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J Lipid Res. 2019 May 29. pii: jlr.P093823. doi: 10.1194/jlr.P093823. [Epub ahead of print]

Cholesterol Efflux Capacity, HDL Cholesterol, and Risk of Coronary Heart Disease: a Nested Case-Control Study in Men.

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Dalhousie University, Canada;
Harvard T.H. Chan School of Public Health, United States.


The capacity of high-density lipoproteins (HDL) to accept cholesterol effluxing from macrophages has been proposed as a new biomarker of HDL's 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 age 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% confidence intervals (CI) 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 1 standard deviation (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 1 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.


Atherosclerosis; Cholesterol/Efflux; Cholesterol/Metabolism; Epidemiology; HDL; case-control study; coronary heart disease; myocardial infarction

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