Coffee Consumption and Incident Tachyarrhythmias: Reported Behavior, Mendelian Randomization, and Their Interactions

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.

Figure 1.. Cumulative Incidence of Any Arrhythmia by Coffee Consumption

Kaplan-Meier curves for the cumulative incidence of any arrhythmia according to daily coffee intake after adjusting for basic demographic characteristics (age, sex, and ethnicity), body mass index, educational level, other comorbid conditions (hypertension, diabetes, hyperlipidemia, coronary heart disease, congestive heart failure, valvular heart disease, cerebrovascular disease, peripheral artery disease, chronic kidney disease, and cancer), smoking habits, alcohol consumption, tea consumption, and physical activity.

Figure 2.. Risks of Incident Arrhythmias for Each Category Increase in Daily Coffee Intake

The relative hazard of each incident arrhythmia for each increasing category of coffee consumption (0-1, 2-3, 4-5, or ≥6 cups per day) is shown. Hazard ratios (HRs) are adjusted for basic demographic characteristics (age, sex, and ethnicity), body mass index, educational level, other comorbid conditions (hypertension, diabetes, hyperlipidemia, coronary heart disease, congestive heart failure, valvular heart disease, cerebrovascular disease, peripheral artery disease, chronic kidney disease, and cancer), smoking habits, alcohol consumption, tea consumption, and physical activity. Error bars indicate 95% CIs.