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Meta-Analysis
. 2022 May 20;17(5):e0268768.
doi: 10.1371/journal.pone.0268768. eCollection 2022.

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

J E Siland  1 , B Geelhoed  1 , C Roselli  1   2 , B Wang  3 , H J Lin  4   5 , S Weiss  6   7 , S Trompet  8   9 , M E van den Berg  10 , E Z Soliman  11 , L Y Chen  12 , I Ford  13 , J W Jukema  7   14   15 , P W Macfarlane  16 , J Kornej  17 , H Lin  18   19 , K L Lunetta  3   17 , M Kavousi  10 , J A Kors  20 , M A Ikram  10 , X Guo  4   5 , J Yao  21 , M Dörr  7   22 , S B Felix  7   22 , U Völker  6   7 , N Sotoodehnia  23 , D E Arking  24 , B H Stricker  10 , S R Heckbert  25 , S A Lubitz  2   26   27 , E J Benjamin  16   28   29 , A Alonso  30 , P T Ellinor  2   26   27 , P van der Harst  1   31   32 , M Rienstra  1
Affiliations
Meta-Analysis

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

J E Siland et al. PLoS One. .

Abstract

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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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Lubitz receives sponsored research support from Bristol Myers Squibb / Pfizer, Bayer AG, Boehringer Ingelheim, Fitbit, and IBM, and has consulted for Bristol Myers Squibb / Pfizer, Bayer AG, and Blackstone Life Sciences. Dr. P.T. Ellinor is supported by a grant from Bayer AG to the Broad Institute focused on the genetics and therapeutics of cardiovascular disease, and consulted for Bayer AG, Novartis, MyoKardia, and Quest Diagnostics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. PRISMA flow diagram.
Fig 2
Fig 2. Visualization of the ratio estimator.
Fig 3
Fig 3. U-shaped association between resting heart rate and incident AF in seven cohorts of the AFGen consortium.
A regression analysis using a quadratic term was performed per cohort to explore a non-linear association. The meta-analysed quadratic term of the association between resting heart rate and incident AF is significant (p-value = 0.028).
See this image and copyright information in PMC

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References

    1. Eppinga RN, Hagemeijer Y, Burgess S, Hinds DA, Stefansson K, Gudbjartsson DF, et al.. Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality. Nat Genet. 2016;48(12):1557–1563. doi: 10.1038/ng.3708 - DOI - PubMed
    1. Sharashova E, Wilsgaard T, Mathiesen EB, Lochen ML, Njolstad I, Brenn T. Resting heart rate predicts incident myocardial infarction, atrial fibrillation, ischaemic stroke and death in the general population: The tromso study. J Epidemiol Community Health. 2016;70(9):902–909. doi: 10.1136/jech-2015-206663 - DOI - PubMed
    1. Jouven X, Empana J, Schwartz PJ, Desnos M, Courbon D, Ducimetière P. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med. 2005;352(19):1951–1958. doi: 10.1056/NEJMoa043012 - DOI - PubMed
    1. Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, et al.. Worldwide epidemiology of atrial fibrillation: A global burden of disease 2010 study. Circulation. 2014;129(8):837–847. doi: 10.1161/CIRCULATIONAHA.113.005119 - DOI - PMC - PubMed
    1. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: The CAPRICORN randomised trial. Lancet. 2001;357(9266):1385–1390. doi: 10.1016/s0140-6736(00)04560-8 - DOI - PubMed

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