Combined activation of complement and coagulation is associated with myocardial injury in ST-elevation myocardial infarction

Abstract Introduction Experimental data indicates that the complement system and the coagulation cascade can activate each other. The magnitude of this interaction in acute myocardial infarction is not known. We aimed to investigate a possible association between complement activation and coagulation activation in patients with acute ST-elevation myocardial infarction (STEMI), as well as how they relate to myocardial injury estimated by troponin T (TnT) and myocardial function assessed by echocardiography. Purpose To increase the understanding of the interaction between complement activation and coagulation activation in STEMI, and the clinical relevance to myocardial injury. Methods Blood samples were drawn after percutaneous coronary intervention (PCI) in 864 patients with STEMI. Myocardial function was measured as left ventricular ejection fraction (LVEF), estimated by visual approximation or Simpson biplane method within 3 months. Complement activation was assessed by ELISA of circulating levels of the terminal complement complex (TCC). Activation of coagulation was assessed by ELISA of prothrombin fragment 1+2 (F1+2) and D-dimer, and endogenous thrombin potential (ETP), analyzed by calibrated automated thrombogram assay. Results TCC was weakly correlated to F1+2 (r=0.086, p=0.012), D-dimer (r=0.176, p<0.001) and ETP (r=0.144, p<0.001). In univariate linear regression analysis, this association persisted for D-dimer and ETP. When adjusting for associated covariables, the association only persisted for ETP (Table 1). Patients with above-median TCC and D-dimer had significantly higher peak TnT (Figure 1). In logistic regression, having combined above-median TCC and D-dimer was predictive of an LVEF ≤40% (Table 2). Conclusion In this large STEMI cohort, complement activation by TCC was weakly associated with coagulation activation. Combined high levels of TCC and D-dimer were linked to higher peak TnT and lower LVEF, possibly reflecting greater myocardial injury. The interaction between complement and coagulation activation might be relevant for clinical outcomes in STEMI patients and warrants further investigation.