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

Shahir S Hamdulay ¹ and Justin C Mason ^1*

¹ Imperial College, United Kingdom

^* To whom correspondence should be addressed. E-mail: justin.mason{at}imperial.ac.uk.

Accepted 4 June 2009

Abstract

Our understanding of the pathogenesis of atherosclerosis has evolved from a lipid deposition disorder to a focal, chronic inflammatory disease of medium-large arteries characterized 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 tumor necrosis factor- (TNF), 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. However, the association between atherosclerosis and RA extends beyond common pathogenic mechanisms. Standardized 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. A similar alarming trend is observed in systemic lupus erythematosus (SLE), with a marked increase in stroke and myocardial infarction (MI) reported. This outcome data reflects the presence of increased carotid artery intima thickening, vascular stiffness and impaired flow-mediated vasodilation (FMD) in RA and SLE, indicating endothelial dysfunction and subclinical atherosclerosis. The current challenge to clinicians is the development of treatment regimens that suppress underlying RA disease activity, inhibit endothelial dysfunction and retard progression of atherosclerosis.