Macrophage migration inhibitory factor and the risk of myocardial infarction or death due to coronary artery disease in adults without prior myocardial infarction or stroke: The EPIC-Norfolk prospective population study

PURPOSE: To determine whether plasma levels of macrophage migration inhibitory factor, a proinflammatory cytokine involved in atherogenesis, are predictive of myocardial infarction or death from coronary artery disease. METHODS: We performed a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. We selected men and women who did not report a history of myocardial infarction or stroke at baseline. Baseline concentrations of macrophage migration inhibitory factor were measured among 777 patients who had a myocardial infarction or died of coronary artery disease during follow-up, and 1554 matched controls who remained free of coronary artery disease. RESULTS: Baseline macrophage migration inhibitory factor concentrations were higher in cases than controls (median, 107.4 mug/L vs. 90.7 mug/L, P = 0.001). The risk of myocardial infarction or death from coronary artery disease increased with increasing quartiles of macrophage migration inhibitory factor (P for linearity < 0.0001). Patients in the highest quartile had the greatest likelihood of myocardial infarction or death due to coronary artery disease (unadjusted odds ratio [OR] = 1.6; 95% confidence interval [Cl]: 1.2 to 2.0). After adjustment for traditional risk factors and C-reactive protein level, the odds ratio decreased slightly (OR = 1.3; 95% CI: 1.0 to 1.7). Upon additional adjustment for white cell count, this association was no longer statistically significant. CONCLUSION: Prospective data suggest that the relation between macrophage migration inhibitory factor and the risk of myocardial infarction or death due to coronary artery disease in adults without a history of myocardial infarction or stroke is not very strong. However, the data support a regulatory role for macrophage migration inhibitory factor in the process of atherosclerosis. (C) 2004 by Elsevier Inc.