• Vivek Thakkar, Wendy Stevens, David Prior, Candice Rabusa, Joanne Sahhar, Jennifer G Walker, Janet Roddy, Susan Lester, Maureen Rischmueller, Jane Zochling, Peter Nash, Eli Gabbay, Peter Youssef, Susanna M Proudman, and Mandana Nikpour.
• Department of Medicine; Department of Rheumatology, St. Vincent's Hospital Melbourne, Fitzroy; Department of Rheumatology, Liverpool Hospital, Liverpool; and School of Medicine, University of Western Sydney, Penrith, Australia.
• Clin Exp Rheumatol. 2016 Sep 1; 34 Suppl 100 (5): 129-136.

ObjectivesAsymmetric 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).MethodsADMA 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.ResultsThe 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.ConclusionsIn 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.

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