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)

项目摘要/摘要 大型随机多中心慢性高血压与妊娠(CHAP)试验(2015-2021年)是 旨在评估药物治疗对患有慢性阻塞性肺疾病的孕妇的短期益处和安全性 轻度慢性高血压(CHTN)。拟议的CHAP产妇后续项目(2021-2026)是一项后续行动 对CHAP中性格良好的女性的研究，以解决关于以下方面的关键知识差距 未来的长期心血管疾病(CVD)和其他结果与1)抗高血压有关 治疗在妊娠早期使用和2)叠加性子痫前期(SI PRE)的发展。CHTN是 妊娠期最常见的重大疾病，通常是轻微的(例如，BP&lt；160/110毫米汞)，以及 与不良后果有关，包括先兆子痫、死亡、早产和小于胎龄 (SGA)婴儿(出生体重&lt；第10百分位)。而抗高血压治疗是一般人的优先事项 人口，美国妇产科医生学会(ACOG)建议克制 妊娠期抗高血压治疗，除非慢性HTN病情严重(BP≥160/110 mm Hg)，原因不明 好处和关注：治疗可能会增加SGA婴儿的风险。一场国际争议关于 这些关于长期结果的数据将为怀孕期间的最佳治疗提供信息。鉴于 无CHTN的妇女先兆子痫增加了她们未来患CHTN和CVD的风险，SI的长期影响 既往有慢性高血压性肾炎的女性的高血压前和降压治疗尚不确定。在此期间，拟议的5- 年项目，我们的联合体多达60个地点，将每6个月跟踪CHAP参与者(面对面 或远程查看病历和管理调查问卷)以获取间隔历史、连续BP和 结果数据，并收集生物标本。我们预计本章2404条中的1804条(75%)将被研究到 实现以下具体目标： 具体目标1：检验假设，妊娠期轻度慢性HTN降压治疗可实现 BP目标&lt；140/90与不治疗相比，母亲心血管疾病结局的频率降低了5至10 产后数年，包括严重CHTN(未来心血管疾病的标志)、心力衰竭、 中风、心肌梗塞/心绞痛、肾功能衰竭、静脉血栓栓塞症(VTE)或死亡。 特定目标2：验证轻度CHTN孕妇发生SI preR的假设 增加产后5至10年孕妇心血管疾病结局的风险，包括主要的 严重CHTN、心力衰竭、中风、心肌梗死/心绞痛、肾功能衰竭、静脉血栓形成和死亡。 具体目标3(探索性)：测试ACC/AHA ASCVD风险评分(年龄、 种族-民族、糖尿病、吸烟状况、基线血压、孕前治疗)和怀孕数据 轻度CHTN患者的治疗和SI Pre可预测产后5-10年的母体CVD结局。我们 还将收集和储存孕妇的血液和尿液，用于未来的生物标记物和生物学研究。

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.