Role of N-terminal Brain Natriuretic Peptide in Scleroderma-associated Pulmonary Arterial Hypertension PDF Print E-mail
Wednesday, 03 March 2010 10:41
Mark H. Williams, Clive E. Handler, Raza Akram, Colette J. Smith, Clare Das, Joanna Smee, Devaki Nair, Christopher P. Denton, Carol M. Black and John G. Coghlan
First published online: April 27, 2006

The aims of this study were to evaluate the diagnostic value and to explore the prognostic value of N-terminal brain natriuretic peptide (N-TproBNP) in patients with systemic sclerosis (SSc) both with and without pulmonary arterial hypertension (PAH).

Methods and Results:
N-TproBNP, six-minute walk distance (SMWD), haemodynamics (at right heart catheterization) or tricuspid gradient (by echocardiography), and survival were assessed in 109 patients with SSc. The study population included 68 individuals with PAH [mean pulmonary artery pressure (PAP) >25 mmHg and pulmonary capillary wedge pressure <15 mmHg] and 41 individuals without PAH. In patients with PAH, the prognostic value of baseline and change in WHO functional class, N-TproBNP levels, and SMWD were compared using Kaplan–Meier survival curves and Cox proportional hazard analysis. The mean duration of follow-up was 10 months (range 1–18 months). One year survival in patients with normal PAP was 100% when compared with 83.5% in those with SSc-PAH (P<0.05). The patients without PAH had a mean N-TproBNP level of 139 pg/mL (SD 151); those with SSc-PAH had a significantly higher mean N-TproBNP level of 1474 pg/mL (SD 2642) (P=0.0002). Among patients with PAH for every order of magnitude increase in N-TproBNP level there was a four-fold increased risk of death (P=0.002 for baseline level and P=0.006 for follow-up level). Baseline N-TproBNP levels were correlated positively with mean PAP (r=0.62; P<0.0001), pulmonary vascular resistance (PVR) (r=0.81; P<0.0001), and inversely with SMWD (r=−0.46; P<0.0001). Among patients with SSc-PAH, 13 patients (19%) were in WHO functional classes II and had mean N-TproBNP levels of 325 pg/mL (SD 388). Fifty-three patients (78%) were in WHO classes III and IV and had significantly higher mean N-TproBNP levels of 1677 pg/mL (SD 2835) (P=0.02). At an N-TproBNP level of 395 pg/mL, the sensitivity and specificity for predicting the presence of SSc-PAH were 56 and 95% respectively.

Raised N-TproBNP levels are directly related to the severity of PAH. In screening programs, SSc patients with an N-TproBNP in excess of 395 pg/mL have a very high probability of having pulmonary hypertension. Baseline and serial changes in N-TproBNP levels are highly predictive of survival. A 10-fold increase in N-TproBNP level on therapy is associated with a greater than three-fold increase in mortality, and may indicate therapeutic failure.

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