Evidence for a role of advanced glycation end products in atrial fibrillation

Background: Recent studies suggested that advanced glycation end-products (AGEs) and their receptor (RAGE) interaction may be promoted by inflammation and oxidative stress. These processes could also contribute to the pathogenesis of atrial fibrillation (AF), but their roles remain poorly defined. We studied the association of AGE-RAGE axis with AF in diabetic and non-diabetic patients, since the axis appears to play a key role in the process.

Methods: Ninety-seven consecutive outpatients were included in this transversal study. Fifty-nine patients were in sinus rhythm (SR) and 38 in permanent AF. Plasma fluorescent AGEs and soluble RAGE (sRAGE) were measured and comparisons between patients with and without AF were performed. A multivariate logistic regression analysis was made to define the independent factors associated with AF.

Results: Fluorescent AGEs and sRAGE were higher in AF group (74.9 ± 25.6 vs. 61.8 ± 20.1a.u. for fluorescent AGEs, p=0.006; 1714.2 ± 1105.5 vs. 996.1 ± 820.7 pg/mL for sRAGE, p=0.001). These differences were specially marked in non-diabetic patients. Both AGEs and sRAGE directly correlated with left atrial dimensions (r=0.496; r=0.536 for atrial area and r=0.491; r=0.511 for atrial volume, for fluorescent AGEs and sRAGE, respectively, p<0.001). In a multivariate analysis, fluorescent AGEs and sRAGE resulted as markers of AF independent of left atrial distension, diabetes and other confounding variables.

Conclusions: AGEs and sRAGE plasma levels were higher in patients with AF, independently of diabetes mellitus, and they positively correlated with atrial dimensions, indicating a role for the AGE-RAGE axis in the arrhythmogenic structural atrial remodelling.