Epidemiology of Cardiovascular Risk Factors in Women

描述（由申请人提供）：这是HL28266的竞争性续期申请。健康妇女研究（HWS）开始于1983-1984年，目的是评估更年期对心血管危险因素的影响。在绝经后第8次随访时，355名妇女接受了冠状动脉和主动脉电子束计算机断层扫描（EBCT）， 3年后又进行了一次，n=193。大约55%的女性在第一次EBCT时没有冠状动脉钙（Ca），第二次EBCT时为45%，新冠状动脉钙的发生率约为25%。冠状动脉钙的进展与先前的冠状动脉钙水平密切相关，估计每年增加50-60%。绝经前（47岁）测量的危险因素是冠状动脉Ca风险的有力预测因子，尤其是脂蛋白、估计的胰岛素抵抗、内脏脂肪和腰围。在这项更新中，我们建议：(a)进一步测试其他血管床的亚临床疾病，如主动脉钙化，是否是第一次EBCT时无冠状动脉钙化的女性发生新冠状动脉钙化风险的决定因素；(b)基线绝经前（20年前）或绝经后早期的危险因素，或绝经后早期危险因素的变化是否可以预测冠状动脉钙化程度、颈动脉斑块和内膜内侧壁厚度（IMT）及其随时间的进展；(c)行为属性是否是亚临床疾病的程度和进展的预测因子。完成第二次EBCT考试的300多名妇女将在第二次和第一次EBCT考试后大约3年和6年进行第三次考试。我们估计，在第一次EBCT时没有冠状动脉Ca的女性中，约有48%会出现新的冠状动脉Ca， n=80。第一次EBCT时冠状动脉钙化的女性冠状动脉钙化每年增加约50%。其他血管床动脉粥样硬化的程度，如主动脉钙化的数量和绝经前和绝经后早期的危险因素可能是冠状动脉钙进展的主要决定因素，特别是低密度脂蛋白（LDL）颗粒的数量，小LDL胆固醇，胰岛素抵抗（高胰岛素水平）。绝经后早期的内脏脂肪量或更高的腰围是冠状动脉Ca的主要决定因素。HWS随访提供了一个独特的机会来研究新的冠状动脉Ca的发展和冠状动脉Ca的进展以及与绝经前和绝经后危险因素的关系。

DESCRIPTION (provided by applicant): 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.