TAMOXIFEN AND CORONARY HEART DISEASE

描述（改编自申请人摘要）：冠心病 (CHD)是女性死亡的主要原因，尽管知识 增加或降低冠心病风险的干预措施， 绝经后妇女是有限的。 他莫昔芬广泛用于 乳腺癌的治疗 有流行病学证据表明， 他莫昔芬降低绝经后乳腺癌妇女冠心病风险， 然而，支持性数据很少， 冠心病风险的影响尚未确定。 关于影响的知识 他莫昔芬对冠心病风险的作用在绝经后妇女中变得重要， 冠心病风险增加，但不接受雌激素替代疗法 因为担心乳腺癌的风险增加， 雌激素替代疗法 这是一项比较5个治疗组（对照组， 他莫昔芬、倍美力、普罗韦拉、倍美力+普罗韦拉） 绝经后的雌性猴子喂食致动脉粥样硬化饮食， 女性的平均血浆总胆固醇浓度 美国的拟议研究的主要目的是 检查他莫昔芬对CHD（冠状动脉）机制的影响 动脉粥样硬化[CAA]、动脉血栓形成和血管痉挛）。 第二 这些研究的目的是确定他莫昔芬的潜力 在冠心病方面取代传统的雌激素替代疗法 风险 每个具体目标的目标是确定他莫昔芬的效果 冠心病的一种机制，然后比较这些影响与那些 传统的雌激素治疗。 具体目标是：1）确定 治疗是否以及在多大程度上抑制CAA的进展; 2） 确定治疗对某些细胞因子表达的影响 和动脉中的生长因子; 3）量化和表征 治疗对血浆脂蛋白分布的影响; 4）确定 治疗对冠状动脉血管反应性的影响 以及治疗调节血管反应性的机制; 5)确定治疗对动脉血栓形成的影响， 高危女性血管损伤后生长因子的变化 猴子

DESCRIPTION (Adapted from Applicant's Abstract): Coronary heart disease (CHD) is the leading cause of death among women, although knowledge about interventions that increase or decrease CHD risk among postmenopausal women is limited. Tamoxifen is used widely for the treatment of breast cancer. There is epidemiologic evidence that tamoxifen reduces CHD risk in postmenopausal women with breast cancer, however, supporting data are sparse and the mechanisms by which tamoxifen affects CHD risk remain undetermined. Knowledge of the effects of tamoxifen on CHD risk becomes important in postmenopausal women who are at increased risk for CHD, but do not take estrogen replacement therapy because of concerns about the increased risk of breast cancer associated with unopposed estrogen replacement therapy. This is a randomized trial comparing 5 treatment groups (control, tamoxifen, Premarin, Provera, Premarin + Provera) of surgically postmenopausal female monkeys fed an atherogenic diet designed to mimic the average total plasma cholesterol concentration of women in the United States. The primary objective of the studies proposed is to examine the effects of tamoxifen on mechanisms of CHD (coronary artery atherosclerosis [CAA], arterial thrombosis, and vasospasm). The second objective of these studies is to determine the potential of tamoxifen to replace conventional estrogen replacement therapy with respect to CHD risk. The goal of each specific aim is to determine the effects of tamoxifen on one mechanism of CHD and then compare these effects with those of conventional estrogen treatment. The specific aims are: 1) to determine if, and to what extent, treatment inhibits progression of CAA; 2) to determine the effects of treatment on expression of certain cytokines and growth factors in arteries; 3) to quantify and characterize the effects of treatment on plasma lipoprotein distribution; 4) to determine the effects of treatment on vascular responsiveness of coronary arteries and the mechanisms by which treatment modulates vascular responsiveness; 5) to determine the effects of treatment on arterial thrombosis and growth factor production in injured arteries of high risk female monkeys.