Intensive postpartum antihypertensive treatment (IPAT) and healthy lifestyle education: Study protocol for a pilot randomized controlled trial for patients with hypertensive disorders of pregnancy

Abstract

Background:

Hypertensive disorders of pregnancy (HDP) complicate about 10% of pregnancies and lead to postpartum hospital readmissions and cardiovascular complications. Following HDP, vascular dysfunction could persist and accelerate the trajectory of cardiovascular disease risk. The benefits of intensive blood pressure (BP) control following HDP have not been adequately investigated. Therefore, no standard guidelines exist to guide the management of mild-to-moderate hypertension in the postpartum period, leading to a wide variation in clinical practice. The present study will investigate the effect of intensive BP control and healthy lifestyle education on maternal cardiovascular health (CVH) and vascular function following HDP.

Methods:

The Intensive Postpartum Antihypertensive Treatment (IPAT) study is a randomized controlled, two-arm, single-site, pilot trial where 60 postpartum HDP patients will be randomized 1:1 to one of two groups: 1) Intensive postpartum BP control – nifedipine initiation at BP ≥140/90 mm Hg to maintain BP <140/90 mm Hg; or 2) Less intensive postpartum BP control – nifedipine initiation at BP ≥150/100 mm Hg to maintain BP <150/100 mm Hg. All participants will also undergo vascular function assessments and receive healthy lifestyle education. The study will primarily test feasibility of all study procedures. It will secondarily examine changes in BP and CVH scores from baseline to 12 months postpartum.

Conclusion:

This pilot trial will study whether the BP threshold of 140/90 is superior to 150/100 for initiation of pharmacotherapy and evaluate feasibility to ultimately conduct a trial capable of generating robust evidence to standardize clinical practice and guidelines in postpartum HDP management.

Introduction

Hypertensive disorders of pregnancy (HDP) complicate one in ten pregnancies and substantially contribute to maternal morbidity and mortality, especially in the postpartum period [1–3]. Hypertension remains one of the leading causes of postpartum hospital readmissions as HDP often persists or worsens in the postpartum period [4, 5]. HDP accounts for almost 75% of maternal hemorrhagic strokes, myocardial infarctions, and deaths, 33% of which occur in the first week after giving birth [6–8]. Surviving immediate postpartum life-threatening complications of HDP may result in a lifelong sequela of cardiovascular disease (CVD) [9]. A history of HDP confers a 3.7-fold increased risk of hypertension, 2.2-fold ischemic heart disease, 1.8-fold stroke, and 1.5-fold overall mortality after 10–15 years [10]. This is largely attributed to the development of new chronic hypertension that can occur as early as 1 year postpartum [11–14].

Following delivery, blood pressures (BPs) do not always normalize and could peak around day 4–7 postpartum, with up to a quarter of patients having persistent hypertension at 6 weeks postpartum [15, 16]. Persistently elevated BP in the first 6 weeks postpartum are associated with higher risk of hospital readmission and related cardiovascular morbidity and mortality, with greater increase in BP over the next 5–10 years [4, 17, 18]. However, the mechanisms behind the increased risk of future CVD remain unclear. It is possible that vascular dysfunction is involved – it is generated by HDP and may be further exacerbated by persistent hypertension postpartum [19, 20]. Studies have demonstrated greater arterial stiffness and endothelial dysfunction in patients with preeclampsia as early as 3–6 months postpartum compared to patients without HDP [21–23]. The UK Physician Optimized Postpartum Hypertension Treatment Trial (POP-HT) of 220 postpartum patients with HDP receiving antihypertensive treatment demonstrated that improved BP control postpartum using self-monitoring and physician-guided antihypertensive management was associated with improved left ventricular and left atrial remodeling at nine months postpartum [24]. The intervention in the POP-HT trial involved dose titration of different antihypertensive medications after hospital discharge that was guided remotely by research team physicians according to remote BP readings based on UK guidelines from the National Institute for Health and Care Excellence [25].

In addition, soluble fms-like tyrosine kinase-1 (sFlt-1), an antiangiogenic protein that increases in HDP and inhibits vascular endothelial growth factor and placental growth factor, leads to vasoconstriction and endothelial damage [26–31] and can remain elevated up to one year postpartum and is associated with cardiovascular dysfunction [32]. Elevated sFlt-1 levels have been linked to cardiovascular dysfunction during pregnancy, and a higher ratio of sFlt-1 to placental growth factor in HDP has been correlated with postpartum hypertension [33, 34]. Since hypertension impairs endothelium-dependent vascular relaxation and accelerates aging-related structural vascular changes [35, 36], persistent postpartum hypertension could impair recovery of vascular function and may explain the increased risk for CVD following HDP.

Despite both short- and long-term risks of postpartum hypertension, there is limited evidence regarding the best management of postpartum HDP. This applies particularly to management of mild-to-moderate postpartum hypertension, defined as 140–159/90–109 mm Hg, due to the paucity of data. Initiating pharmacotherapy currently remains at the provider’s discretion, thereby leading to a wide variation in clinical practice [37]. Moreover, while there is strong evidence for lifestyle interventions in preventing and complementing the treatment of hypertension [38–40], to-date, only three RCTs examined lifestyle modifications following HDP [41–43]. None of the studies had the primary aim of improving BP control or reducing the risk of chronic hypertension.

To address these gaps, we designed the Intensive Postpartum Antihypertensive Treatment (IPAT) study. In this study, we will test the feasibility of antihypertensive pharmacotherapy for 6 weeks postpartum and healthy lifestyle education through 12 months postpartum among 60 patients with HDP. We will examine the effect of the intervention on BP control, cardiovascular health (CVH), and vascular function 12 months postpartum.

Methods and analysis

Study design

The IPAT study is a two-arm parallel, open-label, pragmatic RCT designed to test the central hypothesis that intensive BP control coupled with healthy lifestyle education can improve maternal CVH and accelerate recovery of vascular function by limiting continuous exposure to postpartum hypertension. Given the complexities of conducting an RCT of this nature among postpartum individuals with many competing demands, this single-site pilot RCT will test the feasibility of pharmacological therapy for 6 weeks postpartum and healthy lifestyle education through 12 months postpartum among patients with HDP. This trial was registered on ClinicalTrials.gov (NCT05687344).

Study settings

The IPAT study will be conducted at Froedtert and the Medical College of Wisconsin (F&MCW), a large quaternary academic medical center in Milwaukee, Wisconsin.

Participants and eligibility criteria

A total of 60 postpartum patients with HDP will be randomized into one of two groups: 1) Intervention group – intensive postpartum BP control with nifedipine extended-release (ER) initiation at systolic BP (SBP) ≥140 mm Hg and/or diastolic BP (DBP) ≥90 mm Hg and maintaining BP <140/90 mm Hg during the first 6 weeks postpartum; and 2) Active control group – less intensive postpartum BP control with nifedipine ER initiation at SBP ≥150 mm Hg and/or DBP ≥100 mm Hg and maintaining BP <150/100 mm Hg during the first 6 weeks postpartum. Postpartum patients already receiving antihypertensive therapy during their delivery admission will be excluded since such treatment would most likely be initiated at varying BP thresholds for each patient. Each medical chart will be reviewed in detail to ensure that patients with pre-pregnancy hypertension or hypertension diagnosed prior to 20 weeks’ gestation are excluded. Table 1 describes inclusion and exclusion criteria.

Table 1.

Study enrollment criteria

Inclusion criteria

HDP diagnosis (gestational hypertension or preeclampsia) according to ACOG guidelines [52] o Gestational hypertension: Systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg on two occasions at least 4 hours apart after 20 weeks’ gestation with previously normal blood pressures. o Preeclampsia: Meets gestational hypertension criteria OR SBP ≥160 mm Hg and/or DBP ≥110 mm Hg, and at least one of the following: ▪ Urine protein ≥300 mg in 24 hours or urine protein/creatinine ratio ≥0.3 ▪ Platelets <100 ×109/L ▪ Serum creatinine >1.1 mg/dL or double the baseline value ▪ Serum liver transaminases twice the upper limit of normal ▪ Pulmonary edema ▪ New-onset headache unresponsive to medication and not accounted for by alternative diagnoses or visual symptoms Postpartum day 0–4 Able to communicate in English Age 18–45

Exclusion criteria

Pregestational/chronic hypertension Type 1 or 2 diabetes mellitus (Gestational diabetes is not an exclusion criterion.) Known allergy or contraindication to nifedipine Inability or unwillingness to provide informed consent Already prescribed scheduled antihypertensive pharmacotherapy

Patient consent and randomization

All postpartum patients with HDP will be screened for study participation after delivery of their newborn. Patients who meet all study criteria will be approached after delivery and before delivery admission discharge. Written informed consent will be obtained from participants prior to any study procedures. Participants will be randomized 1:1 to intervention or active control group after eligibility is verified and consent is obtained. Stratified blocked randomization with randomly permuted blocks of sizes 4 and 6 will be used with term (≥37 weeks’ gestation) versus preterm (<37 weeks’ gestation) delivery as a stratification factor given that preterm delivery carries higher long-term CVD risk [44, 45]. Given the racial disparities in HDP and CVD [46–48], Black patients with HDP will be oversampled to comprise approximately half of the study participants. The randomization sequence will be created and maintained centrally by the study statistician using PASS 2023 software (NCSS, LLC. Kaysville, Utah, USA) [49]. Group assignment for a subject will occur solely after the patient’s agreement to participate in the study and the signing of informed consent.

Intervention and active control elements

Per standard of care at F&MCW, all patients with HDP, regardless of research enrollment, are provided with a BP monitor (A&D Medical UA-651 Essential Upper Arm Blood Pressure Monitor for cuff sizes 22–42 cm [50] or A&D Medical UA-789AC PREMIUM+ Extra Large Upper Arm Blood Pressure Monitor for cuff sizes 42–60 cm) and enrolled into a remote postpartum BP monitoring program at no cost. Patients are educated on proper use of the machine, body positioning, and receive the proper cuff sizing from the postpartum nurse. The nurse instructs the patient to download the Babyscripts© MyBloodPressure app, verifies that app log in and set up is successful, and instructs the patient to take BP twice daily for the first 16 days. Froedtert Birth Center has surveillance algorithms to triage patient BP data and to guide treatment plans. A free short-messaging service (SMS) in the app allows participants to submit BP readings, receive feedback about these readings, and report symptoms. If BP entry is missed by the participant, the app sends daily SMS reminders.

For the IPAT study, participants’ BPs will be reviewed remotely daily after hospital discharge for 2 weeks postpartum allowing for medication initiation or titration as needed and reducing the need for additional outpatient clinic visits. Daily review is warranted as BP peaks by days 4–7 postpartum and then decreases until day 14 postpartum [15]. From weeks two to eight postpartum, BP will be reviewed twice weekly, and antihypertensive medications will be initiated, titrated, or discontinued as needed per the study group protocol. When participants send their daily BPs, a survey question will ask whether the individual has started or continued taking the medication per protocol. The research team may also contact the patient or check medical record documentation to confirm medication adherence. From eight weeks postpartum to 12 months postpartum, BPs will be entered and reviewed monthly.

Participants randomized to the intervention group will start nifedipine ER 30 mg once daily if at least one BP reads SBP ≥140 mm Hg and/or DBP ≥90 mm Hg. Participants randomized to the active control group will start nifedipine ER 30 mg once daily if at least one BP reads SBP ≥150 mm Hg and/or DBP ≥100 mm Hg. Figure 1 illustrates the medication management algorithm. The usual care for postpartum hypertension includes the use of either labetalol or nifedipine ER [51–53]. This study’s intervention focuses on the BP-lowering effect, not the pleiotropic effects, of the antihypertensive drugs. With the exception of the extra protective effect of β-blockers given shortly after a myocardial infarction and the additional effect of calcium channel blockers in preventing stroke, all classes of BP-lowering drugs have a similar effect in reducing CVD events and stroke for a given reduction in BP [54, 55]. Therefore, only nifedipine ER will be used to avoid conducting a subgroup analysis in a small sample size if we used both labetalol and nifedipine, and to increase medication adherence with the use of a once-daily medication. Since the intervention targets the immediate postpartum period, we opted for a medication with the greatest evidence for safety in breastfeeding to avoid potentially excluding many patients with neonatal safety concerns.

Fig. 1.

Blood pressure management algorithm.

The Investigational Drug Services at Froedtert Hospital will dispense the medication at no cost to study participants. If the participant starts the medication, the treatment dose will be escalated as needed to achieve and maintain the BP target based on the study arm (<140/90 mm Hg or <150/100 mm Hg in the intervention group and active control group, respectively; Figure 1). Pharmacological treatment will continue until 6 weeks postpartum. Rapid cardiac and vascular remodeling occur during the 6 weeks postpartum, and persistently elevated BP during that period may promote abnormal remodeling and future development of chronic hypertension. Therefore, the 6 weeks postpartum may represent a critical period for intensive BP control as it may improve recovery of cardiovascular function. The intervention in the POP-HT study also lasted for 6 weeks postpartum and demonstrated lower BPs at 9 months postpartum [25]. The research staff will then facilitate the transition of the patient’s medical care to a primary care provider at the postpartum visit if the primary obstetric provider recommends continuing antihypertensive treatment beyond the postpartum period or to preventive cardiology clinic. The preventive cardiology clinic largely focuses on primary prevention of CVD. It aims to optimize cardiovascular risk factors, such as hypertension and high cholesterol, with a strong emphasis on healthy lifestyle in combination with pharmacotherapy when needed. Counseling on healthy eating, regular exercise activity, and weight loss are common. The clinic also offers individualized 10-year and lifetime cardiovascular risk assessments. The F&MCW preventive cardiology clinic currently includes three board-certified cardiologists, one advanced practice nurse practitioner, two clinical pharmacists, and a team of geneticists and registered dieticians.

All study participants will be enrolled in an intensive coaching intervention based on the American Heart Association (AHA) Life’s Essential 8 (LE8) CVH metrics [56]. These metrics include eight components: four modifiable behaviors (healthy diet, physical activity, avoidance of nicotine, healthy sleep) and four biometric measures (healthy weight, healthy levels of blood lipids, blood glucose, and BP) [56]. Using educational material from the AHA, one registered dietician and one registered nurse trained on the study protocol will deliver one-on-one education and goal-setting sessions via monthly telephone calls starting from months 3 to 12 postpartum.

All participants will undergo vascular function assessments at baseline (i.e., during their delivery admission between postpartum days 1–3), 6 weeks postpartum, and 12 months postpartum. All measurements will be performed in the morning in a quiet, temperature-controlled room with the participant supine after 10 minutes of rest and at least 8 hours of fasting. Three BP measurements will be taken using GE DASH Monitors, (3000 or 4000 models) or GE Carescape Dinamap Monitors, model v100.

. Brachial artery flow-mediated dilation (FMD) will then be performed to measure endothelial dysfunction. Baseline brachial artery diameter will be measured using a 7.5–13 MHz linear array vascular ultrasound transducer. A BP cuff placed on the proximal forearm will then be inflated to suprasystolic pressures for 5 minutes. FMD (%) will be the ratio between the brachial artery diameter at 60-seconds after cuff deflation and at baseline. Carotid-femoral pulse wave velocity (cfPWV) will then be done to measure arterial stiffness using the SphygmoCor^® device. PWV (m/s) will be calculated as the distance-to-transit time ratio of the pulse wave. All vascular function studies will be conducted at the F&MCW Vascular Core Lab with a cardiologist’s oversight. Serum samples will be collected after each vascular function study visit and stored for future testing of sFlt-1 levels.

In addition to vascular imaging, participants will undergo dual x-ray absorptiometry (DXA) using the GE Lunar iDXA at 6 weeks and 12 months postpartum to assess body composition (fat tissue, lean mass, and bone density), and assessment of the LE8 CVH score at baseline, 6 weeks postpartum, and 12 months postpartum. The four modifiable behaviors in LE8 will be assessed in all participants using validated questionnaires, physical examinations, and blood collections (Table 2) [56]. The CVH scores range from 0 to 100 and are categorized as low, moderate, or high CVH [56]. Information about breastfeeding and mood will be collected at the same study timepoints.

Table 2.

Study outcome definitions and data collection schedule

Outcome	Outcome definition and measures	Data collection schedule
		PP day 0–4	6 weeks PP	12 months PP
Aim 1: Feasibility outcomes
Randomization	Proportion of patients who enroll out of all approached, eligible patients			X
Dropout rate	Number of enrolled participants who drop out of study participation during the 12-month follow-up			X
Retention rate	Proportion of enrolled patients who complete all study visits during the 12-month follow-up			X
Adherence	Adherence to blood pressure monitoring and medication intake will be evaluated weekly during the first 6 weeks postpartum and before any dose adjustments	X
Acceptability	Rating the phone calls with education on LE8 and DASH as helpful			X
Assessment process	Proportion of planned vascular imaging and biomarkers collection that are completed			X
Contamination	Percent of patients following other antihypertensive treatment regimens			X
Aim 2: Clinical outcomes
Systolic BP Diastolic BP	Appropriately measured systolic and diastolic BPs	X	X	X
Stage I hypertension	BP ≥130/80 mm Hg [38]		X	X
LE8 CVH score	Metrics and methods of measurement and quantitative assessment of CVH [56]: MEPA tool [61] NHANES PAQ [62] NHANES SMQ [63] Self-reported average hours of sleep per night Body mass index Plasma total and HDL cholesterol with calculation of non-HDL cholesterol Fasting blood glucose or HbA1C Blood pressure	X	X	X
LS7 CVH score	Same metrics as LE8 (excluding sleep) [64]	X	X	X
10-year ASCVD score	Score based on sex, age, race, total and HDL cholesterol, systolic BP, and personal history of diabetes, smoking, and treatment for hypertension [65]	X	X	X
Aim 3: Vascular dysfunction measures
Imaging modalities	Brachial artery flow-mediated dilation will assess endothelial dysfunction. Carotid-femoral pulse wave velocity will assess arterial stiffness.	X	X	X
Dual X-ray absorptiometry	Will assess fat tissue, lean mass, and bone density		X	X
Serum biomarker of CVD risk	Antiangiogenic marker sFlt-1	X	X	X

PP, postpartum; LE8, Life’s Essential 8; DASH, Dietary Approaches to Stop Hypertension; BP, blood pressure; CVH, cardiovascular health; MEPA, Mediterranean Eating Pattern for Americans; NHANES, National Health and Nutrition Examination Survey; PAQ, Physical Activity and Physical Fitness Questionnaire; SMQ, Smoking Cigarette Use Questionnaire; LS7, Life’s Simple 7; ASCVD, atherosclerotic cardiovascular disease; CVD, cardiovascular disease; sFlt-1, soluble fms-like tyrosine kinase-1.

Trial objectives

The primary objective of the IPAT study is to test the feasibility of all study procedures. Feasibility parameters will include randomization and the rates of recruitment, dropout, and retention, adherence, acceptability, and contamination [57]. Table 2 summarizes the definition of each of the feasibility parameters and target goal for each parameter. The secondary objectives of the IPAT study are to examine changes in SBP, DBP, rates of stage I hypertension diagnosis, and CVH scores using the LE8 metrics through the first 12 months postpartum. An additional secondary objective is to determine the measure of vascular dysfunction that best reflects BP control in the postpartum period and can hence serve as a surrogate endpoint for CVD. The endothelial function will be assessed using brachial artery FMD and arterial stiffness will be assessed using cfPWV. Table 2 describes the study’s outcomes and the data collection schedule.

Data collection and management

Data will be stored in Research Electronic Data Capture (REDCap), a secure, web-based application designed to support data collection for research [58]. Baseline data including patient sociodemographic data (age, self-reported race and ethnicity, marital status, education, employment status, and insurance status), medical comorbidities, body mass index, type of HDP (gestational hypertension or preeclampsia), gestational age at delivery, and baseline BP will be collected by a trained clinical research nurse using electronic health record abstraction or direct patient interview.

Sample size

A sample size of 60 participants was chosen for this pilot feasibility RCT as an accepted number to estimate the feasibility parameters [59]. A formal sample size calculation was therefore not performed. Thirty patients will be enrolled into each study group to pilot recruitment procedures and to assess feasibility of recruitment and acceptability. With 30 participants per study group, the 95% confidence interval (CI) for the estimation of feasibility proportions of retention and adherence will be within ±12.8% if the observed retention and adherence rates are 85%. Therefore, the lower limit of the 95% CI for the observed retention and adherence rates in either study group should not be lower than 72.2%.

The chosen sample size is not powered to demonstrate efficacy. However, a sample size of 60 participants (randomly assigned in a 1:1 ratio to the two groups) will provide at least 80% power to detect an effect size (Cohen’s d) of 0.74 in SBP, DBP, LE8 CVH score and sFlt-1 levels at an alpha of 0.05. If the prevalence of stage I hypertension in the control group is estimated to be 50%, a sample size of 60 participants will allow detection of an effect size (Cohen’s h) of 0.72 in stage I hypertension with at least 80% power.

Data Safety and Monitoring Board (DSMB)

An independent DSMB has been established to regularly assess the safety data of the IPAT trial. Comprised of specialists in maternal-fetal medicine, cardiovascular medicine, and biostatistics, this board will oversee the study. The research team will continually analyze recruitment, adherence, retention, maintenance of confidentiality, and adverse events data, presenting written reports to the DSMB. Safety outcomes that will be monitored by the DSMB include adverse events and subject safety regarding medication side effects. Meetings will occur every six months for progress review and adverse event monitoring.

Statistical analysis plan

Analyses of the primary outcome, feasibility measures (Table 2), will be primarily descriptive. Proportion of eligible patients who enroll, recruitment rate, retention rate, adherence and dropout rate will be calculated as raw count (%) with 95% CI. For dichotomous feasibility/acceptability outcomes, 95% CI for single proportions will be used to estimate the within group measures. We will determine the amount of and reasons for participants’ noncompliance and discontinuation of treatment through phone interview. Patients who decline to participate will be asked for their reasons, and these reasons will be summarized using (de-identified) grouped frequency data. The analyses of the secondary outcomes will be carried out separately for intent-to-treat (ITT) and those who complete all protocol requirements. A linear mixed effects model will be performed to examine the effects of intervention or active control on change in SBP, DBP, CVH score, FMD (%), cfPWV, and sFlt-1. BP measurements from the three vascular function study visits will be used for statistical analysis to reduce potential variability in BP measurement methods between individual participants. Home BP measurements will be used for any missing BP data. Treatment group, time point (baseline, 6 weeks postpartum, and 12 months postpartum), and the interactions between treatment group and time point will be included in the model. Patients will be treated as random. Stage I HTN will be modeled by generalized linear mixed models. Adjustments will be made for baseline BP. The association between BP measurements and vascular dysfunction markers will be assessed by correlations. Given that repeated observations are measured for both BP measurements and vascular dysfunction markers, the correlation coefficients will be estimated using a mixed effects model approach. A normal approximation procedure will be used to calculate the confidence intervals for the Fisher’s z-transformed correlation coefficients. Changes in markers of vascular dysfunction will be calculated as Cohen’s d effect size [60]. In respect to missing data, for the main analysis, missing data will be assumed to be missing at random (MAR) and mixed models will be used. With mixed models, individuals with missing data will not be excluded and we will be able to use all data available for the analysis. If a significant portion of data is missing, we will explore whether these data are missing completely at random (MCAR) or MAR and sensitivity analysis will be performed. Tukey’s test or Dunnett’s test will be used to adjust for multiple comparisons. A p value of <0.05 will be considered statistically significant. SAS version 9.4 (SAS Institute Inc., Cary, NC), SPSS version 28.0 (IBM Corp., Armonk, NY), and R version 4.3.2 (R Core Team, Vienna, Austria) will be used for the analyses.

Ethics and data sharing

The IPAT study was approved by the F&MCW Institutional Review Board (PRO00046214) and is registered on Clinical Trials Registry (NCT05687344). Every member of the research team will undergo training in human subject research, covering aspects such as data integrity and confidentiality protection, and will adhere to established research protocols. Research staff will obtain written informed consent from all participants meeting eligibility criteria prior to study enrollment. Prior to enrolling in the study, all eligible participants will be required to provide written informed consent, which will be obtained by the research staff. Privacy and confidentiality of data will be performed in accordance with the Medical College of Wisconsin guidelines. The findings generated by this project will be presented at key national scientific meetings. The study team will share data per NIH regulations. All final peer-reviewed manuscripts that arise from this project will be submitted to the digital archive PubMed Central.

Discussion

The IPAT study aims to collect pilot data for a future definitive trial that can investigate the effect of intensive postpartum BP control to the treatment goal of <140/90 mm Hg on CVD risk following HDP. Improved BP control may slow the progression of vascular aging and CVD risk trajectory following HDP. However, there is a wide variation in postpartum HDP management. The gap in postpartum hypertension care calls for the investigation of the optimal BP threshold for pharmacotherapy initiation and the subsequent standardization of treatment guidelines. Given the prevalence and morbidity of postpartum hypertension, the IPAT study will address this gap in knowledge. It will answer important questions that are necessary and sufficient to establish operational feasibility and design of a large-scale trial focused on reducing chronic hypertension and CVD risk following HDP. Specifically, this pilot trial will 1) provide essential information on recruitment and retention metrics through 12 months postpartum, 2) inform scoring and potentially different CVH metrics to be used postpartum, and 3) determine which vascular function assessments are most reflective of BP change in the postpartum period. Since the rate of cardiovascular events among young reproductive age women is low, this study will identify cardiovascular biomarkers that will be most reflective of BP change postpartum and could be used as surrogate end points when testing postpartum interventions.

The strengths of the IPAT study include its randomized controlled trial design, examining how clinical intervention affects the mechanism of CVD by investigating the effect of intensive BP control on vascular dysfunction generated by HDP, assessing the newly updated LE8 CVH score in postpartum patients with HDP, and focusing on a population that experiences a high burden of HDP and CVD by oversampling black patients with HDP.

The limitations of our study include its small sample size, which precludes us from focusing on subgroups of HDP (gestational hypertension, preeclampsia, preeclampsia with severe features) and the effect of the intervention on long-term CVD within each subgroup. In addition, the LE8 CVH score may not be ideal for the postpartum population given inherent sleep deprivation during the first few months postpartum, pregnancy-related changes in lipids, and the effect of breastfeeding on CVH. Finally, this is not a blinded study given that the research team monitoring BPs and treatment adherence must know each participant’s BP target. Thus, both the participants and the researchers were aware of which treatments were being administered. This lack of blinding could introduce potential biases, as participants might alter their behavior based on their knowledge of the treatment they are receiving, and researchers may consciously or unconsciously influence outcomes or interpretation of the data.

Data availability

No data was used for the research described in the article.