title: Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis.
abstract: OBJECTIVE
  To evaluate the possible merit of endothelial markers for the prediction of ischaemic digital ulcers in patients with systemic sclerosis (SSc).
  
  
  METHODS
  Circulating endothelial progenitor cells (EPC), circulating endothelial cells and serum levels of placental growth factor (PlGF), soluble vascular adhesion molecule and vascular endothelial growth factor were measured in a prospective cohort of 100 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up.
  
  
  RESULTS
  After the follow-up period, 17 patients developed new digital ulcers. By multivariate analysis focused on biomarkers, high PlGF serum levels and low EPC counts were identified as predictors of the occurrence of at least one new digital ulcer. In a secondary model including biomarkers together with clinical SSc characteristics all predictors of digital ulcers defined by p≤0.1 in univariate analysis, high PlGF serum levels (HR 7.26, 95% CI 1.92 to 27.41) and a history of digital ulcers (HR 9.32, 95% CI 1.51 to 59.83) were identified as independent predictors of a new digital ulcer. In an alternative model excluding patients with a history of digital ulcers at baseline, high PlGF serum levels (HR 13.46, 95% CI 1.58 to 114.73) and low EPC counts (HR 7.95, 95% CI 2.09 to 30.09) remained predictive of new digital ulcer occurrence during follow-up.
  
  
  CONCLUSIONS
  This study identified high PlGF serum levels and low circulating EPC counts as predictors of new digital ulcers in SSc. It highlights the critical role of angiogenesis in this vascular outcome. These markers may improve digital ulcer risk stratification and therefore allow earlier therapeutic intervention.
authors.affiliation: Rheumatology A department, Paris Descartes University, Cochin Hospital, APHP, Sorbonne Paris Cité, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Avouac
authors.forename: Christophe
authors.initials: C
authors.lastname: Meune
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruiz
authors.forename: Pierre Olivier
authors.initials: PO
authors.lastname: Couraud
authors.forename: Georges
authors.initials: G
authors.lastname: Uzan
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: André
authors.initials: A
authors.lastname: Kahan
authors.forename: Gilles
authors.initials: G
authors.lastname: Chiocchia
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D042783:Endothelial Cells / Q000473:pathology; D004812:Epidemiologic Methods; D005260:Female; D005385:Fingers / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood / Q000209:etiology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000097:blood*; D011379:Prognosis; D012595:Scleroderma, Systemic / Q000097:blood / Q000150:complications*; D012883:Skin Ulcer / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D013234:Stem Cells / Q000473:pathology
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor