Associations of proinflammatory cytokines with the risk of recurrent stroke

Welsh, P. , Lowe, G.D., Chalmers, J., Campbell, D., Rumley, A., Neal, B.C., MacMahon, S.W. and Woodward, M. (2008) Associations of proinflammatory cytokines with the risk of recurrent stroke. Stroke, 39(8), pp. 2226-2230. (doi:10.1161/STROKEAHA.107.504498)



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Background and Purpose: There are few reports on proinflammatory cytokines and risk of primary or recurrent stroke. We studied the association of interleukin (IL)-6, IL-18, and tumor necrosis factor-α (TNF-α) with recurrent stroke in a nested case-control study derived from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).

Methods: We performed a nested case-control study of 591 strokes (472 ischemic, 83 hemorrhagic, 36 unknown subtype) occurring during a randomized, placebo-controlled multicenter trial of perindopril-based therapy in 6105 patients with a history of stroke or transient ischemic attack. Controls were matched for age, treatment group, sex, region, and most recent qualifying event at entry to the parent trial.

Results: IL-6 and TNF-α, but not IL-18, were associated with risk of recurrent ischemic stroke independently of conventional risk markers. Adjusted odds ratios comparing the highest to lowest third of their distributions were 1.33 (95% CI, 1.00 to 1.78) for IL-6 and 1.46 (1.02 to 2.10) for TNF-α. No inflammatory marker was associated with hemorrhagic stroke risk. In multivariable models, IL-6 and TNF-α fully explained observed associations of C-reactive protein and fibrinogen with risk of ischemic stroke, but TNF-α retained borderline significance after full adjustment.

Conclusions: Inflammatory markers associated with the acute-phase response (IL-6, TNF-α, C-reactive protein, and fibrinogen, but not IL-18) are associated with risk of recurrent stroke. These markers are dependent on each other in multivariable models, and once all were included, only TNF-α retained a borderline association. Markers of generalized inflammation of the acute-phase response are associated with recurrent stroke, rather than IL-6, C-reactive protein, or fibrinogen in particular.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Campbell, Professor Duncan and Welsh, Dr Paul and Woodward, Professor Mark and Rumley, Dr Ann and Lowe, Professor Gordon
Authors: Welsh, P., Lowe, G.D., Chalmers, J., Campbell, D., Rumley, A., Neal, B.C., MacMahon, S.W., and Woodward, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Stroke
Publisher:American Heart Association
ISSN (Online):1524-4628
Published Online:19 June 2008
Copyright Holders:Copyright © 2008 American Heart Association
First Published:First published in Stroke 39(8):2226-2230
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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