title: Deletion-type allele of the angiotensin-converting enzyme gene is associated with progressive ventricular dilation after anterior myocardial infarction. Captopril and Thrombolysis Study Investigators.
abstract: OBJECTIVE
  This study sought to determine whether patients who are homozygous for the deletion (D)-type allele of the angiotensin-converting enzyme gene display augmented ventricular dilation after myocardial infarction.
  
  
  BACKGROUND
  Recent evidence suggests that the deletion-type allele of the angiotensin-converting enzyme gene (DD genotype) is associated with an increased prevalence of myocardial infarction and myocardial hypertrophy. However, it is unknown whether the DD genotype is associated with adverse cardiac remodeling. To address this question we determined the genotype in patients enrolled in the Captopril and Thrombolysis Study (CATS), a prospective trial in which patients received either captopril or placebo during and after thrombolysis for a first anterior myocardial infarction.
  
  
  METHODS
  Cardiac volume was determined by echocardiography immediately after thrombolysis and at 1-year follow-up. The genotype for the angiotensin-converting enzyme was determined in 96 patients. Norepinephrine levels were assessed during and immediately after thrombolysis.
  
  
  RESULTS
  Immediately after thrombolysis, cardiac volume did not differ between genotype groups. However, at 1-year follow-up, both end-systolic and end-diastolic left ventricular volumes were significantly greater in the DD-genotype group. Norepinephrine increased to higher levels in the DD-genotype group that received placebo therapy. Captopril treatment effectively blunted both the norepinephrine increase and cardiac dilation in the DD-genotype group.
  
  
  CONCLUSIONS
  This exploratory study suggests that homozygosity for the angiotensin-converting enzyme deletion-type allele is associated with augmented neurohumoral activation as well as augmented cardiac dilation after an acute anterior myocardial infarction, an effect that may be susceptible to angiotensin-converting enzyme inhibition.
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, The Netherlands.
authors.forename: Y M
authors.initials: YM
authors.lastname: Pinto
authors.forename: W H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: J H
authors.initials: JH
authors.lastname: Kingma
authors.forename: H
authors.initials: H
authors.lastname: Schunkert
mesh_terms: D000483:Alleles; D002216:Captopril / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D009638:Norepinephrine / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011446:Prospective Studies; D013300:Streptokinase / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D002216:Captopril; D013300:Streptokinase; D007703:Peptidyl-Dipeptidase A; D009638:Norepinephrine