CRAVE Trial Takes Deep Dive Into the Effects of Caffeine on Overall, Heart Health

Gregory Marcus, MD, MAS

Results of the CRAVE study are providing clinicians and providers with an overview of the apparent benefits and risks associated with consuming caffeinated coffee.

Presented at the American Heart Association (AHA) 2021 Scientific Sessions, data from the CRAVE trial, which was among the most highly anticipated studies to be presented at the conference, suggest consumption of coffee was associated with an increase in physical activity and incidence of premature ventricular contractions but a reduction in episodes of supraventricular tachycardia and sleep per night.

“Coffee is the most commonly consumed beverage in the world, yet its health effects remain uncertain,” said study author Gregory Marcus, MD, MAS, associate chief of cardiology for research and endowed professor of atrial fibrillation research at the University of California, San Francisco, in a statement. “While the majority of long-term observational studies have suggested multiple potential benefits of drinking coffee, this is the first randomized trial to investigate the real-time, physiologic consequences of coffee consumption.”

Few, if any subjects, have been discussed as extensively as the effects of coffee on overall health, but, more specifically, cardiovascular health. Despite this, almost all studies examining the topic have been observational and produced inconclusive evidence. With this in mind, the CRAVE trial was designed to assess the effects of coffee consumption on cardiac ectopy, sleep, and other factors, including serum glucose and physical activity.

Enrolling 100 patients, the trial provided participants with a continuously recording ECG, a wrist-worn Fitbit, a continuous glucose monitor, and asked to download a smartphone mobile application. For the purpose of analysis, patients were randomly assigned to consume or avoid consumption of coffee on a daily basis for a period of 14 days, which was communicated to participants through daily text messages and alerts. Adherence to the assignment was monitored through Zio patch button-presses to timestamp every Tim coffee was consumed and daily surveys assessing coffee consumption on the previous day.

Primary outcomes of interest for the trial included daily premature atrial contractions and daily premature ventricular contractions. Secondary outcomes of interest included daily counts of supraventricular tachycardia, daily counts of ventricular tachycardia, daily mean step counts, nightly mean sleep duration, and daily mean glucose. Associations between coffee consumption and outcomes of interest were assessed using logistic models with robust standard errors, negative binomial models, and linear mixed models.

The 100 patients included in the trial had a mean age of 38±13 years, the median BMI was 24 (IQR, 22-26) kg/m2, 51% were female, and more than 50% reported drinking at least 1 cup of coffee per day at baseline.

Upon analysis, results indicated compliance with randomization assignment according to every metric used to measure compliance (P <.01). Results of the intention-to-treat analyses indicated consumption of coffee was associated with a 54% (95% CI, 19-200; P=.001) increase in incidence of premature ventricular contractions, an increase of 1058 (95% CI, 441-1675; P=.001) steps per day, and a reduction in sleep of 36 (95% CI, 22-50; P <.001) minutes per day. Results of the per-protocol analysis suggested each additional cup of coffee consumed in a day was associated with a 3% (1-6; P=.006) increase in daily premature atrial contractions, 587 (95% CI, 355-820; P <.001) more steps per day, and 18 (95% CI, 13-23; P <.001) fewer minutes of sleep per night. Investigators noted no significant differences were observed when assessing glucose levels based on coffee consumptions.

“More physical activity, which appears to be prompted by coffee consumption, has numerous health benefits, such as reduced risks of Type 2 diabetes and several cancers, and is associated with greater longevity,” Marcus added in the aforementioned statement. “On the other hand, reduced sleep is associated with a variety of adverse psychiatric, neurologic and cardiovascular outcomes. More frequent abnormal heartbeats from the upper heart chambers influence risk of atrial fibrillation, and more frequent abnormal beats from the lower chambers, or ventricles, increase the risk of heart failure. These results highlight the complex relationship between coffee and health.”

This study, “The Coffee And Real-time Atrial And Ventricular Ectopy (CRAVE) Trial,” was presented at AHA 2021.