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.

PROJECT NARRATIVE The long-term goal of our work is to evaluate the effect of intensive postpartum blood pressure control on maternal cardiovascular health, risk of chronic hypertension, and reversal of vascular dysfunction generated by hypertensive disorders of pregnancy, thus attenuating the lifelong trajectory of cardiovascular disease risk.