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

稳态负荷和种族：对妊娠期及以后心血管健康的影响

• 批准号: 10525297
• 负责人: Mitali Ray
• 金额: $ 12.97万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-04 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10525297
• 关键词: Affect; American; Area; Bioinformatics; Biological; Biological Markers; Black Populations; Black race; Cardiac health; Cardiovascular Diseases; Cardiovascular system; Chronic; Chronic stress; Clinical; Competence; Complex; DNA; DNA Methylation; Data; Development; Eclampsia; Evidence based intervention; Faculty; Female; First Pregnancy Trimester; Functional disorder; Funding; Future; Genes; Genetic Polymorphism; Genetic Variation; Genomics; Genotype; Health Disparities Research; Hypertension; Individual; Inflammatory; Institutional Racism; Investigation; Link; Longevity; Maternal Mortality; Measures; Mentors; Mentorship; Metabolic; Methylation; Monitor; Mothers; Nulliparity; Outcome Study; Parents; Participant; Pathway interactions; Phase; Physiological; Physiology; Positioning Attribute; Pre-Eclampsia; Predisposition; Pregnancy; Pregnancy Outcome; Prevalence; Public Health; Quality Control; Race; Reduce health disparities; Research; Research Personnel; Risk; Risk Factors; Sampling; Secure; Stress; Training; Translating; Trauma; United States; Weight; allostatic load; base; black women; cardiovascular health; career development; cohort; data cleaning; data quality; disease disparity; early pregnancy; epigenomics; experience; genome wide association study; health disparity; improved; indexing; innovation; insight; meetings; mortality; multi-ethnic; novel; pregnancy disorder; pregnancy hypertension; pregnant; racial disparity; racial health disparity; social; social health determinants; social structure; symposium; tenure track; training opportunity

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.

项目概要/摘要 几十年来，黑人孕妇被认为面临着最大的风险 妊娠期高血压疾病（HDP）。 HDP 通常会追踪怀孕后很久的个体，表现为 加速心血管疾病（CVD），这也对黑人女性造成不成比例的影响。机制 通过这种方式，种族这一复杂的社会结构的影响在生物学上嵌入并转化为 病理生理学仍不清楚。静态负载 (AL) 并且包括与种族相关的压力。拟议 K99/R00 的目的是 为候选人提供足够的培训和经验来调查健康差异、AL 和组学 - 基于生物标志物，在怀孕期间及之后。 K99 阶段的目标是 (1) 评估 早孕期 AL 对自我认同种族与 HDP 之间关联的影响，(2) 评估关联 早孕期 AL 指数与遗传变异之间的关系，以及 (3) 研究早孕期 DNA 的影响 甲基化对妊娠早期 AL 指数与先兆子痫之间关系的影响，其中 HDP 的影响最大 种族差异。该项目是未产儿妊娠结果研究的辅助项目：监测母亲- be 心脏健康研究 (nuMoM2b-HHS) 并利用之前为 nuMoM2b-HHS 收集的现有数据。 之前收集的孕早期临床和 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、课程作业和会议，以实现 (A) 机制的能力 HDP/孕后心血管健康，(B) 健康差异研究，(C) 生物信息学和分析 组学数据，以及 (D) 职业生涯发展。 R00 阶段将这一调查范围扩展到 同一队列中怀孕后两个时间点（2-7 年和 7-12 年）的心血管健康状况。 R00 该阶段的目标是 (1) 评估 AL 指数轨迹对自我认同之间关系的影响 种族和孕后心血管健康；(2) 评估 DNA 甲基化之间的关联 轨迹和孕后心血管健康。与 K99 阶段一样，之前收集的数据将被 用于执行目标1，而目标2将利用现有的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多种实验机会，可以极大地影响多个领域 研究领域包括：AL、HDP、妊娠后CVD以及各自的种族差异。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和改善 女性的妊娠结局和心血管健康。