Plasma ADMA Levels And Its Clinical Significance In Patients With Pulmonary Arterial Hypertension Associated With Congenital Heart Disease

Objective:This study was designed to determine plasma ADMA levels in patients with PAH associated with CHD (PAH-CHD) and CHD patients without PAH and to investigate the correlation of ADMA with hemodynamic findings, thus estimating the clinical value of using ADMA as a biomarker of CHD-PAH.Methods:This study included80patients with congenital heart disease that were confirmed by echocardiography in the Second Xiangya Hospital, Central South University from May2013to April2014. Patients were divided into three groups according to mean pulmonary arterial pressure:congenital heart disease without pulmonary arterial hypertension group(group A, n=20); congenital heart disease with mild-to-moderate pulmonary arterial hypertension group(group B, n=20); congenital heart disease with severe pulmonary arterial hypertension group(group C, n=40). Twenty healthy adult subjects were recruited as control group. Of all the patients with pulmonary resistant hypertension,10were followed up for6months during treating with sildenafil. All the subjects’ clinical data were collected, cardiac catheterization and echocardiographs were performed. Plasma asymmetric dimethylarginine (ADMA) levels were determined by enzym el inked immunosorbent assay.Results:1. Plasma ADMA levels were significantly increased in patients with CHD-PAH compared with the control group(0.74±0.26vs.0.21±0.11, P<0.001); Plasma ADMA levels were significantly increased in patients with CHD-PAH compared with CHD patients without PAH(0.49±0.17μmol/L vs.0.36±0.13μmol/L, P<0.01;0.74±0.26μmol/L vs.0.36±0.13μmol/L, P<0.001); Plasma ADMA levels were increased in patients of CHD without PAH compared with controls, but no statistic difference was observed(0.36±0.13vs.0.31±0.11, P=0.209).2. In CHD patients with severe PAH, plasma ADMA levels were significantly increased in patients with Eisenmenger’s syndrome(ES) compared with those with dynamic PAH(0.87±0.24vs.0.63±0.18, P<0.001).3. The plasma ADMA levels were significantly positive correlation with MPAP(r=0.605, P<0.001) and PVR(r=0.552, P<0.001) in patients with CHD.4. Severe PAH was identified when the area under the ADMA ROC curve exceeded0.889(P<0.001). This generated a cutoff value for ADMA of0.485μmol/L. This cutoff level had a specificity of82.8%and a sensitivity of90%. ES was identified when the area under the ADMA ROC curve exceeded0.71(P<0.05). This generated a cutoff value for ADMA of0.85μmol/L. This cutoff level had a specificity of85.2%and a sensitivity of64.3%.5. After treating with sildenafil for6month, ADMA levels were significantly decreased(0.91±0.22vs.0.57±0.30, P<0.01) along with the patients’ MPAP and six minutes walk distances improved.Conclusions:Our study suggests that plasma ADMA may be used as a biomarker to identify PAH in patients with CHD and to assess the pulmonary vascular remodeling in patients with CHD-PAH. Furthermore, ADMA level was a marker of treatment response to sildenafil therapy so that it has the potential to be used as a biomarker in the follow-up evaluation of patients with CHD-PAH.