Cholesterol Efflux Capacity Inversely Linked to Cardiovascular Events

Fenofibrate Therapy More Beneficial in Women With Type 2 Diabetes
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Cholesterol efflux capacity demonstrated an adverse association with cardiovascular events.

Cholesterol efflux capacity appears to be inversely associated with incident atherosclerotic cardiovascular (CV) events, according to a new study presented at the American Heart Association’s Scientific Sessions 2014. 

Researchers reported at this meeting that participants in the highest quartile of cholesterol efflux capacity were less likely to suffer a heart attack, stroke or death from heart disease, as compared with those in the lowest quartile. The association was much stronger for cholesterol efflux than for the traditional measurement of HDL cholesterol level.  

This is the first report of a measure of HDL function in a population-based study and supports future studies investigating HDL cholesterol efflux and cardiovascular disease (CVD)

“We were really surprised by the magnitude of the findings,” said study author Anand Rohatgi, MD, of the University of Texas Southwestern Medical Center in Dallas.

Dr. Rohatgi, who presented the study findings at the meeting, said niacin raises HDL cholesterol 20% to 25%, and new cholesterylester transfer protein (CETP) inhibitors raise HDL cholesterol even more. However, he said none of these therapies have been shown to reduce cardiac events.

The whole story of what HDL does, he said, is not being told by HDL cholesterol levels alone.

Dr. Rohatgi and his colleagues conducted a study with stored plasma samples from 2,924 adults aged 30 to 65 years from the Dallas Heart Study. All participants were free from CVD, niacin use or death within 1 year of enrollment. 

The researchers found that HDL cholesterol efflux capacity was robustly and inversely associated with incident atherosclerotic cardiovascular disease (ASCVD). This held true even when the researchers adjusted for HDL cholesterol levels and HDL particle number.

Studies have consistently shown that low HDL cholesterol is a risk factor for ASCVD events. However, several recent clinical trials have suggested that some interventions that increase HDL cholesterol do not reduce CV events.  

Current HDL measurement methods reflect only the circulating levels of HDL and not the functional properties of this lipoprotein. This led Dr. Rohatgi and his colleagues to examine whether measuring HDL function could be a biomarker. 

The researchers measured cholesterol efflux capacity as the fraction of total boron dipyrromethene difluoride (BODIPY)-labeled cholesterol in macrophages efflux to apolipoprotein B-depleted plasma. They also measured HDL particle number by NMR. The primary ASCVD endpoint was a composite of first cardiac event, coronary revascularization and CV death through a median 9.4 years of follow-up. 

The cohort was an unselected population-based sample free from CVD at baseline. The median age of the participants was 43 years and 57% were female. The cohort was 49% black. 

A total of 132 first ASCVD events occurred during follow-up. In an adjusted analysis, baseline HDL level was not linked to CV events (HR=1.08; 95% CI, 0.59-1.59). Conversely, in a fully adjusted model that accounted for traditional CV risk factors, HDL cholesterol level and HDL particle concentration, those in the highest quartile of cholesterol efflux capacity, as compared with the lowest, had a 67% reduction in CV risk (HR=0.33; 95% CI, 0.19-0.55).

The researchers also found that adding cholesterol efflux capacity to traditional risk factors improved discrimination and reclassification indexes.

The findings were simultaneously published online in The New England Journal of Medicine

“I think these findings will be of particular interest to endocrinologists because this appears to be applicable to studying diabetes and the function of HDL cholesterol in diabetes,” Dr. Rohatgi said in an interview with Endocrinology Advisor

“Our next studies are to validate these findings in other populations and to measure this in patients who are on lipid modifying therapies.”


  1. Rohatgi A. CS.04 – Trials and Cardiovascular Registries. High Density Lipoprotein Efflux Capacity and Incident Cardiovascular Events. Presented at: American Heart Association’s Scientific Sessions 2014; Nov. 15-19, 2014; Chicago.
  2. Rohatgi A et al. N Engl J Med. 2014;doi:10.1056/NEJMoa1409065.