In a Single Gene, a Path to Fight Heart Attacks
Posted: June 21, 2014 at 6:52 am
Gretchen Ertl/The New York Times
Dr. Sekar Kathiresan of the Massachusetts General Hospital and the Broad Institute, in Boston, June 17, 2014. Kathiresan led one of two teams to identify a genetic mutation in the Amish community that protects against heart disease by keeping triglyceride
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 that there are no guarantees that 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 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 new studies 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 - 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 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 20 Amish 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 down the gene's role in heart attacks.
Sam, a 55-year-old Amish farmer who declined to have his last name published, saying he was uncomfortable about being conspicuous, has such a beneficial mutation. He recalls little heart disease in his family. On a cold day last fall, as an icy rain fell outside, he sat at a small wooden table in his daughter's house and laid out a sheet of paper that showed he had a triglyceride level of 45. The average in the United States is 147.
"It's nice that something came out that is positive," he said.