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）：房颤前兆可能是新的中风危险因素。这是Hooman Kamel博士的K23重新提交申请，Hooman Kamel博士是一名神经学家和年轻的研究者，致力于以患者为导向的心律失常引起的缺血性卒中临床研究。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途径：1）流行病学和临床试验设计，2）心脏诊断技术，3）生物标志物开发和评估。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，他是一位心脏病专家，擅长心血管流行病学和心脏诊断技术，还有两位共同导师，Mitchell Elkind博士，他是一位神经学家，擅长中风流行病学和临床试验设计，Costantino Iadecola博士，他是一位神经学家，擅长缺血性脑损伤和生物标志物。 根据最近的证据和他自己的初步数据，Kamel博士的中心假设是，室上性心律失常甚至在房颤/扑动（AF）发展之前就会增加中风风险，房颤/扑动是目前唯一被认为会导致中风的心律失常。验证这一假设将解决关于哪些室上性心律失常导致卒中的知识的根本空白。在填补这一知识空白之前，无法完全确定预防心脏病卒中的最佳策略。通过追求以下具体目标，申请人将测试其假设并收集数据， 一项基于人群的室上性心律失常卒中风险研究（将在K23奖励期间的R 01申请中提出）。具体目标1将检验心电图P波离散度（心房电功能障碍和室上性心律失常易感性的早期标志物）与卒中风险增加相关的假设。这一目标将通过分析参加强心研究的无AF队列来实现，强心研究是一项基于人群的流行病学研究，具有基线心电图数据和>375例裁定和分类的卒中病例。具体目标2将检验室上性异位与隐源性卒中相关的假设。在一项前瞻性入组的患者系列中，将比较75例隐源性卒中患者和75例小血管闭塞或大动脉粥样硬化卒中患者在心脏监测期间的室上性异位发生率。次要分析将比较两组之间的心脏栓塞生物标志物，并将室上性异位发生率与这些生物标志物相关联。具体目标3将检验阵发性室上性心动过速的临床诊断与短暂性脑缺血发作后卒中风险相关的假设。将使用经验证的ICD-9-CM阵发性室上性心动过速代码以及加州州住院患者数据库和急诊室数据库中的相关病历来实现这一目标。 拟议的研究是重要的，因为积极的结果将揭示新的中风风险因素，而负面的结果将反对增加标签外使用未经证实的抗凝治疗不明原因中风后的非特异性室上性心律失常。拟议的研究是创新的，因为它试图通过识别一大类新的中风高危患者来改变当前的研究和临床实践范式，这些患者可能从现有的抗凝药物中受益，并且还试图通过心脏病学工具的新应用来桥接心脏病学和神经病学中风研究。