Advanced glycation end-products and arterial stiffness in hypertension

Background: The formation of advanced glycation end-products is associated with arterial stiffness in experimental models and alagebrium (formerly known as ALT-711), an advanced glycation end-product cross-link breaker, has been shown to reduce arterial stiffness in elderly subjects. Methods: We related plasma concentrations of advanced glycation end-products (AGEs), measured using a noncompetitive immunoassay, and markers of aortic stiffness-pulse wave velocity (PWV) and augmentation index (AIx), a measure of aortic wave reflection-in 46 subjects, aged 47 +/- 2 years, comprising 30 untreated hypertensive and 16 normotensive subjects. Results were analyzed using univariate and multiple logistic regression analysis. Results: Plasma AGEs were significantly higher in hypertensive than in normotensive subjects (7.8 +/- 1 v 3 1 mu g/ml; P <.0001). There was a significant relationship between plasma AGEs and aortic PWV (r = 0.49, P <.01), but not with AIx. In a stepwise regression model age, plasma AGE levels, smoking status, and total cholesterol explained 67% of the variability in PWV. For AN, the only variables that entered the model were age, gender, and heart rate (R-2 = 0.53, P <.0001) with no contribution from plasma AGEs. Conclusions: Concentration of plasma AGEs is significantly higher in hypertensive than in normotensive subjects and related to aortic stiffness independent of age and blood pressure, with no relationship with aortic wave reflection. Plasma AGEs may play a blood pressure-independent role in large but not small vessel remodeling in essential hypertension.