Genetic Heart Disease Risk Eased by Healthy Habits, Study Finds


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Is genetics destiny when it comes to heart disease?

A new analysis of data from more than 55,000 people provides an answer. It finds that by living right — by not smoking, by exercising moderately and by eating a healthy diet heavy in fruits, vegetables and grains — people can tamp down even the worst genetic risk.

“DNA is not destiny; it is not deterministic for this disease,” said Dr. Sekar Kathiresan, the director of the Center for Human Genetic Research at Massachusetts General Hospital. “You do have control over the problem, even if you have been dealt a bad genetic hand.”

The research, by Dr. Kathiresan and his colleagues, is the first attempt to use large data sets to tease apart the effects of genes and lifestyle in heart disease, researchers said. It was published on Sunday in The New England Journal of Medicine to coincide with the presentation of the results at the annual meeting of the American Heart Association.

About 365,000 people die of coronary heart disease — the most common type — annually in the United States, and 17.3 million worldwide, making it one of the biggest killers.

The investigators found that genes can double the risk of heart disease, but a good lifestyle cuts it in half. Just as important, they found, a terrible lifestyle erases about half of the benefits of good genetics.

Dr. Michael Lauer, a cardiologist who is the deputy director for extramural research at the National Institutes of Health and was not involved in the analysis, called the study impressive. Its subjects were from four large studies, yet the results were consistent and convincing, even though the populations were quite varied. That sort of research, he said, “is not something we see very often, and certainly not with this degree of rigor.”

One study the group analyzed involved black and white Americans aged 45 to 64. A good lifestyle in those with the highest genetic risk cut the 10-year likelihood of heart disease to 5.1 percent from 10.7 percent. Another study involved 21,222 American women aged 45 and older who were health professionals; their 10-year risk fell to 2 percent from 4.6 percent in the high-risk group if they also had a healthy lifestyle. In a third study, Swedish participants aged 44 to 73 had a 10-year risk reduction to 5.3 percent from 8.2 percent. And finally, in a study of Americans aged 55 to 80, those with genetic risk but a healthy lifestyle had significantly less calcium, a sign of heart disease, in their coronary arteries.

Dr. Lauer also was encouraged by the finding that the fourth study, which used imaging, showed the same pattern as the others that used heart attacks and other signs of heart disease as endpoints.

“That gives us more confidence that the findings are real,” he said.

The results, he said, should quell the cries of both those who emphasize genes above all and those who emphasize elements of lifestyle above all. “It’s not nature or nurture, it’s both,” he said.

The study got its start after Dr. Amit V. Khera, one of Dr. Kathiresan’s postdoctoral fellows, noticed that researchers had looked at genetic risks of heart disease and had, in different studies, looked at the effect of environment and lifestyle risks. So, he wondered, why not look at lifestyles and genetics in the same populations and see how much each contributes?

The researchers began about a year and a half ago, analyzing data from four large studies that not only had genetic data on participants but also had information on lifestyles and on which participants developed heart disease.

The investigators developed a genetic score based on 50 genes associated with heart disease. They developed a lifestyle score based on whether people smoked, whether they exercised at least once a week, whether they followed a healthy diet — one with fruits, vegetables, fish, whole grains and nuts — and whether they were obese.

An optimum lifestyle score was defined as having three or all four of these elements, which is important, Dr. Kathiresan said, because many people who are obese have enormous difficulty losing weight and maintaining their weight loss. “You can get into this group even if you are obese by not smoking, exercising and eating a healthy diet, “ he said.

Even better, said Dr. Lawrence J. Appel, the director of the Welch Center for Prevention, Epidemiology and Clinical Research at Johns Hopkins Medical Institutions, you do not have to have an exemplary lifestyle to reap a big benefit. It looks as if the biggest protective effect by far came from going from a terrible lifestyle to one that was at least moderately good.

Dr. John Michael Gaziano, a preventive cardiologist at the VA Boston Healthcare System and at Brigham and Women’s Hospital, said the work showed the power of large data sets. Until recently, researchers mostly used much smaller data sets, which tend to have a lot of random variation, making results hard to interpret. The Million Veteran Program, a study that he is leading, and the National Institutes of Health’s precision medicine initiative that is recruiting a million participants should provide the sort of data that can make results like Dr. Kathiresan’s more feasible and more powerful.

For Dr. Gaziano, the biggest surprise was that a test based on combining 50 genes, each of which had a tiny role in heart disease, was such a powerful predictor of risk. The larger studies underway now should allow researchers to understand more about how much each of those genes contributes, he added.

Meanwhile, the new study shows a new way to think about genes and lifestyle, researchers say.

“It’s very important,” said Dr. David Maron, the director of preventive cardiology at Stanford, who was not involved in the new study. “If you are dealt a bad hand, there are things you can do to attenuate the risk.”

Dr. Kathiresan is already using the study’s results when he sees patients, he said. The genetic test is not available outside of research studies, he said, but he often gets an idea of who has a worrisome genetic risk when he talks to patients.

“A poor man’s substitute,” he said, “is: ‘My dad died at 45 of a heart attack. I have a strong family history.’”

He now replies, “You have it in your power to change that risk.”

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