Impact of the Polymorphism rs5751876 of the Purinergic Receptor ADORA2A on Periprocedural Myocardial Infarction in Patients Undergoing Percutaneous Coronary Intervention

Aim: Periprocedural myocardial infarction (PMI), a severe complication of Percutaneous Coronary Intervention (PCI) procedures, has a negative prognostic effect, both at short and long-term follow-up. So far, adenosine's role in preventing PMI has shown contrasting results. A genetic variant of ADORA2A receptor, 1976 C > T, has been suggested as a potential determinant of the interindividual response to adenosine, thus conditioning its potential benefits on PMI. In our study, we investigated whether the ADORA2A 1976 C > T polymorphism is associated with PMI occurrence in patients undergoing coronary stenting. Methods: The study included consecutive patients undergoing PCI at the Azienda Ospedaliera-Universitaria “Maggiore della Carità,” Novara, Italy, between January 2010 and January 2016. Their genetic status was assessed using polymerase chain reaction (PCR) and restriction-fragment-length-polymorphism technique. Myonecrosis biomarkers were measured at intervals from 6 to 48 hours. PMI was defined as CKMB increased 3 times over the Upper Limit of Normal (ULN), or 50% of pre-PCI value; periprocedural myonecrosis was defined as troponin I increased 3 times over the ULN or by 50% of the baseline value. Results: We included 1,104 patients undergoing PCI, 863 (78.2%) of whom carried the ADORA2A T-allele. No difference was found for the main demographic, clinical features, or biochemistry parameters. However, C-carriers had lower statin therapy use (p = 0.008) and lower HDL-cholesterol levels (p = 0.01). Homozygous C/C patients had more frequent multivessel disease (p = 0.03), longer lesions (p = 0.01) and Type C lesions (p = 0.01), thus requiring more complex procedures. After correction for baseline confounding factors at multivariate analysis, there was no difference in myocardial necrosis according to the ADORA2A genotype (p = 0.40). In contrast, PMI tended to increase in the homozygous C/C population (p = 0.06), but this trend was attenuated at multivariate analysis after correction for baseline confounding factors (C/C: OR[95%CI]= 1.52 [0.88–2.6], p = 0.14). Conclusions: Our study showed that the polymorphism rs5751876 of the ADORA2A receptor is associated with a higher prevalence of complex coronary lesions and multivessel disease. However, it does not significantly influence the occurrence of periprocedural MI or myonecrosis.