Formation and progression of atherosclerotic lesions. (a) Atherosclerosis disease initiation. Patients with rheumatoid arthritis and systemic lupus erythematosus present with clustering of traditional risk factors, notably low high-density lipoprotein (HDL) levels and pro-atherogenic lipid particles, leading to premature establishment of atherosclerotic lesions compared with age-matched and sex-matched control individuals. (b) Progression. Inflammatory disease activity and duration is emerging as a key determinant of the clinical association between cardiovascular disease (CVD) and inflammatory disease. Pro-inflammatory mediators and immune dysregulation features may enhance susceptibility to risk factors and establish chronic inflammation in vascular lesions. (c) Complications. Both inflammatory features and prothrombotic pathways may enhance the likelihood of acute events, increasing mortality. IFN, interferon; LDL, low-density lipoprotein; Lp(a), lipoprotein(a); MCP, monocyte chemoattractant protein; MIF, macrophage migration inhibitory factor; MMP, matrix metalloproteinase; oxLDL, oxidized low-density lipoprotein; PG, prostaglandin; VCAM, vascular cell adhesion molecule; TF, tissue factor; TNF, tumour necrosis factor.