Association of Intramuscular Fat Infiltration With Incident Venous Thromboembolism: A Population-Based Cohort Study

Venous thromboembolism (VTE) is a major acute cardiovascular condition with high mortality, affecting nearly 10 million individuals worldwide each year. Identifying novel and modifiable risk factors is crucial for advancing prevention strategies. Intramuscular fat infiltration (IMFI), a modifiable condition linked to inflammation and muscle weakness, both established contributors to VTE risk, has not been previously studied in relation to incident VTE. We aimed to examine the association between thigh IMFI and incident VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT).

This population-based cohort study included 24 529 UK Biobank participants with baseline IMFI assessed using magnetic resonance imaging of the thigh muscles. The primary outcome was incident VTE. Secondary outcomes included incident PE and DVT. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of IMFI with incident VTE, PE and DVT, adjusting for potential confounders. Dose-response relationships were evaluated using restricted cubic spline regression models.

Over a mean follow-up of 4.92 years, 227 participants developed incident VTE. The incidence rates across increasing age- and sex-specific anterior thigh IMFI quartiles were 1.34, 1.28, 1.58 and 3.34 per 1000 person-years, respectively. Compared with the lowest anterior thigh IMFI quartile, adjusted HRs for incident VTE were 0.88 (95% CI: 0.57, 1.37), 1.02 (95% CI: 0.67, 1.55) and 1.88 (95% CI: 1.26, 2.80) for the second, third and fourth quartiles, respectively. Similar associations were observed for incident PE and DVT. Restricted spline regression models revealed that VTE risk increased progressively across higher IMFI levels. PE and DVT risk showed similar patterns. Analyses using posterior thigh IMFI showed generally consistent associations with incident VTE, PE and DVT.

Elevated thigh IMFI was associated with higher risks of VTE, PE and DVT. These findings identify thigh IMFI as a potential modifiable risk factor for VTE and support further investigation of strategies targeting muscle fat infiltration for thrombotic disease prevention.