title: Brief report: lack of replication of an association between anti-citrullinated fibrinogen and subclinical atherosclerosis in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Results of a recent study suggested that the excess cardiovascular (CV) risk observed in patients with rheumatoid arthritis (RA) could be partially explained by the presence of immune complexes of antibodies against citrullinated proteins that locally promote and perpetuate inflammation and progression of atherosclerotic plaques. The present study was undertaken to attempt to replicate one of the observations supporting this hypothesis, i.e., association between anti-citrullinated fibrinogen (anti-Cit-fibrinogen) positivity and subclinical atherosclerosis.
  
  
  METHODS
  Three surrogate markers of atherosclerosis were assessed in 124 RA patients with no previous history of CV events: carotid intima-media thickness (CIMT) assessed by carotid ultrasonography, carotid plaques assessed by carotid ultrasonography, and Coronary Artery Calcification Score (CACS) determined by multidetector computed tomography (CT) scanning. We analyzed the relationship of these 3 subclinical atherosclerosis markers to the presence and levels of autoantibodies, including anti-Cit-fibrinogen, anti-cyclic citrullinated peptide 2 (anti-CCP-2), and rheumatoid factor (RF).
  
  
  RESULTS
  Carotid plaques and CIMT >0.90 mm were present in 69.4% and 15.3%, of the patients, respectively, and the CACS was moderate or high in 21.0%. None of these surrogate markers of atherosclerosis showed a significant association with positivity for or the level of anti-Cit-fibrinogen antibodies (either against the whole protein [present in 33.9% of the patients] or against an immunodominant peptide [present in 23.4%]), anti-CCP-2 (present in 60.7%), or RF (present in 58.1%) in this series of patients with RA.
  
  
  CONCLUSIONS
  Our results do not support the notion that there is a relationship between anti-Cit-fibrinogen antibodies and subclinical atherosclerosis in RA, thus calling into question the claim that these antibodies have a role in the increased risk of CV disease observed in patients with RA.
authors.affiliation: Hospital Clínico Universitario de Santiago, Santiago de Compostela, A Coruña, Spain.
authors.forename: Ariana
authors.initials: A
authors.lastname: Montes
authors.affiliation: Hospital Universitario Marqués de Valdecilla and Valdecilla Biomedical Research Institute (IDIVAL), Santander, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Corrales
authors.affiliation: Hospital Clínico Universitario de Santiago, Santiago de Compostela, A Coruña, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Calaza
authors.affiliation: Hospital Universitario Marqués de Valdecilla and Valdecilla Biomedical Research Institute (IDIVAL), Santander, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Lopez-Mejias
authors.affiliation: Hospital Universitario Marqués de Valdecilla and Valdecilla Biomedical Research Institute (IDIVAL), Santander, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Parra
authors.affiliation: Hospital Universitario Marqués de Valdecilla and Valdecilla Biomedical Research Institute (IDIVAL), Santander, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.affiliation: Hospital Clínico Universitario de Santiago, Santiago de Compostela, A Coruña, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: González
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications* / Q000276:immunology; D050197:Atherosclerosis / Q000097:blood / Q000150:complications* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D059168:Carotid Intima-Media Thickness; D005260:Female; D005340:Fibrinogen / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012217:Rheumatoid Factor / Q000097:blood
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; D005340:Fibrinogen; D012217:Rheumatoid Factor