A decline of protective apolipoprotein J and complement factor H concomitant with increase in C5a 3 months after cardiac surgery—Evidence of long-term complement perturbations

Abstract

BackgroundHeart surgery results in complement activation with the potential for collateral end-organ damage, especially if the protective elements (complement factor H, Apolipoprotein J) are inadequate. Here, we have investigated if peri-operative stress results in an imbalance between complement activation and its protective mechanisms up to 3 months after heart surgery.Methods101 patients scheduled for non-emergent cardiac surgery donated blood before the procedure (tbaseline), and 24 h (t24h), 7 days (t7d) and 3 months (t3m) after. Complement activation was measured as a serum level of soluble activated component 5 (sC5a) and soluble terminal complement complex (sTCC). Simultaneously, protective complement factor H (CfH), and apolipoprotein J (ApoJ) were measured. Inflammatory responses were quantified using C-reactive protein (CRP) and interleukin-6 (IL-6). Details regarding anesthesia, intensive care unit (ICU) stay, pre-existing conditions, the incidence of postoperative complications, and mortality were collected from medical records.ResultsC5a declined at t24h to rebound at t7d and t3m. sTCC was significantly depressed at t24h and returned to baseline at later time points. In contrast, CfH and ApoJ were depressed at t3m. Milieu of complement factors aligned along two longitudinal patterns:cluster#1 (C5a/sTTC continuously increasing and CfH/ApoJ preserved at tbaseline) and cluster#2 (transient sC5a/sTTC increase and progressive decline of CfH). Most patients belonged to cluster #1 at t24h (68%), t7d (74%) and t3m (72%). sTCC correlated with APACHE1h (r2 =−0.25; p < 0.031) and APACHE24h (r2 = 0.27; p < 0.049). IL-6 correlated with C5a (r2 =−0.28; p < 0.042) and sTTC (r2 =−0.28; p < 0.015). Peri-operative administration of acetaminophen and aspirin altered the complement elements. Prolonged hospital stay correlated with elevated C5a [t (78) = 2.03; p = 0.048] and sTTC serum levels [U (73) = 2.07; p = 0.037]. Patients with stroke had a decreased serum level of C5a at t7d and t3m.ConclusionThere is a significant decrease in complement protective factors 3 months after cardiac surgery, while C5a seems to be slightly elevated, suggesting that cardiac surgery affects complement milieu long into recovery.