title: Red cell distribution width outperforms other potential circulating biomarkers in predicting survival in idiopathic pulmonary arterial hypertension.
abstract: BACKGROUND
  In addition to N-terminal pro-brain natriuretic peptide (NT-proBNP), red cell distribution width (RDW), growth differentiation factor (GDF)-15, interleukin (IL)-6 and creatinine are all potential circulating prognostic biomarkers in pulmonary arterial hypertension (PAH).
  
  
  OBJECTIVE
  To establish the relative prognostic utility of these biomarkers in patients with idiopathic PAH (IPAH) and to identify independent prognostic markers in this disease.
  
  
  METHODS
  Circulating RDW, GDF-15, IL-6, creatinine and NT-proBNP levels were determined in 139 patients with IPAH (mean follow-up 4.0±2.4 years) and 40 age- and sex-matched healthy volunteers. Coincident clinical data and baseline haemodynamic measurements were also analysed.
  
  
  RESULTS
  All the biomarkers except creatinine correlated with a 6 min walk distance (6MWD; p<0.05), and all but NT-proBNP correlated with WHO functional class (p<0.01). GDF-15, creatinine and NT-proBNP correlated with mean right atrial pressures and cardiac index. RDW outperformed other biomarkers in receiver operating characteristic (ROC) analysis (area under the curve 0.820). Sensitive (>80%) ROC-derived cut-off points of RDW (15.7%, p=0.001), GDF-15 (779 pg/ml, p<0.001), IL-6 (2.5 pg/ml, p=0.019), creatinine (80.5 μmol/l, p=0.010) and NT-proBNP (491 fmol/ml, p<0.001), all predicted survival in patients with IPAH over time. All the plasma biomarkers analysed predicted survival in Cox regression analysis, as did clinical and haemodynamic parameters. However, only RDW predicted survival independently of NT-proBNP and 6MWD.
  
  
  CONCLUSIONS
  Circulating RDW, GDF-15, IL-6, creatinine and NT-proBNP levels are all related to disease severity and may be used to predict survival in patients with IPAH. RDW added significant prognostic value to measurements of NT-proBNP and exercise capacity and may prove valuable in a multiple biomarker approach to disease stratification.
authors.affiliation: Centre for Pharmacology and Therapeutics, Hammersmith Hospital, Imperial College London, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Rhodes
authors.forename: John
authors.initials: J
authors.lastname: Wharton
authors.forename: Luke S
authors.initials: LS
authors.lastname: Howard
authors.forename: J Simon R
authors.initials: JS
authors.lastname: Gibbs
authors.forename: Martin R
authors.initials: MR
authors.lastname: Wilkins
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D048429:Cell Size; D003404:Creatinine / Q000097:blood; D004812:Epidemiologic Methods; D004912:Erythrocytes / Q000473:pathology*; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D015850:Interleukin-6; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D003404:Creatinine