Identifying Early Intervention Targets for Reducing Cardiovascular Risk in Posttraumatic Stress

确定降低创伤后应激中心血管风险的早期干预目标

• 批准号: 10222755
• 负责人: Jennifer A Sumner
• 金额: $ 80.17万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10222755
• 关键词: Adult; Atherosclerosis; Attention; Autonomic nervous system; Biological; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular Physiology; Cause of Death; Communities; Complex; Diagnosis; Dimensions; Disease Surveillance; Early Intervention; Emotions; Endothelial Cells; Endothelium; Event; Exposure to; Extinction (Psychology); Fright; Functional disorder; Future; Galvanic Skin Response; Goals; Health; Impairment; Individual; Inflammation; Intervention; Interview; Knowledge; Link; Measurement; Measures; Mediating; Mental disorders; Modeling; Numbness; Oxidative Stress; Participant; Pathologic; Police officer; Population; Post-Traumatic Stress Disorders; Psychophysiology; Public Health; Recording of previous events; Risk; Risk Factors; Role; Sampling; Stimulus; Stress; Symptoms; Testing; Trauma; United States; Vasodilation; Veterans; Woman; Work; associated symptom; attentional bias; base; cardiovascular disorder risk; cardiovascular risk factor; cell injury; conditioned fear; conditioning; dysphoria; endothelial dysfunction; experience; follow-up; male; men; mortality; population based; post-traumatic stress; prospective; response; stress related disorder; trauma exposure; traumatic event; treatment trial

PROJECT SUMMARY Posttraumatic stress disorder (PTSD) increases risk of incident cardiovascular disease (CVD) by 25-50%. Most individuals (50-90%) experience a traumatic event in their lifetime, and PTSD is the fifth most common psychiatric disorder. Experts have now called for increased CVD surveillance after trauma and for PTSD treatment trials powered to reduce CVD risk. However, both CVD risk and PTSD are complex phenomena that likely interact in nuanced ways. Therefore, for such efforts to be successful, we must first identify the mechanisms by which PTSD influences incident CVD risk. Further, we must understand which of the dimensions underlying PTSD activate those CVD risk mechanisms. This study will determine which PTSD dimension(s) contribute to endothelial dysfunction, one of the earliest modifiable precursors to CVD. Only three studies in select trauma-exposed populations (male veterans and police officers) have tested the association of PTSD symptoms with flow-mediated dilation (FMD), a functional measure of endothelial dysfunction. This early work points to endothelial dysfunction as a potential mechanism of the PTSD-CVD link, but the limited generalizability and lack of nuanced measurement of both posttraumatic stress and endothelial dysfunction in those studies has limited their impact. Indeed, we still do not know whether PTSD and endothelial dysfunction are associated in individuals from the broader community. Knowledge of which aspects of PTSD are most “cardiotoxic” is also lacking, so we do not know which posttraumatic stress dimensions to target. Fear responses are a core component of PTSD with direct biological relevance to cardiovascular function, whereas the dysphoria dimension of PTSD is considered more auxiliary. In this study, we will examine cross-sectional and longitudinal associations of PTSD and its underlying dimensions with functional and, secondarily, cellular measures of endothelial dysfunction (FMD and circulating endothelial cell-derived microparticles, respectively) in a community-dwelling sample of CVD-free adult men and women with a history of trauma (50% with current PTSD). In Primary Aim 1, we will test the association of PTSD diagnosis with endothelial dysfunction. In Primary Aim 2, we will examine which PTSD dimensions (objective measures of fear and dysphoria, as well as interview-assessed lower-order symptom dimensions) are most strongly associated with endothelial dysfunction. In a Secondary Aim, we will examine how these PTSD dimensions predict change in endothelial dysfunction over 2 years in a subset of the sample. Finally, we will explore the role of stress-related biological mechanisms, including autonomic imbalance, inflammation, and oxidative stress, in the associations of PTSD dimensions with endothelial dysfunction. This study will provide the strongest evidence to date for a biologically plausible mechanistic model of PTSD’s influence on incident CVD risk. If our hypotheses are supported, future interventions will be optimized to reduce posttraumatic fear or another PTSD dimension so as to reduce early endothelial damage and offset CVD risk, making CVD surveillance and intervention after trauma worthwhile.

项目概要 创伤后应激障碍 (PTSD) 会使心血管疾病 (CVD) 的风险增加 25-50%。最多 个体（50-90%）在一生中经历过创伤性事件，PTSD 是第五大最常见的事件 精神障碍。专家现在呼吁加强创伤后 CVD 监测和 PTSD 治疗试验有助于降低 CVD 风险。然而，CVD 风险和 PTSD 都是复杂的现象， 可能以微妙的方式互动。因此，为了使这些努力取得成功，我们必须首先确定 PTSD 影响 CVD 风险的机制。此外，我们必须了解哪一个 PTSD 的潜在维度会激活这些 CVD 风险机制。这项研究将确定哪种 PTSD 维度导致内皮功能障碍，这是 CVD 最早可改变的前兆之一。只有三个 对特定遭受创伤的人群（男性退伍军人和警察）的研究测试了 PTSD 症状伴有血流介导的扩张 (FMD)，这是内皮功能障碍的功能测量。这早 工作指出内皮功能障碍是 PTSD-CVD 联系的潜在机制，但有限​​的 创伤后应激和内皮功能障碍的普遍性和缺乏细致入微的测量 这些研究的影响有限。事实上，我们仍然不知道 PTSD 是否与内皮功能障碍有关 与来自更广泛社区的个人相关。了解 PTSD 的哪些方面最重要 也缺乏“心脏毒性”，因此我们不知道要针对哪些创伤后应激维度。害怕 反应是 PTSD 的核心组成部分，与心血管功能有直接的生物学相关性，而 PTSD 的烦躁维度被认为更具辅助性。在本研究中，我们将检查横截面 PTSD 及其潜在维度与功能以及其次是细胞的纵向关联 内皮功能障碍的测量（分别为 FMD 和循环内皮细胞衍生微粒） 在社区居住样本中，有外伤史的无 CVD 成年男性和女性（50% 目前患有 创伤后应激障碍）。在主要目标 1 中，我们将测试 PTSD 诊断与内皮功能障碍的关联。在 主要目标 2，我们将检查 PTSD 的哪些维度（恐惧和烦躁的客观测量，以及 访谈评估的低阶症状维度）与内皮细胞最密切相关 功能障碍。在次要目标中，我们将研究这些 PTSD 维度如何预测内皮细胞的变化 部分样本在 2 年内出现功能障碍。最后，我们将探讨与压力相关的生物的作用 与 PTSD 相关的机制，包括自主神经失衡、炎症和氧化应激 内皮功能障碍的维度。这项研究将为生物学上的证据提供迄今为止最有力的证据 PTSD 对 CVD 风险影响的合理机制模型。如果我们的假设得到支持，未来 将优化干预措施，以减少创伤后恐惧或其他 PTSD 维度，从而减少早期 内皮损伤并抵消 CVD 风险，使得创伤后 CVD 监测和干预变得有价值。