Abstract
Rapid-onset cardiovascular disease (CVD) is a major concern for many patients with systemic lupus erythematosus (SLE). Cardiovascular events occur more frequently and with earlier onset in patients with SLE compared with healthy individuals. Traditional risk factors, such as altered lipid levels, aging and smoking, do not fully explain this increased risk of CVD, strongly suggesting that autoimmunity contributes to accelerated atherosclerosis. Altered immune system function is recognized as the primary contributor to both the initiation and progression of atherosclerosis. Multiple manifestations of autoimmunity, including changes in cytokine levels and innate immune responses, autoantibodies, adipokines, dysfunctional lipids, and oxidative stress, could heighten atherosclerotic risk. In addition, multiple SLE therapeutics seem to affect the development and progression of atherosclerosis both positively and negatively. SLE-specific cardiovascular risk factors are beginning to be discovered by several groups, and development of a comprehensive, clinically feasible biomarker panel could be invaluable for identification and treatment of patients at risk of developing accelerated atherosclerosis. Here, we discuss the epidemiology of CVD in SLE and the implications of immune system dysfunction on the development and progression, monitoring and treatment of atherosclerosis in individuals with this disease.
Key Points
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Cardiovascular disease (CVD) is a substantial contributor to morbidity and mortality in patients with systemic lupus erythematosus (SLE)
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SLE-specific risk factors for accelerated atherosclerosis exist, but are poorly understood
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Endothelial cell dysfunction plays a major part in accelerated atherosclerosis in patients with SLE
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Identification of SLE-specific mechanisms of, and biomarkers, for accelerated atherosclerosis should lead to the development of novel screening protocols for early detection of CVD and discovery of new therapeutic targets
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Acknowledgements
We apologize to the many researchers whose relevant studies were not cited here owing to space constraints. Research pursuits of the authors were supported by funding from NIH/NIAMS (K01 AR-059,095-01 to B. J. Skaggs; K23 AR-053,864-01A1 to M. McMahon), the Arthritis National Research Foundation (B. J. Skaggs), the Arthritis Foundation, Pacific Region (B. J. Skaggs and M. McMahon), Rheuminations, Inc. (B. H. Hahn), Alliance for Lupus Research (B. H. Hahn and M. McMahon), and Lupus Research Institute (B. H. Hahn and M. McMahon). B. H. Hahn is also the recipient of a Kirkland Scholar award.
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Skaggs, B., Hahn, B. & McMahon, M. Accelerated atherosclerosis in patients with SLE—mechanisms and management. Nat Rev Rheumatol 8, 214–223 (2012). https://doi.org/10.1038/nrrheum.2012.14
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