Associations of Serum Complement Biomarkers With Adverse Clinical Outcomes Among Patients With Ischemic Stroke

Background The complement system plays a crucial role in immune regulation and inflammatory response and is believed to be involved in the onset and progression of ischemic stroke. Therefore, we aimed to investigate the associations of baseline serum complement C3 and C4 levels with the prognosis of ischemic stroke. Methods We measured baseline serum complemental C3 and C4 levels in 3979 patients with ischemic stroke from the Minhang Stroke Cohort. The primary outcome was death or major disability at discharge after ischemic stroke. Secondary outcomes included major disability, death, and pneumonia. In addition, we constructed a complement biomarker score based on serum complement C3 and C4 levels to systematically evaluate the impact of the complement system on the prognosis among patients with ischemic stroke. Results Among the 3979 patients with ischemic stroke, 1360 (34.18%) experienced death or major disability at discharge. After multivariable adjustment, the odds ratios of the primary outcome for the highest versus the lowest quartile were 1.34 (95% confidence intervals CI, 1.06–1.69; P trend =0.013) for complement C3, 1.34 (95% CI, 1.06–1.69; P trend =0.014) for complement C4, and 1.32 (95% CI, 1.05–1.67; P trend =0.018) for the complement biomarker score. Multivariable‐adjusted restricted cubic spline analyses indicated linear dose–response relationships of serum complement C3 ( P linearity =0.025), complement C4 ( P linearity =0.021), and complement biomarker score ( P linearity =0.011) with the risk of primary outcome. Adding the complement biomarker score to conventional models resulted in significant improvement in risk discrimination for the poor outcomes after ischemic stroke, as evidenced by integrated discrimination improvement (all P <0.05). Conclusions High serum complement C3 and C4 levels were associated with increased risks of adverse outcomes at discharge after ischemic stroke, suggesting that the complement system might be implicated in the progression of ischemic stroke and could be potential intervention targets for improving prognosis.