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Prospective Study and Meta-Analysis of Chocolate and Reduction of Stroke Risk

Reviewed: Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of stroke: a prospective cohort of men and meta-analysis. Neurology. 2012;79(12):1223-1229.

Much evidence has accumulated to show that cocoa (Theobroma cacao, Sterculiaceae) and chocolate may have benefits for cardiovascular health through antioxidant, antiplatelet, anti-inflammatory, and blood pressure-lowering effects. In this paper, effects on stroke have been examined in four studies, with two having statistically significant results. However, none of these studies examined exclusively male populations, and only one made its evaluation based on stroke type. The prospective study assessed the association between chocolate consumption and risk of stroke and stroke subtypes in a cohort of Swedish men. In addition, the authors conducted a meta-analysis of prospective studies involving chocolate and stroke risk.

The study used data from the 1997 Cohort of Swedish Men (aged 45 to 79 years). Questionnaires with 350 items on diet and lifestyle were gathered from 48,850 men who were a good representation of the general population with respect to age distribution, relative body weight, and education level, compared with representative data from the Official Statistics of Sweden. After excluding questionnaires that were not completely filled in, and patients who had died or had a history of cancer, cardiovascular disease, diabetes, or an implausible total energy intake, 37,103 men remained.

Consumption of chocolate was assessed using a self-administered food-frequency questionnaire that included 96 foods and beverages. Consumption in grams was computed by multiplying the frequency of chocolate consumption by four age-specific portion sizes (43-54 years, 42 g; 55-63 years, 34 g; 64-71 years, 27 g; 72-77 years, 26 g), which were obtained from the authors’ validation study in Swedish men. Approximately 90 percent of chocolate consumption during the time frame of the study was in the form of milk chocolate.

Incidence of stroke was identified via the Swedish Hospital Discharge Registry and was classified as cerebral infarction (ICD-10 [International Statistical Classification of Diseases and Related Health Problems 10th Revision] code I63), intracerebral hemorrhage (I61), subarachnoid hemorrhage (I60), and unspecified stroke (I64).

In 10.2 years of follow-up, 1,995 cases of first-time stroke were identified, including 1,511 cerebral infarctions, 321 hemorrhagic strokes (254 intracerebral hemorrhages and 67 subarachnoid hemorrhages), and 163 unspecified strokes.

Patients in the highest quartile of chocolate consumption (62.9 g/week) had a statistically significantly lower risk of total stroke by 17 percent (95% confidence interval [CI]: 1-30) after adjustment for age and stroke risk factors, including blood pressure. This association was similar across stroke types. There was an inverse relationship between chocolate consumption and risk of total stroke observed in men without hypertension (relative risk [RR]: 0.76; 95% CI: 0.62-0.93), but not in men with a history of hypertension (RR: 1.04; 95% CI: 0.77-1.41; P for interaction = 0.04). The age-standardized incidence rates of stroke were 85 per 100,000 person-years among men in the lowest quartile of chocolate consumption and 73 per 100,000 person-years among men in the highest quartile.

For the meta-analysis, the databases PubMed and EMBASE were searched up to January 13, 2012, with no restrictions imposed. Four prospective studies examining the association between chocolate consumption and stroke were identified, plus the current study, making a total of five. These studies included a total of 4,260 stroke cases over a range of eight to 16 years of follow-up. Highest and lowest consumption of chocolate were compared, and dose response also was analyzed.

The RR of stroke in the highest compared to the lowest quartiles of chocolate consumption was 0.81 (95% CI: 0.73-0.90), with no heterogeneity. Dose response could be assessed in four out of five of the studies; for a 50 g increment per week, the RR was 0.86 (95% CI: 0.76-0.97), with no heterogeneity among studies (P=0.21; I2=34.1%).

The highest levels of chocolate consumption were associated with a decreased risk of stroke in men, and this was confirmed by the meta-analysis. The results can be extrapolated to men in general because of the wide representation of men present in the sample population. Though the exact mechanism of action for the stroke benefit has not been elucidated, it is likely due to the pleiotropic (producing multiple effects from one gene) cardiovascular benefits of chocolate, including the lowering of blood pressure. The strengths of the study are its large population and its nearly complete data regarding stroke incidence. Its limitations include a lack of differentiation between types of chocolate consumed, self-reporting of consumption, and evidence of small study effects in the meta-analysis. The authors caution that chocolate should be consumed in moderation because of its high fat and sugar content.

—Risa Schulman, PhD