PRegnancy OuTcomEs and subclinical Cardiovascular disease sTudy: (PROTECT)

妊娠结局和亚临床心血管疾病研究：（保护）

• 批准号: 10534752
• 负责人: Sadiya Sana Khan
• 金额: $ 74.43万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-06 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10534752
• 关键词: Abnormal placentation; Accounting; Address; Adverse event; Age; Ancillary Study; Angiogenesis Pathway; Biological Assay; Biological Markers; Blood Pressure; Blood Proteins; Blood Vessels; Cardiac health; Cardiovascular Diseases; Carotid Arteries; Chronic; Clinical; Data; Development; Disease; Early identification; Enrollment; Ethnic Origin; Exposure to; Functional disorder; Funding; Future; Geography; Gestational Diabetes; Goals; Guide prevention; Guidelines; Heart; Heart Diseases; Heterogeneity; High Risk Woman; Hypertension; Image; Incidence; Individual; Inflammation; Inflammatory; Interleukin-6; Intervention; Life; Link; Maternal Mortality; Measures; Mediating; Mission; Monitor; Mothers; National Heart, Lung, and Blood Institute; Nulliparity; Outcome Study; Pathogenesis; Pathway interactions; Persons; Phenotype; Placentation; Postpartum Period; Pregnancy; Pregnancy Outcome; Premature Birth; Prevention; Prevention strategy; Process; Proteomics; Public Health; Pulse Pressure; Race; Research; Research Priority; Risk; Risk Factors; Risk Reduction; Sampling; Small for Gestational Age Infant; Testing; Texture; United States; Validation; Vascular Diseases; Vascular Endothelial Growth Factor Receptor-1; Woman; Work; adjudication; adverse pregnancy outcome; antiangiogenesis therapy; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; carotid intima-media thickness; cohort; cytokine; disorder risk; early pregnancy; experience; follow-up; high risk; improved; insight; maternal morbidity; new therapeutic target; novel; novel marker; novel therapeutics; post pregnancy; pregnancy disorder; prepregnancy; recruit; risk prediction; screening; study population; ultrasound; working group; young woman

ABSTRACT The goal of this proposal, PRegnancy OuTcomEs and subclinical Cardiovascular disease sTudy (PROTECT), is to understand the trajectory of risk factors and mechanisms linking interrelated adverse pregnancy outcomes (APOs) and subclinical cardiovascular disease (CVD). Hypertensive disorders of pregnancy, preterm delivery, and small for gestational age are common APOs, increasing in incidence, and currently complicate nearly 1 in 5 pregnancies in the United States. These APOs are associated with increased short- and long-term risk of CVD, which was the focus of a recent NHLBI Working Group. Despite phenotypic heterogeneity in the clinical manifestations of APO subtypes (hypertensive disorders of pregnancy, preterm delivery, and small for gestational age), these APOs are thought to be interrelated vascular disorders with shared underlying pathophysiology related to defective placental development. The processes leading to abnormal placentation begin long before APOs are clinically apparent, and women who later experience any of the APO subtypes (including and in addition to hypertensive disorders of pregnancy) are more likely (but not universally) to enter pregnancy with higher BP levels. Therefore, it is unclear whether APOs reflect latent CVD risk or are themselves independent risk factors for future CVD. Moreover, women who experience any of these APO subtypes have a higher risk of incident hypertension within 5 years post-pregnancy. However, development of hypertension and other traditional CVD risk factors following an APO may only partially explain the increased risk for later CVD. Preliminary data from small-scale biomarker studies suggest underlying mechanisms linking APOs and CVD may be related to inflammation and anti-angiogenesis. Therefore, in order to elucidate the pathways between APOs, and CVD, it is critical to begin with a woman’s first pregnancy and incorporate both intra-pregnancy risk factor levels (upstream of APOs) and longitudinal follow-up post-pregnancy (downstream of APOs). We propose to leverage the ongoing NHLBI-funded Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be Heart Health Study (nuMoM2b-HHS): a racially/ethnically and geographically diverse cohort recruited during the first pregnancy with rigorously adjudicated pregnancy outcomes, extensive exposure data, and longitudinal follow-up. We will perform carotid artery ultrasound to assess standard and novel imaging parameters to examine differences in women who have and have not experienced APOs. In Aim 1, we will quantify the strength and directionality of associations between APOs and subclinical CVD, independent of BP in early pregnancy. In Aim 2, we will determine the extent to which the relationship between APOs and subclinical CVD is mediated by post-pregnancy BP. In Aim 3, we will identify early pregnancy proteomic pathways that are associated with APOs and subclinical CVD. Completion of these aims will yield novel and significant insights into the trajectory and mechanisms of development of subclinical CVD, inform tailored CVD prevention strategies, and advance discovery of new therapeutic targets for women following APOs.

抽象的 该提案，怀孕结局和亚临床心血管疾病研究（Protect）的目标， 是要了解连接相互关联的不良怀孕结果的危险因素和机制的轨迹 （APO）和亚临床心血管疾病（CVD）。怀孕，早产的高血压疾病， 妊娠年龄很小的是常见的APO，发病率增加，目前使近5个中的1个复杂 美国的怀孕。这些APO与CVD的短期和长期风险增加有关， 这是最近NHLBI工作组的重点。尽管临床表型异质性 Apo亚型的表现（怀孕的高血压疾病，早产，并且很小 胎龄），这些APO被认为是相互关联的血管疾病，具有共同的基础 病理生理学与缺陷的位置发育有关。导致异常的过程 胎盘开始早在临床上很明显之前就开始了，后来经历任何APO的女性 亚型（包括怀孕的高血压疾病）更有可能（但不是普遍） 以更高的BP水平进入怀孕。因此，尚不清楚APO是否反映了潜在的CVD风险还是 他们本身是未来CVD的独立风险因素。而且，体验这些apo中任何一个的女性 亚型在怀孕后5年内患有高血压的风险更高。但是，发展 APO之后的高血压和其他传统CVD风险因素可能只能部分解释增加 稍后CVD的风险。来自小规模生物标志物研究的初步数据提出了联系的潜在机制 APO和CVD可能与炎症和抗血管生成有关。因此，为了阐明 Apos和CVD之间的途径，从女性的第一次怀孕开始并结合两者至关重要 怀孕内危险因素水平（APO上游）和纵向后随访后（下游） apos）。我们建议利用正在进行的NHLBI资助的无效妊娠结局研究： 监测准母亲的心脏健康研究（NUMOM2B-HHS）：在种族/地理上 在第一次怀孕期间招募了多样化的队列，并进行了严格调整的怀孕结果，广泛 暴露数据和纵向随访。我们将执行颈动脉超声来评估标准和新颖 成像参数以检查具有和没有经历过APO的女性的差异。在AIM 1中，我们 将量化Apos与亚临床CVD之间关联的强度和方向性，与 怀孕初期的BP。在AIM 2中，我们将确定Apos与Apos之间的关系的程度 亚临床CVD由孕后BP介导。在AIM 3中，我们将确定早期妊娠蛋白质组学 与APO和亚临床CVD相关的途径。这些目标的完成将产生小说，并且 对亚临床CVD的发展轨迹和机制的重要见解，量身定制的CVD 预防策略，并在APO后针对女性发现新的治疗靶标。