• Sanna Kuusisto, Minna K Karjalainen, Therese Tillin, Antti J Kangas, Michael V Holmes, Mika Kähönen, Terho Lehtimäki, Jorma Viikari, Markus Perola, Nishi Chaturvedi, Veikko Salomaa, Olli T Raitakari, Marjo-Riitta Järvelin, Johannes Kettunen, and Mika Ala-Korpela.
• Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland.
• J. Intern. Med. 2022 Jul 1; 292 (1): 146153146-153.

BackgroundObservational findings for high-density lipoprotein (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.ObjectivesA large-scale observational study on the associations of HDL-CEC and other HDL-related measures with CHD and the largest genome-wide association study (GWAS) of HDL-CEC.Participants/MethodsSix 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.ResultsHDL-CEC did not associate with CHD when adjusted for traditional risk factors and HDL cholesterol (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.ConclusionHDL-CEC is not unequivocally associated with CHD in contrast to HDL-C, apolipoprotein A-I, and most of the HDL subclass particle concentrations.© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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