It’s long been known that some people have a genetic profile that puts them at high risk of developing heart disease. It’s also been known that following a healthy lifestyle — particularly, not smoking, keeping off excess weight, eating nutritious foods and getting regular exercise — can reduce the risk of heart disease.
What hasn’t been clear is the extent that these two factors — genes and lifestyle — influence each other.
Until now, perhaps. A major new analysis of data from four large studies has found that, even among people at high genetic risk for heart disease, a healthy lifestyle cuts in half the likelihood of experiencing a heart attack or other heart problem.
The analysis also found that the opposite is true: An unhealthy lifestyle can cancel out the benefits of “good” genes.
“The basic message of our study is that DNA is not destiny,” said Dr. Sekar Kathiresan, director of the Center for Human Genetic Research at Massachusetts General Hospital and the study’s senior author, in a released statement. “Many individuals — both physicians and members of the general public — have looked on genetic risk as unavoidable, but for heart attack that does not appear to be the case.”
For their analysis, Sekar and his colleagues analyzed data collected from more than 55,000 participants in four separate large-scale studies. Three of them — the Atherosclerosis Risk in Communities Study, the Women’s Genome Health Study, and the Malmo Diet and Cancer Study — are prospective cohort studies that followed their participants for up to 20 years. The fourth one, the Biolmage Study, used imaging tests to look for the presence of plaque buildup (atherosclerosis) in its participants’ arteries — a sign of heart disease.
The NEJM analysis assigned each participant in all four studies a genetic risk score for heart disease, which was determined by whether the participant carried any of 50 gene variants associated with an elevated risk for heart attack. The participants were divided into five groups based on these scores.
Each participant also received a lifestyle score, which reflected their adherence to four lifestyle factors cited by the American Heart Association as being most beneficial to heart health: no current smoking, no obesity (defined as a body mass index, or BMI, less than 30), physical exercise at least once weekly, and a healthy dietary pattern.
A lifestyle with at least three of those factors was deemed “favorable,” while a lifestyle with none or one of the factors was considered “unfavorable.”
After analyzing all that data, the researchers found — not unsurprisingly — that people with the highest gene risk were almost twice as likely as those with the lowest risk to develop heart problems.
They found roughly the same doubling of heart-disease risk — again, not unsurprisingly — among the people in the unfavorable lifestyle group compared to those in the favorable group.
The researchers then dug deeper into the data to examine how lifestyle factors predicted heart problems among people within each category of genetic risk. Here they did uncover something unexpected: Adhering to a favorable lifestyle cut in half the risk of experiencing a heart-disease “event” — defined as a heart attack, the need for a procedure to open blocked coronary arteries, or sudden cardiac death — for people at low, intermediate and high genetic risk.
In the Atherosclerosis Risk in Communities Study, for example, which included Americans aged 45 to 64, the 10-year risk of a heart-disease event among people at high genetic risk was 5.1 percent for people with a favorable lifestyle compared to 10.7 percent for those with an unfavorable one.
In the Biomage imaging study, which included Americans aged 55 to 80, people with a favorable lifestyle had significantly less calcium (plaque) buildup in their arteries than those with an unfavorable lifestyle — including among the group of participants with the highest genetic risk for heart disease.
Limitations and implications
The analysis has several limitations. Most important, all the studies used in the analysis were observational, so the relationship between lifestyle factors and the risk of heart disease cannot be interpreted as a causal one. Also, the three cohort studies used slightly different methods of assessing lifestyle behaviors when their participants were enrolled. Those differences may have affected the analysis’ findings. In addition, although the studies did include black participants, their numbers were not large enough to extend the analysis’ findings to them with any “robust” confidence.
Still, the findings are encouraging for people worried about their genetic risk.
“Some people may feel they cannot escape a genetically determined risk for heart attack, but our findings indicate that following a healthy lifestyle can powerfully reduce genetic risk,” said Kathiresan. “Now we need to investigate whether specific lifestyle factors have stronger impacts and conduct studies in more diverse populations, since most of the participants in these studies are white.”