Browsing by Subject "Atherosclerosis"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Open Access
    Dietary lipid modification for mild and severe dyslipidaemias
    (2013) Marais, A David
    The aim of this review is to place a historical perspective on linking dyslipidaemia with atherosclerosis and emphasises previous knowledge about the impact on the lipoprotein profile and health in persons with mild dyslipidaemia and in those with defined genetic disorders. CVD is becoming the leading cause of death and disability in developed and developing countries and is strongly related to lifestyle factors that influence plasma lipoprotein concentrations. It is established that risk of complications from atherosclerosis increases with increasing LDL and decreasing HDL and that there is potentiation of risk when these and other risk factors co-exist. High-fat diets used for losing body mass may increase risk through dyslipidaemia. Pharmaceutical modulation of the lipoproteins has lowered risk powerfully but residual risk persists, possibly relating to existing disease as well as progression relating in many instances to dietary lipids. The impact of various dietary lipids is reviewed as they relate to the conventional lipoprotein profile in persons who do not have significant metabolic defects, as well as the impact on inherited metabolic disease such as familial hypercholesterolaemia, hypertriglyceridaemia and phytosterolaemia. For most persons with dyslipidaemias a significant benefit will be seen on the lipid profile by adopting a low saturated fat diet with less cholesterol intake.
  • Thumbnail Image
    Item
    Open Access
    Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thickness
    (Public Library of Science, 2011) Rahman, Thahira J; Walker, Elizabeth A; Mayosi, Bongani M; Hall, Darroch H; Avery, Peter J; Connell, John M C; Watkins, Hugh; Stewart, Paul M; Keavney, Bernard
    Objective The combined thickness of the intima and media of the carotid artery (carotid intima-medial thickness, CIMT) is associated with cardiovascular disease and stroke. Previous studies indicate that carotid intima-medial thickness is a significantly heritable phenotype, but the responsible genes are largely unknown. Hexose-6 phosphate dehydrogenase (H6PDH) is a microsomal enzyme whose activity regulates corticosteroid metabolism in the liver and adipose tissue; variability in measures of corticosteroid metabolism within the normal range have been associated with risk factors for cardiovascular disease. We performed a genetic association study in 854 members of 224 families to assess the relationship between polymorphisms in the gene coding for hexose-6 phosphate dehydrogenase (H6PD) and carotid intima-medial thickness. METHODS: Families were ascertained via a hypertensive proband. CIMT was measured using B-mode ultrasound. Single nucleotide polymorphisms (SNPs) tagging common variation in the H6PD gene were genotyped. Association was assessed following adjustment for significant covariates including "classical" cardiovascular risk factors. Functional studies to determine the effect of particular SNPs on H6PDH were performed. RESULTS: There was evidence of association between the single nucleotide polymorphism rs17368528 in exon five of the H6PD gene, which encodes an amino-acid change from proline to leucine in the H6PDH protein, and mean carotid intima-medial thickness (p = 0.00065). Genotype was associated with a 5% (or 0.04 mm) higher mean carotid intima-medial thickness measurement per allele, and determined 2% of the population variability in the phenotype. CONCLUSIONS: Our results suggest a novel role for the H6PD gene in atherosclerosis susceptibility.
  • Thumbnail Image
    Item
    Open Access
    Numerical and experimental modeling of atherosclerosis related to MRI
    (1998) Bernsdorf, Stefan; Sayers, A
    This thesis was motivated by the idea of employing non-invasive investigations of atherosclerosis using Magnetic Resonance Imaging (MRI). MRI has the advantage of being able to detect atheroma in blood vessels with no risk to the patient but is still limited in its application to large blood vessels by the low geometrical resolution obtainable. The capability of MRI to measure velocities as well leads to the idea of correlating atheroma dimensions with measured velocities downstream of the blockage. This thesis makes a first step towards obtaining results that can be applied in investigations of atherosclerosis employing MRI. The fluid dynamics of arterial blood flow, the medical procedure of diagnosing and treating atherosclerotic diseases, and the physical principle of MRI are investigated to find out "if' and "how" the correlation between a blockage and the resulting downstream velocities can contribute to the diagnosis of atheroma. Parallel to this background research, experimental and numerical modeling of atheroma is carried out. These two approaches use identical geometrical and fluid parameters to enable a direct validation of the results. An experimental test-rig is designed. Experiments with different types of blockages are performed. The measured flow parameters are pressure and velocity profiles in a crosssection of the modeled artery. A commercial software package is employed for the numerical simulation of blockages with similar geometries to those used in the experiments. The pressure and absolute velocities are again the derived parameters. Both approaches are validated with analytical results obtainable for flow without any blockages. Blockages are then inserted and the results are compared and analyzed for their potential to contribute to the medical application. The results obtained with the two models give good correspondence. The transitional length of the laminar pipe flow corresponds very well to the expectations. A laminar velocity profile is completely built up before the fluid enters a blockage. Blockages with a small flow area cause a high peak velocity and a large wake. Blockages that slightly reduce the flow area have only a small influence on the flow. The length of a blockage has only a secondary influence on the downstream velocity distribution, while the influence of the surface roughness of the blockage is small. The peak velocities and pressure loss caused by the different blockages give good correlation. The prediction of the diameter of the blockage from peak velocities measured with MRI is an improvement on that which is possible from the theory only. In particular, the results obtained in this thesis show that the true maximum velocities are significantly lower than those obtained with theoretical predictions. The change in the velocity profiles, due to angioplasty, is shown in a simplified form with the models. Typical values of reduced areas before and after such surgery, where the atheroma is squeezed against the arterial walls, are analysed. The influence of the post-surgery blockage on the flow is very small, while the pre-surgery blockage shows a dominant influence. A prominent wake exists downstream of a highly reduced flow area, and high velocities occur. A wake is a potential risk area for atherosclerosis, as low shear rates and high turbulence intensities are possible. The blockage with the less reduced area has almost no influence on the flow, and a wake is hardly formed. The influence of different shapes of atheroma, while having a similar reduced area, is also demonstrated. The perfectly symmetrical blockage has less negative influence on the flow than one which is highly asymmetrical. The asymmetrical blockage causes a larger wake and higher maximum velocities.
  • Thumbnail Image
    Item
    Open Access
    The association between HIV and atherosclerotic cardiovascular disease in sub-Saharan Africa: a systematic review
    (2017) Hyle, Emily P; Mayosi, Bongani M; Middelkoop, Keren; Mosepele, Mosepele; Martey, Emily B; Walensky, Rochelle P; Bekker, Linda‐Gail; Triant, Virginia A
    BACKGROUND: Sub-Saharan Africa (SSA) has confronted decades of the HIV epidemic with substantial improvements in access to life-saving antiretroviral therapy (ART). Now, with improved survival, people living with HIV (PLWH) are at increased risk for non-communicable diseases (NCDs), including atherosclerotic cardiovascular disease (CVD). We assessed the existing literature regarding the association of CVD outcomes and HIV in SSA. METHODS: We used the PRISMA guidelines to perform a systematic review of the published literature regarding the association of CVD and HIV in SSA with a focus on CVD surrogate and clinical outcomes in PLWH. RESULTS: From January 2000 until March 2017, 31 articles were published regarding CVD outcomes among PLWH in SSA. Data from surrogate CVD outcomes (n = 13) suggest an increased risk of CVD events among PLWH in SSA. Although acute coronary syndrome is reported infrequently in SSA among PLWH, limited data from five studies suggest extensive thrombus and hypercoagulability as contributing factors. Additional studies suggest an increased risk of stroke among PLWH (n = 13); however, most data are from immunosuppressed ART-naïve PLWH and thus are potentially confounded by the possibility of central nervous system infections. CONCLUSIONS: Given ongoing gaps in our current understanding of CVD and other NCDs in PLWH in SSA, it is imperative to ascertain the burden of CVD outcomes, and to examine strategies for intervention and best practices to enhance the health of this vulnerable population.
  • Thumbnail Image
    Item
    Open Access
    The association between HIV and atherosclerotic cardiovascular disease in sub-Saharan Africa: a systematic review
    (BioMed Central, 2017-12-15) Hyle, Emily P; Mayosi, Bongani M; Middelkoop, Keren; Mosepele, Mosepele; Martey, Emily B; Walensky, Rochelle P; Bekker, Linda-Gail; Triant, Virginia A
    ackground: Sub-Saharan Africa (SSA) has confronted decades of the HIV epidemic with substantial improvements in access to life-saving antiretroviral therapy (ART). Now, with improved survival, people living with HIV (PLWH) are at increased risk for non-communicable diseases (NCDs), including atherosclerotic cardiovascular disease (CVD). We assessed the existing literature regarding the association of CVD outcomes and HIV in SSA. Methods: We used the PRISMA guidelines to perform a systematic review of the published literature regarding the association of CVD and HIV in SSA with a focus on CVD surrogate and clinical outcomes in PLWH. Results: From January 2000 until March 2017, 31 articles were published regarding CVD outcomes among PLWH in SSA. Data from surrogate CVD outcomes (n = 13) suggest an increased risk of CVD events among PLWH in SSA. Although acute coronary syndrome is reported infrequently in SSA among PLWH, limited data from five studies suggest extensive thrombus and hypercoagulability as contributing factors. Additional studies suggest an increased risk of stroke among PLWH (n = 13); however, most data are from immunosuppressed ART-naïve PLWH and thus are potentially confounded by the possibility of central nervous system infections. Conclusions: Given ongoing gaps in our current understanding of CVD and other NCDs in PLWH in SSA, it is imperative to ascertain the burden of CVD outcomes, and to examine strategies for intervention and best practices to enhance the health of this vulnerable population.