| |
| Date: 11-15-2016 | HC# 101631-556 |
De Palma R, Sotto I, Wood EG, et al. Cocoa flavanols reduce N-terminal pro-B-type natriuretic peptide in patients with chronic heart failure. ESC Heart Fail. 2016;3(2):97-106.
Chronic heart failure (HF) affects up to one-fifth of people aged 75 years and older. Age-related endothelial dysfunction, measured as decreased flow-mediated dilatation (FMD), is linked to poor prognosis in chronic HF.New therapies are needed to treat endothelial dysfunction in patients with chronic HF. The consumption of high-flavanol cocoa (Theobroma cacao, Malvaceae) reportedly increases endothelium-dependent vasodilator responses in healthy individuals and in patients with diabetes mellitus and coronary artery disease. The goal of this single-center, randomized, crossover, double-blind, placebo-controlled study was to assess the potential therapeutic value of a high dose of cocoa flavanols in patients with chronic HF.
Thirty-two patients who had documented evidence of previous ischemic heart disease were recruited at the Heart Failure Clinic of the London Chest Hospital in London, United Kingdom. Eligibility criteria included over 45 years of age; chronic HF due to left ventricular (LV) systolic dysfunction confirmed by transthoracic echocardiography or left ventriculogram; classification of 2 or 3 on the New York Heart Association (NYHA) functional classification index, indicating slight or marked limitation of physical activity; and maintenance for at least 6 months on optimal guideline-directed medical therapy (GDMT) in accordance with the UK National Institute for Clinical Excellence guidelines for chronic HF.1
At baseline, all patients were being treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker and a beta-blocker. Thirteen patients were being treated with diuretics, 20 with aspirin, and 21 with statins. Patients were randomly assigned to consume either high-flavanol dark chocolate (HFDC, 50 g daily; Barry Callebaut Belgium NV; Lebbeke-Wieze, Belgium) or placebo low-flavanol dark chocolate (LFDC, 50 g daily; Barry Callebaut Belgium NV) for 4 weeks. At the end of the 4 weeks, the patients consumed the other chocolate for 4 weeks. Of similar taste and appearance, the daily doses of HFDC and LFDC contained 1064 mg and 88 mg of flavanols, respectively. The doses were chosen on the basis of previous studies, which reported that 80 mg of total flavanols daily did not produce a significant effect on endothelial function, whereas doses of about 900 mg daily produced a consistent and marked increase in endothelium-dependent flow-mediated vasodilatation.2 Theobromine content was 395 mg in the HFDC and 420 mg in the LFDC.
The chocolate was provided in 50-g bars and patients were instructed to consume 25 g in the morning and 25 g in the afternoon. Patients were instructed to maintain their normal diet, abstain from drinking red wine (from grapes [Vitis vinifera, Vitaceae]), and not take any herbal medicines for HF.
At baseline and at 4, 8, and 12 weeks, the following assessments were conducted: NYHA classification, body weight, blood pressure, and radial artery tonometry to measure arterial pressure. Blood samples were collected to measure N-terminal pro B-type natriuretic peptide (NT-proBNP), C-terminal pro-endothelin-1 (CT-proET-1), platelet function, high-sensitivity C-reactive protein (CRP), high-sensitivity cardiac troponin I, theobromine, lipids, glycated hemoglobin, and standard hematological and biochemical parameters. Patients were asked to complete a quality-of-life questionnaire at each visit.
Eight patients dropped out for various reasons, including the unpalatable taste (1 with LFDC and 2 with HFDC); a fall; an unscheduled gastrointestinal surgery; conflicting personal commitments; an episode of vomiting after 2 weeks of ingesting HFDC; and planned surgery.
Several of the patients who completed the study reported mild gastrointestinal discomforts (2 patients with LFDC and 6 with HFDC). Four patients who completed the study complained about the taste of the chocolate and had difficulty eating 50 g daily. One patient, whose ankles swelled during the first 4 weeks while consuming LFDC, was prescribed an increased dose of diuretic by her physician. After 4 weeks of HFDC consumption, 1 patient reported paresthesia in the right hand, and another patient experienced troponin-negative chest pain.
Of the 24 (20 males and 4 females) patients who completed the study, only 20 had tonometry recordings of pulse waveforms that were of sufficient quality at all study visits to be included in the analyses.
NT-proBNP levels were significantly lower after HFDC consumption compared with baseline (P=0.016), with LFDC consumption (P=0019), and with the follow-up values 4 weeks after completion of chocolate consumption (P=0.004). The overall mean reduction in NT-proBNP after HFDC consumption compared with baseline, with LFDC consumption, and with follow-up values was 39% ± 56%, with an average decrease ≥30% in 12 of the 24 patients. Brachial artery diastolic blood pressure (DBP) significantly decreased after 4 weeks of HFDC consumption compared with measurements obtained after 4 weeks of LFDC consumption (P<0.001) and at baseline (P=0.045). Central DBP derived from the peripheral pressure waveform also decreased after HFDC compared with LFDC (P=0.002). Central and peripheral systolic blood pressure (SBP) did not change significantly during the study. A nonsignificant increase in central and peripheral pulse pressures was observed after HFDC consumption.
No significant changes were found in platelet function, circulating levels of CT-proET-1, CRP, or cardiac troponin I, and no changes were seen in hematological or biochemical parameters with either of the chocolate interventions. For the 19 patients who completed all quality-of-life assessments, no changes were reported in overall physical or mental well-being scores or in individual component scores. Body weight tended to increase during consumption of both chocolates.
Reporting that current studies indicate that flavanols restore flow-mediated vasodilatation and pointing to the results of this study, the authors hypothesize "flavanol-induced peripheral vasodilatation enables cardiac output to increase, so that SBP is maintained, which in turn further improves flow-mediated vasodilatation."
Study limitations include the lack of a pretreatment phase to assess baseline fluctuations in NT-proBNP before randomization to HFDC or LFDC, a small sample size with a low ratio of female patients, the short duration, and the absence of FMD measurements or assessment of LV function to correlate with blood pressure and reductions in NT-proBNP. Because all patients had a history of ischemic heart disease, the generalizability of the findings is limited. Despite this, the authors conclude that the study indicates that combining cocoa flavanols with GDMT can potentially improve cardiac function in patients with chronic HF.
Co-author R. Corder, a director of FlavoSanté Ltd., received a grant for this study from Barry Callebaut Belgium NV. The Medical Research Council (United Kingdom) provided a grant for the CT-proET-1 assay.
—Shari Henson
References
1National Institute for Clinical Excellence. Chronic Heart Failure: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care. Guideline No. 5. London, UK: Royal College of Physicians; 2003.
2Balzer J, Rassaf T, Heiss C, et al. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients: a double-masked, randomized, controlled trial. J Am Coll Cardiol. 2008;51(22):2141-2149.
