title: Elevated plasma CXCL12α is associated with a poorer prognosis in pulmonary arterial hypertension.
abstract: BACKGROUND
  Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12α were elevated in patients with PAH and related to mortality.
  
  
  METHODS
  Plasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue diseases (CTD-PAH) attending two pulmonary hypertension referral centres (n = 95) and from age and gender matched healthy controls (n = 44). Patients were subsequently monitored throughout a period of five years.
  
  
  RESULTS
  CXCL12α concentrations were elevated in PAH groups compared to controls (P<0.05) and receiver-operating-characteristic analysis showed that plasma CXCL12α concentrations discriminated patients from healthy controls (AUC 0.80, 95% confidence interval 0.73-0.88). Kaplan Meier analysis indicated that elevated plasma CXCL12α concentration was associated with reduced survival (P<0.01). Multivariate Cox proportional hazards model showed that elevated CXCL12α independently predicted (P<0.05) earlier death in PAH with a hazard ratio (95% confidence interval) of 2.25 (1.01-5.00). In the largest subset by WHO functional class (Class 3, 65% of patients) elevated CXCL12α independently predicted (P<0.05) earlier death, hazard ratio 2.27 (1.05-4.89).
  
  
  CONCLUSIONS
  Our data show that elevated concentrations of circulating CXCL12α in PAH predicted poorer survival. Furthermore, elevated circulating CXCL12α was an independent risk factor for death that could potentially be included in a prognostic model and guide therapy.
authors: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland; Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors: Brian N
authors: BN
authors: McCullagh
authors: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.
authors: Christine M
authors: CM
authors: Costello
authors: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.
authors: Lili
authors: L
authors: Li
authors: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland; Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors: Caroline
authors: C
authors: O'Connell
authors: School of Public Health, Physiotherapy and Population Science, University College Dublin, Dublin 4, Ireland.
authors: Mary
authors: M
authors: Codd
authors: Department of Cardiovascular Sciences, University of Sheffield, Sheffield, United Kingdom.
authors: Allan
authors: A
authors: Lawrie
authors: Department of Cardiology, Northern General Hospital, Sheffield, United Kingdom.
authors: Allison
authors: A
authors: Morton
authors: Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom.
authors: David G
authors: DG
authors: Kiely
authors: Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom.
authors: Robin
authors: R
authors: Condliffe
authors: Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom.
authors: Charles
authors: C
authors: Elliot
authors: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.
authors: Paul
authors: P
authors: McLoughlin
authors: Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors: Sean
authors: S
authors: Gaine
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D054377:Chemokine CXCL12 / Q000097:blood*; D065627:Familial Primary Pulmonary Hypertension / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12