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: 10453467
• 负责人: Jennifer A Sumner
• 金额: $ 74.14万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453467
• 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.

项目摘要 创伤后应激障碍（PTSD）将发生心血管疾病（CVD）的风险增加25-50％。最多 个人（50-90％）在其一生中经历了创伤性事件，而PTSD是第五大常见的事件 精神病。专家现在呼吁增加创伤后的CVD监视和PTSD 治疗试验旨在降低CVD风险。但是，CVD风险和PTSD都是复杂的现象 可能以细微差别的方式互动。因此，为了取得成功的努力，我们必须首先确定 PTSD影响事件CVD风险的机制。此外，我们必须了解哪个 PTSD的尺寸激活了这些CVD风险机制。这项研究将确定哪个PTSD 维度有助于内皮功能障碍，这是CVD最早可修改的前体之一。只有三个 在某些受创伤人群（男性退伍军人和警察）中进行的研究已经测试了协会 具有流介导的字典（FMD）的PTSD症状，内皮功能障碍的功能测量。这个早 工作指向内皮功能障碍是PTSD-CVD链接的潜在机制，但有限 在创伤后应力和内皮功能障碍的普遍性和缺乏细微差别的测量 这些研究限制了它们的影响。确实，我们仍然不知道PTSD和内皮功能障碍是否 与广播公司社区的个人相关。了解PTSD的哪些方面最多 还缺乏“心脏毒性”，因此我们不知道要靶标的创伤后应力维度。 响应是PTSD的核心组成部分，与心血管功能直接相关，而 PTSD的吞咽困难被认为更具辅助性。在这项研究中，我们将检查横截面 PTSD的纵向关联及其基础维度与功能和次级细胞 内皮功能障碍的度量（分别为FMD和循环内皮细胞衍生的微粒） 在有创伤史的无CVD成年男性和女性的社区居住样本中（目前为50％ PTSD）。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。 主要目的2，我们将检查哪些PTSD维度（恐惧和烦躁不安的客观度量以及 访谈评估的下级症状维度）与内皮最密切相关 功能障碍。在次要目标中，我们将研究这些PTSD维度如何预测内皮的变化 在样本的一部分中超过2年的功能障碍。最后，我们将探索与压力相关的生物学的作用 PTSD关联中的机制，包括自主性失衡，感染和氧化应激 内皮功能障碍的尺寸。这项研究将为生物学上提供有力的证据 PTSD对事件CVD风险的影响的合理机理模型。如果我们的假设得到支持，未来 干预措施将被优化以减少创伤后恐惧或其他PTSD维度，以便尽早减少 内皮损害和偏移CVD风险，使创伤后的CVD监视和干预。

项目成果

Stressful life events and accelerated biological aging over time in youths.

• DOI: 10.1016/j.psyneuen.2023.106058
• 发表时间: 2023-05
• 期刊: PSYCHONEUROENDOCRINOLOGY
• 影响因子: 3.7
• 作者: Sumner, Jennifer A.;Gao, Xu;Gambazza, Simone;Dye, Christian K.;Colich, Natalie L.;Baccarelli, Andrea A.;Uddin, Monica;McLaughlin, Katie A.
• 通讯作者: McLaughlin, Katie A.

Posttraumatic stress disorder (PTSD), sleep, and cardiovascular disease risk: A mechanism-focused narrative review.

• DOI: 10.1037/hea0001143
• 发表时间: 2022-10
• 期刊: HEALTH PSYCHOLOGY
• 影响因子: 4.2
• 作者: Meinhausen, Corinne;Prather, Aric A.;Sumner, Jennifer A.
• 通讯作者: Sumner, Jennifer A.

Understanding trajectories of underlying dimensions of posttraumatic psychopathology.

• DOI: 10.1016/j.jad.2021.01.086
• 发表时间: 2021-04-01
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Sumner JA;Rünger D;Robles TF;Lowe SR;Elashoff D;Shetty V
• 通讯作者: Shetty V

Key dimensions of post-traumatic stress disorder and endothelial dysfunction: a protocol for a mechanism-focused cohort study.

• DOI: 10.1136/bmjopen-2020-043060
• 发表时间: 2021-05-05
• 期刊: BMJ open
• 影响因子: 2.9
• 作者: Cleveland S;Reed K;Thomas JL;Ajijola OA;Ebrahimi R;Hsiai T;Lazarov A;Montoya AK;Neria Y;Shimbo D;Wolitzky-Taylor K;Sumner JA
• 通讯作者: Sumner JA

Psychological and biological mechanisms linking trauma with cardiovascular disease risk.

• DOI: 10.1038/s41398-023-02330-8
• 发表时间: 2023-01-27
• 期刊: TRANSLATIONAL PSYCHIATRY
• 影响因子: 6.8
• 作者: Sumner, Jennifer A.;Cleveland, Shiloh;Chen, Tiffany;Gradus, Jaimie L.
• 通讯作者: Gradus, Jaimie L.