Substantial evidence exists regarding the favorable influence of estrogen on cardiovascular outcomes in women. These favorable effects extended beyond those explained by estrogen effects on lipid profile and other recognized risk factors. Accumulating evidence strongly supports that these favorable outcomes are in part due to direct effects of estrogen on estrogen receptors expressed in cardiovascular tissues, including both the vasculature and myocardium. Attenuating the untoward effects o current hormone replacement strategies on non-cardiovascular tissues such as uterus and breast by development of tissue selective estrogen modulators (SERMS) will likely provide novel strategies for the treatment of bone, neurologic and cadiovascular diseases. Raloxifene, the first SERM approved, was relased recently for prevention of osteoporosis, but data, including new data presented in the SCOR (Project 3) support the hypothesis that raloxifene also directly activates the estrogen receptors now known to be expressed in the cardiovascular system. This project will examine the effects of raloxifene on parameters of cardiovascular structure and function in a population of post-menopausal women who have had a myocardial infarction (MI). We will test the hypothesis that raloxifene directly and favorably influences cardiovascular function following MI, in four specific aims.
The Specific Aims are to examine indices of: 1. Left ventricular remodeling; 2. Endothelial function; 3. Autonomic tone and neurohormonal activation; 4. Vulnerability to ventricular arrhythmias. This study directly and prospectively tests the overall SCR hypothesis in a human population and will further our understanding of the underlying mechanisms by which estrogen receptor modulation may diminish the burden of cardiovascular diseases and their sequelae in women. Moreover, this study initiates and area of clinical investigation with potential implications for the therapy of ischemic cardiovascular diseases in both women and men.
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