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Rheumatoid factor positivity increases all-cause and cancer mortality: a cohort study

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Abstract

The aim of this study was to determine whether rheumatoid factor (RF) is associated with mortality from all-cause, cardiovascular disease (CVD), and cancer in the healthy adults. We recruited South Korean health check-up examinees without rheumatoid arthritis (RA). A cohort study was performed in 295,837 participants presumably free of osteoarthritis or RA, and who had undergone health screening between 2002 and 2012 and been followed up to determine the risk of all-cause, CVD, and cancer-specific mortality with respect to the presence or titer of RF. To determine whether the participants were deceased, we used National Death Index death certificates. The prevalence of RF positivity (≥20 IU/mL) was 4.4%. During 1,447,403 person-years of follow-up, 1402 participants died. Comparing subjects negative for RF with those positive for RF, the multivariable adjusted hazard ratio (HR; 95% CI) for all-cause and cancer mortality in subjects with RF-positivity was 1.50 (1.19–1.90) and 1.56 (1.12–2.16), respectively. Also, all-cause and cancer mortality risk was significantly greater in subjects with an RF titer greater than 100 IU/mL than in those with RF-negativity (HR = 2.68, 95% CI = 1.72–4.19; HR = 2.89, 95% CI = 1.58–5.28, respectively) after adjusting for multiple confounders. However, the HR for cardiovascular mortality was not higher in subjects with RF positivity than in those with RF negativity (HR = 0.98, 95% CI = 0.45–2.11). In Korean healthy adults, presumably without RA, RF was associated with a greater risk of all-cause and cancer mortality.

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References

  1. Shim CN, Hwang JW, Lee J, Koh EM, Cha HS, Ahn JK (2012) Prevalence of rheumatoid factor and parameters associated with rheumatoid factor positivity in Korean health screening subjects and subjects with hepatitis B surface antigen. Mod Rheumatol 22:885–891

    Article  CAS  PubMed  Google Scholar 

  2. Husby G, Gran JT, Johannessen A (1988) Epidemiological and genetic aspects of IgM rheumatoid factors. Scand J Rheumatol Suppl 75:213–218

    Article  CAS  PubMed  Google Scholar 

  3. van Schaardenburg D, Lagaay AM, Otten HG, Breedveld FC (1993) The relation between class-specific serum rheumatoid factors and age in the general population. Br J Rheumatol 32:546–549

    Article  PubMed  Google Scholar 

  4. Ingegnoli F, Castelli R, Gualtierotti R (2013) Rheumatoid factors: clinical applications. Dis Markers 35:727–734

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wallberg-Jonsson S, Ohman ML, Dahlqvist SR (1997) Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden. J Rheumatol 24:445–451

    CAS  PubMed  Google Scholar 

  6. Mikuls TR, Saag KG, Criswell LA, Merlino LA, Kaslow RA, Shelton BJ, Cerhan JR (2002) Mortality risk associated with rheumatoid arthritis in a prospective cohort of older women: results from the Iowa Women’s Health Study. Ann Rheum Dis 61:994–999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gonzalez A, Icen M, Kremers HM, Crowson CS, Davis JM 3rd, Therneau TM, Roger VL, Gabriel SE (2008) Mortality trends in rheumatoid arthritis: the role of rheumatoid factor. J Rheumatol 35:1009–1014

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ajeganova S, Humphreys JH, Verheul MK, van Steenbergen HW, van Nies JA, Hafstrom I, Svensson B, Huizinga TW, Trouw LA, Verstappen SM, van der Helm-van Mil AH (2016) Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts. Ann Rheum Dis 75:1924–1932

    Article  CAS  PubMed  Google Scholar 

  9. Jacobsson LT, Knowler WC, Pillemer S, Hanson RL, Pettitt DJ, Nelson RG, del Puente A, McCance DR, Charles MA, Bennett PH (1993) Rheumatoid arthritis and mortality. A longitudinal study in Pima Indians. Arthritis Rheum 36:1045–1053

    Article  CAS  PubMed  Google Scholar 

  10. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinheksel SM, Cathey MA (1994) The mortality of rheumatoid arthritis. Arthritis Rheum 37:481–494

    Article  CAS  PubMed  Google Scholar 

  11. Humphreys JH, van Nies JA, Chipping J, Marshall T, van der Helm-van Mil AH, Symmons DP, Verstappen SM (2014) Rheumatoid factor and anti-citrullinated protein antibody positivity, but not level, are associated with increased mortality in patients with rheumatoid arthritis: results from two large independent cohorts. Arthritis Res Ther 16:483

    Article  PubMed  PubMed Central  Google Scholar 

  12. Jonsson T, Thorsteinsson J, Valdimarsson H (1992) Rheumatoid factor isotypes and cancer prognosis. Cancer 69:2160–2165

    Article  CAS  PubMed  Google Scholar 

  13. Heliovaara M, Aho K, Knekt P, Aromaa A, Maatela J, Reunanen A (1995) Rheumatoid factor, chronic arthritis and mortality. Ann Rheum Dis 54:811–814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chang Y, Ryu S, Choi Y, Zhang Y, Cho J, Kwon MJ, Hyun YY, Lee KB, Kim H, Jung HS, Yun KE, Ahn J, Rampal S, Zhao D, Suh BS, Chung EC, Shin H, Pastor-Barriuso R, Guallar E (2016) Metabolically Healthy Obesity and Development of Chronic Kidney Disease: a Cohort Study. Ann Intern Med 164:305–312

    Article  PubMed  Google Scholar 

  15. Kim MK, Lee WY, Kang JH, Kang JH, Kim BT, Kim SM, Kim EM, Suh SH, Shin HJ, Lee KR, Lee KY, Lee SY, Lee SY, Lee SK, Lee CB, Chung S, Jeong IK, Hur KY, Kim SS, Woo JT (2014) 2014 clinical practice guidelines for overweight and obesity in Korea. Endocrinol Metab (Seoul) 29:405–409

    Article  Google Scholar 

  16. Zhang Y, Chang Y, Ryu S, Cho J, Lee WY, Rhee EJ, Kwon MJ, Pastor-Barriuso R, Rampal S, Han WK, Shin H, Guallar E (2014) Thyroid hormones and mortality risk in euthyroid individuals: the Kangbuk Samsung health study. J Clin Endocrinol Metab 99:2467–2476

    Article  CAS  PubMed  Google Scholar 

  17. Chang Y, Kim BK, Yun KE, Cho J, Zhang Y, Rampal S, Zhao D, Jung HS, Choi Y, Ahn J, Lima JA, Shin H, Guallar E, Ryu S (2014) Metabolically-healthy obesity and coronary artery calcification. J Am Coll Cardiol 63:2679–2686

    Article  PubMed  Google Scholar 

  18. Pavillon G, Maguin P (1993) The 10th revision of the International Classification of Diseases. Rev Epidemiol Sante Publique 41:253–255

    CAS  PubMed  Google Scholar 

  19. Ajeganova S, Humphreys JH, Verheul MK, van Steenbergen HW, van Nies JA, Hafstrom I, Svensson B, Huizinga TW, Trouw LA, Verstappen SM, van der Helm-van Mil AH (2016) Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts. Ann Rheum Dis 75:1924–1932

    Article  CAS  PubMed  Google Scholar 

  20. Goodson NJ, Symmons DP, Scott DG, Bunn D, Lunt M, Silman AJ (2005) Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort. Arthritis Rheum 52:2293–2299

    Article  CAS  PubMed  Google Scholar 

  21. Peters MJ, Symmons DP, McCarey D, Dijkmans BA, Nicola P, Kvien TK, McInnes IB, Haentzschel H, Gonzalez-Gay MA, Provan S, Semb A, Sidiropoulos P, Kitas G, Smulders YM, Soubrier M, Szekanecz Z, Sattar N, Nurmohamed MT (2010) EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 69:325–331

    Article  CAS  PubMed  Google Scholar 

  22. Tomasson G, Aspelund T, Jonsson T, Valdimarsson H, Felson DT, Gudnason V (2010) Effect of rheumatoid factor on mortality and coronary heart disease. Ann Rheum Dis 69:1649–1654

    Article  CAS  PubMed  Google Scholar 

  23. Veronese N, Cereda E, Maggi S, Luchini C, Solmi M, Smith T, Denkinger M, Hurley M, Thompson T, Manzato E, Sergi G, Stubbs B (2016) Osteoarthritis and mortality: a prospective cohort study and systematic review with meta-analysis. Semin Arthritis Rheum 46:160–167

    Article  PubMed  Google Scholar 

  24. Hawker GA, Croxford R, Bierman AS, Harvey PJ, Ravi B, Stanaitis I, Lipscombe LL (2014) All-cause mortality and serious cardiovascular events in people with hip and knee osteoarthritis: a population based cohort study. PLoS One 9:e91286

    Article  PubMed  PubMed Central  Google Scholar 

  25. Veronese N, Trevisan C, De Rui M, Bolzetta F, Maggi S, Zambon S, Musacchio E, Sartori L, Perissinotto E, Crepaldi G, Manzato E, Sergi G (2016) Association of Osteoarthritis With Increased Risk of Cardiovascular Diseases in the Elderly: Findings From the Progetto Veneto Anziano Study Cohort. Arthritis Rheumatol 68:1136–1144

    CAS  PubMed  Google Scholar 

  26. Newkirk MM (2002) Rheumatoid factors: what do they tell us? J Rheumatol 29:2034–2040

    CAS  PubMed  Google Scholar 

  27. Thorsteinsson J, Bjornsson OJ, Kolbeinsson A, Allander E, Sigfusson N, Olafsson O (1975) A population study of rheumatoid factor in Iceland. A 5-year follow-up of 50 women with rheumatoid factor (RF). Ann Clin Res 7:183–194

    CAS  PubMed  Google Scholar 

  28. Goodson NJ, Wiles NJ, Lunt M, Barrett EM, Silman AJ, Symmons DP (2002) Mortality in early inflammatory polyarthritis: cardiovascular mortality is increased in seropositive patients. Arthritis Rheum 46:2010–2019

    Article  PubMed  Google Scholar 

  29. Singh AG, Singh S, Matteson EL (2016) Rate, risk factors and causes of mortality in patients with Sjogren’s syndrome: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford) 55:450–460

    Article  Google Scholar 

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Author notes

  1. Yoosoo Chang and Seungho Ryu contributed equally to this work.

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Joong Kyong Ahn

  2. Division of Rheumatology, Department of Internal Medicine, National Police Hospital, Seoul, South Korea

    Jiwon Hwang

  3. Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Yoosoo Chang & Seungho Ryu

  4. Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Yoosoo Chang & Seungho Ryu

  5. Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea

    Yoosoo Chang & Seungho Ryu

Authors
  1. Joong Kyong Ahn
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  2. Jiwon Hwang
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  4. Seungho Ryu
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Corresponding authors

Correspondence to Yoosoo Chang or Seungho Ryu.

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Conflict of interest

All authors declare no conflict of interest. No grant or industry support was received for this study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration Helsinki and its later amendments or comparable ethical standards.

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This study does not have any funding support.

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Ahn, J.K., Hwang, J., Chang, Y. et al. Rheumatoid factor positivity increases all-cause and cancer mortality: a cohort study. Rheumatol Int 37, 1135–1143 (2017). https://doi.org/10.1007/s00296-017-3738-x

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  • DOI: https://doi.org/10.1007/s00296-017-3738-x

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