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(T2D)及其合并症在未来几十年对美国的健康构成重要挑战。与欧洲裔美国人(EA)相比，非裔美国人(AA)的T2D患病率更高，心血管疾病和T2D相关死亡率更高。环境应激被认为在CVD和T2D的发展中起着重要作用，尤其是在腹主动脉系统中，但关于应激与CVD和T2D的早期病因之间的潜在生理机制知之甚少。只有在对遗传影响进行适当控制的情况下，才能评估慢性环境应激对AAS和EAS中CVD和T2D临床前标志物的纵向发展和表现的可能差异影响。采用具有遗传和环境信息的双胞胎研究设计，能够控制导致个体变异的遗传变异[遗传力(H2)]，并量化环境影响[环境心态=1-h2]。这项建议的基本目标是确定慢性应激暴露是否与心血管疾病和T2D的早期风险标记物的发展有关，以及这在腹主动脉和腹主动脉之间是否有所不同。在佐治亚州CV双胞胎研究中另外两个场合(523对、302对EA和221对AA)收集的数据将在T9.5？3.5岁的关键时间跨度内产生5项评估，该时间跨度捕捉到从童年到成年的转变。其中将加入交感神经系统和下丘脑-垂体-肾上腺轴激活(即尿去甲肾上腺素和唾液皮质醇排泄率)、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、工作紧张、感觉到的歧视和不公平、社区社会地位)和血管功能指标(即动脉僵硬)的新指数。与公共卫生的相关性：提高对环境应激相关因素的作用及其潜在的生理机制的了解，这些因素是造成AAs和EAs之间健康差异的因素，这将有助于更早和更好地识别青年和具有更高心血管疾病和T2D风险的年轻人。它还将帮助制定更个人化的初级预防方案，包括生活方式干预，其中将考虑慢性应激的作用，以防止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.