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Updated: Jan 24, 2026
High-throughput Nitrobenzoxadiazole-labeled Cholesterol Efflux Assay
Published on: January 7, 2019
Cholesterol efflux capacity, HDL cholesterol, and risk of coronary heart disease: a nested case-control study in men
Leah E Cahill1,2, Frank M Sacks3,4,5, Eric B Rimm3,5,6
1Departments of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA lcahill@hsph.harvard.edu leah.cahill@dal.ca.
Insights
Cholesterol efflux capacity (CEC) may not independently predict coronary heart disease (CHD) risk. While higher CEC showed reduced CHD risk, this association disappeared when adjusted for HDL cholesterol (HDL-C) levels in healthy men.
Area of Science:
- Cardiovascular Disease Research
- Biomarker Discovery
- Lipid Metabolism
Background:
- High-density lipoproteins (HDLs) play a role in anti-atherogenic function.
- Cholesterol efflux capacity (CEC) is a proposed biomarker for HDL function.
- The independence of CEC from HDL cholesterol (HDL-C) as a coronary heart disease (CHD) biomarker is unclear in primary prevention.
Purpose of the Study:
- To assess whether cholesterol efflux capacity (CEC) is an independent predictor of coronary heart disease (CHD) risk.
- To compare the predictive value of CEC versus HDL cholesterol (HDL-C) for CHD in healthy men.
Main Methods:
- Nested case-control study within the Health Professionals Follow-Up Study.
- Simultaneous assessment of CEC (using J774 cells) and plasma HDL-C levels.
- Conditional logistic regression analysis in 701 matched cases and controls followed for 16 years.
Main Results:
- CEC and HDL-C were significantly correlated (r = 0.50, P < 0.0001).
- Higher CEC was associated with reduced CHD risk (RR per SD = 0.82), but this was attenuated when HDL-C was included in the model (RR = 1.08).
- HDL-C remained a significant predictor of CHD risk even after adjustment for CEC (RR per SD = 0.68).
Conclusions:
- Cholesterol efflux capacity (CEC) may not be an independent predictor of coronary heart disease (CHD) risk in generally healthy men.
- The predictive ability of CEC for CHD appears to be largely explained by HDL cholesterol (HDL-C) levels.
- HDL-C remains a robust biomarker for CHD risk in primary prevention cohorts.
Abstract:
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.
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