PLoS ONE (Jan 2022)

Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium.

  • J E Siland,
  • B Geelhoed,
  • C Roselli,
  • B Wang,
  • H J Lin,
  • S Weiss,
  • S Trompet,
  • M E van den Berg,
  • E Z Soliman,
  • L Y Chen,
  • I Ford,
  • J W Jukema,
  • P W Macfarlane,
  • J Kornej,
  • H Lin,
  • K L Lunetta,
  • M Kavousi,
  • J A Kors,
  • M A Ikram,
  • X Guo,
  • J Yao,
  • M Dörr,
  • S B Felix,
  • U Völker,
  • N Sotoodehnia,
  • D E Arking,
  • B H Stricker,
  • S R Heckbert,
  • S A Lubitz,
  • E J Benjamin,
  • A Alonso,
  • P T Ellinor,
  • P van der Harst,
  • M Rienstra

DOI
https://doi.org/10.1371/journal.pone.0268768
Journal volume & issue
Vol. 17, no. 5
p. e0268768

Abstract

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BackgroundBoth 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 resultsSeven 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: 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.ConclusionsFor resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.