This article is more than 5 years old. Information may no longer be current.
Healthy lifestyle can offset high genetic CAD risk
Click Here to Manage Email Alerts
NEW ORLEANS — In individuals with high genetic risk, those with a favorable lifestyle focusing on no smoking, no obesity, regular physical activity and a healthy diet were less likely to develop CAD compared with those with an unfavorable lifestyle, according to data presented at the American Heart Association Scientific Sessions.
It has been established that lifestyle factors and genetic factors both contribute to CAD risk, but it was previously unknown whether a healthy lifestyle can offset high genetic risk, Sekar Kathiresan, MD, director of the Center for Human Genetic Research at Massachusetts General Hospital, said during a presentation. Kathiresan presented the new data as part of the Robert I. Levy Memorial Lecture and the findings were published in the New England Journal of Medicine.
Kathiresan and colleagues quantified genetic CAD risk in 55,685 individuals from four cohorts: ARIC, the Women’s Genomic Health Study, the Malmo Diet and Cancer Study, and the BioImage Study. Participants were stratified into five quintiles based on genetic risk, determined by prevalence of 55 genetic variants known to increase risk for CAD. The researchers also quantified lifestyle risk by using a scoring system of four factors: not smoking, no obesity, regular physical activity and healthy diet.
Compared with the bottom quintile of genetic risk, participants in the top quintile had higher risk for incident coronary events, defined as fatal or nonfatal MI or coronary revascularization (HR = 1.91; 95% CI, 1.75-2.09), according to the findings presented.
“With a polygenic risk score, we can identify a population at about twofold increased risk for a [CHD] event based on these 55 polymorphisms,” Kathiresan, who is also the Ofer and Shelley Nemirovsky MGH Research Scholar, director of the Cardiovascular Disease Initiative at the Broad Institute and associate professor of medicine at Harvard Medical School, said here. “The next question is, if you are at high genetic risk, can you modify risk based on lifestyle?”
This question is an important one, because many patients assume DNA-based risks are ones they cannot control, he said.
According to the findings, regardless of genetic risk, a favorable lifestyle — which was defined as having three or four of the healthy factors — conferred lower risk for CAD compared with an unfavorable lifestyle — which was defined has having one or none of the healthy factors.
Among those in the highest quintile of genetic risk, a favorable lifestyle conferred a 46% reduced risk for CAD vs. an unfavorable lifestyle (HR = 0.54; 95% CI, 0.47-0.63).
In ARIC, those in the highest quintile of genetic risk had a 10-year incidence for CAD of 10.7% if they followed an unfavorable lifestyle, but it dropped to 5.1% if they followed a favorable lifestyle, Kathiresan and colleagues found. A similar pattern was observed in the Women’s Genomic Health Study (4.6% to 2%) and in the Malmo Diet and Cancer Study (8.2% to 5.3%).
“What was interesting is that this gradation of lifestyle offsetting genetic risk was operative in every risk category,” Kathiresan said. “Another way to look at this, is if you have good genes and a bad lifestyle, the 10-year event rate [in ARIC] was 5.8%. That’s roughly equivalent to bad genes and a good lifestyle, with a 10-year event rate [in ARIC] of 5.1%.”
In the BioImage study, regardless of genetic risk category, a favorable lifestyle was associated with less coronary artery calcification, according to the researchers.
“These data reinforce, at the population level, the real primacy of adherence to a healthy lifestyle for CHD prevention,” Kathiresan said. “It’s important to continue to emphasize this. Patients shouldn’t equate DNA-based risk assessments with lack of control, or loss of control or determinism. Even if you have a family history of high genetic risk, you do have control over your own health by practicing optimal lifestyle.” – by Erik Swain
References:
Kathiresan S. Robert I. Levy Memorial Lecture. Presented at: American Heart Association Scientific Sessions; Nov. 12-16, 2016; New Orleans.
Khera AV, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1605086.
Disclosure: Kathiresan reports financial ties with Alnylam, AstraZeneca, Bayer, Catabasis, Celera, Eli Lilly, Genomics PLC, Ionis Pharmaceuticals, Leerink Partners, Merck, Noble Insights, Novartis, Regeneron, Sanofi and San Therapeutics.
Perspective
Back to Top
Robert Roberts, MD, MACC, FRSC, FRCPC, LLD (Hon.)
I suspect that the major take-home message for physicians, including cardiologists, who are not in the field of genetics, is to recognize that one can modify genetic risk in the same way that one can modify environmental risk. There’s always been a myth that if you have it in your genes, there’s nothing you can do about it. These findings should clearly kill that myth. With more than 55,000 individuals studied, the numbers are there to support the data.
The second message is to recognize that there are now several studies that have confirmed that genetic risk is independent of environmental factors and can be used to estimate one’s risk at any point, at any age, unlike the risk factors used in scores such as Framingham, which are better at predicting risk later in life.
These messages pave the way to use genetic risk scores as a means of predicting risk for both primary and secondary prevention, particularly for primary prevention. It would change the landscape significantly in the sense that with a 45-year-old woman with plasma LDL 185 mg/dL, the guidelines indicate that you can do nothing for that person if they have no other risk factors, even though we all agree that the cholesterol would be better treated and brought down. The way the guidelines are written at the moment, they do not take into account genetic risk. If genetic risk is now going to be recognized — and clearly the tide is moving in that direction, the data and knowledge support it — you can add genetic risk to that person, and now they can be treated on the basis of high, medium or low risk, and we know from a previous study in The Lancet that it will predict response to statin therapy.
These findings get rid of the message that you can’t modify genetic risk factors and pave the way for the guidelines to, sooner or later, include genetic risk as part of risk management, whether it is with statin therapy, lifestyle or other means. This article clearly shows that lifestyle is effective at modifying genetic and environmental risk factors and solidifies its role in prevention of heart disease.
Click Here to Manage Email Alerts