Evidence for a dose–response association of hyperuricemia with stroke incidence: a meta-analysis of cohort studies
TL;DR
Hyperuricemia is associated with increased risks of stroke incidence and mortality, especially in women and ischemic stroke, and a J shaped dose–response relationship was observed for stroke incidence, but not for stroke mortality.
Abstract
Background Uric acid is considered a potential risk factor for stroke; However, whether the association between hyperuricemia and stroke outcomes follows a linear or nonlinear pattern remains unclear. Therefore, this study conducted a dose–response meta-analysis based on cohort studies to investigate the association between hyperuricemia and stroke outcomes. Methods We systematically searched PubMed, the Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP, and the Chinese Biomedical Literature Database from inception to April 2026. Cohort studies reporting the associations of uric acid with stroke incidence and mortality outcomes were included. Dose–response meta-analyses were performed by generalized least-squares estimation and restricted cubic splines with three knots located at the 10th, 50th, and 90th percentiles. Results A total of 25 cohort studies involving 1,300,263 participants were included. Conventional meta-analysis showed that hyperuricemia was significantly associated with stroke incidence (RR = 1.20, 95%CI: 1.11–1.29) and mortality (RR = 1.36, 95%CI: 1.17–1.58). Subgroup analysis indicated that hyperuricemia significantly increased the risks of stroke incidence (RR = 1.22, 95%CI: 1.08–1.38) and mortality (RR = 1.42, 95%CI: 1.15–1.77) among women. Regarding stroke subtype, hyperuricemia was significantly associated with the incidence (RR = 1.21, 95%CI: 1.03–1.42) and mortality (RR = 1.23, 95%CI: 1.01–1.49) of ischemic stroke. A J shaped dose–response relationship was found between uric acid and stroke incidence (p = 0.0023), with risk rising across uric acid levels from104 to 764.5 μmol/L and a nadir at 225 μmol/L, whereas no significant nonlinear relationship was observed for stroke mortality. Conclusion Hyperuricemia is associated with increased risks of stroke incidence and mortality, especially in women and ischemic stroke. A J-shaped dose–response relationship was observed for stroke incidence, but not for stroke mortality. Monitoring uric acid levels and their longitudinal changes may be valuable in stroke prevention strategies. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261394403, identifier PROSPERO (CRD420261394403).