Markers of endothelial and hemostatic activation and progression of cerebral white matter hyperintensities - Longitudinal results of the Austrian Stroke Prevention Study
Markers of endothelial and hemostatic activation and progression of cerebral white matter hyperintensities - Longitudinal results of the Austrian Stroke Prevention Study
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DOI：
10.1161/01.str.0000169924.60783.d4
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发表时间：
2005-07-01
期刊：
影响因子：
8.3
通讯作者：
Schmidt, R
中科院分区：
文献类型：
--
作者：
Markus, HS;Hunt, B;Schmidt, R
背景和目的-脑小血管疾病（SVD）的发病机制尚不清楚，但内皮细胞激活和功能障碍可能起因果作用。横断面研究发现内皮细胞活化循环标志物增加，但本研究设计不能排除继发性升高的因果关系。磁共振成像（MRI）上的汇合性白质高信号（WMHs）似乎代表无症状的脑SVD。在一项前瞻性研究中，我们确定了内皮细胞激活的循环标志物是否能预测WMH的进展。方法：在以社区为基础的奥地利卒中预防研究中，296名受试者在基线时进行MRI检查，并在3年和6年重复。在基线血浆样品上测量以下指标：细胞间粘附分子（ICAM）、血栓调节素、组织因子血浆抑制剂、凝血酶原片段1和2，以及d -二聚体。结果- ICAM分别与3年和6年的年龄和性别调整的WMH病变进展有关；（优势比[OR]， 1.007； 95%置信区间[CI]， 1.002 ~ 1.012; P = 0.004； OR, 1.004; 95% CI, 1.000 ~ 1.009 / ng/mL; P = 0.057）。多因素分析控制其他心血管危险因素和c反应蛋白后，3年OR为1.010 (95% CI, 1.004 ~ 1.017, P = 0.001)， 6年OR为1.008 （1.002 ~ 1.014 / ng/ mL, P = 0.006）。基线对数病变体积是病情进展的独立预测因子，但在控制后仍存在相关性（3年OR， 1.011; 95% CI， 1.002至1.020;P = 0.013； 6年OR， 1.009; 95% CI， 1.000至1.017;P = 0.039 / ng/ mL）。WMH进展与其他指标无关联。结论：MRI显示ICAM水平与WMH的进展有关。前瞻性研究设计增加了这种关联是因果关系的可能性，并支持内皮细胞激活在疾病发病机制中的作用。相反，我们没有发现凝血激活是重要的证据。
Background and Purpose - The pathogenesis of cerebral small vessel disease (SVD) is poorly understood, but endothelial activation and dysfunction may play a causal role. Cross-sectional studies have found increased circulating markers of endothelial activation, but this study design cannot exclude causality from secondary elevations. Confluent white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) appear to represent asymptomatic cerebral SVD. In a prospective study, we determined whether circulating markers of endothelial activation predicted progression of WMH.Methods - In the community-based Austrian Stroke Prevention Study, MRI was performed at baseline in 296 subjects and repeated at 3 and 6 years. The following were measured on baseline plasma samples: intercellular adhesion molecule (ICAM), thrombomodulin, tissue factor plasma inhibitor, prothrombin fragments 1 and 2, and D-dimers.Results - ICAM was associated with age- and gender-adjusted WMH lesion progression at both 3 and 6 years, respectively; (odds ratio [OR], 1.007; 95 % confidence interval [CI], 1.002 to 1.012; P = 0.004; and OR, 1.004; 95 % CI, 1.000 to 1.009 per ng/mL; P = 0.057). After multivariate analysis controlling for other cardiovascular risk factors and C-reactive protein, 3- year OR was 1.010 (95 % CI, 1.004 to 1.017; P = 0.001) and 6- year OR was 1.008 (1.002 to 1.014 per ng/ mL; P = 0.006). Baseline log lesion volume was a strong independent predictor of progression but associations remained after controlling for this ( 3- year OR, 1.011; 95 % CI, 1.002 to 1.020; P = 0.013; and 6- year OR, 1.009; 95 % CI, 1.000 to 1.017; P = 0.039 per ng/ mL). There was no association between WMH progression and other markers.Conclusions - ICAM levels are related to progression of WMH on MRI. The prospective study design increases the likelihood that this association is causal and supports a role of endothelial cell activation in disease pathogenesis. In contrast, we found no evidence for coagulation activation being important.