Elevated Serum Uric Acid Increases the Risk of Ischemic Stroke Recurrence and Its Inflammatory Mechanism in Older Adults.

Han-Yu Zhu,Zhen Wang,Yan Wang,Hao-Ran Cheng,Zhi-Ming Pan,Meng-Li Zhang,Shu-Zhen Zhao,Ke Zhao

doi:10.3389/fnagi.2022.822350

Abstract

BackgroundSerum uric acid (UA) has been reported to be associated with ischemic stroke and inflammation. However, whether or not UA is related to the recurrence of ischemic stroke, and whether inflammation plays a role in the relationship between them remain inconclusive.ObjectiveWe sought to explore the relationship between UA and the recurrence of ischemic stroke and to define the role of neutrophil-to-lymphocyte ratio (NLR) in the aforementioned relationship.MethodsA total of 8,995 patients were included in this study. Basic information and blood samples were collected, and whether or not each participant experienced ischemic stroke recurrence within 3 years was documented. Patients were stratified into three groups according to their UA level, as follows: ≤ 266, 267–339, and ≥ 340 μmol/L. COX regression and restricted cubic spline regression models were used to evaluate the clinical correlation between UA and ischemic stroke recurrence, mediation analysis and interaction and joint analysis were used to evaluate the role of NLR in the association of UA and ischemic stroke recurrence, and sensitivity and subgroup analyses were performed to test the robustness of the data.ResultsIschemic stroke recurrence was related to male sex, older age, higher UA level, higher NLR, hypertension, diabetes, and cardiovascular disease. Following adjustment for potential confounders, a high level of UA (≥ 340 μmol/L) increased the risk of recurrence by 92.6% in patients with previous ischemic stroke. We also found that NLR affects the association between UA and the recurrence of ischemic stroke in older adults, suggesting that patients with high NLR and high UA levels are at greater risk for ischemic stroke recurrence.ConclusionUA level is non-linearly associated with recurrence, and NLR has an additive interaction between UA and ischemic stroke recurrence.

Highlights

Stroke is the second most common cause of death and the third leading cause of disability, with an increasing incidence in developing countries (Campbell and Khatri, 2020)
COX regression and restricted cubic spline regression models were used to evaluate the clinical correlation between uric acid (UA) and ischemic stroke recurrence, mediation analysis and interaction and joint analysis were used to evaluate the role of neutrophil-to-lymphocyte ratio (NLR) in the association of UA and ischemic stroke recurrence, and sensitivity and subgroup analyses were performed to test the robustness of the data
Ischemic stroke recurrence was related to male sex, older age, higher UA level, higher NLR, hypertension, diabetes, and cardiovascular disease

Summary

Introduction

Stroke is the second most common cause of death and the third leading cause of disability, with an increasing incidence in developing countries (Campbell and Khatri, 2020). The Global Burden of Disease Study revealed that, stroke incidence, prevalence, mortality, and disability-adjusted life-years rates declined from 1990 to 2013, the overall stroke burden has increased across the globe in both men and women of all ages (Feigin et al, 2017). Survivors of stroke and transient ischemic attack are at risk for a recurrent stroke, which is often more severe and disabling than the index event. In the last 10 years, the recurrence rate of stroke has not declined further (Flach et al, 2020). Supporting the argument that more research on the recurrence of stroke events is still necessary. Whether or not UA is related to the recurrence of ischemic stroke, and whether inflammation plays a role in the relationship between them remain inconclusive

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