Plasma Biomarkers of Inflammation, Endothelial Function and Hemostasis in Cerebral Small Vessel Disease.
Plasma Biomarkers of Inflammation, Endothelial Function and Hemostasis in Cerebral Small Vessel Disease.
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DOI：
10.1159/000438494
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Wardlaw JM
中科院分区：
文献类型：
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作者：
Wiseman SJ;Doubal FN;Chappell FM;Valdés-Hernández MC;Wang X;Rumley A;Lowe GD;Dennis MS;Wardlaw JM
腔隙缺血性卒中是脑部小血管疾病(SVD)的临床特征，其病因目前尚不清楚。炎症和内皮功能障碍也有牵连。血浆生物标记物可以提供机械性的见解，但目前的数据相互矛盾。脑白质高信号(WMHs)是SVD的重要影像生物标志物。目前尚不清楚血浆生物标记物是否增加了年龄和血管危险因素以外的预测能力来解释WMH。我们前瞻性地招募了表现为非致残性缺血性卒中的患者，在临床和MRI的帮助下将他们分类为腔隙或皮质。我们测量了卒中后1个月的炎症、内皮功能障碍和止血的生物标志物，并比较了不同卒中亚型之间的生物标志物水平。我们定量计算了WMH。我们使用多元线性回归分析建立WMH与年龄、性别、高血压和吸烟的关系模型(基线模型)。我们使用血浆生物标记物作为预测变量来拟合探索性模型，以评估模型对基线的改善。我们招募了125名患者。腔隙组(n=65)的组织纤溶酶原激活物(t-PA)水平在调整前(7.39vs.8.59 ng/ml，p=0.029)和调整后(p=0.035)低于皮质组(n=60)。其他血浆生物标志物差异无统计学意义。T-PA的结果与最新的Meta分析结果一致，尽管其影响仍然不显著(标准化平均差异−为0.08(95%CI−为0.25%至0.09))。基线回归模型解释了定量WMH的29%的变异(R2 0.289)。炎症生物标志物较基线有轻微改善(R2 0.291)，但其他血浆生物标志物并未改善基线模型。血浆t-PA水平在腔隙性卒中和皮质卒中亚型之间、卒中后晚期似乎有所不同，与年龄、性别和血管危险因素无关，可能反映了内皮功能障碍。除了炎症标志物的轻微附加预测作用外，血浆生物标志物与这一小卒中人群的WMH严重程度无关。
The cause of lacunar ischemic stroke, a clinical feature of cerebral small vessel disease (SVD), is largely unknown. Inflammation and endothelial dysfunction have been implicated. Plasma biomarkers could provide mechanistic insights but current data are conflicting. White matter hyperintensities (WMHs) are an important imaging biomarker of SVD. It is unknown if plasma biomarkers add predictive capacity beyond age and vascular risk factors in explaining WMH. We prospectively recruited patients presenting with non-disabling ischemic stroke, classifying them clinically and with the help of MRI as lacunar or cortical. We measured biomarkers of inflammation, endothelial dysfunction and hemostasis for >1 month after stroke and compared biomarker levels between stroke subtypes. We quantitatively calculated WMH. We used multiple linear regression analysis to model WMH as a function of age, sex, hypertension and smoking (the baseline model). We fitted exploratory models using plasma biomarkers as predictor variables to assess model improvement over baseline. We recruited 125 patients. The lacunar group (n = 65) had lower tissue plasminogen activator (t-PA) levels in unadjusted (7.39 vs. 8.59 ng/ml, p = 0.029) and adjusted (p = 0.035) analyses compared with the cortical group (n = 60). There were no significant differences in the other plasma biomarkers. The results for t-PA were consistent with an updated meta-analysis, although the effect remains non-significant (standardized mean difference −0.08 (95% CI −0.25 to 0.09)). The baseline regression model explained 29% of the variance in quantitative WMH (R2 0.289). Inflammatory biomarkers showed minor improvement over baseline (R2 0.291), but the other plasma biomarkers did not improve the baseline model. Plasma t-PA levels appear to differ between lacunar and cortical stroke subtypes, late after stroke, independent of age, sex and vascular risk factors and may reflect endothelial dysfunction. Except for a minor additional predictive effect of inflammatory markers, plasma biomarkers do not relate to WMH severity in this small stroke population.