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Genetic and observational evidence: No independent role for cholesterol efflux over static HDL concentration measures in CHD risk assessment

Kuusisto, Sanna; Karjalainen, Minna K; Tillin, Therese; Kangas, Antti J; Holmes, Michael V; Kähönen, Mika; Lehtimäki, Terho; ... Ala-Korpela, Mika; + view all (2022) Genetic and observational evidence: No independent role for cholesterol efflux over static HDL concentration measures in CHD risk assessment. Journal of Internal Medicine 10.1111/joim.13479. (In press).

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Abstract

BACKGROUND: Observational findings for HDL-mediated cholesterol efflux capacity (HDL-CEC) and coronary heart disease (CHD) appear inconsistent, and knowledge of the genetic architecture of HDL-CEC is limited. OBJECTIVES: A large-scale observational study of the associations of HDL-CEC and other HDL-related measures with CHD and the largest genome-wide association study (GWAS) of HDL-CEC. PARTICIPANTS/METHODS: Six independent cohorts were included with follow-up data for 14,438 participants to investigate the associations of HDL-related measures with incident CHD (1,570 events). The GWAS of HDL-CEC was carried out in 20,372 participants. RESULTS: HDL-CEC did not associate with CHD when adjusted for traditional risk factors and HDL-C. In contradiction, almost all HDL-related concentration measures associated consistently with CHD after corresponding adjustments. There were no genetic loci associated with HDL-CEC independent of HDL-C and triglycerides. CONCLUSION: HDL-CEC is not unequivocally associated with CHD in contrast to HDL cholesterol, apolipoprotein A-I and most of the HDL subclass particle concentrations. This article is protected by copyright. All rights reserved.

Type: Article
Title: Genetic and observational evidence: No independent role for cholesterol efflux over static HDL concentration measures in CHD risk assessment
Location: England
DOI: 10.1111/joim.13479
Publisher version: https://doi.org/10.1111/joim.13479
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: HDL, cholesterol efflux, coronary heart disease, genome-wide association study, observational cohort study, triglycerides
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10145682
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