Pregnancy as a Window to the Future: Outcomes of Antihypertensive Therapy and Superimposed Preeclampsia in Pregnant Women with Mild Chronic Hypertension (CHAP Maternal Follow-up Study)

项目总结/摘要 大型随机多中心慢性高血压与妊娠（CHN）试验（2015-2021）， 旨在评价药物治疗妊娠合并高血压疾病的短期获益和安全性。 轻度慢性高血压（CHTN）。这一拟议中的产妇后续行动项目（2021-2026年）是一项后续行动， 对有充分特征的妇女进行研究，以解决关于以下方面的关键知识差距： 未来长期心血管疾病（CVD）和其他结局与1）抗高血压药物相关 妊娠早期使用治疗和2）发生叠加先兆子痫（SI PRE）。CHTN是 妊娠期最常见的主要医学疾病，通常为轻度（即BP <160/110 mmHg），以及 与不良结局相关，包括先兆子痫、死亡、早产和小于胎龄儿 (SGA)婴儿（出生体重<第10百分位）。而抗高血压治疗是一般的优先事项， 美国妇产科医师学会（ACOG）建议， 妊娠期间接受抗高血压治疗，除非由于不确定的原因，CHTN为重度（BP≥160/110 mm Hg） 治疗的好处和关注可能会增加SGA婴儿的风险。国际争议， 妊娠期间的最佳治疗将由这些长期结果数据提供信息。而 没有CHTN的妇女的先兆子痫增加了他们未来CHTN和CVD的风险，SI的长期影响 对于既存CHTN的女性，PRE和抗高血压治疗尚不确定。在此期间，5- 一个为期一年的项目，我们的联盟多达60个地点，将跟踪调查的参与者每6个月（亲自 或远程地，审查医疗记录和管理问卷）以获得间隔历史、连续BP和 结果数据，并收集生物标本。我们预计，在2404名学生中，有1804名（75%）将接受研究， 实现以下具体目标： 具体目的1：检验妊娠期轻度CHTN的降压治疗是否能达到 与未治疗相比，BP目标<140/90可将母亲CVD结局的频率降低5 - 10 年产后，包括严重CHTN（未来CVD的标志物），心力衰竭， 中风、心肌梗死/心绞痛、肾衰竭、静脉血栓栓塞（VTE）或死亡。 具体目标2：检验轻度CHTN孕妇发生SI PRE的假设 增加了产后5至10年母亲CVD结局的风险，包括以下主要复合因素： 重度CHTN、心力衰竭、卒中、心肌梗死/心绞痛、肾衰竭、VTE和死亡。 具体目标3（探索性）：测试ACC/AHA ASCVD风险评分的可用组成部分（年龄， 人种-种族、糖尿病、吸烟状况、基线BP、孕前治疗）和妊娠数据 （治疗和SI PRE）可预测产后5-10年母亲CVD结局。我们 还将收集和储存孕妇的血液和尿液，用于未来的生物标志物和生物学研究。

PROJECT SUMMARY/ABSTRACT The large randomized multicenter Chronic Hypertension and Pregnancy (CHAP) trial (2015-2021) was designed to evaluate the short-term benefits and safety of pharmacologic treatment of pregnant women with mild chronic hypertension (CHTN). This proposed CHAP Maternal Follow-Up project (2021-2026) is a follow-up study of the well-characterized women in CHAP to address the critical knowledge gaps regarding whether future long-term cardiovascular disease (CVD) and other outcomes are associated with 1) antihypertensive therapy use early in pregnancy and 2) the development of superimposed preeclampsia (SI PRE). CHTN is the most common major medical disorder seen in pregnancy, is most often mild (i.e. BP <160/110 mmHg), and associated with adverse outcomes, including preeclampsia, death, preterm birth and small for gestational age (SGA) infants (birth weight <10th percentile). Whereas antihypertensive therapy is a priority for the general population, the American College of Obstetricians and Gynecologists (ACOG), recommends withholding antihypertensive therapy during pregnancy unless CHTN is severe (BP≥160/110 mm Hg) due to uncertain benefits and concern that therapy may increase the risk of SGA infants. An international controversy regarding optimal treatment during pregnancy will be informed by these data on long-term outcomes. Whereas preeclampsia in women without CHTN increases their future risk of CHTN and CVD, the long-term effects of SI PRE and antihypertensive therapy in women with preexisting CHTN are uncertain. During this proposed 5- year project, our consortium of up to 60 sites, will follow-up the CHAP participants every 6 months (in-person or remotely, review medical records and administer questionnaires) to obtain interval history, serial BPs and outcome data, and collect bio-specimens. We anticipate 1804 (75%) of the 2404 in CHAP will be studied to address the following Specific Aims: Specific Aim 1: Test the hypothesis that antihypertensive therapy for mild CHTN during pregnancy to achieve a BP goal <140/90 compared with no treatment reduces the frequency of maternal CVD outcomes 5 to 10 years postpartum, including the primary composite of severe CHTN (a marker of future CVD), heart failure, stroke, myocardial infarction/angina, renal failure, venous thromboembolism (VTE) or death. Specific Aim 2: Test the hypothesis that the development of SI PRE in pregnant women with mild CHTN increases the risk of maternal CVD outcomes 5 to 10 years postpartum, including the primary composite of severe CHTN, heart failure, stroke, myocardial infarction/angina, renal failure, VTE and death. Specific Aim 3 (Exploratory): Test whether available components of the ACC/AHA ASCVD risk score (age, race-ethnicity, diabetes mellitus, smoking status, baseline BP, pre-pregnancy treatment) and pregnancy data (treatment and SI PRE) in women with mild CHTN predict maternal CVD outcomes 5-10 years postpartum. We will also collect and store maternal blood and urine for future biomarker and biological studies.