Webb Alastair Js, Feakins Karolina, Lawson Amy, Stewart Catriona, Thomas James, Llwyd Osian
Department of Brain Sciences, Imperial College London, London, UK.
Wolfson Centre for Prevention of Stroke and Dementia, University of Oxford, Oxford, UK.
Int J Stroke. 2025 Jun;20(5):581-589. doi: 10.1177/17474930241306987. Epub 2025 Jan 3.
In the Oxford Haemodynamic Adaptation to Reduce Pulsatility trial (OxHARP), sildenafil increased cerebrovascular reactivity but did not reduce cerebral pulsatility, a marker of vascular aging. This analysis of OxHARP tested whether these potentially causative mechanisms were independently associated with the severity of white matter hyperintensities (WMHs).
The aims were to determine independence of the relationship between severity of WMHs with both cerebral pulsatility and cerebrovascular reactivity in the same population.
OxHARP was a double-blind, randomized, placebo-controlled, crossover trial of phosphodiesterase inhibitors in patients with mild-to-moderate WMH and previous minor cerebrovascular events. It determined effects on cerebrovascular pulsatility and reactivity on transcranial ultrasound and reactivity on magnetic resonance imaging (MRI). Associations were determined between baseline ultrasound measures, and averaged MRI measures across follow-up, with the severity of WMH on clinical imaging (Fazekas or modified Blennow scores) and WMH volume in the MRI substudy, by ordinal and linear regression.
In 75/75 patients (median 70 years, 78% male), cerebral pulsatility was associated with age (p < 0.001) whereas reactivity on ultrasound was not (p = 0.29). Severity of WMH in all participants was independently associated with decreased cerebrovascular reactivity and increased cerebral pulsatility (pulsatility p = 0.016; reactivity p = 0.03), with a trend to a synergistic interaction (p = 0.075). Reactivity on ultrasound was still associated with WMH after further adjustment for age (p = 0.017), but pulsatility was not (p = 0.31). Volume of WMH in the MRI substudy was also independently associated with both markers on ultrasound (pulsatility p = 0.005; reactivity p = 0.029) and was associated with reduced cerebrovascular reactivity within WMH on MRI (p < 0.0001).
WMHs are independently associated with cerebral pulsatility and reactivity, representing complementary potential disease mechanisms and treatment targets.
clinicaltrials.org: https://classic.
gov/ct2/show/NCT03855332.
在牛津血流动力学适应以降低搏动性试验（OxHARP）中，西地那非可增加脑血管反应性，但未降低脑搏动性，脑搏动性是血管老化的一个标志物。对OxHARP的这项分析检验了这些潜在的致病机制是否与白质高信号（WMH）的严重程度独立相关。
目的是确定在同一人群中WMH严重程度与脑搏动性和脑血管反应性之间关系的独立性。
OxHARP是一项针对轻度至中度WMH且既往有轻度脑血管事件的患者进行的双盲、随机、安慰剂对照、交叉试验，使用磷酸二酯酶抑制剂。该试验通过经颅超声确定了对脑血管搏动性和反应性的影响，以及通过磁共振成像（MRI）确定了对反应性的影响。通过有序回归和线性回归，确定了基线超声测量值以及随访期间MRI测量值的平均值与临床影像上WMH的严重程度（Fazekas评分或改良的Blennow评分）和MRI子研究中WMH体积之间的关联。
在75/75例患者（中位年龄70岁，78%为男性）中，脑搏动性与年龄相关（p<0.001），而超声反应性则不然（p=0.29）。所有参与者中WMH的严重程度与脑血管反应性降低和脑搏动性增加独立相关（搏动性p=0.016；反应性p=0.03），存在协同相互作用的趋势（p=0.075）。在进一步调整年龄后，超声反应性仍与WMH相关（p=0.017），但搏动性则不然（p=0.31）。MRI子研究中WMH的体积也与超声上的两个标志物独立相关（搏动性p=0.005；反应性p=0.029），并且与MRI上WMH内脑血管反应性降低相关（p<0.0001）。
WMH与脑搏动性和反应性独立相关，代表了互补的潜在疾病机制和治疗靶点。
clinicaltrials.org：https://classic.
gov/ct2/show/NCT03855332。
