Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Genetic Risk & Lifestyle Factors in Coronary Disease

N Engl J Med; 2016 Dec 15; Khera, Emdin, et al

A favorable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease (CAD) than was an unfavorable lifestyle among individuals with high genetic risk, a recent study found. Researchers quantified genetic risk for 4 studies involving 55,685 participants and also determined adherence to a healthy lifestyle using a scoring system consisting of 4 factors: no current smoking, no obesity, regular physical activity, and a healthy diet. They found:

  • Relative risk of incident coronary events was 91% higher among participants at high genetic risk compared to those at low genetic risk (HR, 1.91).
  • A favorable lifestyle was associated with a substantially lower risk of coronary events than an unfavorable lifestyle, regardless of the genetic risk category.
  • A favorable lifestyle among participants at high genetic risk was associated with a 46% lower relative risk of coronary events.


Khera AV, Emdin CA, Drake I, et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med. 2016;375:2349-2358. doi:10.1056/NEJMoa1605086.


It has been clear for many years that a healthy lifestyle leads to greater longevity.1 Exercise, for instance, is such a strong predictor of decreased CV outcomes that it actually appears to offset the effects of other traditional risk factors.2 However, the questions remains of whether the observed effects might just represent the fact that healthier people exercise more. The Finnish Twin Study suggested that this is not the case, showing a decreased risk of death for the identical twin who exercised more in a large cohort of twins, each of whom exercised to different degrees.3 The current study takes all this inquiry to the next level, showing healthy lifestyle yields a substantially decreased incidence of CV disease across all risk categories using genetic risk assessment. Even among those at the highest genetic risk, a healthy lifestyle that includes no current smoking, no obesity, regular physical activity, and a healthy diet can decrease the development of CV disease by almost 50%. —Neil Skolnik, MD

  1. Chomistek AK, Chiuve SE, Eliassen AH, Mukamal KJ, Willett WC, Rimm EB. Healthy lifestyle in the primordial prevention of cardiovascular disease among young women. J Am Coll Cardiol. 2015;65:43-51.
  2. Kokkinos P, Myers J, Faselis C, Doumas M, Kheirbek R, Nylen E. BMI-mortality paradox and fitness in African American and Caucasian men with type 2 diabetes. Diabetes Care. 2012;35:1021–1027.
  3. Kujala UM, Kaprio J, Sarna S, Koskenvuo M. Relationship of leisure-time physical activity and mortality: the Finnish twin cohort. JAMA.1998;279(6):440-444.