Effect of menopause on plaque morphologic characteristics in coronary atherosclerosis.

BACKGROUND Coronary artery disease in women appears 10 to 15 years later than in men. To test the hypothesis that the effects of estrogen may manifest themselves as histologic differences in coronary plaques, we examined the hearts of premenopausal and postmenopausal women who died suddenly from coronary artery disease. METHODS We studied 51 cases of sudden coronary death and 47 deaths in women who died from noncoronary causes. Coronary deaths were classified on the basis of histologic features. The number of acute plaque ruptures, healed plaque ruptures, vulnerable plaques, and acute plaque erosions were compared between groups. Postmortem values of serum total cholesterol, HDL cholesterol, and thiocyanate were measured, and menopausal status was confirmed by calculating body mass index. RESULTS Women older than 50 years of age were much more likely to have a ruptured plaque than were younger, premenopausal women. Plaque rupture was significantly associated with elevated total cholesterol level. In the 51 women who died of coronary disease, the mean number of vulnerable plaques increased significantly as women advanced into the postmenopausal years. CONCLUSIONS Our data suggest that estrogen has an anti-inflammatory effect on atherosclerotic plaques, resulting in plaque stabilization. Plaque erosion, the major substrate for thrombosis in premenopausal women, does not appear to be inhibited by estrogen. Because plaque progression may result both from repeated rupture and repeated erosion, a better understanding of the effect of estrogen on atherosclerosis may yield insights into the nature of coronary artery disease.

[1]  H. S. Klopfenstein,et al.  Estrogen modulates responses of atherosclerotic coronary arteries. , 1990, Circulation.

[2]  W. Roberts,et al.  Composition of atherosclerotic plaques in coronary arteries in women less than 40 years of age with fatal coronary artery disease and implications for plaque reversibility. , 1991, The American journal of cardiology.

[3]  W. Roberts,et al.  Comparison in women versus men of composition of atherosclerotic plaques in native coronary arteries and in saphenous veins used as aortocoronary conduits. , 1993, Journal of the American College of Cardiology.

[4]  M. Frazier-Jessen,et al.  Estrogen modulation of JE/monocyte chemoattractant protein-1 mRNA expression in murine macrophages. , 1995, Journal of immunology.

[5]  R. Virmani,et al.  Sudden coronary death. Frequency of active coronary lesions, inactive coronary lesions, and myocardial infarction. , 1995, Circulation.

[6]  R. Virmani,et al.  Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. , 1996, Circulation.

[7]  GENDER‐RELATED DIFFERENCES IN THE DEVELOPMENT OF ATHEROSCLEROSIS: STUDIES AT THE CELLULAR LEVEL , 1996, Clinical and experimental pharmacology & physiology.

[8]  R. Virmani,et al.  Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. , 1997, The New England journal of medicine.

[9]  E. Barrett-Connor Sex differences in coronary heart disease. Why are women so superior? The 1995 Ancel Keys Lecture. , 1997, Circulation.

[10]  M. Cleman,et al.  Modulation of circulating cellular adhesion molecules in postmenopausal women with coronary artery disease. , 1998, Journal of the American College of Cardiology.

[11]  JoAnn E. Manson,et al.  Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group. , 1998, Controlled clinical trials.

[12]  N. Wenger An update on coronary heart disease in women. , 1998, International journal of fertility and women's medicine.

[13]  S Hulley,et al.  Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. , 1998, JAMA.

[14]  C. Hennekens Risk factors for coronary heart disease in women. , 1998, Cardiology clinics.

[15]  R. D'Agostino,et al.  Sudden coronary death in women. , 1998, American heart journal.

[16]  R. Virmani,et al.  Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. , 1998, Circulation.

[17]  M. Brochier,et al.  Coronary heart disease risk factors in women. , 1998, European heart journal.

[18]  E. Vartiainen,et al.  Sex, age, cardiovascular risk factors, and coronary heart disease: a prospective follow-up study of 14 786 middle-aged men and women in Finland. , 1999, Circulation.

[19]  R. Virmani,et al.  A comparison of the Framingham risk index, coronary artery calcification, and culprit plaque morphology in sudden cardiac death. , 2000, Circulation.