Cardiovascular disease (CVD) is responsible for the annual death of 8.6 million women worldwide and disproportionally affects African American women. Preeclampsia (PEC) affects 3-8% of all pregnancies and is now recognized by the American Heart Association as a potent independent risk factor for CVD. The increased cardiovascular (CV) risk in women with a remote history of PEC is posited to be from the vascular dysfunction that is the hallmark feature of the disease. The development of CVD typically occurs 20-30 years after the exposure to PEC. However, there is a paucity of research investigating the presence of cardiac risk factors in the decade after exposure to PEC ? an intermediate time period between the development of PEC disease and overt CVD, when women are young (30-40's) and might not otherwise be seeking care. Our overarching goal is to understand how a history of PEC modifies a woman's long-term CV health. The first step in this goal is to evaluate whether there are risk factors that identify a woman previously exposed to PEC as high risk for CVD, prior to an overt CV event in order to target early intervention and therapeutic strategies. The fundamental premise of our proposal is that women with a history of PEC will have a higher prevalence of traditional risk factors for CVD and a higher prevalence of an intermediate CV phenotype compared to women without a history of PEC. Women from this study will be followed long-term in order to correlate these risk factors with future CV events. We are uniquely positioned to address this important clinical question. We have a group of women with (n=441) and without PEC (n=591) that were previously enrolled in a prospective study conducted at our institution from 2005-2007. An exceptional advantage to this cohort is that cases and controls were evaluated and well-phenotyped at the time of enrollment by specialized Obstetricians, allowing us to have limited bias regarding initial diagnosis of PEC as well as the ability to control for a large amount of metadata that was collected at the time of enrollment. Adding to the richness of this cohort, more than 75% of these women are African American, providing a unique opportunity to study a high risk yet typically understudied population, in whom PEC and CVD are both more prevalent and more severe. This cohort will serve as the study population for our current proposal. We have a multidisciplinary team of obstetricians, cardiologists, vascular researchers and epidemiologists and are well poised to complete the study given our expertise and prior collaboration. Together, in a feasibility study of 150 women, we demonstrated that 57% of women from the original study, now 10 (+/-1) years from their initial exposure to PEC, can be contacted, agree to participate and present for a study visit. Completion of this study will address significant gaps in knowledge regarding the association between PEC and CVD.

Public Health Relevance

Cardiovascular disease (CVD) is responsible for the death of 8.6 million women annually and the American Heart Association (AHA) has recently concluded that preeclampsia (PEC) is as potent a risk factor for CVD as diabetes or a lifetime of smoking. However, there is a paucity of research investigating the presence of traditional and non-traditional cardiac risk factors in the decade after exposure to PEC ? an intermediate time period between the development of PEC disease and overt CVD, when women are young (30-40's) and might not otherwise be seeking care or receiving early intervention to decrease their subsequent CVD risk. This proposal will address this significant knowledge gap.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56HL136730-01A1
Application #
9769190
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Ludlam, Shari
Project Start
2018-09-15
Project End
2019-08-31
Budget Start
2018-09-15
Budget End
2019-08-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104