Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke

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 Methods - We studied unpublished data from 3 prospective studies of patients with recent transient ischemic attack (TIA) or minor ischemic stroke: the United Kingdom TIA Aspirin (UK-TIA) trial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.