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


IntroductionPulmonary 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 4 clinical groups: a group with right heart catheter (RHC) diagnosed SSc-PAH prior to 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 using ANOVA and correlated with other clinical variables 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 to other groups (p<0.0001), and higher in the risk group compared to 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 [greater than or equal to] 209.8pg/ml, and/or DLCOcorr<70.3% with FVC/DLCOcorr [greater than or equal to] 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 needs to be validated prospectively.

Author: Vivek ThakkarWendy M StevensDavid PriorOwen A MooreJillian ByronDanny LiewKaren PattersonPravin HissariaJanet RoddyJane ZochlingJoanne SahharPeter NashKathleen TymmsDavid CelermajerEli GabbayPeter YoussefSusanna M ProudmanMandana Nikpour
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Published on: 2012-06-12



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