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Synthetic cholesterol may clear blocked heart arteries

Published Sep. 2, 2005

A synthetic form of "good cholesterol" has been shown to quickly shrink blockages clogging coronary arteries, offering for the first time the possibility of a drug that could actually reverse heart disease rapidly, researchers reported Tuesday.

In a small, preliminary study, the laboratory-made substance, which mimics a type of cholesterol discovered in a group of surprisingly healthy villagers in rural Italy, significantly reduced in just six weeks the amount of plaque narrowing arteries of patients, the researchers reported.

Because the approach attacks the underlying source of many heart attacks, the results could mark a milestone in the search for new ways to treat the nation's No. 1 killer, researchers said.

"For the first time, we've shown that you can reverse coronary disease with drug therapy in a matter of weeks," said Steven E. Nissen, a cardiologist at the Cleveland Clinic who coordinated the nationwide study. "We really have, for the first time, the opportunity to attack this disease at its fundamental basis."

Nissen and other researchers cautioned that the study involved only 47 patients and that further studies are needed to confirm the findings, fully evaluate the drug's safety and determine if the treatment actually cuts the risk of heart attacks and strokes.

"It's extremely preliminary," said Susan Bennett, clinical director of the George Washington University Hospital Women's Heart Program, speaking on behalf of the American Heart Association. "But it is very intriguing."

Other experts said the study has opened up an entirely new way to approach treating atherosclerosis, known commonly as hardening of the arteries.

"This is the first true test of the concept that specifically targeting HDL, the good cholesterol, can impact plaque and atherosclerosis in humans," said Daniel J. Rader, director of preventive cardiology at the University of Pennsylvania, who wrote an editorial accompanying the new study in the Journal of the American Medical Association.

Scientists have long known that there are two forms of cholesterol: One is low-density lipoprotein (LDL), which is the "bad cholesterol" because it accumulates inside artery walls. The other is high-density lipoprotein (HDL), called the "good cholesterol" because it protects against heart disease, primarily by lowering LDL levels.

About 30 years ago, researchers discovered about 40 people in the small rural northern Italian town of Limone Sul Garda who had a surprisingly low rate of heart disease despite their extremely low HDL levels. Scientists determined that their HDL was slightly unusual.

Esperion Therapeutics Inc. of Ann Arbor, Mich., developed a genetically engineered form of this version of HDL, dubbed ApoA-I Milano.

In the study, Nissen and colleagues at 10 centers around the country gave weekly infusions of either the synthetic HDL or an inert placebo to 47 heart disease patients for five weeks.

Compared to those who received the placebo, the patients who received the synthetic HDL experienced about a 4 percent reduction in the plaques lining their arteries, a reduction 10 times greater than anything scientists had tried previously, the researchers found.