Evidence map›Paper›PMID 35594314›Full record

SynthesisPloS one2022

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 and 24 more

Open access · goldAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 4 pooled it
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 4 syntheses or guidelines pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Guideline
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  4. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors at 15 institutions in 4 countries.

J E SilandDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
B GeelhoedDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
C RoselliDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
B WangDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America.
H J LinInstitute for Translational Genomics and Population Sciences, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, United States of America.
S WeissInterfaculty Institute for Genetics and Functional Genomics; Department of Functional Genomics; University Medicine Greifswald, Greifswald, Germany.ORCID 0000-0002-3553-4315
S TrompetDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
M E van den BergDepartment of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
E Z SolimanDivision of Public Health Sciences and Department of Medicine, Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
L Y ChenCardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, United States of America.
I FordRobertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
J W JukemaDZHK (German Centre for Cardiovascular Research); partner site Greifswald, Greifswald, Germany.
P W MacfarlaneInstitute of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
J KornejNational Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, United States of America.
H LinNational Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, United States of America.
K L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America.ORCID 0000-0002-9268-810X
M KavousiDepartment of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
J A KorsDepartment of Medical Informatics, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
M A IkramDepartment of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
X GuoInstitute for Translational Genomics and Population Sciences, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, United States of America.
J YaoInstitute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, United States of America.
M DörrDZHK (German Centre for Cardiovascular Research); partner site Greifswald, Greifswald, Germany.
S B FelixDZHK (German Centre for Cardiovascular Research); partner site Greifswald, Greifswald, Germany.
U VölkerInterfaculty Institute for Genetics and Functional Genomics; Department of Functional Genomics; University Medicine Greifswald, Greifswald, Germany.
N SotoodehniaCardiovascular Health Research Unit, Division of Cardiology, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, Unites States of America.
D E ArkingMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University SOM, Baltimore, MD, Unites States of America.
B H StrickerDepartment of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
S R HeckbertCardiovascular Health Research Unit and the Department of Epidemiology, University of Washington, Seattle, WA, Unites States of America.ORCID 0000-0002-7100-512X
S A LubitzCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, United States of America.ORCID 0000-0002-9599-4866
E J BenjaminInstitute of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
A AlonsoDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, Unites States of America.ORCID 0000-0002-2225-8323
P T EllinorCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, United States of America.
P van der HarstDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
M RienstraDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID 0000-0002-2581-070X
Boston University · USErasmus MC · NLUniversitätsmedizin Greifswald · DEUniversity Medical Center Groningen · NLBroad Institute · USUniversity of Glasgow · GBUniversity of Washington · USEmory University · USJohns Hopkins University · USLeiden University Medical Center · NLNational Heart Lung and Blood Institute · USUCLA Medical Center · USUniversity of California, Los Angeles · USUniversity of Minnesota Medical Center · USWake Forest University · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
THE FRAMINGHAM HEART STUDYN01HC25195 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAMACHANDRAN, VASAN S · 2007 to 2014
$83.8M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
FRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
SUBCLINICAL CARDIOVASCULAR DISEASE COORDINATING CENTERN01HC95159 · NHLBI · UNIVERSITY OF WASHINGTON · PI KRONMAL, RICHARD A · 2007 to 2014
$19.6M
Task Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2M
Epidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8M
NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NHGRI NIH HHS U01 HG004402NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201700001CNHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002CNHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003CNHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004CNHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005CNHLBI NIH HHS HHSN268201700005INHLBI NIH HHS K24 HL148521NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N01HC25195NHLBI NIH HHS N01HC95159NHLBI NIH HHS N01HC95160NHLBI NIH HHS N01HC95161NHLBI NIH HHS N01HC95162NHLBI NIH HHS N01HC95163NHLBI NIH HHS N01HC95164NHLBI NIH HHS N01HC95165NHLBI NIH HHS N01HC95166NHLBI NIH HHS N01HC95167NHLBI NIH HHS N01HC95168NHLBI NIH HHS N01HC95169NHLBI NIH HHS N02 HL064278NHLBI NIH HHS N02 HL64278NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL128914NHLBI NIH HHS R01 HL139731NIDDK NIH HHS P30 DK063491
6 · The paper itself

Abstract

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: <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.

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

Indexed as

Atrial FibrillationAgedElectrocardiographyFemaleHeart RateHumansMaleMendelian Randomization AnalysisMiddle AgedRandom AllocationRisk Factors

Identifiers

PMID35594314
PMCPMC9122202
OpenAlexW4280595466

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.