Cardiovascular Diseases, Coronary Disease, Heart Diseases, Hypertension, Myocardial Infarction
Conditions
Brief summary
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
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.
Interventions
DRUGChlorthalidone
participant's drug dose will be titrated from 12.5mg to 25mg over the course of the study
DRUGLisinopril
participant's drug dose will be titrated from 10mg to 40mg over the course of the study
DRUGAmlodipine
participant's drug dose will be titrated from 10mg to 40mg over the course of the study
DRUGDoxazosin
participant's drug dose will be titrated from 2mg to 8mg over the course of the study
Sponsors
University of Minnesota
National Heart, Lung, and Blood Institute (NHLBI)
Donna Arnett, 257-5678
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure | baseline and six month | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of genotype on event rates | 6 years | 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 |
Countries
United States
Outcome results
None listed