Insertion/deletion polymorfism of the angiotensin-I converting enzyme gene and cardiac allograft vasculopathy after heart transplantation

Background: Cardiac allograft vasculopathy (CAV), one of the most serious long-term post-transplantation complications, often remains silent but may lead to myocardial infarction or death. Its etiology is not yet well defined. Experimental animal models have suggested that the renin-angiotensin system may play an important role in the development of CAV. The insertion(I)/deletion(D) polymorphism of the ACE gene partly controls tissue and plasma ACE levels, and might therefore affect the angiographic and clinical outcome of heart transplantation. In particular, as DID subjects have higher ACE levels than those with I/D or I/I, they might be more susceptible to CAV. Methods: We prospectively studied 476 heart-transplanted patients by means of annual coronary angiography and 6-monthly clinical examinations. Cardiac death, myocardial infarction and the development of CAV at angiography were the primary end points. Time dependence failure was analysed by means of Kaplan-Meier survival curves and Cox proportional hazard model was used to adjust for covariates. Results: The patients (402 males, 84%; mean age 48±12 years) were divided into three groups on the basis of their genotype: D/D=194, 41% (164 males, 85%; mean age 48±12 years), I/D=.225, 47% (188 males, 84%; mean age 49±11 years) and 1/1=57, 12% (50 males, 88%; mean age 47±13 years). The mean time follow-up was 93.8±35.9 months. The Kaplan-Meier survival curves did not show any significant differences between the D/D, I/D and I/I groups (log rank test: p=0.31). Cox proportional hazard model showed that previous acute graft rejection (p=0.003) was the only variable significantly associated with primary end points. Age over 50 years and cytomegalovirus infection appeared to increase the risk of primary end points although not significantly.