Inflamed Joints and Stiff Arteries

Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular events, with an estimated 70% excess mortality rate that can be ascribed to cardiovascular causes in up to 50% of cases.1,2 A 3-fold-increased adjusted risk of myocardial infarction has been reported, particularly in subjects with longer disease duration.3 This has prompted recommendations that RA be considered an independent risk factor for atherosclerosis.2 Mechanisms underlying this increased susceptibility remain uncertain and range from exposure to traditional cardiovascular risk factors to enhanced inflammation and oxidative stress emanating from the synovium leading to early vascular disease,4 and extend to adverse cardiovascular effects of medications.Article p 1185 Epidemiological studies have found either no increase or often a decreased prevalence of traditional cardiovascular risk factors in patients with RA.2,5 However, the dyslipidemia observed in RA is associated with low total and HDL cholesterol and high triglyceride levels, a pattern that is associated with a more dense, easily oxidizable, and intensely atherogenic low-density lipoprotein particle.5 Hyperinsulinemia and insulin resistance can occur in RA, an abnormality that correlates with underlying inflammation.6 The potential mechanisms for this include the use of glucocorticoids and the direct effects of cytokines such as tumor necrosis factor (TNF)-α on impeding insulin-mediated glucose uptake in skeletal muscle and on lipolysis.5 It appears that an atherogenic modification of existing cardiovascular risk factors by the RA milieu, presumably as a result of increased systemic inflammation and oxidative stress, accounts for some of the increased cardiovascular risk. This viewpoint is substantiated by the observed increasing gradient between carotid atherosclerosis and the number of cardiovascular risk factors, with an additive impact of disease severity measured as sedimentation rate, in those with multiple risk factors.7 However, the sedimentation rate had little effect on carotid atherosclerosis in the …