Physical activity, genes for physical fitness, and risk of coronary heart disease.

PURPOSE: Both physical activity and physical fitness are associated with decreased coronary heart disease (CHD) risk. Our objective was to determine whether genes associated with physical fitness modify the association between physical activity and CHD.

METHODS: We conducted a prospective cohort study among 23,016 initially healthy women in the Women's Genome Health Study. Leisure time physical activity was reported at entry and during follow-up. A total of 58 single nucleotide polymorphisms associated with physical fitness were identified from published literature and summed to create four separate genetic scores related to phenotypes of endurance, muscle strength, V˙O2max, and overall fitness.

RESULTS: During a median of 14.4 yr, 320 incident CHD events occurred. Increased physical activity was associated with lower CHD risk in multivariable-adjusted models (P = 0.0008). Independent of physical activity, only muscle strength genetic score was inversely associated with CHD risk (P = 0.05). There was no evidence that the inverse relation between physical activity and CHD was modified by any of the genetic scores for physical fitness. For overall fitness genetic score, the hazard ratio (HR) per 500 kcal·wk of physical activity was 0.85 (95% confidence interval [CI] = 0.72-1.00) in the highest quartile of genetic score and 0.79 (95% CI = 0.67-0.92) in the lowest quartile (P, interaction = 0.50). For V˙O2max genetic score, the HR was 0.86 (95% CI = 0.72-1.02) and 0.84 (95% CI = 0.72-0.98), respectively (P, interaction = 0.59).

CONCLUSIONS: In this large prospective cohort of women, genes associated with physical fitness did not modify the inverse association between physical activity and CHD risk.