METABOLIC STUDIES IN HUMAN ATHEROSCLEROSIS

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This project will evaluate the strength of association of alimentary lipemia, after adjustment for traditional and nontraditional risk factors, with obstructive coronary artery disease (CAD), extent of extracranial carotid atherosclerosis (ECA), and progression rates of ECA in men and women whose coronary status is defined at angiography. Women will be oversampled relative to men so that final accrual rates will be similar for both. In particular, new risk factors we will control for include the relation of intraabdominal fat (noninvasively imaged by a new MRI technique), Lp(a) level and isoforms, factors related to thrombosis and thrombolysis, and lipoprotein subfractions (HDL, LDL), and traditional risk factors. We will use multivariate analysis to investigate the independent strength of association of postprandial lipemia to outcome and to assess the possible role of certain factors (e.g. HDL, adipose distribution) as intermediaries in its effects. This work builds on our ongoing research experience in patients with CAD, on our considerable experience with non- invasive imaging of the carotid arteries, on newly developed methodology for imaging intraabdominal fat, on evidence that fat pattern relates to obstructive CAD (recently accepted for publication), and on the considerable expertise with lipids and lipoproteins at this institution. Availability of the General Clinical Research Center will afford us he opportunity, for the first time, to relate metabolic parameters to atherosclerosis.