Current Rheumatology Reports

, Volume 11, Issue 4, pp 241–247

Atherosclerosis risk factors in systemic lupus erythematosus

  • Surabhi Agarwal
  • Jennifer R. Elliott
  • Susan Manzi


Cardiovascular disease (CVD) has emerged as a leading cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Growing evidence suggests that inflammation plays a key role in the pathogenesis of atherosclerosis from initial endothelial dysfunction to rupture of atheromatous plaques. The increased frequency of atherosclerosis in SLE is likely due to a complex interplay among traditional risk factors, disease-related factors such as medications and disease activity, and inflammatory and immunogenic factors. Identification of these novel risk factors will lead to a better understanding of CVD pathogenesis and may also provide targets for potential treatment strategies. When caring for SLE patients, clinicians should be aware of the increased CVD risk and treat the known modifiable risk factors in addition to controlling disease activity and inflammation.


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References and Recommended Reading

  1. 1.
    Bulkley BH, Roberts WC: The heart in systemic lupus erythematosus and the changes induced in it by corticosteroid therapy. A study of 36 necropsy patients. Am J Med 1975, 58:243–264.PubMedCrossRefGoogle Scholar
  2. 2.
    Manzi S, Meilahn EN, Rairie JE, et al.: Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol 1997, 145:408–415.PubMedGoogle Scholar
  3. 3.
    Urowitz MB, Bookman AA, Koehler BE, et al.: The bimodal mortality pattern of systemic lupus erythematosus. Am J Med 1976, 60:221–225.PubMedCrossRefGoogle Scholar
  4. 4.
    Ward MM: Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus. Arthritis Rheum 1999, 42:338–346.PubMedCrossRefGoogle Scholar
  5. 5.
    Petri M, Spence D, Bone LR, Hochberg MC: Coronary artery disease risk factors in the Johns Hopkins Lupus Cohort: prevalence, recognition by patients, and preventive practices. Medicine (Baltimore) 1992, 71:291–302.Google Scholar
  6. 6.
    Roman MJ, Shanker BA, Davis A, et al.: Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003, 349:2399–2406.PubMedCrossRefGoogle Scholar
  7. 7.
    Esdaile JM, Abrahamowicz M, Grodzicky T, et al.: Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 2001, 44:2331–2337.PubMedCrossRefGoogle Scholar
  8. 8.
    Ross R: Atherosclerosis—an inflammatory disease. N Engl J Med 1999, 340:115–126.PubMedCrossRefGoogle Scholar
  9. 9.
    Packard RR, Libby P: Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem 2008, 54:24–38.PubMedCrossRefGoogle Scholar
  10. 10.
    Hansson GK: Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005, 352:1685–1695.PubMedCrossRefGoogle Scholar
  11. 11.
    Manzi S, Selzer F, Suton-Tyrrell K, et al.: Prevalence and risk factors of carotid plaque in women with systemic lupus erythematosus. Arthritis Rheum 1999, 42:51–60.PubMedCrossRefGoogle Scholar
  12. 12.
    Thompson T, Sutton-Tyrrell K, Wildman RP, et al.: Progression of carotid intima-media thickness and plaque in women with systemic lupus erythematosus. Arthritis Rheum 2008, 58:835–842.PubMedCrossRefGoogle Scholar
  13. 13.
    Roman MJ, Crow MK, Lockshin MD, et al.: Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 2007, 56:3412–3419.PubMedCrossRefGoogle Scholar
  14. 14.
    Svenungsson E, Jensen-Urstad K, Heimburger M, et al.: Risk factors for cardiovascular disease in systemic lupus erythematosus. Circulation 2001, 104:1887–1893.PubMedCrossRefGoogle Scholar
  15. 15.
    Colombo BM, Cacciapaglia F, Puntoni M, et al.: Traditional and nontraditional risk factors in accelerated atherosclerosis in systemic lupus erythematosus: role of vascular endothelial growth factor (VEGATS study). Autoimmun Rev 2009, 8:309–315.PubMedCrossRefGoogle Scholar
  16. 16.
    Elliott JR, Sattar A, Santelices LC, et al.: Carotid intimamedia thickness and plaque predict future cardiovascular events in women with systemic lupus erythematosus. Presented at the Annual Scientific Meeting of the American College of Rheumatology. San Francisco, CA; October 24–29, 2008.Google Scholar
  17. 17.
    Asanuma Y, Oeser A, Shintani AK, et al.: Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003, 349:2407–2415.PubMedCrossRefGoogle Scholar
  18. 18.
    Kao AH, Wasko MC, Krishnaswami S, et al.: C-reactive protein and coronary artery calcium in asymptomatic women with systemic lupus erythematosus or rheumatoid arthritis. Am J Cardiol 2008, 102:755–760.PubMedCrossRefGoogle Scholar
  19. 19.
    Von Feldt JM, Scalzi LV, Cucchiara AJ, et al.: Homocysteine levels and disease duration independently correlate with coronary artery calcification in patients with systemic lupus erythematosus. Arthritis Rheum 2006, 54:2220–2227.CrossRefGoogle Scholar
  20. 20.
    Lima DS, Sato EI, Lima VC, et al.: Brachial endothelial function is impaired in patients with systemic lupus erythematosus. J Rheumatol 2002, 29:292–297.PubMedGoogle Scholar
  21. 21.
    El-Magadmi M, Bodill H, Ahmad Y, et al.: Systemic lupus erythematosus: an independent risk factor for endothelial dysfunction in women. Circulation 2004, 110:399–404.PubMedCrossRefGoogle Scholar
  22. 22.
    Svenungsson E, Cederholm A, Jensen-Urstad K, et al.: Endothelial function and markers of endothelial activation in relation to cardiovascular disease in systemic lupus erythematosus. Scand J Rheumatol 2008, 37:1–8.CrossRefGoogle Scholar
  23. 23.
    Hill JM, Zalos G, Halcox JP, et al.: Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003, 348:593–600.PubMedCrossRefGoogle Scholar
  24. 24.
    Lee PY, Li Y, Richards HB, et al.: Type I interferon as a novel risk factor for endothelial progenitor cell depletion and endothelial dysfunction in systemic lupus erythematosus. Arthritis Rheum 2007, 56:3759–3769.PubMedCrossRefGoogle Scholar
  25. 25.
    Ronnblom L, Eloranta ML, Alm GV: The type I interferon system in systemic lupus erythematosus. Arthritis Rheum 2006, 54:408–420.PubMedCrossRefGoogle Scholar
  26. 26.
    Grisar J, Steiner CW, Bonelli M, et al.: Systemic lupus erythematosus patients exhibit functional deficiencies of endothelial progenitor cells. Rheumatology (Oxford), 2008, 47:1476–1483.CrossRefGoogle Scholar
  27. 27.
    Spronk PE, Bootsma H, Huitema MG, et al.: Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease exacerbations in patients with systemic lupus erythematosus (SLE); a long term prospective study. Clin Exp Immunol 1994, 97:439–444.PubMedCrossRefGoogle Scholar
  28. 28.
    Madge LA, Pober JS: TNF signaling in vascular endothelial cells. Exp Mol Pathol 2001, 70:317–325.PubMedCrossRefGoogle Scholar
  29. 29.
    Svenungsson E, Fei GZ, Jensen-Urstad K, et al.: TNF-alpha: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease. Lupus 2003, 12:454–461.PubMedCrossRefGoogle Scholar
  30. 30.
    Pasceri V, Cheng JS, Willerson JT, Yeh ET: Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 2001, 103:2531–2534.PubMedGoogle Scholar
  31. 31.
    Pasceri V, Willerson JT, Yeh ET: Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000, 102:2165–2168.PubMedGoogle Scholar
  32. 32.
    Ballou SP, Lozanski G: Induction of inflammatory cytokine release from cultured human monocytes by C-reactive protein. Cytokine 1992, 4:361–368.PubMedCrossRefGoogle Scholar
  33. 33.
    Paul A, Ko KW, Li L, et al.: C-reactive protein accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2004, 109:647–655.PubMedCrossRefGoogle Scholar
  34. 34.
    Asanuma Y, Chung CP, Oeser A, et al.: Increased concentration of proatherogenic inflammatory cytokines in systemic lupus erythematosus: relationship to cardiovascular risk factors. J Rheumatol 2006, 33:539–545.PubMedGoogle Scholar
  35. 35.
    Svenungsson E, Gunnarsson I, Fei GZ, et al.: Elevated triglycerides and low levels of high-density lipoprotein as markers of disease activity in association with up-regulation of the tumor necrosis factor alpha/tumor necrosis factor receptor system in systemic lupus erythematosus. Arthritis Rheum 2003, 48:2533–2540.PubMedCrossRefGoogle Scholar
  36. 36.
    Sari RA, Polat MF, Taysi S, et al.: Serum lipoprotein(a) level and its clinical significance in patients with systemic lupus erythematosus. Clin Rheumatol 2002, 21:520–524.PubMedCrossRefGoogle Scholar
  37. 37.
    Rath M, Niendorf A, Reblin T, et al.: Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis 1989, 9:579–592.PubMedGoogle Scholar
  38. 38.
    Kiani AN, Magder L, Petri M: Coronary calcium in systemic lupus erythematosus is associated with traditional cardiovascular risk factors, but not with disease activity. J Rheumatol 2008, 35:1300–1306.PubMedGoogle Scholar
  39. 39.
    Feingold KR, Grunfeld C: Role of cytokines in inducing hyperlipidemia. Diabetes 1992, 41(Suppl 2):97–101.PubMedGoogle Scholar
  40. 40.
    Witztum JL, Steinberg D: The oxidative modification hypothesis of atherosclerosis: does it hold for humans? Trends Cardiovasc Med 2001, 11:93–102.PubMedCrossRefGoogle Scholar
  41. 41.
    Frostegard J, Svenungsson E, Wu R, et al.: Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations. Arthritis Rheum 2005, 52:192–200.PubMedCrossRefGoogle Scholar
  42. 42.
    Blankenberg S, Rupprecht HJ, Bickel C, et al.: Circulating cell adhesion molecules and death in patients with coronary artery disease. Circulation 2001, 104:1336–1342.PubMedCrossRefGoogle Scholar
  43. 43.
    Shoji T, Nishizawa Y, Fukumoto M, et al.: Inverse relationship between circulating oxidized low density lipoprotein (oxLDL) and anti-oxLDL antibody levels in healthy subjects. Atherosclerosis 2000, 148:171–177.PubMedCrossRefGoogle Scholar
  44. 44.
    Shoenfeld Y, Wu R, Dearing LD, Matsuura E: Are antioxidized low-density lipoprotein antibodies pathogenic or protective? Circulation 2004, 110:2552–2558.PubMedCrossRefGoogle Scholar
  45. 45.
    Wu R, Nityanand S, Berglund L, et al.: Antibodies against cardiolipin and oxidatively modified LDL in 50-year-old men predict myocardial infarction. Arterioscler Thromb Vasc Biol 1997, 17:3159–3163.PubMedGoogle Scholar
  46. 46.
    Kobayashi K, Matsuura E, Liu Q, et al.: A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages. J Lipid Res 2001, 42:697–709.PubMedGoogle Scholar
  47. 47.
    Hasunuma Y, Matsuura E, Makita Z, et al.: Involvement of beta 2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages. Clin Exp Immunol 1997, 107:569–573.PubMedCrossRefGoogle Scholar
  48. 48.
    Lopez LR, Salazar-Paramo M, Palafox-Sanchez C, et al.: Oxidized low-density lipoprotein and beta2-glycoprotein I in patients with systemic lupus erythematosus and increased carotid intima-media thickness: implications in autoimmune-mediated atherosclerosis. Lupus 2006, 15:80–86.PubMedCrossRefGoogle Scholar
  49. 49.
    Kobayashi K, Kishi M, Atsumi T, et al.: Circulating oxidized LDL forms complexes with beta2-glycoprotein I: implication as an atherogenic autoantigen. J Lipid Res 2003, 44:716–726.PubMedCrossRefGoogle Scholar
  50. 50.
    McMahon M, Grossman J, FitzGerald J, et al.: This study discusses proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 2006, 54:2541–2549.PubMedCrossRefGoogle Scholar
  51. 51.
    McMahon MA, Sahakian L, Skaggs BJ, et al.: PiHDL is a stronger predictor of atherosclerosis than other highrisk inflammatory lipids, and is associated with a 17-fold increased risk of subclinical atherosclerosis in SLE. Presented at the Annual Scientific Meeting of the American College of Rheumatology. San Francisco, CA; October 24–29, 2008.Google Scholar
  52. 52.
    Schonbeck U, Mach F, Sukhova GK, et al.: CD40 ligation induces tissue factor expression in human vascular smooth muscle cells. Am J Pathol 2000, 156:7–14.PubMedGoogle Scholar
  53. 53.
    Petri M: Epidemiology of the antiphospholipid antibody syndrome. J Autoimmun 2000, 15:145–151.PubMedCrossRefGoogle Scholar
  54. 54.
    Vaarala O, Manttari M, Manninen V, et al.: Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men. Circulation 1995, 91:23–27.PubMedGoogle Scholar
  55. 55.
    Bessant R, Duncan R, Ambler G, et al.: Prevalence of conventional and lupus-specific risk factors for cardiovascular disease in patients with systemic lupus erythematosus: a case-control study. Arthritis Rheum 2006, 55:892–899.PubMedCrossRefGoogle Scholar
  56. 56.
    Rajagopalan S, Somers EC, Brook RD, et al.: Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. Blood 2004, 103:3677–3683.PubMedCrossRefGoogle Scholar
  57. 57.
    Cederholm A, Frostegard J: Annexin A5 in cardiovascular disease and systemic lupus erythematosus. Immunobiology 2005, 210:761–768.PubMedCrossRefGoogle Scholar
  58. 58.
    Chung CP, Avalos I, Oeser A, et al.: High prevalence of the metabolic syndrome in patients with systemic lupus erythematosus: association with disease characteristics and cardiovascular risk factors. Ann Rheum Dis 2007, 66:208–214.PubMedCrossRefGoogle Scholar
  59. 59.
    Stampfer MJ, Malinow MR, Willett WC, et al.: A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992, 268:877–881.PubMedCrossRefGoogle Scholar
  60. 60.
    Petri M, Roubenoff R, Dallal GE, et al.: Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus. Lancet 1996, 348:1120–1124.PubMedCrossRefGoogle Scholar
  61. 61.
    Petri M, Lakatta C, Magder L, Goldman D: Effect of prednisone and hydroxychloroquine on coronary artery disease risk factors in systemic lupus erythematosus: a longitudinal data analysis. Am J Med 1994, 96:254–259.PubMedCrossRefGoogle Scholar
  62. 62.
    Bultink IE, Turkstra F, Diamant M, et al.: Prevalence of and risk factors for the metabolic syndrome in women with systemic lupus erythematosus. Clin Exp Rheumatol 2008, 26:32–38.PubMedGoogle Scholar
  63. 63.
    Wasko MC, Hubert HB, Lingala VB, et al.: Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA 2007, 298:187–193.PubMedCrossRefGoogle Scholar
  64. 64.
    Manger K, Kusus M, Forster C, et al.: Factors associated with coronary artery calcification in young female patients with SLE. Ann Rheum Dis 2003, 62:846–850.PubMedCrossRefGoogle Scholar
  65. 65.
    Selzer F, Sutton-Tyrrell K, Fitzgerald S, et al.: Vascular stiffness in women with systemic lupus erythematosus. Hypertension 2001, 37:1075–1082.PubMedGoogle Scholar

Copyright information

© Current Medicine Group, LLC 2009

Authors and Affiliations

  • Surabhi Agarwal
  • Jennifer R. Elliott
  • Susan Manzi
    • 1
  1. 1.Division of Rheumatology and Clinical ImmunologyUniversity of PittsburghPittsburghUSA

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