EDITORIAL Chocolate and cardiovascular disease: a sweet deal? R. Jay Widmer 1 , Lilach O. Lerman 2 , and Amir Lerman 1 * 1 Division of Cardiovascular Diseases; and 2 Division of Nephrology & Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA Online publish-ahead-of-print 20 February 2012 This editorial has been guest edited by Prof. Stefano Taddei, Universita` degli Studi di Pisa, Italy. This editorial refers to ‘Cardiovascular effects of flavanol- rich chocolate in patients with heart failure’ † , by A.J. Flammer et al., on page 2172 ‘Take two of these chocolates daily, and call me in a month.’ Who among us would not want to be able to provide such a delicious prescription to our patients who carry the complicated and even- tually fatal diagnosis of heart failure? Unfortunately, the solution is not that simple, yet the recent study by Flammer et al. 1 may bring us a step closer to understanding the relationship between cocoa, endothelial function, and cardiovascular health. Flammer et al. present a largely positive, double-blind, rando- mized controlled trial (RCT) comparing the effect of commercially available flavonol-rich chocolate (FRC) vs. control chocolate (CC) on endothelial function, an indicator of increased morbidity and mortality, 2 in patients with moderate (New York Heart Associ- ation class ≥ II) heart failure. 1 The authors found significant short-term (2 h) and longer term (4 weeks) improvement in flow- mediated dilation (FMD), their primary endpoint, of the brachial artery after consumption of FRC vs. CC. Importantly, these calor- ically neutral supplements had no effect on the patients’ body weight or fasting glucose measurements. Other pertinent findings in the study include mostly comparable secondary endpoints in these groups, such as blood pressure, body weight, lipid fractions (with the exception of HDL-cholesterol), inflammatory markers, antioxidants, baroreceptor function, and long-term platelet adhe- sion, underscoring the complex relationship between traditional risk factors and vascular function. On the other hand, blood pres- sure tended to decrease in the FRC group, consistent with previ- ous observational studies and RCTs; 3,4 however, the current study may have been underpowered to detect such differences in a small sample size. Finally, while not quite statistically significant, there was a strong trend toward endothelial-independent vasoconstric- tion after 4 weeks of FRC consumption, which was not detected at 2 h after FRC treatment or at any time point after CC consump- tion. While this was not elaborated upon, further elucidation of the underlying mechanisms might help expound upon the implications of the results. Further investigation regarding cocoa and alternative regulatory factors such as endothelin-1, angiotensin II, thrombox- anes, endothelial-derived hyperpolarizing factor (EDHF), prosta- glandins other than 8-isoprostane, or other vasoactive cytokines, and their effect on cardiovascular disease (CVD) parameters affecting those with heart failure could be undertaken as a follow- up study. Additional noteworthy findings regarding secondary endpoints included a reduction in platelet adhesion seen 2 h after FRC admin- istration, and, interestingly, unaltered insulin sensitivity among those consuming FRC for 4 weeks compared with those rando- mized to CC, who had a significant decrease in insulin sensitivity. As longer term FMD assessments were performed after an extended fast, the authors point out that the sustained improve- ment in endothelial function at 4 weeks with a non-sustained amelioration in platelet function indicates that the extended inges- tion of cocoa could lead to phenotypic changes in the endothelium conferring an enduring therapeutic benefit in this population of sick patients. Thus, the proposed mechanism ascribing cocoa with en- during alterations in nitric oxide (NO) bioavailability is certainly plausible, and should prompt further investigation regarding the effect of nutraceuticals on the mechanisms causing heart failure and monitoring such effects via endothelial function. Although few, this study did have some limitations, including small sample size, the inability to control completely the remainder of the subjects’ diet, adherence to study substance, and medica- tions taken by the patients which might mitigate any ill effects or bioavailability of the FRC. Clearly, the authors took measures to reduce the impact of these factors, and the improvements in endo- thelial function are of such magnitude that sample size was not an issue. Additionally, the authors carefully documented flavanol * Corresponding author. Tel: +1 507 255 4152, Fax: +1 507 255 2550, Email: lerman.amir@mayo.edu † doi:10.1093/eurheartj/ehr448. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology. Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2012. For permissions please email: journals.permissions@oup.com European Heart Journal (2012) 33, 2118–2120 doi:10.1093/eurheartj/ehs026 Downloaded from https://academic.oup.com/eurheartj/article-abstract/33/17/2118/481976 by guest on 06 November 2018