Scientists identify aid to heart attacks
Study showing gene mutation that lowers triglyceride levels in blood good news for preventing disease
Two major studies by leading research groups published independently Wednesday identified mutations in a single gene that protect against heart attacks, the leading killer of Americans, by keeping levels of triglycerides — a kind of fat in the blood — 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 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, but since then there have been no major new drugs approved for lowering heart disease risk. About 720,000Americans a year have heart attacks.
Puzzling researchers
Although statins are effective in reducing heart attack risk, many users still often have high levels of triglycerides and go on to have heart attacks. So the results of the newstudies are good news, said Dr. Daniel J. Rader, the director of the Preventive Cardiovascular Medicine and Lipid Clinic at the University of Pennsylvania, who was not involved in the research.
“We’ve been looking for something beyond statins,” Rader said. “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, that would mean about 20 percent of adult Americans. If it was just those with the highest levels, above 500, then 2 percent 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 20A mish people has a mutation that destroys a gene, APOC3, involved in triglyceride metabolism, as compared with one in 150 Americans generally. The scientists were intrigued but did not have enough data to nail downthe gene’s role in heart attacks.
Triglycerides have long puzzled researchers, although they are routinely measured along with cholesterol in blood tests and are often high in people with heart disease. Many experts were unconvinced they caused heart attacks. Clinical trials of drugs that lowered triglycerides by a small amount added to doubts about their role. The drugs had no effect on heart attack rates.
As for triglycerides themselves, “do they just keep bad company or are they independently doing something to risk?” said Dr. Robert Hegele, a heart disease expert at Western University in London, Ontario, whowas not involved with the newstudies. Strong evidence
Those 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,” Hegele said, that triglycerides are in fact a cause of heart attacks.
The researchers discovered that people with a genetic predisposition to higher triglyceride levels had more heart attacks, and those with genetically lower triglyceride levels had fewer.
Their study, published last year in Nature Genetics, did not isolate individual genes, though. They just pointed to signposts on the long stretch of 30 million DNA letters that were near the genes. So the investigators began a hunt for the genes themselves.
One gene, APOC3, stood out. The scientists found four mutations that destroyed the function of this gene. The Amish study had discovered that people with such a mutation could drink a big rich milkshake, loaded with fat, and their triglyceride levels did not budge. For everyone else, they spiked. The studies show what that means to people’s health.