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

Abstract

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.MethodsNT-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.ResultsNT-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.ConclusionWe 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.

Screening patients with scleroderma for pulmonary arterial hypertension and implications for other at-risk populations

“…A similar approach was used by THAKKAR et al [44], who derived a screening algorithm incorporating NT-proBNP and pulmonary function test results, but this score has not yet been validated. MEUNE et al [45] developed a simple score (Cochin risk score) to predict the risk of pulmonary hypertension SSc constituted by simple clinical observations (age, FVC and DLCO).…”

Connective tissue disease-associated pulmonary arterial hypertension in Chinese patients

“…The differences in therapeutic response and prognosis reflect the variations of pathological mechanisms between the two types of CTD-APAH. To improve the poor prognosis of SSc-APAH, some useful tools for early screening of PAH in SSc patients, for instance, tricuspid regurgitation velocity, N-terminal pro-brain natriuretic peptide and pulmonary function tests, have been developed [39][40][41][42], and early screening and management have been recommended and adopted in clinical practice in Europe, North America and Australia [39,43].…”

Is early diagnosis of pulmonary arterial hypertension possible in inflammatory rheumatic diseases? Experience from a single center in Turkey

“…Evaluation of the patients using additional parameters that had been shown to be useful in the diagnosis, prognosis, and/or follow-up of PAH such as serum brain natriuretic peptide levels (BNP), diffusing capacity of carbon monoxide (DLCO), and six minute walk distance before RHC may improve the diagnostic approach (16)(17)(18). Currently, new algorithms for the diagnosis of PH that include components such as patient's clinical features, BNP levels, and DLCO have been suggested (19)(20)(21)(22). DETECT (DETECTion of PAH in SSc) algorithm in SSc patients with DLCO<60% and disease duration>3 years may be useful for early diagnosis (22).…”