Tissue Advanced Glycation end Products are Associated with Diastolic Function and Aerobic Exercise Capacity in Diabetic Heart Failure Patients

AIMS: Advanced glycation end products (AGEs) are increased in patients with diabetes and are associated with diastolic dysfunction through the formation of collagen crosslinks in the heart. The association among AGEs, diastolic function, and aerobic capacity in heart failure (HF) patients with and without diabetes is, however, unknown. We therefore studied the association among tissue AGEs, diastolic function, and aerobic capacity in patients with HF with or without diabetes. METHODS AND RESULTS: In chronic HF patients (with and without left ventricular systolic dysfunction), tissue AGEs skin autofluorescence (AF), diastolic function (echocardiographic mean E' and E/E'), and aerobic capacity peak oxygen uptake (VO(2)) on cardiopulmonary exercise testing were obtained. A total of 49 diabetics and 156 non-diabetics were included. Diabetics were older and had more cardiovascular risk factors, but left ventricular ejection fractions (LVEF) were similar. Tissue AGEs were higher in diabetics compared with non-diabetics (2.8 ± 0.8 vs. 2.3 ± 0.7 a.u.; P < 0.001). Furthermore, there was a correlation between tissue AGEs and mean E' (r = -0.30; P < 0.001, after adjustment for age, r = -0.21; P = 0.004). Aerobic capacity was significantly lower in diabetic patients with HF (peak VO(2): 17.4 ± 5.1 vs. 21.7 ± 6.1 mL/min/kg; P = 0.001), even after adjustment for age and LVEF. Peak VO(2) was related to skin AF (P = 0.03), independent of age, diabetes, LVEF, and New York Heart Association functional class. CONCLUSION: Patients with diabetes and HF have similar LVEF but poorer exercise capacity compared with non-diabetic HF patients. Our data suggest that these findings might be explained by the observed association among tissue AGE levels, diastolic function, and exercise capacity.