Women and Coronary Artery Disease (CAD).ppt

1、Women and Coronary Artery Disease (CAD),Module 2 Risk Factors and Gender Differences,Supported by an unrestricted educational grant from Fujisawa Healthcare, Inc.,Gender Differences in Atherosclerosis,Women undergoing coronary angiography have more diffuse atherosclerosis measured by IVUS, more tota

2、l compromised lumen adjusted for BSA throughout the arterial tree compared to men (WISE study) Women and men have similar magnitude of atherosclerosis, but it looks and functions differently, possibly for estrogen-related reasons. A consequence of more diffuse atherosclerosis might be more microvasc

3、ular disease (limited flow reserve) that is not due to obvious obstructive disease*,*C. Noel Bairey-Merz. WISE study data ACC 3/2002,Gender Differences in Atherosclerosis,1996 Farb et al: two distinct plaque morphologies in sudden coronary death (SCD) Plaque rupture: thin fibrous cap over a large ne

4、crotic core heavily infiltrated by foamy macrophages: 60% of thrombi in SCD Plaque Erosion: thrombus over a base rich in smooth muscle with a proteoglycan-rich matrix (necrotic core is often absent): 40% of thrombi in SCD,Farb A, et al. Circulation. 1996,Gender Differences in Atherosclerosis,1999 Ar

5、bustini et al: Plaque erosion: major substrate for coronary thrombosis in acute myocardial infarction (MI); 291/298 patients (98% with MI) had coronary thrombi at autopsy Of the 25% of this autopsy cohort with plaque erosion: women = 37% and men = 18%,Arbustini E, et al. Heart. 1999,Gender Differenc

6、es in Atherosclerosis,1998 Burke et al: effect of risk factors on the mechanism of acute thrombosis and SCD in women (N = 51 women died from SCD) Plaque erosion was highly correlated with cigarette smoking and was the most frequent type of coronary thrombosis seen in women 50 years and correlated wi

7、th elevated serum total cholesterol,Burke AP, et al. Circulation. 1998,Gender Differences in Atherosclerosis,Older women who die suddenly of coronary thrombosis or hypercholesterolemia have plaque rupture in contrast to plaque erosion and have severe coronary arterial stenosis and a large burden of

8、calcium plaque Younger women who die suddenly of coronary thrombosis: cigarette smokers, plaque erosion, relatively little coronary arterial narrowing, and less calcium plaque at autopsy,Burke AP, et al. Circulation. 1998,Gender Differences in Atherosclerosis,Potential explanations Estrogen reduces

9、cellular hypertrophy and enhances vessel wall elasticity, possibly contributing to less lumen intrusion for the same amount of atherosclerosis Estrogen reduces smooth muscle cell migration and lower collagen deposition in response to injury, which may lead to thinner fibrous plaque in women Estrogen

10、 and progesterone upregulate degradative collagenases and inflammatory markers (hsCRP),Warning Signs and Symptoms of CAD,Gender Differences in Heart Attack Symptoms,Typical in both sexes Pain, pressure, squeezing, or stabbing pain in the chest Pain radiating to neck, shoulder, back, arm, or jaw Poun

11、ding heart, change in rhythm Difficulty breathing Heartburn, nausea, vomiting, abdominal pain Cold sweats or clammy skin Dizziness,Typical in women Milder symptoms (without chest pain) Sudden onset of weakness, shortness of breath, fatigue, body aches, or overall feeling of illness (without chest pa

12、in) Unusual feeling or mild discomfort in the back, chest, arm, neck, or jaw (without chest pain),Gender Differences in Emergency Department Presentation for CAD Without Chest Pain,Milner KA, et al. Am J Cardiol. 1999,Less Common Heart Attack Symptoms in Women,Milder symptoms without accompanying ch

13、est pain Sudden onset of weakness, shortness of breath, fatigue, body aches, overall feeling of illness Burning sensation in the chest, may be mistaken as heartburn An “unusual” feeling or mild discomfort in the back, chest, arm, neck, or jaw,Women and CAD,Which Risk Factors Predispose Women to CAD?

14、,Major Risk Factorsfor Heart Disease,Grundy SM, et al. Circulation. 1998; Grundy SM. Circulation. 1999 Braunwald E. N Engl J Med. 1997; Grundy SM, et al. J Am Coll Cardiol. 1999,Emerging Risk Factors,Lipoprotein (a) Homocysteine Prothrombotic factors Proinflammatory factors Impaired fasting glucose

15、Subclinical atherosclerosis Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) Abnormal internal or common carotid, ankle-arm index 0.9, coronary Ca2+,Correlation of Electron-Beam Tomography (EBT) Calcium a

16、nd Low Density Lipoprotein (LDL) Cholesterol,Hecht. J Am Coll Cardiol. 2001,r = 0.06, P = 0.49,US Adults With High Blood Pressure (1988-1994),American Heart Association. 2002 Heart and Stroke Statistical Update. 2001,Predicted Cardiac Survival by Peak Systolic Blood Pressure,Shaw LJ. AHA abstract. 2

17、000,US Adults With LDL Cholesterol of 130 mg/dL or Higher (1988-1994),American Heart Association. 2002 Heart and Stroke Statistical Update. 2001,Diabetes and CAD in Women,Diabetes Creates Higher Risks for Women With CAD,65% of diabetics die from heart disease or stroke 4.2 million American women hav

18、e diabetes Diabetes increases CAD risk 3-fold to 7-fold in women vs 2-fold to 3-fold in men Diabetes doubles the risk of second heart attack in women but not in men Every year, heart disease kills 50,000 more American women than men Statistics are particularly high among African American women,Ameri

19、can Heart Association Centers for Disease Control and Prevention Manson JE, et al. Prevention of Myocardial Infarction. 1996,Lowest Survival Rates for Diabetic Women,CAD mortality rates in diabetics, especially women, have not decreased to the same extent as those in the general population In a larg

20、e cohort referred for coronary disease, diabetic women had the highest mortality rates Estimate of ischemic burden with stress myocardial perfusion imaging significantly improved risk stratification in diabetic women compared with clinical risk alone Stratification by the number of ischemic vessels

21、demonstrated a significant linear increase in cardiac events with escalating ischemic burden (sex-diabetes interaction, P = .016),Gu K, et al. JAMA. 1999 Giri S, et al. Circulation. 2002,Giri S, et al. Circulation. 2002,Lowest Survival Rates for Diabetic Women,Diabetes: Powerful Risk Factor for CAD

22、in Women,Framingham Heart Study Women with diabetes mellitus had relative risk of 5.4% for CAD vs women without diabetes Men with diabetes had relative risk of 2.4% Nurses Health Study Relative risk of 6.3% for total cardiovascular (CV) mortality Even if women had diabetes for 4 years, their risk of

23、 CAD was significantly elevated,Kannel W. Am Heart J. 1987 Manson J, et al. Arch Intern Med. 1991,Diabetes Mellitus in US: Higher Mortality Risk in Women,Geiss LS, et al. Diabetes in America (2nd ed). 1995,Diabetes: High Blood Sugar,Diabetes is a abnormally high level of blood sugar (or glucose) ind

24、icating the bodys inability to process glucose 6 million women in the US have physician-diagnosed diabetes 3 million are undiagnosed Risk of death from heart disease is 3 times higher in women with diabetes Diabetes doubles the risk of a second heart attack in women but not in men,Gender Differences

25、 in Risk Factors: Diabetes Mellitus,Far more powerful coronary risk factor for women than men, negating much of the protective effects of the female sex Nurses Health Study: maturity onset diabetes 3- to 7-fold increase in risk of a CV event The coronary prognosis is substantially worse for diabetic

26、 women than diabetic men: diabetic women with MI have doubled the risk of reinfarction and 4-fold likelihood of developing heart failure Coronary revascularization: women diabetics male diabetics (may be a factor in the less favorable outcome of women),Diabetes: A Major Risk Factor for Heart Disease

27、,Majority of people with type 2 (adult-onset) diabetes have additional risk factors for heart disease 2 out of 3 people with diabetes die of some type of cardiovascular disease (CVD) Aggressive therapy for diabetes and high blood pressure is usually needed and can reduce your risk of heart disease a

28、nd its associated complications,Robertson C, RN. 2001; Grundy SM et al. Circulation. 1998; American Heart Association. 2001 Heart and Stroke Statistical Update. 2000; Bakris GL, et al, Am J Kid Dis. 2000,Gender Differences in Risk Factors: Elevated Cholesterol,Secondary prevention 4S trial (Scandina

29、vian Simvastatin Survival Study) 4444 men and women with angina or prior MI randomized to placebo or simvastatin 827 women Overall mortality benefit with a 35% reduction in major cardiac events Primary prevention Observational data: decrease in LDL and increase in high density lipoprotein (HDL) redu

30、ced CAD risk Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS): women experienced a 46% reduction in first major coronary event with an average 25% reduction in LDL cholesterol,Clinical Identification of the Metabolic Syndrome,Abdominal obesity Men102 cm (40 in) Women88 cm (35 in) T

31、riglycerides (TG)150 mg/dL HDL cholesterol Women130/85 mm Hg Fasting glucose110 mg/dL,National Heart, Lung, and Blood Institute,Impact of Triglyceride Levels on Relative Risk of CAD,Castelli WP. Can J Cardiol. 1988,Women and CAD Risk Factors,Higher prevalence of avoidable risk factors1 blood cholest

32、erol physical inactivity overweight (body mass index, 25.0-29.9) Diabetes is a more powerful risk factor for CAD2 3- to 7-fold in women vs 2- to 3-fold in men HDL cholesterol levels more predictive of CAD2 Women counseled less about nutrition, exercise, and weight control2,1. American Heart Associat

33、ion. 1999 Heart and Stroke Statistical Update. 1998 2. Mosca L, et al. Circulation. 1999,Comparison of NCEP ATP-III Scores by EBT Calcium Scores,Hecht HS. J Am Coll Cardiol. 2001,MI or Death Often First Sign of CAD,Levy D, et al. Textbook of Cardiovascular Medicine. 1998,Impact of Cholesterol Levels

34、 on Risk of Death,Neaton JD, et al. Arch Intern Med. 1992,Simvastatin Survival StudySignificant Event* Reduction in Men and Women,-50,-40,-30,-20,-10,0,Women,Men,Percent risk reduction,-35% Women n = 827,-34% Men n = 3,617,P = .01,P .00001,The Scandinavian Simvastatin Survival Study. Lancet. 1994,*I

35、ncludes coronary heart disease (CHD) death; definite or probable nonfatal MI; or resuscitated cardiac arrest. Simvastatin reduced the risk of heart attacks* as effectively for women as for men. Because there were only 53 female deaths, the effect of simvastatin on mortality in women could not be ade

36、quately assessed.,Lovastatin Reduced the Risk of First Acute Major Coronary Events in the AFCAPS Trial,Smoking,Single most preventable cause of death in US Smoking by women causes 150% more deaths from heart disease than lung cancer Women who smoke are 2-6 times more likely to suffer a heart attack

37、Use of birth control pills in smokers compounds cardiac risk,Overweight,American Heart Association. 2002 Heart and Stroke Statistical Update. 2001,Overweight and Obesity in US Adults,American Heart Association. 2002 Heart and Stroke Statistical Update. 2001,Moderate or Vigorous Physical Activity in

38、US Adults,American Heart Association. 2002 Heart and Stroke Statistical Update. 2001,Physical Inactivity,Lack of exercise is a proven risk factor for heart disease A lack of regular physical exercise is a growing epidemic in the US Heart disease is twice as likely to develop in inactive people than

39、in those who are more active Physical activity helps maintain weight, blood pressure, and diabetes Women should exercise to increase heart rate for 20-30 minutes a day, 3-5 times per week,CAD Risk Factors: Goals,Grundy SM, et al. Circulation. 1999. American Heart Association Consensus Panel. Circula

40、tion. 1995; The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and the National High Blood Pressure Education Program Coordinating Committee. Arch Intern Med. 1997,Major Risk Factors,Diabetes mellitus CHD risk equivalent Cigarette smoking Hyperten

41、sion (blood pressure 140/90 mm Hg or on anti-hypertensive medications) Low HDL cholesterol (45 years; women 55 years) High LDL cholesterol (160 mg/dL) Risk CategoriesLDL Goal CHD or risk equivalent (DM, ASHD)100 2+ risk factors130 0-1 risk factor160 CHD risk equivalent = 20% - city of Nashville hous

42、eholds w/ female adults (n = 500,000),Shaw LJ. Am J Managed Care. 2001 National Heart, Lung, and Blood Institute,Menopause, Estrogen, and Hormone Replacement Therapy (HRT),Hormonal Effects on Ischemia and Disease Prevalence,Premenopause Estrogen has digoxin-like effect: ST Post-menopause effect on H

43、RT ST - vasodilatory effects of HRT Increase exercise duration/decrease chest pain Women with intact uterus take progestin to protect against uterine malignancies Estrogen and medroxyprogesterone attenuate this effect,Lloyd GW, et al. Heart. 2000; Webb CM, et al. Lancet. 1998; Morise AP, et al. Am J

44、 Cardiol. 1993; Rosano GM, et al. J Am Coll Cardiol. 2000,Hormonal Effects on Ischemia and Disease Prevalence,Estrogen modulates chest pain syndromes Premenopausal CAD: angina/ischemia variation by menstrual cycle Early follicular phase estradiol and progesterone levels - low time to ischemia onset,

45、Lloyd GW, et al. Heart. 2000; Webb CM, et al. Lancet. 1998; Morise AP, et al. Am J Cardiol. 1993; Rosano GM, et al. J Am Coll Cardiol. 2000,Postmenopausal Hormone Therapy and Cardioprotection,First randomized trial HERS trial (Heart and Estrogen/Progestin Replacement Study) Secondary CAD prevention

46、trial Randomized trial of placebo vs estrogen and medroxyprogesterone Follow-up = 4 years N = 2,763 women with an intact uterus Outcome measures Primary: nonfatal MI or cardiac death Secondary: unstable angina, coronary revascularization, congestive heart failure,HERS trial. JAMA. 1998.,Is There a R

47、ole for HRT?,Secondary prevention 1998: HERS 4 years of treatment with conjugated estrogen plus medroxyprogesterone acetate No reduction in the risk of MI and coronary death in women with established CAD,HERS trial. JAMA. 1998.,Secondary prevention 3/2000: Estrogen Replacement and Atherosclerosis tr

48、ial (ERA) 309 postmenopausal women with CAD Placebo vs conjugated estrogen (.625 mg/day) vs conjugated estrogen (.625 mg/day) with medroxyprogesterone acetate (2.5 mg/day) Angiographic analysis of the diameter of the coronary arteries at the start of the study and 3 years later ERA trial results at

49、follow-up angiography The progression of coronary atherosclerosis was unchanged in the women randomized to either of the estrogen groups,Is There a Role for HRT?,ERA trial. J Am Coll Cardiol. 2001,Is There A Role for HRT?,Primary prevention Womens Health Initiative 160,000 women:1991-2005 Initial results: no cardioprotection attributed to HRT in women on HRT American Heart Association: HRT not recommended for primary or s