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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. Published online July 19, 2021. 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 inversely 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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