title: Clinical relevance of angiotensin-converting enzyme gene polymorphisms to predict risk of mechanical ventilation after coronary artery bypass graft surgery.
abstract: OBJECTIVE
  Prolonged mechanical ventilation is a significant complication after coronary artery bypass graft surgery. Angiotensin-converting enzyme mediates ischemia-reperfusion injury, which is an important mechanism of postcoronary artery bypass graft complications. An insertion/deletion polymorphism within the angiotensin-converting enzyme gene is associated with variable concentrations of angiotensin-converting enzyme. Whether this polymorphism is associated with prolonged mechanical ventilation is not known. The primary objective was to determine whether the insertion/deletion angiotensin-converting enzyme gene polymorphism is associated with prolonged mechanical ventilation. The release of inflammatory mediators and risk of prolonged mechanical ventilation are higher after conventional coronary artery bypass graft compared with off-pump coronary artery bypass graft. Therefore, we examined the risk of prolonged mechanical ventilation for angiotensin-converting enzyme genotypes in patients undergoing conventional coronary artery bypass graft and off-pump coronary artery bypass graft separately. Tumor necrosis factor down-regulates angiotensin-converting enzyme concentrations, and functional polymorphisms within the tumor necrosis factor gene have been associated previously with prolonged mechanical ventilation. Therefore, we examined interactions between these polymorphisms.
  
  
  METHODS
  Prospective observational cohort study.
  
  
  METHODS
  Tertiary care center.
  
  
  METHODS
  Patients who underwent coronary artery bypass graft (with or without valve replacement surgery).
  
  
  METHODS
  None.
  
  
  RESULTS
  We measured angiotensin-converting enzyme genotype and time to extubate. Patients with the DD and DI genotypes were at higher risk of prolonged mechanical ventilation compared with those with the II genotypes (hazard ratio = 2.2 and 1.6, respectively, p =.0005). Interactions were seen between the angiotensin-converting enzyme genotypes with surgical technique and with tumor necrosis factor-308/lymphotoxin + 250 GG haplotype for prolonged mechanical ventilation (p =.078 and.0003, respectively). The association was stronger for those undergoing conventional coronary artery bypass graft, whereas neither angiotensin-converting enzyme genotype conferred higher risk to those undergoing off-pump coronary artery bypass graft.
  
  
  CONCLUSIONS
  Angiotensin-converting enzyme gene polymorphisms are associated with respiratory complications postcardiopulmonary bypass. The increased risk associated with genotype may be amenable to alternative surgical technique or pharmacologic manipulation.
authors.affiliation: Physician Research Network (SY), Methodist Healthcare Memphis, Memphis, TN, USA.
authors.forename: Sachin
authors.initials: S
authors.lastname: Yende
authors.forename: Michael W
authors.initials: MW
authors.lastname: Quasney
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Tolley
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wunderink
mesh_terms: D000368:Aged; D000483:Alleles; D044383:Black People / Q000235:genetics; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D015331:Cohort Studies; D001026:Coronary Artery Bypass; D003422:Critical Care; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011183:Postoperative Complications / Q000201:enzymology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000235:genetics*; D012306:Risk; D015300:Ventilator Weaning; D044465:White People / Q000235:genetics
chemical_list: D007703:Peptidyl-Dipeptidase A