Discussion of Treatment Options
The patient was treated with hydroxychloroquine and prednisone, in addition to several disease-modifying agents, to reduce SLE disease activity and prevent accrual of damage. Her development of subclinical atherosclerosis over a 4-year period probably reflects the interplay of traditional risk factors with sub-optimally controlled SLE-related inflammation. Although it is crucial to control traditional risk factors for atherosclerosis in patients with SLE, this case highlights the concurrent need to control SLE disease activity.
Unfortunately, no evidence demonstrating the effectiveness of any strategy for decreasing atherosclerosis in patients with SLE has been published, and clinicians must therefore rely upon evidence-based recommendations for the general population. Traditional risk factors for atherosclerosis, such as hypertension, diabetes, obesity, and smoking, should be aggressively controlled by pharmacotherapy, dietary modification, smoking cessation and increased physical activity. Angiotensin-converting enzyme inhibition reduces the risk of stroke, myocardial infarction and death in high-risk patients and might have been a useful therapeutic adjunct in the case patient when she developed proteinuria and left ventricular hypertrophy. Dyslipidemia should be corrected, although formal guidelines for cholesterol management in patients with SLE are lacking. It has been proposed that SLE be considered a risk for CAD equivalent to that of diabetes, and that patients with SLE be treated with the aim of achieving a target LDL cholesterol level of less than 100 mg/dl; however, aggressive statin therapy must be approached cautiously, as preliminary data indicate an increased incidence of adverse events in patients with SLE treated with atorvastatin, without a reduction in measures of subclinical atherosclerosis.
Elevated homocysteine levels have been associated with atherosclerosis in the general population, as well as in patients with SLE.[8,10,16] This association might be attributable to the toxic effects of homocysteine upon vascular endothelium, as well as its promotion of increased vascular smooth muscle cell proliferation.[1,2] Although dietary folic acid supplementation decreases homocysteine levels, it does not conclusively improve secondary prevention of ischemic disease, and has not been evaluated for primary prevention. Primary prophylaxis with low-dose aspirin can also be considered in patients with SLE with additional atherosclerotic risk factors, but evidence for this intervention is currently insufficient and must be weighted against bleeding risk.[2,14,18]
Importantly, the available data indicate that aggressive management of active SLE might be helpful in forestalling accelerated atherosclerosis. The study that the patient was enrolled in showed that a history of cyclophosphamide use was independently associated with a decreased likelihood of carotid atherosclerosis in patients with SLE, and that hydroxychloroquine use was more prevalent in patients with SLE without plaque. Hydroxychloroquine use might protect against accelerated atherosclerosis, because it has anti-inflammatory, antiplatelet, and cholesterol-lowering properties.[1,2]
The case patient had substantial exposure to corticosteroids over her disease course, but the role of corticosteroids in the development of atherosclerosis remains controversial. Some studies have shown corticosteroids to be associated with increased atherosclerosis in patients with SLE, perhaps as a surrogate for increased SLE disease activity, or via exacerbation of traditional risk factors including hypertension, diabetes, dyslipidemia and obesity.[2,6,8] Conversely, corticosteroids have also been associated with decreased subclinical atherosclerosis, perhaps by ameliorating the overall inflammatory burden.
Nat Clin Pract Rheumatol. 2007;3(8):473-478. © 2007 Nature Publishing Group
Written consent was obtained from this patient to participate in the Hospital for Special Surgery Autoimmune Disease Registry and Accelerated Atherosclerosis in SLE study. Both these protocols were approved by the Hospital for Special Surgery Institutional Review Board.
Cite this: Subclinical Carotid Atherosclerosis in a Patient with Systemic Lupus Erythematosus - Medscape - May 18, 2007.