Fasting and postprandial lipid metabolism will be studied in the plasma of 200 men and women (50-69 years of age) with angiographically documented coronary artery disease (CAD) but with normal (<90th percentile) LDL-cholesterol and plasma triglyceride levels. The data obtained will be compared with those in a normal control group without clinical evidence of CAD, who have a negative stress test. Following a dietary challenge of whole foods supplemented with vitamin A, the removal of chylomicron apo B-48 protein will be followed postprandially, using a new monoclonal antibody method. Over the same time period, circulating levels of retinyl ester, high and low density lipoprotein (HDL and LDL) subfractions, and other metabolic factors will be assayed in order to test three different hypotheses relating to human atherogenesis, In the first, we will test whether chylomicron remnant clearance is delayed, and whether retinyl ester is a marker for apo B-48, in this group of CAD patients. In the second, we will test the hypothesis that plasma cholesterol metabolism is abnormal in CAD and in particular, that reverse cholesterol transport is reduced. In the third, we will test whether an unusual pattern of abnormal HDL and LDL subfractions, characterized by increased prebeta-HDL and/or lipid-poor LDL, is diagnostic for these patients. Together, these studies can be expected to provide new information on an important and little-studied group of men and women with CAD, and have the potential to provide important insights into the mechanism of human atherogenesis in general.
