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

基本信息

批准号：
9334941
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
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9334941
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 Clinical Investigator Clinical Research Clinical Trials Clinical Trials Design Code Comorbidity Data Databases Development Diagnosis Diagnostic Procedure Disease EKG P Wave Embolism Enrollment 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 National Institute of Neurological Disorders and Stroke Neurologist Neurology Outcome Study Paroxysmal supraventricular tachycardia Patients Population Study Predisposition Public Health Recruitment Activity Research Research Personnel Risk Risk Factors Series Severities Source Stroke Stroke prevention Supraventricular Arrhythmia Testing Time Training Transient Ischemic Attack Validation Wolves Work adjudicate base biomarker development cardiovascular disorder epidemiology career career development clinical Diagnosis clinical practice cohort epidemiology study follow-up high risk improved innovation multidisciplinary nervous system disorder novel patient oriented population based prospective public health relevance screening secondary analysis skills stomach cardia technique development tool

项目摘要

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）：心房颤动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 博士是一位神经科医生和年轻研究者，致力于以患者为中心的心律失常引起的缺血性中风临床研究。 K23 奖项将为他提供获得三个关键职业发展领域关键技能的途径：1) 流行病学和临床试验设计，2) 心脏诊断技术，以及 3) 生物标志物开发和评估。通过获得这些技能，卡迈勒博士将实现他成为一名独立临床研究者的长期职业目标。为了实现这一目标，Kamel 博士聘请了一位主要导师 Richard Devereux 博士（一位在心血管流行病学和心脏诊断技术方面具有专业知识的心脏病专家）和两位合作导师 Mitchell Elkind 博士（一位在中风流行病学和心脏诊断技术方面具有专业知识的神经科医生）。临床试验设计，以及具有缺血性脑损伤和生物标志物专业知识的神经学家 Costantino Iadecola 博士。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心房颤动/扑动 (AF) 发生之前就会增加中风风险，房颤/扑动 (AF) 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哪些室上性心律失常导致中风的基本知识空白。在填补这一知识空白之前，无法完全确定预防心脏病引起的中风的最佳策略。通过追求以下具体目标，申请人将检验他的假设并收集数据室上性心律失常引起的中风风险的基于人群的研究（将在 K23 奖励期间的 R01 申请中提出）。具体目标 1 将检验以下假设：心电图 P 波离散（心房电功能障碍和室上性心律失常倾向的早期标志）与中风风险增加相关。该目标将通过分析参加“强心脏研究”的无房颤队列来实现，该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超过 375 例已裁定和分类的中风病例。具体目标 2 将检验室上性异位与隐源性中风相关的假设。在一系列前瞻性入组患者中，将比较 75 名隐源性中风患者和 75 名因小血管闭塞或大动脉粥样硬化导致中风的患者在心脏监测期间的室上性异位发生率。二次分析将比较两组之间心脏栓塞的生物标志物，并将室上性异位率与这些生物标志物相关联。具体目标 3 将检验以下假设：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 代码以及来自加州住院患者数据库和急诊科数据库的链接医疗记录来实现这一目标。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，而消极的结果将抵消越来越多的未经证实的抗凝治疗用于隐源性中风后非特异性室上性心律失常的标签外使用。拟议的研究具有创新性，因为它旨在通过识别一大批新的中风高危患者并可能受益于现有的抗凝药物来改变当前的研究和临床实践范式，并且还试图通过新的方法在心脏病学和神经病学之间架起桥梁。心脏病学工具在中风研究中的应用。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Stratifying Stroke Risk in Atrial Fibrillation: Beyond Clinical Risk Scores.

DOI：
10.1161/strokeaha.117.017084
发表时间：
2017-10
期刊：
Stroke
影响因子：
8.3
作者：
Yaghi S;Kamel H
通讯作者：
Kamel H

Risk of Ischemic Stroke after Intracranial Hemorrhage in Patients with Atrial Fibrillation.

DOI：
10.1371/journal.pone.0145579
发表时间：
2015
期刊：
PloS one
影响因子：
3.7
作者：
Lerario MP;Gialdini G;Lapidus DM;Shaw MM;Navi BB;Merkler AE;Lip GY;Healey JS;Kamel H
通讯作者：
Kamel H

Atrial cardiopathy: a broadened concept of left atrial thromboembolism beyond atrial fibrillation.