Modern therapy of patients with lupus erythematosus must include appropriate management of their heightened rates of atherosclerotic cardiovascular events: a literature update

Abstract

Atherosclerotic cardiovascular disease (ASCVD) remains the biggest killer of patients with lupus erythematosus (LE) and the general non-autoimmune population. In this literature update on LE and ASCVD, we focused on published work since our earlier review article, meaning from 2021 to the present, with an emphasis on cutaneous LE. Several themes emerged. First, new work shows that patients with lupus still exhibit a high burden of conventional risk factors for ASCVD events. Second, recent studies continue to implicate possible effects of lupus disease activity to worsen rates of ASCVD events beyond predictions from conventional risk factors. Third, new work on estimating the risk of future ASCVD events in patients with lupus supports arterial-wall imaging, inclusion of lupus-specific factors, estimators of ASCVD event risk that take lupus status into account and considering lupus as a diabetes equivalent or even as a diabetes-plus-smoking equivalent in this context. Technologies for arterial-wall imaging continue to improve and will likely play an increasing role in ASCVD assessment and management. Fourth, purported cardiovascular benefits from certain disease-modifying antirheumatic drugs such as antimalarials have become less clear. Fifth, earlier treatment of atherosclerosis, which is a lifelong disease, can be accomplished with diet, exercise, smoking cessation and new classes of safe and effective medications for lipid-lowering and blood pressure control. Benefits on subclinical arterial disease by imaging and on ASCVD events have been reported, supporting the concept that ASCVD is eminently manageable in this autoimmune condition. Sixth, despite the heightened risk for ASCVD events in patients with lupus, available therapeutic approaches remain unused or underused and, accordingly, event rates remain high.Raising awareness among patients and healthcare providers about ASCVD assessment and management in patients with LE is essential. Greater vigilance is needed to prevent ASCVD events in patients with lupus by addressing dyslipidaemias, hypertension, smoking, obesity and physical inactivity.

Keywords: Atherosclerosis; Cardiovascular Diseases; Lipids; Lupus Erythematosus, Systemic.

Figure 1. The response-to-retention model for the pathogenesis of atherosclerosis. Arrows are colour coded to indicate crucial mechanisms in retention and modification. The key initiating step in atherogenesis is the retention and aggregation of cholesterol-rich atherogenic apolipoprotein B lipoproteins within the arterial wall (yellow). Then, maladaptive local responses to the retained and modified lipoproteins lead to plaque growth and progression (red). Processes to the left of the vertical dashed line are characteristic of early atherosclerotic plaques and hence remain entirely or nearly entirely reversible, while processes to the right of the vertical dashed line are characteristic of advanced, end-stage plaques and hence appear to be only partially reversible. Foam cell pertains to a macrophage or smooth muscle cell that has accumulated intracellular droplets of lipid. C-TRL, cholesterol and triglyceride-rich lipoprotein; IDL, intermediate-density lipoprotein; IEL, internal elastic lamina; IFN, interferon; IL, interleukin; LDL, low-density lipoprotein; LP, lipoprotein; Lp(a), lipoprotein(a); LpL, lipoprotein lipase; MMPs, matrix metalloproteinases; PGs, proteoglycans; SMase, the secretory acid sphingomyelinase; SMC, smooth muscle cell; TF, tissue factor; UC, unesterified cholesterol. Reproduced with permission from Williams, which was adapted from Williams and Tabas.

Figure 2. Flow chart of management, both primary and secondary prevention, in the context of lupus erythematosus (LE). ACEi, ACE inhibitor; ARB, angiotensin receptor blocker; ASCVD, atherosclerotic cardiovascular disease. Updated with permission from Keyes et al.