Abstract 2132: Impact of Angiotensin II Type 1 Receptor 1166AC Polymorphism on Development of Heart Failure in Patients Treated With Beta-blockers After Acute Myocardial Infarction
Backgrounds: A cross talk between renin-angiotensin-aldosterone system (RAAS) and sympathetic nerve system could play some roles in the cardiovascular system. We investigated an association between DNA polymorphisms of the genes involved in RAAS and development of heart failure in patients treated with beta-blockers after acute myocardial infarction (AMI).
Methods: A total of 2,460 AMI survivors registered in the Osaka Acute Coronary Insufficiency Study (OACIS) were genotyped for angiotensin converting enzyme (ACE; insertion (I)/deletion (D)), angiotensinogen (AGT; 235 MT), angiotensin II type 1 receptor (AT1R; 1166AC) and aldosterone synthase CYP11B2 (−344CT). Impact of the polymorphisms on the combined endpoint of death and re-admission due to heart failure was examined using Kaplan-Meier method and multivariate Cox regression analysis.
Results: At discharge, 959 patients were treated with beta-blockers, whereas 1,501 were not. There were no significant differences in age, sex, and prevalence of diabetes, dyslipidemia, and history of smoking between patients with and without beta-blockers, while those with beta blockers had higher prevalence of hypertension and prescription of ACE inhibitors. Among the polymorphisms investigated, a single nucleotide polymorphism (SNP) of the AT1R gene (1166A→C) was associated with increased incidence of the endpoint when treated with beta-blockers (Log rank, p=0.005; p value for interaction = 0.026), whereas the other three not. Multivariate analysis revealed that beta blocker treatment in patients with the 1166C allele of the AT1R gene was associated with increased incidence of the combined endpoint (Hazard ratio 2.18, 95%CI: 1.02– 4.66).
Conclusions: The AT1R polymorphism (1166A→C) was associated with increased incidence of death and re-admission due to heart failure in post-MI patients, suggesting the impact of the SNP on responsiveness to beta-blockade therapy.