Published Online
on September 2, 2004

A more recent version of this article appeared on October 1, 2004

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Submitted on February 2, 2004
Revised on May 25, 2004
Accepted on July 14, 2004

Fibrinogen Concentration and Risk of Ischemic Stroke and Acute Coronary Events in 5113 Patients With Transient Ischemic Attack and Minor Ischemic Stroke

Peter M. Rothwell FRCP^*; Sally C. Howard DPhil; Dermot A. Power MRCP; Sergei A. Gutnikov DPhil; Ale Algra MD; Jan van Gijn FRCP; Tanne G. Clark DPhil; Michael F.G. Murphy MD; Charles P. Warlow FRCP; for the Cerebrovascular Cohort Studies Collaboration

From the Stroke Prevention Research Unit (P.M.R., S.C.H., D.A.P., S.A.G.), Department of Clinical Neurology, the Centre for Statistics in Medicine (T.G.C.), University of Oxford, UK; the Julius Center for Health Sciences and Primary Care (A.A.), University Department of Neurology (A.A., J.v.G.), University Medical Center, Utrecht, The Netherlands; the Childhood Cancer Research Group (M.F.G.M.), Woodstock Rd, Oxford, UK; the Department of Clinical Neurology (C.P.W.), Western General Hospital, Edinburgh, UK.

^* To whom correspondence should be addressed. E-mail: peter.rothwell{at}clneuro.ox.ac.uk.

Background and Purpose--Fibrinogen is an independent risk factor for coronary events in population-based studies and in patients with coronary heart disease, but there is uncertainty about prediction of stroke, particularly in secondary prevention.

Methods--We studied unpublished data from 3 prospective studies of patients with recent transient ischemic attack (TIA) or minor ischemic stroke: the United Kingdom TIA Aspirin (UK-TIA) trial (n=1860); the Dutch TIA trial (n=2960); and the Oxford TIA Study (n=293). By separate and pooled analysis, we used Cox models to determine the relationship between fibrinogen and risk of ischemic stroke and other vascular events during 23 272 patient-years of follow-up and adjusted for other risk factors.

Results--There was no significant heterogeneity in fibrinogen risk associations between studies. Fibrinogen predicted subsequent ischemic stroke, with a pooled hazard ratio (HR) for values above the median of 1.34 (95% CI, 1.13 to 1.60; P=0.001). The association tended to be stronger in patients with nonlacunar (HR=1.42; 95% CI, 1.13 to 1.78; P=0.002) than lacunar syndromes (HR=1.09; 95% CI, 0.80 to 1.49; P=0.58), but was not significantly so (P=0.18). There was no association with hemorrhagic stroke (adjusted HR=1.09; 95% CI, 0.55 to 2.17; P=0.81). Fibrinogen predicted acute coronary events (adjusted HR=1.42; 95% CI, 1.18 to 1.70; P<0.001) and all ischemic vascular events (adjusted HR=1.31; 95% CI, 1.15 to 1.49; P<0.001), but not nonvascular death (adjusted HR=1.24; 95% CI, 0.90 to 1.70; P=0.19).

Conclusions--In patients with a previous TIA or ischemic stroke, risks of recurrent ischemic stroke and acute coronary events increase linearly with fibrinogen levels, but the relationships are weaker than in some previous population-based studies.

Key words: epidemiology • fibrinogen • risk factors • stroke prevention • thrombosis

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