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Original Investigation
July 19, 2021

Coffee Consumption and Incident Tachyarrhythmias: Reported Behavior, Mendelian Randomization, and Their Interactions

Author Affiliations
  • 1Division of Cardiology, University of California, San Francisco, San Francisco
  • 2Institute for Human Genetics, University of California, San Francisco, San Francisco
  • 3Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco
JAMA Intern Med. 2021;181(9):1185-1193. doi:10.1001/jamainternmed.2021.3616
Key Points

Question  Is moderate, habitual coffee intake associated with the risk of arrhythmia, and is that association modified by genetic variants that affect caffeine metabolism?

Findings  In this large, prospective, population-based community cohort study of more than 300 000 participants, each additional daily cup of coffee was associated with a 3% reduced risk of developing an arrhythmia; these associations were not significantly modified by genetic variants that affect caffeine metabolism. A mendelian randomization study leveraging a polygenic score to capture inherited caffeine metabolism patterns did not reveal evidence that caffeine consumption increases the risk of incident arrhythmias.

Meaning  Neither habitual coffee consumption nor genetically mediated differences in caffeine metabolism was associated with a heightened risk of cardiac arrhythmias.


Importance  The notion that caffeine increases the risk of cardiac arrhythmias is common. However, evidence that the consumption of caffeinated products increases the risk of arrhythmias remains poorly substantiated.

Objective  To assess the association between consumption of common caffeinated products and the risk of arrhythmias.

Design, Setting, and Participants  This prospective cohort study analyzed longitudinal data from the UK Biobank between January 1, 2006, and December 31, 2018. After exclusion criteria were applied, 386 258 individuals were available for analyses.

Exposures  Daily coffee intake and genetic polymorphisms that affect caffeine metabolism.

Main Outcomes and Measures  Any cardiac arrhythmia, including atrial fibrillation or flutter, supraventricular tachycardia, ventricular tachycardia, premature atrial complexes, and premature ventricular complexes.

Results  A total of 386 258 individuals (mean [SD] age, 56 [8] years; 52.3% female) were assessed. During a mean (SD) follow-up of 4.5 (3.1) years, 16 979 participants developed an incident arrhythmia. After adjustment for demographic characteristics, comorbid conditions, and lifestyle habits, each additional cup of habitual coffee consumed was associated with a 3% lower risk of incident arrhythmia (hazard ratio [HR], 0.97; 95% CI, 0.96-0.98; P < .001). In analyses of each arrhythmia alone, statistically significant associations exhibiting a similar magnitude were observed for atrial fibrillation and/or flutter (HR, 0.97; 95% CI, 0.96-0.98; P < .001) and supraventricular tachycardia (HR, 0.96; 95% CI, 0.94-0.99; P = .002). Two distinct interaction analyses, one using a caffeine metabolism–related polygenic score of 7 genetic polymorphisms and another restricted to CYP1A2 rs762551 alone, did not reveal any evidence of effect modification. A mendelian randomization study that used these same genetic variants revealed no significant association between underlying propensities to differing caffeine metabolism and the risk of incident arrhythmia.

Conclusions and Relevance  In this prospective cohort study, greater amounts of habitual coffee consumption were associated with a lower risk of arrhythmia, with no evidence that genetically mediated caffeine metabolism affected that association. Mendelian randomization failed to provide evidence that caffeine consumption was associated with arrhythmias.

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    3 Comments for this article
    Further Analysis and Methodological Considerations for the Arrhythmia risk.
    Ping-Hao Chiang, undergraduate | School of Medicine, Chung Shan Medical University
    We read with interest the article by Eun-jeong Kim et al. [1] The authors concluded that the increasing amounts of habitual coffee intake were associated with a lower risk of arrhythmia. This research does have novel findings on the prevention of arrhythmia, a major cause of mortality and morbidity in patients with heart failure. [2]Consequently, we would like to discuss this topic further.

    First, we suggest that there are some important effect modifiers of arrhythmia and coffee consumption such as diet habit, sleep disorders and life styles that should be considered [3]. These residual confounders can be matched or
    adjusted to minimize the potential bias. Plus, people who are not suitable for caffeine intake might avoid coffee consumption. We are worried about the possible confounding-by-indication since previous studies have pointed out that caffeine intake will increase the risk of arrhythmia.[4]

    Furthermore, we are curious about the definition of habitual coffee consumption. We suggest analyzing dose-dependent effects to clarify the result. Besides, subgroup analysis can be done to find out susceptible sub-populations and strengthen the clinical application.

    1. Kim EJ, Hoffmann TJ, Nah G, Vittinghoff E, Delling F, Marcus GM. Coffee Consumption and Incident Tachyarrhythmias: Reported Behavior, Mendelian Randomization, and Their Interactions. JAMA Intern Med 2021 doi: 10.1001/jamainternmed.2021.3616[published Online First: Epub Date]|.
    2. Zuchinali P, Souza GC, Pimentel M, et al. Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial. JAMA Intern Med 2016;176(12):1752-59 doi: 10.1001/jamainternmed.2016.6374[published Online First: Epub Date]|.
    3. Shamloo AS, Dagres N, Arya A, Hindricks G. Atrial fibrillation: A review of modifiable risk factors and preventive strategies. Rom J Intern Med 2019;57(2):99-109 doi: 10.2478/rjim-2018-0045[published Online First: Epub Date]|.
    4. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2018;138(13):e272-e391 doi: 10.1161/cir.0000000000000549[published Online First: Epub Date]|.

    Ping-Hao Chiang1,2,; Yung-Chih Hsu1,2; James Cheng-Chung Wei, MD, PhD.1,3,4
    1 Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital;
    2School of Medicine, Chung Shan Medical University
    3Institute of Medicine, College of medicine, Chung Shan Medical University
    4Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.

    Correspondence: James Cheng-Chung Wei, MD, PhD.
    RE: Coffee Consumption and Incident Tachyarrhythmias
    Tomoyuki Kawada, MD | Nippon Medical School
    Kim et al. conducted a prospective study to evaluate the association between consumption of common caffeinated products and the risk of arrhythmias (1). The adjusted hazard ratio (HR) (95% confidence interval [CI]) of each additional cup of habitual coffee for incident arrhythmia was 0.97 (0.96-0.98). There were similar risk reductions for atrial fibrillation/flutter and supraventricular tachycardia by coffee consumption, presenting the adjusted HR (95% CI) of 0.97 (0.96-0.98) and 0.96 (0.94-0.99), respectively. In addition, genetically mediated caffeine metabolism did not affect the association between caffeine consumption and arrhythmias. I present information regarding the study.

    Voskoboinik et al. conducted a
    comprehensive review on the association between caffeinated beverages and cardiac rhythm (2). Among 11 human studies, 3 studies demonstrated a risk reduction of atrial arrhythmias by caffeinated beverages, and other studies presented no significant relationship. They also cautioned that individual differences existed in susceptibility to caffeine by citing a paper reporting that 25% of patients self-reported that coffee became a trigger of paroxysmal atrial fibrillation (3).

    Risk assessment of arrhythmias in relation to coffee consumption should therefore also be conducted in different ethnicities adjusting for sex, age, smoking, and comorbidities.

    1. Kim EJ, Hoffmann TJ, Nah G, et al. Coffee Consumption and Incident Tachyarrhythmias: Reported Behavior, Mendelian Randomization, and Their Interactions. JAMA Intern Med 2021 Jul 19:e213616. [Epub ahead of print]
    2. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and Arrhythmias: Time to Grind the Data. JACC Clin Electrophysiol 2018;4(4):425-432.
    3. Hansson A, Madsen-Härdig B, Olsson SB. Arrhythmia-provoking factors and symptoms at the onset of paroxysmal atrial fibrillation: a study based on interviews with 100 patients seeking hospital assistance. BMC Cardiovasc Disord 2004;4:13.

    Comment on "Coffee Consumption and Incident Tachyarrhythmias"
    Jinyun Chen, Ph.D. | Third Affiliated Hospital of Soochow University
    In addition to genetics, many factors are associated with habitual caffeine consumption, such as region, culture, income, work time, stress and other demographic and social factors. This study used participants in the UK Biobank for analysis. However, the genome-wide association studies for for caffeine metabolism were carried out in the United States (PMID: 21490707) and other nations (PMID: 25288136), which would influence the significance and effect size of the genetic polymorphisms. Additionally, as mentioned in the study, the type of coffee is also important. So a randomized clinical trial would be needed to demonstrate clear effects of caffeine consumption.