Early life stress and cardiometabolic health in adolescence

摘要 心脏代谢健康状况不佳，包括心血管和代谢疾病， 全球可预防死亡的主要原因。越来越多的证据表明， 暴露于压力会增加心脏代谢风险。研究报告提出4 美国心脏协会最近发现的文献空白：（1）需要 前瞻性研究，（2）需要更好地指定更容易受到压力的时期， 关于心脏代谢健康，（3）需要更多关于机械途径的证据， （4）需要更多的研究来探索性别差异。我们的核心假设是 婴儿期是一个重要的时期，在运动过程中，增加心脏代谢， 疾病风险。我们的早期生活压力（ELS）模型将是由以下人员经历的童年养育： 国际收养的孩子。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。 我们将比较青少年收养的婴儿或非常年幼的儿童， 资源充足的家庭，年轻人在教育程度相当的纳塔尔家庭中长大， 收入。我们将讨论三个具体目标：1）确定重要 生命最初几年的ELS和青春期的心脏代谢功能，2）决定 介导或部分介导ELS与心脏代谢功能相关的因素 以及青春期功能的变化，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，动脉硬度和空腹血糖， 检查胰岛素和脂质水平。关于第二个目标，ELS对 青春期的心脏代谢功能将通过改变压力的介质进行检查 系统活动、免疫老化指数、躯干脂肪量增加和健康行为较差。 在第三个目标中，将审查目标1结果中的性别差异，以及 目标2中的潜在调解人。这些目标是基于重要的初步数据。的影响 这项研究的目的是（1）提高对生命最初几年的重要性的认识， 心脏代谢健康，（2）更深入地表征通过 哪种ELS-心脏代谢风险是实例化的，以及（3）确定是否存在性别 无论是协会或途径介导的心脏代谢风险的差异。这些 贡献是重要的，因为它们将表明有必要开始干预 并将确定新的治疗靶点，以减轻未来的心脏代谢 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.