Accelerated atherosclerosis in systemic lupus erythematosus

Authors: A. Smržová;  P. Horák;  M. Skácelová;  H. Ciferská
Authors‘ workplace: III. interní klinika FN a LF UP Olomouc
Published in: Čes. Revmatol., 17, 2009, No. 3, p. 173-178.
Category: Overview Reports


Accelerated atherosclerosis (ATS) in connective tissue diseases is a very serious late disease-related complication. In systemic lupus erythematosus (SLE), the risk of ATS is sevenfold increased in comparison to an age-matched healthy population, and comparable to Cushing’s syndrome (e.g. more than threefold increased in comparison to diabetes mellitus). It is therefore important to pay attention to primary, as well as secondary prevention. An inflammatory process involving the vascular wall, presence of some specific antibodies, dyslipidemia, endothelial dysfunction, and an increased appearance of traditional risk factors play a significant role in the pathophysiology of ATS. The existence of these factors has various causes; they result from the autoimmune character of SLE, with participation of the used therapy. High cumulative doses of glucocorticoids, and cyclosporin A have a negative effect on ATS, whereas antimalarial drugs, mycophenolate mofetil, or some new biological agents have a protective effect. Accelerated atherosclerosis in SLE is a very complex and complicated process, and deserves sufficient attention, especially since the consequences of ATS significantly participate in the morbidity and mortality of SLE.

Key words:
accelerated atherosclerosis, systemic lupus erythematosus, dyslipidemia, glucocorticoids, cyclosporin A, antimalarial drugs


1. Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2004; 83: 1–17.

2. Ward MM, Pyun E, Studenski S. Causes of death in SLE. Long-term followup of an inception cohort. Arthritis Rheum 1995; 38: 1492–9.

3. Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2003; 82: 299–308.

4. Bjornadal L, Yin L, Granath F, et al. Cardiovascular disease a hazard despite improved prognosis in patients with systemic lupus erythematosus: results from a Swedish population based study 1964–95. J Rheumatol 2004; 31: 713–9.

5. Moder KG, Miller TD, Tazellar HD. Cardiac involvement in systemic lupus erythematosus. Mayo Clin Proc 1999; 74: 275–84.

6. Evangelopoulos ME, Alevizaki M, Toumanidis S, et al. Mitral valve prolapse in systemic lupus erythematosus patients: clinical and immunological aspects. Lupus 2003; 12: 308–311.

7. Moyssakis I, Tektonidou MG, Vasilliou VA, et al. Libman-Sacks endocarditis in systemic lupus erythematosus: prevalence, associations, and evolution. Am J Med 2007; 120: 636–42.

8. Wallace JD., Hahn BH. DuboisęLupus erythematosus 2007; 663–677.

9. Calvo-Alen, J, Toloza, SM, Fernandez, M, et al. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA). XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients. Arthritis Rheum 2005; 52: 2060–8.9.

10. Farzaneh-Far A, Roman MJ, Lockshin MD, et al. Relationship of antiphospholipid antibodies to cardiovascular manifestations of systemic lupus erythematosus. Arthritis Rheum 2006; 54: 3918–25.

11. Wallace JD, Hahn BH. DuboisęLupus erythematosus 2007; 670–671. 111.

12. Urowitz MB, et al. Atherosclerotic vascular events in a single large lupus cohort: Prevalence and risk factors. J Rheumatol 2007; 34: 70–5.

13. Wei L, et al. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 2004; 141: 764–70.

14. Almdal T, et al. The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death. Arch Intern Med 2004; 164: 1422–26.

15. Denny MF, Thacker S, Mehta H, et al. Interferon-alpha promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis. Blood 2007; 110: 2907–15.

16. 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: 1542–43.

17. Jimenez S. at al, Preclinical vascular disease in SLE a primary AS. Rheumatology 2005; 44: 756–761.

18. Roman MJ, Crow MK, Lockshin MD, et al. Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 2007; 56: 3412–19.

19. Wallace JD, Hahn BH. DuboisęLupus erythematosus 2007; 663–665.

20. Manzi S, et al. Inflammation-mediated rheumatic diseases and atherosclerosis. Ann Rheum Dis 2000; 59: 321–325.

21. Wallace JD, Hahn BH. DuboisęLupus erythematosus 2007; 3591.

22. Vuilleumier N, Reber G, James R, Burger D, de Moerloose P, Dayer JM, Roux-Lombard P. Presence of autoantibodies to apolipoprotein A-1 in patients with acute coronary syndrome further links autoimmunity to cardiovascular disease. J Autoimmun 2004; Dec; 23(4): 353–60.

23. Zhang CY, Lu LJ, et al. People‘s Republic of China. Evaluation of risk factors that contribute to high prevalence of premature atherosclerosis in Chinese premenopausal systemic lupus erythematosus patiens. J Clin Rheumatol 2009 Apr;15(3): 111–6.

24. Petri M. Thrombosis and systemic lupus erythematosus: the Hopkins Lupus Cohort perspective. Scand J Rheumatol 1996; 25: 191–3.

25. Bruce IN, Urowitz MB, Gladman DD, et al. Risk factors for coronary heart disease in women with systemic lupus erythematosus: the Toronto Risk Factor Study. Arthritis Rheum 2003; 349: 2399–406.

26. Bultink IE, Teerlink T, Heijst JA, et al. Raised plasma levels of asymmetric dimethylarginine are associated with cardiovascular events, disease activity, and organ damage in patients with systemic lupus erythematosus. Ann Rheum Dis 2005; 64: 1362–65.

27. Sun SS, Shiau YC, Tsai SC, et al. The role of technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (SPECT) in the detection of cardiovascular involvement in systemic lupus erythematosus patients with non-specific chest complaints. Rheumatology (Oxford) 2001; 40: 1106–11.

28. Asanuma Y, et al. Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003; 349: 2407–15.

29. Thompson T, et al. Progression of carotid intima-media thickness and plaque in women with systemic lupus erythematosus. Arthritis Rheum 2008; 58:835–42.

30. 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: 846–50.

31. Kiani AN, Mahoney JA, Petri M. Asymmetric dimethylarginine is a marker of poor prognosis and coronary calcium in systemic lupus erythematosus. J Rheumatol 2007 Jul; 34(7): 1502–5.

32. 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.

33. Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 2004; 141: 764.

34. Lee AB, et al. Traditional risk factor assessment does not capture the extent of cardiovascular risk in systemic lupus erythematosus. Intern Med J 2006; 36: 237.

35. Hafström I, Rohani M, Deneberg S, Wörnert M, Jogestrand T, FrostegĆrd J. Effects of low-dose prednisolone on endothelial function, atherosclerosis, and traditional risk factors for atherosclerosis in patients with rheumatoid arthritis a randomized study. J Rheumatol 2007; Sep; 34(9): 1810–6.

36. Małyszko J, Małyszko JS, Takada A, Myśliwiec M. Effects of immunosuppressive drugs on platelet aggregation in vitro. Ann Transplant 2002; 7(1): 55–68.

37. Rahman P, Gladman DD, Urowitz MB, et al. The cholesterol lowering effect of antimalarial drugs is enhanced in patients with lupus taking corticosteroid drugs. J Rheumatol 1999; 26: 325–30.

38. Belizna CC, Richard V, Primard E, Kerleau JM, Cailleux N, Louvel JP, Marie I, Hamidou M, Thuillez C, Lévesque H. Early atheroma in primary and secondary antiphospholipid syndrome: an intrinsic finding. Semin Arthritis Rheum 2008; Jun; 37(6): 373–80.

39. Gibson WT, Hayden MR. Centre for Molecular Medicine and Therapeutics, Child and Mycophenolate mofetil and atherosclerosis: results of animal and human studies. Ann N Y Acad Sci 2007 Sep; 1110: 209–21.

40. Roman MJ, Shanker BA, Davis A, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003; 349: 2399–406.

41. Kerekes G, Soltész P, Dér H, Veres K, Szabó Z, Végvári A, Szegedi G, Shoenfeld Y, Szekanecz Z. Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. Clin Rheumatol 2009; Jun; 28(6): 705–10, Epub 2009 Mar 25.

42. Sidiropoulos PI, Siakka P, Pagonidis K, Raptopoulou A, Kritikos H, Tsetis D, Boumpas DT. Sustained improvement of vascular endothelial function during anti-TNFalpha treatment in rheumatoid arthritis patients. Scand J Rheumatol 2009 Jan-Feb; 38(1): 6–10.

Dermatology & STDs Paediatric rheumatology Rheumatology
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.


Don‘t have an account?  Create new account