Pro-apoptotic and Inflammatory Markers Enhance the Ability of MDA-LDL in Circulating Immune Complex to Predict Acute Myocardial Infarction in the VADT Study

Abstract

There is considerable interest in identifying biomarkers indicative of plaque instability and acute events. Previously we reported that MDA-LDL in circulating immune complex predicted acute myocardial infarction (MI) in the VADT study. Interleukin (IL)-6, Fas Ligand, tissue inhibitor of MMP (TIMP)-1 and monocyte chemotactic protein (MCP)-1 have been identified as potentially clinically relevant biomarkers related to plaque instability. Therefore, our objective was to examine the role of these biomarkers in conjunction with MDA-LDL in circulating immune complex as predictors of acute MI in type 2 diabetes. Biomarker levels were measured in 833 VADT patients, a median of 2.0 years after study entry and participants were subsequently followed a median of 3.7 years. Biomarkers were examined individually and as composite scores created by summing z scores across biomarkers. Hazard ratios (HRs) for acute MI were calculated by Cox proportional hazard models. During follow-up, 5.2% had an MI. After adjustment for conventional risk factors, results of composite biomarkers scores were promising with a hazard ratio for acute MI of 4.65 (95% CI: 1.56, 13.9) comparing the fourth to first quartile of our summary composite score which included MDA-LDL-IC, IL-6, Fas Ligand,TIMP-1 and MCP-1 (Table). Disclosure M.F.L. Lopes-Virella: None. K.J. Hunt: None. R. Agarwal: None. N.L. Baker: Research Support; Self; Bristol-Myers Squibb Company. G. Virella: None.