title: Association of anti-citrullinated protein or peptide antibodies with left ventricular structure and function in rheumatoid arthritis.
abstract: High levels of ACPAs in RA are associated with more severe arthritis and worse prognosis. However, the role of ACPAs in mediating the increased risk of heart failure in RA remains undefined. We examined whether specific ACPAs were associated with subclinical left ventricular (LV) phenotypes that presage heart failure.
  
  
  
  Sera from RA patients without clinical cardiovascular disease were assayed for specific ACPAs using a custom Bio-Plex bead assay, and their cross-sectional associations with cardiac magnetic resonance-derived LV measures were evaluated. High ACPA level was defined as ⩾ 75th percentile. Findings were assessed in a second independent RA cohort with an expanded panel of ACPAs and LV measures assessed by 3D-echocardiography.
  
  
  
  In cohort 1 (n = 76), higher levels of anti-citrullinated fibrinogen 41-60 and anti-citrullinated vimentin antibodies were associated with a 10 and 6% higher adjusted mean LV mass index (LVMI), respectively, compared with lower antibody levels (P < 0.05). In contrast, higher levels of anti-citrullinated biglycan 247-266 were associated with a 13% lower adjusted mean LVMI compared with lower levels (P < 0.001). In cohort 2 (n = 74), the association between ACPAs targeting citrullinated fibrinogen and citrullinated vimentin peptides or protein and LVMI was confirmed: higher anti-citrullinated fibrinogen 556-575 and anti-citrullinated vimentin 58-77 antibody levels were associated with a higher adjusted mean LVMI (19 and 15%, respectively; P < 0.05), but no association with biglycan was found.
  
  
  
  Higher levels of antibodies targeting citrullinated fibrinogen and vimentin peptides or protein were associated with a higher mean LVMI in both RA cohorts, potentially implicating autoimmune targeting of citrullinated proteins in myocardial remodelling in RA.
authors.affiliation: Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY.
authors.forename: Laura
authors.initials: L
authors.lastname: Geraldino-Pardilla
authors.affiliation: Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY.
authors.forename: Cesare
authors.initials: C
authors.lastname: Russo
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford.|Department of Medicine, VA Palo Alto Health Care System, Palo Alto.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sokolove
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford.|Department of Medicine, VA Palo Alto Health Care System, Palo Alto.
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.affiliation: Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY.
authors.forename: Afshin
authors.initials: A
authors.lastname: Zartoshti
authors.affiliation: The Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Van Eyk
authors.affiliation: The Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Justyna
authors.initials: J
authors.lastname: Fert-Bober
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Joao
authors.initials: J
authors.lastname: Lima
authors.affiliation: Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Giles
authors.affiliation: Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Bathon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology; D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005340:Fibrinogen / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology*; D013318:Stroke Volume / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000276:immunology* / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000276:immunology / Q000502:physiology; D014746:Vimentin / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D010455:Peptides; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide; D005340:Fibrinogen
keywords: CVD; RA; anti-citrullinated peptide antibody (ACPA); ventricular mass