Absence of an interaction between the angiotensin-converting enzyme insertion-deletion polymorphism and pravastatin on cardiovascular disease in high-risk hypertensive patients: the Genetics of Hypertension-Associated Treatment (GenHAT) study.

TitleAbsence of an interaction between the angiotensin-converting enzyme insertion-deletion polymorphism and pravastatin on cardiovascular disease in high-risk hypertensive patients: the Genetics of Hypertension-Associated Treatment (GenHAT) study.
Publication TypeJournal Article
Year of Publication2007
Authorsvan der Zee, A-HMaitland-, Boerwinkle, E, Arnett, DK, Davis, BR, Leiendecker-Foster, C, Miller, MB, Klungel, OH, Ford, CE, Eckfeldt, JH
JournalAm Heart J
Volume153
Issue1
Pagination54-8
Date Published2007 Jan
ISSN1097-6744
KeywordsAged, Antihypertensive Agents, Coronary Disease, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Male, Middle Aged, Myocardial Infarction, Peptidyl-Dipeptidase A, Pharmacogenetics, Polymorphism, Genetic, Pravastatin, Proportional Hazards Models, Randomized Controlled Trials as Topic, Risk Assessment
Abstract

BACKGROUND: The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) insertion-deletion (ID) polymorphism interacts with pravastatin to modify the risk of coronary heart disease (CHD) and other cardiovascular end points in a large clinical trial.METHODS: GenHAT is an ancillary study of the ALLHAT. The ACE ID genotyped population in the lipid-lowering arm of ALLHAT included 9467 participants randomly assigned to pravastatin (n = 4741) or to usual care (n = 4726). The efficacy of pravastatin in reducing the risk of primary outcome (all-cause mortality) and secondary outcomes (fatal CHD and nonfatal myocardial infarction, cardiovascular disease [CVD] mortality, CHD, stroke, other CVD, non-CVD mortality, stroke, and heart failure) was compared between the genotype strata (dominant model ID + II vs DD, additive model II vs ID vs DD), by examining an interaction term in a Cox proportional hazards model.RESULTS: The relative risk of fatal CHD and nonfatal myocardial infarction among subjects randomized to pravastatin compared with subjects randomized to usual care was similar in subjects with the II genotype (hazard ratio [HR] 0.84, 95% CI 0.59-1.18), the ID genotype (HR 0.84, 95% CI 0.68-1.03), and the DD genotype (HR 0.99, 95% CI 0.77-1.27).CONCLUSIONS: We found no evidence that the ACE ID genotype was a major modifier of the efficacy of pravastatin in reducing the risk of cardiovascular events.

DOI10.1016/j.ahj.2006.10.019
Alternate JournalAm. Heart J.
PubMed ID17174637
PubMed Central IDPMC2766552
Grant ListR01 HL063082-08 / HL / NHLBI NIH HHS / United States
R01 HL063082-01 / HL / NHLBI NIH HHS / United States
R01 HL063082-05 / HL / NHLBI NIH HHS / United States
R01 HL083498 / HL / NHLBI NIH HHS / United States
R01 HL063082-04 / HL / NHLBI NIH HHS / United States
R01 HL063082-06 / HL / NHLBI NIH HHS / United States
R01 HL063082-07A1 / HL / NHLBI NIH HHS / United States
R01 HL063082-03 / HL / NHLBI NIH HHS / United States
R01 HL063082 / HL / NHLBI NIH HHS / United States
R01 HL063082-02 / HL / NHLBI NIH HHS / United States