Published Online
on September 8, 2005

A more recent version of this article appeared on October 1, 2005

This Article Full Text (PDF) All Versions of this Article: 36/10/2143    most recent 01.STR.0000181754.38408.4cv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Woodward, M. Articles by MacMahon, S. W. Search for Related Content PubMed PubMed Citation Articles by Woodward, M. Articles by MacMahon, S. W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Stroke Related Collections Other Stroke Treatment - Medical

Submitted on April 1, 2005
Revised on June 21, 2005
Accepted on July 6, 2005

Associations of Inflammatory and Hemostatic Variables With the Risk of Recurrent Stroke

Mark Woodward PhD; Gordon D.O. Lowe MD^*; Duncan J. Campbell MD, PhD; Sam Colman; Ann Rumley PhD; John Chalmers MD, PhD; Bruce C. Neal PhD; Anushka Patel MD; Alicia J. Jenkins MD, PhD; Bruce E. Kemp PhD; and Stephen W. MacMahon PhD

From the George Institute for International Health (M.W., S.C., J.C., B.C.N., A.P., S.W.M.), University of Sydney, Australia; the Cardiovascular and Medical Division (G.D.O.L., A.R.), University of Glasgow, United Kingdom; the Department of Medicine (D.J.C., B.E.K.), St. Vincent’s Hospital, Melbourne, Australia; the St. Vincent’s Institute of Medical Research (D.J.C., A.J.J., B.E.K.), Melbourne, Australia; and CSIRO Health Sciences and Nutrition (B.E.K.), Parkville, Australia.

^* To whom correspondence should be addressed. E-mail: gdl1j{at}clinmed.gla.ac.uk.

Background and Purpose--Several prospective studies have shown significant associations between plasma fibrinogen, viscosity, C-reactive protein (CRP), fibrin D-dimer, or tissue plasminogen activator (tPA) antigen and the risk of primary cardiovascular events. Little has been published on the associations of these variables with recurrent stroke. We studied such associations in a nested case-control study derived from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).

Methods--Nested case-control study of ischemic (n=472) and hemorrhagic (n=83) strokes 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--Fibrinogen and CRP were associated with an increased risk of recurrent ischemic stroke after accounting for the matching variables and adjusting for systolic blood pressure, smoking, peripheral vascular disease, and statin and antiplatelet therapy. The odds ratio for the last compared with the first third of fibrinogen was 1.34 (95% CI, 1.01 to 1.78) and for CRP was 1.39 (95% CI, 1.05 to 1.85). After additional adjustment for each other, these 2 odds ratios stayed virtually unchanged. Plasma viscosity, tPA, and D-dimer showed no relationship with recurrent ischemic stroke, although tPA was significant for lacunar and large artery subtypes. Although each of these variables showed a negative relationship with recurrent hemorrhagic stroke, none of these relationships achieved statistical significance.

Conclusions--Fibrinogen and CRP are risk predictors for ischemic but not hemorrhagic stroke, independent of potential confounders.

Key words: hemostasis • inflammation • stroke

This article has been cited by other articles:

				P. Welsh, G. D.O. Lowe, J. Chalmers, D. J. Campbell, A. Rumley, B. C. Neal, S. W. MacMahon, and M. Woodward Associations of Proinflammatory Cytokines With the Risk of Recurrent Stroke Stroke, August 1, 2008; 39(8): 2226 - 2230. [Abstract] [Full Text] [PDF]

				G. M. Howard-Alpe, J. W. Sear, and P. Foex Methods of detecting atherosclerosis in non-cardiac surgical patients; the role of biochemical markers Br. J. Anaesth., December 1, 2006; 97(6): 758 - 769. [Abstract] [Full Text] [PDF]

				C. L. Carty, P. Heagerty, K. Nakayama, E. C. McClung, J. Lewis, D. Lum, E. Boespflug, C. McCloud-Gehring, B. R. Soleimani, J. Ranchalis, et al. Inflammatory Response After Influenza Vaccination in Men With and Without Carotid Artery Disease Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2738 - 2744. [Abstract] [Full Text] [PDF]

				T. N. Bongers, M. P.M. de Maat, M.-L. P.J. van Goor, V. Bhagwanbali, H. H.D.M. van Vliet, E. B. Gomez Garcia, D. W.J. Dippel, and F. W.G. Leebeek High von Willebrand Factor Levels Increase the Risk of First Ischemic Stroke: Influence of ADAMTS13, Inflammation, and Genetic Variability Stroke, November 1, 2006; 37(11): 2672 - 2677. [Abstract] [Full Text] [PDF]

				M. S. V. Elkind, W. Tai, K. Coates, M. C. Paik, and R. L. Sacco High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med, October 23, 2006; 166(19): 2073 - 2080. [Abstract] [Full Text] [PDF]

				D. Tanne, M. Benderly, U. Goldbourt, M. Haim, A. Tenenbaum, E. Z. Fisman, Z. Matas, Y. Adler, R. Zimmlichman, and S. Behar C-Reactive Protein as a Predictor of Incident Ischemic Stroke Among Patients With Preexisting Cardiovascular Disease Stroke, July 1, 2006; 37(7): 1720 - 1724. [Abstract] [Full Text] [PDF]

				A. B. Maulaz, D. C. Bezerra, P. Michel, and J. Bogousslavsky Rebound Inflammation and the Risk of Ischemic Stroke After Discontinuation of Aspirin Therapy--Reply Arch Neurol, February 1, 2006; 63(2): 301 - 301. [Full Text] [PDF]

				D. J. Campbell, M. Woodward, J. P. Chalmers, S. A. Colman, A. J. Jenkins, B. E. Kemp, B. C. Neal, A. Patel, and S. W. MacMahon Soluble Vascular Cell Adhesion Molecule 1 and N-terminal Pro-B-Type Natriuretic Peptide in Predicting Ischemic Stroke in Patients With Cerebrovascular Disease Arch Neurol, January 1, 2006; 63(1): 60 - 65. [Abstract] [Full Text] [PDF]