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: 8719849
• 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/8719849
• 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

DESCRIPTION (provided by applicant): Atrial Fibrillation Precursors May Be Novel Stroke Risk Factors. 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 cardia 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 b 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.

描述（由申请人提供）：房颤前体可能是新型中风风险因素。这是对Hooman Kamel博士的K23重新提取申请，他是一名神经病学家和年轻研究者，对心律不齐引起的缺血性中风进行了临床研究。 K23奖将为他提供在三个关键职业发展领域获得关键技能的手段：1）流行病学和临床试验设计，2）心脏诊断技术，以及3）生物标志物的开发和评估。通过获得这些技能，Kamel博士将实现他成为独立临床研究者的长期职业目标。为了实现这一目标，Kamel博士招募了一位主要导师Richard Devereux博士，他是心血管流行病学和心脏诊断技术方面的专业知识的心脏病专家，两位合作社Mitchell Elkind博士，具有与ISCHILAGION和ISCHILION ISCHINE DERECOL INTERISAL和DREDECOLA INTERISAL和DREDECOLA INTERAKE ISCOLA和DRECOLA ISATILICRAINE和DRECHINO IADECOLA ISADECOLA，IADECOLA ISADECOLA，AIDADECOLA的专业知识的神经学家生物标志物。 基于最近的证据和他自己的初步数据，卡梅尔博士的中心假设是，上心律失常甚至在房颤/颤动（AF）的发展之前，也会增加中风风险，这是目前唯一被认为会引起中风的心律失常。检验该假设将解决有关哪些上心律失常引起中风的知识的基本差距。在填补了这些知识差距之前，无法完全确定预防心脏病中风的最佳策略。通过追求以下特定目标，申请人将检验他的假设并收集数据 一项基于人群上心律失常的中风风险的研究（在K23奖励期间提出的R01应用程序提出）。特定的目标1将检验以下假设：心电图P波分散体是心房功能障碍的早期标志，并且倾向于上心律不齐，与中风的风险增加有关。将通过分析一项同类人群而没有参加强大心脏研究，这是一项基于人群的流行病学研究，具有基线心电图数据，> 375裁定和分类的中风病例，将实现这一目标。特定的目标2将检验上室外术与隐性中风有关的假设。在一系列预期的一系列患者中，将比较75例隐源性中风患者和75例来自小血管闭塞或大动脉粥样硬化的中风患者的心脏监测期间的室外肾上腺率。次级分析将比较两组之间心脏栓塞的生物标志物，并将上室外的速率与这些生物标志物相关。具体目标3将检验以下假设：阵发性脑室性心动过速的临床诊断与短暂性缺血性发作后中风的风险有关。该目标将使用经过验证的阵发性室上心动过速的ICD-9-CM守则，并从加利福尼亚州住院数据库和急诊部数据库中链接了病历。 拟议的研究很重要，因为积极的结果将发现新的中风风险因素，而负面结果将抵消标签不可证实的抗凝治疗在隐态性中性疾病后非特异性上心律失常的使用。拟议的研究具有创新性，因为它试图通过识别出大量新的中风风险并可能从现有的抗凝药物中受益，并试图通过心脏病学工具的新应用来启动心脏病学和神经病学来弥合心脏病学和神经病学，以转移当前的研究和临床实践范例。