Background: Research studies in recent years suggested possible role of dark chocolate in preventing cardiovascular diseases due to its high flavonal and procyanidins contents. Whether there is clear clinical benefit and the mechanisms mediating such benefits is controversial. Objective: This systematic review aims to comprehensively examine the current clinical evidence regarding effectiveness and the possible mechanisms of chocolate in reducing the risk and / or surrogate markers of cardiovascular diseases. Methods: Comprehensive electronic literature search was performed using Ovid, Medline and Cochrane database. Only English language literatures published during year 1950 - 2010 were reviewed. All intervention studies and observational studies of adult human subjects taking white or dark chocolate in relation to outcomes of cardiovascular risk were included. All review articles and meta-analysis were also included. Clinical diagnosis of cardiovascular disease and surrogate markers including blood pressure, vascular endothelial function as measured by flowed mediated vasodilation, and blood biomarkers such as lipid profile were studied as outcome variables. Results: The review outlines recent observational and interventional studies and meta-analysis to give an overview of the topic. For observational studies, a cohort studies and two case control studies were found. The observational studies showed that dark chocolate consumption was inversely associated with blood pressure, cardiovascular mortality and C-reactive protein. All interventional studies searched showed that dark chocolate increased FMD and improved platelet function. However, the effects of cocoa on intermediate outcomes such as blood pressure, antioxidant capacity and inflammatory marker changes were inconsistent among interventional studies. Three interventional studies indicated that there was a dose-dependent improvement in immediate outcome variables after 1 month or even 2 hours acute consumption of dark chocolate with procyanidins or cocoa drink with flavonol. However, publication bias and potential conflict of interests may be a potentially important factor in interpreting study results in the current literature. Conclusions: There are some clinical and scientific evidences that consumption of dark chocolate produces positive cardiovascular benefits. A small amount of dark chocolate may be good for the heart. However, gaps in our knowledge such as a lack of long-term RCT in clinical outcomes must be filled in before recommending habitual dark chocolate consumption for reduction of cardiovascular risk. / published_or_final_version / Community Medicine / Master / Master of Public Health

Background Over the past few years, results refuting the causal role of HDL cholesterol (HDL-c) have been reported by a number of randomized controlled trials (RCTs) testing different ways of modifying HDL-c. Results from Mendelian randomization studies showed no difference in cardiovascular disease (CVD) risk among individuals with genetically different serum levels of HDL-c. The causal role of HDL-c in CVD is thus uncertain, raising the question as to whether HDL-c is a worthwhile target of public health interventions and medical treatments. The objective of these meta-analyses is to explore whether changes in HDL-c are symptomatic of prior causes instead of being a causal factor for CVD by first identifying two possible candidates—androgens and zinc—for the investigation of associations. Experimental evidence would then be investigated for whether either of them might underlie (i.e. confound) the observed association of HDL-c with CVD risk factors. Methods This study followed the PRISMA statement. A literature search was conducted through PUBMED, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Keywords of “androgens/testosterone”, “HDL”, “high-density lipoprotein”, “lipid”, “cholesterol”, “lipoprotein”, “CVD”, “cardiovascular”, “heart”, “cardiovascular disease” were used with the search period limited to January 2000 – June 2013 with only human RCTs conducted and reported in English. For locating studies concerning the effect of zinc, the keyword “zinc” was used instead of “androgens/testosterone”. Inclusion and exclusion criteria were applied during study screening and selection. The Cochrane Collaboration’s tool for assessing risk of bias was used for quality assessment. Heterogeneity across included studies was measured using I2 statistic and publication bias was assessed via funnel plots and the Begg’s Rank Correlation test. The “trim and fill” method was also used for the correction of funnel plot asymmetry. The meta-analyses were performed using The Comprehensive R Archive Network Program (Version R 3.0.0), using the function “metacont” from the “meta” package, where the pooled intervention effects were displayed using forest plots, with inverse variance weighting and random effects model. Results A total of twelve and ten RCTs were identified and included in the meta-analyses of androgens and zinc respectively. There were no consistent beneficial effects of androgens on CVD observed, as the results from CVD surrogate markers were inconclusive, despite showing significant overall reduction in HDL-c levels. However, as current findings suggest that lower HDL-c levels are associated with higher cardiovascular risk, it is possible that androgens may increase that risk by influencing HDL metabolism. On the other hand, zinc was associated with healthier CVD profile. This supports the notion of zinc as a cardioprotective agent. Nonetheless, conclusion failed to be drawn concerning the effect of zinc on HDL-c as there were contradictory results across included studies. Conclusion The meta-analyses suggest that androgens could be a factor which lowers HDL-c and thus increases cardiovascular risk, rather than HDL-c being the direct causative agent. This research may serve as a template for more extensive search for other potentially better candidates in this new study focus in cardiovascular epidemiology. / published_or_final_version / Community Medicine / Master / Master of Public Health

Background: Cardiovascular disease is the leading cause of mortality and morbidity in the world and has something to do with daily diet. The polyphenol is the most abundant compound in daily diet, including grape. The red wine was rich in polyphenol because of composing much grape. Early study has already confirmed the “French Paradox” in cardiovascular protection power, which shed light on the dietary modulation on disease. Objective: The main objective of the study was to evaluate the effect of products containing polyphenol such as red wine extract, grape juice and grape extract tablets or powder on cardiovascular disease risk factors. It mainly examined relationship between polyphenol and serum lipid in addition to blood pressure. Methods: Studies working on effects of grape extract products on cardiovascular disease were searched from electronic resources MEDLINE and EMBASE. Nine clinical controlled trials were identified through PubMed and Ovid. CONSORT guideline and Jadad Score were used to appraise the quality of trials. Weighing two assessment guidelines, a total of three studies were in good quality, one was in bad quality while the rest four were fair to middle. Results: The changes before and after intervention on serum lipid and blood pressure were contradictory. Some studies found polyphenol was statistically significant protective factors, while some did not find it siginificant but still showed a protective effect. One study found polyohenol had no effect on cardiovascular disease risk factors. Conclusion: The prevention of polyphenol was not consistent in nine trials and there is no sufficient and strong evidence supporting its cardiovascular protection effect given that the study design of each trial differed. It was not recommeded to use grape polyphenol as cardiovascular protect products. There were limitations and weakness of current study on the association of polyphenol and cardiovascular disease. Further research on this topic is required, both in vivo and in vitro. / published_or_final_version / Public Health / Master / Master of Public Health

Pluripotent stem cells hold great promise in regenerative medicine. Theoretically, a variety of tissues can be generated from this progeny. The production of tailor-made stem cells for individualized patient treatment is the ultimate goal of stem cell based therapy. Human induced pluripotent stem cells (iPSCs) hold the precious key to success and promote the clinical application of stem cells. By reprogramming somatic cells, pluripotent stem cells can be generated in a patient-specific manner and subsequently differentiated into specific tissue for regeneration. Nonetheless exposure of hiPSCs to animal feeder cells and serum during generation and maintenance imposes a risk of transmitting animal pathogens to human subjects, thus hindering their potential therapeutic application. In addition, the efficacy of iPSC generation is < 1% of total somatic cells used. The first part of the study focused on the development of improved methods to produce a more efficient xenogen-free culture system to produce more clinically compatible iPSCs. Specific tissue or cells derived from stem cells may offer a solution and cell therapy using endothelial cells and their progenitors may be possible in treatment of severe cardiovascular diseases. In theory, endothelial cells can be generated from different sources of progenitor cells although no direct comparison of these various derived endothelial cells (ECs) has been reported. Thus in the second part of the study, the functional and physiological properties of BM, ESC and iPSC-ECs will be evaluated to determine their therapeutic potential in ischemic disease. A mouse hind limb ischemia model was used to assess and monitor neovascularization by the derived ECs. The results can provide further insight to evaluate the possibility of using iPSCEC as the cell source for patient-specific treatment. Use of pluripotent stem cells is a promising approach in therapeutic angiogenesis although numerous hurdles continue to hamper their widespread clinical use. Conditioned medium derived from progenitor cells may be another possible strategy in the treatment of ischemic diseases such that direct cell transplantation is avoided. Conditioned media produced from ex vivo culture of endothelial cells contain a combination of angiogenic factors that can be applied to promote neovascularization in ischemic tissue. Nonetheless the efficacy of this angiogenic application is unknown. The third part of the study focused on the potential application of EC-derived conditioned media in the treatment of ischemic disease using a mouse hind limb ischemia model. Some cardiovascular risk factors such as diabetes might affect endothelial cell function such that autologous application of ECs and their conditioned media is not feasible. A human embryonic stem cell line may offer and alternative means to obtain stable quality ECs and conditioned medium for therapeutic use. In summary, advances in stem cell technology hold great promise for the treatment of cardiovascular disease, further improved by the generation of patient-specific stem cells using iPSC technology. Vascular cells can be generated from different sources of stem cells with similar angiogenic properties and may be used in the treatment of ischemic diseases. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

Background Many studies in western countries have suggested a positive association between intake of trans fatty acid (TFA) and risk of cardiovascular diseases (CVDs). In Asia, although intake of TFA was relatively low, it evidenced an increasing trend which was accompanied with an increasing prevalence of CVDs among the population. There was currently no systematic review on the relationship between intake of TFA and CVDs in Asian population. This systematic review was aimed to synthesize the association between intake of TFA and the risk of CVDs in Asian population from published literature. Methods Both English and Chinese literature published before 1st January 2014were retrieved from PubMed, Medline, Google scholaand CNKI with a combination of keywords. Studies that reported the associations between intake of TFA and CVD-related risks and those conducted among Asian population were included. The quality of eligible literature included in the review was assessed based on STROBE. Findings regarding the associations between intake of TFA and risk of CVDs were extracted and synthesized through comparing and evaluating the quality of findings across the included studies. Results Of the 378 articles retrieved from the datasets, nine studies were eligible to be included in this systematic review. The nine studies covered six Asian countries including Iran, China, Korea, Japan, Israel and India. Seven of nine studies indicated a positive association between intake of TFA and risk of CVDs while the other two reported no significant association. However, none of the included studies were interventional studies and only one was prospective cohort study. Conclusion The findings that more intake of TFA was associated with increased risk of CVDs in Asian population were consistent with that in the western population. Specific regulations to restrict the use of TFA and interventions to promote public awareness of the health effects of TFA are recommended in Asian countries. Due to limited eligible studies that covered only six Asian countries, there remains cautious to generalize the findings to other Asian countries. / published_or_final_version / Public Health / Master / Master of Public Health

Background: Qualitative magnetic resonance imaging methods, such as T2-weighted (T2W) imaging, are commonly used for cardiac tissue characterisation. However, these are sensitive to image artefact, and results are unreliable. Modified Look-Locker inversion recovery (MOLLI) provides robust, quantitative T1 imaging in the myocardium, but it is subject to limitations: its T1 measurement accuracy is dependent on heart rate, it exhibits banding artefacts, and a lengthy breath hold is required. In this thesis, some MOLLI variants were developed with the aim of mitigating these problems. Furthermore, MOLLI was applied to two different patient groups for comparison with a typical T2W method. Methods: MOLLI variants used alternative k-space trajectories, gradient-echo readouts, startup preparations, and sampling schemes, and were tested in silico, in vitro and in vivo—in healthy volunteers. In patients, conventional MOLLI was compared to T2W spectral attenuated inversion recovery (SPAIR) for oedema detection in both acute ST-segment elevation myocardial infarction (STEMI), and Takotsubo cardiomyopathy (TCM). RESULTS: Simulation, phantom and volunteer data showed that a linear sweep up (skipped pulse pair) startup preparation enables improved T1 measurements. A MOLLI variant with a reduced sampling scheme performed similarly to conventional MOLLI, allowing for shorter breath holds. Different k-space trajectories did not significantly affect T1 measurement accuracy, but precision varied: possibly due to artefacts. For oedema identification, MOLLI performed significantly better than T2W-SPAIR in STEMI patients, and the two were comparable in TCM patients. In all patients, remote myocardium showed an elevated T1 relative to healthy volunteers, suggesting remote inflammation. Conclusions: It was shown that MOLLI T1 mapping can delineate oedema in acute STEMI and TCM patients, producing measurements that are more robust and reproducible than those made with T2W SPAIR. A number of improvements were suggested in this work, but there is still substantial scope for developing the MOLLI T1 mapping pulse sequence.

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