Document Detail


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.
MedLine Citation:
PMID:  15967849     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Previous studies have reported that blood pressure response to antihypertensive medications is influenced by genetic variation in the renin-angiotensin-aldosterone system, but no clinical trails have tested whether the ACE insertion/deletion (I/D) polymorphism modifies the association between the type of medication and multiple cardiovascular and renal phenotypes. METHODS AND RESULTS: We used a double-blind, active-controlled randomized trial of antihypertensive treatment that included hypertensives > or =55 years of age with > or =1 risk factor for cardiovascular disease. ACE I/D genotypes were determined in 37 939 participants randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatments and followed up for 4 to 8 years. Primary outcomes included fatal coronary heart disease (CHD) and/or nonfatal myocardial infarction. Secondary outcomes included stroke, all-cause mortality, combined CHD, and combined cardiovascular disease. Fatal and nonfatal CHD occurred in 3096 individuals during follow-up. The hazard rates for fatal and nonfatal CHD and the secondary outcomes were similar across antihypertensive treatments. ACE I/D genotype group was not associated with fatal and nonfatal CHD (relative risk of DD versus ID and II, 0.99; 95% CI, 0.91 to 1.07) or any secondary outcome. The 6-year hazard rate for fatal and nonfatal CHD in the DD genotype group was not statistically different from the ID and II genotype group by type of treatment. No secondary outcome measure was statistically different across antihypertensive treatment and ACE I/D genotype strata. CONCLUSIONS: ACE I/D genotype group was not a predictor of CHD, nor did it modify the response to antihypertensive treatment. We conclude that the ACE I/D polymorphism is not a useful marker to predict antihypertensive treatment response.
Authors:
Donna K Arnett; Barry R Davis; Charles E Ford; Eric Boerwinkle; Cathie Leiendecker-Foster; Michael B Miller; Henry Black; John H Eckfeldt
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-06-20
Journal Detail:
Title:  Circulation     Volume:  111     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-28     Completed Date:  2006-02-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3374-83     Citation Subset:  AIM; IM    
Affiliation:
University of Minnesota, Division of Epidemiology, Minneapolis, USA. arnett@ms.soph.uab.edu
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MeSH Terms
Descriptor/Qualifier:
Aged
Amlodipine / administration & dosage,  pharmacology
Antihypertensive Agents / administration & dosage,  pharmacology*
Blood Pressure / drug effects*,  genetics
Cardiovascular Diseases / etiology*
Chlorthalidone / administration & dosage,  pharmacology
Double-Blind Method
Doxazosin / administration & dosage,  pharmacology
Female
Follow-Up Studies
Genotype
Humans
Lisinopril / administration & dosage,  pharmacology
Male
Middle Aged
Peptidyl-Dipeptidase A / genetics*
Pharmacogenetics
Polymorphism, Genetic*
Predictive Value of Tests
Proportional Hazards Models
Risk Factors
Treatment Outcome
Grant Support
ID/Acronym/Agency:
5 R01 HL-63082/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 74191-85-8/Doxazosin; 77-36-1/Chlorthalidone; 83915-83-7/Lisinopril; 88150-42-9/Amlodipine; EC 3.4.15.1/Peptidyl-Dipeptidase A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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