Accelerometer-measured intensity-specific physical activity, genetic predisposition, and the risk of venous thromboembolism: A cohort study.

ABSTRACT

OBJECTIVES: The association between physical activity and venous thromboembolism (VTE) remains unclear. Therefore, we investigated the prospective dose-response associations between accelerometer-measured intensity-specific physical activity and new-onset VTE, accounting for genetic risk. METHODS: In total, 85,116 participants from the UK Biobank were included. Incident VTE was identified via linked hospital records and death registries. A weighted polygenic risk score (PRS) was used to quantifying genetic risk for VTE, with higher values indicating a high genetic risk. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the associations. RESULTS: Overall, 1,182 incident VTE cases were documented during a median follow-up of 6.18 years. In the overall study population, the participants in the highest quartiles of total volume of physical activity (0.60 [0.45, 0.79]), moderate-to-vigorous-intensity physical activity (0.66 [0.51, 0.86]), and light-intensity physical activity (0.66 [0.51, 0.85]) had lower adjusted HRs (95% CIs) for VTE than those of participants in the lowest quartiles. Both total volume of physical activity and light-intensity physical activity were negatively associated with VTE risk in participants with low, intermediate, and high PRS. However, moderate-to-vigorous-intensity physical activity was only protective against VTE in participants with low and intermediate PRS, with a significant interaction (P for interaction=0.02). CONCLUSION: Higher levels of physical activity of any intensity were associated with a lower risk of new-onset VTE. However, the negative association between moderate-to-vigorous-intensity physical activity and new-onset VTE was significant only in participants with low and intermediate genetic predispositions to VTE.

Based on the UK Biobank cohort of 85,116 participants, this study aimed to explore the longitudinal associations between accelerometer-measured intensity-specific physical activity (PA) and risk of venous thromboembolism (VTE) and whether these associations could be modified by genetic predisposition, as reflected by polygenic risk scores (PRS), with higher values indicating a higher genetic risk. Our results showed that the risk of new-onset VTE decreased with increasing PA until total volume of PA, moderate-to-vigorous-intensity PA, and light-intensity PA reached approximately 40 milligravity/day, 45 mins/day, and 350 mins/day, respectively, and then remained relatively constant. The VTE-PRS modified the association between moderate-to-vigorous-intensity PA and VTE risk. The protective association between moderate-to-vigorous-intensity PA and the risk of VTE was more pronounced among participants with the lowest level of VTE-PRS.