Document Detail


Clinical and molecular approaches to individualize antihypertensive drug therapy.
MedLine Citation:
PMID:  22713145     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Abstract Interindividual variation of blood pressure (BP) responses to antihypertensive drugs is extensive. Several clinical, laboratory, and genetic predictors of BP responses to blood pressure-lowering agents have been suggested. We describe here the principal findings from the GENRES Study which is primarily a pharmacogenetic study of antihypertensive drug responses but also includes analysis of certain clinical and laboratory predictors. In this placebo-controlled, double-blinded, and randomized study, more than 200 male subjects with essential hypertension were treated with four antihypertensive drug monotherapies (amlodipine, bisoprolol, hydrochlorothiazide, and losartan) in a cross-over fashion, resulting in more than 800 treatment periods. Generally, placebo BP level was the best predictor of BP responses. In addition, higher baseline plasma renin activity predicted better BP response to losartan and bisoprolol, and weaker response to hydrochlorothiazide. A number of candidate gene polymorphisms analysed so far have given negative results in relation to BP responses, with the exception of an STK39 variant associating with losartan responsiveness. In future, genome-wide association studies on antihypertensive pharmacogenetics may identify novel pathways of BP regulation and provide new tools for both basic research and clinical use.
Authors:
Timo P Hiltunen; Kimmo Kontula
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Annals of medicine     Volume:  44 Suppl 1     ISSN:  1365-2060     ISO Abbreviation:  Ann. Med.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8906388     Medline TA:  Ann Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  S23-9     Citation Subset:  IM    
Affiliation:
Department of Medicine, and Research Program for Molecular Medicine, University of Helsinki and Helsinki University Central Hospital , Helsinki , Finland.
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