title: Plasma thrombin-cleaved osteopontin as a potential biomarker of acute atherothrombotic ischemic stroke.
abstract: We investigated whether thrombin-cleaved osteopontin N-terminal is useful as a blood biomarker of acute atherothrombotic ischemic stroke. Acute ischemic stroke patients were prospectively evaluated with brain magnetic resonance imaging and cardiac evaluations for etiological diagnosis according to the Trial of Org 10172 in Acute Stroke Treatment classification. They were divided into the atherothrombotic and non-atherothrombotic groups. Thrombin-cleaved osteopontin N-terminal, osteopontin, matrix metalloproteinase-9, S100B, C-reactive protein and D-dimer levels were measured from blood samples collected at admission. After excluding patients who met the exclusion criteria or had stroke of other/undetermined etiology, 60 of the 100 patients initially enrolled were included in the final analysis. The ischemic stroke subtypes were atherothrombotic (n=28, 46.7%), cardioembolic (n=19, 31.7%) and lacunar (n=13, 21.7%). Thrombin-cleaved osteopontin N-terminal and matrix metalloproteinase-9 levels were significantly higher in the atherothrombotic than in the non-atherothrombotic group (median (interquartile range): 5.83  (0.0-8.6 ) vs. 0.0  (0.0-3.3) pmol l-1, P=0.03 and 544   (322-749 ) vs. 343   (254-485) ng ml-1, P=0.01, respectively). After adjustment for the prevalence of hypertension, diabetes and dyslipidemia, thrombin-cleaved osteopontin N-terminal levels of >5.47 pmol l-1(odds ratio, 16.81; 95% confidence interval, 3.53-80.10) and matrix metalloproteinase-9 levels of >605.5 ng ml-1(6.59; 1.77-24.60) were identified as independent predictors of atherothrombosis. Within 3 h from stroke onset, only thrombin-cleaved osteopontin N-terminal independently predicted atherothrombosis and thus may add valuable, time-sensitive diagnostic information in the early evaluation of ischemic stroke, especially the atherothrombotic subtype.
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Saya
authors: S
authors: Ozaki
authors: Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Ehime, Japan.
authors: Mie
authors: M
authors: Kurata
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Yoshiaki
authors: Y
authors: Kumon
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Shirabe
authors: S
authors: Matsumoto
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Masahiko
authors: M
authors: Tagawa
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Hideaki
authors: H
authors: Watanabe
authors: Department of Neurosurgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Shiro
authors: S
authors: Ohue
authors: Department of Cardiology, Pulmonary, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Jitsuo
authors: J
authors: Higaki
authors: Department of Neurosurgery, Washokai Sadamoto Hospital, Ehime, Japan.
authors: Takanori
authors: T
authors: Ohnishi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis*; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D020767:Intracranial Thrombosis / Q000097:blood / Q000175:diagnosis*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*; D012307:Risk Factors; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D020521:Stroke / Q000097:blood / Q000175:diagnosis*; D013917:Thrombin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C036309:fibrin fragment D; D053495:Osteopontin; D002097:C-Reactive Protein; D013917:Thrombin; D020780:Matrix Metalloproteinase 9