Clinical relevance of angiotensin-converting enzyme gene polymorphisms to predict risk of mechanical ventilation after coronary artery bypass graft surgery.

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.

DESIGN

Prospective observational cohort study.

SETTING

Tertiary care center.

SUBJECTS: Patients who underwent coronary artery bypass graft (with or without valve replacement surgery).

INTERVENTIONS: None.

MEASUREMENTS AND MAIN

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.