The effect of oligomeric procyanidins on endothelial function and cholesterol homeostasis

PhDOligomeric procyanidins (OPC) are naturally occurring dietary substances, which studies suggest can protect against cardiovascular disease. To explore this further a double-blind randomised controlled crossover trial, EPICURE (Evaluation of high procyanidin intervention with dark chocolate on underlying age-related elements of cardiovascular risk) examined the effects of high procyanidin dark chocolate (HPDC) versus low procyanidin dark chocolate (LPDC) on various cardiovascular parameters in subjects with early hypertension. This was complemented by in vitro studies of OPC on cultured bovine aortic endothelial cells (BAEC) to determine the effect on cellular cholesterol levels. HPDC reduced 24 h blood pressure (-2/0.6 mmHg) and heart rate (-3.3 bpm), but only the latter reached statistical significance (p < 0.001). Augmentation pressure, augmentation index, plasma lipid levels, apolipoproteins, HDL subclasses, and hsCRP were not different amongst the groups. Retrospective analysis suggests that the study was underpowered and there were only 21 subjects with completed data due to technical issues. Future clinical studies should be designed with sufficient statistical power to detect changes in vascular function. In addition, compliance should be checked, technical errors detected earlier and FMD rather than PWA should be used to measure endothelial vascular function. OPC in vitro increased expression of the oxysterol cholesterol 25-hydroxylase (peaking at 1 h; p < 0.001) which suppressed the mRNA levels of HMGCR as previously reported (at 6 h; p < 0.01). In addition the mRNA for ABCG1 was increased (at 24 h p < 0.01), which has not been described to date in the literature. This implicates that OPC favour overall reduced cellular cholesterol via increased efflux and reduced synthesis. But when BAEC were loaded with LDLC, OPC reduced both cell media and solubilised cell extract cholesterol levels, the former being greater, suggesting no enhancement in cholesterol efflux. Also there was poor reproducibility of the ABCG1 mRNA expression which was likely to be due to variable transcription of the reference gene. Despite this the in vitro results support a potential role for OPC in reducing cellular cholesterol levels and future studies should employ radioactive methods to measure cholesterol efflux

Effects of High Flavanol Dark Chocolate on Cardiovascular Function and Platelet Aggregation.

Regular consumption of chocolate and cocoa products has been linked to reduced cardiovascular mortality. This study compared the effects of high flavanol dark chocolate (HFDC; 1064mg flavanols/day for 6 weeks) and low flavanol dark chocolate (LFDC; 88mg flavanols/day for 6 weeks) on blood pressure, heart rate, vascular function and platelet aggregation in men with pre-hypertension or mild hypertension. Vascular function was assessed by pulse wave analysis using radial artery applanation tonometry in combination with inhaled salbutamol (0.4 mg) to assess changes due to endothelium-dependent vasodilatation. HFDC did not significantly reduce blood pressure compared to baseline or LFDC. Heart rate was increased by LFDC compared to baseline, but not by HFDC. Vascular responses to salbutamol tended to be greater after HFDC. Platelet aggregation induced by collagen or the thromboxane analogue U46619 was unchanged after LFDC or HFDC, whereas both chocolates reduced responses to ADP and the thrombin receptor activator peptide, SFLLRNamide (TRAP6), relative to baseline. Pre-incubation of platelets with theobromine also attenuated platelet aggregation induced by ADP or TRAP6. We conclude that consumption of HFDC confers modest improvements in cardiovascular function. Platelet aggregation is modulated by a flavanol-independent mechanism that is likely due to theobromine.This study was supported by a grant (to R. Corder) from Barry Callebaut Belgium N

Selecting patients for interventional procedures to treat hypertension

Purpose: Interventional approaches to treat hypertension are an emerging option that may be suitable for patients whose BP control cannot be achieved with lifestyle and/or pharmacotherapy and possibly for those who do not wish to take drug therapy. Materials and Methods: Interventional strategies include renal denervation with radiofrequency, ultrasound and alcohol-mediated platforms as well as baroreflex activation therapy and cardiac neuromodulation therapy. Presently renal denervation is the most advanced of the therapeutic options and is currently being commercialised in the EU. Results: It is apparent that RDN is effective in both unmedicated patients and patients with more severe hypertension including those with resistant hypertension. Conclusion: However, at present there is no evidence for the use of RDN in patients with secondary forms of hypertension and thus evaluation to rule these out is necessary before proceeding with a procedure. Furthermore, there are numerous pitfalls in the diagnosis and management of secondary hypertension which need to be taken into consideration. Finally, prior to performing an intervention it is appropriate to document presence/absence of hypertension-mediated organ damage