Increasing amounts of habitual coffee consumption were inversely linked with a lower risk for arrhythmia, according to a prospective cohort study of nearly 400,000 adults in the United Kingdom.
Researchers said they found no evidence that genetic variants that mediate caffeine metabolism affected the link.
Reference: Kim E-J, et al. JAMA Intern Med. 2021;doi:10.1001/jamainternmed.2021.3616.
“Most research exploring the associations between coffee and arrhythmias has relied on self-reported coffee consumption,” Eun-Jeong Kim, MD, an assistant clinical professor in the division of cardiology at the University of California, San Francisco, and colleagues wrote in JAMA Internal Medicine. “Because most of these studies are observational rather than randomized trials, decisions to drink coffee and the amounts regularly consumed are likely associated with other variables that may confound observed associations.”
To help fill the data gap, Kim and colleagues conducted a study using mendelian randomization to evaluate the association between genetic polymorphisms that impact caffeine metabolism and arrhythmia. The researchers analyzed the race, ethnicity, educational level, BMI, physical activity level, major medical history and blood, urine or saliva samples of 386,258 adults (mean age, 56 years; 52.3% women) enrolled in the U.K. Biobank from Jan. 1, 2016, through Dec. 31, 2018. They also assessed how much coffee the individuals reported they drank daily. Pregnant women were not included in the analysis.
Kim and colleagues wrote that during a mean follow-up of 4.5 years, 16,979 of the participants developed an incident arrhythmia. After data adjustments, each additional cup of habitual coffee consumed was linked to a 3% lower risk for incident arrhythmia (HR = 0.97; 95% CI, 0.96-0.98).
In analyses of single arrhythmia events, statistically significant links showed a similar magnitude for atrial fibrillation and/or flutter (HR = 0.97; 95% CI, 0.96-0.98) and supraventricular tachycardia (HR = 0.96; 95% CI, 0.94-0.99). In addition, two interaction analyses, one using a caffeine metabolism-related polygenic score of genetic polymorphisms and another restricted to CYP1A2 rs762551 — the gene that metabolizes more than 95% of caffeine, according to the researchers — did not show any evidence of altering the effects of caffeine.
“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,” Kim and colleagues wrote.
The findings indicate that “common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted,” they added.
In an invited commentary, Zachary D. Goldberger, MD, MS, a faculty member within the department of medicine at the University of Wisconsin School of Medicine and Public Health, and Rodney A. Hayward, MD, a professor in the department of internal medicine at the University of Michigan School of Public Health, wrote that the findings “strengthen the evidence that caffeine is not proarrhythmic, but they should not be taken as proving that coffee is an antiarrhythmic.”
“This distinction is of paramount importance,” the pair continued. “Health care professionals can reassure patients that there is no evidence that drinking coffee increases the risk for developing arrhythmias. This is particularly important for the many patients with benign palpitations who are devastated when they think, or are told, that they have to stop drinking coffee.”
However, since the study sample did not include adults with a previous diagnosis of arrhythmia, “it remains unclear if coffee consumption could aggravate atrial or ventricular ectopy,” Goldberger and Hayward wrote.
They encouraged physicians to engage in shared decision-making with patients who report “symptoms in association with coffee or caffeine exposure.”
Goldberger ZD, Hayward RA. JAMA Intern Med. 2021;doi:10.1001/jamainternmed.2021.4073
Kim E-J, et al. JAMA Intern Med. 2021;doi:10.1001/jamainternmed.2021.3616.