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Even 'Good' Cholesterol Can Turn Bad

HDL sometimes inflames immune system and increases heart risk

MONDAY, Nov. 24, 2003 (HealthDayNews) -- HDL cholesterol -- the "good" kind that usually protects arteries -- can turn bad, menacing some heart patients, say researchers who are puzzling out what makes this happen and how its ill effects can be treated.

Low-density lipoprotein, or LDL, cholesterol is the bad kind that clumps together to form plaques that block arteries. Normally, high-density lipoprotein, or HDL, cholesterol reduces that risk, presumably by carrying cholesterol out of the blood to the liver.

But sometimes HDL cholesterol suddenly triggers an inflammatory attack by the immune system that damages arteries and increases the risk of heart attack or stroke, says Dr. Benjamin J. Ansell, director of the University of California at Los Angeles Center for Primary Care-Based Cardiovascular Disease Prevention and member of a research team that has been studying the process for nearly a decade.

It's still not entirely clear when and why the Jekyll-and-Hyde transformation occurs, Ansell says. It is known to happen after surgery or illness in some people, "as an acute phase response where a lot of inflammation in the body tends to create this kind of HDL cholesterol," he says. "Some people with coronary disease have it, and we are in the process of trying to characterize it further."

Their latest attempt at characterization, reported in the Nov. 24 issue of Circulation, used two tests devised at UCLA on two groups of patients.

One group consisted of people who had coronary disease even though their HDL levels were more than twice the American average. The test given to them showed that, in most of them, HDL increased the activity of immune system cells that cause inflammation.

A second test to see whether HDL was inflammatory was given to another group, people with coronary disease who were taking a statin drug to reduce high levels of LDL cholesterol. They were compared with a group of people free of coronary disease.

That test found high levels of inflammatory HDL in the coronary patients but not in the healthy group, Ansell says. Having inflammatory HDL was a better measure of risk than simple measurements of HDL levels, he says.

The goal, Ansell says, is that such a test will be "a way to pick out patients who have a high risk of coronary disease even though they have normal levels of HDL." The study shows that risk can be reduced by statin treatment, but many of these patients are not given statins because their HDL level seems protective, he says.

It will be a while before testing for inflammatory HDL moves into clinical practice, says Dr. Alan M. Fogelman, chair of the department of medicine at UCLA's David Geffen School of Medicine and senior author of the journal report.

All the studies done to date include only a small number of people, Fogelman says. Proof of the test's value requires large-scale trials that would include hundreds of people and probably would run for years, he says.

"We're very excited about the results so far," Fogelman says. "But things that look good in small groups don't always prove out in large populations."

No large-scale clinical trial is currently being planned, he adds.

One notable aspect of the HDL cholesterol work is that it reinforces the growing belief that inflammation plays a major -- and until recently, unappreciated -- role in heart disease and stroke, Fogelman says.

"When we went to medical school, it was thought to be a degenerative disease," he says. "That has changed."

More information

An explanation of the differences between HDL and LDL cholesterol can be found at the American Heart Association. You can learn about cholesterol-lowering therapy from the National Heart, Lung, and Blood Institute.

SOURCES: Benjamin J. Ansell, M.D., director, Center for Primary Care-Based Cardiovascular Disease Prevention, University of California, Los Angeles; Alan M. Fogelman, M.D., chair, Department of Medicine, UCLA David Geffen School of Medicine; Nov. 24, 2003 Circulation
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