Chocolate for Primary Prevention of Atrial Fibrillation
December 1, 2018
Dr. Vetrici is Clinical Teaching Fellow, Department of Clinical Medicine, Ross University School of Medicine, Commonwealth of Dominica, West Indies. Dr. Selfridge is Professor and Chair, Department of Clinical Medicine, Ross University School of Medicine, Commonwealth of Dominica, West Indies.
Dr. Vetrici and Dr. Selfridge report no financial relationships relevant to this field of study.
Summary Points
- Chocolate consumption on a weekly basis was associated with a significantly reduced risk of atrial fibrillation (AF) in a cohort study of Danish men and women 50-64 years of age who were followed for 13.5 years.
- The highest inverse association was seen at two to six servings per week for men and one serving per week for women.
- The cocoa content of chocolate appears to be important. The authors recommended chocolate that has a high proportion of cocoa solids (at least 30%), correlating with higher levels of cocoa flavonoids.
SYNOPSIS: In a large, population-based, prospective cohort study of Danish people aged 50-64 years, researchers found that chocolate intake was inversely related to incidental rates of atrial fibrillation and atrial flutter.
SOURCE: Mostofsky E, Berg Johansen M, Tjønneland A, et al. Chocolate intake and risk of clinically apparent atrial fibrillation: The Danish diet, cancer, and health study. Heart 2017;103:1163-1167.
The most common sustained arrhythmia, atrial fibrillation (AF) is associated with significant morbidity and mortality because of an increased risk of thromboembolism, stroke, heart failure, and cognitive impairment. The U.S. prevalence is 2% in people younger than 65 years of age and 9% in those older than 65 years of age, with people of European descent having higher incidence rates than African Americans.1,2 In people of European descent older than 40 years of age, the lifetime risk of developing AF is 26% in men and 23% in women, and the incidence doubles with every decade of life.1,2 The pathophysiology of AF involves a complex inflammatory cascade that generates cytokines and reactive oxygen species, leading to electrical and structural remodeling ultimately resulting in AF.3,4
Cocoa-containing foods show antioxidant, anti-inflammatory, and vasodilatory properties.5 Ingestion of cocoa flavonoids lowers blood pressure, increases high-density lipoprotein cholesterol, and improves endothelial function.5,6 Moderate chocolate consumption is associated with improved markers of cardiovascular health and lower rates of myocardial infarction and heart failure.5,6 The neuroprotective and neuromodulatory effects of cocoa flavonoids have been shown to protect human cognition and prevent cognitive decline.7
Mostofsky et al set out to determine whether there was an association between chocolate intake and incidental, clinically apparent AF by analyzing data from the Danish Diet, Cancer and Health Study. The authors of this prospective, population-based, cohort study recruited participants from December 1993 to May 1997, and followed them until December 2009. Information about diet and lifestyle was obtained via self-administered questionnaires, including a validated food frequency questionnaire collected at enrollment. Although the questionnaire did not differentiate between milk chocolate and dark chocolate, the authors reported that most of the chocolate consumed in Denmark is milk chocolate, which contains at least 30% cocoa solids as regulated by directive of the European Union.
The cohort subjects were linked to the Danish National Patient Register to identify primary discharge diagnosis for AF or atrial flutter (AFL) from the time of enrollment until December 2009. Participants were excluded for missing chocolate intake, missing inclusion date, multiple confounders, previous record of AF, and history of cancer at baseline. The final sample comprised 55,502 men and women who enrolled between the ages of 50-64 years and were followed for a median of 13.5 years. Participants were considered at risk from the date of the questionnaire until the first hospital admission for AF, death, emigration, or end of follow-up. During follow-up, there were 3,346 cases of incidental AF, which the authors defined as the total occurrences of AF and AFL combined.
Chocolate intake was modeled consistently with other studies using servings of one-ounce bars or packets of chocolate at < 1 serving/month, 1-3 servings/month, 1 serving/week, 2-6 servings/week, and ≥ 1 serving/day. In each chocolate intake group, the proportion of men was 46.3-48.7% and the mean body mass index (BMI) was 25.1-26.4 kg/m2. In each group, fewer than 20% had hypertension (HTN), fewer than 5.4% had type 2 diabetes (DM), fewer than 2% had cardiovascular disease (CVD), and all groups had similar proportions of current smokers (36%), former smokers (29%), and never smokers. About 50% of subjects in each group had total serum cholesterol > 232 mg/dL (> 6 mmol/L).
Multivariate Cox proportional hazard models were constructed to calculate hazard ratios (HR) and confidence intervals (CI). The authors adjusted for potentially confounding variables associated with AF, including sex, BMI, systolic blood pressure, total serum cholesterol, total calories, coffee consumption, alcohol consumption, smoking status, education beyond elementary school, as well as regularly updated information on HTN, DM, and CVD. Another multivariate model was constructed and adjusted for caffeine intake from other sources, such as tea, coffee, and soft drinks, but the results were almost identical to coffee consumption alone.
The authors noted that subjects with higher levels of chocolate intake also reported higher daily caloric intake, a higher proportion of daily calories from chocolate, and higher levels of educational attainment. The study results showed that the rate of AF was highest in the group consuming the least amount of chocolate. Relative to less than one serving of chocolate per month, the AF rate was lower in those consuming 1-3 servings/month (HR, 0.90; 95% CI, 0.82-0.98), 1 serving/week (HR, 0.83; 95% CI, 0.74-0.92), 2-6 servings/week (HR, 0.80; 95% CI, 0.71-0.91), and ≥ 1 serving/
day (HR, 0.84; 95% CI, 0.65-1.09). Men had higher incidence rates at each level compared to women, but a lower risk of AF was observed at higher levels of chocolate consumption in both men and women. For women, the strongest inverse association was noted at 1 serving/week (HR, 0.79; 95% CI, 0.66-0.95); in men, the strongest inverse association occurred at 2-6 servings/week (HR, 0.77; 95% CI, 0.67-0.90).
COMMENTARY
This study highlights a potentially new lifestyle modification that may prevent AF and could be easy to follow. Although counterintuitive based on the known cardiovascular stimulant effects of caffeine, data analyses of multiple studies show that modest caffeine intake through coffee and tea is related to AF risk inversely.8 Thus, the small amount of caffeine in chocolate might have a similar association.8 In the United States, AF treatment costs $6 billion annually, while patients with AF spend $8,705 more per year on medical costs than those without AF.1 Currently, 6 million Americans have AF, and this number is projected to increase to 12 million by 2050.9 There are no cures and no proven strategies for primary prevention of AF, but modifiable risk factors account for 60% of AF incidence.10,11 Prevention is considered the highest quality intervention for AF,11 and lifestyle modifications in the form of weight loss, smoking cessation, and control of DM, cholesterol, and HTN have been identified as possible targets.10,11
With documented cardiovascular, cardioprotective, neuroprotective, cognitive, and anti-inflammatory benefits, chocolate is a possible target for primary prevention of AF. However, not all chocolate is created equal. In the European Union, milk chocolate contains a minimum of 30% cocoa solids and dark chocolate contains a minimum of 43%, but the respective values in America are only 10% and 35%. Even though the participants in the Danish study consumed mostly milk chocolate, it contained a significantly higher dose of cocoa flavonoids than American chocolate. Cocoa flavonoids are responsible for the benefits of chocolate and excess milk or sugar may reduce bioavailability and efficacy.5,12
This prospective cohort study showed that subjects who consumed chocolate on a weekly basis had the lowest risk of incidental AF, with the lowest HR for men at 2-6 servings per week and the lowest HR for women at 1 serving/week. The data presented in the original article appear to show a nonlinear, U-shaped dose response between chocolate intake and HRs, suggesting that there is an ideal dose for different individuals and that the effect disappears at extreme doses. The fact that a small amount of chocolate intake (1 ounce per week in women) had an effect is not atypical of the health impact of many dietary substances. Thus, it appears a little bit of good quality chocolate can go a long way.
The strengths of this study were the large sample size, detailed data on diet, and factors potentially related to AF, multivariate analysis, and almost complete follow-up. These patients were considered to be relatively healthy when compared to patients in similar studies that did not find significant associations, suggesting that results may not be generalizable to all patients.13,14,15 Indeed, the Danish population is white and very homogeneous compared to other European nations, and this cohort was healthier than others. Perhaps this reduced complexities and confounders associated with comorbidities and enabled the authors to detect a small effect due to chocolate.
The researchers acknowledged that they did not have information on silent AF, elective direct current cardioversions or AF reported in outpatient clinics, or emergency department visits and that the incidence of AF may have been underestimated. This study is weakened by the lack of adjustment for socioeconomic status, exercise, renal disease, and sleep apnea. Lower socioeconomic status in the United States is associated with reduced access to healthcare, higher morbidities, and poorer food choices, but perhaps this is not the case in Denmark. Renal disease and sleep apnea are associated with AF, and this may have affected the confidence intervals of the results if included in the multivariate analysis.
The sharpest criticism of this study is that chocolate consumers were healthier at baseline and had higher education levels, which may be associated with improved health habits and health status. Another counterintuitive consideration is the higher calorie intake of those participants who also consumed more chocolate than others. In the Danish study, the number of daily calories and the proportion of calories from chocolate increased with higher amounts of chocolate intake, but the BMI actually trended lower with more chocolate consumption. This effect also was observed in both Swedish cohorts,16 where subjects reporting higher intake of calories and chocolate showed incremental reductions in BMI and incremental increases in educational attainment.
Regular chocolate consumption appears to protect adults, men more than women, with few comorbidities, although appropriate dosing would have to be determined on an individual basis or via an intervention trial. Integration of chocolate into diets reasonably can start in older youths for whom high-quality chocolate with significant flavonoid content may be a better choice than a doughnut. Not only can chocolate potentially reduce the incidence of AF, but chocolate consumption is associated with reductions in other comorbidities associated with AF and aging, such as cognitive decline and heart failure. For these reasons, chocolate may be a positive addition to healthy lifestyle both as preventive and modulatory therapy of AF. While awaiting an interventional trial, we can tell patients who like chocolate that snacking on small amounts may be beneficial.
REFERENCES
- January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol 2014;64:2246-2280.
- Piccini JP, Hammill BG, Sinner MF, et al. Incidence and prevalence of atrial fibrillation and associated mortality among Medicare beneficiaries. Circ Cardiovasc Qual Outcomes 2012;5:85-93.
- Friedrichs K, Klinke A, Baldus S. Inflammatory pathways underlying atrial fibrillation. Trends Mol Med 2011;17:556-563.
- Hu YF, Chen YJ, Lin YJ, et al. Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol 2015;12:230-243.
- Gu Y, Lambert JD. Modulation of metabolic syndrome-related inflammation by cocoa. Mol Nutr Food Res 2013;57:948-961.
- Goya L, Martín MÁ, Sarriá B, et al. Effect of cocoa and its flavonoids on biomarkers of inflammation: Studies of cell culture, animals and humans. Nutrients 2016;8:212.
- Socci V, Tempesta D, Desideri G, et al. Enhancing human cognition with cocoa flavonoids. Front Nutr 2017;4:19.
- Voskoboinik A, Kalman J, Kistler P. Caffeine and arrhythmias: Time to grind the data. Clin Electrophysiol 2018;4:425-432.
- Morillo CA, Banerjee A, Perel P, et al. Atrial fibrillation: The current epidemic. J Geriatr Cardiol 2017;14:195-203.
- Pokorney SD, Piccini JP. Chocolate and prevention of atrial fibrillation: What is bad for the pancreas might be good for the atria? Heart 2017;103:1141-1142.
- Otto CM. Heartbeat: Chocolate and atrial fibrillation. Heart 2017;103:1139-1140.
- Mellor DD, Amund D, Georgousopoulou E, et al. Sweet synergy or bitter antagonisms. Formulating cocoa and chocolate products for health: A narrative review. Int J Food Sci Technol 2017;1:33-42.
- Khawaja O, Petrone AB, Kanjwal Y, et al. Chocolate consumption and risk of atrial fibrillation (from the Physicians’ Health Study). Am J Cardiol 2015;116:563-566.
- Conen D, Chiuve SE, Everett BM, et al. Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr 2010;92:509-514.
- Larsson SC, Drca N, Jensen-Urstad M, et al. Chocolate consumption and risk of atrial fibrillation: Two cohort studies and a meta-analysis. Am Heart J 2018;195:86-90.
- Petrone AB, Gaziano JM, Djoussé L. Chocolate consumption and risk of heart failure in the Physicians’ Health Study. Eur J Heart Fail 2014;16:1372-1376.
In a large, population-based, prospective cohort study of Danish people aged 50-64 years, researchers found that chocolate intake was inversely related to incidental rates of atrial fibrillation and atrial flutter.
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