AMPD1 (C34T) polymorphism and clinical outcomes in patients undergoing myocardial revascularization

Background: C34T variant of adenosine monophosphate deaminase 1 (AMPD1) gene has been associated with a prolonged survival in heart failure and coronary artery disease, hypothetically linked to an enhanced production of adenosine. Design: Since adenosine administration is a promising approach for the prevention of the ischemia-reperfusion in myocardial revascularization, the aim of this study was to investigate whether the AMPD1 (−) allele is associated with a favorable prognosis after coronary revascularization. In addition, we assessed the association between AMPD1 polymorphism and plasma adenosine levels. Methods: We investigated a total of 161 patients receiving coronary revascularization (70 percutaneous transluminal coronary angioplasty and 91 coronary artery bypass graft). They were investigated for a composite endpoint including recurrent angina, non-fatal MI, target vessel revascularization, heart failure and cardiac death. Plasma adenosine was also measured by high-performance liquid chromatography methods on a subset of 25 patients. Results: During the follow-up period (7.0±0.3 months), the overall combined endpoint accounted for 17 events (10 cardiac-related deaths, 6 revascularization procedures and 1 congestive heart failure). The composite endpoint was 9.8% for AMPD1 (−) allele carriers vs. 11.5% for non-carriers (log-rank statistic, p=n.s.). In the logistic analysis only low (≤40%) ejection fraction was an independent predictor of adverse events (p=0.01, OR=3.8, 95% CI 1.3-11.4). Plasma adenosine levels were similar for AMPD1 (−) allele patients (n=7) as compared for AMPD1 (+) allele (n=18) subjects (290.5±31.0 vs. 303.3±28.5 nM, p=n.s.). Conclusions: Our results indicate that AMPD1 (−) allele is not associated with a more favorable outcome after coronary revascularization. Alternative cardioprotective pathways of the AMPD1 gene-involving an enhanced chronic long-term production of adenosine-might be responsible for survival.