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

ABSTRACT: 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.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.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.

SUBMITTER: Zhong C

PROVIDER: S-EPMC5533011 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Zhong Chongke C Zhong Xiaoyan X Xu Tian T Xu Tan T Zhang Yonghong Y

Journal of the American Heart Association 20170329 4

<h4>Background</h4>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.<h4>Methods and results</h4>Prospective studies that reported sex-specific association of UA levels with stroke or reported in a certain sex were included. Dose-r ...[more]

PMID: 28356280

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Project description:Background: Uric acid (UA) is proposed as a potential risk factor for stroke in adult, yet the results from published studies are not generally accordant. Method: We included prospective studies that explored the relationship between serum UA (SUA) and strokes. In this study, strokes include ischemic stroke and hemorrhagic stroke, which consists of intracerebral hemorrhage and subarachnoid hemorrhage. The effect-size estimates were expressed as hazard ratio (HR) and 95% confidence interval (CI). Sensitivity and subgroup analyses were performed to assess the robustness of the pooled estimation and potential sources of heterogeneity between studies. Results: We meta-analyzed 19 prospective cohort articles, which involve 37,386 males and 31,163 females. Overall analyses results showed a significant association between a 1 mg/dl increase in high levels of SUA and the risk of total stroke (HR = 1.13; 95% CI: 1.09-1.18; P < 0.001), ischemic stroke (HR = 1.15; 95% CI: 1.10-1.21; P < 0.001), and hemorrhagic stroke (HR = 1.07; 95% CI: 1.00 to 1.15; P = 0.046). No significant difference was found between ischemic stroke and hemorrhagic stroke. In the subgroup analyses, the association of high SUA levels and the risk of total stroke was statistically significant in females (HR = 1.19; 95% CI: 1.12-1.26; P < 0.001) and males (HR = 1.11; 95% CI: 1.05-1.17; P < 0.001). Coincidentally, the association was also statistically significant for ischemic stroke, both in females (HR = 1.26; 95% CI: 1.17-1.36; P < 0.001) and in males (HR = 1.12; 95% CI: 1.06-1.19; P < 0.001). However, for hemorrhagic stroke, it was only statistically significant in females (HR = 1.19; 95% CI: 1.04-1.35; P = 0.01). Our dose-response research indicated the J-shaped trend between the ascending SUA levels and the higher risk of suffering from a stroke. Conclusions: Our findings indicate that elevated SUA is a significant risk factor for adult stroke, both for ischemic stroke and hemorrhagic stroke, and especially in females.

Project description:Background: Limited studies focused on the association between serum uric acid (SUA) change with ischemic stroke, and their results remain controversial. The present study aimed to investigate the relationship between change in SUA with ischemic stroke among hypertensive patients. Method: This was a retrospective cohort study. We recruited adult hypertensive patients who had two consecutive measurements of SUA levels from 2013 to 2014 and reported no history of stroke. Change in SUA was assessed as SUA concentration measured in 2014 minus SUA concentration in 2013. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan-Meier analysis and log-rank test were performed to quantify the difference in cumulative event rate. Additionally, subgroup analysis and interaction tests were conducted to investigate heterogeneity. Results: A total of 4,628 hypertensive patients were included, and 93 cases of ischemic stroke occurred during the mean follow-up time of 3.14 years. Participants were categorized into three groups according to their SUA change tertiles [low (SUA decrease substantially): <-32.6 μmol/L; middle (SUA stable): ≥-32.6 μmol/L, <40.2 μmol/L; high (SUA increase substantially): ≥40.2 μmol/L]. In the fully adjusted model, setting the SUA stable group as reference, participants in the SUA increase substantially group had a significantly elevated risk of ischemic stroke [HR (95% CI), 1.76 (1.01, 3.06), P = 0.0451], but for the SUA decrease substantially group, the hazard effect was insignificant [HR (95% CI), 1.31 (0.75, 2.28), P = 0.3353]. Age played an interactive role in the relationship between SUA change and ischemic stroke. Younger participants (age < 65 years) tended to have a higher risk of ischemic stroke when SUA increase substantially. Conclusion: SUA increase substantially was significantly correlated with an elevated risk of ischemic stroke among patients with hypertension.

Dataset Information

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

Publications

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

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