Mechanistic Insights Into the Link Between Inflammation and Cardiovascular Disease

Thirty years ago, a diagnosis of rheumatoid arthritis (RA) resigned the majority of patients to a lifetime of chronic inflammation and progressive joint destruction. With the potent disease-modifying antirheumatic drugs (DMARDs) available today, severe disability from RA is the exception rather than the rule. Now, the leading cause of mortality in RA is cardiovascular disease.1 In fact, the risk of cardiovascular disease in RA is 1.5× that of age- and sex-matched individuals from the general population.2 This excess risk in RA has been attributed to chronic inflammation rather than a higher prevalence of traditional cardiovascular risk factors.3 Large observational studies show that treatment with DMARDs, such as methotrexate and tumor necrosis factor inhibitors, is associated with reduced cardiovascular risk.4,5 The exact mechanisms linking inflammation with cardiovascular risk remain unclear. Studying pathways shared by both RA and atherosclerosis may provide insight into potential mechanisms of risk.Article see p 619Patients with RA differ from the general population in both the magnitude and variability of inflammation they experience. As an example, a C-reactive protein (CRP) level of ≥3 mg/L is considered a marker for elevated cardiovascular risk and is high for an individual from the general population.6 In comparison, the mean CRP in a cohort of treated patients with RA at our academic institution is 9.7 mg/L.7 Fluctuations in CRP >50% routinely occur as part of RA flares and treatment. This amplification of fluctuations in the levels of inflammation provides a unique opportunity to study the association of changes in inflammation with physiological parameters of cardiovascular risk such as flow-mediated dilatation and coronary flow reserve.8,9Treatment of RA with DMARDs targets preventing joint damage by controlling inflammation. Anti-cytokine DMARDs are directed at specific inflammatory mediators that are also involved in …