In severe aortic stenosis patients with type 2 diabetes, serum oxPL rose 2.55-fold, MPO 1.38-fold, and valvular oxPL/AGEs increased ~1.7-fold, correlating with AS severity.
Is concomitant type 2 diabetes associated with increased oxidative stress and AGEs accumulation in patients with severe aortic stenosis?
In patients with severe aortic stenosis, concomitant type 2 diabetes is associated with increased systemic and valvular oxidative stress and AGEs accumulation, which correlates with AS severity.
Absolute Event Rate: 0% vs 0%
Abstract Background Diabetes mellitus (DM) is a risk factor of aortic stenosis (AS). Valvular degeneration is associated with enhanced oxidative stress concomitant to DM. Purpose This study aimed to determine whether the coexistence of severe AS and DM is associated with a concurrent increase in oxidative stress within stenotic valves and in circulating blood. Methods We enrolled 70 severe AS patients scheduled for aortic valve replacement, including 40 (57%) subjects with concomitant type 2 DM (AS-DM). We assessed circulating oxidized phospholipids (oxPL), myeloperoxidase (MPO), advanced glycation end products (AGEs), and their soluble receptor (sRAGE). Moreover, valvular expression of oxPL and AGEs was determined using immunostaining of aortic valve samples. Results AS-DM patients presented with higher serum oxPL (+2.55-fold) and MPO (+1.38-fold) compared to AS patients without DM (AS; both p0.001). Moreover, plasma AGEs and sRAGE concentrations were respectively 2.07-fold and 2.22-fold higher in the AS-DM group compared to AS patients (both p0.001). Importantly, serum oxPL and MPO were associated with plasma AGEs in the whole AS population (r=0.66, p0.001 and r=0.53, p0.001). Moreover, serum MPO and oxPL correlated with echocardiographic parameters defining AS severity, namely aortic valve area (AVA; r=-0.49, p0.001 and r=-0.45, p0.001) and maximal transvalvular pressure gradient (PGmax; r=0.29, p=0.016 and r=0.32, p=0.007). The analysis of valvular expression of oxPL and AGEs showed 1.8-fold and 1.6-fold higher amounts of these markers in AS-DM compared to AS patients (both p0.001). Moreover, valvular oxPL and AGEs expression was associated with serum concentration of oxPL (r=0.72, p0.001 and r=0.68, p0.001) and plasma levels of AGEs (r=0.82, p0.001 and r=0.83, p0.001) as well as with AVA (r=-0.63, p0.001 and r=-0.72, p0.001) and peak aortic valve velocity (Vmax; r=0.59, p0.001 and r=0.60, p0.001). Conclusions This study is the first to show that in severe AS patients with concomitant DM, diabetes-driven oxidative stress increases valvular oxPL expression and AGEs accumulation and associates with AS severity. Our findings suggest that achieving good glycemic control may prevent the progression of valvular degeneration.Correlations of valvular oxPL, AGEs Immunostaining analysis of aortic valves
Chudy et al. (Sat,) reported a other. In severe aortic stenosis patients with type 2 diabetes, serum oxPL rose 2.55-fold, MPO 1.38-fold, and valvular oxPL/AGEs increased ~1.7-fold, correlating with AS severity.