This is a competing renewal application of HL28266. The Healthy Women Study (HWS) began in 1983-1984 to evaluate the effects of menopause on cardiovascular risk factors. At the 8th postmenopausal visit, n=355 women had electron-beam computed tomography (EBCT) of the coronaries and the aorta and these were repeated 3 years later, n=193. Approximately 55% of the women had no coronary calcium (Ca) at their 1st EBCT and 45% at the 2nd EBCT, an approximate 25% incidence of new coronary Ca. Progression of coronary Ca was strongly related to prior coronary Ca levels with an estimated 50-60% increase per year. Risk factors measured premenopausally, age 47, were powerful predictors of the risk of coronary Ca, especially lipoproteins, estimated insulin resistance, visceral fat and waist circumference. In this renewal, we propose to: (a) further test whether measures of subclinical disease in other vascular beds, such as aortic calcification, are determinants of the risk of new coronary Ca among women with 0 coronary Ca at their 1st EBCT; (b) whether risk factors at baseline premenopausal (20 years previously) or, early in the postmenopause, or change in risk factors from early postmenopause are predictors of both the extent of coronary calcification and carotid plaque and intimal medial wall thickness (IMT) and progression over time; and (c) whether behavioral attributes are predictors of both the extent and progression of subclinical disease. The 300+ women who have completed their 2nd EBCT examination will have a 3rd examination approximately 3 years after the 2nd and 6 years from the 1st EBCT. We estimate that approximately 48% of women with no coronary Ca at the 1st EBCT will have new incident coronary Ca, n=80. The increase in coronary Ca for women with coronary Ca at 1st EBCT is about 50% per year. The extent of atherosclerosis in other vascular beds such as the number of calcifications in aorta and risk factors pre- and early postmenopause are likely to be primary determinants of progression of coronary Ca, especially number of low density lipoprotein (LDL) particles, small LDL cholesterol, insulin resistance (high insulin levels). The amount of visceral fat or higher waist circumference even early in postmenopause is the primary determinant of coronary Ca. The HWS follow up provides a unique opportunity to study the development of new coronary Ca and progression of coronary Ca and relationship to both pre- and postmenopausal risk factors.
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