Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H)

重度颈动脉狭窄所致脑血流动力学损害可损害认知 即使在没有中风的情况下，也会直接或由此导致认知能力下降 无症状脑梗塞的发生率越高。尽管案件中有很好的初步证据 血流动力学损害影响认知功能的系列生理学研究 颈动脉闭塞症，这种情况的治疗从未在随机临床中进行过测试 审判。我们建议对NINDS赞助的CREST-2试验进行一项辅助研究， 无症状高级别颈动脉患者的结果盲法3期临床试验 颈动脉内膜剥脱术加最佳药物治疗(OMT)与 单纯OMT(n=1240)和颈动脉支架置入术+OMT与单纯OMT(n=1240)预防 中风和死亡。。我们的应用程序解决了一个有趣的问题，即认知 脑血流动力学异常引起的脑损伤可以逆转。 血流动力学受损的CREST-2随机分组患者。我们将招收500人 来自CREST-2的患者，所有人都在基线和每年接受认知评估 之后。我们将确定100名血液动力学受损的患者，通过一项内部 一侧狭窄侧MRI灌注“达峰时间”(TTP)延迟。在那些 被发现血液动力学受损，并有基线认知障碍，认知 基线和1年的电池将决定那些出现流量故障的人是否被分配到 CREST-2中的血管重建手臂将比医学上的手臂有更好的认知结果- 只有ARM与此相比，治疗上有差异，对于那些没有发生血流衰竭的人。我们 假设血流动力学显着的“无症状”颈动脉疾病可能代表 认知障碍的几个可治疗原因的例子。如果认知能力下降可以逆转 在这些患者中，我们将建立颈动脉血运重建的新适应症。 与中风复发的风险无关。

Cerebral hemodynamic impairment due to high-grade carotid artery stenosis can impair cognition even in the absence of stroke, contributing to cognitive decline either directly, or as a consequence of a higher occurrence of silent infarction. Although there is good preliminary evidence from case series and physiological studies that hemodynamic impairment affects cognition in patients with carotid occlusive disease, treatment of this condition has never been tested in a randomized clinical trial. We propose to conduct an ancillary study to the NINDS-sponsored CREST-2 trial, a pair of outcome-blinded, Phase 3 clinical trials for patients with asymptomatic high-grade carotid artery stenosis which will compare carotid endarterectomy plus optimal medical therapy (OMT) versus OMT alone (n=1,240), and carotid artery stenting plus OMT versus OMT alone (n=1,240) to prevent stroke and death. . Our application addresses the intriguing question of whether cognitive impairment can be reversed when it arises from abnormal cerebral hemodynamic perfusion in a hemodynamically impaired subset of the CREST-2 –randomized patients. We will enroll 500 patients from CREST-2, all of whom receive cognitive assessments at baseline and yearly thereafter. We will identify 100 patients with hemodynamic impairment as measured by an inter- hemispheral MRI perfusion “time to peak” (TTP) delay on the side of stenosis. Among those who are found to be hemodynamically impaired and have baseline cognitive impairment, the cognitive batteries at baseline and at 1 year will determine if those with flow failure who are assigned to revascularization arm in CREST-2 will have better cognitive outcomes than those in the medical- only arm compared with this treatment difference for those who have no flow failure. We hypothesize that hemodynamically significant “asymptomatic” carotid disease may represent one of the few examples of treatable causes of cognitive impairment. If cognitive decline can be reversed in these patients, then we will have established a new indication for carotid revascularization independent of the risk of recurrent stroke.