Copyright © 2003 by the European Society of Cardiology.
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Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques
The Copenhagen City Heart Study
a Department of Vascular Surgery, Gentofte University Hospital, Gentofte, Denmark
b Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark
c The Copenhagen City Heart Study, Bispebjerg University Hospital, University of Copenhagen, Copenhagen, Denmark
* Corresponding author. Tel.: +45-4488-3297; fax: +45-4488-3311
E-mail address: brno{at}herlevhosp.kbhamt.dk
revised 2 July 2002; accepted 3 July 2002
Aims Whether the association between fibrinogen and cardiovascular events reflects an association with advanced atherosclerosis in general, or rupture-prone plaques in particular, is unclear. We examined whether fibrinogen predicts incidence of ischaemic stroke, advanced atherosclerosis (measured as carotid artery stenosis) and/or echolucent, rupture-prone plaques.
Methods and results Study 1—8755 Copenhagen City Heart Study stroke-free participants; we observed 235 ischaemic strokes during 6 years of follow-up. Study 2—318 carotid stenosis patients and 1584 age- and gender-matched controls. Study 3—159 patients with echolucent vs 159 patients with echo-rich carotid artery plaques. Fibrinogen above vs below the median value of 3gl–1predicted risk of ischaemic stroke (relative risk: 1.9; 95% CI: 1.4–2.5; 235 events). Significant risk was found in men (2.7; 1.7–4.2; 113 events) and with a similar trend in women (1.4; 0.9–2.0; 122 events), in young (5.2; 1.1–26; eight events) and middle aged (2.9; 1.6–5.4; 64 events) with a similar trend in the elderly (1.4; 1.0–2.0; 163 events). Fibrinogen levels in those with and without ischaemic stroke were 3.6 and 3.1gl–1(ANCOVA: 
). Likewise, in those with and without carotid artery stenosis fibrinogen levels were 4.7 and 3.1gl–1
; equivalent values for high-sensitive C-reactive protein were 3.6 and 1.4mgl–1. Finally, neither fibrinogen nor high-sensitive C-reactive protein levels differed between those with echolucent and echo-rich carotid artery plaques (
and 
); the power to exclude a 15% increase in fibrinogen or a 50% increase in high-sensitive C-reactive protein was 98 and 54%, respectively.
Conclusions Elevated fibrinogen predicts future ischaemic strokes, particularly in men and in the young and middle aged. This is most likely a reflection of advanced atherosclerosis, rather than an association with rupture-prone plaques.
Key Words: Atherosclerosis • Carotid disease • Follow-up study • Stroke • Ultrasonics
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