Abstract 11802: Hypocretin/Orexin Receptor-2 Influences Mortality Risk After Myocardial Infarction

Introduction: Hypocretin/orexin system has been shown to play a role in heart failure. Whether this system also influences all-cause mortality in patients after myocardial infarction (MI) is unknown. The aim of the present study was to evaluate the effect of rs7767652 allele variants, upstream of hypocretin/orexin receptor-2, on prognosis of patients with MI. Methods: Data from a single-center prospectively designed AMBITION registry of consecutive patients hospitalized for MI at a large tertiary cardiology center were analyzed. Patients with type I MI, without previous history of MI or heart failure were included. A random population sample including 1,953 individuals was used to compare allele frequencies in the population. Results: Out of 1,593 patients in the registry, 1,009 fulfilled the inclusion criteria. In total, 6.1% patients were homozygotes and 39.4% heterozygotes for the minor allele. Allele frequencies in patients with MI did not differ from the general population (χ 2 p=0.62), suggesting no influence on the MI risk. During the median follow-up of 27 months (IQR 13-41), mortality rate was 8.4%. Homozygotes for the rs7767652 minor allele had a higher mortality risk as compared to heterozygotes (p=0.001) and homozygotes for the major allele (p=0.001) ( Figure ). After multivariate adjustment, minor allele homozygotes remained at increased mortality risk (HR 2.83, 95% CI 1.55-5.19). Minor allele homozygotes experienced more often ventricular fibrillation (12.9% vs. 4.8%, p=0.01) and required more often CPR (16.1% vs. 7.0%, p=0.02). Among patients with EF<40% at hospital discharge, minor allele homozygotes had a lower increase in EF during the follow-up (2.5±11.0 vs. 8.4±9.4, p=0.04). Conclusions: Our Mendelian randomization study shows that hypocretin/orexin system influences prognosis of patients with MI. This effect may be partially explained by the increased arrhythmic risk and the effect on the left ventricular systolic function recovery.