P.39 The Role of Advanced Glycation End Products in Vascular Ageing. Which Parameter is the Most Suitable as Biomarker?

Abstract

Background

Advanced glycation end products (AGEs) are involved into several pathophysiologic processes in vascular diseases, including progressive loss of elasticity of vessel wall (arterial stiffness). Circulating soluble receptor for AGEs (sRAGE) act as a decoy and counterbalanced the harmful properties of AGEs as the natural protective factor [1,2]. We compared the role of circulating or skin-deposed AGEs and sRAGE regarding natural course of arterial stiffening.

Methods

In a prospective cohort study, we longitudinally followed 536 general-population-based subjects (subsample of Czech post-MONICA study). Aortic pulse wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd.), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE and carboxylmethyl lysine (circulating AGEs) were assessed at follow-up visit by ELISA, while skin AGEs were measured using autofluorescence-based device AGE Reader.

Results

Using multiple regressions, we found significant association between ∆PWV/year as dependent variable and both, sRAGE and skin AGEs as independent ones (each on its own model). However, the closest association to ∆PWV/year were found for ratio of these two factors (skin AGEs/sRAGE) [coeff = 0.0747 (SE 0.0189), p < 0.0001]. In categorized manner, subjects with skin AGEs/sRAGE ratio ≥3.3 showed about two-fold higher risk having PWV/year ≥0.2 m/sec [adjusted odds ratio was 2.09 (95% CI: 1.35–3.22), p = 0.001]. In contrast neither circulating AGEs nor circulating AGEs/sRAGE showed any significant relation to PWV/ year.

Conclusions

Skin AGEs/sRAGE ratio seems to be more sensitive biomarker of vascular ageing than these single factors themselves or circulation status of AGEs [3].