Disease-modifying anti-rheumatic drugs: do they reduce cardiac complications of RA?

Rheumatoid, inflammation and cardiovascular disease

Our understanding of the pathogenesis of atherosclerosis has evolved from a lipid deposition disorder to a focal, chronic inflammatory disease of medium-large arteries characterised by inflammatory plaques susceptible to rupture and thrombosis. Atherogenesis shares certain pathogenic features with other inflammatory diseases including the autoimmune disease rheumatoid arthritis (RA). These include macrophage-activating cytokines such as tumour necrosis factor α (TNFα), interleukin-1 (IL-1) and interleukin-6 (IL-6), the presence of CD4⁺CD28⁻ regulatory T-cells, raised inflammatory markers including C-reactive protein (CRP) and enhanced expression of endothelial adhesion molecules including VCAM-1.1 However, the association between atherosclerosis and RA extends beyond common pathogenic mechanisms. Standardised mortality ratios for cardiovascular disease in RA range from 1.2 to 5, and cardiovascular death accounts for up to 50% of mortality with life expectancy reduced by 10–15 years.2 A similar alarming trend is observed in systemic lupus erythematosus (SLE), with a marked increase in stroke and myocardial infarction (MI) reported.3 These outcome data reflect the presence of increased carotid artery intima thickening, vascular stiffness and impaired flow-mediated vasodilatation (FMD) in RA and SLE, indicating endothelial dysfunction and subclinical atherosclerosis.4

Atherosclerosis may be considered a stereotypical inflammatory response to vascular injury initiated and propagated by traditional risk factors, and the latter may be exacerbated by systemic inflammatory disease. RA and SLE patients …