Is the Gap in Incidence of Cardiovascular Events in Rheumatoid Arthritis Really Closing?

It has been recognized for several decades that individuals with rheumatoid arthritis (RA) have shorter life spans than age- and sex-matched individuals without RA, and that the greatest contribution to this increased mortality in RA is cardiovascular (CV) disease, particularly acute myocardial infarctions (AMIs). In metaanalyses of observational studies, the risk of AMI was 68% higher, and the risk of mortality from AMI 59% higher, in patients with RA compared to general population controls.1,2 The causal factor hypothesized to explain these CV risk differences is the exaggerated inflammatory process that is inherent to RA and persists throughout the disease course of RA to varying degrees. Atherosclerosis has been demonstrated histologically to be an inflammatory process with infiltration of monocytes and T cells as an early event in plaque formation.3 This intraplaque inflammatory process can lead directly to erosion and rupture of plaque membrane through cytokine-induced metalloproteinase production, leading to extrusion of thrombogenic material into the vessel lumen and consequent thrombosis and ischemic events.3 Many of the inflammatory cells and molecules in the inflamed and ruptured plaque are represented in the synovia and blood of patients with RA, suggesting that RA further fuels the atherogenic process. A critical question therefore is whether aggressive reduction of inflammation in RA will reduce the enhanced risk of CV disease relative to the general population, or even to levels below the general population. The treatment of RA has changed dramatically in recent decades, beginning with the introduction of methotrexate (MTX) in the late 1980s, anticytokine and other targeted therapies in the late 1990s, and the emphasis on aggressive treat-to-target management of RA in the 2000s. With these advances, there was an expectation that CV morbidity and mortality in RA would decrease accordingly. Specifically, investigators have asked (1) if CV event … Address correspondence to Dr. J.M. Bathon, MD, Professor of Medicine, Division of Rheumatology, Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, NY 10032, USA. Email: jmb2311{at}columbia.edu.

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