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: 8441743
• 负责人: Karen Lynn Saban
• 金额: $ 9.12万
• 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 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8441743
• 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; experience; health disparity; mortality; novel; novel strategies; peripheral blood; psychosocial; 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. PUBLIC HEALTH RELEVANCE: African American women suffer twice as many ischemic cardiac events and strokes as do non-Hispanic White women. Prior life adversity is linked to increased proinflammatory risk and may contribute to CHD/stroke disease disparities. It is expected that findings from this study will inform the development of novel risk profiles for CHD/stroke and lead to earlier identification and targeting of interventions to reduce disease burden.

描述（由申请人提供）：尽管年龄调整后的心血管（CVD）死亡率下降，但与非西班牙裔白人（NHW）妇女相比，非裔美国人（AA）妇女的冠状动脉疾病（CHD）/中风的发生率几乎是高的两倍。 AA妇女承担的冠心病/中风疾病的额外负担归因于社会经济状况，社会心理压力和更多危险因素等因素。与NHW妇女相比，经济上不利的AA妇女经历的慢性压力水平更高。然而，几乎了解到，诸如儿童虐待，长期/感知的压力，感知的歧视，主观的社会经济地位（SSS）以及社会经济地位（SES）如何有助于AA和NHW妇女之间的CHD/中风疾病差异。此外，已知促炎过程有助于CHD/中风和引人注目的证据表明，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），从而增加了压力反应性和促炎性细胞因子的产生。这项为期三年的研究开发应用程序的目的是提供必要的培训和经验，以允许独立职业，在这种职业中，可以确定CHD/中风疾病差异的心理和促进性机制。培训目标是：（1）扩大对先前生命逆境，促炎性应激反应和与CHD/中风疾病差异有关的全球DNA甲基化状况的知识； （2）在研究设计，招聘，数据收集以及与先前的生命逆境，促炎性压力反应和全球DNA甲基化有关的数据设计，招聘，数据收集和解释方面获得新知识和研究技能的新知识和研究技能； （3）在实验室分析和解释唾液皮质醇，促炎细胞因子和全球DNA甲基化的实验室分析和解释方面获得动手培训并获得知识； （4）在建模方面发展高级统计专业知识。为了实现这些目标并为持续的研究职业提供基础，候选人将进行一项研究，比较46 AA和46 NHW处于CHD/中风风险的风险，以（1）确定先前的生命逆境对CHD/Stroke风险的贡献与NHW级别的急性症状相比，在chd/prom protive的急性压力上，冠军/中风的风险有助于多大化的趋势，并确定与NHW的急性压力相比。预测AA和NHW妇女有冠心病/中风风险的NHW女性的全球DNA甲基化状况，（3）评估全球DNA甲基化状态，作为促炎反应（IL-6）对AA和NHW女性急性压力的预测指标，以危险为CHD/中风。这项研究的意义在于它的潜力有可能阐明CHD/中风疾病易感性的机制，并确定处境不利的少数族裔妇女所表现出的健康差异的可能基础。调查结果将为新型风险概况的发展提供信息，以确定最大风险的CHD/中风负担。 公共卫生相关性：非洲裔美国妇女遭受的缺血性心脏事件和中风是非西班牙裔白人妇女的两倍。先前的生命逆境与促炎风险增加有关，并可能导致冠心病/中风疾病差异。可以预期，这项研究的发现将为冠心病/中风的新风险概况的发展提供信息，并导致较早的鉴定和靶向减轻疾病负担的干预措施。