Early life stress and cardiometabolic health in adolescence

摘要 心脏代谢健康不良，包括心血管和代谢性疾病，是 全球可预防死亡的主要原因。越来越多的证据表明，童年时代 暴露在压力下会增加心脏代谢的风险。拟议的研究涉及4个问题 美国心脏协会最近发现的文献中的空白：(1)需要 前瞻性研究，(2)需要更好地明确更易受压力影响的时期 关于心脏代谢健康，(3)需要更多关于机械途径的证据， 以及(4)有必要进行更多探索性别差异的研究。我们的核心假设是 婴儿期是启动增加心脏代谢的运动过程的重要时期 疾病风险。我们的早期生活压力(ELS)模型将是孤儿院抚养经历的 国际领养的儿童。我们将评估青春期的心脏代谢功能 这些评估与成人心血管健康相关的最早年龄段。 我们将比较从孤儿院收养的婴儿或非常年幼的青少年 资源充足的家庭，有年轻人在他们出生的家庭中长大，受过类似的教育和 收入。我们将解决三个具体目标：1)确定显著的 生命最初几年的ELS和青春期的心脏代谢功能，2)决定 调节或部分调节ELs与心脏代谢功能联系的因素 和青春期功能的变化，以及3)探索ELS的性别差异。 心脏代谢风险关联。在第一个目标下，动脉僵硬和空腹血糖， 胰岛素和血脂水平将被检查。对于第二个目标，ELS对 青春期的心脏代谢功能将用改变的应激介质进行检查。 系统活动、免疫老化指标、躯干脂肪量增加、健康行为较差。 在第三个目标中，性别差异将在目标1的结果中进行检查，并与 目标2中的潜在调解人。这些目标基于重要的初步数据。其影响 这项研究的重点是：(1)更好地理解人生的头几年对 心脏代谢健康，(2)更深层次的表征机制和途径通过 哪些ELS-心脏代谢风险被实例化以及(3)是否有性行为的确定 在调节心脏代谢风险的关联或途径上的差异。这些 捐款意义重大，因为它们将表明开始干预的必要性。 早期开发，并将确定新的治疗靶点，以缓解未来的心脏代谢 风险，并最终改变儿童经历ELS的几率。

Abstract Poor cardiometabolic health, encompassing both cardiovascular and metabolic diseases, is the leading cause of preventable death worldwide. There is growing evidence that childhood exposure to stress increases lifespan cardiometabolic risk. The proposed study addresses 4 gaps in the literature recently identified by the American Heart Association: (1) the need for prospective studies, (2) the need to better specify periods of greater vulnerability to stress with regards to cardiometabolic health, (3) the need for more evidence on mechanistic pathways, and (4) the need for more studies that explore sex differences. Our central hypothesis that infancy is a important period for setting in motion processes that increase cardiometabolic disease risk. Our model of early life stress (ELS) will be orphanage-rearing experienced by children adopted internationally. We will assess cardiometabolic functioning in adolescence, the earliest age period when these assessments are associated with adult cardiovascular health. We will compare adolescents adopted as infants or very young children from orphanages into well-resourced homes with youth reared in their natal families of comparable educations and incomes. We will address three specific aims: 1) Determine the relationship between significant ELS in the first few years of life and cardiometabolic functioning in adolescence, 2) determine factors that mediate or partially mediate the association of ELS with cardiometabolic function and changes in functioning during adolescence, and 3) explore the sex differences in ELS- cardiometabolic risk associations. Under the first aim, arterial stiffness and fasting glucose, insulin, and lipids levels will be examined. For the second aim, the impact of ELS on cardiometabolic functioning in adolescence will be examined with the mediators of altered stress system activity, indices of immune aging, increased trunk fat mass and poorer health behaviors. In the third aim, sex differences will be examined in the outcomes in aim 1 and associations with potential mediators in aim 2. These aims are based on significant preliminary data. The impact of this study will be (1) improved understanding of the importance of the first few years of life for cardiometabolic health, (2) a deeper characterization of the mechanisms and pathways through which ELS-cardiometabolic risk is instantiated and (3) determination of whether there are sex differences in either the association or the pathways mediating cardiometabolic risk. These contributions are significant because they will demonstrate the need to begin interventions earlier in development and will identify novel treatment targets to mitigate future cardiometabolic risk and ultimately shift the odds for children experiencing ELS.