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Published Online
on September 8, 2005

Stroke. 2005
Published online before print September 8, 2005, doi: 10.1161/01.STR.0000181754.38408.4c
A more recent version of this article appeared on October 1, 2005
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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




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