Higher Levels of 'Good' HDL Cholesterol can Cause Heart Attack for Some

Kathleen Blanchard's picture
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Contrary to past belief, patients whose ‘good’-HDL-cholesterol levels are high are at risk for recurrent heart attack. The findings come on the heels of a pharmaceutical study investigating the drug torcetrapib. The drug, in development by Pfizer pharmaceuticals and designed to raise levels of HDL cholesterol, instead caused heart attack and death for patients enrolled in a clinical trial. Researchers halted the study in 2006 as a result. Now scientists find that higher levels of ‘good’ HDL cholesterol can cause heart attack for some patients.

"It seems counterintuitive that increasing good cholesterol, which we've always thought of as protective, leads to negative consequences in some people," said James Corsetti, M.D., Ph.D., professor of Pathology and Laboratory Medicine at the University of Rochester Medical Center and lead author of the study. "We've confirmed that high HDL cholesterol is in fact associated with risk in a certain group of patients."

Charles Sparks, M.D., professor of Pathology and Laboratory Medicine and co-author of the study points out the importance of identifying individuals at risk for heart attack from higher levels of HDL cholesterol and the need to exclude them from studies. With these patients excluded, researchers may find that raising HDL cholesterol in the remaining population is effective in reducing cardiovascular disease risk." The second goal is to make heart disease treatment more personalized by finding patients who could suffer heart attack from elevated HDL cholesterol levels.

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The researchers found that patients with high CRP (C-reactive protein) levels with more HDL cholesterol are at higher risk for heart attack from the way good cholesterol behaves in the body in response to genes and environmental factors. The combination of higher levels of good cholesterol and inflammation actually sets some patients up for heart attack.

The scientists found that ester transfer protein (CETP) that moves cholesterol away from the blood vessels is associated with higher HDL cholesterol. The inflammatory molecule p22phox that causes inflammation and is linked to CRP levels combines to make higher levels of good cholesterol a bad thing for some patients that can lead to, rather than prevent, heart attack.

Despite the findings that higher levels of ‘good’ HDL cholesterol fails to prevent heart attack in some patients, pharmaceutical companies are still investing in drugs that raise cholesterol levels. Merck is now working on a related drug that is a cousin to torcetrapib – anacetrapib - to find out if the medication can raise HDL cholesterol levels and prevent heart attack. In 2011 Merck will begin clinical trials. The researchers suspect that more HDL cholesterol is good for most, but for some patients higher levels of good cholesterol can cause heart attacks.

Arteriosclerosis, Thrombosis, and Vascular Biology
doi: 10.1161/ATVBAHA.110.207977

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