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Abstract Number: 1815

Asymmetric Dimethylarginine Levels In The Early Detection Of Systemic Sclerosis-Related Pulmonary Arterial Hypertension

Vivek Thakkar1, Wendy Stevens2, David Prior3, Joanne Sahhar4, Janet E. Roddy5, Jane Zochling6, Peter Nash7, Peter Youssef8, Susanna Proudman9 and Mandana Nikpour10, 1St Vincent's Hospital, Melbourne, Australia, 2Rheumatology, St Vincent's Hospital, Melbourne, Australia, 3Cardiology, St Vincent's Hospital, Melbourne, Australia, 4Rheumatology Unit, Monash Medical Centre, Clayton, Australia, 5Royal Perth Hospital, Perth, Australia, 6Menzies Research Institute Tasmania, Hobart, Australia, 7Rheumatology Research Unit, Nambour Hospital, Sunshine Coast, Australia, 8Department of Rheumatology, Royal Prince Alfred Hospital, Sydney, Australia, 9Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia, 10Department of Medicine (St Vincent's Hospital), University of Melbourne, Fitzroy, Australia

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Pulmonary complications and scleroderma

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Session Information

Title: Systemic Sclerosis, Fibrosing Syndromes, and Raynaud’s - Clinical Aspects and Therapeutics II

Session Type: Abstract Submissions (ACR)

Background/Purpose: Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc), and alterations in nitric oxide (NO) metabolism and endothelial cell function are implicated in the pathogenesis of SSc-PAH. Asymmetric dimethlyarginine (ADMA) is a novel biomarker of endothelial cell dysfunction. In this study, the clinical utility of ADMA as a screening biomarker for incident SSc-PAH was evaluated

Methods: ADMA levels were measured in 15 consecutive treatment-naive subjects with newly-diagnosed SSc-PAH, and compared with 30 SSc-controls without PAH. ADMA levels were assayed using high performance liquid chromatography with solid phase extraction. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured in the same subjects. Logistic regression models were used to evaluate the independent association of ADMA with PAH. Important correlations of ADMA were assessed using Spearman’s rank correlation coefficient (rho). The optimal cut-points of ADMA and NT-proBNP that maximised desired test properties for screening were determined

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 ≥0.694 μM had a sensitivity of 86.7%, specificity of 90.0% and AUC of 0.86 for diagnosing PAH. An NT-proBNP level ≥209.8ng/mL had a sensitivity of 93.3%, specificity of 100% and AUC of 0.94 for diagnosing PAH. A ‘purely’ biomarker based screening model that combined an NT-proBNP ≥209.8ng/mL and/or ADMA ≥0.694 ng/mL resulted in a sensitivity of 100% and specificity of 90% for the detection of SSc-PAH.

Conclusion: ADMA may be an important screening biomarker for SSc-PAH. A composite ‘purely’ biomarker-based screening algorithm, using NT-proBNP in combination with ADMA, may achieve an excellent sensitivity (and also specificity) for the non-invasive identification of SSc-PAH.


Disclosure:

V. Thakkar,
None;

W. Stevens,
None;

D. Prior,
None;

J. Sahhar,
None;

J. E. Roddy,
None;

J. Zochling,
None;

P. Nash,
None;

P. Youssef,
None;

S. Proudman,
None;

M. Nikpour,
None.

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