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Atrial fibrillation (AF) is the most common arrhythmia, affecting over 33 million patients worldwide, and 25% of adults will develop AF over their lifetime.1 Patients with AF have higher rates of heart failure, hospitalisation, stroke and cognitive impairment as well as lower quality of life; these factors result in large direct and indirect costs to the healthcare system and society.1 The mechanisms of AF are multifactorial and not well understood, although genetic and cardiovascular risk factors are associated with AF.2–4 Because there is no cure for AF and patients are forced to manage AF as a chronic disease, prevention of AF is the optimal approach, although most AF-related studies focus on treatment instead of prevention.4
Unfortunately, there are no effective, proven therapies for the primary prevention of AF. Nearly 60% of AF can be attributed to modifiable risk factors. For example, hypertension accounts for 20% of the risk of AF.4 Lifestyle modification like weight loss and smoking cessation may contribute to AF prevention. Weight loss has been associated with lower AF burden and improved maintenance of sinus rhythm.3 Management of cardiovascular risk factors would also likely result in AF prevention. Better controlled hypertension, diabetes and cholesterol have been shown to improve arrhythmia-free survival after AF ablation,4 whereas coronary artery disease contributes to AF through myocardial fibrosis, atrial dilation, inflammation and ischaemia.1 4 Sleep apnoea is another modifiable factor that has been strongly associated with AF, although no randomised trials have demonstrated that treatment of sleep apnoea prevents AF.2–4 Ultimately, there are multiple potential approaches for the prevention of AF, which have been identified (figure 1).2–4
In this issue, Mostofsky et al 5 present the results of a retrospective analysis of chocolate consumption and risk of incident AF using the Danish Diet, Cancer, and Health Study with linkage to the Danish National Register. They analysed 55 502 patients and found 3346 cases of incident AF or atrial flutter. After adjustment, the authors found that chocolate consumption was associated with a lower incidence of AF. Relative to patients who consumed chocolate less than once per month, consuming one to three servings per month was associated with lower rates of AF (HR 0.90, 95% CI 0.82 to 0.98), and similar findings were noted for one serving per week (HR 0.83, 95% CI 0.74 to 0.91), two to six servings per week (HR 0.80, 95% CI 0.71 to 0.91), and one or more servings per day (HR 0.84, 95% CI 0.65 to 1.09).
It is exciting to think about the potential for fun public health announcements, such as ‘Eat more chocolate and prevent AF!’ or ‘A chocolate bar a day keeps the ablationist away!’ These would obviously be public service announcements that would resonate well, and patients might be more than happy to comply with this heathcare advice. However, is this message too good to be true?
As the authors noted, there have been two previously published prospective cohort studies that evaluated the association between chocolate intake and AF. The Women’s Health Study included 33 638 patients with a median age of 53 years, including 945 cases of incident AF over 14 years of follow-up. There was no statistically significant association between chocolate consumption and AF; however, with each dose of chocolate intake, there was a non-statistically significant trend towards an association between chocolate consumption and lower rates of AF (table 1).6 In another large cohort study, The Physicians’ Health Study, which included 18 819 physicians with a mean age of 66 years, including 2092 incident AF cases over 9 years of mean follow-up, there was no association between chocolate consumption and AF.7
While the study has many strengths, including long-term follow-up linked with the national health register data, there are also some notable limitations. First, there are important differences in the patients compared in the Danish study. The chocolate consumers were healthier as they had less hypertension, less diabetes and lower blood pressure. The chocolate consumers also had higher levels of education, which is often associated with improved health status. Second, the available baseline characteristics in the Danish Diet, Cancer and Health Study allowed for limited adjustment of factors known to be associated with AF, such as renal impairment and obstructive sleep apnoea. Adjustment for exercise would have also been valuable, as the study focused on lifestyle modification through diet. Moreover, although the study characterised education level, other socioeconomic factors, such as income, were not accounted for. Third, the study only identified clinically apparent AF without any AF screening, so it is difficult to determine whether chocolate is associated with a lower risk of any AF or just symptomatic/clinical AF. Finally, there is a high likelihood of residual confounding, particularly given the notable baseline differences between the groups.
Another important question is whether the results of this analysis are applicable to patients with AF outside of the study population. The Danish population is more homogeneous than many other countries, especially outside of Europe. There was no mention of race or ethnicity in the study, as the patients are predominantly, if not exclusively, white. Health behaviours such as tobacco and alcohol use, physical activity and diet vary greatly by geography, and these health behaviours likely play an important role in the development of AF.8 It is also important to note that the patients in this Danish study had a mean age of 57 years and were followed for a median of 13.5 years, yet only 6% of patients developed incident AF over the course of the study. This rate of incident AF is similar to what was seen in the Rotterdam study, but this incidence of AF was lower than was seen in a similar age group within the Framingham Study, a US-based cohort.9 The Danish study only used primary diagnoses of AF or atrial flutter, and this may have resulted in under-reporting of AF. Finally, European chocolate has a higher percentage of cocoa relative to countries such as the USA, and these differences could affect the association between chocolate consumption and AF.
Regardless of the limitations of the Danish chocolate study, the findings are interesting and warrant further consideration, especially given the importance of identifying effective prevention strategies for AF. A double-blind randomised controlled trial is needed to evaluate the true efficacy of chocolate for the prevention of AF and such a trial would need to incorporate quantified doses of cocoa. There is one ongoing study of outcomes in patients taking cocoa extract, and this is the double-blind, randomised, prospective COcoa Supplement and Multivitamin Outcomes Study trial, which is scheduled to enrol 18 000 patients (NCT02422745). The dual primary outcomes of the trial will be cardiovascular events at 5 years as well as cancer events at 5 years. Unfortunately, as currently designed, AF will not be an endpoint included in the cardiovascular events outcome.
AF is a growing public health problem that is difficult to manage. Accordingly, prevention of AF is a high-priority in cardiovascular health. To date, effective preventive therapies have been elusive if not non-existent. Therefore, studies like the Danish chocolate study are important because we need to identify additional potential targets for AF prevention. Pragmatic randomised trials that focus on the efficacy of AF prevention strategies, as well as implementation trials that address dissemination, are needed. The highest quality care for AF is to prevent it in the first place. It will be interesting to see if chocolate is an effective preventive therapy. Perhaps what is bad for the pancreas is good for the atria.
We thank Kim Best for her assistance with the illustration.
Competing interests SDP reports modest consulting support from Boston Scientific and Medtronic; modest research support from Gilead, Boston Scientific, Bristol-Myers Squibb, Pfizer and Janssen Pharmaceuticals. JPP reports grants for clinical research from ARCA biopharma, Boston Scientific, Gilead, St Jude Medical and Spectranetics, and serves as a consultant to Allergan, Amgen, GSK, Medtronic and Spectranetics.
Provenance and peer review Commissioned; internally peer reviewed.