Frailty as a mediator of the association between hyperuricemia and stroke risk: A prospective cohort study

Existing evidence on the interrelationship among hyperuricemia, physical frailty, and stroke remains limited and unclear. This study aimed to examine the associations of hyperuricemia and frailty with the incidence of stroke, and to evaluate the potential mediating role of frailty.

We include Chinese adults aged 45 years and above from the China Health and Retirement Longitudinal Study (CHARLS). Serum urate concentrations were measured using an enzymatic colorimetric method, and hyperuricemia was defined as serum urate ≥420 μmol/L. The frailty index (FI) was constructed based on 28 baseline items. Stroke was ascertained based on self-reported, physician-diagnosed events. Multivariable logistic regression and mediation analyses were conducted to examine the associations among hyperuricemia, physical frailty, and stroke.

A total of 7462 eligible participants were included in the analysis. Hyperuricemia was positively associated with frailty status (OR = 1.54, 95% CI: 1.02-5.84) and with the incidence of stroke (OR = 4.07, 95% CI: 1.25-13.19). Pri-frail and frail participants exhibited a substantially higher risk of incident stroke (OR = 1.55, 95% CI: 1.11-2.92 and OR = 2.87, 95% CI: 1.29-6.37, respectively). Mediation analysis further indicated that the FI partially mediated the relationship between hyperuricemia and incident stroke, accounting for 10.82% (95% CI: 6.51%-21.65%) of the total effect.

Hyperuricemia is associated with an increased risk of stroke, and frailty may partially mediate this association. Early identification and management of frailty in individuals with hyperuricemia may represent a novel, integrative strategy to reduce stroke risk and promote healthy aging.