Preterm Delivery and Maternal Cardiovascular Disease Risk

描述（由研究者提供）：早产和母体心血管疾病风险摘要本申请的目的是确定：1）将早产与以后生活中母体心血管风险联系起来的机制;和2）早产并可能受益于早期跟踪和干预以减少未来心血管疾病（CVD）的女性亚组。早产（PTD）发生在12.5%的怀孕在美国，而且比率还在上升与足月分娩的女性相比，早产儿的女性患心血管疾病的风险更高，但与这些疾病相关的机制尚不清楚。PTD是一种异质性结局，早产妇女的亚群可能有不同的晚年后遗症。我们假设妊娠暴露了CVD的易感性，并且炎症、血脂异常和血栓形成在妊娠中会聚，以损害早产妇女的胎盘形成和/或母体血管完整性。因此，PTD妇女，特别是胎盘血管病变的妇女，在产后和动脉粥样硬化的早期证据中将具有致动脉粥样硬化的特征。我们建议对参加妊娠结局和社区健康（POUCH）研究的妇女进行一项随访研究，该研究是一项前瞻性队列研究，从1998年至2004年招募，旨在检查PTD的途径。在入组时、妊娠15 - 27周时采集血样。提取产前、分娩和分娩记录，并由一名胎盘病理学家以设盲方式检查胎盘。我们计划在此框架的基础上，研究有和没有PTD的女性的心血管特征，并确定参与POUCH研究后6 - 11年与心血管风险证据相关的PTD亚型。我们将入组约896例女性（513例白色/其他和383例非洲裔美国人）;在POUCH研究期间，217例早产，679例足月分娩。我们将收集问卷调查数据和致动脉粥样硬化特征的测量，如人体测量学（身高、体重、腰围）、血压和炎症标志物、脂质和血栓形成因子的血液水平。此外，我们将通过颈动脉超声扫描（颈动脉内膜-中膜厚度）评估动脉粥样硬化的早期证据。我们的目标是比较随访时的结局指标。即，在足月分娩的妇女和以下妇女中的致动脉粥样硬化谱和早期动脉粥样硬化：1）先前患有PTD的妇女; 2）根据临床情况和胎盘病理学分组的患有PTD亚型的妇女;和3）根据妊娠中期血脂异常和炎症生物标志物水平分组的患有PTD亚型的妇女。此外，我们还将研究目标1中的关联是否会受到社会经济地位、种族或母亲抑郁/痛苦等因素的影响。揭示PTD与母体CVD风险相关途径的研究可以为这两种医学问题带来新的干预策略，并有助于在疾病过程的早期识别女性，此时干预可能会延迟或预防疾病的发生。 公共卫生相关性：最近的证据表明，早产的妇女在以后的生活中患心血管疾病的风险可能会增加，但这种联系的性质知之甚少，仍然是一个“黑匣子”。“在这项研究中，我们有一个独特的机会来评估一组女性的致动脉粥样硬化特征和动脉粥样硬化的早期证据，我们有详细的妊娠数据（生物标志物，胎盘病理学）作为早期早产研究的一部分。这项拟议的后续研究将导致更深入地了解连接早产和后来的CVD风险的途径，并将有助于针对CVD高风险妇女和选择适当的早期干预措施。

DESCRIPTION (provided by investigator): Preterm delivery and maternal cardiovascular disease risk Abstract The objective of this applications is to identify: 1) mechanisms that link preterm birth to later life maternal cardiovascular risk; and 2) subgroups of women who deliver preterm and might benefit from early tracking and interventions to reduce future cardiovascular disease (CVD). Preterm delivery (PTD) occurs in 12.5 percent of pregnancies in the U.S., and rates are increasing. Women who have delivered a preterm infant have excess risk of developing CVD compared to those with term deliveries, but mechanisms relating these conditions are not understood. PTD is a heterogenous outcome, and it is likely that subsets of women who deliver preterm may have different later life sequelae. We hypothesize that pregnancy unmasks a predisposition to CVD and that inflammation, dyslipidemia and thrombogenesis converge in pregnancy to compromise placentation and/or maternal vascular integrity among a subset of women who deliver preterm. Therefore women with PTD, particularly those with placental vascular lesions, will have an atherogenic profile post partum and early evidence of atherosclerosis. We propose a follow-up study of women enrolled in the Pregnancy Outcomes and Community Health (POUCH) Study, a prospective cohort enrolled from 1998-2004 designed to examine pathways to PTD. Blood samples were collected at enrollment, 15-27 weeks' gestation. Prenatal, labor and delivery records were abstracted and placentas were examined in a blinded fashion by a single placental pathologist. We plan to build on this framework by studying the cardiovascular profile among women with and without PTD and by identifying subtypes of PTD associated with evidence of cardiovascular risk at 6-11 years after POUCH Study participation. We will enroll approximately 896 women (513 white/other and 383 African Americans); 217 who delivered preterm and 679 who delivered at term during the POUCH Study. We will collect questionnaire data and measures of an atherogenic profile such as anthropometrics (height, weight, waist circumference), blood pressure, and blood levels of inflammatory markers, lipids, and thrombogenic factors. In addition we will assess early evidence of atherosclerosis via carotid ultrasound scans (carotid intimal- medial thickness). Our aims will be to compare the outcome measures at follow-up. i.e. atherogenic profile and early atherosclerosis among women with term births and: 1) women with a prior PTD; 2) women with PTD subtypes grouped by clinical circumstance and placental pathology; and 3) women with PTD subtypes grouped by levels of dyslipidemia and inflammation biomarkers in mid-pregnancy. In addition we will examine whether associations in Aim 1 might be modified by factors such as socioeconomic status, race, or maternal depression/distress. Studies that uncover pathways linking PTD to maternal CVD risk can lead to new intervention strategies for both of these medical problems, and help to identify women very early in the disease process when intervention may delay or prevent onset of disease. PUBLIC HEALTH RELEVANCE: Recent evidence indicates that women who deliver preterm may be at increased risk of CVD later in life, but the nature of this connection is poorly understood and remains a 'black box.' In this study we have a unique opportunity to assess the atherogenic profile and early evidence of atherosclerosis in a cohort of women for whom we have detailed pregnancy data (biomarkers, placental pathology) as part of an earlier study on preterm delivery. This proposed follow-up study will lead to a more in-depth understanding of the pathways that connect preterm delivery and later CVD risk, and will aid in targeting women at high risk for CVD and selecting appropriate early interventions.