Abstract 247: Association of Soluble RAGE Levels with Carotid Atherosclerosis: The Northern Manhattan Study (NOMAS)

Abstract

Introduction The Receptor for Advanced Glycation End-products (RAGE) is a multi-ligand receptor that propagates vascular cell dysfunction leading to proinflammatory disease states. RAGE is produced as a membrane bound and soluble isoform (soluble RAGE (sRAGE)), with the soluble isoform demonstrated to act as a RAGE decoy preventing cellular activation and atherosclerosis. Recent cohort studies have suggested that serum levels of sRAGE are associated with the risk of CVD and therefore may be a novel biomarker for cardiovascular disease states. Hypothesis We hypothesized that sRAGE levels are associated with subclinical atherosclerosis in an ethnically diverse population. Methods We included 1,102 stroke-free participants from the multi-ethnic Northern Manhattan Study (NOMAS) who underwent high-resolution carotid B-mode ultrasound to measure carotid plaque phenotypes (density, thickness, and area) and carotid intima-media thickness (IMT). Plaque density was characterized by Gray Scale Median (GSM). Serum sRAGE was measured by ELISA and log-transformed to stabilize variance. Multiple linear and logistic regressions were employed to estimate sRAGE associations with IMT and plaque measures. Results The mean age at time of ultrasound was 70.7±8.6yrs; 65% were Hispanic, 19% black, and 16% white. The majority of subjects had carotid plaque present (54%) with the median GSM 38(0-190). Mean plaque thickness (IQR) was 1.30(0-3.99)mm and mean area (IQR) 2.43(0-96.75)mm2. Mean IMT was 0.93±0.09mm. High sRAGE levels were associated with more echolucent plaques (OR 1.2, 95% CI 1.03-1.42), especially among Hispanics (OR 1.26, 95% CI 1.04-1.54). These relationships remained after adjusting for sociodemographic and vascular risk factors. No association was seen between sRAGE levels and carotid IMT, plaque thickness or area. Conclusion In the present study, higher sRAGE levels were associated with echolucent (lower density) plaque, especially among Hispanic subjects. Our data suggest sRAGE levels may be associated with atherosclerotic plaque morphology and its vulnerability, especially among minority groups. These findings further support RAGE as a novel target for anti-atherosclerosis interventions.