Epidemiology of Cardiovascular Risk Factors in Women (Healthy Women Study)

描述(申请人提供)：我们建议继续从1983-84年开始的健康女性研究的长期跟踪，这是对围绝经期至绝经后女性风险因素变化的决定因素的第一次研究。HWS最初在1983-84年对541名绝经前妇女进行了抽样调查。这项研究开创了使用新技术评估亚临床心血管疾病(CVD)的先河；首先是1994年的颈动脉内膜中层厚度(IMT)，然后是1997-98年的电子束断层扫描(EBT)的冠状动脉和主动脉钙测量(n=363)。亚临床血管疾病测量重复两次，相隔3年(2002-3和2004-7)。在第一次EBT研究中，女性的平均年龄为62岁；57%的女性冠状动脉钙化(CAC)为零，到第三次EBT时，CAC为零的女性中有37%出现了新的CAC，估计为每年6%。我们确定绝经前的危险因素是CAC的主要决定因素。第1次EBT时测量的外周动脉粥样硬化程度、主动脉和颈动脉是6年后第3次EBT时CAC评分为0的女性发生新CAC风险的重要决定因素。在这项应用中，我们计划重复冠状动脉和主动脉钙化以及颈动脉超声和血管僵硬的研究。我们建议增加最大运动测试来确定功能容量，并测量认知功能、临床抑郁史、身体功能以及睡眠质量和持续时间。我们假设，一小部分女性，估计为25%(N=75)，在73岁时CAC评分将继续为0，绝经前的危险因素仍将是CAC的主要决定因素，即使到73岁。我们假设：(A)对其他血管床的亚临床疾病的测量，即颈动脉和主动脉，将是在4次EBT测量中从第一次EBT时无CAC转变为随后的CAC的主要决定因素；(B)脉搏波速度将是新CAC发展的预测因子；以及(C)CAC为0的女性将比那些CAC评分更高的女性有更好的功能能力、认知功能和更好的睡眠，更少的抑郁和功能损失，即使在没有临床冠心病的情况下也是如此。我们认为绝经后妇女患血管疾病和健康老龄化的风险主要由绝经前的生活方式和危险因素决定。公共卫生相关性：在匹兹堡健康女性研究的下一阶段，我们建议测试以下假设：(A)绝经前心血管风险因素是冠状动脉和主动脉钙化进展的强烈预测因素，以及25年后测量的颈动脉内膜中层厚度；以及(B)无亚临床动脉粥样硬化或亚临床动脉粥样硬化水平较低的绝经后女性同时具有更好的功能能力、认知功能和睡眠，较高水平的女性更少抑郁和残疾。

DESCRIPTION (provided by applicant): We propose to continue the long term follow up of the Healthy Women Study that began in 1983-84 as the first study of the determinants of risk factors changes among women during the peri- to postmenopause. The HWS originally sampled 541 premenopausal women in 1983-84. This study has pioneered the use of new technologies for evaluating subclinical cardiovascular disease (CVD); first, carotid intimal medial thickness (IMT) in 1994 and then the addition of coronary and aortic calcium measurements using electron beam tomography (EBT) in 1997-98 (n=363). The subclinical vascular disease measurements were repeated twice, 3 years apart (2002-3 and 2004-7). At the 1st EBT study, the women had a mean age of 62; 57% of the women had 0 coronary artery calcium (CAC) and by the 3rd EBT 37% of the women with 0 CAC had developed new CAC, an estimated 6% per year. We determined that premenopausal risk factors were the primary determinant of CAC. The extent of peripheral atherosclerosis, aorta and carotid measured at the time of the 1st EBT was an important determinant of the risk of developing new CAC among women with 0 CAC score at the 1st EBT by time of 3rd EBT examination 6 years later. In this application, we plan to repeat the coronary and aortic calcium studies and carotid ultrasound and vascular stiffness. We propose to add maximal exercise testing to determine functional capacity, and to measure cognitive function, history of clinical depression, physical functioning, and sleep quality and duration. We hypothesize that a small number of women, estimated to be 25% (N=75), will continue to have 0 CAC scores at age 73, that premenopausal risk factors will remain the primary determinants of CAC, even to the age of 73. We hypothesize that (a) measures of subclinical disease in other vascular beds, i.e. carotid and aorta, will be a primary determinant of the conversion from no CAC at 1st EBT to subsequent CAC over the 4 EBT measurements; (b) pulse wave velocity will be a predictor of the development of new CAC; and (c) women who have 0 CAC will have better functional capacity, cognitive function, and better sleep, and less depression and functional loss than those who have higher CAC scores, even in the absence of clinical coronary heart disease. We suggest that risk of vascular disease and healthy aging among postmenopausal women is primarily determined by premenopausal lifestyles and risk factors. PUBLIC HEALTH RELEVANCE: In the next phase of the Pittsburgh Healthy Women Study, we propose to test the hypotheses that (a) premenopausal cardiovascular risk factors are strong predictors of progression of coronary and aortic calcification and carotid intima media thickness measured 25 years later; and (b) postmenopausal women with no or low levels of subclinical atherosclerosis have concurrently better functional capacity, cognitive function, and sleep, and less depression and disability than those with higher levels.