Abstract 18073: Prebeta-1 High Density Lipoprotein Levels are Elevated in Dyslipidemic Phenotypes

Abstract

Prebeta-1 HDL is a small molecular species of high-density lipoproteins (HDL) that is the principal acceptor of cholesterol effluxed from macrophages, playing a critical role in the centripetal transport of cholesterol. High levels of prebeta-1 HDL are associated with increased risk of structural coronary artery disease and myocardial infarction. Using a technique employing ultrafiltration and isotope dilution for the quantitation of prebeta-1 HDL, we measured the levels of absolute prebeta 1-HDL in plasma and the percent of total plasma apolipoprotein A-I (apo A-I) that is accounted for in prebeta-1 HDL in individuals with three phenotypes of hyperlipidemia in comparison with those in a group of normolipidemic healthy subjects. We studied 1,930 individuals (794 males; 1,136 females), including 348 normals, 659 with primary hypercholesterolemia (mean LDL serum cholesterol level 265.4+- 60.7 mg/dl), 692 with combined hyperlipidemia (mean total serum cholesterol level 289.4 +- 71.8 mg/dl; mean triglyceride level 263.8+-163.6 mg/dl), and 231 with primary hypertriglyceridemia (mean total serum cholesterol level 283.8 +_155.5 mg/dl; mean triglyceride level 815.7+-950.0 mg/dl). Major physical characteristics of prebeta-1 HDL were unchanged in the presence of hyperlipidemia. Absolute levels of prebeta-1 HDL were increased more than 2 fold above normal in hypertriglyceridemic patients (p<0.005) with a strong positive correlation with log plasma triglycerides across all groups (p< 0.005), possibly reflecting increased acceptor capacity of the lipoproteins for transfer of cholesterol esters. Estrogenized women had a significantly lower percentage of apolipoprotein A-I as prebeta-1 HDL compared to postmenopausal women (not receiving estrogens) (p<0.005). In men, body mass index correlated with prebeta-1 HDL levels (p< 0.05) and women showed a similar trend. Prebeta-1 HDL levels are elevated in the three most common types of hyperlipidemia and are most strongly influenced by hypertriglyceridemia and estrogen status, reflecting reduced acceptor capacity for transfer of cholesteryl esters from the periphery which may contribute to the development of atherosclerosis.