Atrial Fibrillation Precursors May Be Novel Stroke Risk Factors

心房颤动前兆可能是新的中风危险因素

• 批准号: 8634871
• 负责人: Hooman Kamel
• 金额: $ 18.75万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8634871
• 关键词: Accident and Emergency department; Address; Affect; Age-Years; Anticoagulant therapy; Anticoagulants; Anticoagulation; Area; Arrhythmia; Arteries; Atherosclerosis; Atrial Fibrillation; Biological Markers; California; Cardiac; Cardiology; Clinical Investigator; Clinical Research; Clinical Trials; Clinical Trials Design; Code; Commit; Comorbidity; Data; Databases; Development; Diagnosis; Diagnostic Procedure; Disease; EKG P Wave; Embolism; Enrollment; Epidemiologic Studies; Epidemiology; Fibrosis; Fostering; Functional disorder; Goals; Heart; Heart Atrium; Heart Diseases; Holter Electrocardiography; Hour; ICD-9-CM; Incidence; Inpatients; Ischemic Brain Injury; Ischemic Stroke; Knowledge; Label; Link; Medical Records; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Mission; Monitor; Neurologist; Neurology; Outcome Study; Paroxysmal supraventricular tachycardia; Patients; Predisposition; Public Health; Qualifying; Recruitment Activity; Research; Research Personnel; Research Training; Risk; Risk Factors; Series; Severities; Source; Stroke; Stroke prevention; Supraventricular Arrhythmia; Testing; Time; Training; Transient Ischemic Attack; Validation; Wolves; Work; adjudicate; base; cardiovascular disorder epidemiology; career; career development; clinical Diagnosis; clinical practice; cohort; follow-up; high risk; improved; innovation; meetings; multidisciplinary; nervous system disorder; novel; patient oriented; population based; prospective; public health relevance; screening; skills; stomach cardia; tool

TITLE: Atrial Fibrillation Precursors May Be Novel Stroke Risk Factors PROJECT SUMMARY/ABSTRACT This is a K23 resubmission application for Dr. Hooman Kamel, a neurologist and young investigator pursuing patient-oriented clinical research on ischemic stroke caused by cardiac arrhythmias. A K23 award will provide him with the means to acquire critical skills in three key career development areas: 1) epidemiology and clinical trial design, 2) cardiac diagnostic techniques, and 3) biomarker development and assessment. By acquiring these skills, Dr. Kamel will fulfill his long-term career goal of becoming an independent clinical investigator. To pursue this goal, Dr. Kamel has recruited a primary mentor, Dr. Richard Devereux, a cardiologist with expertise in cardiovascular epidemiology and cardiac diagnostic techniques, and two co- mentors, Dr. Mitchell Elkind, a neurologist with expertise in stroke epidemiology and clinical trial design, and Dr. Costantino Iadecola, a neurologist with expertise in ischemic brain injury and biomarkers. Based on recent evidence and his own preliminary data, Dr. Kamel's central hypothesis is that supraventricular arrhythmias increase stroke risk even before the development of atrial fibrillation/flutter (AF), which is currently the only cardiac arrhythmia thought to cause stroke. Testing this hypothesis will address a fundamental gap in knowledge about which supraventricular arrhythmias cause stroke. Until this knowledge gap is filled, optimal strategies for preventing stroke from cardiac disease cannot be fully determined. By pursuing the following specific aims, the applicant will test his hypothesis and gather data for a population- based study of stroke risk from supraventricular arrhythmias (to be proposed in an R01 application during the K23 award period). Specific Aim 1 will test the hypothesis that electrocardiographic P-wave dispersion, an early marker of atrial electrical dysfunction and predisposition to supraventricular arrhythmias, is associated with an increased risk of stroke. This aim will be pursued by analyzing a cohort without AF enrolled in the Strong Heart Study, a population-based epidemiological study with baseline electrocardiographic data and >375 adjudicated and classified cases of stroke. Specific Aim 2 will test the hypothesis that supraventricular ectopy is associated with cryptogenic stroke. In a prospectively enrolled series of patients, rates of supraventricular ectopy during cardiac monitoring will be compared between 75 patients with cryptogenic stroke and 75 patients with stroke from small-vessel occlusion or large-artery atherosclerosis. Secondary analyses will compare biomarkers of cardiac embolism between the two groups, and correlate rates of supraventricular ectopy with these biomarkers. Specific Aim 3 will test the hypothesis that clinical diagnoses of paroxysmal supraventricular tachycardia are associated with the risk of stroke after transient ischemic attack. This aim will be pursued using a validated ICD-9-CM code for paroxysmal supraventricular tachycardia and linked medical records from the California State Inpatient Database and Emergency Department Database. The proposed research is significant because positive results will uncover novel stroke risk factors, while negative results will counter the increasing off-label use of unproven anticoagulant therapy for nonspecific supraventricular arrhythmias after cryptogenic stroke. The proposed research is innovative because it seeks to shift current research and clinical practice paradigms by identifying a large new class of patients who are at high risk for stroke and may benefit from existing anticoagulant drugs, and also seeks to bridge cardiology and neurology via the new application of cardiology tools to stroke research.

标题：心房颤动前兆可能是新的中风危险因素 项目概要/摘要 这是胡曼·卡梅尔 (Hooman Kamel) 博士的 K23 重新提交申请，他是一名神经科医生和年轻研究员 致力于以患者为中心的心律失常引起的缺血性中风的临床研究。 K23 奖将 为他提供获得三个关键职业发展领域关键技能的方法：1）流行病学 和临床试验设计，2) 心脏诊断技术，以及 3) 生物标志物开发和评估。经过 获得这些技能后，Kamel 博士将实现他成为独立临床医生的长期职业目标 研究者。为了实现这一目标，Kamel 博士聘请了一位主要导师 Richard Devereux 博士，他是一名 具有心血管流行病学和心脏诊断技术专业知识的心脏病专家，以及两名共同 导师：Mitchell Elkind 博士，一位在中风流行病学和临床试验设计方面具有专业知识的神经学家，以及 Costantino Iadecola 博士是一位神经科医生，在缺血性脑损伤和生物标志物方面拥有丰富的专业知识。 根据最近的证据和他自己的初步数据，卡迈勒博士的中心假设是 室上性心律失常甚至在心房颤动/扑动 (AF) 发生之前就会增加中风风险， 这是目前唯一被认为会导致中风的心律失常。检验这一假设将解决 关于室上性心律失常导致中风的知识存在根本性差距。直到这个知识 差距已被填补，但预防心脏病引起的中风的最佳策略尚不能完全确定。经过 为了实现以下具体目标，申请人将检验他的假设并收集人口数据 - 基于室上性心律失常的中风风险研究（将在 R01 申请中提出） K23奖励期）。具体目标 1 将检验以下假设：心电图 P 波色散是 心房电功能障碍的早期标志物和室上性心律失常的易感性相关 中风的风险增加。该目标将通过分析未注册 AF 的队列来实现。 强心脏研究，一项基于人群的流行病学研究，具有基线心电图数据和 > 375 例已裁定和分类的中风病例。具体目标 2 将检验室上性的假设 异位与隐源性中风有关。在前瞻性纳入的一系列患者中，发生率 将比较 75 名隐源性患者在心脏监测期间的室上性异位 中风和 75 名因小血管闭塞或大动脉粥样硬化而中风的患者。中学 分析将比较两组之间心脏栓塞的生物标志物，并关联发生率 具有这些生物标志物的室上性异位。具体目标 3 将检验以下假设：临床诊断 阵发性室上性心动过速与短暂性脑缺血发作后中风的风险相关。 将使用经过验证的阵发性室上性心动过速 ICD-9-CM 代码来实现这一目标 链接来自加州住院患者数据库和急诊科数据库的医疗记录。 拟议的研究意义重大，因为积极的结果将揭示新的中风危险因素， 而阴性结果将抵消越来越多的未经证实的抗凝治疗的标签外使用 隐源性中风后的非特异性室上性心律失常。所提出的研究具有创新性 因为它试图通过确定一大类新的药物来改变当前的研究和临床实践范式 中风高危患者可能受益于现有的抗凝药物，并且还寻求 通过心脏病学工具在中风研究中的新应用，将心脏病学和神经学联系起来。