Social Context and Inflammatory Risk for Stroke in African American Women

描述（由申请人提供）：尽管年龄调整后的心血管（CVD）死亡率有所下降，但与非西班牙裔白人（NHW）女性相比，非裔美国人（AA）女性冠心病/中风的发病率几乎是其两倍。AA女性冠心病/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，对于以往的生活逆境，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）如何导致AA和NHW妇女冠心病/中风疾病的差异，我们知之甚少。此外，已知促炎过程有助于冠心病/中风，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甲基化的改变），这反过来又会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研究开发申请的目的是提供必要的培训和经验，使独立的职业生涯能够确定冠心病/中风疾病差异背后的社会心理和促炎机制。培训目标是：(1)扩大对既往生活逆境、促炎应激反应和全球DNA甲基化状态与冠心病/卒中疾病差异之间关系的认识；(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，因为它与少数民族女性冠心病/卒中风险的既往生活逆境、促炎应激反应和整体DNA甲基化有关；(3)获得实践培训，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，候选人将进行一项比较46名AA和46名有冠心病/中风风险的NHW的研究，以便：(1)确定之前的生活逆境对冠心病/中风风险的影响程度，以及与有冠心病/中风风险的NHW女性相比，AA女性对急性应激的促炎反应（IL-6）。(2)确定生活逆境对有冠心病/卒中风险的AA和NHW女性整体DNA甲基化状态的预测程度；(3)评估整体DNA甲基化状态对有冠心病/卒中风险的AA和NHW女性急性应激促炎反应（IL-6）的预测作用。这项研究的意义在于它有可能阐明冠心病/卒中疾病易感性的机制，并确定弱势少数民族妇女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制定提供信息，以确定冠心病/卒中负担风险最高的人群。

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.