European Heart Journal Advance Access originally published online on April 27, 2006
European Heart Journal 2006 27(12):1485-1494; doi:10.1093/eurheartj/ehi891
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Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension
1 Department of Cardiology, Royal Free Hospital, Pond Street, London NW3 2QG, UK
2 Pulmonary Hypertension Service, Royal Free Hospital, Pond Street, London, UK
3 Department of Clinical Biochemistry, Royal Free Hospital, Pond Street, London, UK
4 Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Rowland Hill Street, London, UK
Received 18 November 2005; revised 29 March 2006; accepted 30 March 2006; online publish-ahead-of-print 27 April 2006.
* Corresponding author. Tel: +44 20 7830 2455; fax: +44 20 7472 6291. E-mail address: gerry.coghlan{at}royalfree.nhs.uk
Aims 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.
Conclusion 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.
Key Words: Scleroderma • Pulmonary arterial hypertension • Survival • Natriuretic peptides • Prognosis • Right heart haemodynamics
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