LAUSR

Objectives: Accumulation of advanced glycation end-products (AGEs) is one of pathophysiological processes, responsible for progressive stiffening of vessel wall. In contrast, soluble isoform of receptor for AGEs (sRAGE) act as a “decoy” for circulating AGEs and physiological defense against AGEs. We hypothesized that low levels of sRAGE might be associated with accelerated age-dependent arterial stiffening Methods: We followed 429 population-based subjects (mean age 50.8 (±11.7) years, 41.5% males) in prospective study. Aortic pulse wave velocity (aPWV) was measured using a Sphygmocor device. sRAGE concentrations were assessed in frozen samples by ELISA methods (R&D Systems). Baseline examination was done in 2008/9, while follow-up visit in 2016/17 (median time of follow-up was 7.6 years) Results: Mean intra-individual increase of aPWV during follow-up was 1.37 (±1.88) m/sec and was inversely associated with baseline sRAGE concentration- the aPWVV difference [follow-up minus baseline] across its quintiles was 2.08((±1.89), 1.51(±2.16), 1.20(±2.10), 0.99(±1.70), 1.13(±1.21) in 1st-5th quintiles of sRAGE, resp.; p = 0.003 (adjusted for age, gender, mean arterial pressure) Baseline concentration of sRAGE < 917 pg/mL (1st quintile) was associated with about two-fold higher risk, that aPWV increased by more than 0.8 m/sec (expectable “secular” age-dependent increase) even if adjusted for baseline risk profile and pharmacotherapy [fully adjusted odds ratio was 1.95 (95%CI: 1.12–3.39, p = 0.018]. Conclusion: Low concentration of circulating sRAGE was in our sample of generally healthy subjects associated with markedly accelerated age-dependent arterial stiffening, probably as a consequence of higher deposition of AGEs in vessel wall.