ARTERIAL ENDOTHELIAL FUNCTION--AN EPIDEMIOLOGIC STUDY

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Many young adult subjects have some degree of atherosclerotic coronary and carotid artery disease and experience no symptoms. As time passes, many die suddenly and unexpectedly and only limited therapeutic options are available once symptomatic coronary heart disease and stoke occur. Since the atherosclerotic process begins in youth, a measure of the early manifestations of atheroscleosis may have the potential of identifying subjects at risk for premature coronary and carotid occlusive vascular disease when therapeutic options can be administered. Impaired brachial artery flow mediated dilatory (FMD) capacities have been shown to exist in children and young adults with hypercholesterolemia, hyperhomocysteinemia, diabetes and in those who smoke. Impaired brachial artery FMD has been shown to relate to impaired endothelial function, which is an early manifestation of the atherosclerotic process. If impaired brachial artery FMD is a predictor of the process, then it may be used to non-invasively assess atherosclerosis early in its development and to evaluate the effect of therapeutic interventions. In a cohort of 600 adults, 35 to 43 years of age, from the Muscatine Study, whose risk factors were measured during childhood and young adulthood, we propose to measure contemporaneous risk factors, and brachial artery FMD, along with coronary artery calcification (CAC) and carotid artery intimal-medial thickness (IMT) (the latter two established measures of early atherosclerosis) and again 3 years later. This effort is designed to examine the following hypotheses: 1) Established risk factor levels measured in childhood, adulthood and across the years from childhood through adulthood are predictive of brachial artery FMD; 2) Putative risk factor levels measured in adulthood are related to the degree of brachial artery FMD, CAC and carotid artery IMT; 3) Brachial artery FMD, CAC and carotid artery IMT are related in adults; and 4) Brachial artery FMD is predictive of increased carotid artery IMT. This application is a revision of one previously submitted as a supplement to another grant.