Healthy lifestyle linked to decreased coronary artery disease in persons with high genetic risk

1. Among individuals with high genetic risk for coronary artery disease (CAD), a favorable lifestyle was associated with a nearly 50% lower relative risk compared to an unfavorable lifestyle.

2. The relative risk of CAD was nearly doubled among participants with high genetic risk compared with participants at low genetic risk.

Evidence Rating Level: 1 (Excellent) 

Study Rundown: It is well known that both genetic and lifestyle factors contribute to an individual’s risk of developing CAD, but the extent to which genetic risk can be counterbalanced by a healthy lifestyle is unclear. In a comparison with a polygenic risk score of 50 single-nucleotide polymorphisms (SNPs) with genomewide significance for association with CAD, this study examined the effect of favorable lifestyle factors on the study end point of all CAD events in three prospective cohorts and one cross-sectional study. Favorable lifestyle factors included no current smoking, no obesity, physical activity at least once weekly, and a healthy diet pattern. Among participants at high genetic risk, a favorable lifestyle was associated with a nearly 50% lower relative risk of CAD than an unfavorable lifestyle. This is an impactful study that employed an innovative approach to answering a challenging question regarding the interplay between genetic and lifestyle risk factors for CAD by quantifying both the genetic and lifestyle risks, independently, of more than 50 000 participants. Nonetheless, because lifestyle differences were not randomized in the four studies included in this meta-analysis, one limitation of the study was that its association cannot be interpreted as causal.

Click to read the study, published in NEJM

Relevant Reading: Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010

In-Depth [meta-analysis]: In this meta-analysis of three prospective cohort studies (ARIC, WGHS, and MDCS) and one cross-sectional study (BioImage), each cohort was divided into three lifestyle risk categories: favorable [≥3 healthy lifestyle factors (HLFs)], intermediate (2 HLFs), or unfavorable (≤1 HLFs). Across all three cohorts, the hazard ratio of CAD was 1.91 among participants at high genetic risk compared to those at low genetic risk (95%CI 1.75 to 2.09). Among participants at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk of coronary events than an unfavorable lifestyle (HR, 0.54; 95%CI 0.47 to 0.63). Furthermore, there was a decrease from 10.7% for an unfavorable lifestyle to 5.1% for a favorable lifestyle in ARIC, from 4.6% to 2.0% in WGHS, and from 8.2% to 5.3% in MDCS when analyzing the standardized 10-year incidence of coronary events. A favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category in the BioImage Study.

Image: PD

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