Heart health tied to hdl "good" cholesterol function, not high level

Heart health tied to hdl

Reduced risk of coronary artery disease is more closely linked to the function of HDL, the so-called "good cholesterol", and not so much to its level in the blood as previously thought, according to a new US study published in the New England Journal of Medicine, NEJM.

The discovery could affect the development of drugs that target HDL in treating heart disease, said the researchers.

You can read about the study, led by the University of Pennsylvania School of Medicine (Penn) in Philadelphia, online in the 13 January issue of NEJM.

A major cause of cardiovascular disease is atherosclerosis, caused by the build up of plaques of fatty materials like cholesterol on the linings of artery walls.

When researchers discovered that high levels of high-density lipoprotein (HDL) cholesterol, the so-called "good" cholesterol were linked to reduced risk of cardiovascular disease, there was a rush to develop new drugs to treat heart disease by targeting HDL levels.

However, recent studies have questioned whether using drugs to increase HDL is good for patients.

In this study, Dr Daniel J Rader, director, Preventive Cardiology at Penn, and colleagues, found that a particular measure of HDL function, which they call "efflux capacity", is more closely linked to protection against heart disease than HDL level itself.

Efflux capacity is a measure of how well HDL removes cholesterol from cholesterol-loaded macrophages, a type of white blood cell, that accumulate in arterial plaque.

Recent studies have suggested that perhaps it is how HDL functions rather than how much of it there is in the blood that affects cardiovascular risk and the effectiveness of HDL-targeted drugs, so Rader and colleagues decided to investigate efflux capacity.

"Our study is the first to relate a measure of HDL function - its ability to remove cholesterol from macrophages - to measures of cardiovascular disease in a large number of people," Rader told the press.

For the study, 203 healthy people volunteered to undergo assessment of the thickness of the "intima-media" of their carotid artery, a measure of atherosclerosis. The researchers also recruited 442 patients with coronary artery disease, and 351 patients without the disease.

To measure the efflux capacity of HDL in all three groups of participants, Rader and colleagues used "a validated ex vivo system that involved incubation of macrophages with apolipoprotein B-depleted serum," taken from their blood samples.

The results showed an inverse relationships between cholesterol efflux capacity and the thickness of the carotid intima-media both before and after adjustment for HDL cholesterol levels.

After adjusting for age and gender, the results also showed that increasing efflux capacity was tied to decreased likelihood of having coronary artery disease. The strength of the link did not change after adding traditional risk factors such as HDL cholesterol levels.

The researchers also found that men and current smokers had decreased HDL efflux capacity.

Rader and colleagues suggested that although cholesterol efflux is only one of the many functions of HDL, and represents only a small fraction of the overall flow through the cholesterol pathway, it is probably the one with most impact on protecting against heart disease.

Rader said their findings support the idea that measuring what HDL does gives better information than just measuring its level, and points to the need to measure HDL function in assessing new drugs that target HDL.

"Future studies may prove fruitful in elucidating additional HDL components that determine cholesterol efflux capacity," he said.

"Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis."

Amit V. Khera, Marina Cuchel, Margarita de la Llera-Moya, Amrith Rodrigues, Megan F. Burke, Kashif Jafri, Benjamin C. French, Julie A. Phillips, Megan L. Mucksavage, Robert L. Wilensky, Emile R. Mohler, George H. Rothblat, and Daniel J. Rader.

N Engl J Med, 2011; 364:127-135, online 13 January 2011.

DOI: 10.1056/NEJMoa1001689

Additional source: University of Pennsylvania School of Medicine (press release, 12 Jan 2011).

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Section Issues On Medicine: Cardiology