PlacEntal Acute Atherosis RefLecting Subclinical Atherosclerosis

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.

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.

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.