Levels of prebeta-1 high-density lipoprotein are elevated in 3 phenotypes of dyslipidemia

Abstract

Prebeta-1 high-density lipoprotein (HDL) is a small subspecies of HDL that functions as the HDL quantum particle and is the principal acceptor of cholesterol effluxed from macrophages through the ATP-binding cassette transporter, ABCA1. High levels of prebeta-1 HDL are associated with increased risk of structural coronary artery disease and myocardial infarction. We aimed to compare prebeta-1 HDL levels in normal subjects and in 3 phenotypes of dyslipidemia. We studied 2435 individuals (1388 women; 1047 men). Of these, 2018 were not taking lipid-lowering medication when enrolled: 392 were normolipidemic controls; 713 had elevated levels of low-density lipoprotein cholesterol; 623 had combined hyperlipidemia; and 290 had hypertriglyceridemia. Relative to controls, prebeta-1 HDL levels were increased in all 3 dyslipidemic phenotypes, particularly the combined and hypertriglyceridemia groups. This increase possibly reflects increased acceptor capacity of apolipoprotein B-100 containing lipoproteins for entropically driven transfer of cholesteryl esters from HDL via cholesteryl ester transfer protein. Multiple regression analysis revealed that the main predictor variables significantly associated with prebeta-1 HDL levels were apolipoprotein A-I (apoA-1) (β=0.500), triglyceride (β=0.285), HDL-C (β=-0.237), and age (β=-0.169). There was an interaction between apoA-1 and sex (female vs male; β=-0.110). Among postmenopausal women, estrogenized subjects had a similar level of prebeta-1 HDL compared to those not receiving estrogens. Prebeta-1 HDL levels are elevated in the 3 most common types of hyperlipidemia and are most strongly influenced by the levels of apoA-1, triglyceride, and HDL-C.