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

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.

Association of serum uric acid to lymphocyte ratio, a novel inflammatory biomarker, with risk of stroke: A prospective cohort study

“…Experimental studies have shown that increased SUA as a pro‐oxidant is associated with endothelial dysfunction, increased oxidative stress, elevated plasma renin activity and systemic inflammation mediators, which may contribute to the development of HS 36,37 . Population study found that elevated serum uric acid increases the risk of stroke recurrence 38 . On the other hand, SUA is also an abundant natural antioxidant capable of reducing cellular oxidation, a major cause of neurodegenerative disease 39 .…”

Serum Uric Acid to Serum Creatinine Ratio and Risk of Stroke Recurrence in Young Adults with Ischemic Stroke

“…10 Retrospective research suggested that uric acid was related to stroke recurrence in older adults with interaction to inflammatory factors. 27 Packer et al proved that uric acid could increase the production of reactive oxygen species and enhance oxidative stress. 28 However, uric Abbreviations: CI, confidence interval; HR, hazard ratio; SUA/SCr, serum uric acid/serum creatine.…”

Elevated serum uric acid is associated with cognitive improvement in older American adults: A large, population-based-analysis of the NHANES database

“…As a metabolite, SUA also carries a risk of contributing to development of diabetes ( Lu et al, 2020 ), and diabetes increases the risk of dementia ( Biessels and Despa, 2018 ). It has also been demonstrated that hyperuricemia is a risk factor for cerebrovascular ( Zhu et al, 2022 ) and cardiovascular illnesses ( Mouradjian et al, 2020 ). Further, vascular risk factors have been linked to an increased risk of dementia ( Gottesman et al, 2017 ).…”

“…In the subgroup analysis stratified by age, gender, and race, the model is not adjusted for age, gender, or race, respectively. factor for cerebrovascular (Zhu et al, 2022) and cardiovascular illnesses (Mouradjian et al, 2020). Further, vascular risk factors have been linked to an increased risk of dementia (Gottesman et al, 2017).…”