Replacement Of Wearable-device- measured Sedentary Time By Physical Activity, Genetic Susceptibility, And Risk Of Coronary Heart Disease

Backgrounds: Excess sedentary time (ST) is recognized as an important modifiable risk factor for coronary heart disease (CHD). However, whether the associations of genetic susceptibility with CHD incidence can be modified by replacing wearable-device-measured ST with physical activity (PA) is unknown. This study aims to examine the combined associations of genetic susceptibility to CHD, and wearable-device-measured ST replaced by moderate-to-vigorous PA (MVPA) or light PA in relation to incident CHD. Methods and Findings: This study included 75,545 white British (57% female) with valid wrist-worn accelerometer data and without prevalent CHD/stroke from UK Biobank. Genetic susceptibility to CHD was quantified through weighted polygenic risk scores for CHD based on 300 single-nucleotide polymorphisms. Wrist-worn accelerometer data were used to derive ST, light PA and MVPA. The hazard ratio of CHD was 1.36 (95% CI: 1.03-1.80) for every-30-minute/day-increase in ST relative to other movement behaviors, after adjusting for genetic risk and confounders. Reallocation of any amount of ST (as little as 1 minute/day) into the same MVPA time (but not light PA) was associated with lower CHD hazards overall and within strata of genetic risk: no evidence of interaction between genetic risk and ST (p-value: 0.739). However, differences in absolute risk of CHD for ST replaced by MVPA were greater at high genetic risk versus low genetic risk. Limitations of our study include no causal evidence derived, limited generalizability to individuals of other ethnic groups or with sub-clinical symptoms, and potential residual confounding. Conclusions: Replacing any amount of ST with an equal amount of MVPA time is associated with a lower relative risk of developing CHD at all levels of genetic susceptibility to CHD. Potential reductions in absolute risk of CHD through replacement of ST by MVPA in equivalent amounts may be greater in individuals at high genetic risk of CHD.