Coffee had a complex relationship with arrhythmias, according to a randomised trial with real-time electrocardiography patch monitoring, presented at the American Heart Association virtual meeting.
The Coffee and Real-Time Atrial and Ventricular Ectopy (CRAVE) Trial showed that premature atrial contractions weren’t caused by coffee consumption, whereas premature ventricular contractions (PVCs) were, reported Dr Gregory Marcus of the University of California San Francisco.
PVCs were 54% more likely on coffee-drinking days, with more than a doubling in risk with one or more cups, after adjustment for day of week. Those with genetics expected to yield the fastest caffeine metabolism showed the highest relative risk of PVCs.
Atrial arrhythmias weren’t elevated overall during periods randomised to allow coffee. Supraventricular tachycardia was actually reduced 12% per coffee drink, compared with no coffee.
“Overall, the acute yet everyday physiologic effects of coffee are complex,” Marcus said. “These data add to the growing evidence that those with supraventricular tachycardias or atrial fibrillation…or at risk for those diseases should not necessarily avoid coffee.”
It’s a common question in practice for which there hasn’t been a clear answer to give patients, as data have been conflicting, noted AHA press conference study discussant Dr Sana Al-Khatib of Duke University Medical Center in Durham, North Carolina.
However, the relatively young, normal body-weight population studied without prior arrhythmias is “really not representative of the average patient that we see in clinical practice”, she cautioned.
Small numbers didn’t allow for a good look at non-sustained ventricular tachycardia. Given that limitation along with use of surrogate endpoints, “I think it’s going to be critically important for future researchers to try to validate these results and look at harder endpoints during a longer follow- up of time,” Al-Khatib said.
Press conference moderator Dr Elaine Hylek of Boston University, who introduced her comments with the caveat that she is biased as a coffee drinker, agreed that, despite the small sample size of 100 patients, she was “somewhat reassured that it didn’t appear to induce any atrial arrhythmias. If anything, it seemed as if individuals were somehow increasing their physical activity. Hopefully that would translate to better cardiovascular health, weight, blood pressure.”
Coffee consumers averaged 1,058 more steps per day (P=0.0010) but got 36 less minutes sleep per night (P<0.001) after adjusting for day of week, with each additional drink linked with 587 additional steps per day and 18 fewer minutes of sleep (both P<0.001).
With regard to the PVCs, “we don't have to get too, too worried” for normal hearts in healthy individuals, Hylek suggested.
The trial enrolled 100 coffee-drinking adults and outfitted them with Fitbit Flex 2 devices, continuous electrocardiography with the wearable Zio patch, and a continuous glucose monitor. Participants were randomly assigned to consume at least one coffee (defined as one shot of espresso or a cup of regular caffeinated coffee) or as much as they wanted or to avoid all caffeine for two weeks in a two consecutive days-on, two days-off schedule.
“One of the biggest challenges was finding individuals willing to go without coffee,” Marcus noted. “We recognise that that could introduce some bias,” if people most prone to coffee-induced problems declined to enroll.
However, he pointed out that adherence among those who did enrol was “excellent” by all measures, which included participants pressing the button on the Zio patch each time they drank coffee, answering text messages about their actual coffee consumption on the prior day, reimbursement of coffee receipts, and electronic monitoring of their phone location to show when they were in a coffee shop.
Prior studies that have generally concluded no association or lower risk of atrial fibrillation with coffee consumption have relied on longitudinal and observational data from self-report prone to confounding, Marcus noted. The UK Biobank study, for example. suggested lower risk of supraventricular tachycardia, consistent with the trial findings. There hadn’t been much PVCs data, and what was available was “very conflicting”, he added.
Observational studies had also linked coffee with a reduction in mortality and in diabetes, but the CRAVE trial turned up no signal of effect on glucose.
“This study was really designed to detect acute effects,” Marcus said. “There may be chronic effects that are different. It’s not just that you add up all the acute effects and that leads to the chronic effect. Rather, there may be some cumulative process that leads to the outcomes observed.”
“For example, regular physical activity more commonly . . . perhaps that leads to a reduction on overall mortality perhaps in diabetes, whereas our data would suggest that these observations that coffee is associated with a lower risk of diabetes long-term does not appear to be an acute effect of caffeine on insulin sensitivity,” he said.
Study details
The Coffee and Real-Time Atrial and Ventricular Ectopy (CRAVE) Trial
Gregory M Marcus, David G Rosenthal, Gregory Nah, Eric Vittinghoff, Christina Fang, Kelsey Ogomori, Sean Joyce, Defne Yilmaz, Vivian Yang, Tara Kessedjian,; Dolkun Rahmutula, Emily Wilson, Michelle Yang, Kathleen Chang, Grace Wall, Jeff Olgin,
AHA Scientific Sessions November 2021
Background
Coffee is the most commonly consumed beverage in the world, but its health effects remain uncertain. The majority of coffee-related research has been observational (prone to confounding) and examined long-term effects less relevant to immediate consequences. We sought to perform randomized trials within individuals to capture real-time physiologic consequences of coffee consumption.
Methods
One-hundred consenting adults were fitted with a continuously recording ECG device (iRhythm, San Francisco, CA), a wrist-worn Fitbit (San Francisco, CA), a continuous glucose monitor (Dexcom, San Diego, CA), and downloaded a smartphone mobile application to collect geolocation data (Eureka, UCSF). DNA was genotyped for caffeine metabolism-related single nucleotide polymorphisms.
Participants were randomly assigned to consume or avoid coffee on a daily basis for 14 days, communicated by daily texts and reminders. Adherence to the randomization assignment was assessed by Zio patch button-presses to time-stamp every coffee drink; daily surveys recounting coffee consumed the previous day; reimbursing all date-stamped receipts with coffee purchases; and geofencing visits to coffee shops. Relationships between daily predictors and outcomes accounting for clustering within individuals were examined using logistic models with robust standard errors, negative binomial models, and linear mixed models.
Results
Enrolment and data collection are complete. Preliminary analyses are reported here. Participants were a mean 38 ± 13 years old, 51% women, and 48% non-Hispanic White. Adherence assessments revealed compliance with randomisation assignment by every metric employed (each p<0.01). In intention-to-treat analyses, random assignment to consume coffee was associated with a 54% increase in PVCs (95% CI 19-200% more PVCs, p=0.001), 1,058 additional Fitbit-based steps per day (95% CI 441-1,675, p=0.001), and 36 fewer minutes of sleep per night quantified by Fitbit devices (95% CI 22-50 minutes less sleep, p<0.001). In per-protocol analyses, drinking more than one coffee drinks more than doubled the number of PVCs (RR 2.02, p=0.007), 587 more steps per day (95% CI 355-820, p<0.001) and 18 fewer minutes asleep per night (95% CI 13-23, p<0.001). No significance differences in glucose levels were observed. The ventricular ectopy was not statistically mediated by changes in physical activity or sleep.
Preliminary conclusions
Coffee consumption increases ventricular ectopy, increase physical activity, and reduces sleep duration. Subsequent analyses to characterize differences in caffeine metabolism genetic variants remain forthcoming.
Coffee Causes This One Arrhythmia, Trial Shows (Open access)
AHA study – The Coffee and Real-Time Atrial and Ventricular Ectopy (CRAVE) Trial (Restricted access)
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Prohibitions against caffeine to reduce cardiac arrhythmias ‘unwarranted’ — UK cohort study
Blood metabolites linked to coffee consumption may affect CKD risk — Johns Hopkins
Up to three cups of coffee daily linked to significant health benefits — UK Biobank analysis
Coffee more likely to benefit health than harm it