Increased Serum Complement C3 Levels Are Associated With Adverse Clinical Outcomes After Ischemic Stroke

Background and Purpose: Complement C3 has been implicated in inflammation and ischemia/reperfusion injury, but its impact on the prognosis of ischemic stroke remains unclear. Aim of this study was to prospectively investigate the association between serum complement C3 and adverse clinical outcomes after ischemic stroke. Methods: We measured serum complement C3 levels for 3474 patients with ischemic stroke in 26 participating hospitals and collected data of clinical outcomes at 3 months after ischemic stroke. The primary outcome was composite outcome of death and major disability (modified Rankin Scale score >= 3) at 3 months after stroke onset and secondary outcomes included major disability, death, and vascular events. Results: During 3 months of follow-up, 866 participants (25.4%) developed primary outcome. After multivariate adjustment, elevated serum complement C3 levels were associated with increased risk of primary outcome (odds ratio, 1.30 [95% CI, 1.02-1.65]; P-trend=0.038) when 2 extreme tertiles were compared. Each SD increase of log-transformed complement C3 was associated with 13% (95% CI, 2%-25%) increased risk of primary outcome. Multivariable-adjusted spline regression model showed a linear relationship between serum complement C3 and the risk of primary outcome (P-linearity=0.022). Addition of serum complement C3 to conventional risk factors significantly improved the risk prediction of primary outcome (net reclassification index: 8.87%, P=0.028; integrated discrimination index: 0.19%, P=0.029). Conclusions: High serum complement C3 levels at baseline were associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that serum complement C3 may be a valuable prognostic biomarker for ischemic stroke.