Genetic liability for cardiovascular disease, physical activity, and mortality – findings from The Finnish Twin Cohort

Abstract

AbstractBackgroundAn overall healthy lifestyle may mitigate the risk of all-cause and cardiovascular disease (CVD) mortality despite the inherited risk for CVD. We assessed if similar phenomenon is observed independently with physical activity (PA).MethodsIn a prospective older Finnish Twin Cohort, genetic liability for coronary heart disease, systolic and diastolic blood pressure was estimated with polygenic risk scores (PRSs) derived from the Pan UK Biobank (N≈400,000) and >1,000,000 genetic variants, and leisure-time PA longitudinally with validated and structured questionnaires three times during 1975–1990 among 4,897 participants aged 33–60-years (54.3% women). Interactions of PRSs and PA with mortality and the independent main effects of different PA metrics with mortality were evaluated with Cox proportional hazards models. A co-twin control design with 180 monozygotic twin pairs discordant for physical activity was used for causal inference.ResultsDuring the 17.4-y (mean) follow-up (85,136 person-years), 1,195 participants died with 389 CVD deaths. Although the favorable associations of an overall healthy lifestyle with mortality risk reduction replicated in the cohort, no interactions or significant independent main effects were observed with any of the assessed PA metrics. Adherence to World Health Organizations PA guidelines or vigorous PA during the 15-year observational period did not decrease mortality in more active twins compared to their less active identical twin brother or sister. The findings did not vary with genetic CVD risk.ConclusionsNo evidence was found that PA mitigates inherited CVD risk or is causally associated with mortality challenging some of our current understanding.