ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neuroepidemiology
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1599730
Inflammation mediates the association between hyperuricemia and stroke mortality: a cohort study
Provisionally accepted
- China Three Gorges University, Yichang, China
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Background: Stroke is a leading cause of mortality and disability worldwide. The relationship between hyperuricemia and stroke prognosis remains controversial. This study aims to investigate the association between hyperuricemia and stroke prevalence, as well as the impact of hyperuricemia on mortality risk among stroke patients, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2001-2018.Methods: Hyperuricemia was defined as serum uric acid ≥416 μmol/L (7.0 mg/dL) in men or ≥357 μmol/L (6.0 mg/dL) in women. We conducted weighted logistic regression analyses to assess the association between hyperuricemia and stroke prevalence. Cox proportional hazards regression models were used to evaluate the impact of hyperuricemia on all-cause and cardiovascular mortality among stroke patients. The models were progressively adjusted for demographic factors, lifestyle factors, comorbidities, and biomarkers. Time-dependent ROC curves were constructed to assess predictive performance. Restricted cubic splines were applied to investigate potential nonlinear relationships between serum uric acid and mortality. Subgroup and mediation analyses explored the interactions and indirect effects, respectively. Sensitivity analyses were conducted to ensure the robustness of the results.Results: Hyperuricemia was associated with increased odds of stroke (adjusted OR 1.25; 95% CI:1.07-1.45; P = 0.005). Among 1,579 stroke patients, hyperuricemia was linked to higher risks of all-cause mortality (adjusted HR 1.25; 95% CI: 1.06-1.48; P = 0.008) and cardio-cerebrovascular mortality (adjusted HR 1.38; 95% CI: 1.05-1.80; P = 0.020). Inflammation markers SII and CRP partially mediated these associations.Conclusions: Hyperuricemia is associated with an increased prevalence of stroke. It is also strongly associated with increased mortality in stroke patients, an association mediated in part by inflammation.
Keywords: Hyperuricemia, Stroke, Mortality, Inflammation, NHANES, Mediation analysis
Received: 19 May 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 He, You, Fan, Wang and Qian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Min Qian, China Three Gorges University, Yichang, China
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