Analyzing How Genetics May Affect Response to High Blood Pressure Medications

NCT ID: NCT00563901

Last Updated: 2014-03-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

37939 participants

Study Classification

OBSERVATIONAL

Study Start Date

2000-09-30

Study Completion Date

2004-05-31

Brief Summary

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High blood pressure is one of the most common health problems in the United States. There are many medications to treat high blood pressure, but there is a large variance in how people respond to these medications. It is believed that genetic variations may contribute to the inconsistent treatment response. This study will use genetic analysis to determine whether particular genes interact with high blood pressure medications to modify the risk of certain cardiovascular diseases.

Detailed Description

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High blood pressure affects nearly one in three individuals in the Unites States. There are many factors that can cause high blood pressure, including family history and genetic traits, kidney disease, stress, diabetes, and diet. If left untreated, high blood pressure can increase one's risk for coronary heart disease (CHD), stroke, heart attack, and heart failure. While high blood pressure can be managed with medication, people receiving medication treatment for high blood pressure are still variably at risk for CHD and other cardiovascular conditions. This risk variation may stem from varying drug reactions that are likely due to genetics. This study will use genetic analysis to determine whether particular genes interact with high blood pressure medications to modify the risk of certain cardiovascular diseases.

This is a continuation study to the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT), which included a randomized trial of the four high blood pressure drugs chlorthalidone, amlodipine, lisinopril, and doxazosin. Using samples from ALLHAT participants, this study will analyze the interactions of candidate gene pathways of relevance with medications from the ALLHAT study. Researchers will examine both single DNA building blocks and multiple genes in the candidate gene pathways and determine whether their interaction with the ALLHAT drugs modifies the risk of cardiovascular outcomes. Researchers will perform genetic analysis on 96 genetic markers using structured association testing (SAT) and false discovery rate (FDR) methods. These methods will control for population stratification and multiple testing. Finally, the study will establish a mechanism for other researchers to continue further analysis of the genetic variants examined in this study.

Conditions

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Hypertension Coronary Disease Cerebrovascular Accident

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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1

Adults with a high risk for high blood pressure from the ALLHAT study

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Participant in the ALLHAT study
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

University of Texas

OTHER

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role lead

Responsible Party

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University of Alabama at Birmingham

Principal Investigators

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Donna K. Arnett, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

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University of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Texas Houston

Houston, Texas, United States

Site Status

Countries

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United States

References

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Arnett DK, Boerwinkle E, Davis BR, Eckfeldt J, Ford CE, Black H. Pharmacogenetic approaches to hypertension therapy: design and rationale for the Genetics of Hypertension Associated Treatment (GenHAT) study. Pharmacogenomics J. 2002;2(5):309-17. doi: 10.1038/sj.tpj.6500113.

Reference Type BACKGROUND
PMID: 12439737 (View on PubMed)

Davis BR, Ford CE, Boerwinkle E, Arnett D, Eckfeldt J, Black H. Imputing gene-treatment interactions when the genotype distribution is unknown using case-only and putative placebo analyses--a new method for the Genetics of Hypertension Associated Treatment (GenHAT) study. Stat Med. 2004 Aug 15;23(15):2413-27. doi: 10.1002/sim.1831.

Reference Type BACKGROUND
PMID: 15273956 (View on PubMed)

Arnett DK, Davis BR, Ford CE, Boerwinkle E, Leiendecker-Foster C, Miller MB, Black H, Eckfeldt JH. Pharmacogenetic association of the angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure and cardiovascular risk in relation to antihypertensive treatment: the Genetics of Hypertension-Associated Treatment (GenHAT) study. Circulation. 2005 Jun 28;111(25):3374-83. doi: 10.1161/CIRCULATIONAHA.104.504639. Epub 2005 Jun 20.

Reference Type RESULT
PMID: 15967849 (View on PubMed)

Davis BR, Arnett DK, Boerwinkle E, Ford CE, Leiendecker-Foster C, Miller MB, Black H, Eckfeldt JH. Antihypertensive therapy, the alpha-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study. Pharmacogenomics J. 2007 Apr;7(2):112-22. doi: 10.1038/sj.tpj.6500395. Epub 2006 May 16.

Reference Type RESULT
PMID: 16702981 (View on PubMed)

Maitland-van der Zee AH, Boerwinkle E, Arnett DK, Davis BR, Leiendecker-Foster C, Miller MB, Klungel OH, Ford CE, Eckfeldt JH. Absence of an interaction between the angiotensin-converting enzyme insertion-deletion polymorphism and pravastatin on cardiovascular disease in high-risk hypertensive patients: the Genetics of Hypertension-Associated Treatment (GenHAT) study. Am Heart J. 2007 Jan;153(1):54-8. doi: 10.1016/j.ahj.2006.10.019.

Reference Type RESULT
PMID: 17174637 (View on PubMed)

Sherva R, Ford CE, Eckfeldt JH, Davis BR, Boerwinkle E, Arnett DK. Pharmacogenetic effect of the stromelysin (MMP3) polymorphism on stroke risk in relation to antihypertensive treatment: the genetics of hypertension associated treatment study. Stroke. 2011 Feb;42(2):330-5. doi: 10.1161/STROKEAHA.110.593798. Epub 2010 Dec 23.

Reference Type DERIVED
PMID: 21183746 (View on PubMed)

Other Identifiers

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R01HL063082-07A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1402

Identifier Type: -

Identifier Source: org_study_id

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