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）及其合并症是未来几十年美国面临的重要健康挑战。非裔美国人（AAs）与欧洲裔美国人（EAs）相比，T2D患病率更高，CVD和T2D相关死亡率更高。环境应激一直被认为在CVD和T2D的发展中起着重要作用，特别是在AAs中，但关于应激与CVD和T2D早期病因之间的潜在生理机制知之甚少。只有在适当控制遗传影响的情况下，才能评估慢性环境应激对AAs和ea患者CVD和T2D临床前标志物的纵向发展和表现的可能差异影响。采用遗传和环境信息双胞胎研究设计，可以控制导致个体变异的遗传变异[遗传性（h2）]，并量化环境影响[environmentality = 1-h2]。本提案的基本目的是确定暴露于慢性应激是否与CVD和T2D的早期风险标志物的发展有关，以及这在AAs和ea之间是否存在差异。在Georgia CV Twin研究中另外两次收集数据（523对，302对EA和221对AA），他们将在T9.5 - 3.5岁之间，在捕捉从童年到成年过渡的关键时间跨度内产生5次评估。特别有用的将是增加新的交感神经系统和下丘脑-垂体-肾上腺轴激活指数（即尿中去甲肾上腺素和唾液皮质醇的排泄率），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，感知歧视和不公平，社区社会地位)和衡量血管功能（即动脉硬度）。与公共卫生的相关性：进一步了解环境应激相关因素及其潜在生理机制作为aa和ea之间健康差异的贡献者的作用，将有助于更早、更好地识别心血管疾病和T2D风险增加的青年和青壮年。它还将有助于发展更个性化的初级预防项目，包括生活方式干预，其中慢性压力的作用将被考虑在内，以预防这些疾病的早期发作。

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.