Genetic Epidemiology of Responses to Antihypertensives
Overview
- Phase
- Not Applicable
- Intervention
- Hydrochlorothiazide
- Conditions
- Cardiovascular Diseases
- Sponsor
- Mayo Clinic
- Enrollment
- 1200
- Locations
- 1
- Primary Endpoint
- Change in blood pressure
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
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
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.
Investigators
Stephen T. Turner
Professor of Medicine
Mayo Clinic
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
African American hydrochlorothiazide
300 African American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks.
Intervention: Hydrochlorothiazide
European American hydrochlorothiazide
300 European American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks
Intervention: Hydrochlorothiazide
African American candesartan
300 African American hypertensives were treated with candesartan 16 mg daily for 2 weeks followed by 32 mg daily for 4 weeks
Intervention: Candesartan
European American candesartan
300 European American hypertensives were treated with candesartan 16 mg daily for 2 weeks followed by 32 mg daily for 4 weeks
Intervention: Candesartan
Outcomes
Primary Outcomes
Change in blood pressure
Time Frame: 4 weeks for hydrochlorothiazide; 6 weeks for candesartan
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.
Secondary Outcomes
- Adverse metabolic changes(4 weeks for hydrochlorothiazide only)