Advanced glycation end-products are proteins that become glycated after contact with sugars and are implicated in endothelial dysfunction and arterial stiffening. We hypothesized that advanced glycation end-products associate with vascular stiffness independent of glycemic status. Advanced glycation end-products were measured as skin autofluorescence, vascular stiffness was measured as pulse wave velocity, augmentation index and ankle-brachial index in 3,535 participants from the European Prospective Investigation into Cancer and Nutrition Potsdam cohort (median age 67 years, 60% women). A subset of 1,348 participants underwent an oral glucose tolerance test. Participants were sub-phenotyped into normoglycemic, prediabetes and diabetes groups. Skin autofluorescence associated with pulse wave velocity, augmentation index and ankle-brachial index, adjusted beta coefficients (95% CI) per unit skin autofluorescence increase: 0.38 (0.21; 0.55) for carotid-femoral pulse wave velocity, 0.25 (0.14; 0.37) for aortic pulse wave velocity, 1.00 (0.29; 1.70) for aortic augmentation index, 4.12 (2.24; 6.00) for brachial augmentation index and -0.04 (-0.05; -0.02) for ankle-brachial index. The associations were strongest in men, younger individuals and were consistent across all glycemic strata: for carotid-femoral pulse wave velocity 0.36 (0.12; 0.60) in normoglycemic, 0.33 (-0.01; 0.67) in prediabetes and 0.45 (0.09; 0.80) in diabetes groups; with similar estimates for aortic pulse wave velocity. Augmentation index was associated with skin autofluorescence only in normoglycemic and diabetes groups. Ankle-brachial index inversely associated with skin autofluorescence across all sex, age and glycemic strata. Our findings indicate that advanced glycation end-products are involved in vascular stiffening independent of glycemic status, age and other cardiometabolic risk factors.

Disclosure

A. Birukov: None. R. Cuadrat: None. E. Polemiti: None. F. Eichelmann: None. M. B. Schulze: None.

Funding

German Ministry of Education and Research; State of Brandenburg (82DZD00302)

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