Acetylcholine receptor M2 gene variants, heart rate recovery, and risk of cardiac death after an acute myocardial infarction

Background and aims. We aimed to replicate the previously observed association between acetylcholine receptor subtype M2 (CHRM2) gene polymorphisms and heart rate recovery (HRR) after exercise in patients with a recent acute myocardial infarction (AMI) and assess the prognostic significance of CHRM2 gene variants after AMI.Methods. HRR was determined as the difference between maximal heart rate and heart rate at 1 minute after the symptom-limited bicycle exercise test in 192 post-AMI patients. Genetic variants at the CHRM2 locus in intron 5 (rs324640) and the 3'-UTR of exon 6 (rs8191992) were assessed.Results. The rs324640 C/C and rs8191992 A/A homozygotes had more than a 3-fold risk of being in the lowest HRR quartile (≤ 8 bpm) compared to the T/T homozygotes (odds ratio (OR) 3.2, 95% confidence interval (CI) 1.2–8.6, P=0.017 and OR 3.8, 95% CI 1.3–11.1, P=0.016, respectively). In a larger sample of post-AMI patients (n=491), both C/C and A/A genotypes predicted cardiac mortality (11%) (adjusted relative risk (RR) 2.5, 95% CI 1.4–4.3, P=0.002 and RR 2.1, 95% CI 1.1–3.8, P=0.017, respectively) during a follow-up of 7.7±2.2 years.Conclusions. DNA sequence variation at the CHRM2 locus is a determinant of cardiac autonomic function in the postexercise early recovery phase and predicts cardiac mortality after AMI.