Cardiac Dysfunction and Remodeling in Patients With Preeclampsia (ANGIOCOR)

Cardiac Dysfunction and Remodeling in Patients With Preeclampsia Regulated by Antiangiogenic Environment: Clinical and Experimental Approach

Preeclampsia (PE) is a pregnancy-related hypertensive disorder drive by an anti-angiogenic environment. Women with PE have 2-4 time higher risk of developing cardiovascular disease (CVD), although the specific mechanism relating these two conditions remains elusive. In non-pregnant patients with coronary disease, angiogenic profile proved to be an independent predictor of poor prognosis and is associated with a higher mortality rate. The investigators hypothesized that in PE, the antiangiogenic environment determines the degree of cardiac dysfunction and remodeling and the posterior cardiovascular risk.

Study Overview

• Status: Unknown
• Conditions: Pregnancy Complications; Cardiovascular Risk Factor; Preeclampsia
• Intervention / Treatment: Diagnostic test: Ecocardiographyc ultrasound

Detailed Description

Main objective: To determinie the relationship between antiangiogenic environment and cardioc dysfuntion and remodelin in women at risk and in established PE. M&M: placental dysfunction markers (angiogenic factors (PlGF) and anti-angiogenic factor (sFlt1) and cardiovascular risk variables (BMI, BP, arterial stiffness, copectin, proBNP, high-sensitivity troponin, carotid intima thickness and echocardiography parameters) would be evaluated in 280 patients at risk of PE according to first trimester screening and 100 controls. Additionally, cardiac dysfunction parameters would be evaluated in women with established PE (n=60) and common transcriptomic signatures between cardiovascular disease and preeclampsia would be investigated in placental samples from 10 PE and 10 controls. It will provide evidences to evaluate and characterize the association between angiogenic factors and cardiac dysfunction and remodeling in PE.

• Study Type: Observational
• Enrollment (Anticipated): 440

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Recruiting
    • Hospital De La Santa Creu I Sant Pau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women at high risk of <preeclampsia on first trimestre scan

Description

Inclusion Criteria:

1. >18 and <45 years old.
2. Able to understand the study requirements.
3. Singleton pregnancy.
4. Accept of written informed consent.

Exclusion Criteria:

1. <18 or >45 years old.
2. Not able to understand the study requirements.
3. Multiple pregnancy.
4. Previous conditions: abnormal thrombophilia, alcohol or illicit drug use, type-1 diabetes, hyperthyroidism, renal disease, severe maternal illness, cytomegalovirus or toxoplasma infection, maternal HIV infection, , previous venous or arterial thrombotic event, and
5. known major fetal anomaly or chromosomal abnormality at inclusion
6. denial of written informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
High Risk of Preeclampsia; Women with a singleton pregnancies attending for prenatal care in the maternal and fetal Medicine Unit will be asked to participate if they meet the following criteria: 1)High risk for preeclampsia according to first trimester screening (maternal risk factors, blood preassure, PPAP-A, mean pulsatility index (PIm) of the uterine arteries (UtA) at 11.0 to 13.6 weeks of gestation (n=280). Women in this group will be subdivided in cases and controls according to the later development of preeclampsia: cases: women developing PE (estimated n=40); controls: women not developing PE (estimated n=240)	Diagnostic test: Ecocardiographyc ultrasound; Epidemiological data: Maternal history risk factors. First trimester scan is performed on all patients.; Antropomethric measures; Systemic arterial stiffness: using applanation tonometry with pulse wave analysis and pulse wave velocity.; Carotid Intima Thickness; Echocardiography assessment: It will be performed by a cardiologist specialized in cardiac imaging according to the usual standard protocol. High resolution images will be acquired and post-processed with dedicated software for the speckle tracking analysis. 2D echocardiography parameters to be acquired, tissue Doppler and speckle tracking software; Markers in maternal blood: Angiogenic factor and cardiac function biomarkers: Blood samples will be collected without anticoagulant to obtain serum. sFLT-1, PlGF, High-sensitivity Troponin and NT-proBNP will be measured using automated electrochemiluminescence immunoassays.; Other Names: Blood test; Carotid intima thickness
Patients with Preeclampsia; Women with a singleton pregnancies attending for prenatal care in the maternal and fetal Medicine Unit will be asked to participate if they develop PE. Inclusion criteria: Patients presented with clinical signs and symptoms of preeclampsia (N=60).	Diagnostic test: Ecocardiographyc ultrasound; Epidemiological data: Maternal history risk factors. First trimester scan is performed on all patients.; Antropomethric measures; Systemic arterial stiffness: using applanation tonometry with pulse wave analysis and pulse wave velocity.; Carotid Intima Thickness; Echocardiography assessment: It will be performed by a cardiologist specialized in cardiac imaging according to the usual standard protocol. High resolution images will be acquired and post-processed with dedicated software for the speckle tracking analysis. 2D echocardiography parameters to be acquired, tissue Doppler and speckle tracking software; Markers in maternal blood: Angiogenic factor and cardiac function biomarkers: Blood samples will be collected without anticoagulant to obtain serum. sFLT-1, PlGF, High-sensitivity Troponin and NT-proBNP will be measured using automated electrochemiluminescence immunoassays.; Other Names: Blood test; Carotid intima thickness
Control group; Healthy pregnant women with at low risk PE screening at 11.0 to 13.6 weeks of gestation (n=100).	Diagnostic test: Ecocardiographyc ultrasound; Epidemiological data: Maternal history risk factors. First trimester scan is performed on all patients.; Antropomethric measures; Systemic arterial stiffness: using applanation tonometry with pulse wave analysis and pulse wave velocity.; Carotid Intima Thickness; Echocardiography assessment: It will be performed by a cardiologist specialized in cardiac imaging according to the usual standard protocol. High resolution images will be acquired and post-processed with dedicated software for the speckle tracking analysis. 2D echocardiography parameters to be acquired, tissue Doppler and speckle tracking software; Markers in maternal blood: Angiogenic factor and cardiac function biomarkers: Blood samples will be collected without anticoagulant to obtain serum. sFLT-1, PlGF, High-sensitivity Troponin and NT-proBNP will be measured using automated electrochemiluminescence immunoassays.; Other Names: Blood test; Carotid intima thickness

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To prospectively assess both biochemical and biophysical markers of cardiovascular dysfunction in a cohort of patients with a risk of pe and in healthy pregnant women in the fisrt and third trimester of pregnancy.	- Cardiac dysfunction/remodeling in the first and third trimester of pregnancy and in 12 moths after delivery as defined by: abnormal cardiac performace in the ecocardiographyc ultrasound assessment or/and; abnormal biochemical cardiac markers (copectin, proBNP, high-sensitivity troponin)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the correlation among antiogenic (PlGF) and anti-angiogenic factors (sFlt1) in maternal serum and biochemical and imaging markers of cardiac dysfunction and remodeling in patients with established PE AND	Venous blood will be drawn, with informed consent, from the cubital vein without a tourniquet and using a 20-G needle into Vacutainer CPT	9 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine cardiac dysfunction and metabolic status at 12 months after delivery and its correlation with cardiac and preeclampsia risk variables obtained during pregnancy		12 months
To investigate angiogenesis and cardiovascular related genes in placental samples of women with preeclampsia and controls by microarrays and PCR validation.	Placenta will be collected at delivery time and tissue samples will be frozen in liquid N2 and fixed for histology and immunohistochemistry.	1 month

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Investigators: Principal Investigator: Elisa Llurba, Institut de Recerca Hospital de la Santa Creu i Sant Pau

Publications and helpful links

General Publications

• Ullmo J, Cruz-Lemini M, Sanchez-Garcia O, Bos-Real L, Fernandez De La Llama P, Calero F, Dominguez-Gallardo C, Garrido-Gimenez C, Trilla C, Carreras-Costa F, Sionis A, Mora J, Garcia-Osuna A, Ordonez-Llanos J, Llurba E. Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia: the ANGIOCOR prospective cohort study protocol. BMC Pregnancy Childbirth. 2021 Dec 8;21(1):816. doi: 10.1186/s12884-021-04263-w.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2020
• Primary Completion (ANTICIPATED): January 1, 2022
• Study Completion (ANTICIPATED): January 1, 2023

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: November 11, 2019
• First Posted (ACTUAL): November 14, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy Complications
• Other Study ID Numbers: IIBSP-PRE-2019-63

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No