Circulating soluble receptor for advanced glycation end-product levels are decreased in patients with calcific aortic valve stenosis

Objective: It has been suggested that atherosclerotic mechanisms are involved in the pathogenesis of aortic valve stenosis (AVS). We hypothesised that low levels of the soluble receptor for advanced glycation end-products (sRAGE) might be associated with AVS due to its clinical and pathological associations with atherosclerosis.

Methods: We enrolled 75 consecutive patients with severe AVS scheduled for surgical aortic valve replacement and 39 controls without AVS matched for age and gender. Besides the traditional risk factors, we evaluated plasma levels of sRAGE, C-reactive protein (CRP) and IL-6. All patients underwent transthoracic echocardiography, carotid arteries ultrasound scan and coronary angiography. The aortic and coronary calcium by multislice computed tomography was assessed in AVS patients.

Results: The values of sRAGE were significantly lower (p<0.01) in AVS patients than in controls, while the CRP levels were significantly higher (p<0.05) in AVS patients than in controls. In AVS patients the sRAGE levels correlated inversely with age, cholesterol levels and coronary calcification. In all study subjects, we found an inverse correlation between circulating sRAGE and the number of echographically assessed sites of calcification (ANOVA, p<0.0001). In multivariable logistic regression analysis after adjustment for potential confounders, the sRAGE levels were significantly and independently associated with the risk of AVS (OR=0.997, 95% CI=0.994-1.000, p=0.048).

Conclusion: Since sRAGE could exert antiatherogenic effects by preventing inflammatory responses mediated by cell surface RAGE activation, low levels in AVS patients indicate that ligand-RAGE axis could contribute to pathogenesis of AVS.