Aortic stenosis is associated with elevated plasma levels of asymmetric dimethylarginine (ADMA)

We tested the hypothesis that the presence of aortic stenosis (AS) is associated with elevation of plasma levels of asymmetric dimethylarginine (ADMA), a physiological inhibitor of nitric oxide synthase, a mediator and marker of endothelial dysfunction and an indicator of incremental cardiovascular risk.

The presence of aortic sclerosis (ASC), the precursor of AS is independently associated both with endothelial dysfunction, and with incremental coronary event risk. It remains uncertain whether elevations of ADMA levels might mediate endothelial dysfunction in these conditions.

Forty two consecutive patients referred for echocardiography for evaluation of AS, who had calculated aortic valve areas of <1.4 cm(2) (AS group) were evaluated together with 42 consecutive age-matched referred patients (non-AS group). Plasma ADMA levels were measured by high-performance liquid chromatography (HPLC). Determinants of elevation of plasma ADMA levels were identified via stepwise multiple linear regression analysis.

Plasma ADMA levels were not statistically different between the AS and non-AS group (median 0.59 vs 0.54 micromol/L, p=0.13, Mann-Whitney test) on univariate analysis. However, in backward stepwise multiple linear regression, the presence of AS was a significant predictor of elevated ADMA levels (p=0.04, 95% CI=0.001, 0.072). In addition, elevated plasma ADMA levels were also associated with history of atrial fibrillation (p=0.009, 95% CI=0.015, 0.100), and negatively associated with creatinine clearance (p=0.01, 95% CI=-0.002, 0.000), and the use of statin therapy (p=0.01, 95% CI=-0.081, -0.011).

AS is independently associated with elevation of ADMA levels, beyond that implied by "conventional" risk factors for endothelial dysfunction. The clinical status of AS as an incremental marker of cardiovascular risk may reflect ADMA-mediated endothelial dysfunction.