title: Serum levels of anticyclic citrullinated peptide antibodies, interleukin-6, tumor necrosis factor-α, and C-reactive protein are associated with increased carotid intima-media thickness: a cross-sectional analysis of a cohort of rheumatoid arthritis patients without cardiovascular risk factors.
abstract: The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients.
  
  
  METHODS
  Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P < 0.001). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P < 0.01), and lower levels of high density lipoprotein cholesterol (HDL-c) (P = 0.02). The cIMT correlated with levels of anti-CCP (r = 0.513, P = 0.001), CRP (r = 0.799, P < 0.001), TNFα (r = 0.642, P = 0.001), and IL-6 (r = 0.751, P < 0.001). In multiple regression analysis, cIMT was associated with CRP (P < 0.001) and anti-CCP levels (P = 0.03).
  
  
  CONCLUSIONS
  Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events.
authors.affiliation: Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico ; Departamento de Reumatología, Hospital Civil "Dr. Juan I. Menchaca", Universidad de Guadalajara, Salvador de Quevedo No. 750, 44100 Guadalajara, JAL, Mexico.
authors.forename: Mónica
authors.initials: M
authors.lastname: Vázquez-Del Mercado
authors.affiliation: Hospital Civil de Guadalajara "Fray Antonio Alcalde", Universidad de Guadalajara, Hospital No. 278, 44280 Guadalajara, JAL, Mexico.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Nuñez-Atahualpa
authors.affiliation: Hospital Civil de Guadalajara "Fray Antonio Alcalde", Universidad de Guadalajara, Hospital No. 278, 44280 Guadalajara, JAL, Mexico.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Figueroa-Sánchez
authors.affiliation: Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gómez-Bañuelos
authors.affiliation: Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico.
authors.forename: Alberto Daniel
authors.initials: AD
authors.lastname: Rocha-Muñoz
authors.affiliation: Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico.
authors.forename: Beatriz Teresita
authors.initials: BT
authors.lastname: Martín-Márquez
authors.affiliation: Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico ; Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico.
authors.forename: Esther Guadalupe
authors.identifier: 0000-0002-6540-2444
authors.initials: EG
authors.lastname: Corona-Sanchez
authors.affiliation: Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico ; Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico.
authors.forename: Erika Aurora
authors.initials: EA
authors.lastname: Martínez-García
authors.affiliation: Hospital Civil de Guadalajara "Fray Antonio Alcalde", Universidad de Guadalajara, Hospital No. 278, 44280 Guadalajara, JAL, Mexico.
authors.forename: Héctor
authors.initials: H
authors.lastname: Macias-Reyes
authors.affiliation: Departamento de Medicina Interna-Reumatología, Hospital General Regional No. 110, Instituto Mexicano del Seguro Social, Circunvalación Oblatos No. 2212, Colonia Oblatos, 44700 Guadalajara, JAL, Mexico.
authors.forename: Laura
authors.identifier: 0000-0002-6517-6344
authors.initials: L
authors.lastname: Gonzalez-Lopez
authors.affiliation: Unidad de Investigacion, Unidad Medica de Alta Especialidad, Hospital de Especialidades del Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Belisario Domínguez No. 1000, Independencia Oriente, 44340 Guadalajara, JAL, Mexico.
authors.forename: Jorge Ivan
authors.initials: JI
authors.lastname: Gamez-Nava
authors.affiliation: Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico.
authors.forename: Rosa Elena
authors.initials: RE
authors.lastname: Navarro-Hernandez
authors.affiliation: Facultad de Medicina, Universidad Autónoma de Guadalajara, Avenida Patria 1201, Lomas del Valle, 45129 Zapopan, JAL, Mexico.
authors.forename: María Alejandra
authors.initials: MA
authors.lastname: Nuñez-Atahualpa
authors.affiliation: Facultad de Medicina, Universidad Autónoma de Guadalajara, Avenida Patria 1201, Lomas del Valle, 45129 Zapopan, JAL, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Andrade-Garduño
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000453:epidemiology; D050197:Atherosclerosis / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology; D002340:Carotid Artery Diseases / Q000097:blood* / Q000453:epidemiology; D059168:Carotid Intima-Media Thickness / Q000706:statistics & numerical data; D015331:Cohort Studies; D015897:Comorbidity; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood*; D015995:Prevalence; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D002097:C-Reactive Protein
references.citation: Atherosclerosis. 2008 Jun;198(2):332-7
references.pmid: 18164712
references.citation: Clin Exp Rheumatol. 2008 Jul-Aug;26(4):627-31
references.pmid: 18799094
references.citation: Arthritis Rheum. 1995 Jan;38(1):44-8
references.pmid: 7818570
references.citation: J Clin Rheumatol. 2012 Dec;18(8):422-30
references.pmid: 23188207
references.citation: Clin Exp Rheumatol. 2006 May-Jun;24(3):309-12
references.pmid: 16870100
references.citation: Circulation. 2002 Dec 17;106(25):3143-421
references.pmid: 12485966
references.citation: Clin Rheumatol. 2010 Nov;29(11):1237-43
references.pmid: 20354747
references.citation: Arthritis Rheum. 2003 Jul;48(7):1833-40
references.pmid: 12847676
references.citation: Arthritis Rheum. 2000 Jan;43(1):155-63
references.pmid: 10643712
references.citation: Rheumatology (Oxford). 2007 Jan;46(1):70-5
references.pmid: 16782731
references.citation: Arthritis Rheum. 2007 Feb;56(2):425-32
references.pmid: 17265477
references.citation: Ann Vasc Surg. 2013 Feb;27(2):186-93
references.pmid: 22951063
references.citation: Ann Intern Med. 2007 Jun 5;146(11):816-7
references.pmid: 17548414
references.citation: J Rheumatol. 2005 Jul;32(7):1219-23
references.pmid: 15996055
references.citation: Cerebrovasc Dis. 2007;23(1):75-80
references.pmid: 17108679
references.citation: Maedica (Buchar). 2012 Jun;7(2):153-62
references.pmid: 23399970
references.citation: Arthritis Rheum. 2010 Sep;62(9):2569-81
references.pmid: 20872595
references.citation: J Am Med Assoc. 1949 Jun 25;140(8):659-62
references.pmid: 18150288
references.citation: Atherosclerosis. 2011 May;216(1):125-30
references.pmid: 21420089
references.citation: Semin Arthritis Rheum. 2012 Aug;42(1):17-22
references.pmid: 22475246
references.citation: Arthritis Rheum. 2007 Feb 15;57(1):125-32
references.pmid: 17266100
references.citation: J Rheumatol. 2012 Jun;39(6):1146-54
references.pmid: 22589258
references.citation: Reumatol Clin. 2013 May-Jun;9(3):136-41
references.pmid: 23273674
references.citation: Arthritis Res Ther. 2010;12(4):R158
references.pmid: 20712865
references.citation: Arthritis Rheum. 2013 Jul;65(7):1719-24
references.pmid: 23553485
references.citation: Arthritis Rheum. 2009 Apr 15;61(4):419-24
references.pmid: 19333979
references.citation: Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1702-8
references.pmid: 19608975
references.citation: Clin Exp Rheumatol. 2009 Nov-Dec;27(6):964-70
references.pmid: 20149313
references.citation: Clin Exp Rheumatol. 2008 Mar-Apr;26(2):311-6
references.pmid: 18565254
references.citation: J Rheumatol. 2008 Mar;35(3):398-406
references.pmid: 18203326
references.citation: Arthritis Res Ther. 2008;10(4):R75
references.pmid: 18601717
references.citation: Arthritis Rheum. 2009 Mar;60(3):641-52
references.pmid: 19248103
references.citation: J Womens Health (Larchmt). 2009 Jan-Feb;18(1):21-9
references.pmid: 19105681
references.citation: Arthritis Res Ther. 2012;14(1):R39
references.pmid: 22364592
references.citation: Arthritis Rheum. 1988 Mar;31(3):315-24
references.pmid: 3358796
references.citation: J Clin Rheumatol. 2011 Aug;17(5):249-55
references.pmid: 21778898
references.citation: Swiss Med Wkly. 2012;142:w13705
references.pmid: 23135891
references.citation: Medicine (Baltimore). 2003 Nov;82(6):407-13
references.pmid: 14663290
references.citation: Arthritis Res Ther. 2009;11(1):R7
references.pmid: 19144159
references.citation: Arthritis Res Ther. 2007;9(6):R116
references.pmid: 17986352
references.citation: Clin Biochem. 2013 Aug;46(12):1007-12
references.pmid: 23578742
references.citation: Vasa. 2012 Sep;41(5):343-51
references.pmid: 22915531
references.citation: Annu Rev Med. 2013;64:249-63
references.pmid: 23020882
references.citation: Clin Rev Allergy Immunol. 2008 Feb;34(1):11-5
references.pmid: 18270851
references.citation: J Rheumatol. 2011 May;38(5):828-34
references.pmid: 21362765
references.citation: Kidney Int. 2002 Mar;61(3):1143-52
references.pmid: 11849469
references.citation: Rheumatology (Oxford). 2010 Jun;49(6):1076-81
references.pmid: 20208070
references.citation: Scand J Rheumatol. 2011 Nov;40(6):422-7
references.pmid: 22150462
references.citation: Ann Rheum Dis. 2008 May;67(5):724-5
references.pmid: 18408112
references.citation: Ann Cardiol Angeiol (Paris). 2012 Aug;61(4):267-73
references.pmid: 22794936
references.citation: Vasa. 2012 Sep;41(5):311-2
references.pmid: 23025038
references.citation: Am J Med. 2008 Oct;121(10 Suppl 1):S3-8
references.pmid: 18926167
references.citation: Arthritis Res Ther. 2011;13(3):R101
references.pmid: 21696620
references.citation: Ann N Y Acad Sci. 2005 Jun;1051:281-90
references.pmid: 16126969
references.citation: Stroke. 2001 Oct;32(10):2265-71
references.pmid: 11588311