Haoran Chen,1 Meng Wang,2,3 Lin Yang,1,4 Jiao Li,1,4,* Zixiao Li2,3,5,* 

1Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 4Key Laboratory of Medical Information Intelligent Technology, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jiao Li, Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 3 Yabao Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Email li.jiao@imicams.ac.cn Zixiao Li, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Road, Southern Fourth Ringroad, Fengtai District, Beijing, 100070, People’s Republic of China, Email lizixiao2008@hotmail.com

Aim: The interaction between inflammatory biomarkers (high-sensitivity C-reactive protein, hsCRP) and antioxidants (uric acid, UA) regarding prognosis after ischemic stroke or transient ischemic attack (TIA) remains inadequately explored. This study aimed to assess (1) the individual and joint effects of hsCRP and UA, and (2) the neuroprotective role of UA in patients with elevated hsCRP levels concerning poor functional outcomes at 90 days.
Methods: A prospective cohort study was conducted involving 2140 consecutive ischemic stroke or TIA patients with hsCRP and UA levels. The primary outcome was defined as a poor functional outcome, indicated by a modified Rankin Scale (mRS) score of 3– 6 at 90 days, with a shift in the mRS score as a secondary outcome. Logistic regression and propensity score (PS) analyses were employed to ensure robustness.
Results: Poor functional outcome occurred in 345 (16.1%) patients. Individual effects found that the highest quartiles of hsCRP (adjusted OR = 3.090; 95% CI 2.150– 4.442) and UA (adjusted OR = 0.671; 95% CI 0.551– 0.883) were associated with increased or decreased risk of poor functional outcome, respectively. Joint effects (adjusted OR = 3.994; 95% CI 2.758– 5.640) between hsCRP and UA on the primary outcome were more apparent in patients with high hsCRP levels (hsCRP > 1.60 mg/L) and low UA levels (UA ≤ 291.85 μmol/L). For the patients with high hsCRP levels, patients with low UA levels had a higher risk of primary and secondary outcomes, compared with those with high UA levels, after unadjusted or adjusted for hsCRP. Similar and reliable results were observed in PS-based models.
Conclusion: In patients with ischemic stroke or TIA, joint high levels of hsCRP and low UA levels significantly correlate with increased risk of poor functional outcome at 90 days. In addition, high UA levels could reduce the risk of poor functional outcome for patients with high hsCRP levels.

Keywords: biomarkers, ischemic stroke, poor functional outcome, joint effects, neuroprotective effects