title: High N-terminal pro-brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis.
abstract: OBJECTIVE
  To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc).
  
  
  METHODS
  Routine clinical assessments as well as measurements of the diffusing capacity for carbon monoxide/alveolar volume (DLCO/VA) ratio and N-terminal pro-brain natriuretic peptide (NT-proBNP) level were performed in a prospective cohort of 101 SSc patients who did not have PAH or severe comorbidities. After a planned 36-month followup, we evaluated the predictive value of these parameters for the development of precapillary PAH, as demonstrated by cardiac catheterization, disease progression, and death. Criteria for cardiac catheterization were a systolic pulmonary artery pressure (PAP) of >40 mm Hg on echocardiography, a DLCO value of <50% without pulmonary fibrosis, and unexplained dyspnea.
  
  
  RESULTS
  Eight patients developed PAH, 29 had disease progression, and 10 died during a median followup of 29 months. Kaplan-Meier analysis identified the following baseline parameters as being predictors of PAH: DLCO/VA ratio <70% or <60% (P<0.01 for each comparison), elevated plasma NT-proBNP level (>97th percentile of normal; P = 0.005), echocardiographically estimated systolic PAP >40 mm Hg (P=0.08), and erythrocyte sedimentation rate >28 mm/hour (P=0.015). In multivariate analyses, an elevated baseline NT-proBNP level (hazard ratio [HR] 9.97 [95% confidence interval (95% CI) 1.69-62.42]) and a DLCO/VA ratio <60% (HR 36.66 [95% CI 3.45-387.6]) were predictors of the occurrence of PAH during followup. An increased NT-proBNP level together with a decreased DLCO/VA ratio of <70% was highly predictive of the occurrence of PAH during followup (HR 47.20 [95% CI 4.90-450.33]).
  
  
  CONCLUSIONS
  This prospective study identified a decreased DLCO/VA ratio and an increased NT-proBNP as predictors of PAH in SSc. Use of these markers should result in improved PAH risk stratification and allow earlier initiation of therapy.
authors.affiliation: René Descartes University, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. yannick.allanore@cch.aphp.fr
authors.forename: Y
authors.initials: Y
authors.lastname: Allanore
authors.forename: D
authors.initials: D
authors.lastname: Borderie
authors.forename: J
authors.initials: J
authors.lastname: Avouac
authors.forename: D
authors.initials: D
authors.lastname: Zerkak
authors.forename: C
authors.initials: C
authors.lastname: Meune
authors.forename: E
authors.initials: E
authors.lastname: Hachulla
authors.forename: L
authors.initials: L
authors.lastname: Mouthon
authors.forename: L
authors.initials: L
authors.lastname: Guillevin
authors.forename: O
authors.initials: O
authors.lastname: Meyer
authors.forename: O G
authors.initials: OG
authors.lastname: Ekindjian
authors.forename: S
authors.initials: S
authors.lastname: Weber
authors.forename: A
authors.initials: A
authors.lastname: Kahan
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002196:Capillaries; D002248:Carbon Monoxide / Q000097:blood*; D015897:Comorbidity; D004058:Diffusion; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000401:mortality*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002248:Carbon Monoxide