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Associations of Serum Complement Biomarkers With Adverse Clinical Outcomes Among Patients With Ischemic Stroke
Lulu Sun1, Yong Wang2,3, Yang Liu2,4
1Department of Epidemiology, the Affiliated Guangji Hospital of Soochow University, School of Public Health Suzhou Medical College of Soochow University Suzhou Jiangsu China.
Insights
Elevated serum complement C3 and C4 levels are linked to worse outcomes in ischemic stroke patients. These findings suggest the complement system could be a target for improving stroke prognosis.
Area of Science:
- Immunology
- Neurology
- Cardiovascular Research
Background:
- The complement system is integral to immune regulation and inflammation.
- Its role in ischemic stroke onset and progression is under investigation.
Purpose of the Study:
- To investigate the association between baseline serum complement C3 and C4 levels and ischemic stroke prognosis.
- To evaluate the impact of a complement biomarker score on patient outcomes.
Main Methods:
- Serum complement C3 and C4 levels were measured in 3979 ischemic stroke patients.
- Primary outcome: death or major disability at discharge.
- Secondary outcomes included disability, death, and pneumonia; a complement biomarker score was developed.
Main Results:
- Higher complement C3, C4, and biomarker scores correlated with increased risk of adverse outcomes.
- Linear dose-response relationships were observed between complement levels and poor outcomes.
- The complement biomarker score improved risk prediction for poor outcomes in ischemic stroke.
Conclusions:
- High serum complement C3 and C4 levels are associated with adverse outcomes post-ischemic stroke.
- The complement system may influence ischemic stroke progression.
- Complement system components represent potential therapeutic targets for stroke prognosis improvement.
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; Ptrend=0.013) for complement C3, 1.34 (95% CI, 1.06-1.69; Ptrend=0.014) for complement C4, and 1.32 (95% CI, 1.05-1.67; Ptrend=0.018) for the complement biomarker score. Multivariable-adjusted restricted cubic spline analyses indicated linear dose-response relationships of serum complement C3 (Plinearity=0.025), complement C4 (Plinearity=0.021), and complement biomarker score (Plinearity=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.
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