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.