High plasma levels of macrophage migration inhibitory factor are associated with adverse long-term outcome in patients with stable coronary artery disease and impaired glucose tolerance or type 2 diabetes mellitus.

OBJECTIVES

MIF is proatherogenic and is highly expressed in unstable atherosclerotic plaques. Circulating levels of MIF are increased in patients with impaired glucose tolerance or type 2 diabetes mellitus (IGT/T2DM). We examined whether high circulating levels of macrophage migration inhibitory factor (MIF) are related to increased risk of future coronary events in patients with coronary artery disease (CAD) and IGT/T2DM.

METHODS

Plasma MIF levels after overnight fast were measured by ELISA in 617 patients with stable CAD including 79 patients with IGT and 215 patients with T2DM. All patients were prospectively followed for 60 months or until occurrence of one of the coronary events: cardiac death, nonfatal myocardial infarction, unstable angina pectoris requiring coronary revascularization.

RESULTS

During the follow-up period, an event occurred in 77 (26%) patients with IGT/T2DM and 50 (15%) patients without IGT/T2DM. In patients with IGT/T2DM, higher MIF levels were a significant predictor of coronary events in a multivariate Cox proportional hazards analysis that included the known risk factors, C-reactive protein levels and medication as covariates (HR 3.3, 95% CI 1.6-8.3, p=0.006). The c-statistic showed that the predictive value of MIF levels was incremental over that of the conventional predictors for coronary events (area under ROC curve; 0.70 and 0.61, respectively, p=0.001). In contrast, MIF levels were not significantly related to future coronary events in patients without IGT/T2DM.

CONCLUSIONS

High MIF levels are an independent risk factor for future coronary events in CAD patients with IGT/T2DM.