Genetic and observational evidence: No independent role for cholesterol efflux over static high‐density lipoprotein concentration measures in coronary heart disease risk assessment

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.