Sleep Disturbance as a Mechanism for Ischemic Heart Disease in PTSD

越来越多的证据表明创伤后应激障碍(PTSD)与心血管疾病的发病率和死亡率有关，但 机制还没有完全被理解。异常睡眠是一种可修改的行为，它是已知的影响因素 心血管风险和创伤后应激障碍的标志性症状。我们的初步数据和其他实验室的数据显示 创伤后应激障碍与严重的睡眠障碍和自主神经功能异常有关 (自主性障碍)尤其是在晚上。我们提出了一项严格的孪生研究来测试这一新的异常范式 睡眠与夜间自主神经紊乱是双向联系的，从而增加了创伤后应激障碍的心血管风险。 我们将在NHLBI资助的正在进行的双胞胎研究中增加全面的自主神经和睡眠评估 创伤后应激障碍与缺血性心脏病(IHD)，Emory双胞胎研究随访(ETSF)。ETSF将重新审查 来自越南时代双胞胎登记处的180对同卵和异卵双胞胎(360人)重新评估 PTSD状态和心脏状态使用正电子发射断层扫描(PET)心肌灌注成像。在一个 之前对这一样本的检查，我们发现患有创伤后应激障碍的双胞胎心肌灌注更差， 冠状动脉微血管功能与双胞胎无创伤后应激障碍的比较。作为拟议的辅助研究的一部分， 我们将增加在家中和实验室中的客观睡眠和自主监测，这将允许 世界“和受控的心理生理评估。双胞胎将在实验室接受多导睡眠监测 现场将配备用于心电监测的补丁和睡眠活动腕带 监测在家中使用14天。在访问期间，他们将在受控环境中接受检查 这与他们兄弟的一致，并允许对配对内差异进行最受控的分析。 我们将解决以下假设：(1)患有创伤后应激障碍的双胞胎会表现出更多的睡眠障碍(睡眠时间更短 持续时间、更多的睡眠碎片和更多的睡眠呼吸障碍)与没有创伤后应激障碍的双胞胎相比。 (2)与双胞胎相比，患有创伤后应激障碍的双胞胎表现出更多的夜间自主神经紊乱(夜间心率变异性较低) 没有创伤后应激障碍。(3)睡眠障碍和夜间自主神经障碍与数量呈正相关。 使用PET成像的IHD指标，包括灌注缺陷和冠状动脉血流储备降低。我们还将 在实验室和家里探索创伤后应激障碍、睡眠障碍和自主神经障碍之间的动态联系。 我们提出的双胞胎研究应该会填补关于心血管机制的证据上的一个重大空白 患创伤后应激障碍的风险。如果我们的假设成立，这项研究将把异常睡眠和夜间改变的自主神经 作为相互关联的生物行为通路将创伤后应激障碍与IHD联系起来，发挥着最重要的作用。长期目标是 为新的干预措施提供目标，共同帮助降低IHD风险、睡眠障碍和创伤后应激障碍 症状负担。

Growing evidence links posttraumatic stress disorder (PTSD) to cardiovascular morbidity and mortality, but the mechanisms are incompletely understood. Abnormal sleep is a modifiable behavior that is a known contributor to cardiovascular risk and a hallmark symptom of PTSD. Our preliminary data and data from other labs show that PTSD is associated with profound sleep disturbance and with abnormal autonomic function (dysautonomia) especially at night. We propose a rigorous twin study to test the new paradigm that abnormal sleep is linked in a bidirectional way with nighttime dysautonomia to increase cardiovascular risk in PTSD. We will add comprehensive autonomic and sleep assessments to an ongoing NHLBI-funded twin study of PTSD and ischemic heart disease (IHD), the Emory Twin Study Follow-up (ETSF). The ETSF will re-examine 180 monozygotic and dizygotic twin pairs (360 individuals) from the Vietnam Era Twin Registry to reassess PTSD status and cardiac status using positron emission tomography (PET) myocardial perfusion imaging. In a previous examination of this sample, we found that twins with PTSD had worse myocardial perfusion and coronary microvascular function compared with twins without PTSD. As part of the proposed ancillary study, we will add both at home and in-lab objective sleep and autonomic monitoring, which will allow for both “real- world” and controlled psychophysiological assessments. Twins will undergo in-lab polysomnography when on site and will be equipped patches for electrocardiogram monitoring and actigraphy wristbands for sleep monitoring to use at home for 14 days. During their visit, they will be examined in a controlled environment which matches their brothers' and allows for the most controlled analyses of within-pair difference. We will address the following hypotheses: (1) Twins with PTSD will exhibit more disturbed sleep (shorter sleep duration, more sleep fragmentation, and more sleep-disordered breathing) compared with twins without PTSD. (2) Twins with PTSD will exhibit more nocturnal dysautonomia (lower nighttime HRV) compared with twins without PTSD. (3) Disturbed sleep and nighttime dysautonomia will be positively related to quantitative indicators of IHD using PET imaging, including perfusion deficits and lower coronary flow reserve. We will also explore dynamic associations among PTSD, sleep disturbance and dysautonomia in the lab and at home. Our proposed twin study should fill a significant gap in evidence regarding the mechanisms of cardiovascular risk in PTSD. If our hypotheses are met, this study will place abnormal sleep and nighttime altered autonomic function at the forefront as interrelated biobehavioral pathways linking PTSD to IHD. The long-term goal is to provide targets for novel interventions that collectively help reduce IHD risk, sleep disturbance, and PTSD symptom burden.