WEDNESDAY, Jan. 12 (HealthDay News) -- High levels of HDL cholesterol -- the "good" kind -- have long been thought to help protect against heart disease. But new research finds that having high levels of HDL cholesterol may matter less than how well the good cholesterol functions -- that is, how well it works to rid the body of excess cholesterol.
HDL (high-density lipoprotein) cholesterol performs this clean-up by acting as a boat, removing unwanted cholesterol from cells called macrophages and transporting it to the liver, where the body can get rid of it. That helps prevent the cholesterol from getting stuck in the arterial walls, leading to the plaques that are a hallmark of heart disease, explained Dr. Daniel Rader, director of Preventive Cardiology at the University of Pennsylvania.
Low levels of HDL are strongly associated with an increased risk of heart disease, but the converse isn't always the case. For years, experts were perplexed at why some of those with high levels of HDL cholesterol were still at high risk of heart attacks. In fact, a trial for torcetrapib, a drug that raised levels of HDL cholesterol, was halted in 2006 when it emerged that people taking the drug were at heightened risk of heart attacks and death.
That led researchers to surmise there might be something about the way in which a person's HDL functioned that mattered more than HDL levels.
In the study, Rader and his colleagues took blood samples and measured the thickness of the blood vessel walls in the carotid artery of the necks of 203 healthy adults. The carotid thickness indicates arterial plaque and heart disease risk, Rader noted.
Researchers then took the HDL from the blood and applied it to macrophages derived from mouse cell lines. In humans and mice, macrophages are white blood cells that swallow invading microbes as a front line of defense; they also engulf cholesterol, thus contributing to the formation of plaques and inflammation in the walls of the arteries.
Participants whose HDL cholesterol was less able to remove cholesterol from the macrophages tended to have a thicker carotid artery.
"The function of the HDL was an even better predictor of the thickness of the carotid wall than the HDL level itself," said Rader, the senior study author. The researchers term this function "cholesterol efflux capacity."
The study is published in the Jan. 13 issue of the New England Journal of Medicine.
In a second experiment, the researchers measured the HDL function of 442 people who had undergone bypass surgery due to a blocked artery and 351 people without heart disease.
Those with heart disease had poorer HDL function than those without it, even after adjusting for traditional risk factors, the investigators found.
"We found the people who had blockages had significantly less ability to promote cholesterol removal than those who had no blockages," Rader said. "The measure of HDL function was a much better predictor of the likelihood of having blocked arteries than the measure of HDL cholesterol itself."
That doesn't mean high HDL is of no help, noted Dr. Robert Eckel, past president of the American Heart Association and a professor of medicine at University of Colorado. Generally, people with higher levels of HDL also have better function, Eckel said.
But the findings may help explain why some people with high HDL are still found to have heart disease.
"I see plenty of people who have heart disease but who also have high levels of HDL. So what is going on there? Why aren't they protected? This study may suggest their HDL isn't working properly to carry out its function," Eckel said.
The converse may also be true: even someone with low levels of HDL may never develop heart disease because their HDL may work very well.
"Just because someone's HDL level was high, doesn't necessarily predict their function is going to be high," Rader said. "And just because their HDL is low, doesn't mean their HDL function, or their ability to remove cholesterol, is low."
Statins, a popular cholesterol-lowering medication, lowers levels of LDL, or "bad" cholesterol. When LDL is engulfed by macrophages, it generally gets stuck in the arterial walls, accumulates and forms plaques.
Statins do not effect HDL cholesterol levels, Rader said.
There is no test available to the public for HDL function, nor is there likely to be one soon, Rader noted. He pointed out that researchers also don't know what causes HDL cholesterol to function poorly in removing excess cholesterol, something that will be the subject of future research.
The American Heart Association has more on cholesterol.
SOURCES: Daniel J. Rader, M.D., director, preventive cardiology, University of Pennsylvania, Philadelphia; Robert Eckel, M.D., professor, medicine, University of Colorado, Denver; Jan. 13, 2011, New England Journal of Medicine
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