Opinion | Published:

Rheumatoid arthritis and metabolic syndrome

Nature Reviews Rheumatology volume 10, pages 691696 (2014) | Download Citation


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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

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

  2. 2.

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

  3. 3.

    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).

  4. 4.

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

  5. 5.

    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).

  6. 6.

    , , , & Metabolic syndrome in rheumatoid arthritis. Mediators Inflamm. 2013, 710928 (2013).

  7. 7.

    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).

  8. 8.

    , , & Changes in lipid levels with inflammation and therapy in RA: a maturing paradigm. Nat. Rev. Rheumatol. 9, 513–523 (2013).

  9. 9.

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

  10. 10.

    , & Vascular effects of biologic agents in RA and spondyloarthropathies. Nat. Rev. Rheumatol. 5, 677–684 (2009).

  11. 11.

    , & The metabolic syndrome. Lancet 365, 1415–1428 (2005).

  12. 12.

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

  13. 13.

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

  14. 14.

    , & Metabolic syndrome and subclinical atherosclerosis in rheumatoid arthritis. J. Rheumatol. 33, 2425–2432 (2006).

  15. 15.

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

  16. 16.

    , , & Rheumatoid cachexia and cardiovascular disease. Nat. Rev. Rheumatol. 6, 445–451 (2010).

  17. 17.

    , , & 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).

  18. 18.

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

  19. 19.

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

  20. 20.

    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).

  21. 21.

    , , , & 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).

  22. 22.

    & Insulin resistance and impaired beta cell function in rheumatoid arthritis. Arthritis Rheum. 54, 2765–2775 (2006).

  23. 23.

    & 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).

  24. 24.

    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).

  25. 25.

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

  26. 26.

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

  27. 27.

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

  28. 28.

    , , , & Serum lipoprotein(a) and apolipoprotein(a) phenotypes in patients with rheumatoid arthritis. Arthritis Rheum. 42, 443–447 (1999).

  29. 29.

    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).

  30. 30.

    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).

  31. 31.

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

  32. 32.

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

  33. 33.

    , , & Independent relationship between circulating resistin concentrations and endothelial activation in rheumatoid arthritis. Ann. Rheum. Dis. 72, 1586–1588 (2013).

  34. 34.

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

  35. 35.

    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).

  36. 36.

    , , , & Rheumatoid arthritis impacts on the independent relationships between circulating adiponectin concentrations and cardiovascular metabolic risk. Mediators Inflamm. 2013, 461849 (2013).

  37. 37.

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

  38. 38.

    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).

  39. 39.

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

  40. 40.

    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).

  41. 41.

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

  42. 42.

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

  43. 43.

    , , , & Adiponectin is a mediator of the inverse association of adiposity with radiographic damage in rheumatoid arthritis. Arthritis Rheum. 61, 1248–1256 (2009).

  44. 44.

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

  45. 45.

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

  46. 46.

    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).

  47. 47.

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

  48. 48.

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

  49. 49.

    , & Effects of disease modifying agents and dietary intervention on insulin resistance and dyslipidemia in inflammatory arthritis: a pilot study. Arthritis Res. 4, R12 (2002).

  50. 50.

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

  51. 51.

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

Download references


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.

Author information


  1. Department of Angiology, Institute of Medicine, University of Debrecen Clinical Centre, Moricz Zs str, Debrecen 4032, Hungary.

    • György Kerekes
    •  & Pál Soltész
  2. Departments of Internal Medicine and Rheumatology, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands.

    • Michael T. Nurmohamed
  3. Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, Avenida de Valdecilla s/n, 39011 Santander, Spain.

    • Miguel A. González-Gay
  4. Division of Metabolic Diseases, Institute of Medicine, University of Debrecen Medical and Health Sciences Centre, Nagyerdei str 98, Debrecen 4032, Hungary.

    • Ildikó Seres
    •  & György Paragh
  5. Department of Rheumatology, Szent Ferenc Hospital, Csabai kapu street 41, Miskolc 3529, Hungary.

    • Zsófia Kardos
    • , Zsuzsa Baráth
    •  & László Tamási
  6. Department of Rheumatology, Institute of Medicine, University of Debrecen, Faculty of Medicine, Nagyerdei str. 98, Debrecen 4032, Hungary.

    • Zoltán Szekanecz


  1. Search for György Kerekes in:

  2. Search for Michael T. Nurmohamed in:

  3. Search for Miguel A. González-Gay in:

  4. Search for Ildikó Seres in:

  5. Search for György Paragh in:

  6. Search for Zsófia Kardos in:

  7. Search for Zsuzsa Baráth in:

  8. Search for László Tamási in:

  9. Search for Pál Soltész in:

  10. Search for Zoltán Szekanecz in:


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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Zoltán Szekanecz.

About this article

Publication history




Further reading