Arterial Stiffness and Wave Reflection: Physiological Contributors to CVD after Adverse Pregnancy Outcomes

动脉僵硬度和波反射：不良妊娠结果后 CVD 的生理因素

• 批准号: 10632908
• 负责人: Abbi Danielle Lane
• 金额: $ 73.59万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10632908
• 关键词: Ancillary Study; Angiogenesis Inhibitors; Back; Behavior; Biological Markers; Birth; Blood Vessels; Cardiac health; Cardiovascular Diseases; Cohort Studies; Communities; Data; Data Collection; Data Set; Development; Disease; Dose; Early identification; Enrollment; Fetal Growth Retardation; First Births; Functional disorder; Funding; Goals; Greenland; High Risk Woman; Hypertension; Individual; Inflammatory; Interleukin-6; Intervention; Knowledge; Left; Life Style; Life Style Modification; Link; Measurement; Measures; Mothers; National Heart, Lung, and Blood Institute; Nulliparity; Participant; Pathogenesis; Pathway interactions; Patient Self-Report; Pattern; Persons; Phenotype; Physical activity; Physiological; Pre-Eclampsia; Pregnancy; Premature Birth; Premenopause; Prevention strategy; Procedures; Race; Recording of previous events; Reporting; Research Personnel; Risk; Risk Factors; Sampling; Structural defect; Systolic Pressure; Techniques; Vascular Diseases; Vascular Endothelial Growth Factor Receptor-1; Ventricular; Woman; adequate sleep; adverse pregnancy outcome; arterial stiffness; behavioral phenotyping; biomarker panel; biomarker signature; cardiovascular disorder risk; cohort; comparison control; design; early pregnancy; follow-up; genome sequencing; good diet; heart disease risk; hemodynamics; high risk population; hypertensive; improved; innovation; lifestyle data; middle age; modifiable lifestyle factors; molecular phenotype; participant enrollment; post pregnancy; pregnancy disorder; pressure; sex; time interval; whole genome; young adult

ABSTRACT Adverse pregnancy outcomes (APOs), such as hypertensive disorders of pregnancy, intrauterine growth restriction, and preterm birth, occur in about 20% of pregnancies and are associated with excess lifelong cardiovascular disease (CVD) risk for women. However, levels of traditional CVD risk factors may not identify all women progressing towards CVD after an APO. Data suggest that more sensitive measures are needed to identify premenopausal women on track to develop CVD after APOs, especially non-hypertensive APOs. Pulsatile hemodynamic dysfunction, i.e., high arterial pressure wave reflection magnitude, high systolic pressure augmentation, and high central arterial stiffness, can precede left ventricular structural abnormalities, diastolic dysfunction, hypertension, and overt CVD and can be improved or reversed with lifestyle modification. Small, single center studies have reported changes in vascular function during pregnancies with and without APOs and vascular dysfunction in women after some types of APOs. The NHLBI recently funded a continuation of the nuMoM2b Heart Health Study (HHS2; 1U01HL145358-01A1; PIs: McNeil, Greenland, and Saade), which will be conducted in >4,000 demographically diverse women. The HHS2 was designed to further understanding of early CVD development after APOs. Women were initially enrolled at the beginning of their first pregnancy, and available data include detailed pregnancy information, biospecimens, and CVD risk factor assessment over 7 years of follow-up. We propose the addition of non-invasive pulsatile hemodynamic measurements to data collection procedures for a subset of participants enrolled in HHS2, including central arterial stiffness and arterial wave reflection measurements. Our Aims are as follows: Aim 1: Compare vascular function measurements between women who did and did not have an APO. Account for lifestyle behaviors and APO types. Aim 2. Define associations of early pregnancy biomarkers with poor pulsatile hemodynamics. Our study will aid in sex-specific identification of higher-risk individuals with normal levels of traditional CVD risk factors and define associations with molecular phenotypes in early pregnancy. We will reveal modifiable lifestyle factors associated with pulsatile hemodynamics, thus informing preventive strategies and setting the stage for interventions. The measurements will enrich the HHS2 dataset. The study will fill a key knowledge gap regarding silent CVD in premenopausal women and directly aligns with the objective of improving understanding and identification of early CVD development after different APOs.

摘要 不良妊娠结局（APO），如妊娠期高血压疾病、宫内生长 限制，早产，发生在约20%的怀孕，并与过度的终身 心血管疾病（CVD）的风险。然而，传统的CVD风险因素水平可能无法确定 所有在APO后进展为CVD的女性。数据表明，需要采取更敏感的措施， 确定绝经前妇女在APO后发生CVD的可能性，特别是非高血压APO。 搏动性血流动力学功能障碍，即，高动脉压波反射幅度，高收缩压 压力增加和高中心动脉硬度，可以先于左心室结构异常， 舒张功能障碍、高血压和明显的CVD，并且可以通过改变生活方式来改善或逆转。 小型单中心研究报告了妊娠期间血管功能的变化， 某些类型的APO后女性的APO和血管功能障碍。NHLBI最近资助了一个 继续进行nuMoM 2b心脏健康研究（HHS 2; 1U 01 HL 145358 - 01 A1; PI：McNeil，Greenland，和 Saade），将在4,000多名人口统计学上不同的妇女中进行。HHS 2的设计目的是 进一步了解APO后早期CVD的发展。妇女最初是在2000年初入学的， 他们的第一次怀孕，可用的数据包括详细的怀孕信息，生物标本和CVD风险 随访7年以上的因素评估。我们建议增加非侵入性脉动血流动力学 对于入组HHS 2的受试者子集，包括中心 动脉硬度和动脉波反射测量。我们的目标如下：目标1：比较 有和没有APO的女性之间的血管功能测量。解释生活方式 行为和APO类型。目标2.确定早孕生物标志物与搏动性差的相关性 血流动力学我们的研究将有助于性别特异性识别具有正常水平的高风险个体。 传统的CVD危险因素，并确定与妊娠早期分子表型的相关性。我们将 揭示与脉动血流动力学相关的可改变的生活方式因素，从而为预防策略提供信息 并为干预措施做好准备。这些测量将丰富HHS 2数据集。该研究将填补 关于绝经前女性无症状心血管疾病的关键知识差距，并直接符合 提高对不同APO后早期CVD发展的理解和识别。