SERUM BIOMARKERS, SKIN AUTOFLUORESCENCE AND OTHER METHODS. WHICH PARAMETER BETTER ILLUSTRATES THE RELATIONSHIP BETWEEN ADVANCED GLYCATION END PRODUCTS AND ARTERIAL STIFFNESS

Abstract

Objective: Impaired glucose metabolism plays an important role in the stiffening of large arteries. Advanced glycation end-products (AGEs) are responsible for the onset of specific complications in diabetic subjects; however, they may exert harmful effects on cardiovascular system also in non-diabetics. AGEs bind to specific receptor (RAGE) expressed in various cells. The AGEs-RAGE complex participates in various stages of atherosclerosis and arterial stiffening. Circulating soluble isoform of RAGE (sRAGE) captures circulating AGEs, thus preventing their patophysiological consequences. We aimed to investigate the associaton between aortic pulse wave velocity and multiple paramaters of glucose metabolism. Design and method: 1061 subjects were examined in the Pilsen subsample of Czech Post-MONICA study (= 1% random sample of general population aged 25–74 years). Pulse wave velocity (PWV) was measured using the Sphygmocor device (AtCor Medical Ltd., Australia). Following markers of glucose metabolism were assessed: fasting glucose level, glycated hemoglobin, carboxy-methyl lysine (marker of circulating AGEs), sRAGE (circulating soluble isoform of RAGE), skin AGEs (autofluorescence method). Since ratios may better describe the balance between harmful and protective factors, following risk factors ratios were calculated: CML/sRAGE, skin AGEs/sRAGE. Results: Aortic PWV was strongly associated with fasting glucose, sRAGE, skin AGEs and the skin AGEs / sRAGE ratio. Only weak association with HbA1c was found. All parameters of glucose metabolism were included simultaneously in a stepwise regression of pulse wave velocity. Besides age, mean arterial pressure and male sex, fasting glucose and skin AGEs were positively associated with PWV, while there was a negative association with sRAGE (significant in non-diabetic population only). In contrast, neither CML, nor its ratio to sRAGE showed any association with arterial stiffness. Conclusions: Autofluorescence method allows to assess easily and quickly the contents of skin AGEs, which were associated with aortic stiffness in general population sample. sRAGE level had a negative association with PWV, thus reflecting its protectivity against arterial stiffening. These two parameters influence aortic stiffness over and above fasting glucose level which is per se a strong determinant of aortic PWV even in non-diabetic population.