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Scientists identify mutations that protect against heart attacks

Two major studies by leading research groups published Wednesday independently identified mutations in a single gene that protect against heart attacks by keeping levels of triglycerides, a kind of fat in the blood, very low for a lifetime.

These findings are expected to lead to a push to develop drugs that mimic the effect of the mutations, potentially offering the first new class of drugs to combat heart disease in decades, experts say. Statins, which reduce LDL cholesterol, another cause of heart disease, became blockbusters in the late 1980s. Since then there have been no major new drugs approved for lowering heart disease risk. But experts caution that drug development takes years and there are no guarantees new treatments will work as hoped.

Heart attacks are the leading killer in the United States, and about 720,000 Americans a year have them.

Although statins reduce heart attack risk, many users still often have high levels of triglycerides and go on to have heart attacks.

"We've been looking for something beyond statins," said Dr. Daniel J. Rader, director of the Preventive Cardiovascular Medicine and Lipid Clinic at the University of Pennsylvania, who was not involved in the research. "After we have put people on high-dose statins, what else can we do? Essentially nothing."

Experts differ in their estimates of how many Americans might be candidates for a triglyceride-lowering drug. If the eligible group included all adults with triglyceride levels of 200 or more — the normal level is 150 or less — that would mean about 20 percent of adult Americans. If it was just those with the highest levels, above 500, then 2 to 3 percent of adults would qualify.

The discovery announced Wednesday was hinted at in 2008 in a much smaller study in the Amish conducted by researchers from the University of Maryland's medical school. One in 20 Amish people has a mutation that destroys a gene, APOC3, involved in triglyceride metabolism, as compared with one in 150 Americans generally. Scientists were intrigued but did not have enough data to nail down the gene's role in heart attacks.

Triglycerides have long puzzled researchers. Many experts were unconvinced they actually caused heart attacks.

The new studies, published in the New England Journal of Medicine and funded by the National Institutes of Health and the European Union, provide "a very, very strong type of evidence" that triglycerides are a cause of heart attacks, said Dr. Robert Hegele, a heart disease expert at Western University in London, Ontario, who wasn't involved in the studies.

Scientists identify mutations that protect against heart attacks 06/18/14 [Last modified: Wednesday, June 18, 2014 10:41pm]
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