Monocyte Chemoattractant Protein‐1, Inflammatory Biomarkers, and Prognosis of Patients With Ischemic Stroke or Transient Ischemic Attack: Fndings From a Nationwide Registry Study

Abstract

Background Recent Mendelian randomization and meta‐analysis highlight the relevance of MCP‐1 (monocyte chemoattractant protein‐1) in stroke. We aimed to investigate the associations between MCP‐1 and clinical outcomes in patients with ischemic stroke or transient ischemic attack and test whether inflammation mediates or jointly contributes to the relationships. Methods and Results A total of 10 700 patients from the Third China National Stroke Registry study were included. Multivariable Cox regression was used for recurrent stroke and all‐cause death, and logistic regression was used for poor functional outcome. Mediation analyses were performed to clarify whether inflammation mediates the associations. After adjusting for potential confounders, low MCP‐1 level (<337.6 pg/mL) was associated with a reduced risk of all‐cause death (hazard ratio [HR], 0.65 [95% CI, 0.51–0.82]) and poor functional outcome (odds ratio, 0.81 [95% CI, 0.70–0.94]) but was not associated with recurrent stroke (HR, 1.10 [95% CI, 0.95–1.27]), compared with high MCP‐1 level (≥337.6 pg/mL). The association between MCP‐1 and all‐cause death was partially mediated by highly sensitive C‐reactive protein, interleukin‐6, and YKL‐40 (Chitinase‐3‐like protein 1; mediated proportion: 7.4%, 10.5%, and 7.4%, respectively). The corresponding mediated proportion for poor functional outcome was 9.9%, 17.1%, and 7.1%, respectively. Patients with combined high levels of MCP‐1 and inflammatory biomarkers had the highest risks of all‐cause death and poor functional outcome. Conclusions Low plasma MCP‐1 level was associated with decreased risks of all‐cause mortality and poor functional outcome after ischemic stroke or transient ischemic attack. Inflammation partially mediated and jointly contributed to the associations.