CORONARY ARTERY DISEASE AND POSTPRANDIAL LIPOPROTEINS

Epidemiologic evidence for an association between risk for developing CAD and fasting levels of plasma lipids, lipoproteins and apolipoproteins is derived from international cross-sectional data, prospective within-country population studies, and intervention trials. These latter studies, which used definite cardiac endpoints, including fatal and nonfatal myocardial infarctions, are supported by more recent studies in which coronary angiographic determination of both the extent and the progression of CAD has been documented. Little attention has been paid, however, to the non-fasting or postprandial state, a condition that is present for the majority of each 24 hour period. Thus, despite the strong cross-sectional data which show a positive relationship between intake of dietary fat, particularly saturated fat and both plasma total cholesterol and CAD, and several studies indicating reduced incidence of CAD in populations eating diets low in total fat or high in polyunsaturated fat, only a few investigators have focused on the postprandial period as a potentially atherogenic state. The goal of this project is to determine if the levels of postprandial plasma lipoproteins are associated with atherosclerosis, and, if so, whether the association is independent of that between fasting plasma lipoproteins and atherosclerosis. We propose therefore: 1. To determine if increased postprandial levels of plasma triglycerides are associated with the presence of coronary artery disease, and if so, if this association is independent of fasting levels of plasma lipids and apoproteins that have been previously associated with CAD. 2. To determine if other measures of postprandial plasma lipoproteins that might indicate atherogenic potential, such as plasma levels of retinyl esters or the plasma ratio of apo B48:apo B1OO, are a) independently associated with the presence of CAD and b) more closely associated with the presence of CAD than postprandial levels of plasma triglycerides. Cases and controls will be recruited from individuals undergoing ECG or thallium stress-testing. These subjects will have blood taken before and during an 8 hour period after ingestion of a fat-formula meal, and plasma levels of lipids, lipoproteins, apoproteins, lipolytic enzyme activities, glucose and insulin will be measured. Apo E phenotype and LDL size will determined as well. These factors, along with sex, age, blood pressure, smoking status and waist-hip ratio will be used as covariates in the analysis. A secondary aim will be to conduct exploratory studies, using new methods and approaches, to characterize the atherogenic potential of postprandial remnant lipoproteins. Specifically, we will a) utilize immunoaffinity chromatography to isolate and characterize apo E-enriched remnants of triglyceride-rich lipoproteins during the postprandial period, and b) determine the ability of postprandial serum from cases and controls to increase the cholesterol content of cultured macrophages.