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

基本信息

批准号：
10610456
负责人：
Casey Crump
金额：
$ 66.33万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10610456
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 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 Peripheral Vascular Diseases Phenotype Population Pre-Eclampsia Predisposition 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&apos 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 human old age (65+)improved innovation low socioeconomic status mortality offspring population based post pregnancy pregnancy disorder prevent prospective reproductive screening guidelines sociodemographic factors young woman

项目摘要

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.

怀孕是一项“自然压力测试”，可能会揭示早期较高的心血管疾病 (CVD) 风险成年期，可能早在临床心血管疾病出现之前。多达三分之一的怀孕是受不良妊娠结局（APO）影响，定义为先兆子痫、其他高血压疾病、妊娠糖尿病、胎儿生长受限和/或早产。因此，APO 影响超过 4000 万每年全世界都有女性，其中近 30% 的女性处于育龄期。然而，长期来看与 APO 相关的 CVD 风险仍然知之甚少，也没有很好地融入临床实践。一个更好的理解可以促进对年轻女性的早期干预并改变她们的长期轨迹化学气相沉积。先前的研究因 APO 和 CVD 的表型分析不足、随访时间和评估长期风险的统计能力。 APO 的前瞻性表型分析需要大量队列怀孕前、怀孕期间和怀孕后的CVD以及长期随访。我们假设 APO 是与较高的长期 CVD 风险（缺血性心脏病、中风、心力衰竭、心律失常、周围血管疾病）贯穿生命全程，与家族因素无关。为了检验这个假设，我们建议对前瞻性表型 APO 和长期大型队列的 CVD 风险长达 48 年的随访。我们将分析所有 470 万的国家登记数据 1973 年至 2017 年间瑞典 250 万妇女的怀孕情况以及所有住院和门诊 CVD 诊断和到 2020 年的死亡率。瑞典是一个理想的环境，因为它拥有整个国家的可链接的个人层面数据进行这项史无前例的研究所需的人群，CVD 发生率和机制与我们。我们的目标是 (1) 确定 4 种主要 APO（先兆子痫、其他高血压）之间的关联疾病、妊娠糖尿病、胎儿生长受限）和整个生命过程中的长期心血管疾病风险； (2) 确定最容易受到 APO 对长期 CVD 风险影响的女性高风险亚群； (3) 评估共同的家族（遗传和/或环境）因素的影响； (4) 开发集成的所有 5 种主要 APO（包括早产）与长期 CVD 风险关联的模型。拟议的研究意义重大，因为 CVD 是全世界女性死亡的主要原因，而 APO 是长期 CVD 风险的常见且潜在重要的哨兵，但对此类风险的研究不足且不充分融入临床实践。它是创新的，因为它将提供第一个全面的评估前瞻性表型 APO 和长期 CVD 风险，利用相关设计来解开家族性混淆，并使用 250 万女性的无与伦比的数据为所有 5 个主要 APO 开发一个综合模型。它具有很高的成本效益，因为我们将利用瑞典国家登记处无法提供的数据或者在美国组装成本高昂。研究结果将有助于改善女性健康与 APO 相关的长期 CVD 风险需要指导早期预防和长期临床护理。

项目成果

期刊论文数量（28）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Preterm birth and risk of chronic kidney disease from childhood into mid-adulthood: national cohort study.

早产和从童年到成年中期慢性肾病的风险：国家队列研究。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Crump, Casey;Sundquist, Jan;Winkleby, Marilyn A;Sundquist, Kristina
通讯作者：
Sundquist, Kristina

Pre-term delivery and long-term risk of heart failure in women: a national cohort and co-sibling study.

女性早产和心力衰竭的长期风险：一项全国队列和兄弟姐妹研究。

DOI：
发表时间：
2021-11-24
期刊：
影响因子：
39.3
作者：
Crump, Casey;Sundquist, Jan;McLaughlin, Mary Ann;Dolan, Siobhan M;Sieh, Weiva;Sundquist, Kristina
通讯作者：
Sundquist, Kristina

Hypertension in Pregnancy Among Immigrant and Swedish Women: A Cohort Study of All Pregnant Women in Sweden.

移民和瑞典妇女妊娠期高血压：对瑞典所有孕妇的队列研究。

DOI：
发表时间：
2024-03-05
期刊：
影响因子：
5.4
作者：
Wändell, Per;Crump, Casey;Li, Xinjun;Stattin, Nouha Saleh;Carlsson, Axel C;Sundquist, Jan;Sundquist, Kristina
通讯作者：
Sundquist, Kristina

Preterm Delivery and Long-Term Risk of Stroke in Women: A National Cohort and Cosibling Study.

女性早产和长期中风风险：一项全国队列和共同研究。