Left Atrial Abnormality and Atrial Fibrillation-Related Cerebral Infarcts and Cognitive Decline

左心房异常和心房颤动相关的脑梗塞和认知能力下降

• 批准号: 9900061
• 负责人: Lin Yee Chen
• 金额: $ 33.95万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900061
• 关键词: Accounting; Ancillary Study; Anticoagulation; Atherosclerosis; Atherosclerosis Risk in Communities; Atrial Fibrillation; Attention; Attenuated; Automobile Driving; Brain; Brain Infarction; Cardiac; Cardiovascular system; Cerebral Infarction; Cessation of life; Clinical; Clinical Trials; Data; Dementia; Development; Echocardiography; Electronics; Event; Future; Heart Atrium; Heart failure; Hospitalization; Impaired cognition; Impairment; Incidence; Individual; Ischemic Stroke; Left; Left Atrial Function; MRI Scans; Magnetic Resonance Imaging; Measures; Mediating; Monitor; Morbidity - disease rate; Myocardial Infarction; Outcome; Participant; Patients; Prevalence; Public Health; Risk; Science; Stroke; Stroke prevention; Testing; Visit; adjudicate; adverse outcome; aging population; clinical practice; cognitive change; cognitive testing; effective therapy; heart rhythm; high risk; improved; mild cognitive impairment; novel strategies; prevent; prospective; stroke risk

Atrial fibrillation (AF) is a serious public health problem because of its increasing prevalence in the aging population and its association with elevated risks of ischemic stroke, dementia, heart failure, and death. Recent evidence suggests that an increased stroke risk is also observed in patients with left atrial (LA) enlargement, even in the absence of AF, and that the vast majority of ischemic strokes are not temporally related to AF episodes. These observations raise the tantalizing question whether it is AF or the underlying LA substrate that causes the cardiovascular (CV) outcomes attributed to AF. This proposal will test our hypothesis: It is the abnormal LA substrate of impaired function and/or enlargement, and not AF per se, that is the principal driver of adverse outcomes currently attributed to AF, such as cerebral infarct and cognitive decline. To test this hypothesis, we will not only assess LA enlargement, but also impaired LA function, in relation to development of new MRI-defined brain infarcts and cognitive change, accounting for AF. We will leverage the extensive tests that were performed on Atherosclerosis Risk in Communities (ARIC) Study participants at visit 5 (V5, 2011-13) as baseline data: cognitive tests, 2D-echocardiograms (2DE), and brain MRI scans. We will measure LA function on 3,600 2DEs that were performed at V5 and leverage the data collected by 2 other ancillary studies at V6 and 7 (2016-19): (1) heart rhythm monitoring on 4,000 participants by ZioXT Patch (R01HL126637), and (2) repeat brain MRI scans on 1,000 participants (R01AG05449). Cognitive tests will be repeated and mild cognitive impairment (MCI) and dementia will be adjudicated as part of the V6 and 7 exams. By measuring LA function from V5 2DEs and efficiently leveraging the data collected at V5 and from V6 and 7 ancillary studies, we will accomplish these specific aims: (1) Evaluate the prospective association of LA abnormality with new MRI cerebral infarcts, cognitive change, and incident MCI or dementia, with and without adjusting for AF; (2) Evaluate the prospective association of AF with new MRI cerebral infarcts, cognitive change, and incident MCI or dementia, with and without adjusting for LA abnormality; (3) Define mechanisms for AF-related cognitive decline by evaluating the associations of (a) LA abnormality or AF with longitudinal changes in specific brain MRI findings; (b) LA abnormality or AF with cognitive change, adjusting for clinical ischemic stroke, MRI cerebral infarcts, or other brain MRI abnormalities. If our hypothesis is confirmed, this project will have important public health and clinical impact. Our findings may (1) shift our attention to the atrial substrate as the principal driver of adverse outcomes, re-directing future efforts to discover novel strategies to prevent LA abnormality, in contrast to the current focus on rhythm control of established AF, and (2) motivate future clinical trials to test anticoagulation for patients with LA abnormality to prevent stroke. Ultimately, this project will underscore the importance of the underlying abnormal atrial substrate in understanding AF-related morbidities, and consequently advance the science and clinical practice of AF.

房颤（AF）是一个严重的公共卫生问题，因为它在衰老中的患病率不断增加 人口及其与缺血性中风，痴呆，心力衰竭和死亡风险升高的相关性。最近的 有证据表明，左心房（LA）膨胀患者也观察到中风风险增加， 即使在没有AF的情况下，绝大多数缺血性中风也不暂时与AF有关 情节。这些观察结果提出了一个诱人的问题 导致归因于AF的心血管（CV）结果。该提议将检验我们的假设：这是 功能受损和/或扩展的LA异常LA基质，而不是AF本身，这是主要的 目前不良结果的驱动因素归因于AF，例如脑梗塞和认知能力下降。 为了检验这一假设，我们不仅会评估LA扩展，而且还会削弱LA功能 开发新的MRI定义的大脑Infacts和认知变化，占AF。我们将利用 在访问中对社区（ARIC）研究参与者进行动脉粥样硬化风险进行的广泛测试 5（V5，2011-13）作为基线数据：认知测试，2D-心电图图（2DE）和大脑MRI扫描。我们将 测量在V5上执行的3600个2DE上的LA功能，并利用其他2个收集的数据 V6和7（2016-19）的辅助研究：（1）对4,000名参与者的心律监测ZioxtPatch （R01HL126637）和（2）对1,000名参与者重复大脑MRI扫描（R01AG05449）。认知测试将是 重复和轻度认知障碍（MCI）和痴呆症将作为V6和7检查的一部分进行调整。 通过测量V5 2DE的LA功能，并有效利用V5和V6和7的数据 辅助研究，我们将实现这些特定目的：（1）评估LA的前瞻性关联 新MRI脑梗塞，认知变化和事件MCI或痴呆症的异常，有和没有 调整AF； （2）评估AF与新的MRI脑信息的预期关联，认知 变化和事故MCI或痴呆症，没有调整异常的情况下； （3）定义机制 通过评估（a）异常或AF与纵向的关联，与AF相关的认知下降 特定脑MRI发现的变化； （b）具有认知变化的LA绝对或AF，调整临床 缺血性中风，MRI脑梗塞或其他大脑MRI异常。如果我们的假设得到了证实，那么 项目将具有重要的公共卫生和临床影响。我们的发现可能（1）将我们的注意力转移到 心房基材是不良结果的主要驱动力，重新指导未来发现新颖的努力 与当前对既定AF的节奏控制的关注以及 （2）激励未来的临床试验测试LA异常患者的抗凝抗凝，以防止中风。 最终，该项目将强调基础异常心房基质的重要性 了解与自动房屋相关的病态，并因此推进了AF的科学和临床实践。