HDL function better predicts future atherosclerotic CV events than HDL-level

HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events

News - Nov. 20, 2014

Presented at the AHA Scientific Sessions 2014 by Annan Rohatgi(University of Texas Southwestern Medical Center, Dallas, TX)


To date, it is unclear whether the concentration of HDL cholesterol plays a causal role in atherosclerosis. HDL-c efflux capacity may be an important factor; the ability of HDL to accept cholesterol of macrophages. This is a key step in reverse cholesterol transport.
This study examined the epidemiology of cholesterol efflux capacity and its association with incident atherosclerotic cardiovascular (CV) disease in a large, multi-ethnic population cohort. To this extent, HDL-c levels, HDL particle concentrations and the cholesterol efflux capacity were measured at baseline, in 2924 participants of the Dallas Heart Study, who were free of CV disease. The primary endpoint was atherosclerotic CV disease, defined as a first non-fatal myocardial infarction, non-fatal stroke or coronary revascularisation or death from CV causes. Average follow-up time was 9.4 years.

Main results

  • Increasing quartiles of cholesterol efflux capacity were not or only modestly correlated to traditional CV risk factors other than lipid levels.
  • There was an incremental, reverse relationship between increasing quartiles of cholesterol efflux capacity and the primary endpoint of atherosclerotic CV events (HR for fourth vs. first quartile: 0.44, 95%CI: 0.27-0.73). Correction for traditional risk factors did not alleviate this association (HR: 0.33, 95%CI: 0.19-0.55).
    Comparable results were seen for the secondary endpoint of total CV events.
  • Such strong associations were not seen for HDL-c level and HDL particle concentration.
  • Sensitivity analyses that modelled cholesterol efflux capacity as a continuous measure yielded consistent findings (fully adjusted HR for atherosclerotic CV events per 1 SD increase in efflux capacity: 0.68, 95%CI: 0.55-0.84, and for all CV events: HR: 0.79, 95%CI: 0.67-0.94). Also analyses that were restricted to the hard CV endpoints non-fatal and fatal MI and stroke did not change these findings.


This study showed that a functional property of HDL, namely its cholesterol efflux capacity, was reversely associated with the occurrence of atherosclerotic CV disease in a population-based cohort free from CV disease at baseline. This association was maintained despite multivariate correction, which suggests that HDL function is associated with CV risk via processes other than those related to HDL-c level, HDL particle concentrations or traditional CV risk factors.

The accompanying article was published in NEJM on November 18

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