5.2 SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END-PRODUCTS AND AORTIC STIFFNESS IN GENERAL POPULATION

Abstract

It has been suggested that accumulation of advanced glycation end-products (AGE) is involved in several pathophysiological processes in the vessel wall. Soluble isoform of receptor for AGE (sRAGE) acts as a decoy for capturing circulating AGE, prevents them from binding to the cell-surface receptor and protects against the RAGE-AGE axis-elicited processes. We hypothesized that low sRAGE levels might be associated with increased arterial stiffness. In a cross-sectional design, we analyzed 1077 subjects from the Czech population-based study (“Post-MONICA”). Aortic pulse wave velocity (aPWV) was measured using a Sphygmocor device. sRAGE concentrations were assessed in frozen samples by ELISA methods (R&D Systems). Aortic PWV significantly (p <0.0001) increased across the sRAGE quartiles. After adjustment for all potential confounders, non-diabetic subjects in the bottom quartile of sRAGE (<918 pg/mL) had odds ratio of raised aortic PWV (≥9. m/sec, top quartile), 1.8 (95% CI: 1.19–2.72) with p = 0.006; the association was stronger when only hypertensive non-diabetic individuals were included: odds ratio 2.05 (95%CI: 1.26–3.32) with p = 0.004. In contrast, using similar regression models, low sRAGE was rejected as an independent predictor of raised aortic aPWV in diabetic or in normotensive subjects. In conclusion, low circulating sRAGE was independently associated with increased arterial stiffness in a general population-based sample, but mainly in hypertensive non-diabetic patients. The lack of association in diabetics was probably due to low dispersion of sRAGE values and relatively small number of subjects (9% of the sample).