title: Angiotensin-converting enzyme gene polymorphism interacts with left ventricular ejection fraction and brain natriuretic peptide levels to predict mortality after myocardial infarction.
abstract: OBJECTIVE
  The goal of this study was the exploration of the associations between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and post-myocardial infarction (MI) outcomes, especially any interaction with the accepted clinical prognostic markers brain natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF).
  
  
  BACKGROUND
  The ACE gene I/D polymorphism has been implicated in the development of MI, hypertension, and left ventricular hypertrophy. We examined the association of ACE I/D and prognosis after acute MI.
  
  
  METHODS
  Patients incurring acute MI were genotyped for the ACE I/D polymorphism. Clinical data included assays of neurohormones, radionuclide ventriculography, and mortality over a mean 2.6 years of follow-up.
  
  
  RESULTS
  Patients (n = 978) had a mean age of 62.1 years, and 78% were male. Overall genotype frequencies were II 23.2%, ID 49.5%, and DD 27.3%. Chi-square analysis revealed an association between the ACE D allele and death after MI (88 of 103 who died were DD or ID; p < 0.05), with an odds ratio for mortality of 8.03 (95% confidence interval, 2.16 to 29.88). Patients with the DD genotype had higher (p < 0.05) plasma BNP, N-terminal BNP (N-BNP), and endothelin-1 levels within 96 h after MI than grouped ID/II patients. Multivariate analysis indicated ACE genotype, age, and previous MI were independent predictors of death (p < 0.05). Patients with an ACE D allele in combination with either a lower than median LVEF or greater than median BNP had a higher mortality (p < 0.001 and p < 0.025, respectively) than the risk associated with the D allele itself.
  
  
  CONCLUSIONS
  Angiotensin-converting enzyme genotyping may provide additional prognostic information in patients after MI in combination with the proven utility of LVEF, plasma BNP, and N-BNP measurements.
authors.affiliation: Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Palmer
authors.forename: Anna P
authors.initials: AP
authors.lastname: Pilbrow
authors.forename: Tim G
authors.initials: TG
authors.lastname: Yandle
authors.forename: Chris M
authors.initials: CM
authors.lastname: Frampton
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
authors.forename: M Gary
authors.initials: MG
authors.lastname: Nicholls
authors.forename: Vicky A
authors.initials: VA
authors.lastname: Cameron
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D020097:Natriuretic Peptide, Brain / Q000032:analysis*; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000235:genetics*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013318:Stroke Volume; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000235:genetics* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D007703:Peptidyl-Dipeptidase A