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

描述（由申请人提供）：我们建议继续对1983-84年开始的健康妇女研究进行长期随访，这是对绝经前后妇女危险因素变化决定因素的第一次研究。HWS最初在1983-84年间抽样了541名绝经前妇女。这项研究开创了评估亚临床心血管疾病（CVD）的新技术；首先在1994年测量颈动脉内膜内侧厚度（IMT），然后在1997-98年使用电子束断层扫描（EBT）测量冠状动脉和主动脉钙（n=363）。亚临床血管疾病测量重复两次，间隔3年（2002-3年和2004-7年）。在第一次EBT研究中，这些女性的平均年龄为62岁；57%的女性冠状动脉钙化（CAC）为0，到第三次EBT时，37%的CAC为0的女性发展为新的CAC，估计每年6%。我们确定绝经前危险因素是CAC的主要决定因素。在第一次EBT时测量的外周动脉粥样硬化、主动脉和颈动脉的程度是6年后第三次EBT检查时第一次EBT时CAC评分为0的女性发生新CAC风险的重要决定因素。在这个应用程序中，我们计划重复冠状动脉和主动脉钙研究和颈动脉超声和血管硬度。我们建议增加最大运动测试来确定功能能力，并测量认知功能、临床抑郁史、身体功能、睡眠质量和持续时间。我们假设，少数女性，估计有25% (N=75)，在73岁时CAC评分仍然为0，绝经前危险因素仍然是CAC的主要决定因素，甚至到73岁。我们假设(a)其他血管床（即颈动脉和主动脉）的亚临床疾病测量将是第一次EBT时无CAC到随后4次EBT测量中CAC转换的主要决定因素；(b)脉冲波速度将是新CAC发展的预测指标；(c)即使在没有临床冠心病的情况下，与CAC得分较高的女性相比，CAC得分为0的女性将具有更好的功能能力、认知功能、更好的睡眠、更少的抑郁和功能丧失。我们认为，绝经后妇女血管疾病和健康衰老的风险主要取决于绝经前的生活方式和危险因素。公共卫生相关性：在匹兹堡健康妇女研究的下一阶段，我们建议检验以下假设：(a)绝经前心血管危险因素是25年后测量的冠状动脉和主动脉钙化进展和颈动脉内膜中膜厚度的有力预测因素；(b)没有或低水平亚临床动脉粥样硬化的绝经后妇女同时具有更好的功能能力、认知功能和睡眠，并且比高水平的妇女更少抑郁和残疾。

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.