Shared Antecedents to Pre-term Birth and Cardiovascular Disease in Women

女性早产和心血管疾病的共同原因

• 批准号: 9903432
• 负责人: Janet M Catov
• 金额: $ 12.01万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903432
• 关键词: 37 weeks gestation; Address; Affect; Age; Area; Atherosclerosis; Biochemical; Biological Markers; Birth; Blood Pressure; C-reactive protein; Cardiac; Cardiovascular Diseases; Cause of Death; Cessation of life; Coronary Artery Risk Development in Young Adults Study; Data; Data Set; Detection; Development; Endothelium; Epidemiology; Fetal Growth Retardation; Foundations; Functional disorder; Gestational Diabetes; Goals; Health; Hypertension; Inflammation; Inflammatory; Intercellular adhesion molecule 1; Intervention; Left Ventricular Mass; Left Ventricular Remodeling; Life; Life Style; Link; Lipids; Measures; Metabolic Diseases; Modality; National Heart, Lung, and Blood Institute; Obesity; Outcome; Persons; Phenotype; Play; Predisposition; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prevention; Race; Recording of previous events; Recurrence; Risk; Role; Sampling; Structure; Surveys; TNF gene; Term Birth; Testing; Woman; Work; cardiometabolism; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; carotid intima-media thickness; comorbidity; coronary artery calcification; design; disorder risk; early screening; endothelial dysfunction; follow-up; gestational weight gain; high risk; improved; indexing; insight; maternal risk; middle age; novel; prepregnancy; prepregnancy obesity; primary outcome; prospective; reproductive; sex; young adult; young woman

PROJECT ABSTRACT Cardiovascular disease (CVD) is the leading cause of death among women and rates are rising in young women. Thus, prevention and early screening are essential. Women with preterm births (PTB) have excess CVD risk later in life compared to those with term births. It is unclear, however, if PTB unmasks, instigates or exacerbates a common predisposition. Mechanisms are not understood and pre-pregnancy measures are almost nonexistent. A few studies, including our own, raise the possibility that preterm birth may have lasting cardiometabolic effects that increase CVD risk, but longitudinal biomarker data have been unavailable to directly address this essential question. Inflammation and endothelial function are plausible but under-studied mechanisms linking PTB and CVD in women. The Coronary Artery Risk Development in Young Adults (CARDIA) study uniquely includes multiple assessments in women of reproductive age, both before and after pregnancies. Now in its third decade of follow-up with remarkably strong retention (72%), CARDIA will have conducted up to 9 in-person exams among 1,362 women (50% Black) who delivered 2,389 births from baseline to year 30. Uniquely, and just recently available, inflammatory and endothelial function markers have been measured in 900 CARDIA women from samples obtained both before and after pregnancies. We hypothesize that preterm birth is related to the pre-pregnancy profile, and additionally leaves a lasting pro-inflammatory signature that predisposes affected women to endothelial dysfunction, atherosclerosis and left ventricular remodeling. Our study aims are to 1) relate pre-pregnancy concentrations of high sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (s- ICAM) and tumor necrosis factor-α (TNF-α) to risk of PTB and determine if the change in these markers after delivery differs according to a history of PTB; and 2) evaluate the association of PTB and these profiles with atherosclerosis and cardiac remodeling in midlife. These novel studies will fill a major gap in our understanding of the link between PTB in susceptible women and the potential mechanisms underlying their increased risk of later CVD. These critical data will be the foundation for the discovery of novel mechanisms linking PTB to later CVD in women. The impact of this study is that it will be the first to use pre-pregnancy biomarkers of inflammation and endothelial function to understand the shared link between preterm birth and increased maternal risk of CVD later in life. These critical data will identify underlying inflammatory and endothelial mechanisms predisposing to both preterm birth and CVD in women, and pinpoint the timing and types of interventions needed to improve cardiovascular health in women.

项目摘要 心血管疾病（CVD）是女性死亡的主要原因，并且年轻人的发病率正在上升 女性。因此，预防和早期筛查至关重要。早产 (PTB) 的女性体内有过量的 与足月出生的人相比，晚年的 CVD 风险更高。然而，尚不清楚 PTB 是否揭露、煽动或 加剧了一种常见的倾向。机制尚不清楚，孕前措施尚不明确 几乎不存在。一些研究，包括我们自己的研究，提出了早产可能会持续存在的可能性。 心脏代谢影响会增加 CVD 风险，但尚无纵向生物标志物数据 直接回答这个基本问题。炎症和内皮功能是合理的，但尚未得到充分研究 女性 PTB 和 CVD 的关联机制。年轻人冠状动脉风险的发展 (CARDIA) 研究独特地包括对育龄妇女之前和之后的多项评估 怀孕。现在，CARDIA 已进入第三个十年的后续行动，其保留率非常高 (72%)， 对 1,362 名妇女（50% 黑人）进行了多达 9 次现场检查，这些妇女在 2017 年产下了 2,389 名婴儿 基线至 30 年。独特且最近才获得的炎症和内皮功能标记物 对 900 名 CARDIA 妇女在怀孕前后采集的样本进行了测量。我们 假设早产与怀孕前的情况有关，并且还会留下持久的影响 促炎特征使受影响的女性容易出现内皮功能障碍， 动脉粥样硬化和左心室重构。我们的研究目的是 1) 将怀孕前联系起来 高灵敏度 C 反应蛋白 (hsCRP)、可溶性细胞间粘附分子-1 (s- ICAM）和肿瘤坏死因子-α（TNF-α）与 PTB 风险的关系，并确定这些标志物在治疗后是否发生变化 根据 PTB 病史，分娩方式有所不同； 2) 评估 PTB 和这些配置文件的关联 中年动脉粥样硬化和心脏重塑。这些新颖的研究将填补我们理解上的一个重大空白 易感女性中的 PTB 与其感染风险增加的潜在机制之间的联系 后来CVD。这些关键数据将成为发现将 PTB 与以后联系起来的新机制的基础。 女性CVD。这项研究的影响在于，它将是第一个使用孕前生物标志物的研究 炎症和内皮功能，以了解早产和妊娠增加之间的共同联系 母亲在晚年罹患 CVD 的风险。这些关键数据将识别潜在的炎症和内皮细胞 女性早产和心血管疾病的诱发机制，并查明早产的时间和类型 需要采取干预措施来改善女性心血管健康。