Cardiac Manifestations of Preeclampsia

先兆子痫是一种影响5%-8%的孕妇的高血压疾病，与危及生命有关 母婴后果及其发生率呈上升趋势。长期以来被认为是临时性的产科 病情的影响仅限于怀孕，现在公认有先兆子痫的妇女在 患持续性高血压、早发心血管疾病(CVD)和老年高血压的风险增加 寿命缩短。先兆子痫的病理生理机制包括胎盘释放过多的抗 血管生成蛋白导致高血压、蛋白尿和血管内皮细胞的全身性表现 功能障碍。先兆子痫还与左心室肥厚和左心室功能异常有关， 越来越多的证据表明，心血管异常持续到围产期以后 句号。子痫前期对心血管的影响机制尚不清楚。中心假说 这一建议的结论是，先兆子痫引起的抗血管生成状态直接增加了未来心血管疾病的风险 改变心脏结构和功能。我们将采用最先进的心脏磁共振(CMR) 负荷成像用于量化冠脉微循环并提供心脏深部表型 先兆子痫后结构和功能的变化。我们将在120年中进行一项单站点辅助研究 哥伦比亚大学对40名患有先兆子痫的妇女进行了未分娩妊娠结局研究 监测准妈妈心脏健康研究(nuMoM2B-HHS)以追求以下具体目标：(1) 检查有子痫前期病史的妇女冠脉微循环是否有差异 在nuMoM2B指数妊娠期间与没有先兆子痫的对照妇女进行比较；(2) 确定先兆子痫通过增加左心室重量直接改变后期心脏结构的程度 和单独的纤维化；(3)量化妊娠循环中的抗血管生成蛋白之间的关系 产后7~14年伴有冠脉血流灌注和纤维化。女性心脏综合表型分析 有和没有先兆子痫病史将为未来研究提供信息，检查心血管疾病风险分层和 有先兆子痫病史的妇女的改良。尽管有许多共同的风险因素，包括女性 优势、肥胖和高血压、先兆子痫与冠状动脉微血管的关系 疾病和心肌纤维化尚未进行检查。这项提议是朝着更好的方向迈出的关键一步 了解先兆子痫改变女性未来心血管疾病风险的机制。这一知识 将有助于开发新的知情干预措施，以预防或推迟#年心血管疾病的发生。 有先兆子痫病史的妇女，从而减少早产发病率和死亡率，并提供医疗保健 在年轻且不断扩大的女性群体中付出了代价。

Preeclampsia, a hypertensive disorder affecting 5-8% of pregnancies, is associated with life-threatening maternal-fetal consequences and its incidence is on the rise. Long regarded as a temporary obstetrical condition with implications limited to pregnancy, it is now recognized that women with prior preeclampsia are at elevated risk for the development of sustained hypertension, premature cardiovascular disease (CVD) and a shortened lifespan. The pathophysiology of preeclampsia includes excessive placental release of anti- angiogenic proteins that lead to systemic manifestations of hypertension, proteinuria, and endothelial dysfunction. Preeclampsia is also associated with left ventricular (LV) hypertrophy and abnormal LV function, and growing body of evidence suggests that the cardiovascular abnormalities persist beyond the peripartum period. The mechanism of insult of preeclampsia’s cardiovascular effects are unknown. The central hypothesis of this proposal is that the anti-angiogenic state induced by preeclampsia increases future CVD risk by directly altering cardiac structure and function. We will employ state of the art cardiac magnetic resonance (CMR) stress imaging to quantify the coronary microcirculation and to provide deep cardiac phenotyping of the structural and functional changes after preeclampsia. We will perform a single site ancillary study in 120 women (40 with preeclampsia) followed at Columbia University in the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be Heart Health Study (nuMoM2b-HHS) to pursue the following specific aims: (1) To examine whether there are differences in the coronary microcirculation of women with a history of preeclampsia during their nuMoM2b index pregnancy compared to control women who did not have preeclampsia; (2) To determine the extent to which previous preeclampsia directly alters later cardiac structure by increasing LV mass and separately fibrosis; (3) To quantify the associations between circulating anti-angiogenic proteins of pregnancy with coronary perfusion and fibrosis 7 to 14 years after delivery. Comprehensive cardiac phenotyping of women with and without a history of preeclampsia will inform future studies examining CVD risk stratification and modification in women with a history of preeclampsia. Despite sharing many risk factors, including female predominance, obesity, and hypertension, the associations of preeclampsia with coronary microvascular disease and myocardial fibrosis have not been examined. This proposal is a crucial step towards better understanding the mechanisms through which preeclampsia alters future CVD risk in women. This knowledge will enable the development of novel, informed interventions to prevent or delay the incidence of CVD in women with a history of preeclampsia thereby decreasing premature morbidity and mortality and healthcare costs in a young and expanding subset of women.