Paraoxonase-1 (PON1) is a high density lipoprotein (HDL)-associated enzyme displaying esterase and lactonase activity. PON1 hydrolyzes the oxons of several organophosphorous insecticides (e.g. paraoxon, diazoxon and chlorpyrifos-oxon) and metabolizes lipid peroxides of low density lipoproteins (LDL) and HDL. As such, PON1 plays a relevant role in determining susceptibility of organophosphate toxicity and cardiovascular disease. The objective of this study was to determine associations of PON1 status (i.e. genotype and activity levels) with atherosclerosis (ATH) in individuals from the Southeastern United States. An additional objective was to determine whether PON1 genotype and/or PON1 activity levels influence the capacity of PON1 to metabolize chlorpyrifos-oxon (CPO) at a relatively low concentration. Data indicated increasing PON1 activity assessed by hydrolysis of phenyl acetate is associated with decreased odds of ATH. Furthermore, neither PON1 genotype nor PON1 activity levels influence capacity of PON1 to metabolize CPO at a relatively low concentration.

Mississippi has a very high prevalence of coronary artery disease (CAD) and type 2 diabetes (T2D), especially among African Americans compared to Caucasians. This project determined the L55M genotypes of paraoxonase 1 (PON1) in 187 people and evaluated associations of PON1 single nucleotide polymorphisms (SNPs), Q192R and L55M, with CAD and T2D in a Mississippian (southern) population. Significant associations were found with PON1 SNPs and race: genotypes LL, LM, QR, and RR showed significant associations with race (p values 0.0000955, 0.0024, 0.00001244, and 0.00001676, respectively), and combined genotypes LMQQ and LMRR were significantly associated with race (p values = 0.0001013 and 0.000473, respectively). While no significant associations were found between PON1 SNPs and CAD (p values > 0.2374), combined genotype LMQQ and genotype LM trended towards the likelihood of having T2D with p values = 0.0723 and 0.0931, respectively, and are suggestive of a potential biomarker for T2D risk.

Bakgrund: Trots stark evidens för att fysisk aktivitet och träning vid kranskärlssjukdom är viktiga ur ett livslångt perspektiv för individer med kranskärlssjukdom finns begränsat med forskning kring vilka metoder som kan ha effekt på vidmakthållandet av fysisk aktivitet efter att individen genomgått den centerbaserade träningen. Syfte: Syftet med den här litteraturstudien var att granska effekten av vidmakthållande hjärtrehabilitering på fysisk aktivitet och fysisk kapacitet i sex månader eller mer hos individer med kranskärlssjukdom som genomgått centerbaserad hjärtrehabilitering. Vidare var syftet att undersöka kvalitet och tillförlitlighet i ingående artiklar.  Metod: Systematiska sökningar i databaserna AMED, PubMed och PsycINFO. Tio randomiserade kontrollerade studier inkluderades. Kvalitet bedömdes med PEDro-skalan och resultatens samlade tillförlitlighet bedömdes enligt SBU GRADE.  Resultat: Kvalitén på ingående artiklar var måttlig till medelgod. Tillförlitligheten bedömdes som mycket låg enligt SBU GRADE. Resultatet indikerade, trots stor variation av interventioner, att vidmakthållande hjärtrehabilitering kan ha effekt på fysisk aktivitet och till viss del på fysisk kapacitet (kondition). För muskelstyrka ses ingen effekt.  Konklusion: Kvalitén på de ingående artiklarna var måttlig till medelgod. Enskilda artiklar visar på signifikanta resultat som indikerar att vidmakthållande hjärtrehabilitering kan ha effekt på fysisk aktivitet och kapacitet hos individer med kranskärlssjukdom. Det sammanvägda resultatet för vidmakthållande hjärtrehabiliterings effekt på fysisk aktivitet hos individer med kranskärlssjukdom har låg tillförlitlighet bedömt med SBU GRADE. För vidmakthållande hjärtrehabiliterings effekt på fysisk kapacitet (kondition och styrka) bedöms tillförlitligheten som mycket låg. / Background: Despite evidence that physical activity and training in coronary artery disease are important from a lifelong perspective for individuals with coronary artery disease, there is limited research on which methods that can support physical activity maintenance after center-based training.  Aim: The aim of this literature study was to examine the effect of maintenance cardiac rehabilitation (M-CR) on physical activity and physical capacity for six months or more in individuals with coronary artery disease after center-based cardiac rehabilitation. The aim was also to examine the quality and reliability of included articles. Method: Systematic searches in the AMED, PubMed and PsycINFO databases. Ten randomized controlled trials were included. Quality was assessed using the PEDro scale.The overall reliability of the results was assessed according to SBU GRADE guidelines. Result: The quality of included articles was moderate to average. Reliability was assessed as low to very low according to SBU GRADE. The result indicated, despite variation of interventions, that M-CR can have an effect on physical activity and to some extent on physical capacity (fitness). For muscle strength, no significant effect is seen. Conclusion: Individual articles show significant results indicating that M-CR can have an effect on physical activity and capacity in individuals with coronary artery disease. The quality of the included articles was moderate to average. The overall reliability on physical activity was assessed as low according to SBU GRADE. And the overall reliability on physical capacity (fitness and muscle strength) was assessed as very low according to SBU GRADE.

Evaluation of: Bangalore S, Steg PG, Deedwania P et al. β-Blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA 308(13), 1340–1349 (2012). The number of myocardial infarctions (MIs) in population remains high and this event is a significant predictor of mortality. Information in the literature points to a reduction in mortality, reinfarction and sudden death in first year, especially in patients with high risk, if β-blockers (BBs) are used after MI. In a perspective study, Zuckerman et al. have determined outcome following pharmacotherapy after acute MI in older adults. It is apparent that a number of matters require consideration in evaluation of the effectiveness of BBs. It seems that not all patients benefit equally from treatment with BBs but such an intervention reduces mortality. It is also important to recognize that the beneficial effects of BBs should not be considered in isolation since the biological system is too complex to manipulate with the use of a single class of drugs.

Background: In most countries of the Western world there have been positive reductions in incidence of cardiovascular diseases in the past decades, among both men and women, but still mortality due to these disease groups are very high. Many studies about myocardial infarction have shown that depression after an event is related to poor medical outcomes from the disease. This means prolonged disability events of angina, arrhythmias, re-hospitalization and increased rate of mortality. In post myocardial infarction patients, depression is a major cause of both short and long term mortality. Aim: The aim of this study was to examine the scientific literature by a systematic review in order to find evidence based knowledge about the benefit of physical activity as a tool to reduce depression in patients with coronary artery event.Method: Three databases were searched (Pubmed, CINHAL, Cochrane) systematically and all articles that met inclusion criteria were examined and graded according to the criteria “Grading quality of evidence and strength of recommendations” by Atkins. A special protocol was designed further from AMSTAR by Beverley, for systematic review with and without the meta-analysis study. Results: It was evident that scientific reports fitting to the area was scarce showing that the area of interest was fairly new. Finally ten studies were included in this study, one meta-analysis, five randomized controlled trail and four clinical trials. The results showed low to moderate evidence for the use of high, moderate and low level of exercise as a tool to reduce depression in post coronary artery event patients.Conclusion: The following study concluded that, exercise shows positive effects to reduce the level of depression among coronary artery event patients.

Introduction: Diabetes Mellitus is a metabolic disorder that affects a person’s ability to either produce insulin (Type I diabetes mellitus) or properly use insulin (Type II diabetes mellitus) in order to maintain adequate blood glucose levels. The most severe diabetic complications arise due to hyperglycemia – a state of extremely high blood glucose levels – such as, coronary artery disease (CAD), in which coronary stent therapy is a popular method of treatment. However, research has shown a high rate of in-stent restenosis in diabetic patients with CAD, most likely due to activation of cellular adhesion molecules on endothelial cells exposed to the hyperglycemic environment. Blood vessel mimics (BVMs) have been researched as viable options for in vitro studies on vascular stents; thus, it would be beneficial to create an in vitro diabetic BVM for stent manufactures to evaluate and determine the root cause of the high failure rate of stents in the diabetic population. In addition, a diabetic BVM would help manufactures optimize coatings or stent configurations for diabetic patients. Methods: The purpose of this thesis was to take the initial steps towards the goal of a diabetic BVM. The first aim was to establish a procedure of developing glycemic cell media solutions of various glucose concentrations, and to establish a feasible method of monitoring the glucose concentration of the solutions. Glycemic cell media solutions were developed and their glucose concentrations were evaluated with a blood glucose meter (specifically, the Aviva Accu-Chek blood glucose meter) or visual blood glucose test strips (Glucoflex R visual blood glucose test strips). The second aim was to ensure that the developed glycemic cell media solutions could be monitored in a cell culture environment over time, and to determine if the hyperglycemic conditions induced any change to endothelial cells. Bovine aortic endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) were used to evaluate glucose consumption and cell morphology. Glucose concentration of the cell media was recorded to evaluate glucose consumption, and the cells were evaluated under a microscope in order to determine cell morphology and an increase in cell death. Results & Conclusions: Data accumulated from the first set of experiments confirmed that glycemic cell media solutions can be developed by adding Sigma G6512 D-(+)-glucose to base cell media. Additionally, the Aviva Accu-Chek blood glucose meter recorded the most accurate and precise glucose concentrations of the various glycemic cell media solutions compared to the Glucoflex-R blood glucose visual test strips. Lastly, the series of experiments with BAECs and HUVECs confirmed that the glycemic cell media solutions could be effectively monitored over time, and that these conditions evoked higher glucose consumption by the endothelial cells compared to the normal glycemic cell media solutions. Additionally, neither glycemic environment evoked significant cell death. These results met the aims of this thesis, and therefore provide the foundation for further development of a diabetic BVM.

Coronary artery disease affects millions of people and the ability to detect and treat the disease is advancing at a rapid rate. As a result, the development of intravascular technologies is the focus of many medical device manufacturers. Specifically, coronary stent implantation is being performed in an increasing number of patients and a number of new stent designs have been introduced to the market, resulting in the need for improved preclinical testing methods. An in vitro tissue engineered “blood vessel mimic” (BVM) system has previously been established and its feasibility for the initial testing of newly emerging intravascular technology has been demonstrated. There are limitations that exist with this original design, however, and the focus of this thesis was to both improve and expand upon the original model. Therefore, research was conducted based on two specific aims. The first aim was to develop a more ideal BVM system to accommodate a wider range of stent lengths and diameters, while allowing for easy graft insertion and seal-ability. The second aim was to develop next generation BVM systems,focused on future needs and technology, such as long, angulated and bifurcated geometries. The work described in this thesis demonstrates that a BVM chamber can be created which has the advantages of easy graft insertion and seal-ability, as well as the ability to accommodate varying sizes of vessel scaffolds, all while maintaining the needs of a tissue engineering bioreactor system. The next generation BVM systems presented demonstrate that the BVM concept can be expanded to meet the needs of long, angulated and bifurcated geometries. Overall, the work in this thesis describes the design and optimization of an in vitro blood vessel mimic bioreactor system for the evaluation of intravascular devices, specifically coronary stents, in simple and complex vessel geometries.

Yes / Background: Non-adherence to secondary prevention medicines (SPMs) among patients with coronary artery disease (CAD) remains a challenge in clinical practice. This study attempted to identify actual and potential modifiable barriers to adherence that can be addressed in cardiology clinical practice. Methods: This was a cross-sectional, postal survey-based study of the medicines-taking experience of patients with CAD treated at a secondary/tertiary care centre. All participants had been on SPM for ≥3 months. Results: In total, 696 eligible patients were sent the survey and 503 responded (72.3%). The median age was 70 years, and 403 (80.1%) were male; the median number of individual daily doses of all medicines was 6. The rate of non-adherence to at least one SPM was 43.5% (n=219), but 53.3% of reported non-adherence was to only one SPM. Statins contributed to 66.7% and aspirin to 61.7% of overall non-adherence identified by the Single Question (SQ) tool. In 30.8% of non-adherent patients (n=65), this was at least partly intentional. Barriers included forgetfulness (84.9%; n=186), worry that medicines will do more harm than good (33.8%; n=74), feeling hassled about medicines taking (18.7%; n=41), feeling worse when taking medicines (14.2%; n=31) and not being convinced of the benefit of medicines (9.1%; n=20). In a multivariate analysis, modifiable factors associated with overall non-adherence included being prescribed aspirin (OR: 2.22; 95% CI: 1.18 to 4.17), having specific concern about SPM (OR: 1.12; 95% CI: 1.07 to 1.18) and issues with repeat prescriptions (OR: 2.48; 95% CI: 1.26 to 4.90). Different factors were often associated with intentional versus unintentional non-adherence. Conclusions: Using appropriate self-report tools, patients share actual and potential modifiable barriers to adherence that can be addressed in clinical practice. Non-adherence behaviour was selective. Most non-adherence was driven by forgetfulness, concern about the harm caused by SPM and practical barriers. / The study was partially funded by the Leeds Teaching Hospitals Charitable Foundation.

Yes / Coronary artery bypass graft (CABG) using autologous saphenous vein continues to be a gold standard procedure to restore the supply of oxygen-rich blood to the heart muscles in coronary artery disease (CAD) patients with or without type 2 diabetes mellitus (T2DM). However, CAD patients with T2DM are at higher risk of graft failure. While failure rates have been reduced through improvements in procedure-related factors, much less is known about the molecular and cellular mechanisms by which T2DM initiates vein graft failure. This review gives novel insights into these cellular and molecular mechanisms and identifies potential therapeutic targets for development of new medicines to improve vein graft patency. One important cellular process that has been implicated in the pathogenesis of T2DM is protein O-GlcNAcylation, a dynamic, reversible post-translational modification of serine and threonine residues on target proteins that is controlled by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Protein O-GlcNAcylation impacts a range of cellular processes, including trafficking, metabolism, inflammation and cytoskeletal organisation. Altered O-GlcNAcylation homeostasis have, therefore, been linked to a range of human pathologies with a metabolic component, including T2DM. We propose that protein O-GlcNAcylation alters vascular smooth muscle and endothelial cell function through modification of specific protein targets which contribute to the vascular re-modelling responsible for saphenous vein graft failure in T2DM.

In this thesis, a comprehensive understanding of supervised machine learning algorithms, namely Logistic Regression, Support Vector Machine, Random Forest, and Ensemble Stacking, is performed. This research also extends and further explores different feature selection techniques: correlation analysis, chi-squared, mutual information classification, and Recursive Feature Elimination (RFE). Then, a practical application in the context of coronary artery disease prediction was conducted to apply and analyze models' performance with different feature selection methods on various measures of accuracy, F1 score, and confusion matrix. The outcomes of this experimentation reveal that among models developed, Logistic Regression with chi-squared feature selection is a robust and reliable predictive model, achieving an accuracy of 87.65%. This research advances the understanding of machine learning algorithms and feature selection techniques, with practical implications for reliable prediction of coronary artery disease.