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.
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.
Study Type
OBSERVATIONAL
Enrollment
226
Maastricht University Medical Center (MUMC+)
Maastricht, Netherlands
RECRUITINGRelationship between placental acute atherosis and subclinical coronary atherosclerosis at 1 year postpartum
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.
Time frame: 1 year
Relationship between placental acute atherosis and subclinical coronary atherosclerosis at 15 years postpartum
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.
Time frame: 15 years
Relationship between decidual vasculopathy and subclinical coronary atherosclerosis at 1 year postpartum
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.
Time frame: 1 year
Relationship between placental decidual vasculopathy and subclinical coronary atherosclerosis at 15 years postpartum
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.
Time frame: 15 years
Relationship between placental acute atherosis and clinical coronary atherosclerosis at 1 year postpartum
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.
Time frame: 1 year
Relationship between placental acute atherosis and clinical coronary atherosclerosis at 15 years postpartum
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.
Time frame: 15 years
Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 1 year postpartum
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.
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Time frame: 1 year
Relationship between placental decidual vasculopathy and clinical coronary atherosclerosis at 15 years postpartum
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.
Time frame: 15 years
Incidence of placental acute atherosis at 1 year postpartum
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.
Time frame: 1 year
Incidence of placental acute atherosis at 15 years postpartum
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.
Time frame: 15 years
Incidence of placental decidual vasculopathy at 1 year postpartum
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.
Time frame: 1 year
Incidence of placental decidual vasculopathy at 15 years postpartum
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.
Time frame: 15 years
Incidence of subclinical coronary atherosclerosis at 1 year postpartum
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.
Time frame: 1 year
Incidence of subclinical coronary atherosclerosis at 15 years postpartum
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.
Time frame: 15 years
Incidence of clinical coronary atherosclerosis at 1 year postpartum
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.
Time frame: 1 year
Incidence of clinical coronary atherosclerosis at 15 years postpartum
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.
Time frame: 15 years