N-terminal pro-brain natriuretic peptide as a diagnostic marker of early pulmonary artery hypertension in patients with systemic sclerosis and effects of calcium-channel blockers

Arthritis Rheum. 2003 Dec;48(12):3503-8. doi: 10.1002/art.11345.


Objective: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker of early pulmonary artery hypertension (PAH) and to study changes in the levels of this marker following treatment with dihydropyridine-type calcium-channel blocker (DTCCB) in patients with systemic sclerosis (SSc).

Methods: We evaluated 40 consecutive SSc patients who had been hospitalized for followup care (mean +/- SD age 56 +/- 11 years and mean +/- SD duration of cutaneous disease 9 +/- 9 years; 27 with limited cutaneous and 13 with diffuse cutaneous disease) but who had no clinical symptoms of heart failure and had a normal left ventricular ejection fraction. At baseline, 10 patients had PAH, defined as a systolic pulmonary artery pressure (sPAP) >40 mm Hg, as measured by echocardiography. Levels of NT-proBNP were determined at baseline (after discontinuation of DTCCB treatment for 72 hours), after taking 3 doses of DTCCB following treatment reinitiation (assessment 1), and after 6-9 months of continuous DTCCB treatment (assessment 2) in the 20 patients who attended regular appointments (including the 10 patients with PAH at baseline).

Results: At baseline, 13 patients had high NT-proBNP values for their ages. High NT-proBNP levels identified patients with PAH with a sensitivity of 90%, a specificity of 90.3%, a positive predictive value of 69.2%, and a negative predictive value of 96%. The NT-proBNP level correlated with the sPAP (r = 0.44; P = 0.006). By assessment 1, the number of patients with PAH and high levels of NT-proBNP had decreased from 9 of 10 to 2 of 10 (P = 0.02). This decrease was partially sustained at assessment 2 (4 of 10 patients; P = 0.06).

Conclusion: NT-proBNP is a useful biologic marker that can be used to diagnose early PAH in SSc patients without clinical heart failure. Measurement of NT-proBNP may be valuable for the evaluation of treatment with DTCCB and vasodilators in patients with PAH.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Biomarkers
  • Calcium Channel Blockers / administration & dosage*
  • Calcium Channels, L-Type / metabolism
  • Disease Progression
  • Humans
  • Hypertension, Pulmonary / blood*
  • Hypertension, Pulmonary / diagnosis*
  • Hypertension, Pulmonary / drug therapy
  • Middle Aged
  • Natriuretic Peptide, Brain
  • Nerve Tissue Proteins / blood*
  • Peptide Fragments / blood*
  • Prospective Studies
  • Pulmonary Artery
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / diagnosis*


  • Biomarkers
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Nerve Tissue Proteins
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain