- Open Access
SLE - Practical and theoretical barriers to the prevention of accelerated atherosclerosis in systemic lupus erythematosus
Arthritis Res Thervolume 5, Article number: 178 (2003)
Accelerated atherosclerotic vascular disease (ASVD) is a major cause of death in systemic lupus erythematosus (SLE). Although many authorities are calling for aggressive assessment and management of cardiac risk factors in patients with SLE, both theoretical and practical barriers to this approach exist. It seems that SLE and/or its treatment are themselves strong risk factors for the development of ASVD and it is unclear how much this risk can be decreased by the control of traditional risk factors. Studies from several centers have shown that suboptimal risk factor management and barriers to acceptance of these measures must also be studied further.
Aggressive and accelerated atherosclerosis is a major problem in systemic lupus erythematosus (SLE) and is one of its major causes of death, an observation first made more than 20 years ago by Urowitz . Coronary artery disease develops in 6–9% of SLE patients and accounts for up to 36.4% of deaths in SLE. High rates of atherosclerotic vascular disease (ASVD) are particularly striking in young women with SLE, normally at low risk. The incidence of myocardial infarction in women with SLE aged 35–44 years is 50-fold greater than in women of similar ages from a population-based sample . Non-invasive methods of demonstrating atherosclerotic disease, such as carotid duplex ultrasound, electron-beam computed tomography, and thallium perfusion scanning, and one autopsy study, suggest that symptomatic disease might be the tip of the iceberg. The true incidence could be as high as 74% [3–10].
The pathophysiology of SLE-associated atherosclerosis is unknown, but the emerging picture is that many of the same risk factors as those observed in normal individuals are also involved. This has motivated authorities in both rheumatology and preventive cardiology to advocate more aggressive risk factor assessment and management of risk factors [11–17]. There are theoretical and practical barriers to improving atherosclerosis-related outcomes in SLE suggesting that this approach will be challenging, and the potential benefit is yet unknown.
First, when risk factors are examined quantitatively, SLE and/or its treatment (most probably with corticosteroids) are the most important risk factors. Indeed, data from Esdaile and colleagues suggest that even after adjusting for 'normal risk', SLE and/or its treatment increases the risk of coronary artery disease 5–10-fold . This suggests that even if physicians were perfectly virtuous, sought out risk factors aggressively and followed guidelines scrupulously; and patients were tolerant, compliant, and responsive to lipid-lowering strategies and blood pressure control, for example, there would still be excess mortality and morbidity from ASVD.
Second, studies from Toronto and Baltimore show that risk factor identification and, by implication, treatment fall short of what one would predict from the importance of the problem [13, 19]. We know that patients with chronic diseases such as SLE, rheumatoid arthritis, and diabetes are less likely to receive the highest quality of preventive health care, perhaps because more urgent problems must be dealt with first, or perhaps because of patients' and physicians' exhaustion in dealing with chronic health problems. Patients can find it difficult to change their lifestyles and take additional medications on top of complicated regimens or little reinforcement from their providers. In recruiting patients with SLE and hyperlipidemia for a statin dosing study, our experience has been that the patients who are the most willing to participate are relatively young and healthy, with very mild SLE, and few other health problems or medications. Among those patients with more long-standing and severe SLE, reasons for non-participation have included, 'I'm flaring and don't want to take another medication that might make me sick', 'I'm trying to get healthy', and 'I'm too sick and have too many doctor's appointments already'.
HL Mencken once quipped, 'For every complex problem, there is a solution which is simple, neat and wrong'. We have known for over 20 years of the late complications of SLE. The received wisdom that we need only try harder to implement the known effective preventive strategies for normal individuals is simple and neat, but might be wrong or incomplete.
Several questions remain unanswered in our search for a successful approach to the prevention of ASVD in SLE. The etiologic factors responsible for vascular injury in SLE need to be understood more precisely. For example, do short-term hypertension, hyperlipidemia, and immune complex generation of an SLE flare do as much or more damage to the endothelium as does lower-grade inflammation or exposure to traditional risk factors for many years? In addition, a better understanding of patient social and cultural factors will be essential to achieving acceptance of lifestyle changes and medications. Progress will only be made as basic science brings an understanding of the mechanisms of accelerated atherosclerosis in SLE and as clinical studies address both the efficacy and the effectiveness of existing and improved risk factor control.
atherosclerotic vascular disease
systemic lupus erythematosus.
Urowitz MB, Bookman AAM, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA: The bimodal mortality pattern of systemic lupus erythematosus. Am J Med. 1976, 60: 221-225. 10.1016/0002-9343(76)90431-9.
Manzi S, Meilahn EN, Rairie JE, Conte CG, Medsger TA, Jansen-McWilliams L, D'Agostino RB, Kuller LH: 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.
Badui E, Garcia-Rubi D, Robles E, Jimenez J, Juan L, Deleze M, Diaz A, Mintz G: Cardiovascular manifestations in systemic lupus erythematosus. Prospective study of 100 patients. Angiology. 1985, 36: 431-441.
Bruce IN, Burns RJ, Gladman DD, Urowitz MB: High prevalence of myocardial perfusion abnormalities in women with SLE [abstract]. Arthritis Rheum. 1997, 40 (suppl): S219-
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. 10.1016/0002-9343(75)90575-6.
Kong TQ, Kellum RE, Haserick JR: Clinical diagnosis of cardiac involvement in systemic lupus erythematosus: a correlation of clinical and autopsy findings in thirty patients. Circulation. 1962, 26: 7-11.
Hosenpud JD, Montanaro A, Hart MV, Haines JE, Specht HD, Bennett RM, Kloster FE: Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus. Am J Med. 1984, 77: 286-292. 10.1016/0002-9343(84)90704-6.
Shome GP, Sakauchi M, Yamane K, Takemura H, Kashiwagi H: Ischemic heart disease in systemic lupus erythematosus. A retrospective study of 65 patients treated with prednisolone. Jpn J Med. 1989, 28: 599-603.
Haider YS, Roberts WC: Coronary arterial disease in systemic lupus erythematosus; quantification of degrees of narrowing in 22 necropsy patients (21 women) aged 16 to 37 years. Am J Med. 1981, 70: 775-781. 10.1016/0002-9343(81)90532-5.
Manzi S, Selzer F, Sutton-Tyrrell K, Fitzgerald SG, Rairie JE, Tracy RP, Kuller LH: Prevalence and risk factors of carotid plaque in women with systemic lupus erythematosus. Arthritis Rheum. 1999, 42: 51-60. 10.1002/1529-0131(199901)42:1<51::AID-ANR7>3.0.CO;2-D.
Salmon JE, Roman MJ: Accelerated atherosclerosis in systemic lupus erythematosus: implications for patient management. Curr Opin Rheumatol. 2001, 13: 341-344. 10.1097/00002281-200109000-00001.
Aranow C, Ginzler EM: Coronary artery disease in SLE: high suspicion leads to early recognition. J Musculoskel Med. 2000, 17: 473-482.
Bruce IN, Gladman DD, Urowitz MB: Detection and modification of risk factors for coronary artery disease in patients with systemic lupus erythematosus: a quality improvement study. Clin Exp Rheumatol. 1998, 16: 435-440.
Hallegua DS, Wallace DJ: How accelerated atherosclerosis in SLE has changed our management of the disorder. Lupus. 2000, 9: 228-231. 10.1191/096120300678828181.
Lockshin MD, Salmon JE, Roman MJ: Atherosclerosis and lupus: a work in progress. Arthritis Rheum. 2001, 44: 2215-2217. 10.1002/1529-0131(200110)44:10<2215::AID-ART381>3.3.CO;2-F.
Giri S, Parke AL, Waters DD: Controlling cardiovascular risk factors in systemic lupus erythematosus. J Musculoskel Med. 1998, 15: 42-52.
El-Magadmi M, Ahmad Y, Wajed J, Bruce IN: The bimodal mortality pattern in systemic lupus erythematosus. Curr Med Lit Rheumatol. 2003, 22: 1-6.
Esdaile JM, Abrahamowicz M, Grodzicky T, Li Y, Panaritis C, du Berger R, Cote R, Grover SA, Fortin PR, Clarke AE, Senecal JL: Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum. 2001, 44: 2331-2337. 10.1002/1529-0131(200110)44:10<2331::AID-ART395>3.0.CO;2-I.
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.
KHC is supported by a Physician Scientist Development Award from the Arthritis Foundation and American College of Rheumatology, and a grant from the Arthritis National Research Foundation. MHL is supported by an NIH grant P60 AR47782 and by a Kirkland Scholar Award.