Background: Observational 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.
Objectives: A 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/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 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.
Conclusion: HDL-CEC is not unequivocally associated with CHD in contrast to HDL-C, apolipoprotein A-I, and most of the HDL subclass particle concentrations.
Keywords: HDL; cholesterol efflux; coronary heart disease; genome-wide association study; observational cohort study; triglycerides.
© 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.