A Randomized Trial to Reduce Blood Pressure at One Year Postpartum After Preeclampsia

Background and rationale

Preeclampsia and other adverse pregnancy outcomes (APOs) are associated with an increased risk of hypertension and cardiovascular disease later in life. Pregnancy therefore represents an opportunity to identify women who may benefit from early cardiovascular prevention.

Although current clinical practice guidelines recommend postpartum blood pressure monitoring, cardiovascular risk assessment and appropriate treatment after preeclampsia, evidence remains limited regarding whether a structured, personalized cardiovascular prevention strategy can achieve additional improvements in blood pressure compared with guideline-based standard care.

GESTA-COR aims to address this knowledge gap by evaluating whether early cardiovascular risk identification, personalized clinical interventions and digital health support can improve systolic blood pressure at one year postpartum in women with preeclampsia.

The study will also investigate cardiovascular recovery after other APOs and pregnancies without adverse outcomes, providing a broader understanding of cardiovascular health during the first year after childbirth.

Study design

GESTA-COR is a prospective, randomized, controlled clinical trial with two additional non-randomized observational comparison cohorts.

Women with preeclampsia will be randomized in a 1:1 ratio to either the Intervention group or the Standard care group.

Women with other APOs and women without APOs will be enrolled in separate observational cohorts and will not undergo randomization.

The randomized trial will evaluate whether a personalized cardiovascular prevention strategy achieves a clinically meaningful difference of 6 mmHg in systolic blood pressure at 12 months postpartum compared with guideline-based standard care.

Participants will undergo baseline cardiovascular assessment within the first six weeks after delivery, followed by scheduled follow-up visits at 3, 6 and 12 months postpartum.

Women with preeclampsia will be randomized after completion of the baseline assessment and before initiation of the study intervention.

Women with other APOs and women without APOs will undergo the same scheduled cardiovascular assessments without randomization.

Intervention group: personalized cardiovascular prevention

Women randomized to the Intervention group will receive an early, structured and personalized cardiovascular prevention strategy in addition to appropriate guideline-based medical care.

The intervention will focus on the identification and management of modifiable cardiovascular risk factors, with particular emphasis on blood pressure control.

The intervention will include:

1. Early cardiovascular assessment following preeclampsia, including blood pressure evaluation and identification of cardiovascular risk factors.
2. Personalized blood pressure management, including individualized follow-up and optimization of antihypertensive treatment when clinically indicated.
3. Cardiometabolic risk assessment, including weight, glucose metabolism, lipid profile and other relevant risk factors.
4. Kidney health evaluation, including kidney function and assessment of albuminuria when indicated.
5. Individualized lifestyle recommendations addressing physical activity, diet, weight management, smoking cessation and other modifiable cardiovascular risk factors.
6. Digital health monitoring to support cardiovascular risk identification, patient engagement and clinical follow-up.
7. Structured clinical follow-up with timely reassessment and treatment adjustment according to individual cardiovascular risk and clinical findings.

Digital health tools may include validated home blood pressure devices and wearable technology capable of collecting information on physical activity, heart rate and sleep.

These tools will support clinical assessment and the identification of potentially modifiable cardiovascular risk factors. All clinical decisions, including pharmacological treatment initiation or adjustment, will remain under the responsibility of qualified healthcare professionals.

Standard care group: guideline-based management

Women randomized to the Standard care group will receive postpartum cardiovascular care according to current national and international clinical practice guidelines for the management of preeclampsia, postpartum hypertension and cardiovascular risk.

Standard care will include appropriate blood pressure assessment, antihypertensive treatment when indicated, cardiovascular risk evaluation, lifestyle recommendations and clinical follow-up or specialist referral according to individual clinical needs.

Participants will receive all clinically indicated investigations and treatments, including adjustments to antihypertensive medication when necessary.

The Standard care group will not receive the additional structured, digitally supported and personalized cardiovascular prevention pathway evaluated in the Intervention group.

No clinically indicated treatment will be withheld or delayed because of participation in the study.

The randomized comparison will therefore evaluate the additional benefit of an early, proactive and personalized cardiovascular prevention strategy over current guideline-based standard care.

Observational comparison cohorts

Two additional non-randomized cohorts will be included to characterize cardiovascular recovery during the first year postpartum.

Other-APO cohort

This cohort will include women who have experienced adverse pregnancy outcomes other than preeclampsia, such as gestational diabetes, preterm birth, fetal growth restriction or other predefined pregnancy complications.

These women will receive appropriate clinical care according to current guidelines and will undergo study assessments to evaluate blood pressure, cardiovascular risk factors and postpartum cardiovascular recovery.

No-APO cohort

This cohort will include women who have experienced pregnancies without adverse pregnancy outcomes.

Participants will be recruited consecutively from the same participating centers and during the same recruitment period to provide a contemporaneous reference population.

Women in this cohort will receive usual postpartum care and undergo cardiovascular assessments according to the study protocol.

Neither observational cohort will be randomized to the Intervention or Standard care groups.

The inclusion of these cohorts will allow comparisons of cardiovascular risk profiles and blood pressure evolution after preeclampsia, other APOs and pregnancies without APOs.

Blood pressure measurement protocol

Blood pressure will be assessed during the first six weeks postpartum and at 3, 6 and 12 months after delivery using a standardized automated office blood pressure measurement protocol.

At each scheduled assessment, participants will rest in a seated position for at least five minutes, with their back supported, feet flat on the floor and arm supported at heart level.

Blood pressure will be measured using a validated automated upper-arm blood pressure device with an appropriately sized cuff.

Three consecutive measurements will be obtained at approximately one-minute intervals. All three readings will be recorded, and the average of the second and third readings will be used as the systolic and diastolic blood pressure values for that assessment.

The same measurement procedure will be applied to all study groups and observational cohorts. Whenever possible, the same validated device model will be used across participating centers.

Blood pressure measurements for study outcomes will be performed by trained personnel, preferably blinded to randomized treatment allocation.

The baseline blood pressure value will be obtained during the first six weeks postpartum, before randomization.

The exact postpartum day of the baseline assessment will be recorded to account for potential differences in blood pressure related to the timing of the evaluation after delivery.

The primary endpoint will be based on the standardized office systolic blood pressure measurement obtained at 12 months postpartum.

Primary objective and outcome

The primary objective is to determine whether the personalized cardiovascular prevention strategy achieves a 6 mmHg lower mean systolic blood pressure at 12 months postpartum compared with guideline-based standard care among women with preeclampsia.

The primary outcome will be mean office systolic blood pressure at 12 months postpartum, calculated as the average of the second and third of three consecutive measurements obtained using the standardized protocol.

The primary analysis will compare the randomized Intervention and Standard care groups, adjusting for baseline systolic blood pressure measured during the first six weeks postpartum.

The prespecified target treatment effect is a between-group difference of 6 mmHg in systolic blood pressure.

Secondary objectives

Secondary objectives will include:

1. Evaluating the prevalence of hypertension at 12 months postpartum.
2. Assessing longitudinal changes in systolic and diastolic blood pressure during the first six weeks and at 3, 6 and 12 months postpartum.
3. Evaluating antihypertensive medication requirements and treatment adjustments.
4. Assessing cardiometabolic risk factors, including weight, glucose metabolism and lipid profile.
5. Evaluating kidney function and other relevant cardiovascular risk indicators.
6. Assessing lifestyle changes, physical activity and adherence to preventive recommendations.
7. Comparing blood pressure evolution and cardiovascular recovery among women with preeclampsia, other APOs and no APOs.
8. Exploring whether early postpartum cardiovascular characteristics are associated with blood pressure and cardiovascular health at one year.

Exploratory cardiovascular assessment

Where feasible, additional cardiovascular assessments may be performed to investigate vascular and cardiac changes after pregnancy.

These may include vascular stiffness measurements, central blood pressure assessment, echocardiographic evaluation, and other cardiovascular biomarkers.

Digital health data may also be explored to characterize postpartum cardiovascular recovery patterns and identify factors associated with subsequent hypertension.

These exploratory assessments will not determine the primary efficacy outcome of the randomized trial.

Expected clinical relevance

GESTA-COR will investigate whether an early, structured and personalized cardiovascular prevention strategy can achieve a clinically meaningful reduction in systolic blood pressure compared with current guideline-based standard care in women with preeclampsia.

By combining a randomized clinical trial with observational cohorts of women with other APOs and without APOs, the study will also provide information on differences in postpartum cardiovascular recovery according to pregnancy outcomes.

The findings may help identify effective strategies for early cardiovascular prevention after preeclampsia and contribute to the development of more personalized postpartum cardiovascular care.