Cardiac and Immune Cell Function in Preeclampsia

Summary

Preeclampsia is a multi-system vascular disease which affects 2-5% of pregnancies. It is also a risk factor for the development of cardiovascular disease later in life and a number of functional and structural cardiac changes have been found in this population of patients.

In mouse models disruption of a group of immune cells, neutrophils, has led to alteration of the placenta and offspring consistent with those seen in preeclampsia. These mice also have an abnormal cardiac function and structure (Nadkarni et al 2016). The investigators hypothesis that this may also occur in humans.

This study aims to intimately link the maternal immunological and vascular components of cardiac dysfunction in women preeclampsia. The investigators hypothesise that in preeclampsia activated neutrophils may affect maternal immune system thus leading to myocardial injury and altered cardiac function. The study intends to identify the mechanisms by which the maternal immune system (focusing on neutrophil and T-cell subsets) affects cardiac function in women with preeclampsia. Specific aims to be addressed are:

Aim 1: To correlate specific neutrophil phenotype(s) and function to cardiac function in women with preeclampsia during pregnancy

Aim 2: To test whether specific activated neutrophil phenotype persists postpartum and whether this neutrophil phenotype correlates with cardiac function in women with preeclampsia postpartum

The study population will comprise of 3 groups:

1. Normotensive pregnant (\~33 patients)
2. Pregnancy-induced hypertension (PIH; New-onset hypertension after 20 weeks without proteinuria; \~33 patients)
3. Preeclampsia (\~34 patients)

Cardiac function will be evaluated using cardiovascular magnetic resonance, echocardiography and cardiac markers in the blood. The participants immune system will be assessed from blood samples looking at the immune cells, hormone levels and inflammatory and non-inflammatory mediators.

The secondary research objective is to investigate whether changes in the immune system and cardiac function in participants is persistent after delivery. Therefore participants will have scans and blood tests both antenatally and at 3 months postnatally.

By identifying key changes in immune cell type and function with cardiac abnormalities in women with preeclampsia, data obtained from this study could provide novel insight into how the maternal immune system influences cardiac changes in normal and preeclamptic pregnancies. Identifying such links could pave the way for future therapeutic targets.

Conditions

• Preeclampsia
• Hypertension
• Pregnancy Induced Hypertension
• Pregnancy Related
• Cardiovascular Diseases
• Cardiovascular Risk Factor
• Heart Diseases

Interventions

DIAGNOSTIC_TEST

Cardiovascular magnetic resonance

Imaging of the heart with CMR, without use of contrast agents.

DIAGNOSTIC_TEST

Echocardiography

Imaging of the heart with ultrasound.

DIAGNOSTIC_TEST

Blood test

Time- matched blood samples will be taken from patients to assess immune cell phenotype and function, paying particular attention to neutrophil and T-cell phenotype. Plasma samples will be collected for the analyses of cardiac specific factors (BNP, troponin) as well as measurement of steroid hormones (progesterone and oestradiol), and soluble inflammatory and anti-inflammatory mediators

Sponsors & Collaborators

• British Heart Foundation

  collaborator OTHER

• Barts & The London NHS Trust

  collaborator OTHER

• Queen Mary University of London

  lead OTHER

Principal Investigators

• Suchita Nadkarni · Queen Mary University London

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-01-07

Primary Completion

2024-03-06

Completion

2024-03-06

Countries

• United Kingdom

Study Locations