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


CONCLUSIONS
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.
Department of Rheumatology, St Vincent's Hospital Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.
Vivek
V
Thakkar
Wendy M
WM
Stevens
David
D
Prior
Owen A
OA
Moore
Jillian
J
Byron
Danny
D
Liew
Karen
K
Patterson
Pravin
P
Hissaria
Janet
J
Roddy
Jane
J
Zochling
Joanne
J
Sahhar
Peter
P
Nash
Kathleen
K
Tymms
David
D
Celermajer
Eli
E
Gabbay
Peter
P
Youssef
Susanna M
SM
Proudman
Mandana
M
Nikpour
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000465:Algorithms; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D042241:Early Diagnosis; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D012372:ROC Curve; D012595:Scleroderma, Systemic / Q000097:blood / Q000150:complications*; D012680:Sensitivity and Specificity
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain