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: 10345228
• 负责人: Sadiya Sana Khan
• 金额: $ 62.5万
• 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/10345228
• 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; Enrollment; 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; Research; Research Priority; Risk; Risk Factors; Sampling; Small for Gestational Age Infant; Testing; Texture; United States; Validation; Vascular Diseases; Vascular Endothelial Growth Factor Receptor-1; Woman; Work; adjudicate; adverse pregnancy outcome; antiangiogenesis therapy; base; 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; pregnancy disorder; prepregnancy; racial and ethnic; 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 该提案的目标是妊娠结果和亚临床心血管疾病研究 (PROTECT)， 是了解与相互关联的不良妊娠结局相关的风险因素和机制的轨迹 （APO）和亚临床心血管疾病（CVD）。妊娠高血压疾病、早产、 和小于胎龄儿是常见的 APO，其发病率不断增加，目前使近五分之一的患者变得复杂 在美国怀孕。这些 APO 与 CVD 的短期和长期风险增加有关， 这是最近 NHLBI 工作组关注的焦点。尽管临床上存在表型异质性 APO 亚型的表现（妊娠高血压疾病、早产和小儿高血压） 胎龄），这些 APO 被认为是相互关联的血管疾病，具有共同的潜在基础 与胎盘发育缺陷相关的病理生理学。导致异常的过程 早在 APO 出现临床症状之前，胎盘就开始了，并且后来出现任何 APO 的女性 亚型（包括妊娠期高血压疾病）更有可能（但并非普遍） 以较高的血压水平进入妊娠期。因此，尚不清楚 APO 是否反映了潜在的 CVD 风险或 它们本身是未来 CVD 的独立危险因素。此外，经历过任何这些 APO 的女性 亚型在怀孕后 5 年内发生高血压的风险较高。然而，发展 APO 后高血压和其他传统 CVD 危险因素可能只能部分解释 以后发生 CVD 的风险。小规模生物标志物研究的初步数据表明，潜在的机制将 APO 和 CVD 可能与炎症和抗血管生成有关。因此，为了阐明 APO 和 CVD 之间的途径，从女性第一次怀孕开始并将两者结合起来至关重要 孕期危险因素水平（APO 上游）和孕后纵向随访（APO 下游） APO）。我们建议利用 NHLBI 资助的正在进行的未产妊娠结局研究： 监测准妈妈心脏健康研究 (nuMoM2b-HHS)：种族/民族和地理范围 在第一次怀孕期间招募的不同队列经过严格判定的妊娠结局，广泛 暴露数据和纵向随访。我们将进行颈动脉超声检查以评估标准和新颖 成像参数来检查经历过和未经历过 APO 的女性之间的差异。在目标 1 中，我们 将量化 APO 与亚临床 CVD 之间关联的强度和方向性，独立于 妊娠早期血压。在目标 2 中，我们将确定 APO 和 亚临床CVD是由妊娠后血压介导的。在目标 3 中，我们将鉴定早孕蛋白质组学 与 APO 和亚临床 CVD 相关的途径。完成这些目标将产生新颖且 对亚临床 CVD 发展轨迹和机制的重要见解，为定制 CVD 提供信息 预防策略，并促进 APO 后女性新治疗靶点的发现。