ESTROGEN IN THE PREVENTION OF ATHEROSCLEROSIS TRIAL

描述（申请人的描述逐字）：目前的证据表明， 无对抗性雌激素替代疗法（ERT）可减少心血管疾病， 发病率和死亡率。口服雌激素的心脏保护作用 被认为是由于a）脂质转运模式的改变，B） ERT诱导的对脂质转运的影响不能完全通过测量 胆固醇和甘油三酯水平，和/或c）ERT的非脂质作用。 尽管先前的研究表明，ERT对 绝经后心血管疾病（CVD）的推定危险因素 但是，这些研究对女性的影响信息有限 直接作用于实际的动脉粥样硬化过程， 动脉成像终点。简而言之，ERT与 脂质和非脂质终点，以及ERT的多变量相关性， 绝经后妇女动脉粥样硬化过程中的脂质和非脂质终点 对妇女了解甚少。我们计划在最近的一次会议上解决这些问题， 完成随机化、双盲、安慰剂对照、颈动脉 221例46 ~ 80岁健康绝经后妇女的超声ERT试验 无心血管疾病症状（一级预防）。雌激素在预防中的作用 动脉粥样硬化试验（EPAT）提供了一个独特的机会来评估 非对抗性ERT介导的减少的脂质和非脂质因素的关联 在健康绝经后亚临床动脉粥样硬化的进展中 妇女在消除自我选择和差别待遇的条件下 与医疗保健系统的互动。在EPAT中，无对抗ERT显著 降低颈动脉内膜中层厚度（IMT）的变化率， 与安慰剂相比。通过确定ERT对推定CVD风险的影响， 绝经后妇女的因素，并将这些影响与动脉壁联系起来 改变颈动脉IMT，我们将能够直接研究ERT对 亚临床动脉粥样硬化的进展。具体来说，我们计划研究 ERT对标准血脂水平下脂蛋白代谢的调节作用 措施，以及超越传统的胆固醇措施， 甘油三酯脂质测量、血栓形成/血栓溶解系统、LDL 氧化，碳水化合物，同型半胱氨酸和一氧化氮代谢，以及 各种临床措施。因为EPAT的临床试验阶段是 完成后，一个非常大和丰富的数据库，可节省相当多的费用。 由于90%的女性冠心病死亡发生在绝经后， 非对抗性ERT减少亚临床进展的作用 健康绝经后妇女的动脉粥样硬化具有重要的公共卫生意义 对预防绝经后妇女心血管疾病的意义。

DESCRIPTION (the applicant's description verbatim): Current evidence indicates that unopposed estrogen replacement therapy (ERT) reduces cardiovascular morbidity and mortality. In part, the cardioprotective effects of oral estrogen are believed to be due to a) alteration of lipid transport pattern, b) ERT-induced effects on lipid transport not totally reflected by measurement of cholesterol and triglyceride levels, and/or c) non-lipid effects of ERT. Although previous studies have shown that ERT has beneficial effects on presumptive risk factors for cardiovascular disease (CVD) in postmenopausal women, these studies have yielded limited information concerning these effects directly on the actual atherosclerosis process because of the absence of arterial imaging endpoints. In short, the univariate associations of ERT on lipid and non-lipid endpoints, as well as the multivariate associations of ERT, lipid and non-lipid endpoints on the atherosclerosis process in postmenopausal women are poorly understood. We plan to address these issues with a recently completed randomized, double-blind, placebo-controlled, carotid artery ultrasonographic ERT trial in 221 healthy postmenopausal women 46 to 80 years old without CVD symptoms (primary prevention). The Estrogen in the Prevention of Atherosclerosis Trial (EPAT) provides a unique opportunity to evaluate the association of lipid and non-lipid factors of unopposed ERT-mediated reduction in the progression of subclinical atherosclerosis in healthy postmenopausal women under conditions which eliminate self-selection and differential interaction with the medical care system. In EPAT, unopposed ERT significantly reduced the rate of change of carotid artery intima-media thickness (IMT) as compare to placebo. By determining the effects of ERT on putative CVD risk factors in postmenopausal women and linking these effects to arterial wall change in carotid IMT, we will be able to study the effects of ERT directly on the progression of subclinical atherosclerosis. Specifically, we plan to study the effects of ERT on regulation of lipoprotein metabolism with standard lipid measures as well as with measures beyond the traditional cholesterol and triglyceride lipid measurements, the thrombotic/thrombolytic system, LDL oxidation, and carbohydrate, homocysteine and nitric oxide metabolism, and a variety of clinical measures. Because the clinical trial phase of EPAT is completed, a very large and rich database is available at considerable savings. Since 90 percent of coronary deaths of women occur after menopause, elucidating the effects by which unopposed ERT reduces the progression of subclinical atherosclerosis in healthy postmenopausal women has important public health implications for the prevention of CVD in postmenopausal women.