Association of the sarcopenia index based on the serum creatinine to cystatin C ratio and genetic risk with venous thromboembolism: a population-based cohort study.

Background: Venous thromboembolism (VTE) results from the interplay between environmental and genetic factors. The relationship between sarcopenia index (SI) and VTE risk remains unclear. The combined effects of SI and genetic susceptibility on VTE risk have not been fully elucidated. We therefore investigated these associations using data from the UK Biobank. Methods: Cox proportional hazards models were used to assess the relationship between SI and genetic susceptibility with incident VTE. Restricted cubic spline models were applied to examine the exposure-response relationships. Results: Among 447,681 participants, 12,008 developed VTE during a median follow-up of 13.4 years. Higher SI was associated with a lower risk of VTE. The fully adjusted hazard ratios (HRs) for Q2 to Q4 vs Q1 were 0.88 (95% CI, 0.83-0.92), 0.82 (95% CI, 0.78-0.87), and 0.77 (95% CI, 0.72-0.82), respectively. Restricted cubic spline analysis showed an inverse nonlinear association between SI and VTE ( Conclusion: Participants with lower SI had a significantly higher risk of VTE. Consistent with previous UK Biobank findings, higher polygenic risk score levels were associated with an increased risk of VTE. Moreover, participants with both low SI levels and high genetic risk exhibited the greatest risk of VTE. These findings suggest that SI may serve as a simple and accessible marker for identifying individuals at elevated risk of VTE.