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Thromb Haemost 2016; 116(03): 537-543
DOI: 10.1160/TH15-12-0938
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

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

Annie Pedersen
1   Institute of Biomedicine, the Sahlgrenska Academy at University of Gothenburg, Sweden
,
Petra Redfors
2   Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Sweden
,
Linnea Lundberg
1   Institute of Biomedicine, the Sahlgrenska Academy at University of Gothenburg, Sweden
,
Ann Gils
3   Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
,
Paul J. Declerck
3   Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
,
Staffan Nilsson
4   Department of Mathematical Statistics, Chalmers Univeristy of Technology, Gothenburg, Sweden
,
Katarina Jood
2   Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Sweden
,
Christina Jern
1   Institute of Biomedicine, the Sahlgrenska Academy at University of Gothenburg, Sweden
› Author Affiliations Financial support: This study was supported by the Swedish Research Council (2013–3595), the Swedish Heart and Lung Foundation (20130315), the Swedish State under the ALF agreement (ALFGBG-429981), the Swedish Stroke Association, the Gothenburg Foundation for Neurological Research, the Rune and Ulla Amlöv, the John and Brit Wennerström and the Per-Olof Ahl Foundations.
Further Information

Publication History

Received: 07 December 2015

Accepted after minor revision: 24 May 2016

Publication Date:
29 November 2017 (online)

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Summary

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.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Cardiovascular diseases - disease-free survival - haemostasis - prognosis - stroke

 

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