Per- and Polyfluoroalkyl substances mixtures and maternal cardiovascular disease risk across the reproductive life course

全氟烷基和多氟烷基物质混合物与整个生殖生命过程中孕产妇心血管疾病的风险

• 批准号: 10653011
• 负责人: Tamarra M James-Todd
• 金额: $ 61.58万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-22 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653011
• 关键词: Age; Blood Pressure; Body Weight Changes; Body mass index; Breast Feeding; Cardiovascular Diseases; Cause of Death; Central obesity; Chemical Exposure; Chemicals; Clinical; Data; Development; Diastolic blood pressure; Dyslipidemias; Economic Burden; Elderly; Endocrine Disruptors; Environment; Environmental Exposure; Environmental Impact; Environmental Pollutants; Environmental Risk Factor; Etiology; Evaluation; Exposure to; Fasting; First Pregnancy Trimester; Follow-Up Studies; Future; Genetic; Glucose; Glycosylated hemoglobin A; Health Expenditures; Hour; Hyperglycemia; Hypertension; Individual; Insulin; Knowledge; Life Cycle Stages; Life Style; Lipids; Longitudinal cohort study; Measures; Menopausal Status; Modification; Mothers; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Outcome; Participant; Phase; Plasma; Poly-fluoroalkyl substances; Population; Pre-Eclampsia; Predisposition; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Pregnant Women; Production; Prospective, cohort study; Research; Research Design; Risk; Risk Factors; Risk Reduction; Signal Transduction; Stress Tests; Techniques; Testing; Time; United States; Weight Gain; Woman; cardiometabolism; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; cohort; data access; disorder risk; environmental chemical; fasting glucose; follow-up; high body mass index; indexing; innovation; middle age; modifiable risk; next generation; post pregnancy; pregnancy disorder; pregnancy hypertension; pregnant; reproductive; reproductive outcome

ABSTRACT Cardiovascular disease (CVD) is the leading cause of death among women living in the United States. Progress in identifying modifiable risk factors of CVD has been slow. Growing evidence supports the idea that pregnancy may be a stress test for future CVD risk and also a sensitive window of exposure for endocrine disrupting chemicals (EDCs) and women’s CVD risk. Our study will address the critical need to evaluate EDC exposures in pregnancy and midlife to determine whether these chemicals increase CVD risk across the reproductive life course—a key time period of CVD risk factor development. We will focus on exposure to per- and polyfluoroalkyl substances (PFAS), a class of ubiquitous, persistent chemicals. Our scientific premise is strong as prior studies and our preliminary data suggest that exposure to certain PFAS are associated with adverse cardiometabolic outcomes in both pregnant and non-pregnant women. However, previous studies have not prospectively evaluated CVD risk factor development between pregnancy and mid- life or examined replacement PFAS chemicals. The objective of this study is to determine whether exposures to legacy and replacement PFAS alter CVD risk in women across their reproductive lives. Our central hypothesis is that higher exposure to PFAS during pregnancy and through midlife alters the trajectory of CVD risk, first emerging in pregnancy as hypertension disorders of pregnancy (HDP), with subsequent emergence of CVD risk factors (i.e. obesity, hypertension, hyperglycemia, dyslipidemia) in midlife. This hypothesis will be tested through 3 aims using data from Project Viva, a longitudinal cohort study of 1,563 pregnant women with existing pregnancy PFAS data, of which 1198 are currently participating in a 20 year follow up study. In Aim 1, we will evaluate the association between legacy PFAS concentrations measured at 1st trimester of pregnancy with trajectories of systolic and diastolic blood pressure across pregnancy, and HDP (i.e. gestational hypertension and preeclampsia). In Aim 2, we will examine associations of legacy PFAS concentrations in pregnancy and the change in PFAS concentrations from pregnancy to midlife with CVD risk factors (e.g., body mass index, weight change since index pregnancy, central obesity, fasting glucose, insulin, hemoglobin A1c, hyperglycemia, blood pressure, hypertension, lipid levels, and dyslipidemia) during midlife (i.e.,20 years following pregnancy). In Aim 3, we will assess the association of legacy and replacement PFAS in mid-life with CVD risk factors in midlife. Across all aims, we will examine exposure to individual PFAS and their mixtures using advanced statistical techniques. The innovative aspects of our proposal include: evaluation of pregnancy as a susceptible window for EDCs and women’s CVD risk, examination of next-generation PFAS, and use of a large, well-characterized cohort that is undergoing 20 year follow up. Our findings will fill an important gap about the impact of environmental chemicals on an understudied time period—between pregnancy and midlife—with implications for CVD prevention and risk reduction.

摘要心血管疾病（CVD）是居住在联合的妇女中死亡的主要原因 国家。确定CVD的可修改风险因素的进展一直很慢。越来越多的证据支持 怀孕可能是对未来CVD风险的压力测试的想法，也是敏感的暴露窗口 内分泌破坏化学物质（EDC）和女性CVD风险。我们的研究将解决至关重要的需求 评估EDC在怀孕和中年的暴露，以确定这些化学物质是否增加CVD风险 在整个生殖生活课程中 - CVD风险因素开发的关键时期。我们将重点关注 暴露于多氟烷基物质（PFA），这是一类无处不在的持续化学物质。我们的 科学前提是先前的研究，我们的初步数据表明，某些PFA的接触是 与孕妇和非妊娠妇女的不良心脏代谢结果有关。然而， 先前的研究未预先评估怀孕与中期之间的CVD风险因素的发展 生命或检查的替代PFAS化学物质。这项研究的目的是确定是否 对遗产和替代PFA的暴露改变了女性在复制生活中的CVD风险。我们的 中心假设是，怀孕期间和通过中年较高的PFA暴露在改变轨迹 CVD风险，首先是怀孕的妊娠疾病（HDP），随后序列 中期生活中CVD危险因素的出现（即肥胖，高血压，高血糖，血脂异常）。这 假设将使用来自项目Viva的数据进行测试，该数据是Viva的数据，这是一项1,563的纵向队列研究 现有怀孕PFA数据的孕妇，其中1198目前正在参加20年 后续研究。在AIM 1中，我们将评估测量的传统PFA浓度之间的关联 怀孕的第1个三个月，妊娠的收缩压和舒张压轨迹和HDP （即妊娠高血压和先兆子痫）。在AIM 2中，我们将研究传统PFA的协会 怀孕的浓度以及PFA从怀孕到中年的变化，CVD风险 因素（例如，体重指数，体重变化以来指数妊娠，中央肥胖症，禁食葡萄糖，胰岛素， 中年时期血红蛋白A1C，高血糖，血压，高血压，脂质水平和血脂异常） （即怀孕20年后）。在AIM 3中，我们将评估遗产和替代PFA的关联 在中年有中期危险因素的中年。在所有目标中，我们将研究对单个PFA的接触和 它们使用高级统计技术的混合物。我们提案的创新方面包括：评估 怀孕是EDCS和妇女CVD风险的易感窗口，检查下一代PFA， 并使用了正在进行20年随访的大型，良好的人群。我们的发现将填补 关于环境化学物质对知识时期的影响的重要差距 - 之间 怀孕和中年 - 对CVD预防和降低风险的影响。