Nutraceuticals in the prevention and treatment of Atherosclerosis

Objectives: To investigate the effects of nutraceuticals on key processes associated with atherosclerosis in vitro and in vivo. Background: Atherosclerosis is an inflammatory disease of the vasculature in which macrophages play key roles at all stages and represent promising therapeutic targets. Unfortunately, current therapies against atherosclerosis are not fully effective and associated with other issues such as adverse side effects. In addition, there have been many failures on pharmaceutical agents identified from drug discovery programs. Nutraceuticals represent promising alternatives in the prevention and treatment of atherosclerosis but requires a thorough understanding of their actions together with the underlying mechanisms. The purpose of this study was to address this with emphasis on key macrophage processes associated with atherosclerosis. Methods: A combination of macrophage cell lines and primary cultures were used with gene expression analysed by atherosclerosis profiler arrays and real time quantitative PCR. Foam cell formation was investigated by following the uptake of fluorescently labeled modified LDL, intracellular lipid profiling and cholesterol efflux assays. Inflammasome activation was evaluated by following the release of interleukin (IL)-1beta using an ELISA and ROS production using a kit from Abcam. The effects in vivo were analysed in C57BL/6 mice fed a high fat diet. Results: The studies focused on polyphenols, flavanols and omega-6 polyunsaturated fatty acids. These either inhibited or had no effect on several key macrophage processes associated with atherosclerosis such as pro-inflammatory gene expression, the uptake of modified LDL, macropinocytosis, ROS production and the activation of the inflammasome. In addition, where analysed, the nutraceutical inhibited several atherosclerosis-associated markers in mice fed a high fat diet. The mechanisms underlying such actions will be presented. Conclusions: The studies provide new insights into the beneficial actions of nutraceuticals in atherosclerosis

An Economic Evaluation of a Streamlined Day-Case Atrial Fibrillation Ablation Protocol and Conventional Cryoballoon Ablation versus Antiarrhythmic Drugs in a UK Paroxysmal Atrial Fibrillation Population

Background and Aims Symptom control for atrial fibrillation can be achieved by catheter ablation or drug therapy. We assessed the cost effectiveness of a novel streamlined atrial fibrillation cryoballoon ablation protocol (AVATAR) compared with optimised antiarrhythmic drug (AAD) therapy and a conventional catheter ablation protocol, from a UK National Health Service (NHS) perspective. Methods Data from the AVATAR study were assessed to determine the cost effectiveness of the three protocols in a two-step process. In the first stage, statistical analysis of clinical efficacy outcomes was conducted considering either a three-way comparison (AVATAR vs. conventional ablation vs. optimised AAD therapies) or a two-way comparison (pooled ablation protocol data vs. optimised AAD therapies). In the second stage, models assessed the cost effectiveness of the protocols. Costs and some of the clinical inputs in the models were derived from within-trial cost analysis and published literature. The remaining inputs were derived from clinical experts. Results No significant differences between the ablation protocols were found for any of the clinical outcomes used in the model. Results of a within-trial cost analysis show that AVATAR is cost-saving (£1279 per patient) compared with the conventional ablation protocol. When compared with optimised AAD therapies, AVATAR (pooled conventional and AVATAR ablation protocols efficacy) was found to be more costly while offering improved clinical benefits. Over a lifetime time horizon, the incremental cost-effectiveness ratio of AVATAR was estimated as £21,046 per quality-adjusted life-year gained (95% credible interval £7086–£71,718). Conclusions The AVATAR streamlined protocol is likely to be a cost-effective option versus both conventional ablation and optimised AAD therapy in the UK NHS healthcare setting