Dynamic Complement Activation Predicts 12-Month Major Adverse Cardiovascular Events in Acute Coronary Syndromes

Background: The role of complement activation in acute coronary syndromes (ACS) and its prognostic significance after percutaneous coronary intervention (PCI) remain incompletely understood. Methods: In this prospective single-center study, 76 patients with ACS undergoing PCI were included. Serum complement components C3 and C4 were measured before PCI and again 24-48 h after the procedure. Delta values (ΔC3 and ΔC4) were calculated as post-procedural minus pre-procedural levels. The primary endpoint was major adverse cardiovascular events (MACE) at 12 months. Associations between complement parameters and outcomes were assessed using logistic regression, Cox proportional hazards models, and Kaplan-Meier analysis. A separate cohort of 19 ACS patients not undergoing PCI was analyzed as a non-PCI reference cohort. Results: During follow-up, 21 MACEs occurred, corresponding to an estimated MACE-free survival of 72.4%. Patients with MACE had significantly higher ΔC3 and ΔC4 values. In univariable analyses, both delta values were associated with increased MACE risk. In univariable Cox models, ΔC3 (HR 1.04, 95% CI 1.02-1.06, p = 0.0003) and ΔC4 (HR 1.14, 95% CI 1.05-1.23, p = 0.001) were associated with earlier event occurrence, and both remained significantly associated with outcomes after age-adjusted multivariable analysis (ΔC3: HR 1.03, p = 0.003; ΔC4: HR 1.12, p = 0.006). Baseline complement levels were not associated with outcomes. Conclusions: Periprocedural complement activation dynamics after PCI are associated with adverse outcomes in ACS and may provide incremental prognostic value.