The role of asymmetric dimethylarginine alone and in combination with N-terminal pro-B-type natriuretic peptide as a screening biomarker for systemic sclerosis-related pulmonary arterial hypertension : a case control study

Objective: Asymmetric dimethylarginine (ADMA) is a novel biomarker of endothelial cell dysfunction. In this proof of concept study, we sought to evaluate the role of ADMA as a screening biomarker for incident systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). Methods: ADMA levels were measured using high performance liquid chromatography in 15 consecutive treatment-naive patients with newly-diagnosed SSc-PAH and compared with 30 SSc-controls without PAH. Logistic regression models were used to evaluate the independent association of ADMA with PAH. The optimal cut-point of ADMA for SSc-PAH screening was determined. NT-proBNP levels were previously measured in the same patients and the optimal cut-point of NT-proBNP of >210ng/mL was coupled with the optimal cut-point of ADMA to create a screening model that combined the two biomarkers. Results: The PAH group had significantly higher mean ADMA levels than the control group (0.76±0.14 μM versus 0.59±0.07 μM; p < 0.0001). ADMA levels remained significantly associated with PAH after the adjustment for specific disease characteristics, cardiovascular risk factors and other SSc-related vascular complications (all p < 0.01). An ADMA level ≥0.7 μM had a sensitivity of 86.7%, specificity of 90.0% and AUC of 0.86 for diagnosing PAH. A screening model that combined an NT-proBNP ≥210ng/mL and/or ADMA ≥0.7 ng/mL resulted in a sensitivity of 100% and specificity of 90% for the detection of SSc-PAH. Conclusion: In this small study, use of ADMA in combination with NT-proBNP produced excellent sensitivity and specificity for the non-invasive identification of SSc-PAH. The role of ADMA as a screening biomarker for SSc-PAH merits further evaluation.