Asymmetric dimethylarginine plasma concentrations and L-arginine/asymmetric dimethylarginine ratio in patients with slow coronary flow

Abstract

Elevated levels of nitric oxide synthase inhibitor, asymmetric dimethylarginine (ADMA) is considered to be a marker of endothelial dysfunction and increased risk of cardiovascular disease. Recent reports have implicated endothelial dysfunction as an underlying pathophysiological mechanism of slow coronary flow (SCF) phenomenon. Accordingly, we investigated plasma L-arginine, ADMA concentrations and L-arginine/ADMA ratio in patients with SCF in comparison with participants having normal coronary flow. We measured plasma levels of L-arginine and ADMA by high-performance liquid chromatography in 31 participants with SCF and 31 age and sex matched control participants with normal coronary flow. Coronary flow was quantified using the thrombolysis in myocardial infarction (TIMI) frame count method. The patients with SCF were detected to have significantly higher concentrations of plasma ADMA (P=0.006) and lower L-arginine/ADMA ratio compared with participants with normal coronary flow (P=0.002). In addition, both ADMA and L-arginine/ADMA ratio were significantly correlated with mean TIMI frame count and TIMI frame count for each coronary artery in patients with SCF and multivariate regression analysis identified plasma ADMA as an independent predictor for SCF. In the receiver operator characteristics curve analysis, patients with SCF were detected by plasma ADMA level with a sensitivity, specificity of 64.5%, 74.2%, at a cut-off of >2.4 micromol/l and L-arginine/ADMA ratio with a sensitivity, specificity of 77.4%, 67.7% at a cut-off of <36.6. Our findings provide evidence to support the hypothesis that endothelial dysfunction may be an important factor in the pathogenesis of SCF.