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: 9495380
• 负责人: Lin Yee Chen
• 金额: $ 70.58万
• 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/9495380
• 关键词: Accounting; Ancillary Study; Anticoagulation; Atherosclerosis; Atherosclerosis Risk in Communities; Atrial Fibrillation; Attention; Attenuated; Automobile Driving; Brain; 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; Infarction; 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.

随着年龄的增长，心房颤动（AF）的发病率越来越高，是一个严重的公共卫生问题 研究人群中缺血性卒中、痴呆、心力衰竭和死亡风险升高的相关性。最近 证据表明在左心房（LA）扩大的患者中也观察到中风风险增加， 即使在没有AF的情况下，绝大多数缺血性卒中与AF没有时间关系 情节。这些观察结果提出了一个诱人的问题，究竟是AF还是潜在的LA基质， 导致AF引起的心血管（CV）结局。该提案将检验我们的假设： 功能受损和/或增大的异常LA基质，而不是AF本身，这是主要的 目前归因于AF的不良结局的驱动因素，如脑梗死和认知能力下降。 为了验证这一假设，我们不仅要评估左心房扩大，而且要评估左心房功能受损， 新的MRI定义的脑梗死和认知变化的发展，占AF。 在访视时对社区动脉粥样硬化风险（ARIC）研究参与者进行的广泛测试 5（V5，2011-13）作为基线数据：认知测试、二维超声心动图（2DE）和脑部MRI扫描。我们将 在V5时进行的3，600个2DE上测量LA功能，并利用其他2个2DE收集的数据 V6和V7的辅助研究（2016-19）：（1）通过Zio XT Patch对4，000名受试者进行心律监测 （R 01 HL 126637），和（2）对1，000名参与者进行重复脑部MRI扫描（R 01 AG 05449）。认知测试将是 反复和轻度认知障碍（MCI）和痴呆将作为V6和7检查的一部分进行判定。 通过测量V5 2DE的LA功能并有效利用V5以及V6和V7收集的数据 通过辅助研究，我们将实现以下具体目标：（1）评估LA的前瞻性相关性 伴有新发MRI脑梗死、认知改变和偶发MCI或痴呆的异常，伴和不伴 调整AF;（2）评估AF与新发MRI脑梗死、认知功能障碍、 改变，和事件MCI或痴呆，有和没有调整LA异常;（3）定义机制 通过评估（a）LA异常或AF与纵向 特定脑MRI结果的变化;（B）LA异常或AF伴认知变化，根据临床调整 缺血性中风、MRI脑梗塞或其他脑MRI异常。如果我们的假设得到证实， 该项目将产生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 心房基质作为不良结局的主要驱动因素，重新指导未来的努力，以发现新的 与当前关注已建立AF的节律控制相反，预防LA异常的策略，以及 (2)推动未来的临床试验，以测试LA异常患者的抗凝治疗，以预防卒中。 最终，该项目将强调潜在的异常心房基质在 了解AF相关的发病率，从而推进AF的科学和临床实践。