Abstract 3208: High Plasma Levels of Macrophage Migration Inhibitory Factor Predict Future Cardiovascular Events in Patients with Impaired Glucose Tolerance or Type 2 Diabetes Mellitus
Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator and plays a role in development of cardiovascular disease (CVD). However, the predictive value of MIF levels for future CVD events remains controversial based on previous studies in a healthy population. MIF plays a pathogenetic 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 CVD in IGT/DM. This study examined whether plasma MIF levels may have a predictive value of CVD events in patients with IGT or type 2 DM. Plasma MIF levels after overnight fast were measured by ELISA in 275 patients with chronic coronary artery disease (CAD) including 57 patients with IGT and 88 patients with type 2 DM. Thereafter, all CAD patients were prospectively followed-up for 60 months or until one of the following CVD events: cardiac death, nonfatal myocardial infarction, unstable angina pectoris requiring coronary revascularization, congestive heart failure requiring hospitalization, or ischemic stroke. MIF levels were higher in CAD patients than age- and sex-matched healthy controls (n = 50) (31.8 ± 1.2 vs. 21.1 ± 1.8 ng/mL, p < 0.01). MIF levels had a positive correlation with homeostasis model assessment for insulin resistance in CAD patients (r = 0.35, p = 0.01), and MIF levels were higher in CAD patients with than without IGT/DM (35.8 ± 1.6 vs. 26.3 ± 1.5 ng/mL, p < 0.01). During follow-up period, an event occurred in 60 (41%) patients with IGT/DM and 41 (32%) patients without IGT/DM. In CAD patients with IGT/DM, MIF levels in the highest tertile were a significant predictor of CVD events as compared with the lowest tertile in a multivariate Cox hazards analysis that included CRP levels, use of anti-diabetic medication, and traditional risk factors as covariates (HR 3.0, 95% CI 1.5 – 6.0, p = 0.01). In contrast, MIF levels were not significantly related to future CVD events in CAD patients without IGT/DM. High plasma levels of MIF are an independent risk factor for future CVD events in chronic CAD patients with IGT or type 2 DM. Higher MIF levels may play a possible role in CVD development in IGT and type 2 DM.