CardioExchange Archive

A new study offers important evidence explaining the protective role of HDL cholesterol against cardiovascular disease. Previous studies with drugs that increase HDL levels, including niacin and CETP inhibitors, have not been found beneficial. The new study suggests that simply increasing HDL levels isn’t useful. Instead, cholesterol efflux, the ability of HDL to remove cholesterol from cells — part of the process called reverse cholesterol transport — appears to be the key. The results were presented on Tuesday by Anand Rohatgi at the American Heart Association meeting in Chicago and published in the New England Journal of Medicine.

The investigators followed 2416 people participating in the Dallas Heart Study, who were free of cardiovascular disease at baseline, for 9.4 years. In accord with previous studies, there was a trend suggesting that HDL levels were linked to the development of cardiovascular events, but this association dissolved when other risk factors were considered, so that HDL level did not emerge as a significant independent predictor of cardiovascular disease. By contrast, cholesterol efflux was a strong predictor of outcome, “suggesting that HDL function is associated with cardiovascular risk by means of processes distinct from those reflected by the HDL cholesterol level, HDL particle concentration, or traditional cardiovascular risk factors,” according to the authors.

Daniel Rader, a co-author of the study, was also the discussant at the AHA session. He noted that a previous study had linked cholesterol efflux with prevalent coronary heart disease, but this was the first study to follow people and show that cholesterol efflux was linked to the development of cardiovascular disease over time. Rader expressed optimism about potential roles for cholesterol efflux in the future. According to Rader, efflux may one day be used as a clinical test to assess cardiovascular risk or to assess new therapeutic interventions.

A poster also presented at the AHA meeting provided some of the first results with a therapy intended to enhance cholesterol efflux. CSL112 is a novel formulation of apoA-I, the HDL component that is thought to be the key component in efflux. One study showed that CSL112 significantly increased efflux in 93 people without cardiovascular disease and 44 patients with stable coronary artery disease. This increase occurred in those with both low and high efflux activity at baseline.