title: Predictive value of vascular disease biomarkers for digital ulcers in systemic sclerosis patients.
abstract: OBJECTIVE
  To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk factors and their predictive value for digital ulcers in systemic sclerosis patients.
  
  
  METHODS
  Endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), endostatin and endoglin were measured in an observational prospective cohort of 77 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 3-year follow-up, 40 patients developed new digital ulcers. Logistic regression confirmed VEGF (HR 1.128, 95% CI 1.010-1.260, p=0.033) and ADMA (HR 0.995, 95% CI 0.991-0.998, p=0.006) as independent predictors of new digital ulcers. Patients with serum levels of ET-1>11.9 pmol/ml (p<0.001) and VEGF<422.47 pg/ml (p=0.028) had significantly more DU in the 3-year follow-up. Although not significant, a trend towards increased serum levels of endoglin>4.215 ng/ml (p=0.053) was associated to a new DU episode. No predictive serum value was found for ADMA (p=0.075) and endostatin (p=0.130).
  
  
  CONCLUSIONS
  Endothelial dysfunction and angiogenic vascular biomarkers have an important role in the underlying and in the progression of microvascular disease in systemic sclerosis. Increased serum levels of ET-1, ADMA and VEGF are strong predictors of severe microangiopathy complications, namely ischaemic digital ulcers.
authors.affiliation: Angiology and Vascular Surgery Service and Clinical Immunology Unit, Centro Hospitalar do Porto, Portugal. heitor.ivone@gmail.com.
authors.forename: Ivone
authors.initials: I
authors.lastname: Silva
authors.affiliation: Health Information and Decision Sciences Department, Universidade do Porto; CINTESIS, Center for Research in Health Technologies and Information Systems, Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Teixeira
authors.affiliation: Clinical Pathology Department, Clinical Chemistry, Centro Hospitalar do Porto, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: Clinical Immunology Unit, Centro Hospitalar do Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Almeida
authors.affiliation: Angiology and Vascular Surgery Service, Centro Hospitalar do Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Almeida
authors.affiliation: Clinical Immunology Unit, Centro Hospitalar do Porto; Instituto de Ciências Biomédicas Abel Salazar, University of Porto; Multidisciplinar Unit of biomedical investigation, Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vasconcelos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D019332:Endothelin-1 / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005385:Fingers / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000150:complications* / Q000175:diagnosis; D012720:Severity of Illness Index; D012883:Skin Ulcer / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D066253:Vascular Remodeling; D014661:Vasoconstriction; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C018524:N,N-dimethylarginine; D001120:Arginine