Sociodemographic Regulation of CV Function and Structure

描述（由申请人提供）：心血管疾病（CVD）、2型糖尿病（T2 D）及其合并症在未来几十年对美国构成重要的健康挑战。与欧洲裔美国人（EA）相比，非洲裔美国人（AA）的T2 D患病率更高，CVD和T2 D相关死亡率更高。环境应激已被假定为在CVD和T2 D的发展中起重要作用，特别是在AA中，但对将应激与CVD和T2 D的早期病因学联系起来的潜在生理机制知之甚少。慢性环境应激对AA和EA中CVD和T2 D临床前标志物的纵向发展和表现的可能差异影响的评估只能通过适当控制遗传影响来完成。采用遗传和环境信息双胞胎研究设计，可以控制导致个体变异[遗传力（h2）]的遗传变异，并量化环境影响[环境= 1-h2]。本提案的基本目标是确定暴露于慢性应激是否与CVD和T2 D的早期风险标志物的发展相关，以及AA和EA之间是否存在差异。在格鲁吉亚CV双胞胎研究中，收集了另外2次数据（523对，302对EA和221对AA），这些双胞胎将在T9.5至3.5岁的关键时间跨度内进行5次评价，以捕捉从儿童期到成年期的过渡。特别有用的是增加了交感神经系统和下丘脑-垂体-肾上腺轴激活的新指标（即，去甲肾上腺素和唾液皮质醇的尿排泄率），代谢综合征（即，血压、高密度脂蛋白、甘油三酯、腰围、空腹血糖和胰岛素），环境压力（例如，童年创伤、工作压力、感知到的歧视和不公平、社区社会地位）和血管功能的测量（即，动脉硬化）。与公共卫生的相关性：增加对环境压力相关因素及其潜在生理机制的作用的理解，作为AA和EA之间健康差异的贡献者，将有助于更早和更好地识别CVD和T2 D风险增加的青年和年轻人。它还将帮助制定更个性化的一级预防计划，涉及生活方式干预，其中将考虑慢性压力的作用，以预防这些疾病的早期发病。

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD), type 2 diabetes (T2D) and their comorbidity pose important health challenges for the United States in the coming decades. African Americans (AAs) have a greater prevalence of T2D and have higher CVD and T2D related mortality rates compared with European Americans (EAs). Environmental stress has been postulated as playing an important role in the development of CVD and T2D, particularly among AAs, but little is known about underlying physiological mechanisms linking stress to early etiology of CVD and T2D. Assessment of possible differential impact of chronic environmental stress upon longitudinal development and manifestation of preclinical markers of CVD and T2D in AAs and EAs can be accomplished only with proper control for genetic influences. Employment of a genetically and environmentally informative twin study design enables genetic variation contributing to individual variation [heritability (h2)] to be controlled for and environmental influences [environmentality = 1-h2] to be quantified. The fundamental objective of this proposal is to identify whether exposure to chronic stress is associated with development of early risk markers of CVD and T2D and whether this differs between AAs and EAs. Collecting data on 2 additional occasions in the Georgia CV Twin study (523 pairs, 302 EA and 221 AA) who will be T9.5¿3.5 yrs old will yield 5 evaluations over a crucial time span capturing the transition from childhood into adulthood. Particularly informative will be addition of new indices of sympathetic nervous system and hypothalamic-pituitary-adrenal axis activation (i.e., urinary excretion rate of norepinephrine and salivary cortisol), the metabolic syndrome (i.e., blood pressure, high density lipoprotein, triglycerides, waist circumference, fasting glucose and insulin), environmental stress (e.g., childhood trauma, job strain, perceived discrimination and unfairness, community social status) and a measure of vascular function (i.e., arterial stiffness). Relevance to public health: lncreased understanding of the role of environmental stress related factors and their underlying physiological mechanisms as contributors to health disparities between AAs and EAs will assist in earlier and better identification of youth and young adults at increased risk for CVD and T2D. It will also aid the development of more personalized primary prevention programs involving lifestyle interventions in which the role of chronic stress will be taken into account to prevent early onset of these diseases.