Dark Chocolate May Help Control Elevated Blood Pressure CME

News Author: Laurie Barclay, MD CME Author: Laurie Barclay, MD July 1, 2010 Dark chocolate may help control elevated blood pressure (BP), according to the results of a meta-analysis reported in the June 28 issue of BMC Medicine. "Flavanols have been shown to increase the formation of endothelial nitric oxide, which promotes vasodilation and consequently may lower blood pressure," said lead author Karin Ried, from the University of Adelaide, Adelaide, Australia, in a news release. "There have, however, been conflicting results as to the real-life effects of eating chocolate. We've found that consumption can significantly, albeit modestly, reduce blood pressure for people with high blood pressure but not for people with normal blood pressure." The goal of this meta-analysis was to review recent evidence on the effect of flavanol-rich cocoa products on BP in individuals with hypertension and in those with BP within the normotensive range. To identify randomized controlled trials of the effect of cocoa vs placebo on systolic and diastolic BP (SBP/DBP), the investigators searched MEDLINE, Cochrane, and international trial registries from 1955 to 2009. Minimal duration of included trials was 2 weeks. For all studies meeting the inclusion criteria, the investigators performed random-effects metaanalysis. In addition, they performed subgroup analysis according to baseline BP being in the hypertensive or normotensive range. The relationship between type of treatment, dosage, duration, or baseline BP and BP outcome was examined with meta-regression analysis. Selection criteria were met by 15 trial groups of 13 evaluated studies. Compared with placebo, cocoa-chocolate significantly lowered BP, according to a pooled meta-analysis of all trials, which showed a mean change in SBP of 3.2 1.9 mm Hg (P = .001) and DBP of 2.0 1.3 mm Hg (P = .003). On the basis of subgroup meta-analysis, however, cocoa-chocolate had a significant effect vs placebo only in the hypertensive or prehypertensive subgroups (SBP: 5.0 3.0 mm Hg; P = .0009; DBP: 2.7 2.2 mm Hg; P = .01). In the normotensive subgroups, BP was not significantly decreased for cocoa-chocolate vs placebo (SBP: 1.6 2.3 mm Hg; P = .17; DBP: 1.3 1.6 mm Hg; P = .12). "The practicability of chocolate or cocoa drinks as long-term treatment is questionable," Dr. Ried said. Study design and type of control used were borderline significant, but possibly indirect, predictors for BP outcome, according to results of meta-regression analysis. Limitations of this meta-analysis include high heterogeneity in the hypertensive subgroups. Effect sizes and levels of significance of the subgroup meta-analyses of trials with subjects with (pre-)hypertension at baseline should therefore be interpreted more cautiously. "Our meta-analysis suggests that dark chocolate is superior to placebo in reducing systolic hypertension or diastolic prehypertension," the study authors write. "Flavanol-rich chocolate did not significantly reduce mean blood pressure below 140 mmHg systolic or 80 mmHg diastolic." This study was supported by the Royal Australian College of General Practitioners (RACGP) 2006 Cardiovascular Health Research Grant, and the Australian Government Primary Health Care Research Evaluation Development (PHCRED) Program. The study authors have disclosed no

relevant financial relationships. BMC Medicine. Published online June 28, 2010. Abstract

Clinical Context
Hypertension is a well-known and significant risk factor for cardiovascular disease. Flavanols in dark chocolate increase endothelial nitric oxide formation, which promotes vasodilation and lowers BP. As an alternative treatment of hypertension, dark chocolate and flavanol-rich cocoa products have been studied in several controlled trials. Although previous meta-analyses suggested that cocoa-rich foods may lower BP, several recent trials have shown conflicting findings.

Study Highlights
This meta-analysis aimed to summarize recent findings on the effect of flavanol-rich cocoa products on BP in subjects with hypertension and those with BP within the normal range. The investigators searched MEDLINE, Cochrane, and international trial registries from 1955 to 2009. Selection criteria were randomized controlled trials of cocoa vs placebo on SBP and DBP, with duration of at least 2 weeks. The researchers performed random-effects meta-analysis for all randomized controlled trials meeting selection criteria. Subgroups based on hypertensive or normotensive BP at baseline were also analyzed. Meta-regression analysis evaluated the association between treatment type, dosage, duration, or baseline BP with BP outcome. 15 trial groups of 13 evaluated studies met selection criteria. Of the 15 trial groups, 9 compared chocolate containing 50% to 70% cocoa vs white chocolate or other cocoa-free controls, and 6 trial groups compared high-flavanol vs lowflavanol cocoa products. In the active treatment groups, daily flavanol dosages ranged from 30 to 1000 mg. Duration of the interventions was 2 to 18 weeks. In a pooled meta-analysis of all included randomized controlled trials, cocoa-chocolate vs placebo significantly lowered BP. In the meta-analysis of all included randomized controlled trials, mean change in SBP was 3.2 1.9 mm Hg (P = .001), and mean change in DBP was 2.0 1.3 mm Hg (P = .003). In subgroup meta-analysis, cocoa-chocolate vs placebo had a significant effect only in the hypertensive or prehypertensive subgroups (SBP: 5.0 3.0 mm Hg; P = .0009; DBP: 2.7 2.2 mm Hg; P = .01). For individuals with hypertension, the 5-mm Hg reduction in SBP may be clinically meaningful and is comparable to the effects of 30 daily minutes of physical activity (4 - 9 mm Hg). Theoretic risk reduction of a cardiovascular event for the 5-mm Hg decrease in SBP for individuals with hypertension could be approximately 20% during 5 years. However, the investigators note that long-term treatment with chocolate or cocoa drinks is of questionable practicability. For cocoa-chocolate vs placebo, BP was not significantly decreased in the normotensive subgroups (SBP: 1.6 2.3 mm Hg; P =.17; DBP: 1.3 1.6 mm Hg; P = .12). In meta-regression analysis, study design (parallel vs crossover) and type of control (flavanol-free vs low-flavanol) were borderline significant, but possibly indirect, predictors

for BP outcome. Dosage, duration, quality of trials, age, and body mass index were not associated with BP outcome, based on meta-regression analysis. On the basis of these findings, the investigators concluded that dark chocolate is superior to placebo in reducing systolic hypertension or diastolic prehypertension. However, they noted that flavanol-rich chocolate did not significantly lower mean BP lower than 140 mm Hg systolic or 80 mm Hg diastolic. Limitations of meta-analysis included high heterogeneity in the hypertensive subgroups. Effect sizes and significance of the subgroup meta-analyses of trials in the (pre-)hypertensive groups should therefore be interpreted with caution.

Clinical Implications
In a pooled meta-analysis of all included randomized controlled trials, cocoa-chocolate vs placebo significantly lowered BP. However, the investigators note that long-term treatment with chocolate or cocoa drinks is of questionable practicability. In subgroup meta-analysis, cocoa-chocolate vs placebo had a significant effect only in the hypertensive or prehypertensive subgroups. For individuals with hypertension, the 5-mm Hg reduction in SBP may be clinically meaningful and is comparable to the effects of 30 minutes daily of physical activity.