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

项目摘要 心血管疾病（CVD）是女性死亡的主要原因，在年轻人中， 妇女因此，预防和早期筛查至关重要。早产（PTB）妇女体内有过多的 与足月分娩的人相比，生命后期的CVD风险。目前尚不清楚，但是，如果PTB揭露，煽动或 会加重一种常见的倾向机制不清楚，孕前措施 几乎不存在一些研究，包括我们自己的研究，提出了早产可能具有持久性的可能性。 心脏代谢作用增加CVD风险，但纵向生物标志物数据无法用于 直接回答这个基本问题。炎症和内皮功能是合理的，但研究不足 在女性中PTB和CVD的联系机制。年轻人的冠状动脉风险发展 （CARDIA）研究独特地包括育龄女性的多次评估，包括术前和术后 怀孕。现在，在其第三个十年的后续与非常强大的保留（72%），心脏将有 对1，362名妇女（50%为黑人）进行了多达9次面对面检查，这些妇女从1999年到2009年共分娩了2，389次。 基线至30年。唯一的，最近才可获得的，炎症和内皮功能标志物， 在900名CARDIA妇女中测量了怀孕前后的样本。我们 假设早产与妊娠前的情况有关，并且另外留下持续的 促炎信号使受影响的女性易患内皮功能障碍， 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 高敏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 根据PTB的病史，分娩方式不同; 2）评估PTB与这些特征的相关性， 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的一个主要空白 易感妇女的PTB与其增加的肺结核风险的潜在机制之间的联系 后来的CVD。这些关键数据将为发现PTB与后来的疾病之间的新机制奠定基础。 女性CVD这项研究的影响是，它将是第一个使用孕前生物标志物， 炎症和内皮功能，以了解早产和增加 母亲在以后的生活中患CVD的风险。这些关键数据将确定潜在的炎症和内皮细胞 机制诱发早产和心血管疾病的妇女，并查明时间和类型， 改善妇女心血管健康的干预措施。

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.