Effect of chocolate on blood pressure
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the effect of chocolate or cocoa products versus placebo on blood pressure in people with or without hypertension.
Background
Dark chocolate and flavanol‐rich cocoa products have attracted interest as an alternative treatment option for hypertension, a known risk factor for cardiovascular disease. Even small reductions in blood pressure substantially reduce cardiovascular risk. Current guidelines strongly recommend integration of lifestyle modification and complementary treatment with the use of conventional blood pressure medications.
Description of the condition
Primary hypertension: systolic blood pressure (SBP) ≥ 140 or diastolic blood pressure (DBP) ≥ 90 mm Hg.
Prehypertension: SBP 120‐139 or DBP 80‐89 mm Hg.
Normotension: SBP ≤ 120 or DBP ≤ 80 mm Hg, secondary hypertension.
Description of the intervention
Flavanol‐rich chocolate and cocoa products, compared with control (low‐flavanol products or placebo) consumed on a daily basis for two weeks or more.
How the intervention might work
Polyphenols, in particular flavanols in cocoa products, have been shown to increase the formation of endothelial nitric oxide, which promotes vasodilation and consequently may lower blood pressure.
Why it is important to do this review
Meta‐analyses by Taubert 2007 including five small trials, and Desch 2010, including 10 trials, concluded that cocoa‐rich foods may reduce blood pressure. However, additional trials have been published since, with conflicting results. This systematic review will update the current research on the effect of chocolate or cocoa on blood pressure (Ried 2010) and will explore the influence of baseline blood pressure, dosage, duration, type of control, study design, age, body mass index, and trial quality on blood pressure outcome.
Objectives
To assess the effect of chocolate or cocoa products versus placebo on blood pressure in people with or without hypertension.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled single‐blind, double‐blind and open‐label trials of ≥ 14 days duration, that provide the clinical mean or median SBP or DBP.
Types of participants
Adults, with no further restrictions.
Types of interventions
Trials will be included if the control group received a placebo or a minimal dose of flavanol‐containing cocoa product.
Minimal dose of cocoa accepted as control is defined as: products containing ≤ 10% of the dose of cocoa polyphenols in the active intervention product.
Trials in which the control dose exceeds 10% cocoa polyphenols of the active dose will be excluded.
Trials testing isolated flavanols on blood pressure will be excluded.
Types of outcome measures
Primary outcomes
Change in systolic and diastolic blood pressure from baseline compared with control.
Secondary outcomes
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Number of patients who withdraw due to adverse effects or intolerance.
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Compliance/persistence rates.
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Change in heart rate compared to control.
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Cardiovascular and cerebrovascular events such as myocardial infarction and stroke.
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Total adverse events.
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Change in absolute cardiovascular risk compared to control as defined by the Australian Cardiovascular Risk Charts (NVDPA 2009).
Search methods for identification of studies
Electronic searches
The Database of Abstracts of Reviews of Effectiveness (DARE) and the Cochrane Database of Systematic Reviews will be searched for related reviews.
The following electronic databases will be searched for primary studies:
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The Cochrane Central Register of Controlled Trials (CENTRAL)
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English language databases, including MEDLINE (1950‐) and EMBASE (1980‐)
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International trial registries (clinicaltrials.gov; www.trialregister.nl; www.anzctr.org.au; www.controlled‐trials.com) will be checked for unpublished but completed studies investigating chocolate/cocoa for blood pressure.
Electronic databases will be searched using a strategy combining the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity‐maximizing version (2008 revision) with selected MeSH terms and free text terms relating to cocoa, chocolate, blood pressure, and hypertension. No language restrictions will be used. The MEDLINE search strategy (Appendix 1) will be translated into the other databases using the appropriate controlled vocabulary as applicable.
Searching other resources
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Reference lists of all papers and relevant reviews identified
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Authors of relevant papers will be contacted regarding any further published or unpublished work
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ISI Web of Science will be searched for papers which cite studies included in the review
Data collection and analysis
Selection of studies
Two reviewers will independently assess titles and abstracts of search results for relevant articles. Two independent reviewers will critically appraise the full text of relevant articles according to the inclusion criteria listed above. Any discrepancies will be resolved by discussion and in consultation with a third reviewer.
Data extraction and management
Two reviewers will independently extract data by using a standardized data extraction form, and then cross‐check. A statistician reviewer will confirm all numeric calculations and graphic interpolations.
Assessment of risk of bias in included studies
Two reviewers will assess the risk of bias for each trial by using the Cochrane Collaboration’s tool for assessing risk of bias. If there is evidence of heterogeneity between studies, results of studies at high or unclear risk of bias will be compared with those of studies at low risk of bias by meta‐regression analysis.
Measures of treatment effect
Change of mean difference in SBP/DBP from baseline to follow‐up in mm Hg.
When blood pressure measurements are reported in more than one position, the order of preference will be: 1) sitting; 2) standing; and 3) supine.
When both clinical and ambulatory blood pressure measurements are available, the order of preference will be: 1) clinical; 2) ambulatory.
Unit of analysis issues
If results are reported for several periods of follow‐up, the longest follow‐up from each study will be selected for primary comparison to baseline.
In addition, if available, short‐term and medium‐term follow‐up will be compared in separate analyses.
Dealing with missing data
We will contact the authors of studies with missing information on n/mean SBP/DBP and/or SD in intervention and control groups and will ask them to provide the missing data.
If standard errors are given instead of standard deviations, we will calculate standard deviations at one time point with the formula SD = SE x square root n. We will assume a correlation of 0.68 for the standard deviation of the difference from baseline to follow‐up.
If both standard deviations and standard errors are missing, we will impute standard deviations based on the information in the same trial or from other trials using the same intervention. We will use the following hierarchy to impute standard deviation values:
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standard deviation of change in blood pressure taken in a different position than that of the blood pressure data used.
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standard deviation of blood pressure at the end of treatment.
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standard deviation of blood pressure at the end of treatment measured in a different position than that of the blood pressure data used.
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standard deviation of blood pressure at baseline (except if this measure is used for entry criteria).
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mean standard deviation of change in blood pressure from other trials using the same intervention.
Assessment of heterogeneity
We will assess heterogeneity by I²‐test. We will conduct meta‐regression analyses using Stata version 11 to explore reasons for high heterogeneity in the pooled meta‐analysis of all studies. If applicable, we will test the following variables: dosage of polyphenols, type of chocolate (milk, dark), source of chocolate (company), duration, type of study design, starting SBP or DBP, average body mass index (BMI), average age, geographical location of population.
Assessment of reporting biases
We will assess small study effects by Begg’s funnel plots and Egger’s regression tests.
Data synthesis
For each study, N, mean SBP/DBP, SD of intervention and control groups will be entered into Cochrane Review Manager software. We will use the random‐effects model. We will use the generic inverse variance method to combine both parallel‐group and cross‐over trials.
Subgroup analysis and investigation of heterogeneity
A minimum number of 4 studies will be required for subgroup analysis.
If meta‐regression results indicate that a variable contributes significantly to heterogeneity between studies, sensitivity analysis by this variable will be conducted.
We will perform the following subgroup analyses, if applicable:
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SBP ≥140 mm Hg at baseline
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SBP <140 mm Hg at baseline
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DBP ≥80 mm Hg at baseline
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DBP <80 mm Hg at baseline
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Double‐blind versus single‐blind trials
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Industry‐sponsored versus non‐industry‐sponsored trial
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Any variables tested in meta‐regression analysis indicating significant contribution to heterogeneity (e.g. parallel versus crossover trials)
Sensitivity analysis
We will test the robustness of the results using the following sensitivity analyses:
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Trials with control product containing ≤5% cocoa polyphenols of the product given to the active treatment group
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Exclusion of trials using a unique study design standing out compared to other trials (e.g. longer duration, active treatment with very low cocoa polyphenol content)
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Exclusion of trials with loss of follow up >20%
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Exclusion of trials with poor compliance in >20% of participants
