PlacEntal Acute atherosis RefLecting Subclinical systemic atherosclerosis in women up to 20 years after pre-eclampsia (PEARLS): research protocol for a cohort study
Introduction Despite being a leading cause of female morbidity and mortality, female-specific cardiovascular disease (CVD) is understudied, underdiagnosed and undertreated. Pregnancy complications involving the placenta, including pre-eclampsia, pregnancy-induced hypertension and foetal growth restriction, are thought to reflect global maternal vascular derangements that indicate a twofold to eightfold increased risk of future CVD. This calls for a better understanding of female cardiovascular pathophysiology to allow development of targeted screening and prevention strategies. Acute atherosis is a placental vascular lesion, which histologically resembles systemic atherosclerosis. The PlacEntal Acute atherosis RefLecting Subclinical atherosclerosis study investigates the association between placental acute atherosis lesions and subclinical systemic atherosclerosis up to 20 years postpartum. This study will improve our understanding of the relationship between pregnancy complications and CVD to identify potential prevention targets and treatments. In addition, it could determine whether the placenta can improve identification of young women at high risk of CVD. These women could benefit from risk-reducing interventions. Methods and analysis This longitudinal prospective cohort study will include women who are either currently pregnant or from a historical cohort. Both groups will have placental histopathology and a single postpartum CVD assessment. The CVD assessment will include medical history taking, blood tests, electrocardiography and echocardiography. Additionally, coronary CT angiography focusing on the presence of atherosclerotic plaques and calcium score will be carried out. The currently pregnant women will either have a pre-eclamptic pregnancy (pre-eclamptic group) or an uncomplicated normotensive pregnancy (uncomplicated group), and their placenta will be collected prospectively. The single CVD assessment will be carried out 6–36 months postpartum. Women from the historical cohort had a pre-eclamptic pregnancy 10–20 years ago. Placental tissue is available for reanalysis. The single CVD assessment will take place immediately and corresponds with 10–20 years postpartum. Exclusion criteria are contraindications to diagnostic assessment necessities: iodinated contrast, beta-blockers or glyceryl trinitrate. Women with uncomplicated pregnancies will be excluded if they have a pre-existing auto-immune condition, chronic hypertension or diabetes mellitus. In the pre-eclamptic group, there are no additional exclusion criteria. Ethics and dissemination Ethical approval was granted by the Medical Ethics Committee in Maastricht University Medical Centre+ (NL52556.068.15/METC152019). Participants will give written informed consent. Results will be shared in peer-reviewed journals and conference presentations. Trial registration number NCT05500989 ; ClinicalTrials.gov Identifier.
Meta-analysis of atherosclerosis in formerly pre-eclamptic women
Abstract Background Up to eight percent of pregnant women have pre-eclampsia. These women have an increased risk of future ischemic heart and cerebral disease. This warrants early cardiovascular risk management in early disease stages. This meta-analysis determines how the prevalence of subclinical atherosclerosis in women after pre-eclamptic compared to non-pre-eclamptic pregnancies changes over time. Methods A systematic search was used. Studies reporting the prevalence of systemic atherosclerosis using ultrasound or computed tomography in formerly pre-eclamptic and non-pre-eclamptic women were included. A random-effects meta-analysis provided overall odds ratio’s (OR (95% confidence interval (CI)) for the association between pre-eclampsia and the prevalence of atherosclerosis. Results Eleven articles could be included with a total of 13,217 participants. Maternal age ranged from 33 to 60 years. Within this age period, pooled OR of developing atherosclerosis after pre-eclampsia was 1.57 (95%CI 1.39-1.78). The pooled odds of developing atherosclerotic plaque after a pre-eclamptic versus a non-pre-eclamptic pregnancy increased gradually with age. The odds ratio was not significantly different in the 30-39 age group (OR 0.64 (95%CI 0.10-4.15)), but there was a statistically significantly increased odds of finding an atherosclerotic plaque in the 40-49 (OR 1.59 (95%CI 1.34-1.89)) and 50-60 age groups (OR 2.00 (95%CI 1.30-3.08)) after pre-eclamptic pregnancies compared to non-pre-eclamptic pregnancies. Conclusions Formerly pre-eclamptic women have earlier and more frequent atherosclerosis and occurs ten years earlier than in non-pre-eclamptic women. Targeted prevention strategies are required to prevent premature cardiovascular disease morbidity and mortality in formerly pre-eclamptic women.