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

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

doi:10.3389/fnagi.2022.822350

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

Front Aging Neurosci. 2022 Mar 8:14:822350. doi: 10.3389/fnagi.2022.822350. eCollection 2022.

Authors

Han-Yu Zhu^{1

2}, Shu-Zhen Zhao³, Meng-Li Zhang^{1

2}, Yan Wang^{1

2}, Zhi-Ming Pan^{1

2}, Hao-Ran Cheng¹, Ke Zhao⁴, Zhen Wang¹

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² The First Clinical College, Wenzhou Medical University, Wenzhou, China.
³ Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
⁴ Department of Neurology, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, China.

Abstract

Background: Serum 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.

Objective: We 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.

Methods: A 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.

Results: Ischemic 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.

Conclusion: UA level is non-linearly associated with recurrence, and NLR has an additive interaction between UA and ischemic stroke recurrence.

Keywords: NLR; UA; interaction and joint analysis; ischemic stroke recurrence; mediation analysis; restricted cubic spline regression.