Biological aging mediates and frailty modifies the associations of arterial stiffness with incident probable sarcopenia and sarcopenia: a prospective cohort study of UK biobank.

BACKGROUND

Arterial stiffness may contribute to sarcopenia, but whether biological aging mediates and frailty modifies these associations remains unclear.

METHODS

This prospective cohort study included 32,451 UK Biobank participants free of probable sarcopenia and sarcopenia at baseline. Cause-specific Cox proportional hazards models were used to examine the associations between arterial stiffness index (ASI) and incident probable sarcopenia and sarcopenia. Restricted cubic spline analyses were performed to characterize dose-response relationships. Counterfactual mediation analysis was used to evaluate the mediating role of Klemera-Doubal biological age acceleration (KDM-BAacc), while multiplicative and additive interaction analyses were conducted to assess effect modification by frailty. Sensitivity analyses were performed to evaluate the robustness of the findings.

RESULTS

During follow-up, 1,901 participants developed probable sarcopenia and 277 developed sarcopenia. Compared with the lowest ASI tertile, participants in the highest tertile had higher risks of probable sarcopenia (HR 1.38, 95% CI 1.22-1.55) and sarcopenia (HR 1.56, 95% CI 1.11-2.18). ASI showed a nonlinear association with probable sarcopenia but a linear association with sarcopenia. KDM-BAacc significantly mediated 8.66 and 18.85% of the associations with probable sarcopenia and sarcopenia, respectively. Frailty significantly modified these associations, with the associations largely confined to non-frail participants. These findings were robust in sensitivity analyses.

CONCLUSION

Higher ASI was associated with increased risks of incident probable sarcopenia and sarcopenia. Biological aging partially mediated these associations, whereas frailty modified their magnitude. These findings identify arterial stiffness as a potential upstream determinant of sarcopenia, with biological aging as a mediating pathway and frailty as a modifier of susceptibility.