MARKERS OF CARDIOVASCULAR DYSFUNCTION AFTER PREGNANCIES COMPLICATED BY PRE-ECLAMPSIA

Pre-eclampsia (PE) is a hypertensive disorder of pregnancy characterized by maternal systemic endothelial dysfunction. While the clinical manifestations resolve soon after delivery, a large body of epidemiological evidence indicates significant long-term maternal risk for cardiovascular disease (CVD) after PE. The mechanisms by which PE and future CVD are associated are unclear, although shared constitutional risk factors likely contribute to the features of endothelial dysfunction characteristic to both. We postulate that PE offers a window of opportunity for the identification of unique markers of dysfunction in the earliest stages of disease that may be used to validate cardiovascular risk screening in the early postpartum period. The studies presented in this thesis provide evidence of changes in circulating factors in women with a recent history of PE. Using blood samples collected within the first year of pregnancy, unique patterns of microRNA expression, enrichment of coagulation system proteins and endothelial progenitor cell dysfunction were described. Many of the described changes appear to be independent of cardiovascular risk. In addition to alterations in circulating factors however, longitudinal postpartum assessments demonstrated that microvascular and cardiac abnormalities were evident in the early periods postpartum after a pre-eclamptic pregnancy. Collectively, the data presented in this thesis reveal that physiological alterations in women with a recent history of PE are not necessarily dependent on clinical parameters of cardiovascular risk, and that resulting dysfunction may be demonstrated within the first year postpartum. Importantly, the biomarkers presented herein are all demonstrated elsewhere in the literature to benefit from lifestyle modification and risk reduction. In closing, the findings of this thesis support a need for cardiovascular risk screening based on obstetrical history, namely after pregnancies complicated by PE.