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

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.