Introduction
Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy, affecting 5-8% of pregnancies worldwide.1Importantly, PE is a significant risk indicator for cardiovascular disease (CVD) in later life. Women diagnosed with PE have a ~4-fold increased risk of hypertension and a ~2-fold increased risk of ischemic heart disease and stroke compared to women with uncomplicated pregnancies.2-5 Moreover, evidence suggests that women who develop severe PE during pregnancy are at highest risk of these outcomes.4,6-8 Alarmingly, studies show that onset of CVD and CVD-related death occur at much younger ages than the general female population.6-9 The link(s) between PE and cardiovascular risk are not fully understood but PE may indicate the presence of underlying, often undiagnosed, cardiovascular risk factors (CVRs).10,11 Moreover, underlying CVRs may directly contribute to placental dysfunction associated with PE, however this relationship has yet to be fully elucidated.12,13
Histopathological lesions of maternal vascular malperfusion (MVM) are commonly observed in placentas from PE pregnancies, particularly in cases of severe, early-onset disease.14-16 These lesions, including increased syncytial knots and accelerated villous maturation, are believed to reflect placental hypoxia and oxidative stress arising from incomplete uterine artery modelling and abnormal uteroplacental blood flow.1,17-18 Although common, MVM lesions are not observed in all PE cases and a proportion of PE placentas are histologically normal or exhibit other pathology such as chronic inflammation.19,20 Recent population-based studies have shown an association between placental lesions and future maternal health.21-25 Catov et al observed altered cardiometabolic profiles in women with preterm birth and lesions of MVM compared to women with term deliveries.21Additionally, women with preterm birth and co-morbid placental pathologies (MVM, inflammatory lesions) had the most severe atherogenic profiles.21 Collectively, these studies provide strong evidence that the placenta and its pathology may provide a snapshot into future maternal cardiometabolic health.26
To reduce the burden of CVD on PE women, specialised postpartum cardiovascular health clinics are being established across North America to screen women for CVRs and initiate postpartum CVD prevention including pharmaceutical and lifestyle interventions.27-29 However, these clinics are resource intensive and thus, follow-up of all PE women is prohibitive. Moreover, a proportion of PE women will remain low risk for CVD postpartum and not require follow-up. As placental pathology is inexpensive and readily available, it may offer a unique modality to identify PE women for CVR screening. Here, we investigate the association between placental pathology and postpartum CVD risk in women following PE.