Caffeine and the Risk of Atrial Fibrillation

June 6, 2014

By Joshua Michael Lader, MD

Peer Reviewed

As physicians, we are frequently asked to weigh-in on dinnertime discussions about topics that, despite their relevance to everyday life, were never formally addressed in our medical training. For example, at a recent family gathering the conversation turned to a 78 year-old uncle who was recently diagnosed with atrial fibrillation. While this uncle had longstanding and likely poorly controlled hypertension, he would also typically drink 4 to 5 cups of coffee between breakfast and lunch. The debate then began as to whether my uncle’s morning habit of caffeinating himself could have contributed to his new-onset atrial fibrillation. I chimed in, stating that it was likely his more traditional risk factors (hypertension and old age) playing a role. Feeling smart, I quoted a 2005 study from JAMA demonstrating that habitual coffee consumption was not associated with an increased risk of incident hypertension in women [1]. My 28 year-old cousin then followed with a question that prompted me to do the research for this article:

“I heard that coffee can give you an irregular heartbeat. I also drink 5 cups per day. Should I cut back?”

I didn’t know what to say. No one in medical school listed caffeine ingestion as one of the typical risk factors for atrial fibrillation. However, this was probably something of a loaded question. She likely knew that caffeine has been shown to increase serum concentrations of the catecholamines epinephrine and norepinephrine in those naïve to the substance [2,3]. Furthermore, the alkaloid in question has also been shown to augment intracellular levels of cyclic AMP both directly (by stimulating adenyl cyclase) [4] and indirectly (by inhibiting phosphodiesterase) [5]. These molecular changes are widely recognized to shorten the duration of the myocardial action potential and refractory period and could thereby be expected to facilitate the maintenance of tachyarrhythmias [6]. In a 1983 study published in the New England Journal of Medicine, participants underwent electrophysiologic study before and after the administration of 200mg of oral coffee or IV caffeine citrate. As expected, the study demonstrated significant shortening of the effective refractory period in the high and low right atrium as well as in the AV node. These electrophysiologic changes were accompanied by what appeared to be prolonged duration of the provoked arrhythmias (though no statistical tests were run on the data likely due to the limited sample size) [7]. It is no surprise, then, that the majority of coronary care units at that time allowed only decaffeinated beverages (or so I am told). It seemed as though the case was closed and that my cousin should find herself a new breakfast-time beverage.

Not so fast. Certain other electrophysiologic parameters are unchanged by caffeine administration, including the shape of the P-wave (as assessed by signal-averaged electrocardiograms) [8,9] as well as inter- and intra-atrial conduction intervals (as assessed invasively) [7]. To put this in context, the slowing of atrial electrical impulse propagation, which would manifest as prolongation of the P-wave in the former studies and prolonged conduction intervals in the latter, is also arrhythmogenic. Additionally, intravenous administration of caffeine to canines surprisingly resulted in a reduced propensity for the induction of atrial fibrillation [10]. In a prospective examination of nearly 48,000 patients from the Danish Health Registry, Frost et al failed to find any risk of atrial fibrillation or flutter associated with caffeine consumption [11]. Most recently, Klatsky et al showed that in a large cohort from the Kaiser Permanente Medical Care Program, coffee-drinking and caffeine intake were inversely related to the risk of hospitalization for cardiac dysrhythmias in a dose-dependent fashion [12].

The reason for the disconnect between these studies is unknown. Many subsequent studies do not even acknowledge that a connection between caffeine and atrial fibrillation has ever been demonstrated [13]. The most likely explanation is tachyphylaxis, that the catecholaminergic effects of caffeine are significantly attenuated in habitual users [14,15]. Additionally, the fact that caffeine competitively antagonizes adenosine receptors (whose agonism abbreviates atrial refractory period and promotes atrial fibrillation) may also serve to protect against atrial fibrillation [16]. Furthermore, with a recent New England Journal of Medicine article suggesting that the survival benefit associated with coffee ingestion extends to its decaffeinated varietal [17], one must consider the likelihood that coffee’s biological effects may be attributable to substances other than caffeine.

I told my cousin what I had found and she muttered something about how “nature’s homeostatic mechanisms could not have been designed more perfectly” and then told me that she “would have kept drinking coffee regardless of any data.” Go figure.

Dr. Joshua Michael Lader, Cardiologist, NYU Langone Medical Center

Peer reviewed by David Park, MD, Medicine, Cardio Div., NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References:

1) Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA. 2005 Nov 9;294(18):2330-5. http://jama.jamanetwork.com/article.aspx?articleid=201838

2) Robertson D, Frolich JC, Carr RK, et al. Effects of caffeine on plasma activity, catecholamines and blood pressure. N Engl J Med. 1978;298:181-6. http://www.nejm.org/doi/full/10.1056/NEJM197801262980403

3) Levi L. The effect of coffee on the function of the sympathoadrenomedullary system in man. Acta Med Scand. 1967;181:431-8. http://onlinelibrary.wiley.com/doi/10.1111/j.0954-6820.1967.tb07260.x/abstract

4) Rall TW. The xanthines. In: Gilman AG, Goodman LS, Gilman A. eds. The pharmacological basis of therapeutics. 6th ed. New York: Macmillan. 1980:592-607

5) Braunwald E, Sonnenblick EH, Ross J Jr. Contraction of the normal heart. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. Philadelphia. WB Saunders, 198:419, 1980:413-52

6) Moe GK, Rheinboldt WC, Abildskov JA. A computer model of atrial fibrillation. Am Heart J. 1964 Feb;67:200-20.

7) Dobmeyer DJ, Stine RA, Leier CV, Greenberg R, Schaal SF. The arrhythmogenic effects of caffeine in human beings. N Engl J Med. 1983 Apr 7;308(14):814-6. http://www.nejm.org/doi/full/10.1056/NEJM198304073081405

8) Donnerstein RL, Zhu D, Samson R, Bender AM, Goldberg SJ. Acute effects of caffeine ingestion on signal-averaged electrocardiograms. Am Heart J. 1998;136:643–6. http://www.ahjonline.com/article/S0002-8703%2898%2970011-0/abstract

9) Caron MF, Song J, Ammar R, Kluger J, White CM. An evaluation of the change in electrocardiographic P-wave variables after acute caffeine ingestion in normal volunteers. J Clin Pharm Ther. 2001;26:145–8. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2710.2001.00336.x/abstract

10) Rashid A, Hines M, Scherlag BJ, Yamanashi WS, Lovallo W. The effects of caffeine on the inducibility of atrial fibrillation. J Electrocardiol 2006;39:421–5. http://www.jecgonline.com/article/S0022-0736%2805%2900376-6/abstract

11) Frost L, Vestergaard P. Caffeine and risk of atrial fibrillation or flutter: the Danish diet, cancer, and health study. Am J Clin Nutr. 2005;81:578–82. http://www.ajcn.org/content/81/3/578.abstract

12) Klatsky AL, Hasan AS, Armstrong MA, et al. Coffee, caffeine, and risk of hospitalization for arrhythmias. Perm J. 2011 Summer;15(3):19-25. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200095/

13) Schoonderwoerd BA, Smit MD, Pen L, Van Gelder IC. New risk factors for atrial fibrillation: causes of ‘not-so-lone atrial fibrillation’. Europace. 2008 Jun;10(6):668-73. http://europace.oxfordjournals.org/content/10/6/668.abstract

14) Debrah K, Haigh R, Sherwin R, et al. Effect of acute and chronic caffeine use on the cerebrovascular, cardiovascular and hormonal responses to orthostasis in healthy volunteers. Clin Sci (Lond). 1995 Nov;89(5):475-80. http://www.clinsci.org/cs/089/cs0890475.htm

15) Tarnopolsky MA, Atkinson SA, MacDougall JD, et al. Physiological responses to caffeine during endurance running in habitual caffeine users. Med Sci Sports Exerc. 1989 Aug;21(4):418-24. http://www.setantacollege.com/wp-content/uploads/Journal_db/Original%20investigations.pdf

16) Grant AO. Mechanisms of atrial fibrillation and action of drugs used in its management. Am J Cardiol. 1998 Oct 16;82(8A):43N-49N.

17) Freedman ND, Park Y, Abnet CC, et al. Association of coffee drinking with total and cause-specific mortality. N Engl J Med. 2012 May 17;366(20):1891-904. http://www.nejm.org/doi/full/10.1056/NEJMoa1112010#t=article

 

 

 

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