Allostatic Load and Race: Implications for Cardiovascular Health in Pregnancy and Beyond

项目概要/摘要 几十年来，被认为是黑人的怀孕个体被认为是最危险的。 妊娠期高血压疾病（HDP）。HDP经常跟随怀孕后的个体，表现为 加速心血管疾病（CVD），这也不成比例地影响黑人女性。机制 种族的含义，一个复杂的社会结构，成为生物学嵌入和转化为 病理生理学仍然未知。非稳态负荷（AL） 并且包括与种族有关的压力。建议的K99/R 00的目的是 为候选人提供足够的培训和经验，以调查健康差异，AL和组学- 基于生物标志物，在怀孕和以后的背景下。K99阶段的目标是（1）评估 妊娠早期AL对自认为种族与HDP之间关联的影响，（2）评估这种关联 探讨孕早期AL指数与遗传变异之间的关系;（3）探讨孕早期DNA 甲基化对妊娠早期AL指数和先兆子痫之间的关联性的影响，HDP与最大的 种族差异该项目是对未产妊娠结局研究的辅助：监测母亲对 心脏健康研究（nuMoM 2b-HHS），并利用先前为nuMoM 2b-HHS收集的现有数据。 以前收集的早期妊娠临床和GWAS数据以及最近生成的DNA甲基化数据将 用于实现目标1、2和3。拟议的K99培训计划包括专家指导， 会议和研讨会，课程，和会议，以实现能力（A）的机制， HDP/妊娠后心血管健康，（B）健康差异研究，（C）生物信息学和 组学数据，以及（D）职业生涯发展。R 00阶段将这一调查范围扩展到 在同一队列中，妊娠后2-7年和7-12年两个时间点的心血管健康状况。R00 阶段的目标是（1）评估AL指数轨迹对自我识别之间关系的影响 种族和怀孕后心血管健康和（2）评估DNA甲基化之间的关联 轨迹和怀孕后心血管健康。与K99阶段一样，以前收集的数据将 用于执行目标1，而目标2将使用现有的DNA样本，数据清理和质量控制 管道这种创新的应用程序提供了几个实验机会，大大影响多个 研究领域包括：AL，HDP，怀孕后CVD，以及每个种族的差异。调查结果将告知 制定以证据为基础的干预措施，重点是减少健康差距， 妊娠结局和女性心血管健康。

PROJECT SUMMARY/ABSTRACT For decades, pregnant individuals who identify as Black have been considered at greatest risk for hypertensive disorders of pregnancy (HDP). HDP often follow individuals well past pregnancy, presenting as accelerated cardiovascular disease (CVD), which also disproportionately affects Black females. Mechanisms by which implications of race, a complex social structure, become biologically embedded and translate into pathophysiology remain unknown. Allostatic Load (AL) and is inclusive of race-related stress. The purpose of the proposed K99/R00 is to provide the candidate with adequate training and experience to investigate health disparities, AL and omics- based biomarkers, within the context of pregnancy and beyond. The K99 phase aims are to (1) evaluate the effect of first-trimester AL on the association between self-identified race and HDP, (2) evaluate the association between first-trimester AL index and genetic variation, and (3) investigate the effect of first-trimester DNA methylation on the association between first-trimester AL index and preeclampsia, the HDP with the greatest racial disparity. This project is ancillary to the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to- be Heart Health Study (nuMoM2b-HHS) and leverages existing data previously collected for nuMoM2b-HHS. Previously collected first-trimester clinical and GWAS data and recently generated DNA methylation data will be utilized to accomplish aims 1, 2, and 3. The proposed K99 training plan includes expert mentorship, meetings and seminars, coursework, and conferences, to achieve competency in (A) mechanisms of HDP/post-pregnancy cardiovascular health, (B) health disparities research, (C) bioinformatics and analysis of omics data, and (D) professional career development. The R00 phase extends this line of investigation to cardiovascular health at two timepoints, 2-7 and 7-12 years, following pregnancy in the same cohort. The R00 phase aims are to (1) evaluate the effect of AL index trajectories on the relationship between self-identified race and post-pregnancy cardiovascular health and (2) evaluate the association between DNA methylation trajectory and post-pregnancy cardiovascular health. As with the K99 phase, previously collected data will be utilized to execute aim 1, while aim 2 will employ existing DNA samples, data cleaning and quality control pipelines. This innovative application provides several experimental opportunities to greatly impact multiple fields of research including: AL, HDP, post-pregnancy CVD, and racial disparities of each. Findings will inform the development of evidence-based interventions that focus on reducing health disparities and improving pregnancy outcomes and cardiovascular health in females.