Skip to main content

Advertisement

Log in

Atherosclerotic cardiovascular disease in rheumatoid arthritis

  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

The past 3 years have seen a remarkable growth in the inter-est of cardiovascular disease in rheumatoid arthritis. There have been studies published documenting an increased inci-dence and prevalence of cardiovascular conditions in patients with rheumatoid arthritis compared with individuals without rheumatoid arthritis. There has also been interest in the occurrence of cardiovascular risk factors in rheumatoid arthritis and in the role of antirheumatic therapy, including cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs, methotrexate, corticosteroids, and tumor necrosis fac-tor inhibitors. A number of studies using noninvasive means to detect atherosclerosis have shown that patients with rheu-matoid arthritis may be prone to atherosclerosis. This infor-mation should be important to physicians who provide care to patients with rheumatoid arthritis, given the difficulty of recognizing cardiovascular signs and symptoms among patients with the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. DiGirolamo M, Schlant RC: Etiology of coronary atherosclero-sis. In The Heart, Arteries and Veins. Edited by Hurst JW, Logue RB, Schlant RC, Wenger NK. New York: McGraw-Hill; 1978:1103–1121.

    Google Scholar 

  2. Ross R: Atherosclerosis-an inflammatory disease. N Engl J Med 1999, 340:115–126.

    Article  PubMed  CAS  Google Scholar 

  3. Napoli C, D’Armiento FP, Mancini FP, et al.: Fatty streak forma-tion occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia: intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest 1997, 100:2680–2690.

    PubMed  CAS  Google Scholar 

  4. Koenig W, Sund M, Frohlich M, et al.: C-Reactive protein, a sensitive marker of inflammation, predicts future risk of cor-onary heart disease in initially healthy middle-aged men: results from the MONICA Augsburg Cohort Study, 1984 to 1992. Circulation 1999, 99:237–242.

    PubMed  CAS  Google Scholar 

  5. Stenvinkel P, Heimburger O, Paultre F, et al.: A strong associa-tion between malnutrition, inflammation, and atherosclero-sis in chronic renal failure. Kidney Int 1999, 55:1899–1911.

    Article  PubMed  CAS  Google Scholar 

  6. Zoccali C, Benedetto FA, Mallamaci F, et al.: Inflammation is associated with carotid atherosclerosis in dialysis patients. Creed Investigators: cardiovascular risk extended evaluation in dialysis patients. J Hyperten 2000, 18:1207–1213.

    Article  CAS  Google Scholar 

  7. Slavkin HC, Baum BJ: Relationship of dental and oral pathol-ogy to systemic illness. JAMA 2000, 284:1215–1217.

    Article  PubMed  CAS  Google Scholar 

  8. Jousilahti P, Vartiainen E, Tuomilehto J, Puska P: Symptoms of chronic bronchitis and the risk of coronary disease. Lancet 1996, 348:567–572.

    Article  PubMed  CAS  Google Scholar 

  9. Spodick DH, Flessas AP, Johnson MM: Association of acute respiratory symptoms with onset of acute myocardial infarc-tion: prospective investigation of 150 consecutive patients and matched control patients. Am J Cardiol 1984, 53:13–23.

    Google Scholar 

  10. Manzi S, Selzer F, Sutton-Tyrrell K, et al.: Prevalence and risk factors of carotid plaque in women with systemic lupus erythematosus. Arthritis Rheum 1999, 42:51–60.

    Article  PubMed  CAS  Google Scholar 

  11. Van Doornum S, McColl G, Wicks IP: Accelerated atherosclero-sis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum 2002, 46:862–873.

    Article  PubMed  Google Scholar 

  12. Manicourt DH, Triki R, Fukuda K, et al.: Levels of circulating tumor necrosis factor alpha and interleukin-6 in patients with rheumatoid arthritis. Relationship to serum levels of hyaluran and antigenic keratan sulfate. Arthritis Rheum 1993, 36:490–499.

    Article  PubMed  CAS  Google Scholar 

  13. Tetta C, Camussi G, Modena V, et al.: Tumor necrosis factor in serum and synovial fluid of patients with active and severe rheumatoid arthritis. Ann Rheum Dis 1990, 49:665–667.

    PubMed  CAS  Google Scholar 

  14. Wolfe F: Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in patients with rheumatoid arthritis. J Rheumatol 1997, 24:1477–1485.

    PubMed  CAS  Google Scholar 

  15. Cermak J, Key NS, Bach RR, et al.: C-reactive protein induces human peripheral blood monocytes to synthesize tissue fac-tor. Blood 1993, 82:513–520.

    PubMed  CAS  Google Scholar 

  16. Ardissino D, Merlini PA, Ariens R, et al.: Tissue factor antigen and activity in human coronary atherosclerotic plaques. Lan-cet 1997, 349:769–771.

    CAS  Google Scholar 

  17. Torzewski J, Torzewski M, Bowyer DE, et al.: C-reactive protein frequently co-localizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coro-nary arteries. Arterioscler Thromb Vasc Biol 1998, 18:1386–1392.

    PubMed  CAS  Google Scholar 

  18. Liuzzo G, Kopecky SL, Frye RL, et al.: Perturbation of the T-cell repertoire in patients with unstable angina. Circulation 1999, 100:2135–2139.

    PubMed  CAS  Google Scholar 

  19. Pincus T, Callahan LF, Sale WG: Severe functional declines, work disability and increased mortality in 75 rheumatoid arthritis patients studied over nine years. Arthritis Rheum 1984, 27:864–872.

    Article  PubMed  CAS  Google Scholar 

  20. Mitchell DM, Spitz PW, Young DY, et al.: Survival, prognosis, and causes of death in rheumatoid arthritis. Arthritis Rheum 1986, 29:706–714.

    Article  PubMed  CAS  Google Scholar 

  21. Jacobsson LTH Knowler WC, Pillemer S, et al.: Rheumatoid arthritis and mortality: a longitudinal study in Pima Indians. Arthritis Rheum 1993, 36:1045–1053.

    Article  Google Scholar 

  22. Wolfe F, Mitchell DM, Sibley JT, et al.: The mortality of rheu-matoid arthritis. Arthritis Rheum 1994, 37:481–494.

    Article  PubMed  CAS  Google Scholar 

  23. Wolfe F: Fifty years of antirheumatic therapy: the prognosis of rheumatoid arthritis. J Rheumatol 1990, 17(suppl):24–32.

    Google Scholar 

  24. Wolfe F, Mitchell DM, Sibley JT, et al.: The mortality of rheu-matoid arthritis. Arthritis Rheum 1994, 37:481–494

    Article  PubMed  CAS  Google Scholar 

  25. Myllykangas-Luosujarvi RA, Aho K, Isomaki HA: Mortality in rheumatoid arthritis. Semin Arthritis Rheum 1995, 25:193–202.

    Article  PubMed  CAS  Google Scholar 

  26. Myllykangas-Luosujarvi R, Aho K, Kautiainen H, Isomaki H: Shortening of life span and causes of excess mortality in a population-based series of subjects with rheumatoid arthri-tis. Clin Exp Rheumatol 1995, 13:149–153.

    PubMed  CAS  Google Scholar 

  27. Pincus T, Brooks RH, Callahan LF: Prediction of long term mortality in patients with rheumatoid arthritis according to simple questionnaire and joint count measures. Ann Intern Med 1994, 120:26–34.

    PubMed  CAS  Google Scholar 

  28. Myllykangas-Luosujarvi R, Aho K, Kautiainen H, Isomaki H: Cardiovascular mortality in women with rheumatoid arthri-tis. J Rheumatol 1995, 22:1065–1067.

    PubMed  CAS  Google Scholar 

  29. Monson RR, Hall AP: Mortality among arthritics. J Chronic Dis 1976, 29:459–467.

    Article  PubMed  CAS  Google Scholar 

  30. Vandenbroucke JP, Hazevoet HM, Cats A: Survival and cause of death in rheumatoid arthritis: a 25-year prospective follow-up. J Rheumatol 1984, 11:158–161.

    PubMed  CAS  Google Scholar 

  31. Lewis P, Hazleman BL, Hanka R, Roberts S: Cause of death in patients with rheumatoid arthritis with particular reference to azathioprine. Ann Rheum Dis 1980, 39:457–461.

    PubMed  CAS  Google Scholar 

  32. Jacobsson LTH, Knowler WC, Pillemer S, et al.: Rheumatoid arthritis and mortality: a longitudinal study in Pima Indians. Arthritis Rheum 1993, 36:1045–1053.

    Article  PubMed  CAS  Google Scholar 

  33. Erhardt CC, Mumford PA, Venables PJW, Maini RN: Factors predicting a poor life prognosis in rheumatoid arthritis: and eight-year prospective study. Ann Rheum Dis 1989, 48:7–13.

    PubMed  CAS  Google Scholar 

  34. Allebeck P: Increased mortality in rheumatoid arthritis. Scand J Rheumatol 1982, 11:81–86.

    PubMed  CAS  Google Scholar 

  35. Prior P, Symmons DP, Scott DL, et al.: Cause of death in rheu-matoid arthritis. Br J Rheumatol 1984, 23:92–99.

    Article  PubMed  CAS  Google Scholar 

  36. Mutru O, Laakso M, Isomaki H, Koota K: Cardiovascular mor-tality in patients with rheumatoid arthritis. Cardiology 1989, 76:71–77.

    Article  PubMed  CAS  Google Scholar 

  37. Symmons DPM, Jones MA, Scott DL, Prior P: Long-term mortal-ity outcome in patients with rheumatoid arthritis: early pre-senters continue to do well. J Rheumatol 1998, 25:1072–1077.

    PubMed  CAS  Google Scholar 

  38. Goodson NJ, Wiles NJ, Lunt M, et al.: Mortality in early serop-ositive polyarthritis: cardiovascular mortality is increased in seropositive patients. Arthritis Rheum 2002, 46:2010–2019.

    Article  PubMed  Google Scholar 

  39. del Rincón I, Williams K, Stern MP, et al.: High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 2001, 44:2737–2745. The authors compared the incidence of CV events in a sample of patients with RA with that of a population-based sample. They found that the RA group had a higher incidence, independent of traditional CV risk factors.

    Article  PubMed  Google Scholar 

  40. Wolfe F, Freundlich B, Straus WL: Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthri-tis. J Rheumatol 2003, 30:36–40. The authors surveyed patients with RA or OA from a sample of US community-based rheumatologists, and found that the patients with RA were more likely to have myocardial infarction, congestive heart failure, and stroke.

    PubMed  Google Scholar 

  41. Solomon DH, Karlson EW, Rimm EB, et al.: Cardiovascular morbidity and mortality in women diagnosed with rheuma-toid arthritis. Circulation 2003, 107:1303–1307. Analysis of data from the Nurses Health Study, in which participants diagnosed with RA had a higher rate of cardiovascular events com-pared with participants without RA.

    Article  PubMed  Google Scholar 

  42. Jarenros A, Jacobsson LTH, Turesson C: Increased incidence of myocardial infarction and stroke in rheumatoid arthritis-results from a community based study [abstract]. Arthritis Rheum 2002, 46(suppl):S510.

    Google Scholar 

  43. Kremers HM, Crowson SS, O’Fallon WM, Gabriel SE: The syn-ergistic impact of rheumatoid arthritis and myocardial inf-arction on mortality. Arthritis Rheum 2002, 46(suppl):S616.

    Google Scholar 

  44. Symmons DP, Bankhead CR, Harrison BJ, et al.: Blood transfu-sion, smoking, and obesity as risk factors for the develop-ment of rheumatoid arthritis: results from a primary care-based incident case-control study in Norfolk, England. Arthritis Rheum 1997, 40:1955–1961.

    Article  PubMed  CAS  Google Scholar 

  45. Karlson EW, Lee IM, Cook NR, et al.: A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals. Arthritis Rheum 1999, 42:910–917.

    Article  PubMed  CAS  Google Scholar 

  46. Helióvaara M, Aho K, Knekt P, et al.: Serum cholesterol and risk of rheumatoid arthritis in a cohort of 52,800 men and women. Br J Rheumatol 1996, 35:255–257.

    Article  PubMed  Google Scholar 

  47. Park YB, Lee SK, Lee WK, et al.: Lipid profiles in untreated patients with rheumatoid arthritis. J Rheumatol 1999, 26:1701–1704.

    PubMed  CAS  Google Scholar 

  48. Asanuma Y, Kawai S, Aoshima H, et al.: Serum lipoprotein (A) and apolipoprotein (B) phenotypes in patients with rheuma-toid arthritis. Arthritis Rheum 1999, 42:443–447.

    Article  PubMed  CAS  Google Scholar 

  49. Kavanaugh A: Dyslipoproteinemia in a subset of patients with rheumatoid arthritis. Ann Rheum Dis 1994, 53:551–552.

    Article  PubMed  CAS  Google Scholar 

  50. Dessein PH, Joffe BI, Stanwix A, et al.: The acute phase response does not fully predict the presence of insulin resis-tance and dyslipidemia in inflammatory arthritis. J Rheumatol 2002, 29:462–466.

    PubMed  Google Scholar 

  51. Dessein PH, Stanwix AE, Joffe BI: Cardiovascular risk in rheuma-toid arthritis versus osteoarthritis: acute phase response-related decreased insulin sensitivity and high density lipopro-tein cholesterol as well as clustering of metabolic syndrome features in rheumatoid arthritis. Arthritis Res 2002, 4:R5.

    Article  PubMed  Google Scholar 

  52. McEntegart A, Capell HA, Creran D, et al.: Cardiovascular risk factors, including thrombotic variables, in a population with rheumatoid arthritis. Rheumatology 2001, 40:640–644.

    Article  PubMed  CAS  Google Scholar 

  53. Kaplan D: Age of death of parents of patients with rheumatoid arthritis: a preliminary study. J Rheumatol 1986, 13:903–906.

    PubMed  CAS  Google Scholar 

  54. Kaplan D, Feldman J: A preliminary study of excess risk of car-diovascular disease in the mothers of patients with rheuma-toid arthritis. Am J Epidemiol 1991, 133:715–720.

    PubMed  CAS  Google Scholar 

  55. Wolfe F: Age of death of parents with rheumatoid arthritis: data from a middle class sample. J Rheumatol 1989, 16:735–739.

    PubMed  CAS  Google Scholar 

  56. Spector TH, Silman AJ: Parental mortality and rheumatoid arthritis. J Rheumatol 1988, 15:150–151.

    PubMed  CAS  Google Scholar 

  57. Lemmey A, Maddison P, Breslin A, et al.: Association between insulin-like growth factor status and physical activity levels ion rheumatoid arthritis. J Rheumatol 2001, 28:29–34.

    PubMed  CAS  Google Scholar 

  58. Hernanz A, Plaza A, Martin-Mola E, de Miguel E: Increased plasma levels of homocysteine and other thiol compounds in rheumatoid arthritis women. Clin Biochem 1999, 32:65–70.

    Article  PubMed  CAS  Google Scholar 

  59. Cisternas M, Gutierrez MA, Klaassen J, et al.: Cardiovascular risk factors in Chilean patients with rheumatoid arthritis. J Rheumatol 2002, 29:1619–1622.

    PubMed  Google Scholar 

  60. Seriolo B, Fasciolo D, Sulli A, Cutolo M: Homocysteine and antiphospholipid antibodies in rheumatoid arthritis patients: relationships with thrombotic events. Clin Exp Rheu-matol 2001, 19:561–564.

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  62. Wallberg-Jonsson S, Backman C, Johnson O, et al.: Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis. J Rheumatol 2001, 28:2597–2602. This study, conducted in Sweden, found that patients with RA had sig-nificantly greater carotid intima-media thickness than individuals from the general population.

    Google Scholar 

  63. Kumeda Y, Inaba M, Goto H, et al.: Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis. Arthritis Rheum 2002, 46:1489–1497. In this study, authors compared a highly selected sampled of Japanese patients with RA with control individuals, and found a significantly greater carotid intima-media thickness among patients with RA. The authors carefully excluded patients with other CV risk factors.

    Article  PubMed  Google Scholar 

  64. Park YB, Ahn CW, Choi HK, et al.: Atherosclerosis in rheuma-toid arthritis: morphologic evidence obtained by carotid ultrasound. Arthritis Rheum 2002, 46:1714–1719. In this study, the authors compared Korean women aged 50 to 59 with RA with matched control individuals without RA. They found that the patients with RA had significantly greater carotid intima-media thickness.

    Article  PubMed  Google Scholar 

  65. Bombardier C, Laine L, Reicin A, et al.: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000, 343:1520–1528.

    Article  PubMed  CAS  Google Scholar 

  66. Mukherjee D, Nissen SE, Topol EJ: Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001, 286:954–959.

    Article  PubMed  CAS  Google Scholar 

  67. Solomon DH, Glynn RJ, Levin R, Avorn J: Nonsteroidal anti-inflammatory drug use and acute myocardial infarction. Arch Intern Med 2002, 162:1099–1104.

    Article  PubMed  CAS  Google Scholar 

  68. Watson DJ, Rhodes T, Cai B, Guess HA: Lower risk of throm-boembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Arch Intern Med 2002, 162:1105–1110.

    Article  PubMed  CAS  Google Scholar 

  69. Rahme E, Pilote L, LeLorier J: Association between naproxen use and protection against acute myocardial infarction. Arch Intern Med 2002, 162:1111–1115.

    Article  PubMed  CAS  Google Scholar 

  70. Ray WA, Stein CM, Hall K, et al.: Non-steroidal anti-inflamma-tory drugs and risk of serious coronary heart disease: an observational cohort study. Lancet 2002, 359:118–123.

    Article  PubMed  CAS  Google Scholar 

  71. Welch GN, Loscalzo J: Mechanisms of disease: homocysteine and atherothrombosis. N Engl J Med 1998, 338:1042–1050.

    Article  PubMed  CAS  Google Scholar 

  72. van Ede AE, Laan RFJM, Blom HJ, et al.: Homocysteine and folate status in methotrexate-treated patients with rheuma-toid arthritis. Rheumatology 2002, 41:658–665.

    Article  PubMed  Google Scholar 

  73. Morgan SL, Baggott JE, Lee JY, Alarcon GS: Folic acid supple-mentation prevents deficient blood folate levels and hyper-homocysteinemia during long-term, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovas-cular disease. J Rheumatol 1998, 25:441–446.

    PubMed  CAS  Google Scholar 

  74. Landewé RB, van den Borne BEEM, Breedveld FC, Dijkmans BAC: Methotrexate effects in patients with rheumatoid arthritis with cardiovascular comorbidity. Lancet 2000, 355:1616–1617.

    Article  PubMed  Google Scholar 

  75. Choi HK, Hernán MA, Seeger JD, et al.: Methotrexate and mor-tality in patients with rheumatoid arthritis: a prospective study. Lancet 2002, 359:1173–7. This paper describes an interesting non-interventional study in which the use of methotrexate was associated with a reduction in mortality in patients with RA.

    Article  PubMed  CAS  Google Scholar 

  76. Coletta AP, Clark AL, Cleland JGF: Clinical trials update: RENEWAL (RENAISSANCE and RECOVER) and ATTACH. Eur J Heart Fail 2002, 4:559–561.

    Article  PubMed  CAS  Google Scholar 

  77. Weisman MH: What are the risks of biologic therapy in rheu-matoid arthritis? An update on safety. J Rheumatol Suppl 2002, 65:33–38.

    PubMed  CAS  Google Scholar 

  78. Kwon HJ, Cote TR, Cuffe MS, et al.: Case reports of heart fail-ure after therapy with tumor necrosis factor antagonist. Ann Intern Med 2003, 138:807–811.

    PubMed  Google Scholar 

  79. de Clari F, Salani I, Safwan E, Giannacco A: Sudden death in a patient without heart failure after a single infusion of 200 mg infliximab: does TNF-a have protective effects on the failing heart, or does infliximab have direct harmful cardiovascular effects? Circulation 2002, 105:E183.

    Article  Google Scholar 

  80. Persson J, Formgren J, Israelsson B, Berglund G: Ultrasound-determined intima-media thickness and atherosclerosis: direct and indirect validation. Atheroscl Thromb 1994, 14:261–264.

    CAS  Google Scholar 

  81. Young W, Gofman JW, Tandy R, et al.: The quantification of atherosclerosis, III: the extent of correlation of degrees of atherosclerosis within and between the coronary and cere-bral vascular beds. Am J Cardiol 1960, 6:300–308.

    Article  Google Scholar 

  82. O’Leary DH, Polak JF, Kronmal RA, et al.: Distribution and cor-relates of sonographically detected carotid artery disease in the Cardiovascular Health Study. Stroke 1992, 23:1752–1760.

    PubMed  CAS  Google Scholar 

  83. O’Leary DH, Polack JF, Kronmal RA, et al.: Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 1999, 340:14–22.

    Article  PubMed  CAS  Google Scholar 

  84. Rodriguez G, Sulli A, Cutolo M, et al.: Carotid atherosclerosis in patients with rheumatoid arthritis: preliminary case-con-trol study. Ann NY Acad Sci 2002, 966:478–482.

    Article  PubMed  CAS  Google Scholar 

  85. del Rincón I, Williams K, Stern MO, et al.: Association between carotid atherosclerosis and systemic inflammation in rheuma-toid arthritis and healthy people. Arthritis Rheum 2003, in press. A study of patients with RA and age- and gender-matched control individuals recruited from San Antonio, TX, in which carotid intima-media thickness, and carotid plaque, were significantly associated with the ESR and the concentration of CRP in the serum.

  86. O’Leary DH, Polak JF, Kronmal RA, et al.: Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 1999, 340:14–22.

    Article  PubMed  CAS  Google Scholar 

  87. Kao A, Manzi S, Cunningham A, et al.: Atherosclerosis in RA women: inflammatory risk factors for vascular calcification [abstract]. Arthritis Rheum 2002, 46(suppl):S512.

    Google Scholar 

  88. Van Doornum S, McColl G, Green DJ, Wicks IP: Screening for atherosclerosis in patents with rheumatoid arthritis: compar-ison of two tests of vascular function. Arthritis Rheum 2003, 48:72–80.

    Article  PubMed  Google Scholar 

  89. Wong M, Toh L, Wislon A, et al.: Reduce arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation. Arthritis Rheum 2003, 48:81–89.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rincón, I.d., Escalante, A. Atherosclerotic cardiovascular disease in rheumatoid arthritis. Curr Rheumatol Rep 5, 278–286 (2003). https://doi.org/10.1007/s11926-003-0006-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-003-0006-8

Keywords

Navigation