Cardioembolism as a Mechanism of Central Retinal Artery Occlusion

心源性栓塞作为视网膜中央动脉闭塞的机制

• 批准号: 10525030
• 负责人: Brian Mac Grory
• 金额: $ 16.66万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10525030
• 关键词: Academic Medical Centers; Acute; Address; Affect; Age; Anticoagulation; Applied Research; Area; Atrial Fibrillation; Attenuated; Awareness; Back; Biological Markers; Biometry; Blood Vessels; Blood coagulation; Brain imaging; Caliber; Cardiac; Cardiac Electrophysiologic Techniques; Cardiology; Carotid Atherosclerotic Disease; Carotid Stenosis; Central Retinal Artery Occlusion; Cerebrovascular Disorders; Cerebrum; Clinic; Clinical Investigator; Clinical Research; Coagulation Process; Collaborations; Comparative Effectiveness Research; Cross-Sectional Studies; Data; Data Science; Data Set; Databases; Death Rate; Development; Diagnostic; Disease; Etiology; Eye; Failure; Fright; Functional disorder; Future; Goals; Heart; Heart Atrium; Heart Diseases; Incidence; Internal Carotid Artery Stenosis; Investigation; Ipsilateral; Ischemic Stroke; K-Series Research Career Programs; Knowledge; Left; Life; Link; Medicare; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Monitor; Neurology; Observation in research; Observational Study; Ophthalmology; Pathogenesis; Pathology; Pathway interactions; Patients; Persons; Pharmacy facility; Physicians; Physiological; Play; Population; Prevention strategy; Publications; Recurrence; Research; Research Design; Research Personnel; Retina; Risk; Risk Factors; Role; Sampling; Savings; Scientist; Secondary Prevention; Sentinel; Serum; Societies; Stenosis; Stroke; Structure; Testing; Therapeutic Embolization; Thrombus; Time; Training; Ventricular; Ventricular Dysfunction; Walking; base; beneficiary; cardiovascular risk factor; career; cohort; comorbidity; disability; evidence base; heart rhythm; indexing; insight; multidisciplinary; novel; patient oriented; patient subsets; population based; prevent; prospective; sex; skills

ABSTRACT This is a K23 resubmission application for Dr. Brian Mac Grory, a vascular neurology investigator pursuing patient-oriented clinical research focused on the identification of novel populations with underexplored cerebrovascular disorders requiring personalized secondary prevention strategies. Based on his own preliminary data and recent publications, the central hypothesis of this proposal is that central retinal artery occlusion (CRAO) – a form of ischemic stroke affecting the retina – may be an indicator of underlying cardiac disease and a sentinel of future, potentially lethal, cardioembolic stroke. CRAO is formally recognized as a form of ischemic stroke but there is an incomplete understanding of its mechanistic underpinnings, with most research to-date focused on its association with carotid artery stenosis. Testing this application’s central hypothesis will address a fundamental knowledge gap about the mechanisms of CRAO. This K23 award proposes to generate key preliminary data linking CRAO with cardioembolic substrates and set the stage for a future, multi-center, observational study that will definitively test this hypothesis. Dr. Mac Grory will leverage a very large population-based dataset (the Medicare 5% Sample) as well as both retrospective and prospective institutional cohorts. Specific Aims 1A & 1B will determine the association of each of atrial fibrillation and left ventricular failure with the development of CRAO. Specific Aims 2A & 2B will determine the association of cardiac, serum and ultrasonographic biomarkers of embolic risk with CRAO and their interplay with carotid artery stenosis. As part of this proposal, Dr. Mac Grory will undertake a linked, didactic training plan with the goal of developing as an independent investigator through acquisition of the following key skills: 1) Biostatistics in observational research including advanced causal inference methodology, 2) Data science applied to administrative claims databases, 3) Prospective, observational study design, and 4) Vascular biomarker interpretation. Advanced training in these areas will permit Dr. Mac Grory to realize his long-term career goal of becoming an independent clinical investigator who leverages interdisciplinary expertise to provide insights in to the management of understudied cerebrovascular disorders. In pursuit of this goal, Dr. Mac Grory has assembled a mentoring team with distinct though complementary skillsets in stroke medicine, comparative effectiveness research, causal inference methodology, cardiac electrophysiology, and neuro-ophthalmology. Results supportive of this application’s central hypothesis would reveal a new population who may harbor occult cardioembolic disease. Results that are neutral or negative with respect to this central hypothesis would be equally valuable as they would allow us to refine the future study of CRAO by focusing on atherothrombotic mechanisms. With the preliminary data and training obtained from the proposed research, Dr. Mac Grory will be uniquely equipped to execute future, larger-scale studies uncovering novel populations in whom evidence- based, potentially life-saving secondary prevention strategies may be deployed.

摘要 这是Brian Mac Grory博士的K23重新提交申请，他是一名血管神经学研究员， 以患者为导向的临床研究，重点是确定新的人群， 需要个性化二级预防策略的脑血管疾病。根据自己的 根据初步数据和最近的出版物，该提议的中心假设是视网膜中央动脉 视网膜阻塞（CRAO）--一种影响视网膜的缺血性中风--可能是潜在的心血管疾病的指标。 疾病和未来潜在致命的心源性栓塞性中风的前哨。CRAO被正式承认为 缺血性中风的一种形式，但对其机制基础的理解不完全， 迄今为止的研究集中在其与颈动脉狭窄的关联上。测试此应用程序的中心 假设将解决有关CRAO机制的基本知识差距。K23奖项 建议生成将CRAO与心源性栓塞基质联系起来的关键初步数据， 未来，多中心，观察性研究，将明确测试这一假设。麦克·格罗里博士将利用 非常大的基于人群的数据集（Medicare 5%样本）以及回顾性和前瞻性 机构的同伙。具体目标1A和1B将确定心房颤动和左心房颤动中的每一个的关联。 CRAO的发展导致心室衰竭。具体目标2A和2B将决定 CRAO栓塞风险的心脏、血清和超声生物标志物及其与颈动脉的相互作用 动脉狭窄作为该提案的一部分，Mac Grory博士将与 目标是通过掌握以下关键技能发展成为一名独立调查员：1）生物统计学 在观察研究中，包括先进的因果推理方法，2）数据科学应用于 行政索赔数据库，3）前瞻性、观察性研究设计，和4）血管生物标志物 解释。在这些领域的高级培训将使麦克·格罗里博士能够实现他的长期职业目标， 成为一名独立的临床研究者，利用跨学科的专业知识， 未充分研究的脑血管疾病的管理。为了实现这一目标，麦克·格罗里博士 组建了一个指导团队，他们在中风医学方面具有独特但互补的技能， 有效性研究，因果推理方法，心脏电生理学和神经眼科学。 支持本申请中心假设的结果将揭示一个新的人群， 隐匿性心源性栓塞病对于这一中心假设，中性或负面的结果将 同样有价值，因为它们将使我们能够通过关注动脉粥样硬化血栓形成来完善未来的CRAO研究。 机制等通过从拟议研究中获得的初步数据和培训，Mac Grory博士将 具备独特的条件，可以执行未来更大规模的研究，发现新的人群，其中证据- 可以部署基于基础的、可能挽救生命的二级预防战略。