Abstract 822: High Plasma Levels of Macrophage Migration Inhibitory Factor Adversely Affect Long-term Outcome in Patients With Acute Coronary Syndromes and With Impaired Glucose Tolerance or Type 2 Diabetes Mellitus
Macrophage migration inhibitory factor (MIF) is a proinflammatory and proatherogenic mediator and is highly expressed in unstable atherosclerotic plaques. MIF plays a pathogenic role in insulin resistance, and circulating levels of MIF are increased in patients with impaired glucose tolerance (IGT) or type 2 diabetes mellitus (DM). Thus, we hypothesized that high MIF levels may play a role in the increased risk of recurrent cardiovascular disease (CVD) after acute coronary syndromes (ACS) in patients with IGT/DM. We examined whether plasma MIF levels may predict future CVD events in ACS patients with IGT or type 2 DM.
Methods: Plasma MIF levels on day 3 after ACS were measured by ELISA in 443 patients with ACS including 39 patients with IGT and 174 patients with type 2 DM. All patients were prospectively followed for 60 months or until occurrence of one of the CVD events: cardiac death, nonfatal myocardial infarction, unstable angina pectoris requiring coronary revascularization, heart failure requiring hospitalization or ischemic stroke.
Results: MIF levels were higher in ACS patients than age-and sex-matched healthy controls (n=50) (29.1±1.2 vs. 20.2±1.8 ng/mL, p<0.01). MIF levels had a positive correlation with homeostasis model assessment for insulin resistance in ACS patients (r=0.31, p=0.01). During the follow-up period, an event occurred in 62 (29%) patients with IGT/DM and 44 (19%) patients without IGT/DM. In ACS patients with IGT/DM, MIF levels in the highest tertile were a significant predictor of CVD events compared with the lowest tertile in a multivariate Cox proportional hazards analysis that included CRP levels, use of anti-diabetic medication, and traditional risk factors as covariates (HR 3.0, 95% CI 1.5–5.6, p=0.001). The c-statistic showed that the predictive value of MIF levels was incremental over that of the traditional predictors for CVD events (area under the ROC curve; 0.81 and 0.72, respectively, p=0.001). In contrast, MIF levels were not significantly related to future CVD events in ACS patients without IGT/DM.
Conclusions: High plasma levels of MIF are an independent risk factor for future CVD events in ACS patients with IGT/DM. Higher MIF levels may play a possible role in future CVD events in ACS patients with IGT or type 2 DM.