Social Context and Inflammatory Risk for Stroke in African American Women

非洲裔美国女性中风的社会背景和炎症风险

基本信息

批准号：
8551703
负责人：
Karen Lynn Saban
金额：
$ 9.15万
依托单位：
LOYOLA UNIVERSITY CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-26 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8551703
关键词：
Address Affect African American Age Age Factors Behavioral Sciences Biological Biological Markers Body mass index Cardiac Cardiovascular Diseases Cardiovascular system Child Abuse and Neglect Childhood Chronic Chronic Disease Chronic stress Coronary heart disease DNA Methylation Data Data Collection Development Disadvantaged Discrimination Disease Disease susceptibility Early identification Economically Deprived Population Epigenetic Process Evaluation Event Exhibits Foundations Future Genes Goals Health Health behavior Hydrocortisone Incidence Individual Inflammation Inflammatory Interdisciplinary Study Interleukin-6 Intervention Investigation Knowledge Laboratories Lead Leukocytes Life Life Experience Life Stress Life Style Link Longevity Measures Mentors Minority Mission Modeling Not Hispanic or Latino Outcome Pharmaceutical Preparations Physiological Play Populations at Risk Process Production Psychosocial Stress Reporting Research Research Design Research Training Risk Risk Factors Salivary Social Environment Social support Socioeconomic Status Stress Stroke Training Woman Work acute stress allostatic load base biological adaptation to stress burden of illness career cytokine epigenetic marker experience health disparity mortality novel novel strategies peripheral blood psychosocial public health relevance research and development response skills stressor theories

项目摘要

DESCRIPTION (provided by applicant): Despite declines in age-adjusted cardiovascular (CVD) mortality, the incidence of coronary heart disease (CHD)/ stroke is almost twice as high in African American (AA) women compared to non-Hispanic White (NHW) women. The additional burden of CHD/stroke disease borne by AA women is attributed to factors such as socioeconomic status, psychosocial stress, and greater number of risk factors. Economically disadvantaged AA women experience higher levels of chronic stress than NHW women. Yet, little is known about how prior life adversity, such as childhood maltreatment, chronic/perceived stress, perceived discrimination, subjective socio-economic status (SSS), and socioeconomic status (SES) contribute to the disparity in CHD/stroke disease between AA and NHW women. Further, proinflammatory processes are known to contribute to CHD/stroke and compelling evidence demonstrates that adverse prior life experiences result in epigenetic alterations (i.e., changes in DNA methylation), which, in turn, increase stress reactivity and proinflammatory cytokine production. The purpose of this three-year mentored research development application is to provide the necessary training and experience to allow for an independent career in which the psychosocial and proinflammatory mechanisms that underlie CHD/stroke disease disparities can be identified. The training objectives are to: (1) Expand knowledge of the relationships among prior life adversity, proinflammatory stress response, and global DNA methylation status in relation to CHD/stroke disease disparities; (2) Acquire new knowledge and research skills in study design, recruitment, data collection, and interpretation of data as it relates to prior life adversity, proinflammatory stress response, and global DNA methylation in minority women at risk for CHD/stroke; (3) Obtain hands-on training and gain knowledge in the laboratory analysis and interpretation of salivary cortisol, proinflammatory cytokines, and global DNA methylation; and (4) Develop advanced statistical expertise in modeling. To accomplish these objectives and provide a foundation for a sustained research career, the candidate will conduct a study comparing 46 AA and 46 NHW at risk for CHD/stroke in order to (1) Determine the extent to which prior life adversity contributes to CHD/stroke risk and the proinflammatory response (IL-6) to acute stress in AA compared to NHW women at risk for CHD/stroke, (2) Determine the degree to which prior life adversity predicts global DNA methylation status in AA and NHW women at risk for CHD/stroke, and (3) Evaluate global DNA methylation status as a predictor of the proinflammatory response (IL-6) to acute stress in AA and NHW women at risk for CHD/stroke. The significance of this study lies in its potential to clarify mechanisms of CHD/stroke disease susceptibility and to determine the possible basis for the health disparity exhibited by disadvantaged, minority women. Findings will inform the development of novel risk profiles to identify those at most risk for CHD/stroke burden.

描述（由申请人提供）：尽管年龄调整心血管 (CVD) 死亡率有所下降，但非裔美国 (AA) 女性的冠心病 (CHD)/中风发病率几乎是非西班牙裔白人 (NHW) 的两倍）女性。 AA 女性承受的 CHD/中风疾病的额外负担归因于社会经济地位、社会心理压力和更多危险因素等因素。经济上处于不利地位的 AA 女性比 NHW 女性承受更高水平的慢性压力。然而，人们对先前生活中的逆境（例如童年虐待、慢性/感知压力、感知歧视、主观社会经济地位（SSS）和社会经济地位（SES））如何影响 AA 之间的冠心病/中风疾病差异知之甚少。和 NHW 女性。此外，已知促炎症过程会导致冠心病/中风，并且令人信服的证据表明，不良的先前生活经历会导致表观遗传改变（即 DNA 甲基化的变化），从而增加应激反应性和促炎细胞因子的产生。这项为期三年的指导性研究开发应用的目的是提供必要的培训和经验，以实现独立的职业生涯，从而可以确定导致冠心病/中风疾病差异的心理社会和促炎症机制。培训目标是： (1) 扩展对前世逆境、促炎症应激反应和与 CHD/中风疾病差异相关的整体 DNA 甲基化状态之间关系的了解； (2) 在研究设计、招募、数据收集和数据解释方面获得新的知识和研究技能，因为这与有先心病/中风风险的少数妇女的先前生活逆境、促炎症应激反应和整体 DNA 甲基化有关； (3) 获得实践培训并获得唾液皮质醇、促炎细胞因子和整体 DNA 甲基化的实验室分析和解释方面的知识； (4) 发展建模方面的高级统计专业知识。为了实现这些目标并为持续的研究生涯奠定基础，候选人将进行一项研究，比较 46 名 AA 和 46 名 NHW 有患 CHD/中风风险的人，以便 (1) 确定先前的生活逆境对 CHD/中风的影响程度与有 CHD/中风风险的 NHW 女性相比，AA 中的中风风险和对急性应激的促炎反应 (IL-6)，(2) 确定先前生活逆境预测 AA 中总体 DNA 甲基化状态的程度(3) 评估整体 DNA 甲基化状态，作为有 CHD/中风风险的 AA 和 NHW 女性对急性应激的促炎反应 (IL-6) 的预测因子。这项研究的意义在于它有可能阐明冠心病/中风疾病的易感性机制，并确定弱势少数族裔女性所表现出的健康差异的可能基础。研究结果将为新的风险概况的开发提供信息，以确定那些最有可能罹患冠心病/中风负担的人。