Coffee Consumption and Incident Tachyarrhythmias | Cardiology | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Coffee Consumption and Incident TachyarrhythmiasReported Behavior, Mendelian Randomization, and Their Interactions

Educational Objective
To assess the association between consumption of common caffeinated products and the risk of arrhythmias.
1 Credit CME
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.

Abstract

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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Accepted for Publication: May 23, 2021.

Published Online: July 19, 2021. doi:10.1001/jamainternmed.2021.3616

Corresponding Author: Gregory M. Marcus, MD, MAS, Division of Cardiology, University of California, San Francisco, 400 Parnassus Ave, San Francisco, CA 94122 (greg.marcus@ucsf.edu).

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.

Supervision: 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.

References
1.
Ludwig  IA , Clifford  MN , Lean  MEJ , Ashihara  H , Crozier  A .  Coffee: biochemistry and potential impact on health.   Food Funct. 2014;5(8):1695-1717. doi:10.1039/C4FO00042K PubMedGoogle ScholarCrossref
2.
Blomström-Lundqvist C, Scheinman MM, Aliot EM, et al; Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines.  Circulation. 2003;108(15):1871-909. doi:10.1161/01.CIR.0000091380.04100.84PubMed
3.
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 PubMedGoogle Scholar
4.
Prineas  RJ , Jacobs  DR  Jr , Crow  RS , Blackburn  H .  Coffee, tea and VPB.   J Chronic Dis. 1980;33(2):67-72. doi:10.1016/0021-9681(80)90029-6 PubMedGoogle ScholarCrossref
5.
Dixit  S , Stein  PK , Dewland  TA ,  et al.  Consumption of caffeinated products and cardiac ectopy.   J Am Heart Assoc. 2016;5(1):e002503. doi:10.1161/JAHA.115.002503 PubMedGoogle Scholar
6.
Bodar  V , Chen  J , Gaziano  JM , Albert  C , Djoussé  L .  Coffee consumption and risk of atrial fibrillation in the Physicians’ Health Study.   J Am Heart Assoc. 2019;8(15):e011346. doi:10.1161/JAHA.118.011346 PubMedGoogle Scholar
7.
Moura-Nunes  N , Perrone  D , Farah  A , Donangelo  CM .  The increase in human plasma antioxidant capacity after acute coffee intake is not associated with endogenous non-enzymatic antioxidant components.   Int J Food Sci Nutr. 2009;60(suppl 6):173-181. doi:10.1080/09637480903158893PubMedGoogle ScholarCrossref
8.
Furman  D , Chang  J , Lartigue  L ,  et al.  Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states.   Nat Med. 2017;23(2):174-184. doi:10.1038/nm.4267 PubMedGoogle ScholarCrossref
9.
Bøhn  SK , Blomhoff  R , Paur  I .  Coffee and cancer risk, epidemiological evidence, and molecular mechanisms.   Mol Nutr Food Res. 2014;58(5):915-930. doi:10.1002/mnfr.201300526 PubMedGoogle ScholarCrossref
10.
Santos  RMM , Lima  DRA .  Coffee consumption, obesity and type 2 diabetes: a mini-review.   Eur J Nutr. 2016;55(4):1345-1358. doi:10.1007/s00394-016-1206-0 PubMedGoogle ScholarCrossref
11.
Qi  H , Li  S .  Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson’s disease.   Geriatr Gerontol Int. 2014;14(2):430-439. doi:10.1111/ggi.12123 PubMedGoogle ScholarCrossref
12.
Ding  M , Satija  A , Bhupathiraju  SN ,  et al.  Association of coffee consumption with total and cause-specific mortality in 3 large prospective cohorts.   Circulation. 2015;132(24):2305-2315. doi:10.1161/CIRCULATIONAHA.115.017341 PubMedGoogle ScholarCrossref
13.
Swirski  FK , Nahrendorf  M .  Inflammation: old, caffeinated, and healthy.   Nat Rev Cardiol. 2017;14(4):194-196. doi:10.1038/nrcardio.2017.22PubMedGoogle ScholarCrossref
14.
Hughes  JR , Amori  G , Hatsukami  DK .  A survey of physician advice about caffeine.   J Subst Abuse. 1988;1(1):67-70. doi:10.1016/S0899-3289(88)80009-9 PubMedGoogle ScholarCrossref
15.
Poole  R , Kennedy  OJ , Roderick  P , Fallowfield  JA , Hayes  PC , Parkes  J .  Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes.   BMJ. 2017;359:j5024. doi:10.1136/bmj.j5024 PubMedGoogle Scholar
16.
Sudlow  C , Gallacher  J , Allen  N ,  et al.  UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age.   PLoS Med. 2015;12(3):e1001779. doi:10.1371/journal.pmed.1001779 PubMedGoogle Scholar
17.
Smith  GD , Davies  NM , Dimou  N ,  et al.  STROBE-MR: guidelines for strengthening the reporting of mendelian randomization studies.   Peerj Prepr. Published online July 15, 2019. doi:10.7287/peerj.preprints.27857v1Google Scholar
18.
Bycroft  C , Freeman  C , Petkova  D ,  et al.  Genome-wide genetic data on ~500,000 UK Biobank participants.   Biorxiv. Preprint posted online July 20, 2017. doi:10.1101/166298 Google Scholar
19.
Thorn  CF , Aklillu  E , Klein  TE , Altman  RB .  PharmGKB summary: very important pharmacogene information for CYP1A2.   Pharmacogenet Genomics. 2012;22(1):73-77. doi:10.1097/FPC.0b013e32834c6efd PubMedGoogle ScholarCrossref
20.
Cornelis  MC , Kacprowski  T , Menni  C ,  et al; Swiss Kidney Project on Genes in Hypertension (SKIPOGH) Team.  Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior.   Hum Mol Genet. 2016;25(24):5472-5482. doi:10.1093/hmg/ddw334 PubMedGoogle Scholar
21.
Gunes  A , Dahl  ML .  Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms.   Pharmacogenomics. 2008;9(5):625-637. doi:10.2217/14622416.9.5.625 PubMedGoogle ScholarCrossref
22.
Kalow  W , Tang  BK .  The use of caffeine for enzyme assays: a critical appraisal.   Clin Pharmacol Ther. 1993;53(5):503-514. doi:10.1038/clpt.1993.63 PubMedGoogle ScholarCrossref
23.
Zhou  A , Hyppönen  E .  Long-term coffee consumption, caffeine metabolism genetics, and risk of cardiovascular disease: a prospective analysis of up to 347,077 individuals and 8368 cases.   Am J Clin Nutr. 2019;109(3):509-516. doi:10.1093/ajcn/nqy297 PubMedGoogle ScholarCrossref
24.
Cornelis  MC , Monda  KL , Yu  K ,  et al.  Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption.   PLoS Genet. 2011;7(4):e1002033. doi:10.1371/journal.pgen.1002033 PubMedGoogle Scholar
25.
Cornelis  MC , Byrne  EM , Esko  T ,  et al; Coffee and Caffeine Genetics Consortium; International Parkinson’s Disease Genomics Consortium (IPDGC); North American Brain Expression Consortium (NABEC); UK Brain Expression Consortium (UKBEC).  Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.   Mol Psychiatry. 2015;20(5):647-656. doi:10.1038/mp.2014.107 PubMedGoogle ScholarCrossref
26.
Loftfield  E , Cornelis  MC , Caporaso  N , Yu  K , Sinha  R , Freedman  N .  Association of coffee drinking with mortality by genetic variation in caffeine metabolism: findings from the UK Biobank.   JAMA Intern Med. 2018;178(8):1086-1097. doi:10.1001/jamainternmed.2018.2425 PubMedGoogle ScholarCrossref
27.
Cornelis  MC , El-Sohemy  A , Kabagambe  EK , Campos  H .  Coffee, CYP1A2 genotype, and risk of myocardial infarction.   JAMA. 2006;295(10):1135-1141. doi:10.1001/jama.295.10.1135 PubMedGoogle ScholarCrossref
28.
Burgess  S , Davey Smith  G , Davies  NM ,  et al.  Guidelines for performing Mendelian randomization investigations.   Wellcome Open Res. 2020;4:186. doi:10.12688/wellcomeopenres.15555.2 PubMedGoogle ScholarCrossref
29.
Yang  Q , Sanderson  E , Tilling  K , Borges  MC , Lawlor  DA .  Exploring and mitigating potential bias when genetic instrumental variables are associated with multiple non-exposure traits in mendelian randomization.   Medrxiv. Preprint posted online October 18, 2019. doi:10.1101/19009605 Google Scholar
30.
D’Alessandro  A , Boeckelmann  I , Hammwhöner  M , Goette  A .  Nicotine, cigarette smoking and cardiac arrhythmia: an overview.   Eur J Prev Cardiol. 2012;19(3):297-305. doi:10.1177/1741826711411738 PubMedGoogle ScholarCrossref
31.
Team  RC .  R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; 2014.
32.
Yavorska  OO , Burgess  S .  MendelianRandomization: an R package for performing mendelian randomization analyses using summarized data.   Int J Epidemiol. 2017;46(6):1734-1739. doi:10.1093/ije/dyx034 PubMedGoogle ScholarCrossref
33.
Taylor  AE , Davey Smith  G , Munafò  MR .  Associations of coffee genetic risk scores with consumption of coffee, tea and other beverages in the UK Biobank.   Addiction. 2018;113(1):148-157. doi:10.1111/add.13975 PubMedGoogle ScholarCrossref
34.
van Dam  RM , Hu  FB , Willett  WC .  Coffee, caffeine, and health.   N Engl J Med. 2020;383(4):369-378. doi:10.1056/NEJMra1816604 PubMedGoogle ScholarCrossref
35.
Robertson  D , Frölich  JC , Carr  RK ,  et al.  Effects of caffeine on plasma renin activity, catecholamines and blood pressure.   N Engl J Med. 1978;298(4):181-186. doi:10.1056/NEJM197801262980403 PubMedGoogle ScholarCrossref
36.
Schlotthauer  K , Bers  DM .  Sarcoplasmic reticulum Ca(2+) release causes myocyte depolarization: underlying mechanism and threshold for triggered action potentials.   Circ Res. 2000;87(9):774-780. doi:10.1161/01.RES.87.9.774 PubMedGoogle ScholarCrossref
37.
Wilhelmsen  L , Rosengren  A , Lappas  G .  Hospitalizations for atrial fibrillation in the general male population: morbidity and risk factors.   J Intern Med. 2001;250(5):382-389. doi:10.1046/j.1365-2796.2001.00902.x PubMedGoogle ScholarCrossref
38.
Caldeira  D , Martins  C , Alves  LB , Pereira  H , Ferreira  JJ , Costa  J .  Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies.   Heart. 2013;99(19):1383-1389. doi:10.1136/heartjnl-2013-303950 PubMedGoogle ScholarCrossref
39.
Mostofsky  E , Johansen  MB , Lundbye-Christensen  S , Tjønneland  A , Mittleman  MA , Overvad  K .  Risk of atrial fibrillation associated with coffee intake: findings from the Danish Diet, Cancer, and Health study.   Eur J Prev Cardiol. 2016;23(9):922-930. doi:10.1177/2047487315624524 PubMedGoogle ScholarCrossref
40.
Groh  CA , Faulkner  M , Getabecha  S ,  et al.  Patient-reported triggers of paroxysmal atrial fibrillation.   Heart Rhythm. 2019;16(7):996-1002. doi:10.1016/j.hrthm.2019.01.027 PubMedGoogle ScholarCrossref
41.
Emdin  CA , Khera  AV , Kathiresan  S .  Mendelian randomization.   JAMA. 2017;318(19):1925-1926. doi:10.1001/jama.2017.17219 PubMedGoogle ScholarCrossref
42.
Holmes  MV , Ala-Korpela  M , Smith  GD .  Mendelian randomization in cardiometabolic disease: challenges in evaluating causality.   Nat Rev Cardiol. 2017;14(10):577-590. doi:10.1038/nrcardio.2017.78 PubMedGoogle ScholarCrossref
43.
Clarke  TK , Adams  MJ , Davies  G ,  et al.  Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117).   Mol Psychiatry. 2017;22(10):1376-1384. doi:10.1038/mp.2017.153 PubMedGoogle ScholarCrossref
44.
Kranzler  HR , Zhou  H , Kember  RL ,  et al.  Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations.   Nat Commun. 2019;10(1):1499. doi:10.1038/s41467-019-09480-8 PubMedGoogle ScholarCrossref
45.
Cornelis  MC , Munafo  MR .  Mendelian randomization studies of coffee and caffeine consumption.   Nutrients. 2018;10(10):1343. doi:10.3390/nu10101343 PubMedGoogle ScholarCrossref
46.
Cheng  M , Hu  Z , Lu  X , Huang  J , Gu  D .  Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies.   Can J Cardiol. 2014;30(4):448-454. doi:10.1016/j.cjca.2013.12.026 PubMedGoogle ScholarCrossref
47.
Casiglia  E , Tikhonoff  V , Albertini  F ,  et al.  Caffeine intake reduces incident atrial fibrillation at a population level.   Eur J Prev Cardiol. 2018;25(10):1055-1062. doi:10.1177/2047487318772945 PubMedGoogle ScholarCrossref
48.
Dobmeyer  DJ , Stine  RA , Leier  CV , Greenberg  R , Schaal  SF .  The arrhythmogenic effects of caffeine in human beings.   N Engl J Med. 1983;308(14):814-816. doi:10.1056/NEJM198304073081405 PubMedGoogle ScholarCrossref
49.
Rashid  A , Hines  M , Scherlag  BJ , Yamanashi  WS , Lovallo  W .  The effects of caffeine on the inducibility of atrial fibrillation.   J Electrocardiol. 2006;39(4):421-425. doi:10.1016/j.jelectrocard.2005.12.007 PubMedGoogle ScholarCrossref
50.
Brandts  B , Borchard  R , Dirkmann  D ,  et al.  Diadenosine-5-phosphate exerts A1-receptor-mediated proarrhythmic effects in rabbit atrial myocardium.   Br J Pharmacol. 2003;139(7):1265-1272. doi:10.1038/sj.bjp.0705361 PubMedGoogle ScholarCrossref
51.
Corrêa  TAF , Monteiro  MP , Mendes  TMN ,  et al.  Medium light and medium roast paper-filtered coffee increased antioxidant capacity in healthy volunteers: results of a randomized trial.   Plant Foods Hum Nutr. 2012;67(3):277-282. doi:10.1007/s11130-012-0297-x PubMedGoogle ScholarCrossref
52.
Vonderlin  N , Siebermair  J , Kaya  E , Köhler  M , Rassaf  T , Wakili  R .  Critical inflammatory mechanisms underlying arrhythmias.   Herz. 2019;44(2):121-129. doi:10.1007/s00059-019-4788-5 PubMedGoogle ScholarCrossref
53.
Hu  YF , Chen  YJ , Lin  YJ , Chen  SA .  Inflammation and the pathogenesis of atrial fibrillation.   Nat Rev Cardiol. 2015;12(4):230-243. doi:10.1038/nrcardio.2015.2 PubMedGoogle ScholarCrossref
54.
Marcus  GM .  Evaluation and management of premature ventricular complexes.   Circulation. 2020;141(17):1404-1418. doi:10.1161/CIRCULATIONAHA.119.042434 PubMedGoogle ScholarCrossref
55.
Mandyam  MC , Vedantham  V , Scheinman  MM ,  et al.  Alcohol and vagal tone as triggers for paroxysmal atrial fibrillation.   Am J Cardiol. 2012;110(3):364-368. doi:10.1016/j.amjcard.2012.03.033 PubMedGoogle ScholarCrossref
56.
Schliep  KC , Schisterman  EF , Mumford  SL ,  et al.  Validation of different instruments for caffeine measurement among premenopausal women in the BioCycle study.   Am J Epidemiol. 2013;177(7):690-699. doi:10.1093/aje/kws283 PubMedGoogle ScholarCrossref
57.
Modi  AA , Feld  JJ , Park  Y ,  et al.  Increased caffeine consumption is associated with reduced hepatic fibrosis.   Hepatology. 2010;51(1):201-209. doi:10.1002/hep.23279 PubMedGoogle ScholarCrossref
58.
Yuan  C , Spiegelman  D , Rimm  EB ,  et al.  Validity of a dietary questionnaire assessed by comparison with multiple weighed dietary records or 24-hour recalls.   Am J Epidemiol. 2017;185(7):570-584. doi:10.1093/aje/kww104 PubMedGoogle ScholarCrossref
59.
Dewland  TA , Glidden  DV , Marcus  GM .  Healthcare utilization and clinical outcomes after catheter ablation of atrial flutter.   PLoS One. 2014;9(7):e100509. doi:10.1371/journal.pone.0100509 PubMedGoogle Scholar
60.
Whitman  IR , Agarwal  V , Nah  G ,  et al.  Alcohol abuse and cardiac disease.   J Am Coll Cardiol. 2017;69(1):13-24. doi:10.1016/j.jacc.2016.10.048 PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close