The primary aim of this renewal is to determine the risk factors for subclinical cardiovascular disease, and the determinants of progression, as estimated from change in coronary and aortic calcification measured by electron beam computerized tomography (EBCT) at 8 and 12 years after menopause, and from change in carotid plaque index at 5 and 8 years postmenopause, in 350 women. The investigators hypothesize that premenopausal measures of risk factors, particularly LDLc, HDLc, and smoking, will strongly predict progression of coronary and aortic calcification, and carotid disease. This is based on their preliminary data analyses which found a very strong relationship between high LDLc levels, low HDLc levels, and smoking in predicting coronary and aortic calcification at the 8th postmenopausal visit. Risk factors measured during premenopause were much more strongly related to subclinical disease than concurrently measured risk factors, or change in risk factors, suggesting a long 'incubation' phase. They believe that aortic calcification and carotid plaque are earlier manifestations of subclinical cardiovascular disease than coronary calcification, as these were much more frequent than coronary calcification at the 8th visit. They will test the hypothesis that incident coronary calcification at the 12th menopausal year is more likely to occur in women with prior aortic calcification or carotid plaque compared with women without calcification or plague at the 8th year. The Healthy Women Study has documented the evolution of cardiovascular risk factors and subclinical cardiovascular disease from premenopause through menopause in a cohort of 541 women, aged 42-50 at the time of their recruitment in 1983-84. Participation in this study continues to be very high with only 51% dropping out and 7 deaths prior to the 8th visit. Currently, most women are 6-12 years postmenopause. Risk factors, including lipids, insulin, glucose, fatness and fat distribution, endogenous sex-steroid hormones, hormone replacement therapy, and behavioral and psychosocial factors, have been studied in detail. The investigators note that this will be the first study to tract progression of coronary and aortic calcification by EBCT, and carotid plaque and wall thickness, in younger postmenopausal women. They further note that the identification of early and modifiable risk factors for subclinical disease should lead to prevention or reduction of clinical cardiovascular disease among postmenopausal women.
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