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

• 批准号: 8700171
• 负责人: Karen Lynn Saban
• 金额: $ 8.97万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-26 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8700171
• 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

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）：尽管年龄调整的心血管（CVD）死亡率下降，但非裔美国人（AA）女性的冠心病（CHD）/卒中发生率几乎是非西班牙裔白色（NHW）女性的两倍。AA妇女所承受的CHD/中风疾病的额外负担归因于社会经济地位、心理社会压力和更多风险因素等因素。经济上处于不利地位的AA妇女比NHW妇女经历更高水平的慢性压力。然而，鲜为人知的是如何以前的生活逆境，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）的AA和NHW妇女之间的CHD/中风疾病的差距。此外，已知促炎过程有助于CHD/中风，并且令人信服的证据表明，不良的先前生活经历导致表观遗传改变（即，DNA甲基化的变化），这反过来又增加了应激反应性和促炎细胞因子的产生。这个为期三年的指导研究开发应用程序的目的是提供必要的培训和经验，以允许一个独立的职业生涯，其中可以确定冠心病/中风疾病差异的心理社会和促炎机制。培训的目的是：（1）扩大以前的生活逆境，促炎性应激反应和全球DNA甲基化状态与CHD/中风疾病差异之间的关系的知识;（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，因为它与先前的生活逆境，促炎性应激反应，在有CHD/中风风险的少数民族妇女中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;以及（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提供基础，候选人将进行一项研究，比较46名AA和46名NHW的CHD/中风风险，以（1）确定与NHW女性CHD/中风风险相比，AA中既往生活逆境对CHD/中风风险和急性应激的促炎反应（IL-6）的贡献程度，（2）确定既往生活逆境预测AA和NHW女性CHD/中风风险的总体DNA甲基化状态的程度，（3）评估总体DNA甲基化状态作为AA和NHW女性CHD/中风风险的急性应激促炎反应（IL-6）的预测因子。这项研究的意义在于它有可能澄清冠心病/中风疾病的易感性机制，并确定弱势群体妇女所表现出的健康差异的可能基础。研究结果将为开发新的风险特征提供信息，以确定那些最有可能发生CHD/卒中负担的人群。