Epigenomic Dysregulation in Preeclampsia-Associated Chronic Hypertension

Study Overview
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Brief Summary
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Preliminary data from the investigator's lab identified novel patterns of differential DNA methylation in genes regulating cardiovascular and metabolic function in blood from women during the first trimester of pregnancy who were destined to develop preeclampsia (PE) in the third trimester. Further, common patterns of differential DNA methylation were found in the common genes from placental tissue at time of birth in the same women after diagnosis with PE, suggesting that the epigenomic patterns that predict pregnancy-induced hypertension may also underlie the development of chronic hypertension years after. It is unknown whether aberrant DNA methylation in pregnancy-induced hypertension is the mechanism by which chronic hypertension develops in these women remote from pregnancy nor is it known if hypertension remote from PE is as responsive to therapeutic treatment of hypertension compared to women who develop hypertension without history of PE. The investigators plan to objectively test the central hypothesis and attain the objective of this project

Detailed Description
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Women comprise 51% of the total heart disease deaths in the United States (NC with an estimated economic cost expected to climb to more than $258 billion. Hypertension, a prevalent manifestation of early cardiovascular disease, is a silent condition that contributes to significant adverse health consequences. Preeclampsia (PE), a form of pregnancy-induced hypertension diagnosed in the second half of pregnancy, is now established as a non-modifiable risk factor for future development of hypertension. As PE carries a familial risk for future development of PE in female offspring, the implications of increased risk for PE-associated future development of chronic hypertension further compounds the significance of this unique cardiovascular risk. This raises an important health concern, though little is known about the mechanisms underlying risk of PE-associated future chronic hypertension. As epigenetic patterns of DNA methylation are associated with transfer across generations and are known to be dysregulated in PE, we propose to test the central hypothesis that differential DNA methylation patterns in key cardiovascular genes identified in women with PE serve as a biomarker and predictor for therapeutic responsiveness for the remote diagnosis and prognosis of chronic hypertension, respectively. Therefore, the purpose of this study is to identify distinct epigenetic patterns of DNA methylation associated with preeclampsia (PE) that underlie the future development of hypertension and to determine the implication on responses to moderators and therapeutic interventions in the management of chronic hypertension.Univariate analysis of variance will be used to test associations between DNA methylation in genes and chronic hypertension among women with and without a history of preeclampsia. We will use multiple linear regression to examine differences in treatment responses to high blood pressure based on DNA methylation patterns in candidate cardiovascular genes.

Official Title
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Observational Study of Epigenomic Dysregulation in Preeclampsia-Associated Chronic Hypertension

Conditions
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Preeclampsia, Hypertension, Pregnancy Induced Hypertension

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female gender history of prior pregnancy diagnosis of chronic hypertension current treatment of chronic hypertension age 30 - 50 years old Exclusion Criteria: presence of comorbid conditions that influence cardiovascular health (SLE, congenital cardiac anomalies

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| History of Preeclampsia<br>Chronic hypertension with history of preeclampsia Chronic hypertension without history of preeclampsia | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DNA methylation pattern | Determine DNA methylatiion patterns in women with hypertension who have/have not had a prior diagnosis of preeclampsia | age 30-65 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular function | Determine differences in vascular function among women aged 30-65, diagnosed with hypertension and who have/have not had a prior diagnosis of preeclampsia | aged 30-65 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preeclampsia, hypertension, blood pressure, pregnancy induced hypertension, chronic hypertension