Preeclampsia, a hypertensive disorder affecting 5-8% of pregnancies, is associated with life-threatening maternal-fetal consequences and its incidence is on the rise. Long regarded as a temporary obstetrical condition with implications limited to pregnancy, it is now recognized that women with prior preeclampsia are at elevated risk for the development of sustained hypertension, premature cardiovascular disease (CVD) and a shortened lifespan. The pathophysiology of preeclampsia includes excessive placental release of anti- angiogenic proteins that lead to systemic manifestations of hypertension, proteinuria, and endothelial dysfunction. Preeclampsia is also associated with left ventricular (LV) hypertrophy and abnormal LV function, and growing body of evidence suggests that the cardiovascular abnormalities persist beyond the peripartum period. The mechanism of insult of preeclampsia?s cardiovascular effects are unknown. The central hypothesis of this proposal is that the anti-angiogenic state induced by preeclampsia increases future CVD risk by directly altering cardiac structure and function. We will employ state of the art cardiac magnetic resonance (CMR) stress imaging to quantify the coronary microcirculation and to provide deep cardiac phenotyping of the structural and functional changes after preeclampsia. We will perform a single site ancillary study in 120 women (40 with preeclampsia) followed at Columbia University in the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be Heart Health Study (nuMoM2b-HHS) to pursue the following specific aims: (1) To examine whether there are differences in the coronary microcirculation of women with a history of preeclampsia during their nuMoM2b index pregnancy compared to control women who did not have preeclampsia; (2) To determine the extent to which previous preeclampsia directly alters later cardiac structure by increasing LV mass and separately fibrosis; (3) To quantify the associations between circulating anti-angiogenic proteins of pregnancy with coronary perfusion and fibrosis 7 to 14 years after delivery. Comprehensive cardiac phenotyping of women with and without a history of preeclampsia will inform future studies examining CVD risk stratification and modification in women with a history of preeclampsia. Despite sharing many risk factors, including female predominance, obesity, and hypertension, the associations of preeclampsia with coronary microvascular disease and myocardial fibrosis have not been examined. This proposal is a crucial step towards better understanding the mechanisms through which preeclampsia alters future CVD risk in women. This knowledge will enable the development of novel, informed interventions to prevent or delay the incidence of CVD in women with a history of preeclampsia thereby decreasing premature morbidity and mortality and healthcare costs in a young and expanding subset of women.

Public Health Relevance

Preeclampsia, a hypertensive disorder of pregnancy that affects up to 8% of women, is an important risk factor for the development of premature cardiovascular disease (CVD), though the mechanisms through which it exerts its effects on the heart are unknown. This project will determine alterations in (1) the coronary microcirculation and (2) myocardial structure, including the presence of increased left ventricular mass and fibrosis, using novel cardiac magnetic resonance stress imaging in a diverse, well-phenotyped cohort of women to define the contribution of preeclampsia and associated anti-angiogenic proteins of pregnancy to the development of pathologic changes in cardiac structure and function. There has been a recent stagnation in the reduction of CVD events particularly among younger women (<55 years), thus, a better understanding of the role sex-specific risk factors such as preeclampsia play in the development of premature CVD is critical to closing the growing mortality gap.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
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Pemberton, Victoria
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Columbia University (N.Y.)
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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