By Joseph E. Scherger, MD, MPH

Vice President, Primary Care, Eisenhower Medical Center; Clinical Professor, Keck School of Medicine, University of Southern California

Dr. Scherger reports no financial relationships relevant to this field of study.

SYNOPSIS: Adherence to a healthy lifestyle of no smoking, no obesity, weekly physical activity, and a healthy diet reduces the genetic risk of coronary disease by almost half for all levels of genetic risk.

SOURCE: 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.

Led by the Center for Human Genetic Research and the Cardiology Division at Massachusetts General Hospital, and the Division of Preventive Medicine, Department of Medicine at Brigham and Women’s Hospital in Boston, a team of investigators used four databases totaling 55,685 people with genomic information regarding risk for coronary artery disease.

Three of the databases were prospective cohorts. The Atherosclerosis Risk in Communities study included white and black participants 45-64 years of age (7,814 participants). The Women’s Genome Health Study (21,222 participants) was derived from the larger Women’s Health Study of health professionals (mostly nurses). The Malmo Diet and Cancer Study was comprised of 22,389 participants between 44-73 year of age. The fourth database came from the cross-sectional BioImage Study for whom genotype and covariate data were available. The parameters of the healthy lifestyle were: no current smoking, no obesity, regular physical activity, and a healthy diet according to the American Heart Association guidelines.

The authors reported three noteworthy conclusions. First, inherited DNA variation and lifestyle factors contribute independently to risk of coronary artery disease. Second, a healthy lifestyle was associated with similar relative risk reductions across each stratum of genetic risk. Third, genetic risk does not indicate a determinism that a negative outcome will occur and the genetic risk is modifiable through a healthy lifestyle.


Lifestyle matters. Most physicians know that intuitively, but it is nice to study data that demonstrate that lifestyle matters and the degree to which it affects genetic risk. Because these data are observational, they do not prove that lifestyle was the impact factor like a randomized, controlled trial would. A study of this magnitude can only look at lifestyle in the most general terms. The authors relied on self-reported information. Just three of the four factors were needed to be classified as constituting a healthy lifestyle, so some of those classified as healthy might be obese or might engage in physical activity infrequently. The nutrition recommendations matched the low-fat, high-fiber (including grains) diet recommended by the American Heart Association. This diet is under modification thanks to the loosening of restrictions on saturated fats from natural foods. Also, accumulating data have demonstrated that carbohydrates are the macronutrient most associated with overweight and obesity.1,2

How well are physicians trained to teach a healthy lifestyle? Is lifestyle medicine a part of the culture of American medicine, or do we overemphasize the use of medications and procedures? How skilled are we in motivational counseling? Although most of us excel in smoking cessation, we may not even put overweight or obesity on the medical problem list, know little about prescribing exercise, and have very limited nutrition education. Knowledge about lifestyle medicine is growing among physicians and the public alike, by the formation of a new organization3 and the rapid growth in functional medicine education.4

Since an unhealthy lifestyle is the dominant cause of chronic illnesses, such as type 2 diabetes, overweight and obesity, hyperlipidemia, and hypertension, promoting a healthy lifestyle may enhance health and reduce the burden of disease at very low cost. We may be entering by necessity an era of lifestyle medicine.


  1. Scherger JE. The obesity epidemic and how we got it wrong. Intern Med Alert 2014;36:89-90.
  2. Scherger JE. Welcome back, saturated fat. Intern Med Alert 2016;38:81-82.
  3. The Institute of Lifestyle Medicine.
  4. The Institute for Functional Medicine.