title: Endothelial dysfunction, microvascular damage and ischemic peripheral vasculopathy in systemic sclerosis.
abstract: OBJECTIVE
  To evaluate endothelial dysfunction and microvascular damage in secondary Raynaud Phenomenon (SRP) and Systemic sclerosis (SSc)-associated patients as possible predictors of ischemic fingertip digital ulcers (DU) in a 3-year clinical follow-up.
  
  
  METHODS
  Flow-mediated dilatation (FMD), nailfold videocapillaroscopy (NVC), endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) were analysed in a 3-year observational cohort study of 77 SRP patients with systemic sclerosis. The primary outcome was the occurrence of a new DU.
  
  
  RESULTS
  Risk factors for DU at baseline were low FMD% (p < 0.001), NVC pattern (p < 0.001), high microangiopathy evolution score (MES) (p < 0.001), increased ET-1 (p < 0.001) and increased ADMA serum levels (p = 0.001). Median time to the occurrence of a new DU was 4.50 (1.25-16.25) months. The risk factors for the occurrence of at least one new DU episode in follow-up included a history of at least one DU before enrolment (p < 0.001), autoantibody anti-scleroderma-70 (p = 0.012), NVC late pattern (p < 0.001), high MES score (p < 0.001), low FMD% (p < 0.001) and increased ET-1 serum levels (p < 0.001).We used univariate Cox regression analysis to show that FMD >9.41% (HR: 0.37 95% CI: 0.14-0.99) and ET-1 >11.85 pmol/L (HR: 3.81 95% CI: 1.41-10.26) and NVC (HR: 2.29 95% CI: 0.97-5.38) were predictors of DU recurrence. In terms of first DU event in naïve DU patients at baseline, late NVC pattern (HR: 12.66 95% CI: 2.06-77.89) and MES score (HR: 1.693 95% CI: 1.257-2.279) were independent predictors.
  
  
  CONCLUSIONS
  This study identified endothelium dysfunction biomarkers (FMD and ET-1) and severe microvascular damage in NVC as strong predictors of new DU in SSc patients.
authors.affiliation: Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Multidisciplinar Unit of Biomedical Investigation, Porto, Portugal.
authors.forename: Ivone
authors.initials: I
authors.lastname: Silva
authors.affiliation: Department of Health Information and Decision Sciences, Universidade do Porto, CINTESIS - Centre for Research in Health Technologies and Information Systems, Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Teixeira
authors.affiliation: Department of Clinical Pathology, Clinical Chemistry, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Multidisciplinar Unit of Biomedical Investigation, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Almeida
authors.affiliation: Clinical Immunology Unit, Centro Hospitalar do Porto (CHP), Instituto de Ciências Biomédicas Abel Salazar, University of Porto (ICBAS/UP), Multidisciplinar Unit of biomedical investigation (UMIB), Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vasconcelos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005385:Fingers / Q000473:pathology*; D006801:Humans; D008297:Male; D020678:Microscopic Angioscopy / Q000379:methods*; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000209:etiology* / Q000473:pathology; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000150:complications* / Q000473:pathology; D014456:Ulcer / Q000209:etiology*; D055815:Young Adult
keywords: ADMA; Allen test; ET-1; Systemic sclerosis; and microangiopathy evolution score; capillaroscopy; digital ulcers; flow-mediated dilatation