Abstract 531: Association of D-Dimer With Oxidized Phospholipids, Antibodies to Oxidation-Specific Epitopes and Plaque Morphology in Coronary Artery Disease

Abstract

Objective: Lp(a) is the prominent lipoprotein carrier of oxidized phospholipids (OxPLs) in plasma and OxPLs on Lp(a) are thought to contribute to its atherothrombotic effects. IgM antibodies to oxidation-specific epitopes (OSE) block proinflammatory properties of OxPLs and higher plasma levels in humans associate with reduced CAD and lower risk of cardiovascular (CV) events. Coronary thrombosis upon rupture of an unstable plaque leads to CV events. We hypothesize that plasma D-dimer, a marker of thrombosis, associates inversely with IgM antibodies to OSE and positively with OxPLs on apoB-100 (OxPL-apoB), Lp(a) and indices of unstable plaques as determined by VH-IVUS. Methods and Results: OxPL-apoB, Lp(a) and IgM to OSE (phosphocholine-BSA (PC-BSA) and a malondialdehyde (MDA) mimotope) were measured in 106 subjects with stable CAD undergoing angiography. The plasma D-dimer level was 367.8 ng/mL (range 78.3- 2098.8 ng/mL) and 37 subjects had D-dimer levels (mean ± SD; 918.52 ± 482.81 ng/mL) above the threshold for healthy subjects (>500 ng/mL). D-dimer positively associated with OxPL-apoB (r=0.45, p=0.001) and Lp(a) (r=0.44, p=0.001; n=50) and inversely associated with IgM antibodies to PC-BSA and MDA mimotope (r=0.25, p=0.01 and r=0.20, p=0.04 respectively). Moreover, D-dimer associated inversely with plaque fibrosis (r=0.21, p=0.03), positively with coronary artery calcium (r=0.30, p=0.002) and trended to associate positively with necrosis (r=0.15, p=0.13) in univariate analysis. In multivariable analysis, significant association between D-dimer and calcium persisted while association with fibrosis was nearly significant (p=0.07). Notably, in subjects with D-dimer levels above 500 ng/mL, these associations were stronger (fibrosis; r=-0.45, p=0.006, calcium; r= 0.39, p=0.016, necrosis; r=0.45, p= 0.005). Conclusions: Our results suggest associations between Lp(a), OxPLs and potentially atheroprotective IgM antibodies to OSE and markers of thrombosis. While associations are modest and a larger study is needed, results raise the interesting possibility that plasma D-dimer may identify subjects prone to Lp(a)/OxPL-induced subclinical thrombosis, which may increase risk for future adverse events.