title: Red cell distribution width is associated with endothelial progenitor cell depletion and vascular-related mediators in rheumatoid arthritis.
abstract: OBJECTIVE
  The role of Red Cell Distribution Width (RDW) as a predictor of cardiovascular (CV) events has been proposed in a variety of conditions, including Rheumatoid Arthritis (RA). However, the mechanisms underlying this effect are still unknown. Since inflammation and Endothelial Progenitor Cells (EPCs) imbalance have been reported in RA patients to be related to CV disease, we wondered whether RDW could be linked to endothelial repair failure in RA.
  
  
  METHODS
  EPCs (CD34+VEGFR2+CD133+) were quantified by flow cytometry in peripheral blood samples from 194 RA patients. IFNα, TNFα, IFNγ, IL-8, VEGF, GM-CSF, MCP-1, ICAM-1, EGF, Leptin and Resistin serum levels were quantified by immunoassays. Clinical and immunological parameters as well as history of traditional CV risk factors and CV events were registered from medical records. RDW was measured in complete blood cell count analyses.
  
  
  RESULTS
  RDW was negatively related to EPC counts in patients with established disease (>1 year, n=125) (r=-0.306, p<0.001). Moreover, RDW was independently associated to an EPC depletion in the whole group (β [95% CI]: -3.537 [-6.162, -0.911], p=0.009) after adjusting for clinical parameters, disease duration, treatments and traditional CV risk factors. Additionally, RDW was positively correlated with IFNα serum levels, a cytokine related to endothelial damage, and with IL-8, VEGF and neutrophil to lymphocyte ratio, thus supporting the association with inflammation and vascular remodelling.
  
  
  CONCLUSIONS
  RDW was associated to EPC depletion and increased levels of different mediators linked to endothelial damage and vascular repair failure, thereby shedding new light on the nature of RDW as CV-predictor.
authors.affiliation: Area of Immunology, Department of Functional Biology, University of Oviedo, Asturias, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Carrio
authors.affiliation: Department of Rheumatology, Hospital Universitario Central de Asturias, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alperi-López
authors.affiliation: Area of Immunology, Department of Functional Biology, University of Oviedo, Asturias, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: López
authors.affiliation: Department of Rheumatology, Hospital Universitario Central de Asturias, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Alonso-Castro
authors.affiliation: Area of Immunology, Department of Functional Biology, University of Oviedo, Asturias, Spain.
authors.forename: Santiago Rubén
authors.initials: SR
authors.lastname: Carro-Esteban
authors.affiliation: Department of Rheumatology, Hospital Universitario Central de Asturias, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ballina-García
authors.affiliation: Area of Immunology, Department of Functional Biology, University of Oviedo, Asturias, Spain. Electronic address: anasua@uniovi.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Suárez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D066026:Endothelial Progenitor Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004909:Erythrocyte Indices; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007118:Immunoassay; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D013997:Time Factors; D066253:Vascular Remodeling; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators
keywords: Cardiovascular; Cytokines; Endothelial progenitor cells; Inflammation; Red cell distribution width; Rheumatoid arthritis