Objective To examine whether chocolate consumption is associated with a reduced risk of ischaemic heart disease, we used data from a prospective study of Swedish adults and we performed a meta-analysis of available prospective data.
Methods and results The Swedish prospective study included 67 640 women and men from the Cohort of Swedish Men and the Swedish Mammography Cohort who had completed a food-frequency questionnaire and were free of cardiovascular disease at baseline. Myocardial infarction (MI) cases were ascertained through linkage with the Swedish National Patient and Cause of Death Registers. PubMed and EMBASE databases were searched from inception until 4 February 2016 to identify prospective studies on chocolate consumption and risk of ischaemic heart disease.
Results The results from eligible studies were combined using a random-effects model. During follow-up (1998–2010), 4417 MI cases were ascertained in the Swedish study. Chocolate consumption was inversely associated with MI risk. Compared with non-consumers, the multivariable relative risk for those who consumed ≥3–4 servings/week of chocolate was 0.87 (95% CI 0.77 to 0.98; p for trend =0.04). Five prospective studies on chocolate consumption and ischaemic heart disease were identified. Together with the Swedish study, the meta-analysis included six studies with a total of 6851 ischaemic heart disease cases. The overall relative risk for the highest versus lowest category of chocolate consumption was 0.90 (95% CI 0.82 to 0.97), with little heterogeneity among studies (I2=24.3%).
Conclusions Chocolate consumption is associated with lower risk of MI and ischaemic heart disease.
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Mounting evidence from randomised controlled trials indicates beneficial effects of chocolate and cocoa flavanols on blood pressure, endothelial function, insulin sensitivity and lipoprotein concentrations.1–3 Furthermore, prospective studies have shown that chocolate consumption is inversely associated with stroke incidence and cardiovascular disease (CVD) mortality.4–6 Findings from prospective studies of chocolate consumption in relation to risk of ischaemic heart disease (IHD) have been less consistent.7–11 Most previous studies on chocolate consumption and IHD were based on a small number of IHD cases,8–10 assessed a narrow range of chocolate consumption7 ,10 and/or examined the association of chocolate consumption with recurrent myocardial infarction (MI) in patients with MI.8 Only one previous study has assessed the association between chocolate consumption and first event of MI specifically.9
To further clarify the association between chocolate consumption and incidence of IHD, we used data from two large prospective cohorts of Swedish men and women to investigate the association between chocolate consumption and MI incidence. We also evaluated whether the association was modified by overweight and history of diabetes, hypertension and hypercholesterolaemia. Moreover, we performed a meta-analysis by incorporating results from the current study with published prospective data on chocolate consumption and risk of MI or IHD.
We used data from two prospective population-based cohorts of men and women from three Swedish counties (Västmanland, Örebro and Uppsala): the Cohort of Swedish Men (COSM) and the Swedish Mammography Cohort (SMC). In the late autumn of 1997, 48 850 men and 39 227 women responded to a 350-item questionnaire that sought information on diet and other risk factors for chronic diseases. We omitted men and women with a missing or an erroneous personal registration number (n=297 men and n=243 women), those who died before start of follow-up (n=55 men and n=26 women), those with a history of cancer (n=2592 men and n=1811 women) or CVD (IHD, heart failure and stroke; n=5761 men and n=4319 women) and those with implausible total energy intake (ie, 3 standard deviations from the loge-transformed mean energy intake; n=441 men and n=405 women) or with missing data on chocolate consumption (n=3169 men and n=3155 women). After these exclusions, 67 640 participants (36 535 men and 31 105 women) aged 45−83 years remained for the analysis. The Regional Ethical Review Board at Karolinska Institutet in Stockholm, Sweden approved the study. Completion of the self-administered questionnaire was considered to imply informed consent.
Assessment of chocolate consumption
Information on consumption of chocolate and other foods was obtained from a self-administered 96-item food-frequency questionnaire (FFQ) completed by participants at baseline in 1997. Participants were asked to report how often on average over the past year they had consumed chocolate. The FFQ had only one question on chocolate consumption (type of chocolate was not specified). The FFQ had eight predefined frequency consumption categories (never, 1–3/month, 1–2/week, 3–4/week, 5–6/week, 1/day, 2/day and ≥3/day). Participants were categorised into four groups according to their chocolate consumption: never, 1–3/month, 1–2/week and ≥3–4/week. The five highest frequency categories were collapsed because only 8.7% of participants consumed chocolate ≥3–4 times/week. The validity and reproducibility of the FFQ have been previously published.12
Assessment of covariates
Information on education, family history of MI before 60 years of age, smoking, aspirin use, physical activity (including walking/bicycling and leisure-time exercise), body weight, height, history of diabetes, hypertension and hypercholesterolaemia, and alcohol intake was obtained by a self-administered questionnaire. Information on history of diabetes and hypertension was also obtained from the Swedish National Diabetes Register (diabetes only) and the Swedish National Patient Register. Body mass index (BMI) was calculated as weight (in kg) divided by the square of height (in metres). Pack-years of smoking history were computed by multiplying the number of packs of cigarettes smoked per day by the number of years of smoking.
Incident MI cases (including fatal cases) were ascertained by linkage of participants (using the unique personal registration number assigned to each Swedish resident) to the Swedish National Patient Register and the Swedish Cause of Death Register at the National Board of Health and Welfare. MI was classified using the International Classification of Diseases 10th Revision code I21 for acute MI. Deaths were ascertained by linkage with the Swedish Cause of Death Register.
For each participant, person-years of follow-up accrued from 1 January 1998 until the date of diagnosis of MI, date of death (from any cause) or 31 December 2010, whichever came first. Cox proportional hazards regression models were used to estimate hazard ratios (hereafter referred to as relative risks (RR)) with 95% CI of MI according to categories of chocolate consumption. The first multivariable model was stratified by baseline age (in years) and sex and included education (less than high school, high school, university), family history of MI before 60 years of age (no, yes), smoking (never; past <20 or ≥20 pack-years; current <20 or ≥20 pack-years), aspirin use (never, 1–6 tablets/week, ≥7 tablets/week or users with unknown number of tablets), walking/bicycling (almost never, <20 min/day, 20–40 min/day, 40–60 min/day, >1 h/day), exercise (<1 h/week, 1 h/week, 2–3 h/week, 4–5 h/week, >5 h/week) and intakes of total energy (kcal/day; continuous), alcohol (g/day; quintiles), processed meat (servings/week; quintiles) and fruits and vegetables (servings/day; quintiles). In a second multivariable model, we included the above covariates plus potential intermediates: BMI (kg/m2; continuous) and history and diagnosis of diabetes (no, yes), hypertension (no, yes) and hypercholesterolaemia (no, yes) at baseline. A separate category for missing was used to handle missing covariate data (missing was ≤3%, with the exception for exercise (5.5%)). Further adjustment for intake of unprocessed red meat, fish, dairy products, sweetened beverages, coffee and tea did not alter the results; therefore, these variables were not included in the multivariable model. The proportional hazards assumption was tested using Schoenfeld residuals and was found to be satisfactory.
Tests for linear trend across categories of chocolate consumption were performed by creating a variable containing the median value of chocolate consumption for each category and treating this variable as a continuous variable in the Cox model. In a sensitivity analysis, we excluded cases diagnosed during the first 3 years of follow-up. We examined whether the association between chocolate consumption and MI risk was modified by sex, high educational level (high school or university), overweight (BMI ≥25 kg/m2) and history of diabetes, hypertension and hypercholesterolaemia at baseline. The statistical significance of the potential effect modifications was tested using the likelihood ratio test, comparing models with and without interaction terms. Analyses were performed with SAS V.9.3 (SAS Institute, Cary, North Carolina, USA). All p values were 2-tailed and the significance level was set at an α of 0.05.
We performed a meta-analysis that incorporated results from the current Swedish study into findings from previous prospective studies of the association of chocolate consumption with risk of MI or IHD. Inclusion criteria were prospective study and results for chocolate intake in relation to MI/IHD incidence or mortality. We excluded letters, abstracts, systematic reviews and meta-analyses; case–control, cross-sectional, ecological and experimental studies. We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and EMBASE (http://www.embase.com) from inception until 4 February 2016, using the search terms chocolate or cocoa combined with cardiovascular disease or myocardial infarction or heart disease. No restrictions were applied. Reference lists of pertinent articles were reviewed to identify further relevant studies. From each study, we extracted the following data: the first author's last name, publication year, the name of the study, study location, sex and age of participants, years of follow-up, sample size (number of events and total number of participants), chocolate intake categories, covariates adjusted for in the multivariable model and the most fully adjusted RRs.
We combined the RRs for the highest versus lowest category of chocolate consumption. We also performed a dose–response meta-analysis using the method by Greenland and Longnecker13 and Orsini et al14 to compute the trend from the correlated log RRs across categories of chocolate consumption. Studies were included in the dose–response meta-analysis if they reported RRs for at least three categories of chocolate consumption. If results were reported in servings of chocolate, we assumed that one serving equals 30 g chocolate, which is the approximate serving size of chocolate in Swedish men.12 Study-specific RRs were combined using a random-effects model,15 which considers both within-study and between-study variation (weighting was based on the inverse of the variance). The I2 statistic16 was used to quantify heterogeneity between studies. Publication bias was assessed with Egger's test.17 We used Stata V.14.1 (StataCorp, College Station, Texas, USA) to analyse the data.
Over 13 years (mean 12.0±2.6 years, median 13 years) of follow-up, we identified 4417 incident cases of MI (3067 in men and 1350 in women), including 897 fatal cases, among the 67 640 Swedish adults. Compared with non-consumers of chocolate, men and women who consumed ≥3–4 servings/week of chocolate were more likely to have a university education but less likely to be current smokers, overweight and to have a history of diabetes, hypertension and hypercholesterolaemia (table 1). They also had higher intakes of total energy and processed meat.
Chocolate consumption was inversely associated with MI risk (table 2). In the minimally adjusted multivariable Cox model, men and women who consumed ≥3–4 servings/week of chocolate had a 20% (95% CI 10% to 30%) lower risk of MI compared with non-consumers (table 2). The association was attenuated, but remained statistically significant after further adjustment for BMI and history of diabetes, hypertension and hypercholesterolaemia at baseline; the corresponding reduction in MI risk was 13% (95% CI 2% to 23%). The association between chocolate consumption and MI risk was not modified by sex (p for interaction between chocolate consumption and sex in relation to MI =0.38). Excluding cases of MI diagnosed during the first 3 years of follow-up did not change the results, but widened the CI owing to fewer cases in the analysis (n=3551) (RR 0.87, 95% CI 0.76 to 1.00, for the highest vs lowest category).
In stratified analysis, the association between chocolate consumption and MI risk appeared to be stronger in individuals with diabetes (multivariable model 2: RR 0.69, 95% CI 0.46 to 1.05, for highest vs lowest category) than in non-diabetics (corresponding RR 0.93, 95% CI 0.82 to 1.06) (p for interaction between chocolate consumption and diabetes in relation to MI =0.002), but results for diabetics were based on a small number of individuals (n=3434) and were not statistically significant. The relation between chocolate consumption and MI was not modified by high education, overweight or history of hypertension or hypercholesterolaemia (p for interaction between chocolate intake and the potential effect modifier in relation to MI risk >0.25 for all).
Our literature search identified five prospective studies investigating the association between chocolate consumption and risk of IHD (see online supplementary eFigure 1). Together with the Swedish study, six studies from five different countries (two from Sweden and one each from Germany, the UK, the USA and Australia) with a total of 6851 IHD cases ascertained among 144 823 adults were included in the meta-analysis (table 3). Only two studies defined type of chocolate consumption.9 ,11 In the Postdam arm of the European Prospective Investigation into Cancer (EPIC) study, chocolate consumption included chocolate bars.9 In the EPIC-Norfolk cohort, chocolate consumption included plain chocolate, chocolate snack bars and cocoa powder (for cocoa drinks).11 When results from all six studies were combined, the overall RR for the highest versus lowest category of chocolate consumption was 0.90 (95% CI 0.82 to 0.97), with little between-study heterogeneity (I2=24.3%) (figure 1). Excluding the Swedish study did not alter the results appreciably, although the CI was somewhat widened (RR, 0.89; 95% CI 0.79 to 1.01). We found no statistically significant publication bias (p=0.12).
The current Swedish study and three other studies8 ,9 ,11 reported results for three or more categories of chocolate consumption and were included in the dose–response meta-analysis. The overall RR per 50 g/week increment of chocolate consumption was 0.95 (95% CI 0.92 to 0.98), without heterogeneity among studies (I2=0%) (see online supplementary eFigures 2 and 3).
In this large prospective study of Swedish adults, high chocolate consumption was associated with a significant 13% reduced risk of MI. In a complementary meta-analysis, including the Swedish study and five published prospective studies, we observed that a high consumption of chocolate was associated with a significant 10% lower risk of IHD.
Although several studies have examined the association between chocolate consumption and risk of total IHD incidence or mortality,7 ,10 ,11 only one previous study has assessed the relation between chocolate consumption and risk of MI in a population without previous MI.9 That study included 166 MI cases and found a statistically non-significant 27% lower risk of MI when comparing the highest with the lowest quartile of chocolate consumption.9 The present study of Swedish adults is the largest study to date on chocolate consumption and risk of MI or IHD. Because of the large number of MI cases, we had high statistical power to detect an association.
A beneficial effect of chocolate consumption on risk of MI/IHD is biologically plausible. Findings from a meta-analysis of several short-term randomised controlled trials showed that interventions with chocolate or cocoa significantly improved insulin sensitivity and endothelial function as well as reduced fasting insulin concentration, diastolic blood pressure and mean arterial pressure.1 Chocolate or cocoa flavanol intake was also found to increase high-density lipoprotein cholesterol and to decrease low-density lipoprotein cholesterol and triglycerides.1 A randomised trial conducted in 90 individuals showed that those who were allocated to daily consume a drink high in cocoa flavanols for 8 weeks had statistically significant improvements in insulin sensitivity, blood pressure and lipid profile as well as reduced lipid peroxidation and plasma glucose and insulin concentrations compared with the control group who consumed a drink low in flavanols.2 Another recent randomised controlled trial showed that a high cocoa flavanol intake, compared with control, increased flow-mediated vasodilation by 1.2%, decreased systolic and diastolic blood pressure by respectively 4.4 and 3.9 mmHg, decreased pulse wave velocity by 0.4 m/s and improved blood lipid concentrations.3 Not all trials, however, have found significant effects of cocoa flavanols on blood pressure.18
Major strengths of the current study of Swedish adults are the large sample size, the large number of incident MI cases, the possibility to adjust for major potential confounders and the objective data on MI diagnoses obtained through linkage with Swedish registries. A limitation is that chocolate consumption was assessed with only one question in the FFQ and the lack of information on type of chocolate (eg, plain chocolate or chocolate bars). Moreover, we could not distinguish between dark chocolate and milk chocolate. An inverse association between chocolate consumption and MI is assumed to be stronger for dark chocolate, which has higher cocoa content than milk chocolate. Swedish milk chocolate normally contains at least 30% cocoa solids.8 Although we had no information on the proportion of dark versus milk chocolate intake in the whole study population, in a subsample of participants who had completed an extensive FFQ in 2010, 54% of participants reported that they consumed more dark chocolate than milk chocolate (unpublished data). Another limitation is that chocolate intake was self-reported and measured at baseline only, which may have resulted in some misclassification of long-term chocolate intake. In a reproducibility study conducted in subsample of women from the study cohort, the reliability of chocolate consumption assessed by two FFQs administered 1 year apart was found to be relatively high (correlation coefficient for the unadjusted data was 0.65; unpublished data). Because the study population comprised middle-aged and older Caucasian men and women, our findings may not be generalisable to younger individuals and other ethnic groups. Finally, as in any observational study, we cannot rule out the possibility of residual confounding.
In summary, results from this Swedish prospective study and a complementary meta-analysis indicate that chocolate consumption is inversely associated with risk of MI and IHD. Although chocolate consumption may lower the IHD risk, chocolate should be consumed in moderation because it is high in sugar, calories and saturated fat.
What is already known on this subject?
Available evidence indicates beneficial effects of chocolate and cocoa flavanols on cardiovascular health. Furthermore, prospective studies have reported an inverse association between chocolate consumption and stroke incidence and cardiovascular disease mortality.
What might this study add?
In this prospective study of 67 640 Swedish adults, chocolate consumption was significantly inversely associated with risk of myocardial infarction. In a complementary meta-analysis, high consumption of chocolate was associated with a 10% lower risk of ischaemic heart disease.
How might this impact on clinical practice?
Chocolate consumption in moderation might lower the risk of ischaemic heart disease.
Contributors SCL analysed the data, conducted the literature review and wrote the manuscript. AW participated in the data collection. SCL, AÅ, BG and AW interpreted the data and critically reviewed the paper. All authors read and approved the final manuscript.
Funding This work was supported by the Swedish Research Council and by a Young Scholars Award grant from the Strategic Research Area in Epidemiology at Karolinska Institutet.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Regional Ethical Review Board at Karolinska Institutet, Stockholm, Sweden.
Provenance and peer review Not commissioned; externally peer reviewed.