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Cardiovascular disease is associated with extra-articular manifestations in patients with rheumatoid arthritis

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Abstract

The objective of this study was to examine the clinical and genetic variables associated with extra-articular rheumatoid arthritis (ExRA). This was a cross-sectional study in which 538 Northwestern Colombian patients with rheumatoid arthritis (RA) were included. Information about demographics and clinical characteristics including disease activity, inflammatory markers, co-morbidities, cardiovascular (CV) risk factors, history of familial autoimmunity and therapy was recorded. The presence of HLA “shared epitope” (SE) alleles and TNF gene polymorphism was assessed. A multivariate statistical analysis was performed. ExRA was found in 32% of the patients, of which nodulosis, Sjögren’s syndrome, and lung involvement were registered in 21%, 9%, and 4% of patients, respectively. Patients with ExRA were older than patients without it and they presented longer disease duration as well. Thus, an association between disease duration and ExRA manifestations was also observed. Patients with ExRA presented significant higher titers of anti-CCP antibodies as compared to patients without ExRA. Hypertension and thrombosis were significantly associated with ExRA. Never having smoked constituted a protective factor against ExRA onset. Associations between ExRA and the presence of traditional CV risk factors were also found. Our results show that duration of RA, CV disease and high titers of anti-CCP antibodies are associated with ExRA in Colombian patients with RA, and highlight the importance of preventing smoking in those who are prone to develop autoimmune diseases including RA.

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References

  1. Erhardt CC, Mumford PA, Venables PJ, Maini RN (1989) Factors predicting a poor life prognosis in rheumatoid arthritis: an eight year prospective study. Ann Rheum Dis 48:7–13

    Article  PubMed  CAS  Google Scholar 

  2. Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D (2008) Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 59:1690–1697

    Article  PubMed  Google Scholar 

  3. Ward MM (2008) Interpreting studies of cardiovascular mortality in rheumatoid arthritis: the importance of timing. Arthritis Rheum 59:1687–1689

    Article  PubMed  Google Scholar 

  4. Turesson C, O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL (2003) Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis 62:722–727

    Article  PubMed  CAS  Google Scholar 

  5. Turesson C, McClelland RL, Christianson TJ, Matteson EL (2007) Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis. Ann Rheum Dis 66:70–75

    Article  PubMed  CAS  Google Scholar 

  6. Calgüneri M, Ureten K, Akif Oztürk M, Onat AM, Ertenli I, Kiraz S, Akdogan A (2006) Extra-articular manifestations of rheumatoid arthritis: results of a university hospital of 526 patients in Turkey. Clin Exp Rheumatol 24:305–308

    PubMed  Google Scholar 

  7. Nikolaisen C, Rekvig OP, Nossent HC (2005) Rheumatoid factor by laser nephelometry and Waaler-Rose assay: prognostic value in patients with recent-onset rheumatoid arthritis. Scand J Rheumatol 34:269–276

    Article  PubMed  CAS  Google Scholar 

  8. Turesson C, Jacobsson L, Bergström U, Truedsson L, Sturfelt G (2000) Predictors of extra-articular manifestations in rheumatoid arthritis. Scand J Rheumatol 29:358–364

    Article  PubMed  CAS  Google Scholar 

  9. Bongartz T, Cantaert T, Atkins SR, Harle P, Myers JL, Turesson C, Ryu JH, Baeten D, Matteson EL (2007) Citrullination in extra-articular manifestations of rheumatoid arthritis. Rheumatology (Oxford) 46:70–75

    Article  CAS  Google Scholar 

  10. Albano SA, Santana-Sahagun E, Weisman MH (2001) Cigarette smoking and rheumatoid arthritis. Semin Arthritis Rheum 31:146–159

    Article  PubMed  CAS  Google Scholar 

  11. Turesson C, O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL (2002) Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis. J Rheumatol 29:62–67

    PubMed  Google Scholar 

  12. Turesson C, Eberhardt K, Jacobsson LT, Lindqvist E (2007) Incidence and predictors of severe extra-articular disease manifestations in an early rheumatoid arthritis inception cohort. Ann Rheum Dis 66:1543–1544

    Article  PubMed  CAS  Google Scholar 

  13. Liang KP, Liang KV, Matteson EL, McClelland RL, Christianson TJ, Turesson C (2006) Incidence of noncardiac vascular disease in rheumatoid arthritis and relationship to extraarticular disease manifestations. Arthritis Rheum 54:642–648

    Article  PubMed  Google Scholar 

  14. Turesson C, McClelland RL, Christianson TJ, Matteson EL (2007) Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis. Ann Rheum Dis 66:70–75

    Article  PubMed  CAS  Google Scholar 

  15. Libby P (2008) Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med 121:S21–S23

    Article  PubMed  CAS  Google Scholar 

  16. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  17. Gomez LM, Ruiz-Narvaez EA, Pineda-Tamayo R, Rojas-Villarraga A, Anaya JM (2007) TNF microsatellites polymorphism is associated with rheumatoid arthritis. Confirming evidence in north-western Colombians. Clin Exp Rheumatol 25:443–448

    PubMed  CAS  Google Scholar 

  18. Anaya JM, Correa PA, Mantilla RD, Jimenez F, Kuffner T, McNicholl JM (2001) Rheumatoid arthritis in African Colombians from Quibdo. Semin Arthritis Rheum 31:191–198

    Article  PubMed  CAS  Google Scholar 

  19. Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48

    Article  PubMed  CAS  Google Scholar 

  20. Patrick DL, Cheadle A, Thompson DC, Diehr P, Koepsell T, Kinne S (1994) The validity of self-reported smoking: a review and meta-analysis. Am J Public Health 84:1086–1093

    Article  PubMed  CAS  Google Scholar 

  21. Rojas-Villarraga A, Ortega-Hernandez OD, Gomez LF, Pardo AL, López-Guzmán S, Arango-Ferreira C et al (2008) Risk factors associated with different stages of atherosclerosis in colombian patients with rheumatoid arthritis. Semin Arhritis Rheum 38:71–82

    Article  Google Scholar 

  22. British Cardiac Society, British Hyperlipidaemia Association, British Hypertension Society, endorsed by the British Diabetic Association (1998) Joint British recommendations on prevention of coronary heart disease in clinical practice. Heart 80:S1–S29

    Google Scholar 

  23. Correa PA, Tobón GJ, Citera G, Cadena J, Schneeberger E, Camargo JF et al (2004) Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: relation with clinical features, cytokines and HLA-DRB1. Biomedica 24:140–152

    PubMed  Google Scholar 

  24. Hollingsworth PN, Dawkins RL, Peter JB (1996) Precise quantitation of antinuclear antibodies on HEp-2-cells without the need for serial dilution. Clin Diagn Lab Immunol 3:374–377

    PubMed  CAS  Google Scholar 

  25. Correa PA, Gomez LM, Cadena J, Anaya JM (2005) Autoimmunity and tuberculosis. Opposite association with TNF polymorphism. J Rheumatol 32:219–224

    PubMed  CAS  Google Scholar 

  26. Lee YH, Ji JD, Song GG (2007) Tumor necrosis factor-alpha promoter -308 A/G polymorphism and rheumatoid arthritis susceptibility: a metaanalysis. J Rheumatol 34:43–49

    PubMed  CAS  Google Scholar 

  27. Anaya JM, Correa PA, Mantilla RD, Arcos-Burgos M (2002) Rheumatoid arthritis association in Colombian population is restricted to HLA-DRB1*04 QRRAA alleles. Genes Immun 3:56–58

    Article  PubMed  CAS  Google Scholar 

  28. Gregersen PK, Silver J, Winchester RJ (1989) The shared epitope hypothesis: an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30:1205–1213

    Article  Google Scholar 

  29. Tezenas du Montcel S, Michou L, Petit-Teixeira E, Osorio J, Lemaire I, Lasbleiz S et al (2005) New Classification of HLA-DRB1 Alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility. Arthritis Rheum 52:1063–1068

    Article  CAS  Google Scholar 

  30. Anaya JM (2006) Severe rheumatoid valvular heart disease. Clin Rheumatol 25:743–745

    Article  PubMed  Google Scholar 

  31. Kim SK, Park SH, Shin IH, Choe JY (2008) Anti-cyclic citrullinated peptide antibody, smoking, alcohol consumption, and disease duration as risk factors for extraarticular manifestations in Korean patients with rheumatoid arthritis. J Rheumatol 35:995–1001

    Article  PubMed  Google Scholar 

  32. Turesson C, Jacobsson L, Bergström U (1999) Extra-articular rheumatoid arthritis: prevalence and mortality. Rheumatology (Oxford) 38:668–674

    Article  CAS  Google Scholar 

  33. Saag KG, Cerhan JR, Kolluri S, Ohashi K, Hunninghake GW, Schwartz DA (1997) Cigarette smoking and rheumatoid arthritis severity. Ann Rheum Dis 56:463–469

    Article  PubMed  CAS  Google Scholar 

  34. Zonana-Nacach A, Santana-Sahagún E, Jiménez-Balderas FJ, Camargo-Coronel A (2008) Prevalence and factors associated with metabolic syndrome in patients with rheumatoid arthritis and systemic lupus erythematosus. J Clin Rheumatol 14:74–77

    Article  PubMed  Google Scholar 

  35. Libby P (2008) Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med 121:S21–S31

    Article  PubMed  CAS  Google Scholar 

  36. Dessein PH, Joffe BI, Singh S (2005) Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis. Arthritis Res Ther 7:R634–R643

    Article  PubMed  CAS  Google Scholar 

  37. Korkmaz C, Us T, Kaşifoğlu T, Akgün Y (2006) Anti-cyclic citrullinated peptide (CCP) antibodies in patients with long-standing rheumatoid arthritis and their relationship with extra-articular manifestations. Clin Biochem 39:961–965

    Article  PubMed  CAS  Google Scholar 

  38. Turesson C, Jacobsson LT, Sturfelt G, Matteson EL, Mathsson L, Rönnelid J (2007) Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis. Ann Rheum Dis 66:59–64

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank all participants in this study, and our colleagues Luis M. Gomez, Lina M. Díaz and John Castiblanco for their assistance. This work was supported by grants from TCC Foundation, Medellin, School of Medicine, Rosario University, Bogotá, and the Fernando Chalem Rheumatology Award, Bogota, Colombia to J-MA.

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Correspondence to Juan-Manuel Anaya.

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Ortega-Hernandez, OD., Pineda-Tamayo, R., Pardo, A.L. et al. Cardiovascular disease is associated with extra-articular manifestations in patients with rheumatoid arthritis. Clin Rheumatol 28, 767–775 (2009). https://doi.org/10.1007/s10067-009-1145-8

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  • DOI: https://doi.org/10.1007/s10067-009-1145-8

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