Dark Chocolate: Sweet Prevention for CV Events
By Kristina Fiore, Staff Writer, MedPage Today|
Published: May 31, 2012
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· A "best case scenario" analysis based on a Markov model concluded that daily consumption of dark chocolate could reduce the risk of cardiovascular events over a 10-year period in patients with metabolic syndrome.
· Note that the model also predicted that this prevention approach was cost-effective assuming 100% compliance.
Dark chocolate may be an inexpensive way to help prevent cardiovascular events in patients at risk for heart disease, researchers found.
A modeling study predicts that patients with metabolic syndrome who eat dark chocolate every day could have 85 fewer events per 10,000 population over 10 years, Chris Reid, PhD, of Monash University in Melbourne, and colleagues reported online in BMJ.
At a cost of only $42 per year, treatment with dark chocolate falls into an acceptable category of cost-effectiveness, at an incremental cost-effectiveness ratio (ICER) of $50,000 per years of life saved.
"Chocolate benefits from being by and large a pleasant, and hence sustainable, treatment option," they wrote. "Evidence to date suggests that the chocolate would need to be dark and of at least 60% to 70% cocoa, or formulated to be enriched with polyphenols."
Several recent studies have suggested that eating dark chocolate has blood-pressure and lipid-lowering effects. To assess whether it could be an effective and cost-effective treatment option in patients potentially at risk for cardiovascular events, the researchers looked at data from patients in the Australian Diabetes, Obesity, and Lifestyle study.
They used a Markov model to assess health effects and associated costs of daily consumption of plain dark chocolate compared with no chocolate in a population with metabolic syndrome but without diabetes or cardiovascular disease.
The investigators also used risk-prediction algorithms and population life tables to determine the probability of patients developing or dying from heart disease or other noncardiovascular causes each year.
Data on the blood-pressure-lowering effects of dark chocolate were taken from a meta-analysis of 13 randomized controlled trials, and lipid-lowering effects from a meta-analysis of eight short-term trials.
Costs were taken from a review of the costs of cardiovascular complications in a healthy population, and included the direct costs of myocardial infarction and stroke.
They calculated the number of deaths prevented by determining the difference in the number of deaths between those consuming and not consuming dark chocolate.
The final model included a total of 2,013 patients with metabolic syndrome, mean age 53.6, mean systolic blood pressure 141.1 mmHg, mean total cholesterol 6.1 mmol/L, mean HbA1c 34.4 mmol/mol, and mean waist circumference 100.4 cm.
Reid and colleagues found that daily consumption of dark chocolate -- a polyphenol content equivalent to 100 grams of dark chocolate -- can reduce cardiovascular events by 85 per 10,000 population over 10 years.
Specifically, with 100% compliance, treatment would prevent 70 non-fatal and 15 fatal cardiovascular events per 10,000 population over that time. The authors noted that this was a "best case scenario" analysis.
When compliance was reduced to 90%, the number of preventable non-fatal and fatal events fell to 60 and 10, respectively, and at a compliance of 80%, was reduced to 55 and 10, respectively. Even at these levels, however, daily dark chocolate was still considered an effective and cost-effective intervention strategy, they wrote.
At a cost of $42 per person per year, dark chocolate prevention strategies came to an estimated ICER of $50,000 per years of life saved -- a figure well within typical cost-effectiveness thresholds, the researchers said.
That $42 could be spent on advertising, educational campaigns, or subsidization of dark chocolate in higher-risk populations, they wrote.
Reid and colleagues noted that the study was limited by its reliance on the Framingham algorithm, which may underestimate risk in a high-risk population, and by assumptions about the risk of death following a cardiovascular event.
The study was also limited by the assumption that the benefits of dark chocolate, which have only been observed in short-term trials, extend to 10 years. Still, they concluded that the findings suggest dark chocolate may be an effective and cost-effective strategy for preventing heart disease in patients with metabolic syndrome.
The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model
BMJ (Published 31 May 2012)
Objective To model the long term effectiveness and cost effectiveness of daily dark chocolate consumption in a population with metabolic syndrome at high risk of cardiovascular disease.
Design Best case scenario analysis using a Markov model.
Setting Australian Diabetes, Obesity and Lifestyle study.
Participants 2013 people with hypertension who met the criteria for metabolic syndrome, with no history of cardiovascular disease and not receiving antihypertensive therapy.
Main outcome measures Treatment effects associated with dark chocolate consumption derived from published meta-analyses were used to determine the absolute number of cardiovascular events with and without treatment. Costs associated with cardiovascular events and treatments were applied to determine the potential amount of funding required for dark chocolate therapy to be considered cost effective.
Results Daily consumption of dark chocolate (polyphenol content equivalent to 100 g of dark chocolate) can reduce cardiovascular events by 85 (95% confidence interval 60 to 105) per 10 000 population treated over 10 years. $A40 (25; 31; $42) could be cost effectively spent per person per year on prevention strategies using dark chocolate. These results assume 100% compliance and represent a best case scenario.
Conclusions The blood pressure and cholesterol lowering effects of dark chocolate consumption are beneficial in the prevention of cardiovascular events in a population with metabolic syndrome. Daily dark chocolate consumption could be an effective cardiovascular preventive strategy in this population.
Cardiovascular disease is the leading cause of death worldwide, with the death rate estimated at 17.5 million in 2004 (29% of all deaths).1 The metabolic syndrome describes a cluster of risk factors that significantly increase the risk of developing cardiovascular disease and diabetes,2 and the syndrome is becoming increasingly prevalent owing to rising rates of obesity and diabetes and an aging population. Lifestyle changes such as dietary modifications and behavioural adaptations constitute first line treatment in the prevention of diseases associated with the metabolic syndrome. Dietary modifications that increase the intake of vegetables, fruit, and grains and decrease the intake of saturated fats and refined sugars are recommended. It is believed that the high content of polyphenolic antioxidants in some fruit, vegetables, whole grains, nuts, and tea may contribute to their cardioprotective effects.3 Dark chocolate, derived from cocoa beans, is another food rich in polyphenols, specifically flavonoids. Flavonoids exhibit antihypertensive, anti-inflammatory, antithrombotic, and metabolic effects, all of which may contribute to their protective effect.4
Several recent studies have suggested that the consumption of dark chocolate may have blood pressure lowering effects.5 6 The mechanisms for these effects remain under investigation, but flavanols have been shown to stimulate the production of endothelial nitric oxide, causing blood vessels to dilate and thus lowering blood pressure.7 8 A recent meta-analysis showed that a diet high in cocoa rich products significantly reduced blood pressure in both hypertensive and prehypertensive states.9 Studies exploring the effect of dark chocolate on blood pressure thus far have been relatively short, with a maximum intervention period of 18 weeks in the studies contributing to a recent meta-analysis.10
Dark chocolate consumption has also been suggested to have lipid modifying effects, decreasing total and low density lipoprotein cholesterol levels and increasing high density lipoprotein cholesterol levels.11 However, these changes have also only been explored in short term trials, lasting 2-18 weeks. The logistical difficulties and considerable expense of long term placebo controlled clinical trials of dietary components mean it is unlikely that high level evidence linked to cardiovascular disease outcome will be obtained in the near future. We utilised available data and statistical modelling techniques to estimate the long term effects and associated cost effectiveness, from a healthcare system perspective, of dark chocolate consumption in a population with metabolic syndrome at high risk of cardiovascular disease.
Overall, 3069 participants (27.3%) from the Australian Diabetes, Obesity and Lifestyle study were classified as having metabolic syndrome according to the joint interim statement for metabolic syndrome published in 2009, and free of diagnosed cardiovascular disease or frank diabetes. Of these, 1056 (34.4%) were receiving antihypertensive therapy or had systolic blood pressures below 121 mm Hg. With these excluded, a total of 2013 (65.6%) participants were included in our model. Table 3⇓ summarises the characteristics of the modelled population. The cohort was relatively young, with a mean age of 53.6 years. Because this was a high risk population and selected for hypertension, the cohort had increased blood pressure (mean systolic blood pressure 141.1 mm Hg), cholesterol levels (mean total cholesterol 6.1 mmol/L), glucose levels (mean HbA1c 34.4 mmol/mol), and waist circumference (mean 100.4 cm).
Table 4[t4] summarises the results of the base case and probabilistic sensitivity analyses. With 100% compliance, dark chocolate consumption could potentially prevent 70 non-fatal (interquartile range 55-85) and 15 fatal (5-20) cardiovascular events per 10 000 population treated over 10 years. The estimated incremental cost effectiveness ratio was $A50 000 (31 150; 38 555; $52 500) per years of life saved when $A40 (interquartile range $A29-55; $42, $31-58) per person per year was assumed to have been spent on a prevention strategy using dark chocolate.
When compliance levels were reduced from 100% (best case) to 90%, the number of non-fatal and fatal events potentially preventable was reduced to 60 (interquartile range 50-80) and 10 (5-20) per 10 000 population treated over 10 years, respectively. When compliance levels were further reduced to 80%, the equivalent figures were 55 (40-70) and 10 (5-20). The potential monies available for prevention strategies per person for the incremental cost effectiveness ratios to be considered cost effective were estimated at $A37 (interquartile range $A26-51; $39, $27-54) when 90% of individuals complied with dark chocolate consumption and $A32 ($A22-45; $34, $23-47) when 80% complied.
Daily consumption of dark chocolate for 10 years in a population with metabolic syndrome that was free of diabetes and cardiovascular disease at baseline and classified as being prehypertensive or hypertensive, would be effective in the prevention of cardiovascular events. The blood pressure and cholesterol lowering properties associated with dark chocolate consumption could potentially prevent 70 (interquartile range 55-85) non-fatal (defined as non-fatal stroke and non-fatal myocardial infarction) cardiovascular events and 15 (5-20) cardiovascular related deaths per 10 000 population treated over 10 years. To our knowledge this is the first study to model the long term effects of dark chocolate consumption in reducing cardiovascular risk.
Assuming that $A40 ($42) is spent per person per year on a dark chocolate prevention strategy in this population, the strategy would be cost effective (based on the commonly accepted, albeit arbitrary, threshold of $50 000 per years of life saved25). The $A40 per person per year could be devoted to advertising, educational campaigns, or potentially subsidisation of dark chocolate in this high risk population.
Analyses of lower compliance levels indicated that although the number of preventable non-fatal and fatal cardiovascular events would be reduced, the incremental cost effectiveness ratios remained below accepted cost effective thresholds. Therefore, even if only 80% of individuals with metabolic syndrome were compliant with the daily consumption of dark chocolate over 10 years, it could still be considered an effective and cost effective intervention strategy.
Only non-fatal stroke and non-fatal myocardial infarction were explored in this analysis, and the potential effectiveness of dark chocolate consumption on other cardiovascular events, such as heart failure, were not assessed. It is also important to note that the cardiovascular protective effects of cocoa, and more specifically flavonoids, have only been shown for dark chocolate, rather than for milk or white chocolate. This is possibly a result of higher levels of flavonoids in dark chocolate and an inhibitory effect in the absorption of flavonoids found in the milk varieties as a result of interactions of milk proteins.26 Therefore any effects shown in this analysis pertain specifically to dark chocolate (or equivalent amounts of cocoa or polyphenol enriched chocolate).
Comparison with other studies
The effects of dark chocolate consumption on blood pressure and total cholesterol, although beneficial, are not as profound as those of drug interventions. A meta-analysis27 found that blood pressure lowering drugs can reduce systolic blood pressure by 9.1 mm Hg at a standard dose and 7.1 mm Hg at a half dose. The Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial28 estimated that statins (at a dose of 20 mg/day) could reduce total cholesterol concentrations to between 1.20 and 2.64 mmol/L. Despite the lower efficacy of dark chocolate consumption, short term clinical trials thus far have shown low (if any) adverse events and high rates of compliance. The blood pressure lowering and total cholesterol lowering effects of dark chocolate consumption provide a non-drug treatment option, either alone or in combination with therapeutic interventions.
Limitations of the study
A few limitations to our analyses warrant mention. Firstly, no algorithm for risk prediction of cardiovascular events in a population with metabolic syndrome is available. The Framingham algorithm was developed from a healthy 20th century cohort and therefore may under-predict events in a higher risk population. Other available algorithms for higher risk populations, such as those of the United Kingdom Prospective Diabetes Study (intended specifically for use in people with diabetes), may conversely over-predict risk. The Framingham algorithm was chosen for the present analyses as it was likely to represent a conservative estimate of the effects of dark chocolate consumption.
A second limitation pertained to the estimations of risk of death after a non-fatal cardiovascular event. Owing to limitations in the availability of subgroup specific data, we assumed the risks of dying from both cardiovascular and non-cardiovascular causes to be the same for all those with established cardiovascular disease. We also assumed that the risk of dying from non-cardiovascular related causes was the same for those with cardiovascular disease as without. This is of course not accurate, as risk of dying is influenced not only by the type and severity of the initial non-fatal event but also by other risk factors that may increase mortality risk. The likely consequence was an underestimation of risk of death among those with cardiovascular disease, and again reflected our erring on the side of conservatism.
We did not consider several other effects of dark chocolate. On the one hand, dark chocolate or cocoa polyphenols have been shown to generate beneficial metabolic effects (including decreased low density lipoprotein cholesterol levels,29 increased high density lipoprotein cholesterol levels,30 and increased insulin sensitivity31); improve endothelial function and cause anti-inflammatory and antithrombotic effects32 33; reduce stress34; and improve mood.35 Conversely, dark chocolate contains sugar and imposes an additional caloric and glycaemic load32 that may need to be accounted for by modification of the background diet to reduce the risk of weight gain (as usually occurs in dietary intervention studies). While in many cases this could be achieved through substitution of chocolate for other snack foods in the diet, we were not able to account for other dietary changes in the modelling analyses. However, recent studies have found that dark chocolate also increases satiety,33 potentially countering the additional caloric and carbohydrate load imposed by the dark chocolate.
A further limitation to our analyses was the assumption that the benefits of dark chocolate, observed in short term trials, extended to 10 years. This assumption is common in any long term therapy, including drug treatment. Heterogeneity among treatment effects was also noted, owing to one trial in the meta-analysis being a statistical outlier. We excluded this study in a revised meta-analysis (which improved homogeneity), and derived a systolic blood pressure reducing effect of -3.0 mm Hg (95% confidence interval -4.31 to -2.38 mm Hg). When applied to the model, the revised potential monies available for prevention was only marginally decreased, to $A32 (interquartile range $A21-43; $34, $22-45).
Finally, it is acknowledged that the present analysis assumed compliance rates with dark chocolate ranging from 80% to 100%. The studies contributing to the recent meta-analysis9 11 reported no side effects and also optimal compliance. However, one study noted that 20% of participants did not consider dark chocolate to be an acceptable long term treatment option.36
Conclusions and implications of study findings
The findings of this study suggest that the blood pressure lowering and lipid effects of plain dark chocolate could represent an effective and cost effective strategy for the prevention of cardiovascular disease in people with metabolic syndrome (and no diabetes). Chocolate benefits from being by and large a pleasant, and hence sustainable, treatment option. Evidence to date suggests that the chocolate would need to be dark and of at least 60-70% cocoa, or formulated to be enriched with polyphenols.
What is already known on this topic
· Dark chocolate has antihypertensive, anti-inflammatory, antithrombotic, and metabolic effects
· Short term trials have shown that dark chocolate consumption can potentially reduce systolic blood pressure by 5 mm Hg (interquartile range 2-8 mm Hg) and total cholesterol concentration by 0.21 mmol/L (0.05-0.36 mmol/L)
What this study adds
· A modelling analysis predicted that dark chocolate consumption in populations at high risk of cardiovascular disease could potentially avert cardiovascular events over the long term owing to its antihypertensive and metabolic effects
· The model also suggested that $A40 (25; 31; $42) could be cost effectively spent per person per year on prevention strategies using dark chocolate
· This best case analysis suggests that dark chocolate/cocoa consumption with a polyphenol content of 500-1000 mg would be an effective and cost effective primary prevention strategy for those with multiple cardiovascular disease risk factors