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.
Sun Y, Liu T, et al. • Research and practice in thrombosis and haemostasis • 2026
Higher sarcopenia index (based on serum creatinine to cystatin C ratio) was associated with lower VTE risk, and participants with both low SI and high genetic risk exhibited the greatest risk of VTE (HR = 3.60; 95% CI, 3.14-4.12) compared to those with high SI and low genetic risk.
Key Findings
Results
Higher sarcopenia index (SI) was associated with a lower risk of incident venous thromboembolism (VTE) in a dose-dependent fashion.
Among 447,681 participants, 12,008 developed VTE during a median follow-up of 13.4 years.
Fully adjusted hazard ratios for Q2, Q3, and Q4 vs Q1 (lowest) SI 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.
Results were derived from Cox proportional hazards models using UK Biobank data.
The association was monotonically inverse, with each higher quartile of SI corresponding to progressively lower VTE risk.
Results
Restricted cubic spline analysis revealed an inverse nonlinear association between SI and VTE risk.
P for nonlinearity < .001.
Restricted cubic spline models were applied to examine the exposure-response relationship between SI and VTE.
The nonlinear nature of the association suggests the relationship between muscle mass proxy and VTE risk does not follow a simple linear pattern.
Results
High genetic risk (polygenic risk score) was independently associated with a substantially increased risk of VTE.
Participants with high genetic risk had an HR of 2.56 (95% CI, 2.42–2.72) compared to those with low genetic risk.
Polygenic risk score was used to quantify genetic susceptibility to VTE.
This finding was described as consistent with previous UK Biobank findings linking higher polygenic risk score levels to increased VTE risk.
Results
Participants with both low SI and high genetic risk exhibited the greatest risk of VTE compared to those with high SI and low genetic risk.
The combined low SI/high genetic risk group had an HR of 3.60 (95% CI, 3.14–4.12).
This represents a greater risk than either low SI or high genetic risk alone, suggesting a possible additive or synergistic interaction.
The reference group was participants with high SI and low genetic risk.
The study examined the combined effects of SI and genetic susceptibility on VTE risk in the UK Biobank cohort.
Conclusions
The sarcopenia index, defined as the serum creatinine to cystatin C ratio, was investigated as a simple and accessible marker for identifying individuals at elevated VTE risk.
SI was used as a proxy measure for muscle mass, with higher values reflecting greater muscle mass.
The study population comprised 447,681 UK Biobank participants.
The authors propose that SI 'may serve as a simple and accessible marker for identifying individuals at elevated risk of VTE.'
Serum creatinine and cystatin C are routinely measured biomarkers, making the SI potentially practical for clinical use.
What This Means
This research suggests that people with lower muscle mass — as estimated by a blood-based measure called the sarcopenia index (SI), which uses the ratio of creatinine to cystatin C — face a higher risk of developing dangerous blood clots in veins (venous thromboembolism, or VTE). The study followed nearly 450,000 UK Biobank participants for about 13 years, during which over 12,000 developed VTE. People in the lowest quarter of SI scores had roughly 30% higher clot risk than those in the highest quarter, and this relationship was not perfectly straight-line — the risk rose more steeply at very low SI levels.
The study also found that having a high genetic predisposition to blood clots (measured by a polygenic risk score) more than doubled VTE risk. Critically, people who had both low muscle mass (low SI) and high genetic risk faced more than 3.5 times the VTE risk compared to people with high muscle mass and low genetic risk — a combination that represents the highest-risk group identified in the study.
This research suggests that the sarcopenia index could be a practical screening tool to flag individuals who may be at elevated risk for blood clots, since creatinine and cystatin C are commonly measured in routine blood tests. The findings highlight that both lifestyle-related factors like muscle mass and inherited genetic factors contribute independently — and possibly together — to VTE risk, pointing to potential value in combining clinical and genetic information for risk assessment.
Sun Y, Liu T, Deng J, Cao X, Tang L, Hao X, et al.. (2026). 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.. Research and practice in thrombosis and haemostasis. https://doi.org/10.1016/j.rpth.2026.106973