Genetics of Hypertension Associated Treatments (GenHAT)

Study Overview
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Brief Summary
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To examine whether the association between selected hypertensive genes and combined fatal coronary heart disease and nonfatal myocardial infarction in high-risk hypertensives is modified by the type of antihypertensive treatment, leading to differential risks of coronary heart disease.

Detailed Description
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BACKGROUND: The study might shed important light on the variation in patient response to antihypertensive agents, and improve the ability to pick the right antihypertensive for specific patients. GenHAT is an ancillary study to ALLHAT (the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial). ALLHAT recruited 42,515 hypertensives and randomized them to one of four antihypertensive agents (lisinopril, chlorthalidone, amlodipine, and doxazosin); follow-up will be completed in March, 2002. DESIGN NARRATIVE: GenHAT, a prospective study ancillary to ALLHAT, will characterize hypertension genetic variants and determine their interaction with antihypertensive treatments in relation to coronary heart disease (CHD). DNA from frozen clots stored at the ALLHAT Central Laboratory will be used to genotype variants of hypertension genes (angiotensinogen -6, angiotensin converting enzyme insertion/deletion, angiotensin type- 1 receptor, alpha-adducin, beta2 adrenergic receptor, lipoprotein lipase, and 10 new hypertension variants expected to be discovered during the course of the study). In addition to the primary aim, a number of secondary aims will be undertaken to evaluate gene- treatment interactions in relation to other endpoints, including all-cause mortality, stroke, heart failure, left ventricular hypertrophy, decreased renal function, peripheral arterial disease, and blood pressure lowering. Because of the ethnic and gender diversity of ALLHAT, an assessment will be made of the effects of these variants on outcomes in key subgroups (age >65 years, women, African Americans, Type II diabetics), and whether the gene-treatment interactions in relation to outcomes are consistent across subgroups.

Official Title
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Pharmacological Association of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Blood Pressure and Cardiovascular Risk in Relation to Anti-hypertensive Treatment

Conditions
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Cardiovascular Diseases, Heart Diseases, Hypertension, Coronary Disease, Myocardial Infarction

Intervention / Treatment
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* Drug: Chlorthalidone
* Drug: Lisinopril
* Drug: Amlodipine
* Drug: Doxazosin


Participation Criteria
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Eligibility Criteria
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not taking anti-hypertensive medication use of anti-hypertensives for less than two months with a baseline blood pressure between 140/90 and 180/110 use of anti-hypertensives for greater than two months with a blood pressure not greater than 160/100 at least one additional cardiovascular risk factor such as previous MI, stroke, type 2 diabetes, smoking, left ventricular hypertrophy or dyslipidemia

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Chlorthalidone<br>Participants will take chlorthalidone at recommended doses to control hypertension | Drug: Chlorthalidone<br>* participant's drug dose will be titrated from 12.5mg to 25mg over the course of the study<br>* Other names: Hygroton, Thalitone, Chlorthalid;|
| Amlodipine<br>Participants will take Amlodipine at recommended doses to control hypertension | Drug: Amlodipine<br>* participant's drug dose will be titrated from 10mg to 40mg over the course of the study<br>* Other names: Norvasc;|
| Lisinopril<br>Participants will take Lisinopril at recommended doses to control hypertension | Drug: Lisinopril<br>* participant's drug dose will be titrated from 10mg to 40mg over the course of the study<br>* Other names: Zestoretic;|
| Doxazosin<br>Participants will take Doxazosin at recommended doses to control hypertension | Drug: Doxazosin<br>* participant's drug dose will be titrated from 2mg to 8mg over the course of the study<br>* Other names: Cardura;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Pressure | Blood pressure will be measured to determine the effect of the prescribed anti-hypertensive . Data will be presented as the change in blood pressure over the course of six months | baseline and six month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of genotype on event rates | The rate of fatal myocardial infarction (MI) was evaluated in relation to the ACE I/D genotype and anti-hypertensive used. Data are presented as the incidence of fatal MI after six years of follow up | 6 years |