Advanced glycation end-products in chronic heart failure

Abstract

The number of patients with chronic heart failure (HF) is increasing. HF is a functional cardiac disorder, impairing the ability of the ventricle to fill with or eject blood combined with symptoms of fatigue and/or breathlessness. The prognosis and quality of life are poor. In this thesis the potential role of advanced glycation end-products (AGEs; glycated proteins) accumulation in the development and progression of HF was studied. AGEs accumulate during ageing and form collagen cross links, causing stiffening of heart and vessels. The main findings are 1) Higher levels of AGEs are associated with diastolic dysfunction; 2) Elevated AGEs levels are related to the severity of HF and its clinical outcome; 3) When used in patients with systolic HF the AGE-breaker alagebrium showed no improvement on either the exercise capacity or cardiac function. Furthermore, no changes in AGE levels were observed in the blood.