Atherosclerotic cardiovascular disease in systemic lupus erythematosus: from preclinical lupus to atherosclerotic plaque erosion

Abstract

Patients with systemic lupus erythematosus (SLE) have increased risk of developing atherosclerotic cardiovascular disease (ASCVD). This excessive risk starts to accumulate during the earliest stages of SLE. ASCVD in SLE is associated with an adverse outcome. SLE-enhanced atherogenesis is most likely the consequence of a complex interplay between traditional risk factors and chronic auto-immune inflammation. This underscores the importance of conscientious management of traditional risk factors as well as maintaining low SLE disease activity. Shared immune pathways in SLE and ASCVD can affect the vascular biology of the atherosclerotic process in patients with SLE. In this review, we will discuss how the ASCVD risk evolves during the SLE disease course, and we consider whether patients with SLE are prone to developing superficial erosion of atherosclerotic plaques. This is highly relevant as pilot studies in the general population suggest antithrombotic therapy without stenting could be the better therapeutic approach in patients with plaque erosion.

Keywords: atherosclerosis; cardiovascular disease; endothelium; plaque erosion; plaque rupture; systemic lupus erythematosus.

Graphical abstract

Figure 1.

Timeline of major findings relating to the association between traditional risk factors and the increased risk of ASCVD and SLE. AMI: acute myocardial infarction; ASCVD: atherosclerotic cardiovascular disease; CAD: coronary artery disease; MI: myocardial infarction

Figure 2.

In plaque rupture, a gradually growing lipid and necrotic atherosclerotic plaque is being shielded from the arterial circulation by an overlying fibrous cap. Indolent progression with ongoing inflammation renders this fibrous cap prone to rupture. This is immediately followed by forming of a (often occlusive) red thrombus, which is rich in fibrin and trapped erythrocytes. A ruptured plaque is characterized by a thin (ruptured) fibrous cap, large lipid core, vast infiltration of inflammatory cells (predominantly macrophages) and a fibrin-rich thrombus. In plaque erosion, immune activation results in superficial desquamation of the endothelial cells from the basement membrane and their subsequent death by apoptosis. Neutrophils undergo NETosis and can entrap circulating platelets, thereby facilitating the formation of a (often non-occlusive) platelet-rich thrombus (white thrombus). An eroded plaque is characterized by a thick and intact fibrous cap, small or absent lipid core, intima rich in smooth muscle cells and proteoglycan matrix and a platelet-rich thrombus