Joint Effect of Muscle Strength and Obesity on the Risk of Venous Thromboembolism

Weak hand grip strength (HGS) and obesity separately increase the risk of venous thromboembolism (VTE). Whether the combination of these risk factors yields excess VTE risk is unclear. We aimed to investigate the joint effect of HGS and obesity on the risk of VTE in a population-based cohort.A total of 13,616 participants from the Tromsø study (enrolled: 1994-2016) were included, and incident VTEs were recorded throughout 2020. HGS was categorized into weak (≤25th percentile) and normal (>25th percentile). Obesity was defined as a body mass index ≥ 30 kg/m². Cox regression was applied to estimate hazard ratios (HRs) with 95% confidence intervals (CI) according to combined categories of HGS and obesity adjusted for age, sex, height, cardiovascular disease, cancer, and physical activity. Relative excess risk due to interaction (RERI) and attributable proportion (AP) were calculated with 95% CI.The combination of weak HGS and obesity yielded an additive 1.8-fold increased risk of overall VTE (95% CI: 1.25-2.55) compared with nonobese individuals with normal HGS. The corresponding HR was 1.23 (95% CI: 0.97-1.56) in nonobese with weak HGS, and 1.47 (95% CI: 1.14-1.90) in obese with normal HGS. In subgroup analyses of unprovoked VTE, risk estimates were supra-additive in those obese with weak HGS (HR: 2.68, (95% CI: 1.64-4.37), RERI 1.63 (95% CI: 0.36-2.91), AP 0.61 (95% CI: 0.34-0.88)), supporting biological interaction between the exposures.The joint effect of weak HGS and obesity was additive for overall VTE, and supra-additive for unprovoked VTE, where 61% of the unprovoked VTEs in the combined category could be attributed to the interaction between HGS and obesity.