Reducing the risk of chronic hypertension and improving vascular function following preeclampsia - 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. The postpartum period is a time of high vascular remodeling following pregnancy, and even more so following a hypertensive pregnancy. Patients who had HDP have lower flow mediated dilation (FMD) and higher arterial stiffness measured by pulse wave velocity (PWV) compared to patients with no HDP. They also have higher levels of soluble fms-like tyrosine kinase-1 (sFlt-1), an anti-angiogenic protein that causes vasoconstriction and endothelial damage. Our preliminary studies demonstrate that intensive blood pressure (BP) control to target of <140/90 mmHg for 6 weeks after giving birth is safe and leads to lower rates of immediate postpartum complications. However, two critical gaps in knowledge remain: 1) Does more intensive postpartum therapy during vascular remodeling reduce the number of individuals with chronic HTN at one-year postpartum, and 2) Does the favorable impact of lowering BP translate into improved vascular function and biomarkers of cardiovascular risk, known to predict future adverse CV events. We plan to address these gaps with Reducing the risk of chronic hypErtension and imProving vAscular functIon following pReeclampsia (REPAIR) study, a multicenter randomized controlled trial of 618 patients with HDP randomized to tight BP control postpartum versus usual care. Our central hypothesis is that intensive short-term (for 6 weeks) BP control during vascular remodeling that happens after childbirth, will accelerate recovery of vascular function and reduce the risk of chronic HTN and future CVD. We will pursue the following two specific aims: 1) Determine the effect of intensive postpartum BP control on new diagnosis of chronic HTN at one year postpartum; and 2) Determine the effect of intensive postpartum BP control on vascular function and biomarkers of cardiovascular risk following HDP. We will utilize remote BP monitoring with daily medication adjustment the first 6 weeks postpartum, the time when there are substantial fluctuations in BP. Given racial disparities in HDP and CVD, oversampling of Black patients with HDP will be done to ensure they comprise 50% of study participants. The primary outcome, new onset chronic HTN, defined as stage I HTN ≥130/80 mmHg, and secondary outcomes, change in FMD, PWV, and sFlt-1, will be evaluated at one year postpartum. The REPAIR study will provide high-level evidence for BP management postpartum and will have a direct impact on clinical practice. If proven effective, the REPAIR study will lead to standardization of postpartum BP management and to reduction in the long-term risk of CVD following HDP. This contribution will be significant because the at-risk population for HDP is growing and our impact will increase over time.
