Abstract
Rationale: Asymmetric dimethylarginine (ADMA), a potent endogenous nitric oxide synthase inhibitor, is increased in pulmonary hypertension (PH), and associated with unfavorable outcome. We hypothesized that plasma ADMA may serve as a biomarker to monitor disease progression under PH-specific treatment.
Methods: ADMA was measured at baseline and at least after 24 weeks of treatment in consecutive patients (pts) under advanced PH-targeted treatments. Therapy responders were defined by decrease of pulmonary vascular resistance (PVR) of at least 200dynes.cm-1.s-5, 6-minute walking distance > 380m, and improvement of WHO at follow-up and were compared with non-responders.
Results: 51 consecutive patients (44 pts with pulmonary arterial hypertension and 7 patients with PH due to lung disease) were enrolled in this study. According to our definition; there were 16 non-responders, and 23 responders to treatments. 11 patients showed no change.
ADMA plasma levels did not change significantly under treatment in the whole group. There was a significant drop of ADMA in responder group (p <0.0001). Furthermore, ADMA change in responders and nonresponders was significantly different (p=0.003).
The decrease of ADMA correlated with the decrease of PVR (r=0.56, p<0.0001), with the decrease of mean pulmonary arterial pressure (r=0.44, p=0.001). Furthermore, the difference of ADMA correlated with the increase of cardiac index (r=-0.38, p=0.005) and mixed venous saturation (r=-0.3, p=0.03).
Conclusions: ADMA parallels the hemodynamic benefit of PH-specific treatment in patients with PH of various etiologies. ADMA can serve as a biomarker for the effect of PH-specific treatments.
- © 2012 ERS
