Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques: the Copenhagen City Heart Study.
OBJECTIVE
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.


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 3 g l(-1)predicted 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 3.1 g l(-1)(ANCOVA: P<0.0001). Likewise, in those with and without carotid artery stenosis fibrinogen levels were 4.7 and 3.1 g l(-1)(P<0.0001); equivalent values for high-sensitive C-reactive protein were 3.6 and 1.4 mg l(-1)(P<0.0001). Finally, neither fibrinogen nor high-sensitive C-reactive protein levels differed between those with echolucent and echo-rich carotid artery plaques (P=0.61 and P=0.28); 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.
Kofoed
S C
SC
Department of Vascular Surgery, Gentofte University Hospital, Denmark.
Wittrup
H H
HH
Sillesen
H
H
Nordestgaard
B G
BG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000097:blood / Q000175:diagnosis*; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis*; D002097:C-Reactive Protein / Q000032:analysis; D016893:Carotid Stenosis / Q000097:blood / Q000175:diagnosis*; D015331:Cohort Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors
D005340:Fibrinogen; D002097:C-Reactive Protein