Key result
ADRB1 Gly389 homozygotes linked to ~102% higher MACE risk vs Arg389 in post-AMI metoprolol patients.
Why the study?
To investigate the association between beta1-adrenergic receptor (ADRB1) polymorphisms and cardiovascular events in patients treated with metoprolol after acute myocardial infarction.
Do β1-adrenergic receptor (ADRB1) polymorphisms affect the risk of major adverse cardiovascular events and cardiovascular death in patients treated with metoprolol after acute myocardial infarction?
Observational (n=1,584)
No
Do β1-adrenergic receptor (ADRB1) polymorphisms affect the risk of major adverse cardiovascular events and cardiovascular death in patients treated with metoprolol after acute myocardial infarction?
Hazard Ratio: 2.02 (95% CI 1.01–4.02)
Absolute Event Rate: 10.5% vs 5.5%
p-value: p=0.046
In post-AMI patients treated with metoprolol, the ADRB1 Gly389 homozygous polymorphism is associated with a doubled risk of MACE compared to Arg389 homozygotes.
Gly389 homozygosity was associated with higher MACE risk on metoprolol post-AMI; hypothesis-generating and requires prospective validation before any clinical use.
PURPOSE: To investigate the association between β1-adrenergic receptor (ADRB1) polymorphisms on cardiovascular events in patients treated with metoprolol after acute myocardial infarction (AMI). METHODS: Patients hospitalized for AMI (n = 1584) who were treated with metoprolol at discharge were genotyped for the ADRB1 variants Arg389Gly and Ser49Gly. The association between the ADRB1 variants and major adverse cardiovascular events (MACE) and cardiovascular death were assessed by the Cox proportional hazards model, using both a dominant and a codominant genetic model, as well as by haplotype copy number. RESULTS: After three years of follow-up, MACE occurred in 105 and cardiovascular death in 47 patients. Gly389 homozygotes (n = 105, 11 events; hazard ratio [HR] 2.02 [1.01, 4.02], p = 0.046), but not heterozygotes (n = 588, 45 events, HR 1.40 [0.90, 2.13], p = 0.12) were at increased risk of MACE, compared with Arg389 homozygotes (n = 891, 49 events). The risk was not significantly different when all Gly389 carriers were merged (p = 0.052). No primary events occurred in Gly49 homozygotes (n = 28); however, when merged with Gly49 heterozygous carriers (n = 383, 6 events) we found a numerical, but not statistically significant difference in cardiovascular deaths relative to Ser49 homozygotes (n = 1173, 41 events) (p = 0.07). The Arg389Ser49 haplotype was not associated with a primary outcome. CONCLUSION: In post-AMI patients treated with metoprolol, Gly389 homozygotes, but not heterozygotes were associated with an increased risk of MACE compared with Arg389 homozygotes. Our observations raise the possibility of a protective association of the Gly49 variant on cardiovascular death, but this hypothesis requires validation in larger, future studies.
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Bruun et al. (2026) conducted an observational in Acute myocardial infarction (n=1,584). ADRB1 Gly389 homozygote variant vs. ADRB1 Arg389 homozygote variant was evaluated on Major adverse cardiovascular events (MACE) (HR 2.02, 95% CI 1.01-4.02, p=0.046). In post-AMI patients treated with metoprolol, the ADRB1 Gly389 homozygote variant was associated with a significantly increased risk of MACE compared with Arg389 homozygotes (HR 2.02).
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