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.

心房颤动（AF）是一个严重的公共卫生问题，因为它在老年人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关系。 有证据表明，左心房（LA）扩大的患者中风风险也增加， 即使没有房颤，并且绝大多数缺血性中风在时间上与房颤无关 这些观察提出了一个诱人的问题：到底是 AF 还是潜在的 LA 底物？ 导致 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/或增大的异常 LA 基质，而不是 AF 本身，这是主要的 目前归因于房颤的不良后果的驱动因素，例如脑梗塞和认知能力下降。 为了检验这一假设，我们不仅要评估 LA 扩大，还要评估 LA 功能受损，与 我们将利用 MRI 定义的新脑梗塞和认知变化来解释 AF。 对访问时的社区动脉粥样硬化风险 (ARIC) 研究参与者进行了广泛的测试 5 (V5, 2011-13) 作为基线数据：认知测试、2D 超声心动图 (2DE) 和脑部 MRI 扫描。 测量在 V5 上执行的 3,600 个 2DE 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) 通过 ZioXT Patch 对 4,000 名参与者进行心律监测 (R01HL126637)，以及 (2) 对 1,000 名参与者进行重复脑部 MRI 扫描 (R01AG05449)。 重复性轻度认知障碍 (MCI) 和痴呆症将作为 V6 和 7 检查的一部分进行判定。 通过测量 V5 2DE 的 LA 功能并有效利用 V5 以及 V6 和 7 收集的数据 通过辅助研究，我们将实现这些具体目标：（1）评估 LA 的前瞻性关联 新发 MRI 脑梗死、认知改变以及偶发 MCI 或痴呆（伴或不伴）的异常 调整 AF；（2）评估 AF 与新发 MRI 脑梗塞、认知的前瞻性关联 变化、MCI 或痴呆事件，无论是否调整 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 伴有认知变化，根据临床进行调整 缺血性中风、MRI 脑梗塞或其他脑部 MRI 异常 如果我们的假设得到证实，则这会发生。 项目将对公共卫生和临床产生重要影响。我们的研究结果可能（1）将我们的注意力转移到 心房基质作为不良结果的主要驱动因素，重新指导未来发现新药物的努力 预防 LA 异常的策略，与目前关注已建立的 AF 的节律控制相反，以及 (2) 推动未来的临床试验测试 LA 异常患者的抗凝治疗以预防中风。 最终，该项目将强调潜在的异常心房基质在 了解 AF 相关疾病，从而推进 AF 的科学和临床实践。