Is moderate, habitual coffee intake associated with the risk of arrhythmia, and is that association modified by genetic variants that affect caffeine metabolism?
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.
Neither habitual coffee consumption nor genetically mediated differences in caffeine metabolism was associated with a heightened risk of cardiac arrhythmias.
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.
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.
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.
A total of 386 258 individuals (mean [SD] age, 56  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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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: May 23, 2021.
Published Online: July 19, 2021. doi:10.1001/jamainternmed.2021.3616
Correction: This article was corrected on February 6, 2023, to fix data errors in Table 1 and eTable 1, as well as to add missing explanatory text in the caption of Figure 2.
Corresponding Author: Gregory M. Marcus, MD, MAS, Division of Cardiology, University of California, San Francisco, 400 Parnassus Ave, San Francisco, CA 94122 (firstname.lastname@example.org).
Author Contributions: Drs Kim and Marcus had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Kim, Marcus.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Kim, Marcus.
Critical revision of the manuscript for important intellectual content: Kim, Hoffmann, Nah, Vittinghoff, Delling.
Statistical analysis: Kim, Hoffmann, Nah, Vittinghoff.
Obtained funding: Marcus.
Administrative, technical, or material support: Delling, Marcus.
Conflict of Interest Disclosures: Dr Vittinghoff reported receiving salary support from the National Institutes of Health during the conduct of the study. Dr Marcus reported receiving grants from Baylis, Medtronic, and Eight Sleep outside the submitted work and reported being a consultant for Johnson & Johnson and InCarda and holding equity in InCarda. No other disclosures were reported.
Funding/Support: This research was conducted using the UK Biobank resource. The UK Biobank was established by the Wellcome Trust, the Medical Research Council, the UK Department of Health, and the Scottish Government. The UK Biobank has also received funding from the Welsh Assembly Government, the British Heart Foundation, and Diabetes United Kingdom, Northwest Regional Development Agency, Scottish Government.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Information: Dr Kim is currently in cardiac electrophysiology fellowship training at the University of California, San Francisco, San Francisco.
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