Adverse pregnancy outcomes and long-term risk of cardiovascular disease in women

女性不良妊娠结局和心血管疾病的长期风险

• 批准号: 10446071
• 负责人: Casey Crump
• 金额: $ 68.05万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10446071
• 关键词: Address; Affect; African ancestry; Age; Arrhythmia; Body mass index; Cardiovascular Diagnostic Techniques; Cardiovascular Diseases; Cause of Death; Child; Clinical; Cohort Analysis; Data; Diabetes Mellitus; Early Intervention; Environmental Risk Factor; Family Relationship; Fetal Growth Retardation; Genetic; Gestational Diabetes; Heart failure; Hyperlipidemia; Hypertension; Individual; Inpatients; Intervention; Journals; Life; Life Cycle Stages; Long-Term Care; Long-Term Effects; Longterm Follow-up; Mediating; Mediation; Modeling; Mothers; Myocardial Ischemia; Outpatients; PF4 Gene; Peripheral Vascular Diseases; Phenotype; Population; Pre-Eclampsia; Pregnancy; Premature Birth; Prevention; Registries; Relative Risks; Research; Risk; Risk Assessment; Risk Factors; Sentinel; Siblings; Smoking; Socioeconomic Status; Stress Tests; Stroke; Subgroup; Sweden; Testing; Time; Time trend; Woman; Women' s Health; adverse pregnancy outcome; cardiovascular disorder risk; clinical care; clinical practice; cohort; cost; cost efficient; data registry; design; disease disparity; emerging adult; follow-up; high body mass index; high risk; improved; innovation; low socioeconomic status; mortality; offspring; population based; pregnancy disorder; prevent; prospective; reproductive; screening guidelines; sociodemographic factors; young woman

Pregnancy is a "natural stress test" that may reveal higher cardiovascular disease (CVD) risks in early adulthood, potentially long before the emergence of clinical CVD. Up to one-third of all pregnancies are affected by an adverse pregnancy outcome (APO), defined as preeclampsia, other hypertensive disorders, gestational diabetes, fetal growth restriction, and/or preterm delivery. Consequently, APOs affect >40 million women worldwide each year and nearly 30% of all women during their reproductive years. However, long-term CVD risks associated with APOs remain poorly understood and not well integrated into clinical practice. A better understanding could facilitate earlier interventions in young women and alter their long-term trajectory of CVD. Prior studies have been limited by insufficient phenotyping of APOs and CVD, follow-up time, and statistical power to assess long-term risks. Large cohorts are needed with prospective phenotyping of APOs and CVD before, during, and after pregnancy, and long-term follow-up. We hypothesize that APOs are associated with higher long-term CVD risks (ischemic heart disease, stroke, heart failure, arrhythmias, peripheral vascular disease) across the life course, independently of familial factors. To test this hypothesis, we propose to conduct the first comprehensive assessment of prospectively phenotyped APOs and long-term CVD risks in a large cohort with up to 48 years of follow-up. We will analyze national registry data for all 4.7 M pregnancies in 2.5 M women in Sweden during 1973-2017 and all inpatient and outpatient CVD diagnoses and mortality through 2020. Sweden is an ideal setting because it has linkable individual-level data for the entire population needed to enable this first-of-its-kind study, and CVD rates and mechanisms are comparable to the US. Our aims are to (1) determine associations between 4 major APOs (preeclampsia, other hypertensive disorders, gestational diabetes, fetal growth restriction) and long-term CVD risks across the life course; (2) identify high-risk subgroups of women who are most susceptible to effects of APOs on long-term CVD risks; (3) assess the influence of shared familial (genetic and/or environmental) factors; and (4) develop an integrated model for association of all 5 major APOs (including preterm delivery) with long-term CVD risks. The proposed research is significant because CVD is the leading cause of death in women worldwide, and APOs are common and potentially important sentinels of long-term CVD risks, yet such risks are understudied and poorly integrated into clinical practice. It is innovative because it will provide the first comprehensive assessment of prospectively phenotyped APOs and long-term CVD risks, utilize co-relative designs to disentangle familial confounding, and develop an integrated model for all 5 major APOs using unparalleled data for 2.5 M women. It is highly cost-efficient because we will leverage data from national registries in Sweden that are unavailable or prohibitively costly to assemble in the US. The results will will help improve women's health by identifying the long-term CVD risks associated with APOs needed to guide early prevention and long-term clinical care.

怀孕是一种“自然压力测试”，可能会揭示早期的心血管疾病（CVD）风险更高 成年，可能在临床CVD出现之前很久。最多三分之一的怀孕是 受不良怀孕结局（APO）的影响，定义为先兆子痫，其他高血压疾病， 妊娠糖尿病，胎儿生长限制和/或早产。因此，APO影响> 4000万 在全球范围内，妇女在生殖年份中，所有妇女中有近30％的妇女。但是，长期 与APO相关的CVD风险仍然很少理解，并且没有很好地整合到临床实践中。一个 更好的理解可以促进年轻妇女的早期干预措施，并改变其长期轨迹 CVD。先前的研究受到了APO和CVD的表型不足，随访时间以及 评估长期风险的统计能力。 APO的前瞻性表型需要大的队列 和CVD之前，期间和怀孕后以及长期随访。我们假设APO是 与较高的长期CVD风险有关（缺血性心脏病，中风，心力衰竭，心律不齐， 整个生命过程中的周围血管疾病）与家族因素无关。为了检验这一假设， 我们建议对前瞻性表型Apo和长期进行首次全面评估 在大型队列中，CVD风险多达48年。我们将分析所有4.7 m的国家注册表数据 1973 - 2017年瑞典2.5 m女性的怀孕以及所有住院和门诊CVD诊断和 到2020年的死亡率。瑞典是理想的环境 启用这项首先研究所需的人群，CVD率和机制与 我们。我们的目的是（1）确定4个主要APO之间的关联（先兆子痫，其他高血压 疾病，妊娠糖尿病，胎儿生长限制）和整个生活过程中的长期CVD风险； （2） 确定最容易受到APO对长期CVD风险影响的妇女的高风险亚组； （3） 评估共同的家族性（遗传和/或环境）因素的影响； （4）开发一个集成的 与长期CVD风险的所有5个主要APO（包括早产）的关联模型。提议 研究很重要，因为CVD是全球女性死亡的主要原因，Apos是 长期CVD风险的常见且潜在的重要哨兵，但这些风险被研究不足且较差 整合到临床实践中。它具有创新性，因为它将提供对 前瞻性表型APO和长期CVD风险，利用共同层面的设计将家族性解散 使用无与伦比的2.5 m女性的无与伦比的数据混淆，并为所有5个主要APO开发一个集成模型。 这是高度成本效益的，因为我们将利用瑞典国家注册处的数据 或在美国组装的昂贵。结果将通过识别来帮助改善妇女的健康 与APO相关的长期CVD风险需要指导早期预防和长期临床护理。