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， 机制尚未完全理解。不正常的睡眠是一种可以改变的行为， 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异常的自主神经功能有关 （dysautonomia）特别是在晚上。我们提出了一个严格的双胞胎研究来测试新的范式， 睡眠与夜间自主神经功能障碍以双向方式联系在一起，从而增加PTSD患者的心血管风险。 我们将在一项由NHLBI资助的双胞胎研究中增加全面的自主神经和睡眠评估， PTSD和缺血性心脏病（IHD），埃默里双胞胎研究随访（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对（360名个体）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。中 在之前对该样本的检查中，我们发现患有创伤后应激障碍的双胞胎的心肌灌注更差， 冠状动脉微血管功能与无PTSD的双胞胎相比。作为拟议的辅助研究的一部分， 我们将增加在家里和实验室客观的睡眠和自主监测，这将允许“真实的- 世界”和受控的心理生理评估。双胞胎将接受实验室多导睡眠图， 并将配备心电图监测贴片和睡眠活动记录腕带 在家使用14天。在访问期间，他们将在受控环境中接受检查 这与他们的兄弟相匹配，并允许对配对内差异进行最严格的控制分析。 我们将讨论以下假设：（1）患有PTSD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，更多的睡眠呼吸障碍）与双胞胎相比，没有创伤后应激障碍。 (2)与双胞胎相比，患有PTSD的双胞胎会表现出更多的夜间自主神经功能障碍（较低的夜间HRV） 没有创伤后应激障碍(3)睡眠障碍和夜间自主神经功能障碍将与定量 使用PET成像的IHD指标，包括灌注缺陷和较低的冠状动脉血流储备。我们还将 在实验室和家中探索创伤后应激障碍、睡眠障碍和自主神经功能障碍之间的动态联系。 我们提出的双胞胎研究应该填补了关于心血管疾病机制的证据空白。 PTSD的风险如果我们的假设成立，这项研究将把睡眠异常和夜间自主神经功能改变 作为联系PTSD和IHD的相互关联的生物行为途径，它们处于最前沿。长期目标是 为新的干预措施提供目标，这些干预措施共同有助于降低IHD风险、睡眠障碍和PTSD 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.