Interaction of accelerometer-measured physical activity and genetic risk on cardiovascular diseases: a prospective cohort study from UK Biobank.

Objectives: This study aimed to evaluate the interactions of physical activity and polygenic risk score (PRS) on risks of atrial fibrillation, coronary heart disease (CHD), hypertension, and ischaemic stroke.

Methods: This study included 91 629 participants from UK Biobank in this study, all of whom had worn a wrist-worn accelerometer for 7 consecutive days. We computed total volume of physical activity (TPA) and time spent in moderate to vigorous intensity physical activity (MVPA) and light intensity physical activity (LPA). Cox proportional hazard models were used to evaluate associations of physical activity with the four cardiovascular outcomes. Interactions between physical activity and PRS were investigated on multiplicative and additive scales.

Results: During a median follow-up of 7.9 years, 3811 atrial fibrillation, 3994 CHD, 7345 hypertension and 1001 ischaemic stroke cases were recorded. TPA, MVPA and LPA were all negatively associated with risks of the four cardiovascular outcomes, generally independent of genetic risk. Association between LPA and atrial fibrillation was U-shaped among low-PRS stratum (p=0.01), and association between TPA and hypertension was attenuated with genetic risk increasing (p=0.02). Attributable risk (AR) of inactivity was higher in the high-PRS population. For example, increasing MVPA resulted in a twofold greater reduction in CHD cases among individuals with high PRS (AR=2.17%) than among those with low PRS (AR=1.09%).

Conclusions: Increasing physical activity, including LPA, was associated with a reduced risk of cardiovascular diseases. The extent of this benefit may differ among individuals with different genetic risks.