‘Doomed’ by Genetics? Lifestyle Still Matters in Preventing CVD and Diabetes

Lifestyle improvements will lower the risks of cardiovascular disease and diabetes in all individuals regardless of genetic predisposition to these conditions, but those at highest genetic risk will see the greatest absolute risk reductions, according to a new analysis.

The findings replicate those of previous genetic studies looking at coronary artery disease and the effect of exercise specifically on CVD and mortality, but this is “the first to report the associations of combined health behaviors and factors in different genetic risk groups for atrial fibrillation, stroke, hypertension, and diabetes,” write M. Abdullah Said, BSc (University Medical Center Groningen, the Netherlands), and colleagues.

“This study shows that genetic composition and lifestyle have a log-additive effect on the risk of developing disease and that the relative effects of poor lifestyle are comparable between genetic risk groups,” they add.

The authors sourced data from more than 339,000 people from the UK Biobank database who were deemed to have an overall lifestyle that was either ideal (20.3%), intermediate (74.5%), or poor (5.2%). Their results, published online June 27, 2018, ahead of print in JAMA: Cardiology, show over a median follow-up of 6.2 years that in people with high genetic risk, all lifestyles were associated with higher absolute risks of incident events.

Compared with individuals with an ideal lifestyle and low genetic risk, those adhering to poor lifestyles at high genetic risk were at higher risk for CAD (HR 4.54; 95% CI 3.72-5.54), A-fib (HR 5.41; 95% CI 4.29-6.81), stroke (HR 2.26; 95% CI 1.63-3.14), hypertension (HR 4.68; 95% CI 3.85-5.69), and type 2 diabetes (HR 15.46; 95% CI 10.82-22.08). The effects of lifestyle on risk of diabetes were the strongest, with an ideal lifestyle bringing the risk of those with any genetic risk toward the null.

“These findings indicate the strong potential benefits of adherence to multiple ideal behavioral lifestyle factors regardless of genetic risk,” write Said and colleagues. “Therefore, preventive policies should promote stricter adherence to multiple ideal behavioral lifestyle factors (eg, eliminating smoking, eating a healthy diet, maintaining a healthy weight, and engaging in regular physical activity) for all.”

Quantifying Genetic Risk

Speaking with TCTMD, Amit Khera, MD (Broad Institute, Boston, MA), who led the aforementioned genetic study on coronary artery disease risk but was not associated with the current paper, said that the motivation for this kind of work stems from the patients who come into the clinic with family histories of early heart attacks and don’t know what to do to prevent one for themselves.

In some cases, this “can lead them to think that they're doomed or predestined to have a heart attack and suffer a similar fate,” he explained.

Today it’s possible to quantify genetic susceptibility to all kinds of health conditions, “which I think in and of itself is pretty cool,” Khera said. But going deeper still, it is possible “actually to show that if you are adhering to a healthy lifestyle, you can basically normalize your inherited risk.”

This study goes a step further in that it uses data from a large database—something Khera pointed out as notable because it’s only been a recent development that comprehensive data like that from the UK Biobank have been accessible—and expands upon previous studies to look at multiple cardiovascular complications. Previously, he said, physicians and patients only had family histories to go by, but using those can be “very complicated [since] you don't know if the family history is related to shared DNA or . . . shared lifestyle.”

With data such as those used in this study, genetic risk scores are being developed that can “quantify genetic susceptibility in a little bit more rigorous way,” Khera explained.

The science is exciting, he said, but “also opens up a whole range of questions.” For example, would physicians treat their patients differently if they knew more about their genetic risk? How could this information affect insurance premiums? How can this information be used to “redesign clinical medicine and what studies will we need to convince people that that's the future?”

“Knowledge of genetic risk may lead individuals to believe they are destined to develop diseases regardless of their lifestyle and may insufficiently motivate behavior changes,” the study authors add.

The big picture message for now should be that “if you're just going to tell people to behave in terms of lifestyle, then I think you should do that for everybody,” Khera said. “But if you had some potential lifestyle intervention that had some cost and you wanted to figure out how to target it, that's where I think it actually could make sense to target it in those people with the highest risk.”

He specifically mentioned the intensive diabetes prevention program that has been shown to reduce risk by at least half but hasn’t “gotten into large-scale use because it's kind of expensive and kind of a hassle to do.” Also, genetic data could help target which patients suspected of A-fib could benefit from a wearable patch or device that could detect it. “If you can enrich the population with genetic susceptibility and basically find people who are at five times increased risk, then all of a sudden that wearable technology and the cost-effectiveness of that technology may make more sense,” he said.