title: Beta-adrenergic receptor blockade and the angiotensin-converting enzyme deletion polymorphism in patients with chronic heart failure.
abstract: BACKGROUND
  Beta-adrenergic receptor blockade is an established treatment of chronic heart failure (HF). Previous studies have suggested a potential pharmacogenetic interaction between beta-blocker therapy and the angiotensin-converting enzyme (ACE) I/D polymorphism in patients with HF.
  
  
  OBJECTIVE
  We designed this study to analyze changes in myocardial function of HF patients in response to beta-blocker therapy as a function of the ACE I/D polymorphism.
  
  
  RESULTS
  We studied 199 consecutive patients with chronic HF not treated with beta-blockers. Before initiation of beta-blockers and 3 months after the maximal tolerated dose was reached, patients underwent echocardiography, radionuclide angiography, and a cardiopulmonary exercise test. We extracted genomic DNA from white blood cells and determined the ACE I/D polymorphism. Thirty-five (18%) patients had the II genotype, 86 (43%) the ID genotype and 78 (39%) the DD genotype. A significant and similar improvement in left ventricular ejection fraction (LVEF) was observed in II (from 0.30+/-0.10 to 0.41+/-0.13; P<0.0001), ID (from 0.29+/-0.11 to 0.39+/-0.13; P<0.0001) and DD patients (from 0.31+/-0.11 to 0.40+/-0.13; P<0.0001). Peak Vo(2) before and after beta-blockade was similar among the three groups. The proportion of responders to beta-blockers (patients without cardiac events during titration who had an increase in LVEF >5% after beta-blockers) was similar among the three groups (II: 65.9%%, ID: 60.6%%, DD: 65.9%; P=NS). During a median follow-up of 933 days, there was no evidence for any effect of ACE I/D polymorphism on cardiac survival.
  
  
  CONCLUSIONS
  We observed no evidence of pharmacogenetic interaction between the ACE I/D polymorphism and the effects of beta-blockade on LVEF and other prognostic parameters in patients with chronic HF. Our results support the initiation of beta-blockers in HF patients with the II or the ID genotype as well as in those with the DD genotype.
authors.affiliation: Service de Cardiologie C, Hôpital Cardiologique, Centre Hospitalier Universitaire de Lille, Boul Prof J Leclercq, 59037 Lille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: de Groote
authors.forename: Nicole
authors.initials: N
authors.lastname: Helbecque
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lamblin
authors.forename: Xavier
authors.initials: X
authors.lastname: Hermant
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: Christophe
authors.initials: C
authors.lastname: Bauters
authors.forename: Jean
authors.initials: J
authors.lastname: Dallongeville
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000235:genetics
chemical_list: D000319:Adrenergic beta-Antagonists; D007703:Peptidyl-Dipeptidase A