Large-Scale Analysis of Determinants, Stability, and Heritability of High-Density Lipoprotein Cholesterol Efflux Capacity.pdf (244.39 kB)
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Large-Scale Analysis of Determinants, Stability, and Heritability of High-Density Lipoprotein Cholesterol Efflux Capacity.

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journal contribution
posted on 27.11.2017, 15:11 by Andrea L. Koekemoer, Veryan Codd, Nicholas G. D. Masca, Christopher P. Nelson, Muntaser D. Musameh, Bernhard M. Kaess, Christian Hengstenberg, Daniel J. Rader, Nilesh J. Samani
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.

Funding

The GRAPHIC study (Genetic Regulation of Arterial Pressure of Humans in the Community) was funded by the British Heart Foundation (BHF). Drs Codd, Nelson, and Samani are funded by the BHF, and Dr Samani is a National Institute for Health Research Senior Investigator.

History

Citation

Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37 (10), pp. 1956-1962

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

VoR (Version of Record)

Published in

Arteriosclerosis

Publisher

American Heart Association, Lippincott, Williams & Wilkins

issn

1079-5642

eissn

1524-4636

Copyright date

2017

Available date

27/11/2017

Publisher version

http://atvb.ahajournals.org/content/37/10/1956

Notes

An online visual overview is available for this article. The online-only Data Supplement is available with this article at http://atvb.ahajournals.org/lookup/suppl/doi:10.1161/ATVBAHA.117.309201/-/DC1.

Language

en