Kern Kyle C, Nasrallah Ilya M, Bryan Robert Nick, Reboussin David M, Wright Clinton B
Intramural Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
medRxiv. 2023 Feb 23:2023.02.22.23286329. doi: 10.1101/2023.02.22.23286329.
Brain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure.
This is a secondary analysis of the Systolic PRessure INTervention (SPRINT) Trial MRI Substudy: a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs. < 140 mm Hg. Participants had increased cardiovascular risk, pre-treatment SBP 130-180, and no clinical stroke, dementia, or diabetes. Brain MRIs acquired at baseline and follow-up were used to automatically segment PVS in the supratentorial white matter and basal ganglia using a Frangi filtering method. PVS volumes were quantified as a fraction of the total tissue volume. The effects of SBP treatment group and major antihypertensive classes on PVS volume fraction were separately tested using linear mixed-effects models while covarying for MRI site, age, sex, black race, baseline SBP, history of cardiovascular disease (CVD), chronic kidney disease, and white matter hyperintensities (WMH).
For 610 participants with sufficient quality MRI at baseline (mean age 67±8, 40% female, 32% black), greater PVS volume fraction was associated with older age, male sex, non-Black race, concurrent CVD, WMH, and brain atrophy. For 381 participants with MRI at baseline and at follow-up (median = 3.9 years), intensive treatment was associated with decreased PVS volume fraction relative to standard treatment (interaction coefficient: -0.029 [-0.055 to -0.0029] p=0.029). Reduced PVS volume fraction was also associated with exposure to calcium channel blockers (CCB) and diuretics.
Intensive SBP lowering partially reverses PVS enlargement. The effects of CCB use suggests that improved vascular compliance may be partly responsible. Improved vascular health may facilitate glymphatic clearance. Clincaltrials.gov : NCT01206062.
脑周血管间隙（PVS）是类淋巴系统的一部分，有助于清除代谢副产物。由于扩大的PVS与血管健康相关，我们测试了强化收缩压（SBP）治疗是否会影响PVS结构。
这是收缩压干预（SPRINT）试验MRI子研究的二次分析：一项强化SBP治疗至目标值<120 mmHg与<140 mmHg的随机试验。参与者心血管风险增加，治疗前SBP为130 - 180，且无临床中风、痴呆或糖尿病。在基线和随访时获得的脑MRI用于使用Frangi滤波方法自动分割幕上白质和基底节中的PVS。PVS体积被量化为总组织体积的一部分。使用线性混合效应模型分别测试SBP治疗组和主要抗高血压药物类别对PVS体积分数的影响，同时对MRI部位、年龄、性别、黑人种族、基线SBP、心血管疾病（CVD）史、慢性肾病和白质高信号（WMH）进行协变量调整。
对于610名在基线时具有足够质量MRI的参与者（平均年龄67±8岁，40%为女性，32%为黑人），更大的PVS体积分数与年龄较大、男性、非黑人种族、并发CVD、WMH和脑萎缩相关。对于381名在基线和随访时进行MRI检查的参与者（中位数 = 3.9年），与标准治疗相比，强化治疗与PVS体积分数降低相关（交互系数：-0.029 [-0.055至-0.0029]，p = 0.029）。PVS体积分数降低也与使用钙通道阻滞剂（CCB）和利尿剂有关。
强化降低SBP可部分逆转PVS扩大。使用CCB的效果表明血管顺应性改善可能部分起作用。改善血管健康可能有助于类淋巴清除。Clinicaltrials.gov：NCT01206062。
