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Open Access Highly Accessed Research article

N-terminal pro-brain natriuretic peptide in a novel screening algorithm for pulmonary arterial hypertension in systemic sclerosis: a case-control study

Vivek Thakkar1, Wendy M Stevens1, David Prior2, Owen A Moore1, Jillian Byron1, Danny Liew3, Karen Patterson4, Pravin Hissaria45, Janet Roddy6, Jane Zochling7, Joanne Sahhar8, Peter Nash9, Kathleen Tymms10, David Celermajer11, Eli Gabbay12, Peter Youssef13, Susanna M Proudman14 and Mandana Nikpour115*

Author Affiliations

1 Department of Rheumatology, St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia

2 Department of Cardiology, St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia

3 Department of Epidemiology, Biostatistics and Health Research, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050

4 Institute of Medical and Veterinary Science/SA Pathology, 72 King William Road, North Adelaide, South Australia 5000, Australia

5 Departments of Clinical Immunology and Immunopathology, Royal Adelaide Hospital, North Terrace, South Australia 5000, Australia

6 Department of Rheumatology, Royal Perth Hospital, Wellington Street (GPO Box X2213), Perth, Western Australia 6001, Australia

7 Department of Rheumatology, The Menzies Institute, Private Bag 23, Hobart, Tasmania 7001, Australia

8 Department of Rheumatology, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, Victoria 3168, Australia

9 Sunshine Coast Rheumatology, PO Box 368, Maroochydore, Sunshine Coast, Queensland 4558, Australia

10 Canberra Rheumatology, 40 Markus Clarke Street, Canberra, Australian Capital Territory 2601, Australia

11 Department of Cardiology, Royal Prince Alfred Hospital, Missendon Road, Camperdown, New South Wales 2050, Australia

12 Advanced Lung Disease Unit and Pulmonary Hypertension Service, Royal Perth Hospital, GPO Box X2213, Perth, WA 6001, Australia

13 Institute of Rheumatology and Orthopaedics, Royal Prince Alfred Hospital, Queen Elizabeth II Building, Missendon Road, Camperdown, New South Wales 2050, Australia

14 Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000

15 The University of Melbourne Department of Medicine, St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia

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Arthritis Research & Therapy 2012, 14:R143  doi:10.1186/ar3876

Published: 12 June 2012

Abstract

Introduction

Pulmonary arterial hypertension is a major cause of mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide (NT-proBNP) has emerged as a candidate biomarker that may enable the early detection of systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). The objective of our study was to incorporate NT-proBNP into a screening algorithm for SSc-PAH that could potentially replace transthoracic echocardiography (TTE) as a more convenient and less costly "first tier" test.

Methods

NT-proBNP levels were measured in patients from four clinical groups: a group with right heart catheter (RHC)-diagnosed SSc-PAH before commencement of therapy for PAH; a group at high risk of SSc-PAH based on TTE; a group with interstitial lung disease; and systemic sclerosis (SSc) controls with no cardiopulmonary complications. NT-proBNP levels were compared by using ANOVA and correlated with other clinical variables by using simple and multiple linear regression. ROC curve analyses were performed to determine the optimal cut point for NT-proBNP and other clinical variables in prediction of PAH.

Results

NT-proBNP was highest in the PAH group compared with other groups (P < 0.0001), and higher in the risk group compared with controls (P < 0.0001). NT-proBNP was positively correlated with systolic pulmonary artery pressure (PAP) on TTE (P < 0.0001), and mean PAP (P = 0.013), pulmonary vascular resistance (P = 0.005), and mean right atrial pressure (P = 0.006) on RHC. A composite model wherein patients screened positive if NT-proBNP was ≥ 209.8 pg/ml, and/or DLCOcorr was < 70.3% with FVC/DLCOcorr ≥ 1.82, had a sensitivity of 100% and specificity of 77.8% for SSc-PAH.

Conclusion

We have proposed a screening algorithm for SSc-PAH, incorporating NT-proBNP level and PFTs. This model has high sensitivity and specificity for SSc-PAH and, if positive, should lead to TTE and confirmatory testing for PAH. This screening algorithm must be validated prospectively.