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; 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.

抽象的 这是Brian Mac Grory博士的K23重新提交申请，这是一名血管神经病学研究者 面向患者的临床研究重点是鉴定新的人群 需要个性化次要预防策略的脑血管疾病。基于他自己的 初步数据和最新出版物，该提议的中心假设是中央永久性伪像 阻塞（CRAO） - 一种影响视网膜的缺血性中风形式 - 可能是基础心脏的指标 疾病和未来的哨兵，潜在的致命，心脏骨骼中风。 Crao正式被公认为 缺血性中风的形式，但对其机械基础有一个不完全的理解，大多数 研究待定的重点是其与颈动脉狭窄的关联。测试此应用程序的中央 假设将解决有关CRAO机制的基本知识差距。这个K23奖 提出生成密钥初步数据将CRAO与心脏符号底物联系起来的建议，并为A设置阶段 未来，多中心的观察性研究将确定检验这一假设。麦克格里博士将利用 非常大的基于人群的数据集（Medicare 5％样本）以及回顾性和潜在的 机构队列。具体目的1a和1b将确定每个房颤的关联，然后左 随着CRAO的发展，心室衰竭。具体目标2a和2b将确定 CRAO的栓塞风险及其与Carotid的相互作用的心脏，血清和超声生物标志物 动脉狭窄。作为该提案的一部分，Mac Grory博士将与 通过获得以下关键技能来发展为独立研究者的目标：1）生物统计学 在包括先进因果推理方法的观察研究中，2）应用于数据科学 行政索赔数据库，3）预期，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Mac Grory博士能够实现他的长期职业目标 成为一个独立的临床研究者，他利用跨学科专业知识来提供见解 理解的脑血管疾病的管理。为了实现这一目标，麦克格里博士拥有 组装了一个心理团队，具有不同但互补的技能，在中风医学中，比较 有效性研究，因果推理方法，心脏电生理学和神经跨性研究。 结果支持该应用程序的中心假设，将显示一个新的人群 神秘的心符号疾病。相对于此中心假设的中性或负面的结果将 同样有价值，因为它们可以通过专注于动脉粥样硬化来完善CRAO的未来研究 机制。通过从拟议的研究获得的初步数据和培训，Mac Grory博士将 独特等同于执行未来的大规模研究，揭示了新的人群 可以部署基于基于生命的二级预防策略。