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Cardiovascular Risk in Rheumatoid Arthritis and Systemic Autoimmune Rheumatic Disorders: a Suggested Model of Preventive Strategy

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Abstract

The pathogenesis of accelerated cardiovascular damage commonly characterizing patients affected by systemic chronic inflammatory and autoimmune rheumatic disorders is quite complex and still not fully clarified. However, it is well accepted that a strong relationship between multiple factors, including both traditional cardiovascular risk factors and disease-related inflammatory and autoimmune mechanisms, may in part explain the precocious atherosclerotic vessel damage and the increased incidence of cardiovascular events. Nevertheless, although several recent studies focused their attention on the investigation of these complex mechanisms, data regarding possible preventive strategies aimed to reduce long-term cardiovascular risk in these subjects are still lacking and not conclusive. In this setting, the early introduction of evidence-based preventive measures for the correct management of patients with systemic autoimmune disorders would be of extreme importance to reduce subclinical atherosclerosis incidence and possible major cardiovascular events.

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References

  1. Holmqvist ME, Wedrén S, Jacobsson LTH et al (2010) Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis among patients diagnosed between 1995 and 2006. J Intern Med 268:578–585

    Article  PubMed  CAS  Google Scholar 

  2. Shoenfeld Y, Gerli R, Doria A et al (2005) Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 112:3337–3347

    Article  PubMed  Google Scholar 

  3. Nurmohamed MT (2009) Cardiovascular risk in rheumatoid arthritis. Autoimmun Rev 8:663–667

    Article  PubMed  Google Scholar 

  4. Bartoloni Bocci E, Luccioli F, Angrisani C, Moscatelli S, Alunno A, Gerli R (2007) Accelerated atherosclerosis in systemic lupus erythematosus and other connective tissue diseases. Expert Rev Clin Immunol 3:531–541

    Article  PubMed  CAS  Google Scholar 

  5. Sarzi-Puttini P, Azteni F, Gerli R et al (2010) Cardiac involvement in systemic rheumatic diseases: an update. Autoimmun Rev 9:849–852

    Article  PubMed  Google Scholar 

  6. Gerli R, Vaudo G, Bocci EB et al (2010) Functional impairment of arterial wall in primary Sjögren’s syndrome: combined action of immunological and inflammatory factors. Arthritis Care Res 62:712–718

    Article  Google Scholar 

  7. Vaudo G, Bocci EB, Shoenfeld Y et al (2005) Precocious intima-media thickening in patients with primary Sjögren’s syndrome. Arthritis Rheum 52:3890–3897

    Article  PubMed  Google Scholar 

  8. Bartoloni E, Shoenfeld Y, Gerli R (2010) Inflammatory and autoimmune mechanisms in the induction of atherosclerotic damage in systemic rheumatic diseases: two faces of the same coin. Arthritis Care Res. doi:10.1002/acr.20322

  9. Bartoloni E, Alunno A, Luccioli F et al (2010) Atherosclerotic vascular damage and rheumatoid arthritis: a complex but intriguing link. Expert Rev Cardiovasc Ther 8:1309–1316

    Article  PubMed  Google Scholar 

  10. Bartoloni E, Alunno A, Bistoni O, Gerli R (2010) How early is the atherosclerotic risk in rheumatoid arthritis? Autoimmun Rev 9:701–707

    Article  PubMed  CAS  Google Scholar 

  11. Holmqvist ME, Wedrèn S, Jacobsson LT et al (2010) No increased occurrence of ischemic heart disease prior to the onset of rheumatoid arthritis. Results from two Swedish population-based rheumatoid arthritis cohorts. Arthritis Rheum 60:2861–2869

    Article  Google Scholar 

  12. Gabriel SE, Crowson CS, Kremers HM et al (2003) Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years. Arthritis Rheum 48:54–58

    Article  PubMed  Google Scholar 

  13. Solomon DH, Goodson NJ, Katz JN et al (2006) Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis 65:1608–1612

    Article  PubMed  CAS  Google Scholar 

  14. Peters MJ, Symmons DP, McCarey D et al (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  PubMed  CAS  Google Scholar 

  15. Toms TE, Panoulas VF, Douglas KM et al (2010) Statin use in rheumatoid arthritis in relation to actual cardiovascular risk: evidence for substantial undertreatment of lipid-associated cardiovascular risk? Ann Rheum Dis 69:683–688

    Article  PubMed  CAS  Google Scholar 

  16. Metsios G, Stavropoulos-Kalinoglou A, Sandoo A et al (2010) Vascular function and inflammation in rheumatoid arthritis: the role of physical activity. Cardiovasc Med J 4:89–96

    Google Scholar 

  17. Libby P, Okamoto Y, Rocha V, Folco E (2010) Inflammation in atherosclerosis: transition from theory to practice. Circ J 74:213–220

    Article  PubMed  CAS  Google Scholar 

  18. Turesson C, Matteson EL (2007) Cardiovascular risk factors, fitness and physical activity in rheumatic diseases. Curr Opin Rheumatol 19:190–196

    Article  PubMed  Google Scholar 

  19. Volkmann ER, Grossman JM, Sahakian LJ et al (2010) Low physical activity is associated with proinflammatory high-density lipoprotein and increased subclinical atherosclerosis in women with systemic lupus erythematosus. Arthritis Care Res 62:258–265

    Article  Google Scholar 

  20. McMahon M, Grossman I, Skaggs B et al (2009) Dysfunctional proinflammatory high density lipoproteins confer increased risk for atherosclerosis in women with systemic lupus erythematosus. Arthritis Rheum 60:2428–2437

    Article  PubMed  CAS  Google Scholar 

  21. Steiner G, Urowitz M (2009) Lipid profiles in patients with rheumatoid arthritis: mechanisms and the impact of treatment. Arthritis Rheum 38:372–381

    Article  CAS  Google Scholar 

  22. Gerli R, Bocci EB, Vaudo G, Marchesi S, Vitali C, Shoenfeld Y (2006) Traditional cardiovascular risk factors in primary Sjögren’syndrome: role of dyslipidemia [letter]. Rheumatology 45:1580–1581

    Article  PubMed  CAS  Google Scholar 

  23. Abeles AM, Pillinger MH (2006) Statins are anti-inflammatory and immunomodulatory agents: a future in rheumatologic therapy. Arthritis Rheum 54:393–407

    Article  PubMed  CAS  Google Scholar 

  24. Tristano AG, Fuller K (2006) Immunomodulatory effects of statins and autoimmune rheumatic diseases: novel intracellular mechanism involved. Int Immunopharmacol 6:1833–1846

    Article  PubMed  CAS  Google Scholar 

  25. Bisoendial RJ, Stroes ES, Kastelein JJ, Tak PP (2010) Targeting cardiovascular risk in rheumatoid arthritis: a dual role for statins. Nat Rev Rheumatol 6:157–164

    Article  PubMed  CAS  Google Scholar 

  26. Jick SS, Choi H, Li L, McInnes IB, Sattar N (2009) Hyperlipidaemia, statin use and the risk of developing rheumatoid arthritis. Ann Rheum Dis 68:546–551

    Article  PubMed  CAS  Google Scholar 

  27. Paraskevas KI (2008) Statin treatment for rheumatoid arthritis: a promising novel indication. Clin Rheumatol 27:281–287

    Article  PubMed  Google Scholar 

  28. McCarey D, McInnes IB, Madhok R et al (2004) Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet 363:2015–2021

    Article  PubMed  CAS  Google Scholar 

  29. Lodi S, Evans SJ, Egger P, Carpenter J (2010) Is there an anti-inflammatory effect of statins in rheumatoid arthritis? Analysis of a large routinely collected claims database. Br J Clin Pharmacol 69:85–94

    Article  PubMed  CAS  Google Scholar 

  30. Petri M, Kiani AN, Post W et al (2006) Lupus Atherosclerosis Prevention Study (LAPS): randomized double blind placebo controlled trial of atorvastatin versus placebo. Arthritis Rheum 54:S520

    Google Scholar 

  31. Choy E, Sattar N (2009) 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

    Article  PubMed  CAS  Google Scholar 

  32. Dixon WG, Watson KD, Lunt M et al (2007) Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis α therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 56:2905–2912

    Article  PubMed  CAS  Google Scholar 

  33. Pérez-De-Lis M, Akasbi M, Sisó A et al (2010) Cardiovascular risk factors in primary Sjögren’s syndrome: a case–control study in 624 patients. Lupus 19:941–948

    Article  PubMed  Google Scholar 

  34. Kitas G, Gabriel SE (2011) Cardiovascular disease in rheumatoid arthritis: state of the art and future perspectives. Ann Rheum Dis 70:8–14

    Article  PubMed  Google Scholar 

  35. Panoulas VF, Douglas KM, Smith JP et al (2009) Transforming growth factor-beta1 869T/C, but not interleukin-6-174G/C, polymorphism associates with hypertension in rheumatoid arthritis. Rheumatology 48:113–118

    Article  PubMed  CAS  Google Scholar 

  36. Panoulas VF, Toms TE, Metsios GS et al (2010) Target organ damage in patients with rheumatoid arthritis: the role of blood pressure and heart rate. Atherosclerosis 209:255–260

    Article  PubMed  CAS  Google Scholar 

  37. Serelis J, Panagiotakos DB, Mavrommati M, Skopouli FN (2010) Cardiovascular disease is related to hypertension in patients with rheumatoid arthritis: a Greek Cohort Study. J Rheumatol. doi:10.3899/jrheum.100564

  38. Danowski A, Leitão N, de Azevedo M, de Souza Papi JA, Petri M (2009) Determinants of risk for venous and arterial thrombosis in primary antiphospholipid syndrome and in antiphospholipid syndrome with systemic lupus erythematosus. J Rheumatol 36:1195–1199

    Article  PubMed  CAS  Google Scholar 

  39. Flammer AJ, Sudano I, Hermann F et al (2008) Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis. Circulation 117:2262–2269

    Article  PubMed  CAS  Google Scholar 

  40. Perry ME, Chee MM, Ferrell WR, Lockhart JC, Sturrock RD (2008) Angiotensin receptor blockers reduce erythrocyte sedimentation rate levels in patients with rheumatoid arthritis. Ann Rheum Dis 67:1646–1647

    Article  PubMed  CAS  Google Scholar 

  41. Durán-Barragán S, McGwin G Jr, Vilá LM, Reveille JD, Alarcón GS (2008) Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus—results from LUMINA (LIX): a multiethnic US cohort. Rheumatology 47:1093–1096

    Article  PubMed  Google Scholar 

  42. Bussone G, Bérezné A, Pestre V, Guillevin L, Mouthon L (2010) The scleroderma kidney: progress in risk factors, therapy, and prevention. Curr Rheumatol Rep. doi:10.1007/s11926-010-0145-7

  43. van Halm VP, Peters MJ, Voskuyl AE et al (2009) Rheumatoid arthritis versus diabetes as a risk factor for cardiovascular disease: a cross-sectional study, the CARRE investigation. Ann Rheum Dis 68:1395–1400

    Article  PubMed  Google Scholar 

  44. Parker B, Bruce IN (2010) The metabolic syndrome in systemic lupus erythematosus. Rheum Dis Clin North Am 36:81–97

    Article  PubMed  Google Scholar 

  45. Sabio JM, Vargas-Hito J, Zamora-Pasadas M et al (2009) Metabolic syndrome is associated with increased arterial stiffness and biomarkers of subclinical atherosclerosis in patients with systemic lupus erythematosus. J Rheumatol 36:2204–2211

    Article  PubMed  CAS  Google Scholar 

  46. Shahin D, Eltoraby E, Mesbah A, Houssein M (2010) Insulin resistance in early untreated rheumatoid arthritis patients. Clin Biochem 43:661–665

    Article  PubMed  CAS  Google Scholar 

  47. Chung CP, Oeser A, Solus JF et al (2008) Inflammation associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthritis Rheum 58:2105–2112

    Article  PubMed  CAS  Google Scholar 

  48. Venegas-Pont M, Sartori-Valinotti JC, Maric C et al (2009) Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus. Am J Physiol Regul Integr Comp Physiol 296:R1282–R1289

    Article  PubMed  CAS  Google Scholar 

  49. Zhao W, Thacker SG, Hodgin JB (2009) The peroxisome proliferator-activated receptor gamma agonist pioglitazone improves cardiometabolic risk and renal inflammation in murine lupus. J Immunol 183:2729–2740

    Article  PubMed  CAS  Google Scholar 

  50. Kaprove Penn S, Kao AH, Schott LL et al (2010) Hydroxychloroquine and glycemia in women with rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol 37:1136–1142

    Article  Google Scholar 

  51. Morris SJ, Wasko MC, Antohe JL et al (2010) Hydroxychloroquine use is associated with improvement in lipid profiles in rheumatoid arthritis patients. Arthritis Rheum. doi:10.1002/acr.20393

  52. Jung H, Bobba R, Su J et al (2010) The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus. Arthritis Rheum 62:863–868

    Article  PubMed  CAS  Google Scholar 

  53. Turesson C, Jacobsson LT, Matteson E (2008) Cardiovascular co-morbidity in rheumatic diseases. Vasc Health Risk Manag 4:605–614

    PubMed  Google Scholar 

  54. del Rincon I, O’Leary DH, Haas RW et al (2004) Effect of glucocorticoids on the arteries in rheumatoid arthritis. Arthritis Rheum 50:3813–3822

    Article  PubMed  Google Scholar 

  55. Westlake SL, Colebatch AN, Baird J (2010) The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology 49:295–307

    Article  PubMed  CAS  Google Scholar 

  56. Hochberg MC, Johnston SS, John AK (2008) The incidence and prevalence of extra-articular and systemic manifestations in a cohort of newly-diagnosed patients with rheumatoid arthritis between 1999 and 2006. Curr Med Res Opin 24:469–480

    Article  PubMed  Google Scholar 

  57. Ristic G, Lepic T, Glisic B et al (2010) Rheumatoid arthritis is an independent risk factor for increased carotid intima-media thickness: impact of anti-inflammatory treatment. Rheumatology 49:1076–1081

    Article  PubMed  CAS  Google Scholar 

  58. Georgiadis AN, Voulgari PV, Argyropoulou MI et al (2008) Early treatment reduces the cardiovascular risk factors in newly diagnosed rheumatoid arthritis patients. Semin Arthritis Rheum 38:13–19

    Article  PubMed  CAS  Google Scholar 

  59. Angel K, Aarrestad Provan S, Lovahl Gulseth H, Mowinckel P, Kvien K, Atar D (2010) Tumor necrosis factor-α antagonists improve aortic stiffness in patients with inflammatory arthropathies. A controlled study. Hypertension 55:333.38

    Article  Google Scholar 

  60. Kerekes G, Soltsèz P, Dèr H et al (2009) Effects of biologics on vascular function and atherosclerosis associated with rheumatoid arthritis. Ann N Y Acad Sci 1173:814–821

    Article  PubMed  Google Scholar 

  61. Gallaraga B, Belch JJ, Pullar T, Ogston S, Khan F (2010) Clinical improvement in rheumatoid arthritis is associated with healthier microvascualr function in patients who respond to antirheumatic therapy. J Rheumatol 37:521–528

    Article  Google Scholar 

  62. Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Miranda-Filloy JA, Llorca J (2010) Insulin resistance in rheumatoid arthritis: the impact of the anti-TNF-alpha therapy. Ann N Y Acad Sci 1193:153–159

    Article  PubMed  CAS  Google Scholar 

  63. Gerli R, Schillaci G, Giordano A et al (2004) CD4+CD28null T lymphocytes contribute to early atherosclerotic damage in rheumatoid arthritis patients. Circulation 109:2744–2748

    Article  PubMed  CAS  Google Scholar 

  64. Gerli R, Vaudo G, Bartoloni Bocci E, Schillaci G, Bistoni O, Shoenfeld Y (2009) Different roles for anti-cyclic citrullinated peptide antibodies and CD4+CD28null cells in the acceleration of atherosclerosis in rheumatoid arthritis: comment on the article by Farragher et al. Arthritis Rheum 60:631–632

    Article  PubMed  Google Scholar 

  65. Gerli R, Bocci EB, Shoenfeld Y (2006) Effect of tumor necrosis factor α inhibition on CD28 surface expression on CD4+ T cells. Arthritis Rheum 54:3060–3061

    Article  PubMed  Google Scholar 

  66. Kerekes G, Soltsez P, Der H et al (2009) Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis and lipid profile in rheumatoid arthritis. Clin Rheumatol 28:705–710

    Article  PubMed  Google Scholar 

  67. Bruce IN (2005) Cardiovascular disease in lupus patients: should all patients be treated with statins and aspirin? Best Pract Res Clin Rheumatol 19:823–838

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Via Enrico Dal Pozzo, 06122, Perugia, Italy

    Elena Bartoloni, Alessia Alunno, Onelia Bistoni & Roberto Gerli

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  1. Elena Bartoloni
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  2. Alessia Alunno
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  3. Onelia Bistoni
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  4. Roberto Gerli
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Correspondence to Roberto Gerli.

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Bartoloni, E., Alunno, A., Bistoni, O. et al. Cardiovascular Risk in Rheumatoid Arthritis and Systemic Autoimmune Rheumatic Disorders: a Suggested Model of Preventive Strategy. Clinic Rev Allerg Immunol 44, 14–22 (2013). https://doi.org/10.1007/s12016-010-8251-x

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