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Atherosclerosis and inflammation: insights from rheumatoid arthritis

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Abstract

Cardiovascular disease is a major health care problem and the most common cause of death among individuals from developed nations. Our understanding of atherosclerosis has evolved from a passive process resulting in narrowing of the lumen and consequent myocardial ischemia to a dynamic process that involves inflammation. The study of atherosclerosis in patients with chronic inflammation, such as rheumatoid arthritis (RA), will provide insights into the relationship between inflammation and atherosclerosis. We review the relationship between atherosclerosis and inflammation within the context of RA, providing evidence that patients with RA have increased cardiovascular morbidity and mortality and accelerated coronary and extra-coronary atherosclerosis. In addition, traditional and novel cardiovascular risk factors are discussed. Finally, actions that a rheumatologist can take to better control this cardiovascular morbidity are suggested. These can be summarized as follows: (1) careful assessment and treatment of cardiovascular risk, (2) better control of inflammation, and (3) individual risk–benefit evaluation of need for cyclo-oxygenase-2 inhibitors, nonsteroidal anti-inflammatory drugs, and high doses of corticosteroids.

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References

  1. Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T, Zheng ZJ, Flegal K, O’Donnell C, Kittner S et al (2006) Heart disease and stroke statistics—2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 113(6):e85–e151, Feb 14

    Article  PubMed  Google Scholar 

  2. Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340(2):115–126, Jan 14

    Article  PubMed  CAS  Google Scholar 

  3. Ridker PM, Hennekens CH, Buring JE, Rifai N (2000) C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342(12):836–843, Mar 23

    Article  PubMed  CAS  Google Scholar 

  4. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101(15):1767–1772, Apr 18

    PubMed  CAS  Google Scholar 

  5. Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC (2003) Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 107(9):1303–1307, Mar 11

    Article  PubMed  Google Scholar 

  6. Cobb S, Anderson F, Bauer W (1953) Length of life and cause of death in rheumatoid arthritis. N Engl J Med 249(14):553–556

    Article  PubMed  CAS  Google Scholar 

  7. Pincus T, Callahan LF, Sale WG, Brooks AL, Payne LE, Vaughn WK (1984) Severe functional decline, work disability and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. Arthritis Rheum 27(8):864–872

    Article  PubMed  CAS  Google Scholar 

  8. Prior P, Symmons DP, Scott DL, Brown R, Hawkins CF (1984) Cause of death in rheumatoid arthritis. Br J Rheumatol 23(2):92–99

    Article  PubMed  CAS  Google Scholar 

  9. Mutru O, Laakso M, Isomaki H, Koota K (1989) Cardiovascular mortality in patients with rheumatoid arthritis. Cardiology 76(1):71–77

    Article  PubMed  CAS  Google Scholar 

  10. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinheksel SM, Cathey MA (1994) The mortality of rheumatoid arthritis. Arthritis Rheum 37(4):481–494

    Article  PubMed  CAS  Google Scholar 

  11. Myllykangas-Luosujarvi R, Aho K, Kautianien H, Isomaki H (1995) Cardiovascular mortality in women with rheumatoid arthritis. J Rheumatol 22(6):1065–1067

    PubMed  CAS  Google Scholar 

  12. Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE (2005) Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum 52(3):722–732, Mar

    Article  PubMed  Google Scholar 

  13. del Rincon ID, Willliams K, Stern MP, Freeman GL, Escalante A (2001) High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 44(12):2737–2745

    Article  PubMed  Google Scholar 

  14. Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen SJ, Gabriel SE (2005) Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum 52(2):402–411, Feb

    Article  PubMed  Google Scholar 

  15. Chung CP, Oeser A, Raggi P, Gebretsadik T, Shintani AK, Sokka T, Pincus T, Avalos I, Stein CM (2005) Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors. Arthritis Rheum 52(10):3045–3053, Oct

    Article  PubMed  Google Scholar 

  16. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Vaimonte M Jr, Detrano R (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15(4):827–832

    Article  PubMed  CAS  Google Scholar 

  17. Warrington KJ, Kent PD, Frye RL, Lymp JF, Kopecky SL, Goronzy JJ, Weyand CM (2005) Rheumatoid arthritis is an independent risk factor for multi-vessel coronary artery disease: a case control study. Arthritis Res Ther 7(5):R984–R991

    Article  PubMed  CAS  Google Scholar 

  18. Park YB, Choi HK, Lee SH, In BH, Lee HC, Nam CM, Lee SK (2003) Atherosclerosis in rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound. Arthritis Rheum 46(7):1714–1719

    Article  Google Scholar 

  19. Kumeda Y, Inaba M, Goto H, Nagata M, Henmi Y, Furumitsu Y, Ishimura E, Inui K, Yutani Y, Miki T et al (2002) Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis. Arthritis Rheum 46(6):1489–1497

    Article  PubMed  Google Scholar 

  20. Gonzalez-Juanatey C, Llorca J, Testa A, Revuelta J, Garcia-Porrua C, Gonzales-Gay MA (2003) Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease. Medicine 82(6):407–413

    Article  PubMed  Google Scholar 

  21. Nagata-Sakurai M, Inaba M, Goto H, Kumeda Y, Furumitsu Y, Inui K, Koyama H, Emoto M, Ishimura E, Shoji T et al (2003) Inflammation and bone resorption as independent factors of accelerated arterial wall thickening in patients with rheumatoid arthritis. Arthritis Rheum 48(11):3061–3067

    Article  PubMed  Google Scholar 

  22. Roman MJ, Moeller E, Davis A, Paget SA, Crow MK, Lockshin MD, Sammaritano L, Devereux RB, Schwartz JE, Levine DM et al (2006) Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern Med 144(4):249–256, Feb 21

    PubMed  Google Scholar 

  23. Dessein PH, Joffe BI (2006) When is a patient with rheumatoid arthritis at risk for cardiovascular disease? J Rheumatol 33(2):201–203, Feb

    PubMed  Google Scholar 

  24. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97(18):1837–1847, May 12

    PubMed  CAS  Google Scholar 

  25. Chung CP, Oeser A, Avalos I, Gebretsadik T, Shintani AK, Raggi P, Sokka T, Pincus T, Stein CM (2006) Utility of the Framingham risk score to predict the presence of coronary atherosclerosis in patients with rheumatoid arthritis. Arthritis Res Ther 8(6):R186

    Article  PubMed  Google Scholar 

  26. Chung CP, Oeser A, Avalos I, Raggi P, Stein CM (2006) Cardiovascular risk scores underestimate the presence of subclinical coronary-artery atherosclerosis in women with systemic lupus erythematosus. Lupus 15:562–569

    Article  PubMed  CAS  Google Scholar 

  27. Svenson KL, Pollare T, Lithell H, Hallgren R (1988) Impaired glucose handling in active rheumatoid arthritis: relationship to peripheral insulin resistance. Metabolism 37(2):125–130, Feb

    Article  PubMed  CAS  Google Scholar 

  28. Chung CP, Oeser A, Solus JF, Avalos I, Gebretsadik T, Shintani AK, Raggi P, Sokka T, Pincus T, Stein CM (2007) Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. Atherosclerosis (in press)

  29. Dessein PH, Tobias M, Veller MG (2006) Metabolic syndrome and subclinical atherosclerosis in rheumatoid arthritis. J Rheumatol 33(12):2425–2432, Dec

    PubMed  Google Scholar 

  30. Greenland P, Grundy S, Pasternak RC, Lenfant C (1998) Problems on the pathway from risk assessment to risk reduction. Circulation 97(18):1761–1762, May 19

    PubMed  CAS  Google Scholar 

  31. Costenbader KH, Wright E, Liang MH, Karlson EW (2004) Cardiac risk factor awareness and management in patients with systemic lupus erythematosus. Arthritis Rheum 51(6):983–988, Dec 15

    Article  PubMed  Google Scholar 

  32. Third report of the National Cholesterol Education Program (NCEP) (2002) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation 106(25):3143–3421, Dec 17

    Google Scholar 

  33. McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakova O, Ford I, Capell HA, Sattar N (2004) Trial of atorvastatin in rheumatoid arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet 363(9426):2015–2021, Jun 19

    Article  PubMed  CAS  Google Scholar 

  34. Davis JM III, Maradit-Kremers H, Gabriel SE (2005) Use of low-dose glucocorticoids and the risk of cardiovascular morbidity and mortality in rheumatoid arthritis: what is the true direction of effect? J Rheumatol 32(10):1856–1862, Oct

    PubMed  Google Scholar 

  35. Wei L, MacDonald TM, Walker BR (2004) Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 141(10):764–770, Nov 16

    PubMed  Google Scholar 

  36. Del Rincon I, O’Leary DH, Haas RW, Escalante A (2004) Effect of glucocorticoids on the arteries in rheumatoid arthritis. Arthritis Rheum 50(12):3813–3822, Dec

    Article  PubMed  CAS  Google Scholar 

  37. Tannenbaum H, Bombardier C, Davis P, Russell AS (2006) An evidence-based approach to prescribing nonsteroidal antiinflammatory drugs. Third Canadian consensus conference. J Rheumatol 33(1):140–157, Jan

    PubMed  Google Scholar 

  38. Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F (2002) Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 359(9313):1173–1177, Apr 6

    Article  PubMed  CAS  Google Scholar 

  39. Suissa S, Bernatsky S, Hudson M (2006) Antirheumatic drug use and the risk of acute myocardial infarction. Arthritis Rheum 55(4):531–536, Aug 15

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Rheumatology, Department of Medicine, Vanderbilt University, 1161 21st Avenue T-3219 MCN, Nashville, TN, 37232, USA

    Cecilia P. Chung, Ingrid Avalos & C. Michael Stein

  2. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN, USA

    Cecilia P. Chung & C. Michael Stein

  3. Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, USA

    Paolo Raggi

Authors
  1. Cecilia P. Chung
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  2. Ingrid Avalos
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  3. Paolo Raggi
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  4. C. Michael Stein
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Correspondence to Cecilia P. Chung.

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Chung, C.P., Avalos, I., Raggi, P. et al. Atherosclerosis and inflammation: insights from rheumatoid arthritis. Clin Rheumatol 26, 1228–1233 (2007). https://doi.org/10.1007/s10067-007-0548-7

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  • DOI: https://doi.org/10.1007/s10067-007-0548-7

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