Cholesterol efflux capacity, HDL cholesterol, and risk of coronary heart disease: a nested case-control study in men

J Lipid Res. 2019 Aug;60(8):1457-1464. doi: 10.1194/jlr.P093823. Epub 2019 May 29.


The capacity of HDLs to accept cholesterol effluxing from macrophages has been proposed as a new biomarker of HDLs' anti-atherogenic function. Whether cholesterol efflux capacity (CEC) is independent of HDL cholesterol (HDL-C) as a biomarker for coronary heart disease (CHD) risk in a generally healthy primary-prevention population remains unanswered. Therefore, in this nested case-control study, we simultaneously assessed CEC (using J774 cells) and plasma HDL-C levels as predictors of CHD in healthy middle-aged and older men not receiving treatment affecting blood lipid concentrations. We used risk-set sampling of participants free of disease at baseline from the Health Professionals Follow-Up Study, and matched cases (n = 701) to controls 1:1 for age, smoking, and blood sampling date. We applied conditional logistic regression models to calculate the multivariable relative risk and 95% CIs of CHD over 16 years of follow-up. CEC and HDL-C were correlated (r = 0.50, P < 0.0001). The risk (95% CI) of CHD per one SD higher CEC was 0.82 (0.71-0.96), but completely attenuated to 1.08 (0.85-1.37) with HDL-C in the model. The association per one SD between HDL-C and CHD (0.66; 0.58-0.76) was essentially unchanged (0.68; 0.53-0.88) after adjustment for CEC. These findings indicate that CEC's ability to predict CHD may not be independent of HDL-C in a cohort of generally healthy men.

Keywords: atherosclerosis; cholesterol metabolism; cholesterol/efflux; epidemiology; high density lipoprotein; myocardial infarction; prospective study.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Cholesterol, HDL / blood*
  • Coronary Disease / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Cardiovascular*
  • Risk Assessment


  • Biomarkers
  • Cholesterol, HDL