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Haemostatic biomarkers are associated with long-term recurrent vascular events after ischaemic stroke

Journal article
Authors Annie Pedersen
Petra Redfors
Linnea Lundberg
Ann Gils
Paul J. Declerck
Staffan Nilsson
Katarina Jood
Christina Jern
Published in Thrombosis and Haemostasis
Volume 116
Issue 3
Pages 537-543
ISSN 0340-6245
Publication year 2016
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Department of Mathematical Sciences, Applied Mathematics and Statistics
Pages 537-543
Language en
Keywords Cardiovascular diseases; disease-free survival; haemostasis; prognosis stroke
Subject categories Cardiac and Cardiovascular Systems, Cardiovascular medicine


Ischaemic stroke patients continue to be at risk for recurrent vascular events for many years. Predictors of long-term prognosis are needed. It was the objective of this study to investigate levels of four haemostatic proteins as long-term predictors of recurrent vascular events after ischaemic stroke. We prospectively followed 548 ischaemic stroke patients, 18-69 years, and registered recurrent vascular events. Plasma levels of tissue-type plasminogen activator (t-PA), von Willebrand factor (VWF), fibrinogen and thrombin activatable fibrinolysis inhibitor activation peptide (TAFI-AP) were measured three months after index stroke. Cox regression models were used to assess associations to outcomes for single biomarkers and for a combined biomarker measure. For single biomarkers significantly associated with any of the outcomes, we performed subanalyses stratified for age, sex, diabetes and atherosclerosis. During 5,637 person-years of follow-up, we registered 74 vascular deaths, 90 recurrent strokes and 62 coronary events. Levels of t-PA, VWF and fibrinogen were significantly associated with vascular death and coronary events. After adjustment, the association between t-PA and vascular death remained (HR per 1 SD increase in plasma level 1.27, 95 % CI 1.00-1.61, p=0.047). The combined effect of t-PA, VWF and fibrinogen was associated with coronary events (adjusted HR 1.35, 1.02-1.80, p=0.04). In non-diabetic patients, an association with coronary events was seen for VWF levels (adjusted HR 2.23,1.45-3.43, p<0.01). In conclusion, plasma levels of haemostatic factors were associated with vascular death and coronary events, but not with recurrent stroke. Our results suggest that the predictive value of biomarkers differ by specific outcome measure and subgroup of patients.

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