The placenta as a window to maternal microvascular disease risk
PI: Janet M. Catov, PhD
Magee-Womens Research Institute and Foundation
Department of Medicine
Women with pregnancies complicated by preeclampsia, preterm birth or fetal growth restriction have excess cardiovascular disease in the years after delivery compared to women with uncomplicated pregnancies. A pathophysiological feature of these adverse pregnancy outcomes is evidence of maternal malperfusion of the placenta characterized by incomplete vascular remodeling or vessel wall impairments similar to atherosclerosis. We hypothesize that women with placental malperfusion will have excess risk of cardiometabolic and microvascular disease 8-10 years post partum compared to those without these lesions. The innovative component of our study is that we consider the placenta as a routinely examined but under-studied organ that provides a unique window into maternal vascular adaptations and insults that presage clinical cardiovascular disease later in life.
Our population science project builds upon an assembled retrospective cohort of women with pregnancies delivered in 2008 to 2009 that includes placental pathology reports and specimens (n=6,677). The sample studied here will consist of 500 randomly selected women. We combine placental data with clinical features routinely measured across gestation to characterize the pregnancy profile. Our project relates placental vascular pathology and the pregnancy profile to blood pressure, hypertension and microvascular dysfunction 8-10 years after delivery. Our primary endpoints are clinic and home blood pressure, sublingual microvasculature rarefication and glycocalyx thinning, and circulating concentrations of asymmetric dymethylarginine, an endogenous inhibitor of nitric oxide synthesis. In a subset (n=150), assessments of coronary flow reserve using myocardial contrast echocardiography and digital endothelial function will be obtained.
We seek to determine if: 1) placental malperfusion can identify hypertension, higher blood pressure and microvascular endothelial injury after delivery; 2) placental malperfusion and the pregnancy profile predict these cardiovascular endpoints independent of adverse pregnancy outcomes; and 3) placental malperfusion is associated with impaired coronary and endothelial microvascular function. The impact of our project is that we test the placenta as a marker of microvascular disease in women, and develop a platform to test personalized medicine interventions, such as home blood pressure monitoring, to reduce long term cardiovascular risk in affected women.
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