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

V. Thakkar, W. Stevens, D. Prior, C. Rabusa, J. Sahhar, J.G. Walker, J. Roddy, S. Lester, M. Rischmueller, J. Zochling, P. Nash, E. Gabbay, P. Youssef, S.M. Proudman, M. Nikpour

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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.

Original languageEnglish
Pages (from-to)S129-S136
Number of pages8
JournalClinical and Experimental Rheumatology
Issue number5
Publication statusPublished - 2016
Externally publishedYes


  • Asymmetric dimethylarginine (ADMA)
  • Biomarker
  • Pulmonary arterial hypertension
  • Screening
  • Systemic sclerosis

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