Coronary heart disease (CHD) is the leading cause of death in the United States. The pathogenesis of atherosclerosis and CHD is thought to be initiated by endothelial dysfunction or injury. Factors that contribute to oxidative stress, such as elevated cholesterol-rich lipoproteins, result in endothelial dysfunction. The goal of this study is to evaluate an intervention for the prevention and treatment of endothelial dysfunction in young adults who are at high risk for premature CHD due to genetic lipid disorders or nephrosis. This experimental, randomized, double-blind, placebo-controlled, clinical trial will include 16 young adults (18-30 years) with genetic lipid disorders and 20 young adults (18-30 years) with nephrosis who will receive antioxidant vitamins C and E. The following hypothesis will be evaluated: Antioxidant vitamins will have direct beneficial vascular effects and/or indirect effects on lipoprotein composition which will in turn decrease oxidation and the level of vascular oxidative stress, thereby improving endothelial function. The primary specific aims are (1) to determine whether antioxidants improve endothelial function assessed by vascular reactivity in young adults prone to early CHD and (2) to evaluate the effects of these antioxidants on plasma lipoprotein profiles, composition, lipoprotein-associated antioxidant enzymes, and blood pressure. The GCRC will be used to provide infrastructure support for this clinical trial. Space will be utilized in the outpatient clinic to evaluate patients in the study, and nursing expertise will be used to collect blood samples.
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