Healthy lifestyle reduces CAD risk in individuals with genetic risk
Khera AV, Emdin CA, Drake I, et al.
N Engl J Med 2016; published online ahead of print
BackgroundSeveral independent genetic loci associated with the risk of coronary artery disease (CAD) have been identified, and a polygenic risk score is predictive of incident coronary events [1,2]. On the other hand, a healthy lifestyle, including not smoking, avoiding obesity, regular physical activity, and a healthy diet, is also associated with reduced rates of incident cardiovascular (CV) events [3,4].
In this study, it was evaluated whether genetic factors and a healthy lifestyle contribute both independently to the risk of incident coronary events and to prevalent subclinical atherosclerosis, in three prospective cohorts (ARIC [n=7814], WGHS [n=21,222], and MDCS [n=22,389]) and one cross-sectional study (BioImage [n=4260]). Moreover, the extent to which a healthy lifestyle is associated with a reduced risk of CAD in individuals with a high genetic risk was determined.
- In all three cohorts, the relative risk of incident coronary events was 91% higher among participants at high genetic risk compared with those at low genetic risk (HR: 1.91; 95% CI: 1.75 - 2.09).
- Healthy lifestyle factors were associated with a decreased risk of coronary events: no current smoking HR: 0.56 (95% CI: 0.47 - 0.66), no obesity HR: 0.66 (95% CI: 0.58 - 0.76), regular physical activity HR: 0.88 (95% CI: 0.80 - 0.97), healthy diet HR: 0.91 (95% CI: 0.83 - 0.99).
- Participants with an unfavourable lifestyle had higher rates of hypertension and diabetes, a higher BMI, and less favourable levels of circulating lipids compared with those with a favourable lifestyle. Compared with a favourable lifestyle, an unfavourable lifestyle was associated with a higher risk of coronary events in all three cohorts: ARIC cohort adjusted HR: 1.71 (95% CI: 1.47 - 1.98), WGHS cohort adjusted HR: 2.27 (95% CI: 1.92 - 2.67), MDCS cohort adjusted HR: 1.77 (95% CI: 1.61 - 1.95).
- Lifestyle factors were strong predictors of coronary events within each category of genetic risk. A favourable lifestyle, as compared with an unfavourable lifestyle, was associated with a 45% lower RR for participants at low genetic risk, a 47% lower RR for participants at intermediate genetic risk and a 46% lower RR for participants at high genetic risk (HR: 0.54; 95% CI: 0.47 - 0.63).
- Among participants at high genetic risk, the standardized 10-year coronary event rates for the ARIC cohort was 10.7% for participants with an unfavourable lifestyle and 5.1% for participants with a favourable lifestyle, for the WGHS cohort was 4.6% for participants with an unfavourable lifestyle and 2.0% for participants with a favourable lifestyle and for the MDCS cohort was 8.2% for participants with an unfavourable lifestyle and 5.3% for participants with a favourable lifestyle.
- The cross-sectional analysis of the BioImage Study showed that both genetic and lifestyle factors were associated with coronary artery calcification. The standardised calcification score was 46 Agatston units (95% CI: 39 - 54) for participants at high genetic risk, and 21 Agatston units (95% CI: 18 - 25) for those at low genetic risk (P<0.001).
ConclusionAdherence to a healthy lifestyle was associated with a substantially reduced risk of CAD within each category of genetic risk in three prospective cohorts (ARIC, WGHS, and MDCS) and one cross-sectional study. These data suggest that the risk for a coronary event may be determined by genetics, but is still modifiable through a healthy lifestyle.
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