Cardiovascular disease in systemic lupus erythematosus: A comprehensive update

- Accelerated atherosclerosis is prominent feature of systemic lupus erythematosus.
- Traditional and disease related features contribute to the enhanced cardiovascular burden.
- Imbalance between endothelial insults and atheroprotective mechanisms leads to atherogenesis in lupus.

Heightened rates of both cardiovascular (CV) events and subclinical atherosclerosis, documented by imaging and vascular function techniques are well established in systemic lupus erythematosus (SLE). While traditional CV factors such as smoking, dyslipidemia, diabetes mellitus (DM), hypertension, central obesity and hyperhomocysteinemia have been reported to be prevalent in lupus patients, they do not fully explain the high rates of ischemic events so far reported, implying that other factors inherent to disease itself could account for the enhanced risk, including disease duration, activity and chronicity, psychosocial factors, medications, genetic variants and altered immunological mechanisms. Though the exact pathogenesis of atherosclerosis in the setting of lupus remains ill defined, an imbalance between endothelial damage and atheroprotection seems to be a central event. Insults leading to endothelial damage in the setting of lupus include oxidized low density lipoprotein (oxLDL), autoantibodies against endothelial cells and phospholipids, type I interferons (IFN) and neutrophil extracellular traps (NETs) directly or through activation of type I IFN pathway. Increased oxidative stress, reduced levels of the normally antioxidant high density lipoprotein (HDL), increased levels of proinflammatory HDL (piHDL) and reduced paraoxonase activity have been related to increased oxLDL levels. On the other hand, impaired atheroprotective mechanisms in lupus include decreased capacity of endothelial repair-partly mediated by type I IFN- and dampened production of atheroprotective autoantibodies. In the present review, traditional and disease related risk factors for CV disease (CVD) in the setting of chronic autoimmune disorders with special focus on SLE will be discussed.