Saudi Cultural Missions Theses & Dissertations
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Item Restricted The Effect of Dietary Interventions on Arterial Stiffness in Men. A Systematic review of the literature(University of Nottingham, 2024) Almutairi, Mohammed; Rocha, LuciaAbstract Background and introduction Cardiovascular diseases (CVDs) are the leading cause of death globally, encompassing conditions like coronary heart disease and strokes. Risk factors include hypertension, diabetes, and lifestyle choices such as smoking. Arterial stiffness is a crucial risk factor in hypertension, refers to the reduced flexibility of the arterial walls. This condition arises as blood vessels age and is associated with various cardiovascular diseases. Studies have shown that dietary interventions can significantly reduce CVD risks by improving factors like blood pressure and arterial stiffness, particularly in men. This paper is to systematically review the current literature on the effects of different dietary interventions on arterial stiffness in men Methodology This systematic review adheres to PRISMA guidelines, employing a flow diagram to outline the article selection process, focusing on adult males at risk for cardiovascular diseases. It assesses the impact of dietary interventions on arterial stiffness, measured by carotid-femoral pulse wave velocity (PWV). The review specifically includes randomized controlled trials (RCTs) published from January 2015 to June 2024 that are in English and utilize PWV for measuring arterial stiffness. Excluded are non-RCT studies, those combining diet with exercise, and those involving females, children, or mixed groups. Primary outcomes are changes in PWV, while secondary outcomes include variations in systolic blood pressure, heart rate, and triglycerides. Results The systematic review process identified five randomized controlled trials (RCTs) met the inclusion criteria out of an initial 1,131 papers after rigorous screening. Only one study using cocoa flavanol intervention achieved significant reduction on the pulse wave velocity, the same study also showed significant decrease in systolic blood pressure, also another study showed significant reduction in systolic blood pressure after consumption of high fat beef patties. Conclusion This review indicated that cocoa flavanols can significantly improve arterial stiffness and systolic blood pressure, but other dietary interventions lacked similar impactful results. The findings suggest that effective strategies might need to integrate diet with exercise and other lifestyle changes to significantly enhance cardiovascular health.14 0Item Restricted The use of plasminogen activator inhibitor-1 specific Affimers as a tool to modulate fibrin clot properties and thrombosis risk(Leeds University, 2024-03-05) Altalhi, Rawan; Ajjan, RamziThe ability to form a blood clot is critical for preventing blood loss following vessel injury. After restoring vascular integrity, the haemostatic system allows for the closure of impaired blood vessels, the preservation of blood in a fluid state, and the removal of clots. Blood clots are made up of a network of fibrin fibres that include platelets, red blood cells, and white blood cells. Imbalances and changes in coagulation factors, as well as the several components of the coagulation cascade, may have an effect on fibrinolysis. This turn may lead to increased risk of unwanted vascular occlusion through the failure to remove intravascular clots and maintain blood flow, consequently resulting in reduced blood supply to an organ. Hypofibrinolysis is a key abnormality in conditions associated with high vascular risk such as diabetes, contributing to the adverse vascular outcome in this population. Plasminogen activator inhibitor (PAI)-1 is an important regulator of the fibrinolytic process and levels of this antifibrinolytic protein are elevated in diabetes and insulin resistant states. An increase in PAI-1 levels results in impaired fibrinolysis and increases the risk of thrombus formation. Therefore, modulating PAI-1 activity has the potential to improve the fibrinolytic process and decrease intravascular clot formation. One difficulty with modulating PAI-1 function is the reliance of this protein on vitronectin that stabilises PAI-1 and enhances its function. I hypothesised that plasminogen activator inhibitor-1 specific Affimers, which are small synthetic proteins, may be used to modulate fibrinolysis, consequently reducing the risk of thrombosis. The main aims of my work were to i) isolate PAI-1- specific Affimers, ii) investigate the effects of PAI-1-specific Affimers on fibrinolysis, and iii) characterise the mechanistic pathways for Affimer-mediated modulation of clot lysis. My work shows that PAI-1 binding Affimers do not adequately modulate protein function and only Affimers that bind both PAI-1 and vitronectin demonstrate an ability to significantly alter both protein function and consequently the fibrinolytic process. I also explore the mechanistic pathways that are responsible for Affimer-mediated PAI- 1 inhibition, in the hope that this may help to develop effective therapies to reverse the hypofibrinolytic environment in high vascular risk conditions.32 0Item Restricted The role of fibrin clot structure and fibrin film in venous thromboembolism(University of Leeds, 2023-12-21) Alkarithi, Ghadir; Ariens, Robert; Duval, Cedric; Macrae, FraserBlood clot formation is triggered by vascular injury and plays crucial roles in both haemostasis and thrombosis. Changes in clot structure are linked to deep vein thrombosis (DVT) and pulmonary embolism (PE). Blood clots are composed of fibrin fibres, platelets and red blood cells. Recent studies showed that fibrin films develop on the surface of clots and thrombi. This thesis investigates the effect of haematocrit on fibrin films, the role of fibrin films in platelet adhesion and fibrinolysis, and the impact of inflamed endothelial cells on fibrin film formation. It also investigates whether clot properties predict vein patency in DVT patients. Finally, it will investigate if microscopic aggregates are present in PE patients’ plasma. High haematocrit clots showed more fibrin film coverage than low haematocrit clots. Platelet adhesion was reduced on clots with film compared to clots without film. Fibrinolysis was faster in clots without film than with film. Plasma clots on top of tumour necrosis factor-α-stimulated endothelial cells showed less fibrin film coverage and were characterised by higher fibre density and shorter lag time compared to those formed on the top of control cells. Clot properties of patients who have difficulty achieving patency after DVT with standard treatment were characterised by higher maximum absorbance, shorter lag time and higher maximum clotting rate compared to patients with patency. Finally, microscopic aggregates were found in the plasma of PE patients. These findings reveal new insights into the roles of fibrin film and clot structure in thrombosis. Fibrin film reduction under inflammation may contribute to continued clot growth. Analysing clot properties could be useful in predicting patients who most likely will not achieve patency after DVT. Finally, the finding of aggregates in PE patients’ plasma raises a number of important questions regarding their presumed role in thrombosis39 0Item Restricted The effects of exercise training on low-density lipoprotein mediated blood flow in coronary artery disease: a systematic review(Saudi Digital Library, 2023-11-06) Barnawi, Aziza; Richard, WinsleyRegular exercise reduces the risk factors for cardiovascular disease (CVD). In recent years, interventions have been developed to prevent coronary artery disease (CAD). Elevated low- density lipoproteins (LDL) contribute to the development of atherosclerosis by constricting the endothelium and impairing the endothelial function of coronary arteries. For this reason, flow-mediated dilation (FMD) is used for assessment. Electronic databases were searched for exercise interventions performed over a period of ≥6 weeks that affected LDL levels and/or FMD in CAD patients and healthy subjects. Twenty randomized controlled trials met the eligibility criteria for this systematic review. Endurance training resulted in greater reductions in LDL levels and their subfractions and had significant effects on FMD (~P<0.0001). Other exercise interventions had various benefits, including improved physical fitness and quality of life. Participants who exercised supervised for ≥60 minutes/session, 3-4 times per week, at moderate to vigorous intensity showed significant FMD response and/or LDL improvement (P<0.05) compared to those with lower intensity, frequency, and duration (P>0.05). Exercise training (ET) might correlate positively with improved FMD, but the limited LDL evidence might not be significantly related to improved blood flow. The aim of this review is to determine the optimal exercise programme to prevent the progression of CAD. In conclusion, the relationship between ET, LDL levels, and FMD is complex but shows promise for secondary prevention of CAD.24 0Item Restricted Anti-atherogenic actions of hydroxytyrosol(Saudi Digital Library, 2023-11-02) Alotibi, Reem Mansour; Ramji, DipakIntroduction: Atherosclerosis is a chronic inflammatory disorder characterised by the accumulation of lipids in the arterial wall, and is considered to be a major contributor to cardiovascular disease (CVD). Worldwide, CVD is responsible for a third of all deaths. Current pharmacological therapeutic agents for CVD, such as statin therapy, are not fully effective and have considerable residual risk for the disease. Alternative agents for the prevention and treatment of the disease are therefore required. Hydroxytyrosol (HT) is a polyphenol compound found mainly in olive oil. HT has been reported to prevent CVD predominantly due to its antioxidant effects. HT is the only polyphenol recognised by the European Food Safety Authority as a protector against low-density lipoprotein-mediated oxidative damage. Previous investigations carried out in the host laboratory showed that HT altered multiple atherosclerosis-associated risk factors in wild-type mice fed a high-fat diet (HFD) for 3 weeks, as well as various anti-inflammatory and anti-atherogenic actions on human monocytes/macrophages in vitro. Unfortunately, the actions of HT in atherosclerosis in vivo are poorly understood. The aim of this study therefore was to elucidate its effects on atherosclerosis progression and regression in a mouse model system. Methods: In order to study the development of atherosclerosis in vivo, 8-week-old male or female low-density lipoprotein receptor-deficient (ldlr-/-) mice were given HFD alone or in combination with 10 mg/kg/day of HT for 12 weeks. For regression studies, the mice were fed a HFD for 12 weeks to promote the formation of established lesions, and then switched to normal chow diet (NCD) alone or in combination with HT. The two procedures were then followed up by an in-depth investigations of atherosclerosis- associated risk factors and the plaques that formed in the aortic root. RNA-sequencing and bioinformatic analyses was used to assess changes in gene expression and associated pathways in the thoracic aorta. The liver was also analysed in relation to non-alcoholic fatty liver disease (NAFLD) that is often associated with atherosclerosis and extended via the use of an in vitro hepatoma HepG2 cell culture model system. Results: As part of the progression study, female ldlr-/- mice that had received HT supplemented HFD for 12 weeks had attenuated weight gain, plaque size in the aortic root and neutrophil content in the peripheral blood, while male ldlr-/- mice had attenuated occlusion and T cells in the peripheral blood. In both cases, there was reduced plaque inflammation and improved plasma lipid profile and plaque stability. As part of the regression studies on male ldlr-/- mice, intervention with HT combined with NCD reversed hepatic injury and enhanced plaque stability (to a greater extent than NCD intervention alone). Conclusions: These findings provide support for the anti-atherogenic actions of HT as well as its possible use as an alternative nutraceutical agent for preventing the development of atherosclerosis. This is potentially possible due to the lack of adverse effects as well as the relatively low cost in comparison to that of typical pharmacological treatments. Additional research is necessary in order to determine the mechanisms that are responsible for these favourable anti-atherogenic and other beneficial changes.16 0Item Restricted 24-Hour Movement Guidelines and Cardiorespiratory Fitness in Relation to Cardiovascular Disease Risk Factors in Adolescents from Saudi Arabia(University of Exeter, 2022) Alkhraiji, Mohummed Hamad; Williams, Craig A; Barker, Alan RPhysical activity in the form of moderate-to-vigorous physical activity (MVPA), sedentary behaviour in the form of recreational screen time (ST), and sleep, are individually associated with cardiovascular disease (CVD) risk factors in adolescents. Commonly, researchers investigate these three movement behaviours in relation to CVD risk factors in isolation. However, after the launch of the Canadian 24-Hour Movement Guidelines for children and youth, there have been calls to integrate all three 24-hour behaviours (PA, ST, & sleep). Furthermore, a scientific statement from the American Heart Association highlights the importance of cardiorespiratory fitness (CRF) as a measurement for health screening in children and adolescents as CRF is a strong predictor of CVD risk. Previous studies have individually explored how the 24-hour movement guidelines or CRF are associated with CVD risk factors in adolescents; however, which of the two (24-hour movement guidelines or CRF) is more strongly associated with CVD risk factors in adolescents is unknown. Currently, most studies have been conducted in North America and Europe, with the Middle East neglected, including Saudi Arabia, which has a very different lifestyle, environment, climate, school system, and culture compared to North America and Europe. Therefore, to address this gap in the literature in the context of Saudi Arabia, the studies included in this thesis aimed to investigate the prevalence of 24-hour movement guidelines and CRF and their relationship with CVD risk factors in adolescents from Saudi Arabia aged 12–15 years old. Chapter 4 narratively reviewed movement guidelines and CRF in relation to CVD risk factors in children and adolescents from the Gulf Cooperation Council Countries, which indicated gaps in the literature investigating the 24-hour movement guidelines. In addition, Chapter 4 highlighted that there is poor evidence for an association between single movement guidelines and CRF with multiple CVD risk factors; most studies have only examined associations with weight status. Chapter 5 examined the reliability and validity of using the Global School-Based Student Health Survey (GSHS) to assess the 24-hour movement guidelines in (n = 120; 50% females) adolescents aged 12–15 years old, from Saudi Arabia and found acceptable reliability and validity. In Chapter 6, the GSHS was used to examine the prevalence of the 24-hour movement guidelines and their associations with overweight/obesity in a sample of (n = 4224; 52% females) participants aged 12–15 years old. The results indicated that only 2.7% achieved the recommended 24-hour movement guidelines and highlighted weak, non-significant associations with the risk of overweight/obesity. In Chapter 7 a subsample of (n = 120; 50% females) participants aged 12–15 years old from the study in Chapter 6 underwent a 24-hour movement guidelines assessment using GENEActiv accelerometers (for MVPA and sleep) and the GSHS (for ST). In addition, CRF was assessed using the Progressive Aerobic Cardiovascular Endurance Run test, and fasting blood samples, blood pressure, and anthropometrics were collected. None of the adolescents in this subsample met all three of the 24-hour movement guidelines, and there were no favourable significant associations with individual or clustered CVD risk factors. In addition, few males (16%) and almost half of the female (46.3%) participants had a healthy CRF. However, in males only, having a CRF was significantly and negatively associated with waist circumference (WC) and clustered CVD risk. Collectively, the results presented in this PhD thesis contribute to enhancing the literature in four ways. Firstly, it demonstrates that there is a lack of studies on the 24-hour movement guidelines and CRF in relation to CVD risk factors for adolescents from the Gulf Cooperation Council countries. Secondly, it is the first study to examine a questionnaire for its reliability and validity to measure the 24-hour movement guidelines, which found an acceptable reliability and validity. Thirdly, it shows that via a questionnaire few adolescents (2.7%) from Saudi Arabia are meeting the 24-hour movement guidelines, which is not significantly associated with being at risk of overweight/obesity. Lastly, it shows that when using device-based accelerometry, none of the adolescents from Saudi Arabia are meeting the 24-hour movement guidelines, which is not significantly associated with individual or clustered CVD risk factors profiles in both sexes. Moreover, healthy CRF was not significantly associated with individual or clustered CVD risk factors in females, while in males, healthy CRF was only significantly and inversely associated with WC and clustered CVD risk factors. Based on the above findings, it is suggested that 24-hour movement guidelines are not favourable strongly associated with individual or clustered CVD risk factors in adolescents of both sexes from Saudi Arabia. In addition, in females it appears that there are no significant associations between CRF and individual or clustered CVD risk factors. Initiatives should be developed to encourage male adolescents from Saudi Arabia aged 12–15 years old to achieve a healthy CRF to reduce the risk of WC and clustered CVD risk factors. However, future longitudinal studies with larger sample sizes would enable further insight into the associations between 24-hour movement guidelines and CRF in relation to CVD risk factors in adolescents from Saudi Arabia and should provide specific recommendations for both sexes.31 0Item Restricted RACIAL/ETHNIC AND SOCIOECONOMIC DISPARITIES IN THE UTILIZATION OF GLP-1RA AND SGLT2I AMONG US ADULTS WITH TYPE 2 DIABETES BY CARDIOVASCULAR AND RENAL DISEASE INDICATIONS (2018-2019)(2023) Alshehri, Alaa; Shao, HuiNewer glucose-lowering drugs (GLP-1RA, and SGLT2i) are expensive with high cost-sharing. This would lead to racial and socioeconomic disparities and inequities but has never been proved. This study aims to examine the racial/ethnic and socioeconomic disparities in the utilization of newer drugs among type 2 diabetes with a history of cardiovascular disease, renal disease, or at high cardiovascular disease risk in the US. We conducted a cross-sectional study, using the MEPS database from 2018 to 2019. We enrolled adults with type 2 diabetes and have indication for benefit drugs use. Multivariable logistic regression was used to investigate the use of newer drugs among the eligible population by indications. A total of 3305 individuals with diabetes were identified, among whom 1391 had CVD, 379 had CKD, and 2996 had a higher risk of ASCVD. Non-Hispanic Asian (OR 0.43, 95%CI 0.20-0.92), and non-Hispanic Black (OR 0.62, 95%CI 0.42-0.91) were associated with lower probability of using GLP-1RA/SGLT2i compared to non-Hispanic White. Compared to high-income individuals, near poor (OR 0.56, 95%CI 0.33-0.96) and low income (OR 0.61, 95%CI 0.39-0.95) had a lower probability of using benefit drugs. Compared to privately insured, publicly insured participants (OR 0.65, 95%CI 0.48-0.89) were associated with a lower probability use of benefit drugs. In conclusion, there were an association between lower use of GLP-1RA/SGLT2i among patients with indication and racial/ethnicity, and lower socioeconomic status. Policymakers' interventions are needed to ensure equitable access of GLP-1RA/SGLT2i for the potential undertreatment in population racial/ethnic and socioeconomic subgroups.14 0