Gene Study Questions Impact of Increasing 'Good' Cholesterol Levels
By Salynn Boyles
WebMD Health News
Reviewed by Laura J. Martin, MD
Millions of people take statin drugs like Crestor, Lipitor, Pravachol, and Zocor to lower their low-density lipoprotein (LDL), or "bad" cholesterol. Studies have shown that high LDL levels are linked to an increase in heart attack risk.
But the benefits of increasing HDL are less clear, and studies of HDL-raising drugs have been largely disappointing.
Higher HDL Not Protective
In the newly reported study, investigators from Harvard Medical School used a relatively new research technique that tests connections between genes and disease to examine whether HDL has a direct impact on heart attack risk.
In earlier studies, the researchers identified a gene variant found in about 2.6% of the population associated with elevated HDL levels.
People with the gene variant have levels that are, on average, about six points higher than people without it.
When the researchers looked for the variant in about 21,000 people who had experienced heart attacks and 95,000 people with no heart attack history, they found that carriers did, indeed, have higher HDL levels.
But they saw no evidence that these people also had a lower susceptibility to heart attacks.
"The expectation was that the people who carried this genetic variant would have a lower heart attack risk, but that is not what we found," says researcher Sekar Kathiresan, MD, of Harvard Medical School and Massachusetts General Hospital.
In a second study, which involved 14 more common gene variants also associated with HDL, the researchers once again found no evidence that the variants had a direct, protective role in heart attack risk.
Kathiresan tells WebMD that HDL remains an important tool for assessing heart disease risk, but he says the new research raises even more questions about the benefits of taking drugs to raise HDL levels.
HDL Drug Trials Disappointing
The trial was halted early a year ago when it was determined that people with heart disease who had low HDL levels did not benefit from the treatment.
There was even a suggestion that taking high doses of niacin raised stroke risk.
The drug company Pfizer abandoned its experimental HDL-boosting drug torcetrapib in 2006 when trials showed an increase in heart attack and stroke risk among users.
And earlier this month, Roche Pharmaceuticals abruptly stopped late-phase trials of its similar drug, dalcetrapib, finding no evidence of a lower heart attack risk in users.
American Heart Association past president Robert Eckel, MD, says the new research casts even more doubt on the strategy of raising HDL to lower heart and stroke risk.
Eckel is a professor of medicine at the University of Colorado School of Medicine in Aurora.
"HDL levels are related to risk, but that doesn't mean that raising HDL is beneficial," he says. "What we do know is that lowering LDL has a big impact on risk, so the take-home message remains, 'Get those LDL numbers down,'" he says.
Kathiresan says his research team will continue to search for genes that alter HDL and lower heart attack risk.
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