Aortic Stiffness, Increased White Matter Free Water, and Altered Microstructural Integrity: A Continuum of Injury.
Aortic Stiffness, Increased White Matter Free Water, and Altered Microstructural Integrity: A Continuum of Injury.
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DOI：
10.1161/strokeaha.116.016321
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发表时间：
2017-06
期刊：
影响因子：
8.3
通讯作者：
DeCarli C
中科院分区：
文献类型：
--
作者：
Maillard P;Mitchell GF;Himali JJ;Beiser A;Fletcher E;Tsao CW;Pase MP;Satizabal CL;Vasan RS;Seshadri S;DeCarli C
弗雷明汉心脏研究的先前报告已经确定了动脉僵硬度（颈动脉-股动脉脉搏波速度（CFPWV）和收缩压（SBP））与血管性脑损伤之间的横截面关联。本研究的目的是检查弗雷明汉后代和第三代队列受试者中自由水 (FW)、分数各向异性 (FA) 和白质高信号 (WMH) 与动脉僵硬度的关系。在 2422 名年龄为 51.3±11.6 岁的参与者中，使用基于体素的线性和广义线性回归并调整相关协变量，FA、FW 和 WMH 与 CFPWV 相关。平均 FW、平均 FA 和 WMH 负荷（对数转换）是在白质 (WM) 区域内计算的，并使用多重中介分析与 SBP 和 CFPWV 相关。研究发现，CFPWV 与分别覆盖 WM 面罩 356.1、211.8 和 10.9cc 的 WM 区域中较高的 FW、较低的 FA 和较高的 WMH 发生率相关。中介分析显示，SBP 对 FW 的影响是由 CFPWV 介导的（直接和间接影响：a=0.040，p<0.001 和 a'=0.020，p>0.05）。此外，CFPWV对FA的影响是由FW介导的（直接和间接影响：b=-0.092，p<0.001和b'=0.012，p>0.05），而FW对WMH的影响又是由FA介导的（直接和间接影响：c=0.246，p<0.001和c'=0.116，p>0.05）。根据这些数据，我们提出了一个为未来研究实验设计的生物力学假设，以解释血流动力学改变如何通过影响脑含水量和更微妙的 WM 完整性而导致 WM 损伤，最终导致 WMH 的发展。
Prior reports from the Framingham Heart Study have identified cross-sectional associations of arterial stiffness, as reflected by carotid-femoral pulse wave velocity (CFPWV), and systolic blood pressure (SBP) with vascular brain injury. The purpose of this study is to examine free water (FW), fractional anisotropy (FA) and white matter hyperintensities (WMH) in relation to arterial stiffness among subjects of the Framingham Offspring and 3rd generation cohorts. In 2422 participants aged 51.3±11.6 years, FA, FW and WMH were related to CFPWV using voxel-based linear and generalized linear regressions, adjusting for relevant covariables. Mean FW, mean FA and WMH burden (log-transformed) were computed within white matter (WM) region and related to SBP and CFPWV using multiple mediation analyses. CFPWV was found to be associated with higher FW, lower FA and higher WMH incidence in WM areas covering respectively 356.1, 211.8 and 10.9cc of the WM mask. Mediation analyses revealed that the effect of SBP on FW was mediated by CFPWV (direct and indirect effects: a=0.040, p<0.001 and a′=0.020, p>0.05). Moreover, the effect of CFPWV on FA was mediated by FW (direct and indirect effects: b=−0.092, p<0.001 and b′=0.012, p>0.05), whose effect on WMH was in turn mediated by FA (direct and indirect effects: c=0.246, p<0.001 and c′=0.116, p>0.05). From these data, we propose a biomechanical hypothesis designed for future research experiments to explain how hemodynamic alteration may lead to WM injury by impacting cerebral water content and more subtly WM integrity, to finally lead to WMH development.