Sex‐Specific Relationship Between Serum Uric Acid and Risk of Stroke: A Dose‐Response Meta‐Analysis of Prospective Studies

BACKGROUND Conflicting findings of the association between serum uric acid (UA) and stroke have been reported in both men and women, and it is unclear whether this association was different between men and women. We preformed this meta-analysis to assess the sex-specific effect of serum UA on the risk of stroke and its subtypes. METHODS AND RESULTS Prospective studies that reported sex-specific association of UA levels with stroke or reported in a certain sex were included. Dose-response relationships were assessed by the generalized least squares trend estimation, and summary effect estimates were evaluated with random-effect models. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation. Altogether, 13 prospective studies were identified in this study. The summary of relative risks (95% CIs) of stroke for a 1-mg/dL increase in serum UA levels were 1.10 (1.05-1.14) for men and 1.11 (1.09-1.13) for women. There is no significant difference in the effect of UA on future stroke risk between men and women (Pinteraction=0.736). Subgroup analyses showed that the significant associations persisted in most stratifications, and sensitivity analyses according to various inclusion criteria yielded similar results. A nonlinear relationship was observed in men (Pnon-linearity<0.001), with risk increasing significantly from a UA of 6 mg/dL and more steeply at higher UA levels. CONCLUSIONS Elevated serum UA levels were significantly associated with modestly increased risk of stroke in both men and women and have similar adverse effects on development of stroke in both sexes.