Abstract
Inflammatory pathways have been implicated in the initiation and progression of cardiovascular diseases. Accelerated atherosclerosis has been described in patients with chronic inflammatory diseases, particularly rheumatoid arthritis, disproportionate to individuals' detectable traditional vascular risk factors. This finding suggests that other pathways associated with inflammation might account for increased vascular risk in such diseases. Highly specific biologic agents can precisely block the activity of cytokines generated during inflammatory cascades; the effects of these inflammatory moieties on vascular physiology and overall risk of cardiovascular events has been directly evaluated. This Review summarizes key epidemiologic, physiologic and model data, which together suggest that tumor necrosis factor, a pivotal cytokine in the inflammatory cascade, is directly involved in vascular pathophysiology and that its inhibition might confer an overall advantage to the recipient. Moreover, such data obtained in chronic inflammatory diseases likely have relevance to primary atherosclerosis.
Key Points
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A variety of chronic inflammatory disorders confer increased risk of cardiovascular disease and attendant early mortality
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Tumor necrosis factor (TNF) is a key cytokine that mediates effector pathways in both inflammatory disease target tissues and in atherosclerotic vessels
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Clinical TNF blockade for treating inflammatory arthritis modulates vascular risk factors, generally in a beneficial direction, but there is a need for further data
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Epidemiologic data suggest that TNF blockade, and inflammatory suppression in general, might have beneficial effects on vascular outcomes in patients with inflammatory arthritis; however, definitive data are lacking
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Current data do not support the use of TNF antagonists as the primary intervention for the treatment or prevention of cardiovascular disease
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G. E. McKellar has received speaker fees from Abbott. D. W. McCarey has served on an advisory board for Wyeth, and has received speaker fees and conference funding from Wyeth and Abbott. N. Sattar has consulted on TNF blockers for Abbott, consulted for Roche, and received speakers fees from both companies. I. B. McInnes consulted on TNF blockers for, and received unrestricted research grant support from, Schering, Wyeth and Abbott.
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McKellar, G., McCarey, D., Sattar, N. et al. Role for TNF in atherosclerosis? Lessons from autoimmune disease. Nat Rev Cardiol 6, 410–417 (2009). https://doi.org/10.1038/nrcardio.2009.57
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DOI: https://doi.org/10.1038/nrcardio.2009.57
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