PTSD and Ischemic Heart Disease Progression: A Longitudinal Twin Study

 描述(由申请人提供)：创伤后应激障碍(PTSD)和缺血性心脏病(IHD)之间可能存在联系，但由于缺乏使用IHD客观测量的前瞻性研究，因此因果联系的证据有限。此外，潜在的机制仍不清楚。创伤后应激障碍的一个生物学特征是应激时交感神经系统(SNS)活动增强，特别是对创伤回忆刺激的反应。我们的主要假设是，创伤提示的PTSD患者反复激活SNS会导致微血管功能障碍、内皮损伤和免疫激活，进而增加心肌缺血和急性冠状动脉综合征的风险。这项拟议的项目是对越南时代双胞胎登记处的281对男性双胞胎(562人)进行跟踪研究，他们在基线访问10年后进行了广泛的表型分析，包括用正电子发射断层扫描(PET)心肌灌注成像评估IHD。在大约180对中，我们将重复PET成像，以获得IHD的纵向定量指标。此外，我们将执行标准化的创伤记忆任务，以检查血管和免疫对压力的反应。除了纵向设计、IHD的最新措施和考虑新的机制外，该项目还具有双胞胎样本的优势，这将使我们能够控制遗传和家族影响，并分析基因和共享/非共享环境对创伤后应激障碍和IHD之间关联的相对贡献。其目的是：(1)检查PTSD是否与纵向测量的IHD恶化有关(心肌灌注和冠脉血流储备的总严重程度评分)；(2)检查PTSD是否与创伤记忆任务中的不良血管和免疫反应有关(通过搏动性动脉血压测量的外周血管收缩，以及内皮损伤和炎症的标志物：循环前体细胞和黏附分子)。对于这两个目标，我们将评估影响是否独立于遗传学、共同的环境和传统的心血管危险因素。此外，我们将调查脆弱性和复原力因素，包括创伤类型(例如， 研究对象包括儿童创伤、抑郁共病、社会支持和创伤后应激障碍轨迹(创伤后应激障碍持续时间、创伤后应激障碍缓解)，以及对创伤提醒的血管和免疫反应是否能预测IHD。我们严格的双胞胎研究将加深对创伤后应激障碍和IHD之间联系的理解，并测试新的范式，即创伤提醒中的免疫和血管反应性发挥着基础性作用。这项研究将填补关于创伤后应激障碍长期心血管后果的证据的重大空白，并可能有助于开发新的风险预测和预防方法，以减轻创伤后应激障碍患者的IHD负担。这些数据应该有助于将应激过程纳入心血管研究和临床实践的主流，这是非常早就应该的。

 DESCRIPTION (provided by applicant): A possible link between posttraumatic stress disorder (PTSD) and ischemic heart disease (IHD) has been suggested, but evidence for a causal connection is limited due to shortage of prospective studies using objective measures of IHD. In addition, potential mechanisms remain unclear. A biological hallmark of PTSD is enhanced sympathetic nervous system (SNS) activity with stress, especially in response to trauma-reminiscent stimuli. Our overarching hypothesis is that repeated SNS activation with trauma reminders in PTSD leads to microvascular dysfunction, endothelial injury and immune activation which, in turn, increase the risk of myocardial ischemia and acute coronary syndromes. The proposed project is a follow-up study of 281 male twin pairs (562 individuals) from the Vietnam Era Twin Registry 10 years after their baseline visit when they were extensively phenotyped, including assessment of IHD with positron emission tomography (PET) myocardial perfusion imaging. In about 180 pairs, we will repeat PET imaging to obtain longitudinal quantitative indicators of IHD. Furthermore, we will administer standardized traumatic memory tasks to examine vascular and immune responses to stress. In addition to a longitudinal design, state-of-the art measures of IHD, and consideration of novel mechanisms, this project has the advantage of a twin sample, which will allow us to control for genetic and familial influences and parse the relative contributions of genes and shared/unshared environment to the association between PTSD and IHD. The aims are: (1) Examine if PTSD is related to worsening of IHD measured longitudinally with PET myocardial perfusion imaging (summed total severity score of myocardial perfusion, and coronary flow reserve); (2) Examine if PTSD is related to adverse vascular and immune responses during traumatic memory tasks (peripheral vasoconstriction by means of pulsatile arterial tonometry, and markers of endothelial injury and inflammation: circulating progenitor cells and adhesion molecules). For both aims, we will assess if effects are independent of genetics, shared environment and traditional cardiovascular risk factors. In addition, we will investigate vulnerability and resilience factors, including type of trauma (e.g., combat vs. noncombat), childhood trauma, depression comorbidity, social support, and PTSD trajectory (duration of PTSD, PTSD remission), and whether vascular and immune responses to trauma reminders predict IHD. Our rigorous twin study will sharpen the understanding of the links between PTSD and IHD, and test the new paradigm that immune and vascular reactivity during trauma reminders play a fundamental role. This research should fill a significant gap in evidence regarding the long-term cardiovascular consequences of PTSD, and potentially help in the development of new methods for risk prediction and prevention to reduce the burden of IHD among persons with PTSD. These data should facilitate incorporating stress processes into the mainstream of cardiovascular research and clinical practice, which is exceedingly overdue.