PTSD and Incident Cardiovascular Disease Risk in OIF/OEF Veterans

OIF/OEF 退伍军人的 PTSD 和心血管疾病事件风险

• 批准号: 8733338
• 负责人: Robert Soufer
• 金额: --
• 依托单位: VA CONNECTICUT HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8733338
• 关键词: Anger; Behavioral; Biological; Biological Process; Blood Vessels; Cardiovascular Diseases; Cell Line; Clinical; Development; Diagnosis; Diagnostic; Disease; Dose; Early Intervention; Emotional; Emotional Stress; Endothelin-1; Endothelium; Evaluation; Failure; Freedom; Health; Health Services; Healthcare; Homeostasis; Human Resources; Impairment; Individual; Intervention; Laboratories; Link; Mental Health; Meta-Analysis; Military Personnel; Onset of illness; Pharmacologic Substance; Population; Post-Traumatic Stress Disorders; Prevalence; Process; Protocols documentation; Public Health; Relative (related person); Research; Risk; Risk Marker; Risk Reduction; Secondary to; Series; Services; Severities; Staging; Stratification; Stress; Symptoms; Testing; Time; Trauma; Vascular Endothelium; Veterans; Vietnam; burden of illness; cardiovascular disorder risk; combat; cost; cost effective; disorder risk; early onset; endothelial dysfunction; experience; follow-up; hazard; high risk; improved; indexing; meetings; molecular marker; mortality; operation; reactive hyperemia; response; risk mitigation

DESCRIPTION (provided by applicant): PTSD is a disabling condition consequent to trauma exposure. Recent evidence demonstrates PTSD secondary to combat exposure prospectively increases risk of early incident cardiovascular disease (CVD), with a meta-analyses we have recently completed revealing that PTSD is associated with a hazard ratio of 1.34 for incident CHD or CHD-specific mortality. The rate of PTSD among Veterans who have served during Operations Iraqi Freedom, Enduring Freedom, and New Dawn (OIF/OEF/OND) is more than double that seen in the non-veteran population and consistent with that previously seen among Vietnam era veterans. It is essential for purposes of risk stratification, risk reduction, and health services planning that we establisha more complete understanding of the illness burden associated with military service, and develop PTSD associated risk markers that predict early onset of CVD. Endothelial dysfunction is the earliest indicator of risk for incident CVD. In a pilot series with 23 OIF/OEF/OND veterans we have found that, compared to individuals without any symptoms of PTSD, those diagnosed with PTSD secondary to military service demonstrate significant impairment in endothelial function and that even those with sub-syndromal PTSD symptoms demonstrate impairment relative to those without symptoms. The Specific Aim of this proposed study is therefore to examine endothelial (dys) function as a promising mechanistic link between PTSD and risk for incident CVD. OIF/OEF veterans with a range of PTSD symptom severity (N=300) will complete our laboratory protocol that includes assessment of the endothelial response during standard hyperemic probe and during emotional stress, administered under controlled conditions, with the majority (N=230) repeating this protocol approximately 1 year late. Assessment of autonomic and HPA axis activity, and of contributors to vascular homeostasis (e.g., endothelin-1) will be accomplished during the protocol. We hypothesize that: 1) a diagnosis of PTSD will be associated with endothelial dysfunction; we will explore (1a) whether there is a dose response relationship such that, as severity of PTSD symptoms increase we observe greater endothelial dysfunction.; 2) A change in PTSD symptom severity from time 1 to time 2, will be associated with a concomitant change in the endothelial response to both hyperemic and emotional challenge. We will also explore the association of endothelial (dys) function during emotional stress with markers of sympathetic, parasympathetic, and HPA axis activity and with associated contributors to vascular homeostasis.

描述（由申请人提供）： PTSD是造成创伤暴露的残疾状况。最近的证据表明，接触暴露的PTSD前瞻性增加了早期入射心血管疾病（CVD）的风险，我们最近完成了荟萃分析，发现PTSD与入射CHD或CHD特异性死亡率的危险比为1.34有关。在伊拉克自由，持久的自由和新黎明（OIF/OEF/OND）行动中服役的退伍军人的PTSD率是非退伍军人人口中的两倍多，并且与以前在越南时代退伍军人中看到的是一致的。对于风险分层，降低风险和卫生服务计划的目的，我们对与兵役相关的疾病负担更加完全了解，并开发PTSD相关的风险标记，以预测CVD早期发作，这是至关重要的。内皮功能障碍是最早发生CVD风险的指标。在具有23个OIF/OEF/OND退伍军人的试点系列中，我们发现，与没有PTSD症状的个体相比，诊断为继发于兵役的PTSD的个体相比，患有兵役的PTSD的人也表现出严重的内皮功能障碍，即使患有症状的患有症状的下皮PTSD症状也表现出障碍。因此，这项拟议的研究的具体目的是将内皮（DYS）的功能作为PTSD与入射CVD风险之间有希望的机械联系。具有一系列PTSD症状严重程度（n = 300）的OIF/OEF退伍军人将完成我们的实验室协议，其中包括评估标准高血症探针和情绪压力期间的内皮反应，在受控条件下进行，大部分（n = 230）重复该方案大约1年。在协议期间，将对自主神经和HPA轴活动的评估以及血管稳态的贡献者（例如，内皮素-1）。我们假设：1）PTSD的诊断将与内皮功能障碍有关；我们将探索（1a）是否存在剂量反应关系，以至于随着PTSD症状的严重程度增加，我们观察到更大的内皮功能障碍。 2）从时间1到时间2，PTSD症状严重程度的变化将与对高血症和情感挑战的内皮反应伴随变化有关。我们还将在情绪压力期间探索内皮（DYS）功能与交感神经，副交感神经和HPA轴活动以及血管稳态的相关贡献者的关联。