Posttraumatic Stress and Cardiovascular Risk in Women: Tests of Biological Mechanisms

 描述（由申请人提供）：这个K 01职业发展奖将为Jennifer Sumner博士提供必要的技能，以建立一个独立的研究职业生涯，重点是阐明创伤经历导致女性心血管疾病（CVD）的心理和生物机制，这是全球死亡的主要原因。创伤后应激障碍（PTSD），典型的应激相关精神障碍，前瞻性预测心血管疾病的发病率增加。然而，PTSD是一种复杂的异质性疾病，PTSD驱动CVD风险的方面尚不清楚。机械知识，特别是妇女的机械知识也缺乏。这些限制阻碍了抵消CVD风险的临床应用的发展。本K 01提案的总体目标是 开始测试基于理论的生物模型，通过该模型，PTSD的核心要素-创伤后恐惧反应（例如，过度警觉，再体验）-与女性心血管疾病和心血管健康的中间标志物有关。在多学科专家导师团队的支持下，萨姆纳博士将研究创伤后恐惧反应（通过自我报告和心理生理学分析水平测量）与女性心血管健康的关系。培训计划将为Sumner博士提供几个领域所需的背景和技能，以便成为一名独立的研究人员，对创伤的心理后遗症导致女性CVD的机制进行综合研究。通过课程作业，实践培训和指导会议，萨姆纳博士将解决培训中的先前差距，并发展以下方面的技能：1）心血管，神经和临床流行病学，2）分析流行病学和纵向数据的定量方法，3）CVD相关生理学和生物标志物，以及4）恐惧反应的心理生理学测量。培训计划还包括完成哥伦比亚大学的以患者为导向的研究理学硕士学位。拟议的研究计划利用两个具有丰富特征的正在进行的队列研究来测试创伤后恐惧反应与女性心血管风险的关系。使用来自护士健康研究II（NHS II）的数据，这是一项关于女性健康的纵向流行病学研究，Sumner博士将确定自我报告的创伤后恐惧症状是否与高血压和CVD发病率以及CVD相关生物标志物有关。在急性护理和住院反应（REACH）研究中，一项关于急性冠状动脉综合征后PTSD风险及其与纽约长老会医院复发性心脏事件关系的研究，Sumner博士将收集数据，以测试多层次分析-自我报告症状和心理生理指标（即，皮肤电导和心率）-再入院和心脏事件复发。这些研究和培训活动将为R 01应用程序提供信息，该应用程序将全面测试创伤后恐惧症状在多个分析水平上导致女性CVD的生物学机制。

 DESCRIPTION (provided by applicant): This K01 Career Development Award will provide Dr. Jennifer Sumner with the necessary skills to establish an independent research career focused on elucidating the psychological and biological mechanisms by which traumatic experiences contribute to cardiovascular disease (CVD) in women, the leading cause of death worldwide. Posttraumatic stress disorder (PTSD), the quintessential stress-related mental disorder, prospectively predicts increased CVD incidence. However, PTSD is a complex and heterogeneous disorder, and the aspects of PTSD that drive CVD risk are unknown. Mechanistic knowledge, particularly in women, is also lacking. These limitations impede the development of clinical applications to offset CVD risk. The overall aim of this K01 proposal is to begin to test a theoretically based biological model by which a core element of PTSD-posttraumatic fear responses (e.g., hypervigilance, re-experiencing)- relates to CVD and intermediate markers of cardiovascular health in women. Supported by a multidisciplinary team of expert mentors, Dr. Sumner will examine how posttraumatic fear responses (measured across self- report and psychophysiological levels of analysis) relate to cardiovascular health in women. The training plan will provide Dr. Sumner with required background and skills in several domains in order to become an independent investigator with an integrative research program on the mechanisms by which the psychological sequelae of trauma contribute to CVD in women. Through coursework, hands-on training, and mentored meetings, Dr. Sumner will address prior gaps in training and develop skills in 1) cardiovascular, neurological, and clinical epidemiology, 2) quantitative methods for analyzing epidemiologic and longitudinal data, 3) CVD- related physiology and biomarkers, and 4) psychophysiological measures of fear responses. The training plan also includes completion of a Master's of Science degree in Patient-Oriented Research from Columbia University. The proposed research program harnesses two richly characterized ongoing cohort studies to test how posttraumatic fear responses relate to cardiovascular risk in women. Using data from the Nurses' Health Study II (NHS II), a longitudinal epidemiologic study of women's health, Dr. Sumner will determine if self- reported posttraumatic fear symptoms relate to hypertension and CVD incidence and CVD-related biomarkers. In the REactions to Acute Care and Hospitalization (REACH) study, a study of risk for PTSD after acute coronary syndrome and its relation to recurrent cardiac events at New York-Presbyterian Hospital, Dr. Sumner will collect data to test associations between fear responses at multiple levels of analysis-self-report symptoms and psychophysiological indicators (i.e., skin conductance and heart rate)-with hospital readmission and cardiac event recurrence. These research and training activities will inform an R01 application that will comprehensively test the biological mechanisms by which posttraumatic fear symptoms across multiple levels of analysis contribute to CVD in women.