Genetic Epidemiology of Responses to Antihypertensives

Study Overview
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Brief Summary
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To determine whether measured variation in genes coding for components of vasoconstriction and volume regulating systems predict interindividual differences in blood pressure response to therapy with a thiazide diuretic, hydrochlorothiazide, or an angiotensin II receptor blocker, candesartan, in hypertensive African-Americans (N=300 treated with each drug) and in hypertensive European Americans (N=300 treated with each drug).

Detailed Description
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BACKGROUND: Essential hypertension is a common disorder that contributes to morbidity, mortality, and cost of health care, especially among African-Americans. Although a single-drug therapy is commonly prescribed for treatment of hypertension, blood pressure levels are controlled in some individuals but not in others. The study has the potential to identify genes contributing to the etiology of interindividual differences in blood pressure response to diuretic therapy in African-Americans and European Americans. DESIGN NARRATIVE: Hypertensive adults were treated with the diuretic hydrochlorothiazide, 25 mg/day, for four weeks; or with the angiotensin II receptor blocker candesartan, 16 mg/day for 2 weeks followed by 32 mg/day for 4 weeks. Interindividual variations in blood pressure responses and in candidate genes coding for components of systems regulating vasoconstriction and volume were measured. In addition, a panel of 500,000 single nucleotide polymorphisms genome-wide was measured in subsets of the most extreme responders and nonresponders to each drug for genome-wide association of analyses.

Official Title
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Genetic Epidemiology of Responses to Antihypertensives

Conditions
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Cardiovascular Diseases, Heart Diseases, Hypertension

Intervention / Treatment
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* Drug: Hydrochlorothiazide
* Drug: Candesartan


Participation Criteria
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Eligibility Criteria
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Primary (essential) hypertension

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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 |
| --- | --- |
| African American hydrochlorothiazide<br>300 African American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks. | Drug: Hydrochlorothiazide<br> <br> |
| European American hydrochlorothiazide<br>300 European American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks | Drug: Hydrochlorothiazide<br> <br> |
| African American candesartan<br>300 African American hypertensives were treated with candesartan 16 mg daily for 2 weeks followed by 32 mg daily for 4 weeks | Drug: Candesartan<br> <br> |
| European American candesartan<br>300 European American hypertensives were treated with candesartan 16 mg daily for 2 weeks followed by 32 mg daily for 4 weeks | Drug: Candesartan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood pressure | The blood pressure response to antihypertensive drug therapy was defined by the difference between blood pressure levels prior to and at the end of drug therapy. | 4 weeks for hydrochlorothiazide; 6 weeks for candesartan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse metabolic changes | Potentially adverse metabolic changes in response to hydrochlorothiazide include changes in fasting serum glucose and insulin; serum potassium; serum lipids (triglycerides, HDL-cholesterol, total cholesterol); and serum uric acid. | 4 weeks for hydrochlorothiazide only | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Pharmacogenetics, Hydrochlorothiazide, Candesartan