Rheumatoid arthritis and metabolic syndrome


Rheumatoid arthritis (RA), especially active disease, is associated with considerable changes in body composition, lipids, adipokines and insulin sensitivity. Metabolic changes, such as increased total cholesterol, LDL cholesterol and triglyceride levels, occur even in preclinical RA. Active RA is associated with decreased lipid levels, BMI, fat and muscle mass, as well as altered lipid profiles. Some of these changes are also seen in metabolic syndrome, and could increase cardiovascular mortality. Importantly, the systemic inflammation underlying RA is an independent risk factor for cardiovascular disease. This Perspectives article summarizes data on the associations of various components of metabolic syndrome with RA, and discusses the effects of biologic therapy on these factors. The authors propose that components of metabolic syndrome should be monitored in patients with RA throughout the disease course, and argue that optimal disease control using biologic agents might attenuate several adverse effects of metabolic syndrome in these patients.

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Figure 1: Obesity and cachexia and their association with markers of metabolic syndrome in RA.


  1. 1

    Dessein, P. H. et al. Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis. J. Rheumatol. 32, 435–442 (2005).

    PubMed  Google Scholar 

  2. 2

    Shoenfeld, Y. et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 112, 3337–3347 (2005).

    Article  Google Scholar 

  3. 3

    Kerekes, G. et al. Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity. J. Rheumatol. 35, 398–406 (2008).

    CAS  PubMed  Google Scholar 

  4. 4

    Nurmohamed, M. T. Cardiovascular risk in rheumatoid arthritis. Autoimmun. Rev. 8, 663–667 (2009).

    Article  Google Scholar 

  5. 5

    Peters, M. J. et al. 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 (2010).

    CAS  Article  Google Scholar 

  6. 6

    Ferraz-Amaro, I., González-Juanatey, C., López-Mejias, R., Riancho-Zarrabeitia, L. & González-Gay, M. A. Metabolic syndrome in rheumatoid arthritis. Mediators Inflamm. 2013, 710928 (2013).

    Article  Google Scholar 

  7. 7

    Myasoedova, E. et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann. Rheum. Dis. 70, 482–487 (2011).

    CAS  Article  Google Scholar 

  8. 8

    Robertson, J., Peters, M. J., McInnes, I. B. & Sattar, N. Changes in lipid levels with inflammation and therapy in RA: a maturing paradigm. Nat. Rev. Rheumatol. 9, 513–523 (2013).

    CAS  Article  Google Scholar 

  9. 9

    Gómez, R. et al. What's new in our understanding of the role of adipokines in rheumatic diseases? Nat. Rev. Rheumatol. 7, 528–536 (2011).

    Article  Google Scholar 

  10. 10

    Szekanecz, Z., Kerekes, G. & Soltész, P. Vascular effects of biologic agents in RA and spondyloarthropathies. Nat. Rev. Rheumatol. 5, 677–684 (2009).

    CAS  Article  Google Scholar 

  11. 11

    Eckel, R. H., Grundy, S. M. & Zimmet, P. Z. The metabolic syndrome. Lancet 365, 1415–1428 (2005).

    CAS  Article  Google Scholar 

  12. 12

    Zhang, J. et al. The risk of metabolic syndrome in patients with rheumatoid arthritis: a meta-analysis of observational studies. PLoS ONE 8, e78151 (2013).

    CAS  Article  Google Scholar 

  13. 13

    da Cunha, V. R. et al. Metabolic syndrome prevalence is increased in rheumatoid arthritis patients and is associated with disease activity. Scand. J. Rheumatol. 41, 186–191 (2012).

    CAS  Article  Google Scholar 

  14. 14

    Dessein, P. H., Tobias, M. & Veller, M. G. Metabolic syndrome and subclinical atherosclerosis in rheumatoid arthritis. J. Rheumatol. 33, 2425–2432 (2006).

    PubMed  Google Scholar 

  15. 15

    Wolfe, F. & Michaud, K. Effect of body mass index on mortality and clinical status in rheumatoid arthritis. Arthritis Care Res. (Hoboken) 64, 1471–1479 (2012).

    Article  Google Scholar 

  16. 16

    Summers, G. D., Metsios, G. S., Stavropoulos-Kalinoglou, A. & Kitas, G. D. Rheumatoid cachexia and cardiovascular disease. Nat. Rev. Rheumatol. 6, 445–451 (2010).

    Article  Google Scholar 

  17. 17

    Dessein, P. H., Woodiwiss, A. J., Norton, G. R. & Solomon, A. Rheumatoid arthritis is associated with reduced adiposity but not with unfavorable major cardiovascular risk factor profiles and enhanced carotid atherosclerosis in black Africans from a developing population: a cross-sectional study. Arthritis Res. Ther. 15, R96 (2013).

    Article  Google Scholar 

  18. 18

    Giles, J. T. et al. Abdominal adiposity in rheumatoid arthritis: association with cardiometabolic risk factors and disease characteristics. Arthritis Rheum. 62, 3173–3182 (2010).

    CAS  Article  Google Scholar 

  19. 19

    Symmons, D. P. Epidemiology of rheumatoid arthritis: determinants of onset, persistence and outcome. Best Pract. Res. Clin. Rheumatol. 16, 707–722 (2002).

    Article  Google Scholar 

  20. 20

    Wesley, A. et al. Association between body mass index and anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis: results from a population-based case–control study. Arthritis Care Res. (Hoboken) 65, 107–112 (2013).

    Article  Google Scholar 

  21. 21

    van der Helm-van Mil, A. H., van der Kooij, S. M., Allaart, C. F., Toes, R. E. & Huizinga, T. W. A high body mass index has a protective effect on the amount of joint destruction in small joints in early rheumatoid arthritis. Ann. Rheum. Dis. 67, 769–774 (2008).

    CAS  Article  Google Scholar 

  22. 22

    Dessein, P. H. & Joffe, B. I. Insulin resistance and impaired beta cell function in rheumatoid arthritis. Arthritis Rheum. 54, 2765–2775 (2006).

    CAS  Article  Google Scholar 

  23. 23

    Choy, E. & Sattar, N. Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions. Ann. Rheum. Dis. 68, 460–469 (2009).

    CAS  Article  Google Scholar 

  24. 24

    Georgiadis, A. N. et al. Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment—a prospective, controlled study. Arthritis Res. Ther. 8, R82 (2006).

    Article  Google Scholar 

  25. 25

    Myasoedova, E. et al. Total cholesterol and LDL levels decrease before rheumatoid arthritis. Ann. Rheum. Dis. 69, 1310–1314 (2010).

    CAS  Article  Google Scholar 

  26. 26

    Rizzo, M. et al. Atherogenic lipoprotein phenotype and LDL size and subclasses in drug-naïve patients with early rheumatoid arthritis. Atherosclerosis 207, 502–506 (2009).

    CAS  Article  Google Scholar 

  27. 27

    Kim, S. H. et al. Serum oxidized low-density lipoproteins in rheumatoid arthritis. Rheumatol. Int. 24, 230–233 (2004).

    CAS  Article  Google Scholar 

  28. 28

    Asanuma, Y., Kawai, S., Aoshima, H., Kaburaki, J. & Mizushima, Y. Serum lipoprotein(a) and apolipoprotein(a) phenotypes in patients with rheumatoid arthritis. Arthritis Rheum. 42, 443–447 (1999).

    CAS  Article  Google Scholar 

  29. 29

    Filippatos, T. D. et al. Effects of 12 months of treatment with disease-modifying anti-rheumatic drugs on low and high density lipoprotein subclass distribution in patients with early rheumatoid arthritis: a pilot study. Scand. J. Rheumatol. 42, 169–175 (2013).

    CAS  Article  Google Scholar 

  30. 30

    Charles-Schoeman, C. et al. Abnormal function of high-density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis. Arthritis Rheum. 60, 2870–2879 (2009).

    CAS  Article  Google Scholar 

  31. 31

    Tanimoto, N. et al. Serum paraoxonase activity decreases in rheumatoid arthritis. Life Sci. 72, 2877–2885 (2003).

    CAS  Article  Google Scholar 

  32. 32

    Schäffler, A. et al. Adipocytokines in synovial fluid. JAMA 290, 1709–1710 (2003).

    Article  Google Scholar 

  33. 33

    Dessein, P. H., Norton, G. R., Woodiwiss, A. J. & Solomon, A. Independent relationship between circulating resistin concentrations and endothelial activation in rheumatoid arthritis. Ann. Rheum. Dis. 72, 1586–1588 (2013).

    Article  Google Scholar 

  34. 34

    Ryo, M. et al. Adiponectin as a biomarker of the metabolic syndrome. Circ. J. 68, 975–981 (2004).

    CAS  Article  Google Scholar 

  35. 35

    Choi, H. M. et al. Adiponectin may contribute to synovitis and joint destruction in rheumatoid arthritis by stimulating vascular endothelial growth factor, matrix metalloproteinase-1, and matrix metalloproteinase-13 expression in fibroblast-like synoviocytes more than proinflammatory mediators. Arthritis Res. Ther. 11, R161 (2009).

    Article  Google Scholar 

  36. 36

    Dessein, P. H., Norton, G. R., Badenhorst, M., Woodiwiss, A. J. & Solomon, A. Rheumatoid arthritis impacts on the independent relationships between circulating adiponectin concentrations and cardiovascular metabolic risk. Mediators Inflamm. 2013, 461849 (2013).

    PubMed  PubMed Central  Google Scholar 

  37. 37

    Tilg, H. & Moschen, A. R. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat. Rev. Immunol. 6, 772–783 (2006).

    CAS  Article  Google Scholar 

  38. 38

    Otero, M. et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann. Rheum. Dis. 65, 1198–1201 (2006).

    CAS  Article  Google Scholar 

  39. 39

    González-Gay, M. A. et al. Anti-TNF-α therapy does not modulate leptin in patients with severe rheumatoid arthritis. Clin. Exp. Rheumatol. 27, 222–228 (2009).

    PubMed  Google Scholar 

  40. 40

    González-Gay, M. A. et al. Visfatin is not associated with inflammation or metabolic syndrome in patients with severe rheumatoid arthritis undergoing anti-TNF-α therapy. Clin. Exp. Rheumatol. 28, 56–62 (2010).

    PubMed  Google Scholar 

  41. 41

    Kaneko, K. et al. Chemerin activates fibroblast-like synoviocytes in patients with rheumatoid arthritis. Arthritis Res. Ther. 13, R158 (2011).

    CAS  Article  Google Scholar 

  42. 42

    Ha, Y. J. et al. Plasma chemerin levels in rheumatoid arthritis are correlated with disease activity rather than obesity. Joint Bone Spine 81, 189–190 (2014).

    CAS  Article  Google Scholar 

  43. 43

    Giles, J. T., Allison, M., Bingham, C. O. 3rd, Scott, W. M. Jr & Bathon, J. M. Adiponectin is a mediator of the inverse association of adiposity with radiographic damage in rheumatoid arthritis. Arthritis Rheum. 61, 1248–1256 (2009).

    CAS  Article  Google Scholar 

  44. 44

    Metsios, G. S. et al. Blockade of tumour necrosis factor-α in rheumatoid arthritis: effects on components of rheumatoid cachexia. Rheumatology (Oxford) 46, 1824–1827 (2007).

    CAS  Article  Google Scholar 

  45. 45

    Soubrier, M. et al. Effects of anti-tumor necrosis factor therapy on lipid profile in patients with rheumatoid arthritis. Joint Bone Spine 75, 22–24 (2008).

    CAS  Article  Google Scholar 

  46. 46

    van Sijl, A. M. et al. The effect of TNF-α blocking therapy on lipid levels in rheumatoid arthritis: a meta-analysis. Semin. Arthritis Rheum. 41, 393–400 (2011).

    CAS  Article  Google Scholar 

  47. 47

    McInnes, I. B. et al. Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study. Ann. Rheum. Dis. 73, 124–131 (2014).

    CAS  Article  Google Scholar 

  48. 48

    González-Gay, M. A. et al. Anti-TNF-α therapy modulates resistin in patients with rheumatoid arthritis. Clin. Exp. Rheumatol. 26, 311–316 (2008).

    PubMed  Google Scholar 

  49. 49

    Dessein, P. H., Joffe, B. I. & Stanwix, A. E. Effects of disease modifying agents and dietary intervention on insulin resistance and dyslipidemia in inflammatory arthritis: a pilot study. Arthritis Res. 4, R12 (2002).

    Article  Google Scholar 

  50. 50

    González-Gay, M. A. et al. Anti-tumor necrosis factor-α blockade improves insulin resistance in patients with rheumatoid arthritis. Clin. Exp. Rheumatol. 24, 83–86 (2006).

    PubMed  Google Scholar 

  51. 51

    González-Gay, M. A. et al. High-grade inflammation, circulating adiponectin concentrations and cardiovascular risk factors in severe rheumatoid arthritis. Clin. Exp. Rheumatol. 26, 596–603 (2008).

    PubMed  Google Scholar 

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The authors' research work is supported by research grant TÁMOP-4.2.2.A-11/1/KONV-2012-0031 for projects co-financed by the European Union and the European Social Fund (Z.S.); a bridging fund from the University of Debrecen Medical and Health Sciences Centre (Z.S.); a grant from Fondo de Investigaciones Sanitarias PI12/00060 (M.A.G.-G.) and RETICS programme RD12/0009/0013 from the Instituto de Salud Carlos III (M.A.G.-G.). The authors thank D. Kerekes for her expertise in preparing Figure 1.

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Z.S., G.K., Z.K. and Z.B. researched data for the article; Z.S. and G.K. wrote the manuscript. All authors made substantial contributions to discussion of content and to review and/or editing of the manuscript before submission.

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Correspondence to Zoltán Szekanecz.

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The authors declare no competing financial interests.

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Kerekes, G., Nurmohamed, M., González-Gay, M. et al. Rheumatoid arthritis and metabolic syndrome. Nat Rev Rheumatol 10, 691–696 (2014). https://doi.org/10.1038/nrrheum.2014.121

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