Interventional Cardiology Soluble form of membrane attack complex independently predicts mortality and cardiovascular events in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention Søren Lindberg, MD, a Sune H. Pedersen, MD, PhD, a Rasmus Mogelvang, MD, PhD, a Søren Galatius, MD, DMSc, a Allan Flyvbjerg, MD, DMSc, b,c Jan Skov Jensen, MD, PhD, DMSc, a,d and Mette Bjerre, PhD b,c Copenhagen, and Aarhus C., Denmark Background The complement system is an important mediator of inflammation, which plays a pivotal role in atherosclerosis and acute myocardial infarction (AMI). Animal studies suggest that activation of the complement cascade resulting in the formation of soluble membrane attack complex (sMAC), contributes to both atherosclerosis and plaque rupture and may be the direct cause of tissue damage related to ischemia/reperfusion injury. However clinical data of sMAC during an AMI is sparse. Accordingly the aim was to investigate the prognostic role of sMAC in patients with ST-segment elevation myocardial infarction (STEMI). Methods We included 725 STEMI-patients admitted to a single, high-volume invasive heart centre, treated with primary percutaneous coronary intervention (PCI), from September 2006 to December 2008. Blood samples were drawn immediately before PCI. Plasma sMAC was measured using an in-house immunoassay. Endpoints were all-cause mortality (n = 62) and the combined endpoint (n = 122) of major cardiovascular events (MACE) defined as cardiovascular mortality and admission due recurrent AMI or heart failure. Follow-up time was 12 months. Results During 12 months of follow-up 62 patients died from all causes and 122 patients reached the combined end-point of MACE. Patients with high sMAC (N75th percentile) had increased risk of both all-cause mortality and MACE. Even after adjustment for confounding risk factors by Cox-regression analyses, high levels of sMAC remained an independent predictor of all-cause mortality (hazard ratio 1.81 [95% CI 1.06-3.06; P = .029]) and MACE (hazard ratio 1.70 [95% CI 1.16-2.48; P = .006]). Conclusions High plasma sMAC independently predicts all-cause mortality and MACE in STEMI-patients treated with PCI. (Am Heart J 2012;164:786-92.) The importance of inflammation in the pathogenesis of cardiovascular disease (CVD) is well established. Inflam- mation plays a pivotal role both in atherosclerosis and in the rupture of atherosclerotic plaques, which have been identified to account for the majority of acute coronary syndromes. 1,2 Several mechanisms for the immune activation in CVD have been suggested. The complement system has been shown to play a major role in myocardial inflammation and especially tissue injury following ischemia/reperfusion (I/R). 3-6 Patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI) experience ischemia followed by rapid reperfusion and are conse- quently at risk of I/R-injury. During ischemia, myocardial cells undergo changes in surface molecule expression making the affected cells targets for the complement system, a part of the innate immune system, which is a central mediator of inflammation. 7,8 Complement activation results in the formation of the membrane attack complex (MAC) (also known as C5b-9, From the a Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark, b Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus C., Denmark, c The Medical Research Laboratories, Department of Clinical Medicine, Faculty of Health Sciences, Aarhus University C, Denmark, and d Clinical Institute of Surgery and Internal Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark. Submitted June 11, 2012; accepted August 22, 2012. Reprint requests: Søren Lindberg MD, Department of Cardiology P, Gentofte University Hospital, Niels Andersens Vej 65, DK-2900 Hellerup, Denmark. E-mail: soerenli@hotmail.com 0002-8703/$ - see front matter © 2012, Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ahj.2012.08.018