Complement Components C1r and C8 Serve as Potential Inflammatory Biomarkers for Coronary Heart Disease Severity: The Mediating Role of C-Reactive Protein

Purpose: Inflammation plays an important role in the occurrence and development of coronary heart disease (CHD). We investigated serum complement C1r, C1s, C7, C8, C9 as potential biomarkers and the mediating role of C-reactive protein (CRP) in CHD severity. The severity of coronary artery stenosis was quantified using the validated Gensini score. Patients and Methods: In this prospective cross-sectional study (n=314), patients were categorized into a control group (n=102) and a CHD group (n=212) via coronary angiography. CHD severity was quantified by the Gensini score (mild ≤ 31; moderate-to-severe > 31). The study incorporated multiple known pathogenic factors such as demographic characteristics, underlying diseases, and metabolic indicators for comprehensive analysis. Serum complement levels were measured by ELISA. Spearman correlation, multivariate logistic regression, ROC analysis, and mediation modeling assessed associations and CRP’s role. Results: Serum C1r and C8 were significantly elevated in CHD and severe stenosis groups. While C1s showed a slight increase in the severe stenosis group, it, along with C7 and C9, showed limited overall diagnostic utility for CHD. Spearman analysis revealed that C1r and C8 were positively correlated with both Gensini score and cTnT levels. In the fully adjusted model (Model 4), C1r remained a robust independent predictor of moderate-to-severe stenosis (continuous OR=2.10, 95% CI: 1.41– 3.12; Q4 vs Q1 OR=5.61, 95% CI: 2.12– 14.89). C8 also maintained statistical significance as a continuous variable (OR=1.98, P=0.004). Furthermore, mediation analysis indicated that CRP mediated 31.6% and 46.2% of the effects of C1r and C8 on disease severity, respectively. The combined AUC of C1r and C8 for predicting CHD was 0.769. Conclusion: C1r is an independent predictor of CHD severity, while C8 exhibits a dose-dependent association modulated by systemic status. Integrating anatomical and physiological markers confirms the complement-CRP axis’s pivotal role in CHD risk stratification, providing evidence for inflammatory biomarkers in lesion assessment. Keywords: complement activation, Gensini score, mediation analysis, coronary heart disease, risk stratification