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NCT Number: NCT05500989

PlacEntal Acute Atherosis RefLecting Subclinical Atherosclerosis

Pregnancy is considered a cardiovascular (CV) stress test, and complicated pregnancies are associated with an increased risk for cardiovascular disease (CVD) later in life. Moreover, it is known that often the pregnancy induced CV adaptation does not resolve completely after a short postpartum (PP) period and it is not clear whether these induced changes will resolve over a longer period of time (i.e. in the upcoming months/years after delivery).

Understanding the cardiac adaptation during pregnancy and the reversal process in the postpartum period, as well as the factors that influence this these processes, may provide us not only insight in this mechanism, but may help us in identifying factors that may be target points for modification.

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Key information

Conditions

Pre-eclampsia Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases and Pregnancy Complications Fetal Diseases Fetal Growth Retardation Growth Disorders HELLP Syndrome Hypertension, Pregnancy-Induced Intrauterine Growth Restriction Pathologic Processes Pathological Conditions, Signs and Symptoms Pregnancy Pregnancy Complications Urogenital Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Observational

Primary location

About this study

The main goal of this study is to determine whether the presence of placental acute atherosis after pre-eclamptic pregnancies compared to normotensive pregnancies is related to the future development of subclinical atherosclerosis in the coronary arteries.

This information can be used to improve our prediction of which women have an increased risk of future cardiovascular disease and which women do not. This will allow us to better inform our postpartum population of the potential future risks of cardiovascular disease and could allow the timely implementation of primary prevention strategies. The investigators would also like to determine which blood biomarkers can also predict cardiovascular disease at an earlier stage as well as determining which of these biomarkers are present in hypertensive pregnancies.

This study is a longitudinal cohort study including women with pre-eclamptic pregnancies and normotensive pregnancies. Cases consist of women with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (early and late PE, with or without intra uterine growth restriction (IUGR)), whereas controls are women with an uncomplicated pregnancy.

The placenta is collected after the delivery and undergoes histopathological analyses. There are two follow up periods whereby one group of women is followed up 6 to 36 months postpartum and another group is followed up 10 to 20 years postpartum. At the follow up (6 to 36 months or 10 to 20 years), women attend for a series of measurements including CT angiography, transthoracic echocardiography, Flow medicated dilatation (FMD) and carotid intima media thickness (IMT) measurement. The visit will last approximately 5 hours in the Maastricht University Medical Centre (MUMC+). The only invasive procedure is a venepuncture where 75 ml blood will be extracted. The only unfavourable side effect can be a small hematoma (rare). Clinically, participants will be advised based on their risk profile following standard "cardiovascular (CV) risk management". Glycocalyx measurements and a FibroScan may be performed. Experience shows that this investigation is not experienced as uncomfortable. Also, 3 liters of exhaled air may be collected for volatile organic compound (VOCs) analysis. All measurements will be performed or supervised by an experienced researcher. These investigations are already approved previously in other Medical Ethics Committee (METC) applications (CMO-nr: 2008/226; 2009/004; 10-2-066). The other measurements (questionnaires, blood pressure (BP), weight measurement, urine collection, glycocalyx measurement, FibroScan and exhaled air collection) do not cause any discomfort for the patient aside from the time that it takes. On the other hand, potential health improvement and early detection of CV risk profiles and initiation of already existing effective prevention strategies that improve lifestyle are important benefits.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Women aged ≥ 18 years
  • Controls: Women with an uncomplicated pregnancy at the moment of inclusion (i.e no foetal or maternal placental complications, such as pregnancy induced hypertension, preeclampsia or HELLP-syndrome, or small for gestational birth infancies)
  • Cases: Women diagnosed with a preeclamptic pregnancy at the moment of inclusion

Exclusion criteria

  • Women who do not want to be informed about the results of the tests, or women who do not want their general practitioner and specialist(s) to be informed about the test results
  • Allergy or intolerance to glyceryl trinitrate, betablockers or iodinated contrast media.
  • Controls: Pre-existing chronic hypertension treated with antihypertensive medication or autoimmune disorder.

Treatment and study plan

Primary outcomes

  1. Relationship between placental acute atherosis and subclinical coronary atherosclerosis at 1 year postpartum

    Time frame: 1 year

    Acute atherosis will be defined as the presence of subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as either present or absent.

    Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.

    The incidence of acute atherosis will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 1 year postpartum.

  2. Relationship between placental acute atherosis and subclinical coronary atherosclerosis at 15 years postpartum

    Time frame: 15 years

    Acute atherosis will be defined as the presence of subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as either present or absent.

    Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.

    The incidence of acute atherosis will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 15 years postpartum.

  3. Relationship between decidual vasculopathy and subclinical coronary atherosclerosis at 1 year postpartum

    Time frame: 1 year

    Decidual vasculopathy will be defined as the presence of subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. It will be measured as either present or absent.

    Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.

    The incidence of decidual vasculopathy will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 1 year postpartum.

  4. Relationship between placental decidual vasculopathy and subclinical coronary atherosclerosis at 15 years postpartum

    Time frame: 15 years

    Decidual vasculopathy will be defined as the presence of subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. It will be measured as either present or absent.

    Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.

    The incidence of decidual vasculopathy will be compared with each of the subcategories of subclinical coronary atherosclerosis for the pre-eclamptic and normotensive groups at 15 years postpartum.

Secondary outcomes

  1. Relationship between placental acute atherosis and clinical coronary atherosclerosis at 1 year postpartum

    Time frame: 1 year

    Acute atherosis will be defined as subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as present or absent.

    Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Calcification score of their coronary arteries is based on the calcification seen on the CT scan. This is a continuous scoring system.

    The Agatston method uses the weighted sum of lesions with a density above 130 hounsfield units (HU), multiplying the area of calcium by a factor related to maximum plaque attenuation.

    The agatston score ranges from 0 and has no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk of coronary events, >400 = high risk of coronary events.

    The incidence of acute atherosis will be compared with the average agatston score for the pre-eclamptic and normotensive groups at 1 year postpartum.

  2. Relationship between placental acute atherosis and clinical coronary atherosclerosis at 15 years postpartum

    Time frame: 15 years

    Acute atherosis will be defined as subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as present or absent.

    Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Calcification score of their coronary arteries is based on the calcification seen on the CT scan. This is a continuous scoring system.

    The Agatston method uses the weighted sum of lesions with a density above 130 HU, multiplying the area of calcium by a factor related to maximum plaque attenuation.

    The agatston score ranges from 0 and has no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk of coronary events, >400 = high risk of coronary events.

    The incidence of acute atherosis will be compared with the average agatston score for the pre-eclamptic and normotensive groups at 15 years postpartum.

  3. Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 1 year postpartum

    Time frame: 1 year

    Decidual vasculopathy defined as subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. (Present or absent) Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Calcification score of their coronary arteries is based on the calcification seen on the CT scan. This is a continuous scoring system.

    The Agatston method uses the weighted sum of lesions with a density above 130 HU, multiplying the area of calcium by a factor related to maximum plaque attenuation.

    Range 0 to no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk, >400 = high risk.

    The incidence of decidual vasculopathy compared with average agatston score for the pre-eclamptic and normotensive groups at 1 year postpartum.

  4. Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 15 years postpartum

    Time frame: 15 years

    Decidual vasculopathy defined as subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. (Present or absent) Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Calcification score of their coronary arteries based on the calcification seen on the CT scan. This is a continuous scoring system.

    The Agatston method uses the weighted sum of lesions with a density above 130 HU, multiplying the area of calcium by a factor related to maximum plaque attenuation.

    Range 0 to no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk, >400 = high risk.

    The incidence of decidual vasculopathy compared with average agatston score for the pre-eclamptic and normotensive groups at 15 years postpartum.

  5. Incidence of placental acute atherosis at 1 year postpartum

    Time frame: 1 year

    Acute atherosis will be defined as the presence of subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as either present or absent.

    The incidence of acute atherosis will be compared for the pre-eclamptic and normotensive groups at 1 year postpartum.

  6. Incidence of placental acute atherosis at 15 years postpartum

    Time frame: 15 years

    Acute atherosis will be defined as the presence of subendothelial lipid-filled foam cells on placental histopathological analysis. It will be measured as either present or absent.

    The incidence of acute atherosis will be compared for the pre-eclamptic and normotensive groups at 15 years postpartum.

  7. Incidence of placental decidual vasculopathy at 1 year postpartum

    Time frame: 1 year

    Decidual vasculopathy will be defined as the presence of subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. It will be measured as either present or absent.

    The incidence of decidual vasculopathy will be compared for the pre-eclamptic and normotensive groups at 1 year postpartum.

  8. Incidence of placental decidual vasculopathy at 15 years postpartum

    Time frame: 15 years

    Decidual vasculopathy will be defined as the presence of subendothelial lipid-filled foam cells, fibrinoid necrosis, mural hypertrophy, chronic perivasculitis, absence of spiral artery remodelling and/or persistence of intramural endovascular trophoblast in the third trimester on placental histopathological analysis. It will be measured as either present or absent.

    The incidence of decidual vasculopathy will be compared for the pre-eclamptic and normotensive groups at 15 years postpartum.

  9. Incidence of subclinical coronary atherosclerosis at 1 year postpartum

    Time frame: 1 year

    Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.

    The incidence of each of the subcategories of subclinical coronary atherosclerosis will be compared for the pre-eclamptic and normotensive groups at 1 year postpartum.

  10. Incidence of subclinical coronary atherosclerosis at 15 years postpartum

    Time frame: 15 years

    Subclinical coronary atherosclerosis will be measured using CT contrast angiography. This will be measured visually and split into the following categories: any atherosclerosis, wall irregularities, soft plaque and calcified plaque/stenosis.

    The incidence of each of the subcategories of subclinical coronary atherosclerosis will be compared for the pre-eclamptic and normotensive groups at 15 years postpartum.

  11. Incidence of clinical coronary atherosclerosis at 1 year postpartum

    Time frame: 1 year

    Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Each patient will receive a calcification score of their coronary arteries based on the calcification seen on the CT scan. This is a continuous scoring system.

    The Agatston method uses the weighted sum of lesions with a density above 130 HU, multiplying the area of calcium by a factor related to maximum plaque attenuation: 130-199 HU, factor 1; 200-299 HU, factor 2; 300-399 HU, factor 3; and ≥ 400 HU, factor 4.

    The agatston score ranges from 0 and has no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk of coronary events, >400 = high risk of coronary events.

    The average agatston score will be compared for the pre-eclamptic and normotensive groups at 1 year postpartum.

  12. Incidence of clinical coronary atherosclerosis at 15 years postpartum

    Time frame: 15 years

    Clinical coronary atherosclerosis will be measured using CT contrast angiography and the agatston score. Each patient will receive a calcification score of their coronary arteries based on the calcification seen on the CT scan. This is a continuous scoring system.

    The Agatston method uses the weighted sum of lesions with a density above 130 HU, multiplying the area of calcium by a factor related to maximum plaque attenuation: 130-199 HU, factor 1; 200-299 HU, factor 2; 300-399 HU, factor 3; and ≥ 400 HU, factor 4.

    The agatston score ranges from 0 and has no upper maximum. 0 = absent, 1-100 = low risk of coronary events, 101-400 = medium risk of coronary events, >400 = high risk of coronary events.

    The average agatston score will be compared for the pre-eclamptic and normotensive groups at 15 years postpartum.

Study contacts

Contact information is provided by the study sponsor or research team.

Gwyneth Jansen, MBBS

CONTACT

[email protected]

043-38774145

Marc Spaanderman, MD, PhD

CONTACT

[email protected]

043-38774774 ext. 0031

Sponsors and collaborators

Lead sponsor

Maastricht University Medical Center

Other

Registry information

Acronym: PEARLS

Important dates

Study start
2016
Primary completion
2028
Study completion
2028
First posted
Aug 15, 2022
Registry last updated
Dec 5, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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