Table 2. Specific processes in LE that may accelerate atherosclerosis and hence ASCVD event risk (Reproduced with permission from Keyes et al⁵).

Pathogenetic step	Explanation	References
Plaque initiation	Worsening of causative agents (dyslipoproteinaemia: elevated plasma triglycerides, with low levels of high-density lipoprotein cholesterol) and exacerbators (hypertension, renal disease), associated with LE and LE therapies, particularly glucocorticoids.Possible effects beyond conventional factors: increased LDL retention through effects on arterial matrix and susceptibility of LDL to aggregate owing to changes in its lipidome specific to LE.Endothelial dysfunction, a known feature of LE, might include increased permeability to the entry of LDL and other apolipoprotein B lipoproteins.	87102 107
Plaque growth	Worsening of causative agents (dyslipoproteinaemia) and exacerbators (hypertension, renal disease).Increased immune cell responses to retained lipoproteins, a finding in mouse models of LE after they are made hypercholesterolaemic. Endothelial dysfunction in this context might include increased expression of chemoattractants and cell adhesion molecules.Increased induction and intra-arterial secretion of local proaggregation enzymes (lipoprotein lipase and the secretory acid sphingomyelinase) released from activated endothelium and local persistent immune cells.	108 113
Plaque destabilisation	Decreased collagen synthesis; increased protease production.	114 115
Formation of occlusive thrombus	Systemic procoagulant state and hyperresponsive platelets that increase the likelihood of the formation of an occlusive thrombus after plaque rupture or erosion. Procoagulant microvesicles have been implicated, particularly tissue factor-positive microvesicles. Endothelial dysfunction in this context might include impairment of the anticoagulant luminal surface and impaired vasodilation, thereby facilitating occlusion.	116

ASCVDatherosclerotic cardiovascular diseaseLDLlow-density lipoproteinLElupus erythematosus