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Title: Large-Scale Analysis of Determinants, Stability, and Heritability of High-Density Lipoprotein Cholesterol Efflux Capacity.
Authors: Koekemoer, Andrea L.
Codd, Veryan
Masca, Nicholas G. D.
Nelson, Christopher P.
Musameh, Muntaser D.
Kaess, Bernhard M.
Hengstenberg, Christian
Rader, Daniel J.
Samani, Nilesh J.
First Published: 31-Aug-2017
Publisher: American Heart Association, Lippincott, Williams & Wilkins
Citation: Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37 (10), pp. 1956-1962
Abstract: OBJECTIVE: Cholesterol efflux capacity (CEC) has emerged as a biomarker of coronary artery disease risk beyond plasma high-density lipoprotein (HDL) cholesterol (HDL-C) level. However, the determinants of CEC are incompletely characterized. We undertook a large-scale family-based population study to identify clinical, biochemical, and HDL particle parameter determinants of CEC, characterize reasons for the discordancy with HDL-C, quantify its heritability, and assess its stability over 10 to 12 years. APPROACHES AND RESULTS: CEC was quantified in 1988 individuals from the GRAPHIC (Genetic Regulation of Arterial Pressure of Humans in the Community) cohort, comprising individuals from 2 generations from 520 white nuclear families. Serum lipid and lipoprotein levels were determined by ultracentrifugation or nuclear magnetic resonance and HDL particle size and number quantified by nuclear magnetic resonance. Ninety unrelated individuals had repeat CEC measurements in samples collected after 10 to 12 years. CEC was positively correlated with HDL-C (R=0.62; P<0.0001). Among clinical and biochemical parameters, age, systolic blood pressure, alcohol consumption, serum albumin, triglycerides, phospholipids, and lipoprotein(a) were independently associated with CEC. Among HDL particle parameters, HDL particle number, particle size, and apolipoprotein A-II level were independently associated with CEC. Serum triglyceride level partially explained discordancy between CEC and HDL-C. CEC measurements in samples collected 10 to 12 years apart were strongly correlated (r=0.73; P<0.0001). Heritability of CEC was 0.31 (P=3.89×10(-14)) without adjustment for HDL-C and 0.13 (P=1.44×10(-3)) with adjustment. CONCLUSIONS: CEC is a stable trait over time, is influenced by specific clinical, serum, and HDL particle parameters factors beyond HDL-C, can be maintained in persons with a low plasma HDL-C by elevated serum triglyceride level, and is modestly independently heritable.
DOI Link: 10.1161/ATVBAHA.117.309201
ISSN: 1079-5642
eISSN: 1524-4636
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: An online visual overview is available for this article. The online-only Data Supplement is available with this article at
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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