Statin Neuroprotection & Cognitive Dysfunction after Carotid Endarterectomy: Safety, Feasibility, & Outcomes.

他汀类药物神经保护

基本信息

项目摘要

For the past 15 years, we have studied cognitive changes in patients treated for carotid artery stenosis by carotid endarterectomy (CEA) or carotid artery angioplasty and stenting (CAS). Using neurocognitive tests, we have defined post-operative cognitive dysfunction (CD), a subtle measure of cerebral injury. Post-operative cognitive dysfunction is part of a continuum of injury to the brain. Early cognitive dysfunction (eCD) is observed in ~ 25% of patients within 1 day of CEA, and less so 30 days after CEA (delayed CD [dCD]). Over the last 10 years of our NIH grant (RO1 AG17604), we have demonstrated that 1. Asymptomatic patients taking statinspre-operatively exhibit significantly less eCD than those not taking statins, 2. Simvastatin is associated with significantly less eCD than atorvastatin, 3. Statins are also neuroprotective against eCD in CAS patients, 4.Patients with eCD and not taking statins have significantly higher risk of mortality than those with eCD taking statins, 5. Pro-inflammatory polymorphisms and marker concentrations are significantly associated with increased eCD, and 6. Statins are associated with lower levels of pro-inflammatory markers. Based on these findings, we hypothesize that in asymptomatic patients undergoing CEA, 1. Pre-operative statin use is neuroprotective against eCD and lowers the risk of early mortality, 2. Statin type and dose may be important in achieving optimal neuroprotection, and 3. The anti-inflammatory effects of statins may partially account for the observed neuroprotection. To address these hypotheses, we will prospectively evaluate 1000 asymptomatic patients with a neurocognitive battery for eCD and dCD before and after CEA in a multi-center randomized trial. Lipid profiles and markers of systemic inflammation will be obtained before and after statin therapy. Patients will be randomized into one of three arms for 2 weeks pre-operatively and 4 weeks-post operatively depending on their statin status upon enrollment. Arms: 1. Patients on optimal daily doses of either simvastatin (40mg), atorvastatin (80mg) or rosuvastatin (20mg) will be tested and observed, 2. Patients on one of the three statins at less than optimal dosage (simvastatin <40mg, atorvastatin <80mg or rosuvastatin <20mg) will be randomized to receive an optimal dose or remain at their suboptimal dosage using re-encapsulated blinded medication, and 3. Patients who are not already taking statins, will be randomized to a daily dose ofreencapsulated blinded atorvastatin 10mg (suboptimal) or atorvastatin 80mg (optimal). Overall, we expect that high-dose simvastatin, atorvastatin and rosuvastatin will be neuroprotectiveagainst eCD and dCD. We think that statin neuroprotection occurs because of anti-inflammatory mechanisms and will be reflected in reduced levels of systemic inflammatory markers. The findings of this prospective randomized trial will provide important data for clinicians attempting to make this common procedure safer, and will elucidate whether statins are neuroprotective in human ischemic cerebral injury. Our results may guide the development of these agents for other indications.
在过去的15年里,我们研究了颈动脉病变患者的认知变化

项目成果

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EDWARD SANDER CONNOLLY其他文献

EDWARD SANDER CONNOLLY的其他文献

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{{ truncateString('EDWARD SANDER CONNOLLY', 18)}}的其他基金

Stroke Trials Network of Columbia and Cornell
哥伦比亚大学和康奈尔大学中风试验网络
  • 批准号:
    10767024
  • 财政年份:
    2023
  • 资助金额:
    $ 117.29万
  • 项目类别:
Stroke Trials Network of Columbia and Cornell
哥伦比亚大学和康奈尔大学中风试验网络
  • 批准号:
    9571820
  • 财政年份:
    2018
  • 资助金额:
    $ 117.29万
  • 项目类别:
Stroke Trials Network of Columbia and Cornell
哥伦比亚大学和康奈尔大学中风试验网络
  • 批准号:
    9983213
  • 财政年份:
    2018
  • 资助金额:
    $ 117.29万
  • 项目类别:
Stroke Trials Network of Columbia and Cornell
哥伦比亚大学和康奈尔大学中风试验网络
  • 批准号:
    10468292
  • 财政年份:
    2018
  • 资助金额:
    $ 117.29万
  • 项目类别:
Stroke Trials Network of Columbia and Cornell
哥伦比亚大学和康奈尔大学中风试验网络
  • 批准号:
    9764512
  • 财政年份:
    2018
  • 资助金额:
    $ 117.29万
  • 项目类别:
Stroke Trials Network of Columbia and Cornell
哥伦比亚大学和康奈尔大学中风试验网络
  • 批准号:
    10306036
  • 财政年份:
    2018
  • 资助金额:
    $ 117.29万
  • 项目类别:
Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H)
无症状颈动脉狭窄试验的颈动脉血运重建和医疗管理 - 血流动力学 (CREST-H)
  • 批准号:
    9311842
  • 财政年份:
    2017
  • 资助金额:
    $ 117.29万
  • 项目类别:
Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H)
无症状颈动脉狭窄试验的颈动脉血运重建和医疗管理 - 血流动力学 (CREST-H)
  • 批准号:
    9923010
  • 财政年份:
    2017
  • 资助金额:
    $ 117.29万
  • 项目类别:
Topical Vancomycin for Craniotomy Wound Prophylaxis
外用万古霉素用于预防开颅手术伤口
  • 批准号:
    8868935
  • 财政年份:
    2014
  • 资助金额:
    $ 117.29万
  • 项目类别:
Topical Vancomycin for Craniotomy Wound Prophylaxis
外用万古霉素用于预防开颅手术伤口
  • 批准号:
    8674351
  • 财政年份:
    2014
  • 资助金额:
    $ 117.29万
  • 项目类别:

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