Plasma lipoproteins are generally accepted risk factors for cardiovascular disease (CVD). Recently it has been recognized that the lipoproteins are markedly heterogeneous; individual, traditional species, such as high density and low densitylipoproteins are now known to be composed of multiple subspecies associated with (apparently) varying risk for CVD. While much is known about the effects of diet on plasma cholesterol and, to a somewhat lesser extent, on lipoprotein species, relatively little is known about diet and the lipoprotein subspecies. The central hypothesis for the studies proposed is that postprandial elevations in certain lipoprotein subspecies represent a risk for CVD independent of fasting lipoprotein levels. We postulate that periodic elevations in highly atherogenic lipoproteins may be more of a risk for CVD than constant elevations in less atherogenic lipoproteins. Because less than 50% of the risk for CVD can be accounted for by the standard risk factors, and because the best indication of the risk for CVD in a given individual is family history, a corollary hypothesis is that postprandial elevations in specific lipoprotein subspecies may correlate strongly with family history for CVD. We intend to study postprandial changes, and the effects of diet on these changes, in lipoprotein subspecies from a randomly selected human white male population. Compositional (Project 1) and metabolic (Project 2) changes in lipoprotein species will be studied and correlated with family history and other risk factors. The human studies will be complemented with closely related animal studies (Project 3). An ultimate goal of the studies is to test the hypothesis that postprandial changes represent familially-determined risk factors for CVD. In order to accomplish these objectives, we propose three projects and two resource units. Because dietary manipulations of the human subjects under metabolic ward conditions do not constitute an independent research project, we include the metabolic ward portion as a Resource Unit to provide postprandial lipoprotein samples for compositional and metabolic studies. Resource Unit B is the coordinating unit that will provide administration, central coordination, statistics and computer services.
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