Epigenomic Dysregulation in Preeclampsia-Associated Chronic Hypertension

Observational Study of Epigenomic Dysregulation in Preeclampsia-Associated Chronic Hypertension

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

Study Overview

• Status: Completed
• Conditions: Hypertension; Preeclampsia; Pregnancy Induced Hypertension

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Females diagnosed with chronic hypertension with a prior pregnancy

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
History of Preeclampsia; Chronic hypertension with history of preeclampsia Chronic hypertension without history of preeclampsia

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ohio State University
• Investigators: Principal Investigator: Cindy M Anderson, PhD, Ohio State University

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: September 5, 2012
• First Submitted That Met QC Criteria: September 5, 2012
• First Posted (Estimate): September 10, 2012

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: hypertension; blood pressure; preeclampsia; pregnancy induced hypertension; chronic hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pregnancy Complications; Hypertension; Pre-Eclampsia; Hypertension, Pregnancy-Induced
• Other Study ID Numbers: GFHNRC611