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PII‐26
Author(s) -
Johnson J. A.,
Karnes J. H.,
Brunner M.,
Gong Y.,
Langaee T. Y.,
CooperDeHoff R. M.,
Pepine C. J.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.151
Subject(s) - trandolapril , medicine , odds ratio , adverse effect , stroke (engine) , antihypertensive drug , genotype , angiotensin converting enzyme , blood pressure , ace inhibitor , biology , genetics , gene , mechanical engineering , engineering
BACKGROUND Genetic association between adverse cardiovascular (CV) outcomes and AGTR1 1166A>C as been studied by several groups, with conflicting results. We tested association of this SNP and a composite of adverse CV outcomes (death, nonfatal MI, nonfatal stroke) in the genetic substudy of INVEST, a trial of hypertensive coronary artery disease (CAD) patients randomly assigned to a calcium antagonist or β‐blocker strategy, to either of which the ACE inhibitor (ACEI) trandolapril and/or the diuretic hydrochlorothiazde could be added for blood pressure (BP) control. Previous studies did not include stroke as an outcome. METHODS 270 patients with adverse CV outcomes during the study and 777 age‐, sex‐ and race‐matched controls were genotyped by pyrosequencing. Genotype, age, gender, body mass index, percentage of visits with BP under control, race, previous MI or stroke, history of heart failure or diabetes, smoking, study drug use and an interaction term between ACEI use and genotype were included in a logistic regression model to differentiate cases and controls. RESULTS Allele frequencies were 0.77 and 0.23 for the A and C allele, respectively. Neither genotype nor the interaction term of genotype and ACEI use were significantly associated with adverse CV outcome. Odds ratio of adverse CV outcome for A/A vs. C carriers was 1.09 (95% CI 0.80–1.48). CONCLUSIONS These data suggest that the AGTR1 1166A>C genotype is not associated with adverse CV and cerebrovascular outcomes in hypertensive CAD patients. Clinical Pharmacology & Therapeutics (2005) 79 , P43–P43; doi: 10.1016/j.clpt.2005.12.151