Association of Posttraumatic Stress Disorder with Cardiac Electrical Instability: A Twin Study

创伤后应激障碍与心脏电不稳定的关联：一项双胞胎研究

• 批准号: 10299148
• 负责人: Amit Jasvant Shah
• 金额: $ 74.15万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10299148
• 关键词: Accelerometer; Acute; Acute Post Traumatic Stress Disorder; Address; Age; Area; Arrhythmia; Attenuated; Autonomic Dysfunction; Autopsy; Behavior; Behavioral; Behavioral Mechanisms; Brain; Cardiac; Cardiac Electrophysiologic Techniques; Cardiomyopathies; Cardiovascular system; Chronic; Chronic Post Traumatic Stress Disorder; Collaborations; Communities; Coronary heart disease; Country; Data; Diagnosis; Ecological momentary assessment; Electrocardiogram; Enrollment; Event; Exposure to; Feasibility Studies; Funding; Future; General Population; Genes; Genetic; Health Technology; Heart; Heart Diseases; Heterogeneity; Home; Individual; International; Interview; Investigation; Lead; Machine Learning; Measures; Medical center; Methodology; Methods; Monitor; Monozygotic twins; Morphology; Natural experiment; Outcome; Outcome Study; Participant; Physical activity; Pilot Projects; Play; Polysomnography; Post-Traumatic Stress Disorders; Prevalence; Protocols documentation; Psyche structure; Psychological Stress; Publications; Recurrence; Registries; Research; Research Design; Research Personnel; Risk; Risk Factors; Risk Marker; Role; Sampling; Savings; Sex Differences; Site; Sleep; Sleep Fragmentations; Sleep disturbances; Social Distance; Stress; Symptoms; Tachyarrhythmias; Techniques; Time; Travel; Twin Multiple Birth; Twin Studies; United States; United States Department of Veterans Affairs; Ventricular; Veterans; Vietnam; Viola; Woman; Work; adjudicate; base; behavior influence; biobehavior; clinical Diagnosis; cohort; cost; design; experience; heart rate variability; improved; indexing; innovation; mHealth; male; men; modifiable behavior; mortality risk; multidisciplinary; novel; physical inactivity; poor sleep; prospective; psychological trauma; recruit; sedentary lifestyle; signal processing; sleep behavior; stress related disorder; sudden cardiac death; telehealth; traumatic stress; virtual

ABSTRACT Psychological stress is a potentially major risk factor for sudden cardiac death (SCD), but unfortunately not studied very well. This may in part be is due to the fact that many SCDs are unwitnessed, which makes the study of SCD triggers difficult. As a possible solution to this problem, we propose to study electrocardiographic (ECG) markers of cardiac electrical instability in a cohort of 1,000 Veteran male twins who are recruited from the Vietnam Era Twin Registry. Dr. Shah is an Early Stage Investigator who is poised to lead this effort that follows from his previous work on arrhythmia risk due to acute mental stress (K23 HL127251). His team includes several established investigators in the field of PTSD and heart disease (Viola Vaccarino, Douglas Bremner), stress and arrhythmia (Rachel Lampert), and signal processing/mobile health technologies (Gari Clifford, Larry Jamner). Dr. Shah, over the past several years, has worked closely with the Vietnam veteran twins and is an experienced investigator with this cohort. They have generated important preliminary data that demonstrates a potential relationship between PTSD and TWA; in addition, they have demonstrated feasibility of studying Veterans continuously for one week in their currently funded study which measures PTSD, autonomic function, and sleep. Dr. Shah is also leading telehealth efforts at the Atlanta Veterans Affairs Medical Center, which has provided important methodologies for the current study to recruit and enroll participants from around the United States remotely. The first aim seeks to evaluate the relationship of PTSD symptoms and cardiac electrical instability using two ECG-based markers for arrhythmia: microvolt T-wave alternans (TWA) and morphological beat variability (MVB). Both are expected to be associated with higher PTSD symptoms, suggesting an acutely increased risk of sudden cardiac death. The relationship is also hypothesized to be moderated by genetic factors: when adjusting for genetic factors by evaluating monozygotic twin pairs discordant for PTSD, the relationship is attenuated. Aim 2 examines the relationship between everyday PTSD symptoms with an ecological momentary assessment and MVB/TWA. We hypothesize that acute increases in PTSD symptoms and stress also increase cardiac electrical instability, measured by higher TWA and MVB. Finally, aim 3 explores fragmented sleep and other behavioral correlates of PTSD as possible mechanisms through which PTSD may indirectly impact SCD risk through modifiable behaviors. Our hypothesis is that sleep fragmentation and other maladaptive behaviors such as low physical activity will result higher TWA/MVB on a daily basis. Overall, Dr. Shah is a poised and well-equipped to carry out this large project with novel methods and unprecedented reach in terms of impact and

摘要 心理压力是心源性猝死(SCD)的潜在主要危险因素，但不幸的是不是 学得很好。这可能在一定程度上是因为许多SCD没有被目击，这使得 对SCD的研究很困难。作为这个问题的一个可能的解决方案，我们建议研究心电图 1,000对老年男性双胞胎的心电不稳定的心电标记物 越南时代双胞胎登记处。Shah博士是一名早期调查员，他准备领导这项工作 根据他之前关于急性精神压力引起的心律失常风险的工作(K23 HL127251)。他的团队 包括创伤后应激障碍和心脏病领域的几位知名研究人员(维奥拉·瓦卡里诺、道格拉斯 (Bremner)、压力和心律失常(Rachel Lampert)和信号处理/移动医疗技术(GARI Clifford，Larry Jamner)。在过去的几年里，沙阿博士一直与这位越战老兵密切合作 是一对双胞胎，是这个队列中的一名经验丰富的调查员。他们产生了重要的初步数据， 展示了创伤后应激障碍和创伤后应激障碍之间的潜在关系；此外，它们还展示了可行性 在他们目前资助的评估创伤后应激障碍的研究中，对退伍军人进行持续一周的研究， 自主神经功能和睡眠。沙阿博士还在亚特兰大退伍军人事务部领导远程医疗工作 医学中心，为本研究的招募和招生提供了重要的方法 来自美国各地的远程参与者。第一个目标是评估创伤后应激障碍的关系 两种基于心电图的心律失常标志物：微伏T波的症状和心电不稳定性 交替(TWA)和形态节拍变异性(MVB)。预计两者都与更高的 创伤后应激障碍症状，表明心源性猝死的风险急剧增加。这种关系也是 假设受到遗传因素的调节：通过评估单合子来调整遗传因素 双胞胎对创伤后应激障碍不协调，这种关系减弱。目标2考察了两者之间的关系 每天的创伤后应激障碍症状与生态瞬时评估和MVB/TWA。我们假设 创伤后应激障碍症状和压力的急剧增加也增加了心脏的电不稳定，通过更高的 环球航空和MVB。最后，《目标3》探讨了零碎的睡眠和其他与创伤后应激障碍相关的行为 创伤后应激障碍可能通过可改变的行为间接影响SCD风险的机制。我们的 假说是睡眠碎片和其他不适应行为，如低体力活动会导致 每天更高的TWA/MVB。总体而言，沙阿博士是一位泰然自若、装备精良的人，可以进行这项大规模的 具有新方法和前所未有的影响力和影响力的项目