Association between intrinsic capacity, genetic predisposition, and risk of venous thromboembolism.

OBJECTIVE

Association between intrinsic capacity (IC) and venous thromboembolism (VTE) remains unclear, we aim to explore the relationship among IC, genetic predisposition, and incident VTE.

METHODS

In this large retrospective cohort study using the UK Biobank, IC, defined as the composite of all physical and mental capacities of an individual, was assessed across 7 factors (such as exhaustion, sleep duration, eye problems, hearing difficulty, weight loss, gait speed, and grip strength) and scored from 0 (best) to 7 (worst). Participants were grouped into five IC categories: 0, 1, 2, 3, and ≥4 factors. Incident VTE was identified through national medical records. Genetic predisposition to VTE was determined by the tertiles of polygenic risk score (PRS) derived from external genome-wide association data from the UK Biobank. Cox proportional hazards models were used to investigate the associations with multiple variables adjusted.

RESULTS

A total of 415,581 participants (median age, 57.0 years; interquartile range, 50.0-63.0; 54.96% female; 94.89% White) were included in the final analysis. Over a median follow-up of 14.37 years, 8299 (2.00%) developed VTE, including 3878 (0.94%) with and 4421 (1.07%) without a history of cancer. Higher IC scores were associated with increased VTE risk compared to those with IC = 0 (for IC = 1: hazard ratio (HR), 1.08; 95% confidence interval (CI), 1.01-1.16; P = .029; for IC = 2: HR, 1.12; 95% CI, 1.04-1.22; P = .005; for IC = 3: HR, 1.19; 95% CI, 1.06-1.34; P = .003; for IC ≥ 4: HR, 1.46; 95% CI, 1.23-1.75; P < .001). Similar associations were observed in both cancer and noncancer subgroups. Furthermore, individuals with both the highest PRS and the worst IC (≥4 factors) had the greatest VTE risk, with significant interactions between PRS and IC.

CONCLUSIONS

Our large-scale study suggests that poor IC is an independent risk factor for VTE. Moreover, integrating IC with genetic risk can identify a high-risk subgroup, which supports the clinical utility of IC assessment in VTE risk stratification.