PEARLS: PlacEntal Acute Atherosis RefLecting Subclinical Atherosclerosis
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
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. We 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 to 18 months postpartum and another group is followed up 10 to 20 years postpartum. At the follow up (18 months or 10 to 20 years), women attend for a series of measurements including CT angiography, transthoracic echocardiography, MFD and carotid IMT measurement. The visit will last approximately 5 hours in the MUMC+. The only invasive procedure is a venapunction 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 VOCs analysis. All measurements will be performed or supervised by an experienced researcher. These investigations are already approved previously in other 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Short track controls Controls are women (18 years or older) with an uncomplicated pregnancy (i.e no foetal or maternal placental complications, such as pregnancy induced hypertension, preeclampsia or HELLP-syndrome, or small for gestational birth infancies). Follow up roughly 18 months postpartum. |
Other: Venapuncture
The only invasive procedure is a venapunction where 100 ml blood will be extracted. The only unfavourable side effect can be a small hematoma (rare).
|
| Short track early PE with IUGR These cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
Other: Venapuncture
The only invasive procedure is a venapunction where 100 ml blood will be extracted. The only unfavourable side effect can be a small hematoma (rare).
|
| Short track early PE without IUGR Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
Other: Venapuncture
The only invasive procedure is a venapunction where 100 ml blood will be extracted. The only unfavourable side effect can be a small hematoma (rare).
|
| Short track late PE with IUGR Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
Other: Venapuncture
The only invasive procedure is a venapunction where 100 ml blood will be extracted. The only unfavourable side effect can be a small hematoma (rare).
|
| Short track late PE without IUGR Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
Other: Venapuncture
The only invasive procedure is a venapunction where 100 ml blood will be extracted. The only unfavourable side effect can be a small hematoma (rare).
|
| Long term follow up track controls Controls are women (18 years or older) with an uncomplicated pregnancy (i.e no foetal or maternal placental complications, such as pregnancy induced hypertension, preeclampsia or HELLP-syndrome, or small for gestational birth infancies). Follow up 10 to 20 years postpartum. |
Other: Venapuncture
The only invasive procedure is a venapunction where 100 ml blood will be extracted. The only unfavourable side effect can be a small hematoma (rare).
|
| Long term follow up track cases Cases consist of women (18 years or older) with preeclampsia (PE) and/or HELLP syndrome in the current pregnancy (PE is defined as hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with de novo proteinuria (≥ 300 mg/ 24 hours)) Cases will be subdivided into early and late PE, with or without IUGR (Early PE is defined as the occurence of PE < 34 weeks of gestation, whereas late PE is defined as the occurence of PE ≥ 34 weeks of gestation. IUGR is defined as birthweight below the 10th percentile). Follow up roughly 18 months postpartum. |
Other: Venapuncture
The only invasive procedure is a venapunction where 100 ml blood will be extracted. The only unfavourable side effect can be a small hematoma (rare).
|
Outcome Measures
Primary Outcome Measures
- Relationship between placental acute atherosis and subclinical coronary atherosclerosis at 1 year postpartum [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.
- Relationship between placental acute atherosis and subclinical coronary atherosclerosis at 15 years postpartum [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.
- Relationship between decidual vasculopathy and subclinical coronary atherosclerosis at 1 year postpartum [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.
- Relationship between placental decidual vasculopathy and subclinical coronary atherosclerosis at 15 years postpartum [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 Outcome Measures
- Relationship between placental acute atherosis and clinical coronary atherosclerosis at 1 year postpartum [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. 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 incidence of acute atherosis will be compared with the average agatston score for the pre-eclamptic and normotensive groups at 1 year postpartum.
- Relationship between placental acute atherosis and clinical coronary atherosclerosis at 15 years postpartum [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. 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 incidence of acute atherosis will be compared with the average agatston score for the pre-eclamptic and normotensive groups at 15 years postpartum.
- Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 1 year postpartum [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. 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 incidence of decidual vasculopathy will be compared with the average agatston score for the pre-eclamptic and normotensive groups at 1 year postpartum.
- Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 15 years postpartum [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. 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 incidence of decidual vasculopathy will be compared with the average agatston score for the pre-eclamptic and normotensive groups at 15 years postpartum.
- Incidence of placental acute atherosis at 1 year postpartum [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.
- Incidence of placental acute atherosis at 15 years postpartum [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.
- Incidence of placental decidual vasculopathy at 1 year postpartum [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.
- Incidence of placental decidual vasculopathy at 15 years postpartum [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.
- Incidence of subclinical coronary atherosclerosis at 1 year postpartum [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.
- Incidence of subclinical coronary atherosclerosis at 15 years postpartum [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.
- Incidence of clinical coronary atherosclerosis at 1 year postpartum [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 average agatston score will be compared for the pre-eclamptic and normotensive groups at 1 year postpartum.
- Incidence of clinical coronary atherosclerosis at 15 years postpartum [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 average agatston score will be compared for the pre-eclamptic and normotensive groups at 15 years postpartum.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Maastricht University Medical Center (MUMC+) | Maastricht | Netherlands | 6202 AZ |
Sponsors and Collaborators
- Maastricht University Medical Center
Investigators
- Principal Investigator: Marc Spaanderman, MD, PhD, Maastricht University Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Modified NL52556.068.15
- METC 152019