Eveline Oestreicher Stock1, Christine T Ferrara2, Patricia M O'Connor3, Josefina M Naya-Vigne4, Philip H Frost1, Mary J Malloy5, John P Kane6, Clive R Pullinger7. 1. Cardiovascular Research Institute, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA. 2. Department of Pediatrics, University of California, San Francisco, CA, USA. 3. St James Hospital Dublin, Trinity College Dublin, Dublin, Republic of Ireland. 4. Cardiovascular Research Institute, University of California, San Francisco, CA, USA. 5. Cardiovascular Research Institute, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA; Department of Pediatrics, University of California, San Francisco, CA, USA. 6. Cardiovascular Research Institute, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA. 7. Cardiovascular Research Institute, University of California, San Francisco, CA, USA; Department of Physiological Nursing, University of California, San Francisco, CA, USA. Electronic address: clive.pullinger@ucsf.edu.
Abstract
BACKGROUND: 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. OBJECTIVE: We aimed to compare prebeta-1 HDL levels in normal subjects and in 3 phenotypes of dyslipidemia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVE: We aimed to compare prebeta-1 HDL levels in normal subjects and in 3 phenotypes of dyslipidemia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Andrew S Geller; Eliana Y Polisecki; Margaret R Diffenderfer; Bela F Asztalos; Sotirios K Karathanasis; Robert A Hegele; Ernst J Schaefer Journal: J Lipid Res Date: 2018-10-17 Impact factor: 5.922