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