High density lipoproteins (HDL) are heterogeneous particles, and have been classified based on their apolipoprotein composition. ApoA-l and apoA-Il are the two major apolipoproteins associated with HDL. The two major classes of HDL particles include LpA-I, which contains apoA-l but not apoA-ll, and LpA-I,A-Il, which contains both apoA-l and apoA-ll. LPA-I, but not LpA-I,A-II, has been found to be associated with coronary heart disease risk. The major goal of this project is to determine the factors which regulate the plasma levels of LpA-I and LpA-I,A-11 in both normal subjects as well as patients with low levels of HDL, who may be at increased risk for premature coronary disease. The metabolism of these two major HDL particles in normal subjects was determined to be different, with LpA-I having a significantly faster catabolic rate than LpA-I,A-ll. Several subjects with significantly low levels of HDL (less than 25) but no evidence of coronary disease were studied in order to determine the etiology of the low HDL utilizing radiolabeled apoA-l and apoA-Il. All subjects were shown to have rapid catabolism of both apolipoproteins. Therefore, hypercatabolism of HDL apolipoproteins may be the major cause of significantly decreased HDL levels. This metabolic defect does not appear to markedly predispose to premature coronary artery disease. These studies included subjects of age 21 to 57 years. 56 percent of the subjects were women. The studies included two Asian and one East Indian subject.
