Advanced glycation endproducts in chronic heart failure

Advanced glycation endproducts (AGEs) have been proposed as factors involved in the development and progression of chronic heart failure (CHF). Cross-linking by AGEs results in vascular and myocardial stiffening, which are hallmarks in the pathogenesis of CHF. Additionally, stimulation of receptors by AGEs may affect endothelial function and myocardial calcium uptake and may perpetuate coronary sclerosis in CHF. CHF is common in conditions with AGE accumulation, such as diabetes and renal failure. This review describes in detail the interrelation of plasma AGEs, renal function, and the severity and prognosis in clinical CHF patients with mild to moderate loss of renal function. This association is compared with the relation between tissue AGE accumulation (marked by skin autofluorescence) and diastolic dysfunction in renal failure. The evidence reviewed here provides support for the assumed role of AGEs in determining the severity and prognosis of CHF, but also highlights the differences in this relation between plasma and tissue AGEs and between patients with and without advanced renal failure. Ongoing clinical intervention trials to reduce AGE accumulation in patients with CHF may elucidate the causal role of AGEs in the development and course of CHF.