Nonstenotic bicuspid aortic valve is associated with elevated plasma asymmetric dimethylarginine

Background Recently, it has been reported that nonstenotic bicuspid aortic valve (BAV) with dilated proximal aorta is linked with increased matrix metalloproteinase-2 (MMP-2) and endothelial dysfunction. Objective We wondered whether asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor, might be altered and associated with MMP-2 in BAV patients. We assessed the relation between ADMA levels and aortic diameters and hypothesized that elevated ADMA might be an independent predictor of progressive aortic dilatation in BAV patients. Methods We studied 20 patients with nonstenotic BAV (17 men and 3 women, median age 27, range 24-33 years). Twenty age-matched patients with tricuspid aortic valves served as controls. Plasma levels of ADMA, symmetric dimethylarginine (SDMA), L-arginine, serum MMP-2, MMP-9, and plasma total homocysteine (tHcy), together with parameters of aortic elasticity, were measured. Results ADMA and MMP-2 levels were higher in the BAV group compared with controls (medians, 0.55 vs. 0.43 mu mol/l, P<0.001 and 1.25 vs. 1.00 mu mol/l, P<0.001, respectively). The BAV patients also had higher SDMA and tHcy levels than controls (0.39 vs. 0.35 mu mol/l, P<0.001 and 11.5 vs. 9.7 mu mol/l, P = 0.006). ADMA levels in BAV patients correlated with aortic annulus (r = 0.4, P = 0.043), peak aortic velocity (r = 0.6, P = 0.001), aortic distensibility (r = 0.6, P = 0.004), aortic stiffness index (r = 0.7, P<0.001), and aortic strain (r = 0.7, P<0.001) as well as with MMP-2 (r = 0.6, P = 0.002) and tHcy (r = 0.4, P = 0.042). Conclusions This study is the first to show that circulating ADMA together with MMP-2 is a marker of proximal ascending aortic dilatation and impaired aortic elastic properties in nonstenotic BAV patients. It might be speculated that plasma ADMA could be helpful in identifying BAV patients at a higher risk of aortic aneurysm.