Obesity, adipose tissue and cardiovascular risk in rheumatoid arthritis


Authors: L. Šenolt;  M. Kuklová;  H. Hulejová;  L. Andres Cerezo
Authors‘ workplace: Revmatologický ústav, Klinika revmatologie 1. LF UK Praha
Published in: Čes. Revmatol., 20, 2012, No. 2, p. 43-52.
Category: Overview Reports

Overview

Obesity is associated with low inflammatory activity and is a risk factor for severe cardiovascular and metabolic diseases. The occurrence of cardiovascular diseases in rheumatoid arthritis is two times higher than in the general population. Rheumatoid arthritis is associated with an unfavourable metabolic condition - chronic inflammation, and lack of exercise causes loss of muscle mass and increased accumulation of adipose tissue. This condition is referred to as rheumatoid cachexia or sarcopenic obesity and occurs in individuals with increased or mainly with normal body mass index. Obesity in rheumatoid arthritis affects many aspects. It can be a potential risk factor for seronegative subset of the disease. Obese patients with rheumatoid arthritis tend to have more active disease course and worse quality of life. On the other hand, there is some evidence that obese patients with rheumatoid arthritis have less joint erosions, and slower structural progression. The higher incidence of cardiovascular disease and increased mortality in rheumatoid arthritis are probably not directly dependent on the body mass index, but rather dependent on the inflammatory activity of the disease. On the contrary, very thin patients appear to be the more vulnerable group. The aim of this review is to summarize the relationship between obesity, the severity of rheumatoid arthritis and cardiovascular risk profile in the context of new knowledge on the role of adipokines in the pathogenesis of metabolic and inflammatory diseases.

Key words:
rheumatoid arthritis, obesity, adipose tissue, mortality, inflammation, adipokines


Sources

1. Ebrahim S, Taylor F, Ward K, Beswick A, Burke M, Davey Smith G. Multiple risk factor interventions for primary prevention of coronary heart disease. Cochrane Database Syst Rev 2011;(1):CD001561.

2. Gabriel SE. Heart disease and rheumatoid arthritis: understanding the risk. Ann Rheum Dis 2010;69(Suppl) :i61–4.

3. World Health Organisation. Obesity: preventing andmanaging the global epidemic. Report of a WHO Consultation. World Health Organ Tech Rep Ser 2000;894:i– xii:1–253.

4. Summers GD, Metsios GS, Stavropoulos-Kalinoglou A, Kitas GD. Rheumatoid cachexia and cardiovascular disease. Nat Rev Rheumatol 2010;6:445-51.

5. Summers GD, Deighton CM, Rennie MJ, Booth AH. Rheumatoid cachexia: a clinical perspective. Rheumatology (Oxford) 2008;47:1124-31.

6. Bartfai T, Waalen J, Buxbaum JN. Adipose tissue as a modulator of clinical inflammation: does obesity reduce the prevalence of rheumatoid arthritis? J Rheumatol 2007;34(3):488-92.

7. Stavropoulos-Kalinoglou A, Metsios GS, Koutedakis Y et al. Redefining overweight and obesity in rheumatoid arthritis patients. Ann Rheum Dis 2007;66:1316–21.

8. Armstrong DJ, McCausland EM, Quinn AD, Wright GD. Obesity and cardiovascular risk factors in rheumatoid arthritis. Rheumatology 2006;45:782.

9. Giles JT, Ling SM, Ferrucci L, Bartlett SJ, Andersen RE, Towns M, et al. Abnormal body composition phenotypes in older rheumatoid arthritis patients: association with disease characteristics and pharmacotherapies. Arthritis Rheum 2008;59:807-15.

10. Rajbhandary R, Khezri A, Panush RS. Rheumatoid cachexia: what is it and why is it important? J Rheumatol 2011;38:406-8.

11. Rall LC, Roubenoff R. Rheumatoid cachexia: metabolic abnormalities, mechanisms and interventions. Rheumatology (Oxford). 2004;43:1219-23.

12. Rho YH, Chung CP, Solus JF, Raggi P, Oeser A, Gebretsadik T, et al. Adipocytokines, insulin resistance, and coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheum 2010;62:1259-64.

13. Cutolo M. Androgens in rheumatoid arthritis: when are they effectors? Arthritis Res Ther 2009;11:126.

14. Symmons DP, Bankhead CR, Harrison BJ et al. Blood transfusion, smoking, and obesity as risk factors for the development of rheumatoid arthritis: results from a primary care-based incident case-control study in Norfolk, England. Arthritis Rheum 1997;40:1955–61.

15. van der Helm-van Mil AH, van der Kooij SM, Allaart CF, Toes RE, Huizinga TW. 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 2008;67:769-74.

16. Pedersen M, Jacobsen S, Klarlund M, Pedersen BV, Wiik A, Wohlfahrt J, et al. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides. Arthritis Res Ther 2006;8(4):R133.

17. Mandl LA, Costenbader KH, Simard JF, Karlson EW. Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort study. Ann Rheum Dis 2009;68:514-8.

18. Stavropoulos-Kalinoglou A, Metsios GS, Panoulas VF, Nevill AM, Jamurtas AZ, Koutedakis Y, et al. Underweight and obese states both associate with worse disease activity and physical function in patients with established rheumatoid arthritis. Clin Rheumatol 2009;28(4):439-44.

19. Garcia-Poma A, Segami MI, Mora CS, Ugarte MF, Terrazas HN, Rhor EA, et al. Obesity is independently associated with impaired quality of life in patients with rheumatoid arthritis. Clin Rheumatol 2007; 26:1831-5.

20. Kaufmann J, Kielstein V, Kilian S, Stein G, Hein G. Relation between body mass index and radiological progression in patients with rheumatoid arthritis. J Rheumatol 2003;30:2350-5.

21. Westhoff G, Rau R, Zink A. Radiographic joint damage in early rheumatoid arthritis is highly dependent on body mass index. Arthritis Rheum 2007;56:3575-82.

22. Baker JF, George M, Baker DG, Toedter G, Von Feldt JM, Leonard MB. Associations between body mass, radiographic joint damage, adipokines and risk factors for bone loss in rheumatoid arthritis. Rheumatology (Oxford) 2011;50:2100-7.

23. Stavropoulos-Kalinoglou A, Metsios GS, Koutedakis Y, Kitas GD. Obesity in rheumatoid arthritis. Rheumatology (Oxford). 2011;50:450-62

24. Gómez R, Conde J, Scotece M, Gómez-Reino JJ, Lago F, Gualillo O. What’s new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol 2011;7:528-36.

25. Giles JT, Allison M, Bingham CO 3rd, Scott WM Jr, Bathon JM. Adiponectin is a mediator of the inverse association of adiposity with radiographic damage in rheumatoid arthritis. Arthritis Rheum 2009;61:1248-56.

26. Giles JT, van der Heijde DM, Bathon JM. Association of circulating adiponectin levels with progression of radiographic joint destruction in rheumatoid arthritis. Ann Rheum Dis 2011;7:1562-8.

27. Rho YH, Solus J, Sokka T, Oeser A, Chung CP, Gebretsadik T, et al. Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis. Arthritis Rheum 2009;60:1906-14.

28. Kozera L, Andrews J, Morgan AW. Cardiovascular risk and rheumatoid arthritis—the next step: differentiating true soluble biomarkers of cardiovascular risk from surrogate measures of inflammation. Rheumatology (Oxford). 2011;50(11):1944-54.

29. Gremese E, Ferraccioli G. The metabolic syndrome: the crossroads between rheumatoid arthritis and cardiovascular risk. Autoimmun Rev 2011;10:582-9.

30. Gonzalez A, Maradit Kremers H, Crowson CS, Ballman KV, Roger VL, Jacobsen SJ, et al. Do cardiovascular risk factors confer the same risk for cardiovascular outcomes in rheumatoid arthritis patients as in non-rheumatoid arthritis patients? Ann Rheum Dis 2008;67(1):64-9.

31. John H, Toms TE, Kitas GD. Rheumatoid arthritis: is it a coronary heart disease equivalent? Curr Opin Cardiol 2011;26(4):327-33.

32. Wolfe F, Michaud K. The risk of myocardial infarction and pharmacologic and nonpharmacologic myocardial infarction predictors in rheumatoid arthritis: a cohort and nested case-control analysis. Arthritis Rheum 2008;58(9): 2612-21.

33. Escalante A, Haas RW, del Rincón I. Paradoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammation. Arch Intern Med 2005;165(14):1624-9.

34. Naranjo A, Sokka T, Descalzo MA, Calvo-Alén J, HŅrslev-Petersen K, Luukkainen RK, et al; QUEST-RA Group. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Res Ther 2008;10(2):R30.

35. Greenberg JD, Furer V, Farkouh ME. Cardiovascular safety of biologic therapies for the treatment of RA. Nat Rev Rheumatol. 2011;8:13-21.

36. Atzeni F, Turiel M, Caporali R, Cavagna L, Tomasoni L, Sitia S, et al. The effect of pharmacological therapy on the cardiovascular system of patients with systemic rheumatic diseases. Autoimmun Rev 2010;9:835-9.

37. Giles JT, Allison M, Blumenthal RS, Post W, Gelber AC, Petri M, et al. Abdominal adiposity in rheumatoid arthritis: association with cardiometabolic risk factors and disease characteristics. Arthritis Rheum 2010;62(11):3173-82.

38. Engvall IL, Tengstrand B, Brismar K, Hafström I. Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months. Arthritis Res Ther 2010;12(5):R197.

39. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005;115:911-9.

40. Gómez R, Conde J, Scotece M, Gómez-Reino JJ, Lago F, Gualillo O. What’s new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol 2011;7(9):528-36.

41. Stofkova A. Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity. Endocr Regul 2009;43:157-68.

42. Batra A, Okur B, Glauben R, Erben U, Ihbe J, Stroh T, et al. Leptin: a critical regulator of CD4+ T-cell polarization in vitro and in vivo. Endocrinology. 2010;151:56-62.

43. Bokarewa M, Bokarew D, Hultgren O, Tarkowski A. Leptin consumption in the inflamed joints of patients with rheumatoid arthritis. Ann Rheum Dis 2003;62:952–6.

44. Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gómez-Reino JJ, et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 2006;65:1198–201.

45. Popa C, Netea MG, de Graaf J, van den Hoogen FH, Radstake TR, Toenhake-Dijkstra H, et al. Circulating leptin and adiponectin concentrations during tumor necrosis factor blockade in patients with active rheumatoid arthritis. J Rheumatol. 2009;36:724-30.

46. Šenolt L, Kuklová M, Cerezo LA, Hulejová H, Filková M, Bošanská L, et al. Adipokine profile is modulated in subcutaneous adipose tissue by TNFαinhibitors in patients with rheumatoid arthritis. Ann Rheum Dis 2011;70:2054-6.

47. Stannus OP, Jones G, Quinn SJ, Cicuttini FM, Dore D, Ding C. The association between leptin, interleukin-6, and hip radiographic osteoarthritis in older people: a cross-sectional study. Arthritis Res Ther 2010;12(3):R95.

48. Haluzík M, Parízková J, Haluzík MM. Adiponectin and its role in the obesity-induced insulin resistance and related complications. Physiol Res 2004;53(2):123-9.

49. Senolt L, Pavelka K, Housa D, Haluzík M. Increased adiponectin is negatively linked to the local inflammatory process in patients with rheumatoid arthritis. Cytokine 2006;35:247-52.

50. Frommer KW, Zimmermann B, Meier FM, Schröder D, Heil M, Schäffler A, et al. Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritis. Arthritis Rheum 2010;62:2886-99.

51. Filková M, Haluzík M, Gay S, Senolt L. The role of resistin as a regulator of inflammation: Implications for various human pathologies. Clin Immunol 2009;133:157-70.

52. Senolt L, Housa D, Vernerová Z, Jirásek T, Svobodová R, Veigl D, Anderlová K, et al. Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum. Ann Rheum Dis 2007;66:458-63.

53. Gonzalez-Gay MA, Garcia-Unzueta MT, Gonzalez-Juanatey C, Miranda-Filloy JA, Vazquez-Rodriguez TR, De Matias JM, et al. Anti-TNF-alpha therapy modulates resistin in patients with rheumatoid arthritis. Clin Exp Rheumatol 2008;26:311-6.

54. Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A. Resistin, an adipokine with potent proinflammatory properties. J Immunol 2005;174:5789-95.

55. Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, et al. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 2007;178:1748–58.

56. Brentano F, Schorr O, Ospelt C, Stanczyk J, Gay RE, Gay S, et al. Pre-B cell colonyenhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities. Arthritis Rheum 2007;56:2829–39.

57. Gonzalez-Gay MA, Vazquez-Rodriguez TR, Garcia-Unzueta MT, Berja A, Miranda-Filloy JA, de Matias JM, et al. Visfatin is not associated with inflammation or metabolic syndrome in patients with severe rheumatoid arthritis undergoing anti-TNF-alpha therapy. Clin Exp Rheumatol 2010;28:56-62.

58. Senolt L, Kryštůfková O, Hulejová H, Kuklová M, Filková M, Cerezo LA, et al. The level of serum visfatin (PBEF) is associated with total number of B cells in patients with rheumatoid arthritis and decreases following B cell depletion therapy. Cytokine 2011;55:116-21.

59. Busso N, Karababa M, Nobile M, Rolaz A, Van Gool F, Galli M, et al. Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD. PLoS One 2008;3(5):e2267.

60. Senolt L, Polanská M, Filková M, Cerezo LA, Pavelka K, Gay S, et al. Vaspin and omentin: new adipokines differentially regulated at the site of inflammation in rheumatoid arthritis. Ann Rheum Dis 2010;69:1410-1.

61. Makowski L, Brittingham KC, Reynolds JM, Suttles J, Hotamisligil GS. The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor χ and I@ kinase activities. J Biol Chem 2005; 280:12888-12895.

62. Peeters W, de Kleijn DP, Vink A, van de Weg S, Schoneveld AH, Sze SK, et al. Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events. Eur Heart J 2011;32:1758-68.

63. Klaasen R, Wijbrandts CA, Gerlag DM, Tak PP. Body mass index and clinical response to infliximab in rheumatoid arthritis. Arthritis Rheum 2011;63:359-64.

Labels
Dermatology & STDs Paediatric rheumatology Rheumatology
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account