Why the study?
Although resting heart rate has a suggested U-shaped relationship with AF, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited.
Does genetically-determined resting heart rate causally affect the risk of incident atrial fibrillation in individuals of European ancestry?
Does genetically-determined resting heart rate causally affect the risk of incident atrial fibrillation in individuals of European ancestry?
A genetically determined lower resting heart rate is causally associated with an increased risk of incident atrial fibrillation in individuals with a resting heart rate below 65 bpm.
Stratified MR indicates inverse causal association at lower heart rates without U-shape; leaves open implications for AF prevention strategies.
BACKGROUND: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. METHOD AND RESULTS: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65-75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. CONCLUSIONS: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.
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Siland et al. (2022) studied this question.
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