Ozaki Saya, Kurata Mie, Kumon Yoshiaki, Matsumoto Shirabe, Tagawa Masahiko, Watanabe Hideaki, Ohue Shiro, Higaki Jitsuo, Ohnishi Takanori
Department of Neurosurgery, Ehime University Graduate School of Medicine, Ehime, Japan.
Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Ehime, Japan.
Hypertens Res. 2017 Jan;40(1):61-66. doi: 10.1038/hr.2016.110. Epub 2016 Aug 25.
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, P=0.03 and 544 (322-749 ) vs. 343 (254-485) ng ml, 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 (odds ratio, 16.81; 95% confidence interval, 3.53-80.10) and matrix metalloproteinase-9 levels of >605.5 ng ml (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.
我们研究了凝血酶切割的骨桥蛋白N端是否可作为急性动脉粥样硬化血栓形成性缺血性卒中的血液生物标志物。根据急性卒中治疗中Org 10172试验的分类，对急性缺血性卒中患者进行前瞻性脑磁共振成像和心脏评估以进行病因诊断。他们被分为动脉粥样硬化血栓形成组和非动脉粥样硬化血栓形成组。从入院时采集的血样中检测凝血酶切割的骨桥蛋白N端、骨桥蛋白、基质金属蛋白酶-9、S100B、C反应蛋白和D-二聚体水平。在排除符合排除标准或患有其他/病因未明的卒中患者后，最初纳入的100例患者中有60例纳入最终分析。缺血性卒中亚型为动脉粥样硬化血栓形成型（n = 28，46.7%）、心源性栓塞型（n = 19，31.7%）和腔隙型（n = 13，21.7%）。动脉粥样硬化血栓形成组的凝血酶切割的骨桥蛋白N端和基质金属蛋白酶-9水平显著高于非动脉粥样硬化血栓形成组（中位数（四分位间距）：5.83 （0.0 - 8.6） vs. 0.0 （0.0 - 3.3） pmol/L，P = 0.03；544 （322 - 749） vs. 343 （254 - 485） ng/ml，P = 0.01）。在调整高血压、糖尿病和血脂异常的患病率后，凝血酶切割的骨桥蛋白N端水平>5.47 pmol/L（比值比，16.81；95%置信区间，3.53 - 80.10）和基质金属蛋白酶-9水平>605.5 ng/ml（6.59；1.77 - 24.60）被确定为动脉粥样硬化血栓形成的独立预测因素。在卒中发作后3小时内，只有凝血酶切割的骨桥蛋白N端能独立预测动脉粥样硬化血栓形成，因此在缺血性卒中尤其是动脉粥样硬化血栓形成亚型的早期评估中可能会提供有价值的、对时间敏感的诊断信息。
