'Good cholesterol' may be overstatement

The name alone sounds so encouraging: HDL, the "good cholesterol." The more of it in your blood, the lower your risk of heart disease. So bringing up HDL levels has got to be good for health.

Or so the theory went.

Now, a new study that makes use of powerful databases of genetic information has found that raising HDL levels may not make any difference to heart disease risk. People who inherit genes that give them naturally higher HDL levels throughout life have no less heart disease than those who inherit genes that give them slightly lower levels. If HDL were protective, those with genes causing higher levels should have had less heart disease.

Researchers not associated with the study, published online Wednesday in The Lancet, found the results compelling and disturbing. Companies are actively developing and testing drugs that raise HDL, although three recent studies of such treatments have failed. And patients with low HDL levels are often told to try to raise them by exercising or dieting or even by taking niacin, a drug that raised HDL but failed to lower heart disease risk in a recent clinical trial.

"I'd say the HDL hypothesis is on the ropes right now," said James A. de Lemos, a University of Texas Southwestern Medical Center professor of medicine who was not involved in the study.

Michael Lauer, director of the division of cardiovascular sciences at the National Heart, Lung and Blood Institute, agreed. "The current study tells us that, when it comes to HDL, we should seriously consider going back to the drawing board -- in this case meaning back to the laboratory," said Dr. Lauer, who also was not connected to the research. "We need to encourage basic laboratory scientists to figure out where HDL fits in the puzzle -- just what exactly is it a marker for?"

But Steven Nissen, the Cleveland Clinic's chairman of cardiovascular medicine, who is helping conduct studies of HDL-raising drugs, said he remained hopeful. HDL is complex, he said, and it is possible that some types of HDL molecules might in fact protect against heart disease. "I am an optimist," Dr. Nissen said.

The study's authors emphasize that they are not questioning the well-documented finding that higher HDL levels are associated with lower heart disease risk. But the relationship may not be causative. High HDL levels may be a sign that something else is going on that makes heart disease less likely. But HDL itself may not be directly reducing risk.