title: 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.
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.
authors.affiliation: School of Public Health, University of Texas Health Science Center at Houston, 1200 Hermann Pressler, Houston TX, USA. a.h.maitland@pharm.uu.nl
authors.forename: Anke-Hilse
authors.initials: AH
authors.lastname: Maitland-van der Zee
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.forename: Catherine
authors.initials: C
authors.lastname: Leiendecker-Foster
authors.forename: Michael B
authors.initials: MB
authors.lastname: Miller
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
authors.forename: Charles E
authors.initials: CE
authors.lastname: Ford
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents; D003327:Coronary Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000453:epidemiology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment
chemical_list: D000959:Antihypertensive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007703:Peptidyl-Dipeptidase A; D017035:Pravastatin