When good cholesterol is even better

HDL's efficiency, not just quantity, appears important for heart health

How much good cholesterol a person has is not as important as how well that good cholesterol works to stop heart disease, a new study suggests.

High-density lipoprotein — also known as HDL, or “good” cholesterol — is healthy for the heart, previous studies have indicated. People with high blood levels of the molecule tend to have lower risk of developing heart disease than people with low levels.

But a new study suggests that the amount of good cholesterol in the blood may not be the most important factor in protecting against clogged arteries and cardiovascular disease. The study, published January 13 in the New England Journal of Medicine, shows that HDL’s efficiency at removing fats from arteries is a better predictor of who will develop heart disease than is the level of good cholesterol in the blood.

The results “suggest that just measuring HDL levels isn’t enough to figure out what’s going on,” says Jay Heinecke, an endocrinologist at the University of Washington in Seattle, who wrote an editorial comment on the research in the same issue of the journal. “It opens up the idea that there’s a lot we don’t know about HDL.”

In the study, some people’s good cholesterol was more efficient at relieving the white blood cells of a cholesterol burden than other people’s, found researchers led by Daniel Rader at the University of Pennsylvania School of Medicine in Philadelphia. Healthy people with this trait, known technically as a higher cholesterol efflux capacity, had less thickening of their carotid arteries than did people with less efficient cholesterol-clearing HDL. And, in a separate group of people, HDL functioning was a better indicator than HDL levels of whether the person had heart disease, the team found.

Doctors won’t be able to test their patients’ HDL efficiency any time soon. “We don’t yet have an assay or a test that can be used in a clinical setting,” says Rader. But the work does shed light on some important questions about how good cholesterol works.

“It says that the good cholesterol is more complicated than the bad cholesterol story,” says Christopher Cannon, a cardiologist at Brigham and Women’s Hospital in Boston. Bad cholesterol can build up in arteries, thickening the vessels and narrowing the space blood can squeeze through, so reducing artery damage is as straightforward as lowering the amount of bad cholesterol in the blood. “But good cholesterol actually has to do something to pull bad cholesterol out of the arteries” and send it to the liver for disposal, Cannon says. Exactly how the molecule accomplishes that task efficiently remains to be seen, and is next on the list for Rader and his colleagues to study.

“Now they have to put themselves to work,” says Valentin Fuster, director of the Mount Sinai Heart center in New York City, ticking off a list of research questions raised by the finding. Measurements of thickening of the carotid artery, which feeds oxygen-rich blood to the head and neck, aren’t good indicators of what is happening to arteries feeding the heart, he notes. While the study has value, Fuster would like to see more work showing how HDL efficiency affects arterial disease and how cholesterol-clearing capacity relates to other heart disease risk factors, such as age.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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