Chocolate consumption has been shown to protect against various cardiovascular end points; however, little is known about the association between chocolate consumption and incident atrial fibrillation (AF). Therefore, we prospectively examined the association between chocolate consumption and incident AF in a cohort of 18,819 US male physicians. Chocolate consumption was ascertained from 1999 to 2002 through a self-administered food frequency questionnaire. Incident AF was ascertained through yearly follow-up questionnaires. Cox regression was used to estimate relative risks of AF. The average age at baseline was 66 years (±9.1). During a mean follow-up of 9.0 years (±3.0), 2,092 cases of AF occurred. Using <1 per month of chocolate consumption as the reference group, multivariable adjusted hazard ratios (95% confidence interval) for AF were 1.04 (0.93 to 1.18), 1.10 (0.96 to 1.25), 1.14 (0.99 to 1.31), and 1.05 (0.89 to 1.25) for chocolate intake of 1 to 3 per month and 1, 2 to 4, and ≥5 per week (p for trend 0.25), respectively. In a secondary analysis, there was no evidence of effect modification by adiposity (p interaction = 0.71) or age (p interaction = 0.26). In conclusion, our data did not support an association between chocolate consumption and risk of AF in US male physicians.
Atrial fibrillation (AF) is an extremely common cardiac arrhythmia in clinical practice. Approximately 2.2 million subjects in the United States and 4.5 million subjects across Europe are diagnosed with AF. The annual incidence of AF increases from <0.1% in those <40 years to 1.5% in women and 2% in men >80 years. The prevalence of AF increases with advancing age (approaching 8% in those >80 years ). Although AF can be associated with structural heart disease, a large proportion of AF occurs in the absence of known cardiac disease. Data from previous studies have demonstrated beneficial effects of light-to-moderate physical activity on AF risk. In contrast, there is a positive relation between obesity, inflammation, heavy alcohol consumption, hypertension, type 2 diabetes mellitus (T2DM), and dyslipidemia with AF. There is evidence for a beneficial effect of certain foods, such as olive oil, nuts, fish, fruits, vegetables, fiber, and whole grains on cardiovascular health. Recent studies have shown beneficial effects of chocolate consumption on several risk factors for AF including hypertension, T2DM, coronary heart disease (CHD), and heart failure. However, the association between chocolate consumption and incident AF has not been investigated in a prospective cohort study. Therefore, the present study sought to prospectively assess the association of chocolate consumption with incident AF in US male physicians.
Methods
The Physicians’ Health Study (PHS) I is a completed, randomized, double-blind, placebo-controlled trial, designed to study the effects of low-dose aspirin and beta-carotene on cardiovascular disease and cancer in US male physicians. In 1997, PHS II trial enrolled 7,641 physicians from PHS I along with 7,000 newly recruited physicians to study the effects of vitamins on cardiovascular disease and cancer. A detailed description of the PHS I and II has been published. Of the 29,071 total participants in the PHS, 21,075 completed a food frequency questionnaire (FFQ) from 1999 to 2002. We excluded subjects with prevalent AF (n = 1,962) and missing data on chocolate consumption (n = 294). Thus, a final sample of 18,819 participants was used for current analyses. Each participant gave written informed consent, and the Institutional Review Board at the Brigham and Women’s Hospital approved the study protocol.
Information on chocolate consumption was obtained using an FFQ. Participants were asked to report average consumption of 1 oz (∼28.4 g) of chocolate during the past year. Possible responses were never or <1 per month, 1 to 3 per month, 1 per week, 2 to 4 per week, 5 to 6 per week, 1 per day, 2 to 3 per day, 4 to 5 per day, and 6+ per day. The validity and reproducibility of FFQs have been previously published.
Incident AF was ascertained through follow-up questionnaires. In PHS, self-reported AF has been previously validated in a random sample of 400 PHS participants, using a more detailed questionnaire on the diagnosis of AF and the review of medical records by cardiologists.
Data on demographics, anthropometrics, smoking, alcohol, exercise frequency, energy intake, along with history of hypertension, T2DM, and CHD were obtained at baseline. For alcohol consumption, subjects were asked the following question: “How often do you usually consume alcoholic beverages?” Possible responses were rarely/never, 1 to 3 times per month, 1 time per week, 2 to 4 times per week, 5 to 6 times per week, daily, and ≥2 times per day. Hypertension was defined as anyone who self-reported a diagnosis of hypertension, blood pressure >140/90 mm Hg, or use of antihypertensive drugs. CHD diagnosis (angina, myocardial infarction, and coronary artery bypass grafting) was validated by the PHS Endpoint Committee. T2DM diagnosis was self-reported and validated by detailed review of the medical records in a subsample.
We classified each subject into one of the following categories of chocolate consumption: <1 per month, 1 to 3 per month, 1 per week, 2 to 4 per week, and ≥5 per week. We computed person-time of follow-up from the time when chocolate consumption was assessed until the first occurrence of (1) AF, (2) death, or (3) the date of last available follow-up. Baseline demographic variables were recorded and compared across the categories of chocolate consumption.
We used Cox proportional hazard models to compute multivariable adjusted hazard ratios with corresponding 95% confidence intervals using participants reporting <1 per month chocolate consumption as the reference group. Potential confounding was assessed for established risk factors of AF. First, we adjusted for age (≤55, >55 to ≤65, >65 to ≤75, and >75 years) in model 1. Second, we additionally controlled for body mass index (continuous), smoking status (never, past, and current smokers), alcohol consumption (never, monthly, weekly, and daily), exercise frequency (rarely/never, 1 to 2 days/week, 3 to 4 days/week, and 5 to 7 days/week), and energy intake (quintiles) in model 2. Finally, in model 3, we adjusted for factors included in model 2 and potential mediators, such as history of hypertension, T2DM, and CHD.
In secondary analysis, we evaluated whether there were statistically significant interactions between chocolate consumption and body mass index or age using a product term of both variables in a hierarchical model. Assumptions for proportional hazard models were tested (by including main effects and product terms of chocolate consumption and logarithmic-transformed person-time of follow-up) and were met (all p values >0.05). All analyses were conducted using SAS, version 9.3 (SAS Institute, Cary, North Carolina). Significance level was set at 0.05.
Results
Table 1 lists baseline characteristics according to chocolate consumption. Mean age of the study participants at baseline was 66.0 ± 9.1 years. Compared with chocolate consumption of <1 per month, higher chocolate consumption was associated with a higher energy intake, higher proportion of being white or never smoker, and a lower proportion of daily alcohol consumption, exercising frequency <1 per week, T2DM, hypertension, CHD, and higher energy intake.
| Variables | Chocolate Consumption | ||||
|---|---|---|---|---|---|
| <1/month (n=4930) | 1-3/month (n=5513) | 1/week (n=3655) | 2-4/week (n=2993) | ≥5/week (n=1728) | |
| Age (years) | 67 ± 9 | 66 ± 9 | 66 ± 9 | 66 ± 10 | 66 ± 10 |
| Body mass index (kg/m 2 ) | 26 ± 3 | 26 ± 3 | 26 ± 3 | 26 ± 3 | 26 ± 3 |
| White | 85 % | 91 % | 94 % | 95 % | 96 % |
| Smoker | |||||
| Never | 51 % | 54 % | 57 % | 58 % | 57 % |
| Past | 45 % | 42 % | 40 % | 38 % | 39 % |
| Current | 4 % | 3 % | 3 % | 3 % | 4 % |
| Exercise (days a week) | |||||
| <1 | 38 % | 38 % | 36 %) | 37 % | 37 % |
| 1-2 | 15 % | 17 % | 17 % | 16 % | 15 % |
| 3-4 | 28 % | 29 % | 30 % | 31 % | 30 % |
| 5-7 | 17 % | 15 % | 15 % | 14 % | 16 % |
| Alcohol Consumption | |||||
| Never | 17 % | 15 % | 17 % | 19 % | 20 % |
| Monthly | 7 % | 7 % | 8 % | 9 % | 9 % |
| Weekly | 36 % | 39 % | 40 % | 40 % | 39 % |
| Daily | 39 % | 37 % | 35 % | 32 % | 32 % |
| Prevalent hypertension | 49 % | 45 % | 44 % | 41 % | 43 % |
| Prevalent diabetes mellitus | 12 % | 7 % | 5 % | 5 % | 5 % |
| Prevalent coronary heart disease | 14 % | 12 % | 10 % | 10 % | 11 % |
| Prevalent heart failure | 1 % | 1 % | 1 % | 1 % | 2 % |
| Calories (kcal) | 1534 ± 484 | 1622 ± 481 | 1703 ± 497 | 1792 ± 512 | 2040 ± 588 |
During a mean follow-up of 9.0 years (±3.0), 2,092 cases of AF occurred. Using <1 per month chocolate consumption as the reference group, multivariable adjusted hazard ratios (95% confidence intervals) for AF were 1.04 (0.93 to 1.18), 1.10 (0.96 to 1.25), 1.14 (0.99 to 1.31), and 1.05 (0.89 to 1.25) for subjects reporting an average chocolate consumption of 1 to 3 per month, 1 per week, 2 to 4 per week, and ≥5 per week (p for trend 0.25), respectively ( Table 2 ).
| Chocolate Consumption | Cases/n | Crude Incidence Rate (per 1000 person-years) | Hazards Ratio (95% Confidence Interval) | |||
|---|---|---|---|---|---|---|
| Unadjusted | Model 1 | Model 2 | Model 3 | |||
| <1/month | 522/4930 | 11.92 | 1.0 | 1.0 | 1.0 | 1.0 |
| 1-3/month | 613/5513 | 12.22 | 1.02 (0.91-1.15) | 1.06 (0.95-1.20) | 1.04 (0.92-1.17) | 1.04 (0.93-1.18) |
| 1/week | 417/3655 | 12.54 | 1.05 (0.92-1.20) | 1.09 (0.96-1.24) | 1.07 (0.94-1.22) | 1.10 (0.96-1.25) |
| 2-4/week | 352/2993 | 12.85 | 1.08 (0.94-1.23) | 1.12 (0.98-1.28) | 1.10 (0.96-1.26) | 1.14 (0.99-1.31) |
| ≥5/week | 188/1728 | 12.23 | 1.02 (0.87-1.21) | 1.03 (0.88-1.22) | 1.03 (0.87-1.22) | 1.05 (0.89-1.25) |
| p for linear trend | 0.45 | 0.33 | 0.38 | 0.25 | ||
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