Genetic Risk, Healthy Lifestyle, and Coronary Disease

Study Questions:

Population studies have shown that a healthy lifestyle defined as a healthy diet, not smoking, physical activity, and avoiding obesity is associated with a marked reduction in cardiovascular event rates. To what extent can a high genetic risk for coronary artery disease (CAD) be offset by a healthy lifestyle?


A polygenic risk score was used to quantify genetic risk for CAD in three prospective cohorts assessing cardiovascular outcomes (ARIC [Atherosclerosis Risk in Communities] study, Women’s Genome Health Study, and Malmo Diet and Cancer Study cohorts) and the BioImage study, which evaluated coronary artery calcium scores. The four healthy lifestyle factors were assessed in each individual. The primary endpoint for the prospective cohort studies was a composite of hard CAD events. Genetic risk was characterized as high, intermediate, and low based on quintiles, with intermediate being quintiles 2-4.


There were a total of 55,685 participants. The risk of incident coronary events was 91% higher in those with a highest genetic risk quintile compared with the lowest quintile. A favorable lifestyle (at least three of the four healthy lifestyle factors) was associated with a significantly lower coronary event rate in each of the genetic risk categories. Among those at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk than an unfavorable lifestyle (e.g., 10-year cardiovascular events, 10.7% for unfavorable and 5.1% for favorable in ARIC). Similarly, in the BioImage Study, a favorable lifestyle was associated with less coronary artery calcification within each genetic risk category.


Genetic and lifestyle factors were independently associated with susceptibility to CAD in four studies involving more than 50,000 participants. Among those with a high genetic risk, a favorable lifestyle was associated with nearly a 50% lower relative risk of CAD compared with an unfavorable lifestyle.


Since the first genetic risk variant, 9p21, which is independent of known risk factors, the international consortium of CARDIoGRAM has identified a total of 50 risk variants. Of the 50, 35 mediate their risk by unknown mechanisms. To what degree genetics influences CAD risk is not known. Estimates are at least two-fold, but for inherited high low-density lipoprotein cholesterol, which markedly increases the risk of premature and lifelong CAD. Fortunately, we have data that genetic risk for CAD is not destiny. Interestingly, risk prediction for CAD using genetic risk scores is independent of self-reported family history, which may be better correlated with an undesirable lifestyle.

Keywords: AHA Annual Scientific Sessions, Coronary Artery Disease, Diet, Exercise, Genetic Testing, Life Style, Obesity, Neoplasms, Plaque, Atherosclerotic, Primary Prevention, Risk Assessment, Smoking Cessation

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