Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease.
Level 3 - non-randomized controlled study
Prospective cohort studies combined with a cross-sectional cohort analysis
PubMed 27959714 · doi:10.1056/NEJMoa1605086
What was done
Researchers assessed the relationship between genetic risk, lifestyle adherence, and coronary artery disease across four cohorts totaling 55,685 participants: three prospective cohorts (ARIC [n = 7,814], WGHS [n = 21,222], and MDCS [n = 22,389]) and one cross-sectional cohort (BioImage [n = 4,260]). Genetic risk was quantified using a polygenic risk score. Lifestyle was categorized based on four factors: no current smoking, no obesity, regular physical activity, and a healthy diet (favorable: ≥3 factors; unfavorable: 0-1 factor). Outcomes evaluated included incident coronary events and coronary-artery calcification.
What was found
Participants at high genetic risk (top quintile) had a 91% higher relative risk of incident coronary events compared to those at low genetic risk (bottom quintile) (hazard ratio [HR], 1.91; 95% CI, 1.75 to 2.09). Across all genetic risk tiers, a favorable lifestyle was associated with lower risk. Among participants at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk of coronary events compared to an unfavorable lifestyle (HR, 0.54; 95% CI, 0.47 to 0.63). Standardized 10-year incidence of coronary events decreased from 10.7% to 5.1% in ARIC, 4.6% to 2.0% in WGHS, and 8.2% to 5.3% in MDCS. In the BioImage study, a favorable lifestyle was associated with significantly less coronary-artery calcification across all genetic risk groups.
Why it matters
High genetic risk for coronary artery disease can be substantially offset; adhering to a healthy lifestyle is associated with nearly halving coronary event risk even among individuals in the highest genetic risk tier.
Limits
The observational design cannot establish causality. Ancestry, detailed demographic characteristics, and residual confounding factors are not described in the abstract. One cohort (BioImage) was cross-sectional and measured coronary-artery calcification rather than clinical outcomes.
Cited by
- supports Multiple studies show that high polygenic disease risk can be neutralized by adopting healthy lifestyle factors.