Genetic variation in the β1-adrenergic receptor is associated with the risk of atrial fibrillation after cardiac surgery

Abstract

Background: Postoperative atrial fibrillation (PoAF) after cardiac surgery is common and associated with increased morbidity and mortality. Increased sympathetic activation after surgery contributes to PoAF, and β-blockers are the first-line recommendation for its prevention. We examined the hypothesis that common functional genetic variants in the β1-adrenoreceptor, the mediator of cardiac sympathetic activation and drug target of β-blockers, are associated with the risk for PoAF and with the protective effect of β-blockers.

Methods: In a prospective cohort study, we studied 947 adult European Americans who underwent cardiac surgery at Vanderbilt University between 1999 and 2005. We genotyped 2 variants in the β1-adrenoreceptor, rs1801253 (Arg389Gly) and rs1801252 (Ser49Gly), and used logistic regression to examine the association between genotypes and PoAF occurring within 14 days after surgery, before and after adjustment for demographic and clinical covariates.

Results: Postoperative atrial fibrillation occurred in 239 patients (25.2%) and was associated with rs1801253 genotype (adjusted P = .008), with Gly389Gly having an odds ratio of 2.63 (95% CI 1.42-4.89) for PoAF compared to the common Arg389Arg (P = .002). In a predefined subgroup analysis, this association appeared to be stronger among patients without β-blocker prophylaxis (adjusted odds ratio 7.00, 95% CI 1.82-26.96, P = .005) compared to patients with β-blocker prophylaxis, among whom the association between rs1801253 genotype and PoAF was not statistically significant (adjusted P = .11).

Conclusion: The Gly389 variant in the β1-adrenoreceptor is associated with PoAF, and this association appears to be modulated by β-blocker therapy. Future studies of the association of other adrenergic pathway genes with PoAF will be of interest.

Figure 1. Study cohort flow diagram depicting patient exclusions

Starting with a total of 1,288 patients in the VCSR registry, 341 patients (26%) were excluded, resulting in a study cohort of 947 patients.

Figure 2. Adjusted odds ratios for PoAF in ADRB1 rs1801253 genotypes, stratified by use of prophylactic beta blockers

The Gly389Gly genotype was associated with significantly increased risk for PoAF, and this effect appeared to be more prominent in patients not using beta blocker prophylaxis. Points represent the point estimate of the OR, horizontal bars the 95% CI. ORs represent risks compared to the reference genotype (Arg389Arg).