ReviewDo all lupus patients need statins?
Section snippets
Mechanism of action of statins
Statins inhibit the enzyme HMG-CoA reductase, which catalyzes the transformation of HMG-CoA into mevalonate [5], thereby blocking the pathway for cholesterol synthesis from mevalonate. Another effect of HMG-CoA reductase inhibition is a decrease in isoprenylated proteins such as farnesyl, geranyl, and geranyl-generanyl, which play a key role in anchoring signaling proteins (Ras, Rho, and heterotrimeric G proteins) to the cell membrane. The result is a wide variety of intracellular effects that
Epidemiology
Sound evidence of excess cardiovascular morbidity and mortality in SLE patients has been obtained [10]. Urowitz et al. first drew attention to the cardiovascular complications seen in SLE, based on an analysis of causes of death in 81 patients [11]. They found two mortality peaks: one occurred within the first year and was related to SLE activity and adverse effects of immunosuppressive drugs, and the other occurred more than 5 years after the diagnosis and was due to atherosclerosis [11].
Statins and subclinical atheroma
As indicated above, no therapeutic trials have specifically evaluated whether statin therapy diminishes morbidity and mortality rates in SLE patients. However, this issue has been addressed by evaluations of statin effects on atheroma in animal models and on markers for subclinical atheroma.
Animal models
The potential of statin therapy for decreasing disease activity in SLE has been evaluated in both animal models and human patients. The results are somewhat conflicting. In murine models, intraperitoneal atorvastatin diminished renal disease severity, anti-DNA antibody titers, and Class II antigen expression on monocytes and lymphocytes, whereas the same drug given orally had no effect [50], [51]. Pravastatin failed to affect renal disease, survival, or SLE activity, despite a significant
Statins as inducers of systemic lupus erythematosus
Statins have been reported to induce lupus. Between 1996 and 2005, 10 cases of SLE and three of subacute cutaneous SLE induced by statin therapy were reported [56]. However, the causal relationship between statin exposure and lupus development remains unclear.
Conclusion
Statins should not be given routinely to patients with SLE. Potential immunomodulating effects of statins have not been convincingly established. Although the effects of statins on subclinical atheroma remain unclear and no studies have demonstrated the efficacy of statin therapy as primary or secondary cardiovascular prevention, we believe a serum lipid profile must be obtained once a year in every SLE patient. We agree with recommendations that the LDL-cholesterol level be kept below 100 mg/dL
Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.
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Cited by (17)
Targeting abnormal lipid metabolism of T cells for systemic lupus erythematosus treatment
2023, Biomedicine and PharmacotherapyTreatment of Lipid Metabolism Disturbances in Autoimmune Diseases
2017, Handbook of Systemic Autoimmune DiseasesCitation Excerpt :Until clear and specific international guidelines are available, the clinical indication for statin use in autoimmune diseases should be established based on the patient general profile in terms of disease activity, lipid levels, comorbidities, and drug use, considering that the autoimmune disease itself is a strong ATH risk factor. Suggestions for LDL-C targets have been given for RA (Hollan et al., 2015) and SLE (Soubrier et al., 2013). In any case, statin treatment should be added to a healthy diet and adequate physical exercise, and attention should be paid to possibly use the less atherogenic drugs available for the control of each disease.
The antiphospholipid syndrome in patients with systemic lupus erythematosus
2017, Journal of AutoimmunityCitation Excerpt :In persistently aPL-positive patients, fluvastatin was shown to reversibly reduce proinflammatory and prothrombotic biomarkers [121]. LDL cholesterol level in primary prophylaxis of CV events in SLE patients should be kept below 100 mg/dL, and the statin therapy requires monitoring precautions (transaminase levels) given the high prevalence of comorbidities and the use of concomitant medications in SLE patients [122]. There are also negative reports on statins, as atorvastatin was not able to reduce subclinical measures of atherosclerosis (helical CT scan and carotid duplex) or disease activity in SLE patients [123].
Dyslipidemia in systemic lupus erythematosus: Just another comorbidity?
2016, Seminars in Arthritis and RheumatismCitation Excerpt :On the other hand, SCORE was shown to independently predict increased carotid IMT [100]. Nevertheless, it was recently suggested that all lupus patients should be monitored for lipid profile annually and administered lipid-lowering agents, mainly statins, when required (LDL target 100 mg/dL for primary prevention and 70 mg/dL for secondary prevention of CV events) [101]. First-line therapy in children and adolescents involves diet and exercise interventions for 6 months, then HCQ, then statins and bile acid sequestrants, then niacin and fibrates in a multidisciplinary lipid clinic [102].
Assessing the cardiovascular risk in patients with systemic lupus erythematosus
2014, Revue de Medecine Interne