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

摘要 心理压力是心源性猝死（SCD）的一个潜在的主要危险因素，但不幸的是， 学得很好。这可能部分是由于许多SCD是未经见证的，这使得 SCD触发器研究困难。作为一个可能的解决这个问题，我们建议研究心电图 (ECG)心脏电不稳定性的标志物在1,000名退伍军人男性双胞胎队列中， 越南时代双胞胎登记处Shah博士是一名早期研究人员，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研究（K23 HL 127251）。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者（Viola Vaccarino，道格拉斯 Bremner）、压力和心律失常（Rachel Lampert）以及信号处理/移动的健康技术（Gari Clifford，Larry Jamner）.在过去的几年里，沙阿博士与这位越战老兵密切合作， 双胞胎，并且是该队列的经验丰富的研究者。他们已经产生了重要的初步数据， 证明了PTSD和TWA之间的潜在关系;此外，他们已经证明了可行性 在他们目前资助的测量创伤后应激障碍的研究中， 自主神经功能和睡眠。沙阿博士还领导着亚特兰大退伍军人事务部的远程医疗工作 医学中心，为本研究的招募和入组提供了重要的方法 来自美国各地的远程参与者。第一个目的是评估创伤后应激障碍与 使用两种基于ECG的心律失常标记物：微伏T波 交替（TWA）和形态搏动变异性（MVB）。预计两者都将与更高的 创伤后应激障碍症状，表明心脏性猝死的风险急剧增加。这种关系也是 假设受遗传因素调节：当通过评估单合子 如果双胞胎的创伤后应激障碍表现不一致，那么这种关系就会减弱。目标2考察了 每天的PTSD症状与生态瞬时评估和MVB/TWA。我们假设 PTSD症状和压力的急性增加也会增加心脏电不稳定性， TWA和MVB。最后，目标3尽可能地探索了碎片化睡眠和其他与PTSD相关的行为 PTSD可能通过可改变的行为间接影响SCD风险的机制。我们 一种假设是，睡眠碎片和其他适应不良行为，如低体力活动，将导致 TWA/MVB每天都在增加。总的来说，沙阿博士是一个泰然自若，装备精良，以执行这一大 项目具有新颖的方法和前所未有的影响力，

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