline from the American Heart Association 1 1-2 2-3 3-4 Years Since Quitting osca L, Benjamin EJ, Berra K, et al. J Am Coll Cardiol 211;57:144-23 and Circulation 211;123:1243-1262 * 1. represents no increased risk compared with lifetime nonsmokers. Source: Rosenberg NEJ; 1985 & 199. Ideal Cardiovascular Health (all are required!) Total cholesterol < 2 mg/dl (untreated) BP < 12/8 mmhg (untreated) asting blood glucose < 1 mg/dl (untreated) Body mass index < 25 kg/m2 Abstinence from smoking Physical activity at goal for adults > 2 years of age >15 min/week moderate intensity >75 min/week vigorous activity or combination Healthy diet (DASH or similar) But fewer than 4% of women meet these criteria! WHI Estrogen+Progestin Trial indings, July 22 (mean follow-up 5.2 yrs) Risks Coronary Heart Disease 29% Stroke 41% Pulmonary Embolism 113% Breast Cancer 26% STOPPED Early, Clear Harm Stopped 3.3 years early Adapted from: Writing Group for the s Health Initiative. JAA 22;288:321-333. Benefits Hip racture 34% Colorectal Cancer 34% Threshold Level WHI Estrogen-Alone and Health Outcomes (N=1,739; mean age 63.6 yrs; mean follow-up 6.8 yrs) Relative Risks and 95% CI* for Selected Health Outcomes by Years Since enopause in the WHI Trials of Hormone Therapy (E+P and E-Alone) Risks Stroke 39% Null CHD (.91) Pulm Emb (1.34) Breast Cancer (.77) Colorectal Cancer (1.8) Total ortality (1.4) Global Index (1.1) Benefits Hip racture 39% By years since menopause: CHD <1 y 1-19 y 2+ y Total mortality <1 y 1-19 y 2+ y Global index <1 y 1-19 y 2+ y.76 1.1 1.28.76.98 1.14 1.5 1.12 1.9 p=.2 p=ns p=ns STOPPED Early Source: JAA 24; 291:171-12. Stopped 1 year early Threshold Level.2.7 1 1.2 1.7 2.2 * Confidence intervals plotted as error bars. p values for trend. The global index is a composite outcome of CHD, stroke, PE, breast cancer, colorectal cancer, endometrial cancer (estrogen+progestin trial only), hip fracture, and mortality. Source: Rossouw JE, et al. JAA 27;297:1465-1477. Copyright 213 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any 5
Primary Care Congress for Cardiometabolic Health 213 Hormone Therapy (HT) Decision-aking lowchart CHD Risk Over 1 Years (ramingham CHD Risk Score) Significant symptoms of menopause (moderate-to-severe hot flashes, night sweats)? No Assess CHD risk and years since last menstrual period Years Since Last enstrual Period <5 6 to 1 >1 Very low (<5%) HT OK HT OK Low (5% to <1%) HT OK HT OK (Choose transdermal) oderate (1% to 2%) HT OK HT OK (Choose transdermal) (Choose transdermal) High (more than 2%) Yes ree of contraindications to HT and no h/o CHD, stroke, or TIA? AND No increased risk of stroke (<1% by ramingham Stroke Score)? Yes DECISION ABOUT DURATION O USE: continued moderate-to-severe symptoms; patient preference; weigh baseline risks of breast cancer vs osteoporosis No Antiplatelet Therapy in Secondary Prevention of CVD Overview of 25 randomized trials (N=29,) Aspirin and/or dipyridamole or sulfinpyrazone 32% reduction in nonfatal I 27% reduction in nonfatal stroke 15% reduction in CVD mortality 25% reduction in total important vascular events Adapted from: J anson and S Bassuk. In: Harrison s Principles of Internal edicine 28 Low-Dose Aspirin in CVD Primary Prevention eta-analysis Aspirin and Primary Prevention of CVD in the WHS According to Age Group+ Infarction yocardial Stroke All Participants.76 (.62.95).97 (.83 1.13) (N=95,456) en.68 (.54.86) 1.13 (.96 1.33) (N=44,114).99 (.83 1.19).81 (.69.96) (N=51,342) 1.8 1.6 1.4 1.2 1..8.6.4.2. 1.1.85 1.23.98.84 1.17.74 Total CVD Stroke I.78.66 45-54 55-64 >65 Age Group (years) P for interaction by age =.5 for total CVD and.3 for I + p for interaction not significant for ramingham CHD Risk Score or Number of CHD Risk actors Source: NEJ 25; 352:1293-34. Source: NEJ 25; 352:1293-34. Calcium and Vitamin D Supplements: Cardiovascular Events by Treatment Group Assignment Acknowledgments Calcium/ Vitamin D Placebo Hazard Ratio P (N=18,176) (N=18,16) (95% CI) Cases Cases yocardial infarction or CHD death 499 475 1.4 (.92-1.18).5 Stroke 362 377.95 (.82-1.1).51 CABG indicates coronary artery bypass grafting. PCI, percutaneous coronary intervention. Number of events do no add up to the totals for categories because some women had >1 event. Colleagues in the s Health Initiative, s Health Study, Nurses Health Study and other research studies. volunteers in research studies. RebeccaThurston, ScD irian Limacher, D Puja ehta, D Karol Watson, D Source: Hsia J, et al. Circulation 27. Copyright 213 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any 6
Primary Care Congress for Cardiometabolic Health 213 Conclusions There is the potential for greater progress in decreasing risk of cardiovascular disease in women. ore attention must be given to: Prevention (incl. behavioral changes) Early detection Aggressive risk factor modification and treatment Copyright 213 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any 7