title: Haemostatic biomarkers are associated with long-term recurrent vascular events after ischaemic stroke.
abstract: 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.
authors.affiliation: Annie Pedersen, MD, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Box 440, SE-405 30 Gothenburg, Sweden, Tel.: +46 31 343 48 11, Fax: +46 31 842 160, E-mail: annie.pedersen@vgregion.se.
authors.forename: Annie
authors.initials: A
authors.lastname: Pedersen
authors.forename: Petra
authors.initials: P
authors.lastname: Redfors
authors.forename: Linnea
authors.initials: L
authors.lastname: Lundberg
authors.forename: Ann
authors.initials: A
authors.lastname: Gils
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Declerck
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Katarina
authors.initials: K
authors.lastname: Jood
authors.forename: Christina
authors.initials: C
authors.lastname: Jern
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D025901:Carboxypeptidase B2 / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D020521:Stroke / Q000097:blood* / Q000150:complications; D010959:Tissue Plasminogen Activator / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014841:von Willebrand Factor; D005340:Fibrinogen; D025901:Carboxypeptidase B2; C067262:PLAT protein, human; D010959:Tissue Plasminogen Activator
keywords: Cardiovascular diseases; disease-free survival; haemostasis; prognosis; stroke