AB0393 Increased in serum soluble receptor for advanced glycation end products levels are associated with improvement in augmentation index in patients with early rheumatoid arthritis- a prospective observational study
Authors: L.-S. Tam
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin super family of cell surface molecules that is expressed in a variety of cell lines. The interaction of RAGE-ligands effectively modulates several steps of atherogenesis. Soluble C-truncated RAGE (sRAGE) lacks the transmembrane and cytosolic domains of the full-length receptor and can prevent proinflammatory effects of RAGE signaling by acting as a decoy. Whether sRAGE levels in patients with RA are associated with premature atherosclerosis or arterial stiffness has never been examined. <h3>Objectives</h3> To explore the predictors of the changes in sRAGE levels and the association between sRAGE levels and the progression of carotid atherosclerosis and arterial stiffnessindexes in a cohort of early RA patients. <h3>Methods</h3> RA patients with symptoms onset &lt;2 years were recruited. Patients received protocolized treatment using traditional or biologic DMARDs aiming at DAS remission (DAS &lt;2.6). Vascular assessments and serum sRAGE levels were measured at baseline and 1 year later. Arterial stiffness wasdetermined by pulse wave velocity (PWV) and augmentation index (AIx). Carotid intima-media thickness (IMT) was measured using high-resolution ultrasound. <b>Results:</b>Ninety-four patients completed the 1 year study. Fifty-three (56.4%) achieved DAS remission at month 12. Improvement in arterial stiffness was observed as reflected by the significant reduction in AIx (30.7±10.5% to 26.3±11.1%, p&lt;0.05) and PWV (left brachial ankle PWV [baPWV] 15.09±3.32 m/s to 14.54±2.88 m/s, p&lt;0.05; right baPWV 14.94±3.37 m/g to 14.47±3.27 m/s, p&lt;0.05). Mean and maximum IMT remained unchanged (mean IMT 0.60±0.09 mm to 0.61±0.13 mm; maximum IMT 0.68±0.14mm to 0.71±0.19mm, p=NS). At 12 months, the sRAGE levels increased significantly compared to baseline (939.8±517.7 pg/ml to 1272.1±567.3 pg/ml, p&lt;0.001). Changes in sRAGE levels were significantly higher in men compared to women (768±510 pg/ml vs 271±490 pg/ml, p&lt;0.05), and was negatively associated with the change in AIx (r=-0.259, p=0.023).Changes in sRAGE level were not associated with other demographic, clinical, cardiovascular risk factors or treatment. Changes in sRAGE level were not associated with changes in PWV or IMT. In the final multivariable prediction model, gender (B:-506, 95% confidence interval [95%CI]:-850,-161, p=0.005) and changes in AIx (B:-12.4, 95%CI:-22.1,-2.72, p=0.013) were independent predictors for the changes in sRAGE levels. Since we have found that changes in sRAGE level were negatively associated with the change in AIx, we also modeled the associations of baseline and cumulative average patient characteristics with the change in AIx to see if sRAGE is an independent predictor of the change in AIx. In the final multivariable prediction model,baseline HDL-C level (B:9.9, 95%CI:2.8,16.9, p=0.007) and the changes in sRAGE level (B:-0.006, 95%CI:-0.01,-0.001, p=0.018) were independent predictors for the change in AIx. <h3>Conclusions</h3> Arterial stiffness improved significantly in patients with early RA after effective control of inflammation. Increase in sRAGE level was associated with a decrease in AIx, suggesting that sRAGE may play an important role on ligand–RAGE interaction propagated inflammation and vascular stiffness in these patients. <h3>Disclosure of Interest</h3> None Declared