Complement Activation and Prognosis in Patients With Type 2 Diabetes and Myocardial Infarction

Abstract

OBJECTIVEThe activation of the complement system may be involved in the pathology of myocardial infarction (MI) and type 2 diabetes. To explore their potential as prognostic markers, we characterized two factors in the complement cascade, the end product sC5b-9 and the mannose-binding lectin–associated Ser protease-2 (MASP-2), in type 2 diabetic patients with suspected MI.RESEARCH DESIGN AND METHODSPlasma sC5b-9 and MASP-2 were determined in patients with MI and type 2 diabetes (n = 397; median age 70; male 68%). The adjudicated end points were cardiovascular events (CVEs), including cardiovascular mortality and nonfatal MI or stroke.RESULTSThe median sC5b-9 was 134 μg/L (interquartile range [IQR] 101–190 μg/L) and the median MASP-2 was 333 μg/L (IQR 235–463 μg/L), with no significant correlation between them. Women had higher sC5b-9 than men (median 152 vs. 130 μg/L; P = 0.02). Both sC5b-9 and MASP-2 were correlated to age and creatinine clearance, while MASP-2 was also correlated to BMI. During a median follow-up of 2.4 years, CVEs occurred in 141 patients (36%). Both sC5b-9 (hazard ratio 1.37 [95% CI 1.13–1.65]; P < 0.01) and MASP-2 (0.68 [0.51–0.92]; P = 0.01) predicted CVEs in unadjusted analyses. After multiple adjustments, the predictive capacity remained for sC5b-9 (1.30 [1.02–1.66]; P = 0.04) but not for MASP-2.CONCLUSIONSIn type 2 diabetic patients with MI, high levels of sC5b-9 predict future CVE. This indicates that the complement system may play a significant role in the pathology of the subsequent myocardial damage and that the pathways leading to complement activation warrant further exploration as potential therapeutic targets to improve the prognosis for these patients.

Molecular Biology of Atherosclerosis

“…The protective effects of CD59 were confirmed by another group (1017), although more equivocal results were reported by others (60,2052). These animal studies are consistent with an epidemiological study finding mildly increased risk of cardiovascular events in those having higher plasma levels of soluble C5b-9 as evidence of an activated complement system (1189). Factors earlier in the pathway were less strongly or nonsignificantly associated with risk (479).…”

A vital role for complement in heart disease

“…It has later been confirmed that plasma sC5b-9 at hospital admittance is a negative prognostic factor in acute myocardial infarction (Lindberg et al, 2012;Mellbin et al, 2012).…”

Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation

“…MASP-2 levels were lower in both MI and stroke patients compared with healthy controls, while MASP-3 and MAp44 did not differ between groups (Frauenknecht et al, 2013). In a cohort study of individuals with T2DM, MASP-2 levels were significantly decreased in patients with acute cardiovascular events (Mellbin et al, 2012). MASP-2 levels were also lower in another study in patients with acute MI (Zhang et al, 2013).…”