Skin autofluorescence and pentosidine are associated with measures of arterial stiffness- The Maastricht Study

Marcelle GA van Eupen, Miranda T Schram, Thomas T van Sloten, Simone JS Sep, Carla J van der Kallen, Pieter C Dagnelie, Annemarie Koster, Nicolaas Schaper, Ronald MA Henry, Abraham A Kroon, Andries J Smit, Coen DA Stehouwer, Casper G Schalkwijk

Background and aims:
Arterial stiffening, as characterised by an increase in carotid to femoral pulse wave velocity (cfPWV) or pulse pressure (PP), increases the risk of cardiovascular disease (CVD), especially among individuals with type 2 diabetes mellitus (T2DM). Advanced glycation endproducts (AGEs) are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence (SAF), an estimate of tissue AGEs, and plasma AGEs on the one hand and cfPWV and 24-hour ambulatory PP (aPP) on the other in individuals with normal glucose metabolism (NGM), impaired glucose metabolism(IGM), or type 2 diabetes mellitus (T2DM).

Materials and methods:
We studied a cohort of 862 individuals from The Maastricht Study (469 NGM, 140 IGM and 253 T2DM) with a mean age of 60 years and 45% females. SAF was measured by use of the AGE Reader. Plasma levels of protein-bound pentosidine were measured with HPLC and fluorescence detection. Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) were measured with UPLC and tandem mass spectrometry. cfPWV was measured by use of applanation tonometry. aPP was measured with 24-hour ambulatory blood pressure monitoring. Associations were analysed with linear regression analysis and adjusted for potential confounders.

Results:
Higher SAF (sβ 0.09; 95%CI 0.03-0.16) and plasma pentosidine (0.09; 0.03-0.16) were independently associated with higher cfPWV. These associations were more pronounced in individuals with T2DM (SAF: sβ 0.12; -0.03-0.26, pentosidine: sβ 0.12; -0.02-0.26, p-interaction<0.10). Associations between SAF (0.06; -0.01-0.12), plasma pentosidine (0.05; -0.01-0.11) and plasma CML (0.05; -0.01-0.12) on the one hand and aPP on the other were positive but not statistically significant. The association between SAF and aPP was more pronounced in individuals with T2DM (sβ 0.17; 0.04-0.29, p-interaction<0.10).

Conclusion:
These results support the hypothesis that AGE accumulation is involved in the development of arterial stiffness, and may explain part of the increased CVD risk in individuals with T2DM.