Maillard Pauline, Mitchell Gary F, Himali Jayandra J, Beiser Alexa, Fletcher Evan, Tsao Connie W, Pase Matthew P, Satizabal Claudia L, Vasan Ramachandran S, Seshadri Sudha, DeCarli Charles
From the Imaging of Dementia and Aging (IDeA) Laboratory, Davis, CA (P.M., E.F., C.D.); Department of Neurology and Center for Neurosciences, University of California, Davis (P.M., E.F., C.D.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); The Framingham Heart Study, MA (J.J.H., A.B., M.P.P., C.L.S., S.S.); Department of Neurology (J.J.H., A.B., M.P.P., C.L.S., S.S.) and Department of Medicine (R.S.V.), Boston University School of Medicine, MA; Department of Biostatistics, Boston University School of Public Health, MA (J.J.H., A.B.); Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (C.W.T.); and Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Australia (M.P.P.).
Stroke. 2017 Jun;48(6):1567-1573. doi: 10.1161/STROKEAHA.116.016321. Epub 2017 May 4.
Previous 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 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 Third-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 systolic blood pressure 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 10.9 mL of the WM mask. Mediation analyses revealed that the effect of systolic blood pressure on FW was mediated by CFPWV (direct and indirect effects: a=0.040; <0.001, and a'=0.020; >0.05). Moreover, the effect of CFPWV on FA was mediated by FW (direct and indirect effects: b=-0.092; <0.001, and b'=0.012; >0.05), whose effect on WMH was, in turn, mediated by FA (direct and indirect effects: c=0.246; <0.001, and c'=0.116; >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.
弗明汉心脏研究先前的报告已确定，颈动脉 - 股动脉脉搏波速度（CFPWV）和收缩压所反映的动脉僵硬度与脑血管损伤存在横断面关联。本研究的目的是在弗明汉后代队列和第三代队列的受试者中，研究与动脉僵硬度相关的自由水（FW）、分数各向异性（FA）和白质高信号（WMH）。
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分析FA、FW和WMH与CFPWV的关系，并对相关协变量进行校正。计算白质（WM）区域内的平均FW、平均FA和WMH负担（对数转换），并使用多重中介分析研究其与收缩压和CFPWV的关系。
发现CFPWV与WM区域中分别覆盖356.1、211.8和10.9 mL WM模板的较高FW、较低FA和较高WMH发生率相关。中介分析显示，收缩压对FW的影响由CFPWV介导（直接和间接效应：a = 0.040；<0.001，a' = 0.020；>0.05）。此外，CFPWV对FA的影响由FW介导（直接和间接效应：b = -0.092；<0.001，b' = 0.012；>0.05），而FW对WMH的影响又由FA介导（直接和间接效应：c = 0.246；<0.001，c' = 0.116；>0.05）。
基于这些数据，我们提出了一个生物力学假设，用于未来的研究实验，以解释血液动力学改变如何通过影响脑含水量以及更细微的WM完整性，最终导致WMH的发生，从而引发WM损伤。
