Intensive postpartum antihypertensive treatment to improve women's cardiovascular health

项目摘要/摘要 妊娠期高血压疾病(HDP)是一个重大的公共卫生问题，尤其是产后。产后 高血压(HTN)占产妇出血性中风、心力衰竭和死亡的近75%，其中 其中三分之一发生在出生后的第一周。在这些毁灭性并发症中幸存下来的患者将面临 心血管疾病(CVD)的终身后遗症。心血管疾病风险增加背后的机制包括 HDP引起的血管功能障碍，产后HTN进一步加重。目前，产后 仅推荐对重度HTN(≥160/≥110毫米汞柱)进行降压治疗。没有任何指导方针 关于轻度HTN的治疗，定义为血压140-150-90-100毫米汞柱。因此， 对于轻度HTN，产后开始降压药物治疗由提供者自行决定，有广泛的 实践中的变化。鉴于产后HTN的患病率和发病率，以及专注于 如何严格控制产后血压，关键是要产生证据来指导管理的最佳实践 产后HTN。我们的中心假设是产后持续接触HTN是一个关键的驱动因素 用于HDP的短期并发症和心血管疾病的长期风险。我们工作的总体目标是测试 假设强化的血压控制和健康的生活方式教育可以改善产妇 通过以下途径限制接触HTN，从而促进心血管健康(CVH)和加速血管功能的恢复 大型多点随机对照试验(RCT)。鉴于进行这种性质的RCT的复杂性， 这份R34的总体目标是“加强产后降压治疗以改善 妇女心血管健康“(IPAT)将试行为期6周的药物治疗RCT 产后1年对60例HDP患者进行产后及健康生活方式教育。我们会 确定IPAT的可行性及其改善HDP后心血管疾病风险的潜力。IPAT将随机化60 产后HDP患者加强血压控制与常规护理比较。这两组人都将获得健康的生活方式 关于美国心脏协会生命必需8(LE8)CVH指标和DASH饮食的教育 营养师和生活教练。所有参与者都将接受血管功能评估：内皮功能障碍 肱动脉血流介导的扩张，动脉僵硬与颈动脉-股动脉脉搏波速度，以及收集 内皮损伤的HDP相关生物标记物，可溶性FMS样酪氨酸激酶-1，基线(分娩后)， 产后6周和12个月。目标1将测试所有研究程序的可行性，包括招募、 保留力和忠诚度。AIM 2将检查从基线到12个月的BP和LE8 CVH评分的变化 产后。目标3将确定哪个血管生物标志物最能反映患者的血压控制情况 产后期。这项先导性研究具有重要意义，因为它将回答必要的重要问题 并足以确定更大规模试验的操作可行性和设计，以产生证据指导 产后HTN管理的最佳实践。

Project Abstract/Summary Hypertensive disorder of pregnancy (HDP) is a major public health problem especially postpartum. Postpartum hypertension (HTN) accounts for nearly 75% of maternal hemorrhagic strokes, heart failures, and deaths, one- third of which occurs in the first week after birth. Patients who survive these devastating complications face a lifelong sequela of cardiovascular disease (CVD). The mechanisms behind the increased risk of CVD involve vascular dysfunction generated by HDP and further exacerbated by postpartum HTN. Currently, postpartum antihypertensive treatment is recommended only for severe HTN (≥160/≥110 mmHg). There are no guidelines regarding treatment of mild HTN, defined as blood pressures (BP) of 140s-150s/90s-100s mmHg. Consequently, initiation of antihypertensive medications postpartum for mild HTN is at a provider’s discretion with a wide variation in practice. Given the prevalence and morbidity of postpartum HTN and limited research focused on how tight to control postpartum BP, it is critical to generate evidence to guide best practices for management of postpartum HTN. Our central hypothesis is that continuous exposure to HTN postpartum is a key driving factor for short-term complications of HDP and long-term risk of CVD. The overall objective of our work is to test the hypothesis that intensive BP control coupled with healthy lifestyle education can improve maternal cardiovascular health (CVH) and accelerate recovery of vascular function by limiting exposure to HTN through a large multisite randomized controlled trial (RCT). Given the complexities of conducting an RCT of this nature, the overall objective of this R34, titled “Intensive Postpartum Antihypertensive Treatment to Improve Women’s Cardiovascular Health” (IPAT) is to pilot test an RCT of pharmacological therapy for 6 weeks postpartum and healthy lifestyle education through 1 year postpartum among 60 patients with HDP. We will determine IPAT feasibility and its potential to ameliorate CVD risk following HDP. The IPAT will randomize 60 postpartum patients with HDP to intensive BP control versus usual care. Both groups will receive healthy lifestyle education on American Heart Association’s Life’s Essential 8 (LE8) CVH metrics and DASH diet by a registered dietician and a life coach. All participants will undergo vascular function assessment: endothelial dysfunction with brachial artery flow mediated dilation, arterial stiffness with carotid-femoral pulse wave velocity, and collection of an HDP-related biomarker of endothelial damage, soluble fms-like tyrosine kinase-1, at baseline (after delivery), 6 weeks, and 12 months postpartum. Aim 1 will test feasibility of all study procedures, including recruitment, retention, and adherence. Aim 2 will examine changes in BP and in LE8 CVH score from baseline to 12 months postpartum. Aim 3 will determine which vascular biomarker would be most reflective of BP control in the postpartum period. This pilot study is significant because it will answer important questions that are necessary and sufficient to establish operational feasibility and design of the larger trial that will generate evidence to guide best practices for management of postpartum HTN.