Electronic Theses and Dissertations (Masters)

Permanent URI for this collectionhttps://hdl.handle.net/10539/37981

Browse

Search Results

Now showing 1 - 10 of 25
  • Thumbnail Image
    Item
    Is 24-hour augmentation index a better indicator of arterial stiffness compared to clinic augmentation index?
    (University of the Witwatersrand, Johannesburg, 2024) Mukhovha, Wantonda Papinah; Maseko, Muzi
    Arterial Stiffness is a major independent risk factor that is strongly associated with an increased risk of developing cardiovascular diseases (CVDs), making it an important marker in the assessment of CVD risk. Therefore, in an effort to reduce the rising incidence of cardiovascular diseases in South Africa, it is crucial to determine the best indicator for arterial stiffness. Currently two indices are used to measure arterial stiffness, pulse wave velocity (PWV) and augmentation index (AI). Since arterial stiffness measurement techniques were developed much later than blood pressure (BP) measurement techniques, important lessons can be learned from BP measurement. Studies have indicated that 24-hour BP measurement is a much better tool of measurement compared to a once off conventional BP measurement. This creates a possibility that 24-hour arterial stiffness assessment is a better tool for measuring arterial stiffness compared to a once off clinic arterial stiffness measurement. Therefore, in this study we compared 24-hour AI to in-clinic AI and also assessed gender differences. Previous studies conducted on 24-hour AI were focused on establishing normal 24-hour AI reference values. To date, no studies have been conducted to compare 24-hour AI to in-clinic AI. Moreover, gender differences in the 24-hour arterial stiffness profile have never been studied. We recruited 125 individuals of black African descent and took anthropometric measurements. We measured both conventional BP and 24-hour BP. Pulse wave analysis was performed to obtain both in-clinic and 24-hour AI. In the total population, 24-hour augmentation index (AI24) was significantly higher than in-clinic augmentation index (AIC) (p<0.0001). When participants were stratified according to gender, AI24 was significantly higher than AIC in both men (p<0.0001) and women (p<0.0001). Night-time augmentation index (AIN) in the total population was significantly higher than daytime augmentation index (AID) (p=0.0143). When participants were stratified according to gender, our results show that AIN was only significantly higher in women (p=0.0291) and not in men. Our results show that AIC may grossly be underestimating the prevalence of arterial stiffness and its adverse effects on cardiovascular target organs. Secondly, our results also show that there are gender differences in arterial stiffness fluctuations over the 24-hour period. In men, daytime arterial stiffness does not differ from night-time arterial stiffness. However, in women arteries become stiffer during the night-time compared to the daytime. These findings indicate that special attention must be given to night-time arterial stiffness because it may be more closely related to target organ damage than daytime arterial stiffness.
  • Thumbnail Image
    Item
    The association between poor sleep quality and cardiometabolic risk in HIV+ individuals and the general population living in a rural area of South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Reddy, Tracy; Scheuermaier, Karine; Karstaedt, Alan
    Studies show that both poor sleep quality and HIV infection independently increase cardiometabolic risk (CMR). Additionally, poor sleep quality is common with HIV infection. Our study investigated whether HIV infection interacts with poor sleep quality to affect CMR in people living with HIV (PLWH) in a rural area of South Africa. We recruited 200 HIV+ participants and 200 controls from Qwa Qwa in Free State in South Africa and assessed their CMR, sleep quality, daytime sleepiness, risk of obstructive sleep apnoea and degree of depressive symptoms. Sleep quality (p = 0.15), daytime sleepiness (p = 0.31) and the cardiometabolic risk score (MetScore) (p = 0.93) were similar between HIV+ and control participants. Fewer HIV+ participants had a high risk of sleep apnoea (p = 0.019) but more HIV+ participants had symptoms of clinical depression (p = 0.0007). Poorer sleep quality in the HIV+ participants was associated with pain (p = 0.0006), more severe depressive symptoms (p<0.0001) and longer HIV duration (p = 0.011). However, HIV infection was not associated with a higher MetScore (p = 0.18) once age, sex and sleep and depression markers were adjusted for. Additionally, HIV infection increased the risk of hypertension (p = 0.016). HIV status did not interact with sleep quality (p = 0.32) to affect CMR. Our findings indicate that healthcare facilities should consider monitoring CMR factors in HIV+ individuals.
  • Thumbnail Image
    Item
    Comparison of Aortic Haemodynamics in Community Participants and Patients with Systolic Heart Failure and the Impact of Blood Pressure Control
    (University of the Witwatersrand, Johannesburg, 2024) Lebelo, Ntapo Marcus
    In patients with systolic heart failure (HF), both decreases and increases in pulse pressure (PP) are associated with poor prognosis. If aortic PP in systolic HF is decreased due to systolic dysfunction, then improvements in stroke volume (SV) or forward wave pressure (Pf) would be beneficial. Alternatively, if hypertension is the primary cause of systolic HF, aortic PP may be increased as a consequence of high aortic characteristic impedance (Zc) and backward wave pressure (Pb), which would be detrimental. Accordingly, blood pressure (BP) lowering would be advantageous. However, the changes in central hemodynamics that accompany systolic HF are currently unclear. Hence, I aimed to assess central hemodynamics in systolic HF patients compared to community participants. I therefore compared aortic haemodynamics (central pressures [SphygmoCor], aortic tract outflow [echocardiography]), and the impact of controlled BP (SBP/DBP<140/90 mm Hg or SBP/DBP<130/80 mm Hg) between stable systolic HF patients (n=42) and age and sex-matched community participants (n=298). Systolic HF patients had lower central PP and Pb (p<0.005) and higher HR (p<0.005) than community participants. However, no other differences were noted. When assessing the impact of BP control (SBP/DBP<140/90 mm Hg), HF patients with uncontrolled BP had higher Zc (p<0.005), Pf (p<0.05), and systemic vascular resistance (SVR) (p<0.05) than both HF patients and community participants with controlled BP. Moreover, despite similar peripheral and central PP to community participants with uncontrolled BP, Zc (p<0.005) and SVR (p<0.05) were higher in HF patients with uncontrolled BP. However, when assessing more intense BP control (SBP/DBP<130/80 mm Hg), the differences in Zc, QxZc, and SVR between the systolic HF patients with uncontrolled BP and the community participants with uncontrolled BP were eliminated. In conclusion, a lower aortic PP, which was not due to decreased SV, was observed in stable systolic HF patients. However, in the presence of uncontrolled BP (SBP/DBP≥140/90 mm Hg), but not SBP/DBP≥130/80 mm Hg, Zc, QxZc and SVR were increased in patients with systolic HF. Hence, BP control and its level of control are imperative in patients with systolic HF to protect the heart from the detrimental effects of increased afterloads.
  • Thumbnail Image
    Item
    Investigating the mechanism of action of Aristea ecklonii’s suspected antipyretic properties
    (University of the Witwatersrand, Johannesburg, 2024) Muller, Miles Christopher
    Aristea ecklonii (A. ecklonii) (Baker) is an indigenous, evergreen perennial medicinal plant used amongst South Africans to treat fever. This study aimed to investigate the antipyretic properties of aqueous A. ecklonii root extracts. Male Sprague-Dawley rats (250 – 300 g) received a subcutaneous (s.c.) injection of zymosan (300 mg/kg) or saline before receiving an intraperitoneal injection (i.p.) of paracetamol (50 mg/kg), aqueous A. ecklonii root extract (55 mg/kg) or saline. The i.p. injection was administered 15 h after the s.c. injection. Abdominal temperature was measured using temperature sensitive radio-transmitters. Blood, cerebrospinal fluid (CSF) and hypothalamic tissue was collected 90 min after the i.p. injection for the measurement of cytokines, prostaglandin E2 (PGE2) and enzymes involved in PGE2 synthesis. Zymosan increased abdominal temperature which peaked at 39.42 ± 0.14 °C. Compared to rats that received saline, rats receiving zymosan had increased concentrations of blood plasma IL- 1β and IL-6, increased PGE2 in the CSF and increased hypothalamic expression of COX-2 and mPGES1 (P < 0.05). Paracetamol and aqueous A. ecklonii root extract reduced the zymosan- induced fevers. Rats that received saline, followed by an i.p. injection of aqueous A. ecklonii root extract, had a decrease in abdominal temperature and an increase in blood plasma IL-1β, IL-6, TNF-α and IL-10 concentrations compared to rats that received saline (P < 0.05). Thus, the antipyretic properties of the A. ecklonii root extract seems to be related to its ability to induce systemic inflammation and not reduce the synthesis of hypothalamic PGE2 and thus should be used with caution in ill individuals.
  • Thumbnail Image
    Item
    Sexual dimorphism and renin-angiotensin-aldosterone system (RAAS) in hypertension and left ventricular hypertrophy in Spontaneously Hypertensive Rat (SHR)
    (University of the Witwatersrand, Johannesburg, 2024) Selebano, Kopano
    Background: The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and is linked to hypertensive left ventricular hypertrophy. Sex differences in the involvement of the RAAS in the development of hypertension and left ventricular hypertrophy are unclear, specifically in spontaneously hypertensive rats (SHRs). This study aimed to investigate the sexual difference in the RAAS effects on hypertension and ventricular remodelling in spontaneously hypertensive rats (SHRs). Methods: Thirty SHRs and Wistar Kyoto rats (WYKs) were assigned to four groups, namely; male SHR (n=8), female SHR (n=8), male WKY (n=7), and female WKY (n=7). Body weight, blood pressure and echocardiography parameters were measured before termination. Concentrations of RAAS parameters were measured using enzyme-linked immunosorbent assays (ELISA) at termination (after 7 months). The picrosirius red stain was used to determine collagen content in the left ventricle. Results: SHRs, in comparison to WKYs, had significantly higher blood pressure, greater heart and left ventricular mass, greater heart wall thickness, greater area of collagen and impaired left ventricular relaxation (reduced lateral e’), and increased filling pressures (increased E/e’) (p<0.05). SHRs also had significantly reduced end- diastolic volume, stroke volume and mid-wall fractional shortening (p<0.05). Females, in comparison to males, had reduced end-diastolic volume, stroke volume and mid- wall fractional shortening but had greater physiological growth (p<0.05). Female SHRs exhibited higher conscious and anaesthetised systolic and diastolic blood pressures, along with greater plasma concentrations of angiotensin II (ANG II) compared to other groups (p<0.05). v Conclusion: Compared to WKYs, SHRs developed concentric hypertrophy, impaired diastolic and systolic function. Compared to males, females developed greater physiological left ventricular growth with lower left ventricular relaxation and systolic function. The physiological cardiac differences may partly be influenced by factors such as body weight and blood volume. Additionally, female SHRs had elevated blood pressure, which may be due to increased plasma concentrations of ANG II.
  • Thumbnail Image
    Item
    Determination of Characteristic Impedance in a Retrospective Cohort of Coronary Artery Disease in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Els, Danelle; Peterson , Vernice R.; Peters, Ferande
    The relationship between coronary artery disease (CAD) and proximal aortic stiffness-induced increases in central arterial forward wave pressures (Pf) is uncertain. Using central pressure and aortic velocity and diameter measurements, we compared aortic characteristic impedance (Zc) (n=71) and central arterial pressure wave morphology (n=189) in patients with CAD to central arterial function in 210 age- and sex-matched controls from a community study. The results showed that Zc was markedly increased in patients with CAD compared to community controls (p<0.0001). In addition, after adjustment for mean arterial pressure and aortic root diameter, the early systolic pressures generated by the product of peak aortic flow (Q) and Zc (PQxZc) and Pf were markedly increased in patients with CAD as compared to controls (p<0.0001). This increase in Pf was accounted for by an enhanced PQxZc at peak PPc rather than increases in re-reflected wave pressures. Further adjustments for either brachial PP or systolic blood pressure (SBP) showed that higher Pf values were retained in the CAD patients (p<0.05, p<0.01, p<0.0001). After adjusting for conventional risk factors, peak central aortic PPc was higher in patients with CAD as compared to controls (p<0.05, p<0.005, p<0.0001). However, after adjusting for brachial SBP and confounders, central aortic PPc did not differ between the groups. Thus, increases in stiffness-associated proximal aortic Zc in patients with CAD translate into marked increases in Pf, but not peak PPc beyond brachial BP. These findings suggest that pulsatile load responsible for CAD is beyond brachial BP and poorly indexed by peak PPc.
  • Thumbnail Image
    Item
    The Impact of Urinary Uromodulin (Tamm-Horsfall Protein) on Renal Function and Haemodynamic Factors in a Community Sample with a High Prevalence of Hypertension
    (University of the Witwatersrand, Johannesburg, 2024) Charles, Aaliah; Peterson, Vernice
    Populations of African ancestry have a high prevalence of primary hypertension and its comorbidities. As they primarily exhibit a volume-dependent form of hypertension, the role of nephron components needs to be explored. Uromodulin is a potential biomarker for renal function and tubular reserve; however, its relationship with renal function, haemodynamic parameters, and hypertension in a population of African ancestry is unknown. I therefore explored the relationship between urinary uromodulin (uUMOD) concentration and renal as well as hemodynamic parameters in an African community with a high prevalence of volume-dependent hypertension. Haemodynamics (central pressures [SphygmoCor], echocardiographic aortic velocity and diameter in the outflow tract), uUMOD concentrations (ELISA assay), renal function (creatinine clearance from 24-hour urine [n = 370]) were determined in a community of African ancestry (n = 397). No relationships between uUMOD concentrations and renal function, age, BMI, BP or hypertension were noted. However, uUMOD concentrations were higher in females than males, even after adjusting for confounders (P = 0.0007). An inverse relationship was observed between stroke volume (SV) and uUMOD (P = 0.0023). This inverse relationship was independent of confounders and present in hypertensives (P= 0.007) but not normotensives (P = 0.43). Hypertensives had a higher SV than normotensives (P = 0.047). In a community sample with a high prevalence of volume-dependent primary hypertension, uUMOD was inversely related to SV, particularly in hypertensives. Although uUMOD is not a biomarker for renal function in this population, these data suggest the need to investigate mechanisms linking uUMOD to SV to assist in identifying novel pathways to better treat volume-dependent hypertension.
  • Thumbnail Image
    Item
    The effect of two modalities of sleep disruption on immunity in healthy young female participants
    (University of the Witwatersrand, Johannesburg, 2023-07) Ajlan, Zuha; Scheuermaier, Karine; Iacovides, Stella
    Studies have shown that sleep deprivation leads to an inappropriate immune response by elevating pro-inflammatory markers, including interleukin (IL-)1, IL-6, and tumour necrosis factor (TNF-)α. This inappropriate immune activation increases the risk of developing autoimmune disorders. Despite women representing 80% of patients with autoimmune disorders and having a greater prevalence of poor sleep quality and sleep disorders, most experimental human studies investigating sleep and immunity focused on men. Therefore, this study assessed the effect of sleep fragmentation vs sleep restriction on sleep parameters. I then compared the immune response after the two types of sleep disruptions relative to a normal sleep episode and I investigated the association between sleep architecture and immune markers in healthy young women in the follicular phase of their menstrual cycle. Fourteen healthy females underwent a randomised-crossover controlled study consisting of one adaptation night and three randomised, non-consecutive sleep conditions, namely: baseline night (BN, uninterrupted 8 hours of sleep); restriction night (RN, sleep was limited to the first 4 hours of their habitual sleep episode); fragmentation night (FN, eight randomised forced awakenings through an 8-hour sleep opportunity night). Polysomnographic (PSG) sleep recordings were obtained for each condition, and plasma was collected 2.5 hours after their habitual waketime following each condition. A multiplex Luminex assay was used to measure the concentration of nine cytokines. I compared PSG-extracted sleep variables between the three experimental nights. I ran mixed models analyses testing cytokine levels in each sleep condition (RN vs. FN vs. BN) in unadjusted analyses and then adjusting for order of the condition (first vs. second vs. third experimental night), day of follicular phase of the menstrual cycle and age. I also used an unadjusted mixed model analysis to test the association between cytokine levels and each sleep variable. Total sleep time, non-rapid eye movement (NREM) and rapid eye movement (REM) were reduced in FN and RN but were lowest during RN (p<0.001). I found an effect of sleep condition on IL-8 (F = 3.40, P = 0.05) with IL-8 being lower in RN vs FN or BN. There was no effect of condition on the other cytokines in unadjusted or adjusted analyses. Lower wake after sleep onset (WASO) and higher NREM were associated with higher IL-8 concentration regardless of the sleep condition. Lower stage 2 (N2) (F = 6.28, β = -0.001, P = 0.02) and higher stage 3 (N3) (F = 7.01, β = 0.004, P = 0.01) was associated with a higher TNF-α regardless of the sleep condition. In conclusion, the study shows that acute sleep disruption alters sleep architecture and leads to an inappropriate immune activity in young healthy women. Future studies should try and investigate chronic sleep fragmentation vs chronic sleep restriction on the immune system.
  • Thumbnail Image
    Item
    The effect of circadian misalignment on cardiometabolic parameters in a rat model of estrogen deficiency
    (University of the Witwatersrand, Johannesburg, 2024) Nthlane, Refentshe Amandu’s; Michel, Frédéric
    Menopausal women engaging in shift work are at an increased risk of cardiometabolic disorders (CMD). The increased risk is due to the dual impact of menopause-associated estrogen withdrawal and the shiftwork-induced irregular light exposure, which disrupts circadian rhythms, leading to chronic circadian misalignment. However, the combination of circadian misalignment related to shift work and menopause on cardiometabolic health remains poorly understood. Therefore, the present study aimed to determine whether circadian misalignment worsens cardiometabolic parameters in estrogen-deficient female spontaneously hypertensive rats (SHR). Circadian misalignment was induced by a 10-week chronic phase shift (CPS) protocol, and estrogen deficiency was induced by ovariectomy. Thirty-six female SHR were ovariectomized or sham- operated 7 weeks after birth, and then subjected to a CPS or control lighting (ctr light) schedule (n=9 per group). Body mass, food and water intake, blood pressure and fasting blood glucose concentrations were measured throughout the 10-week protocol. An oral glucose tolerance test was performed 3 days before the end of the 10-week protocol, while ventricular systolic and diastolic function were assessed by echocardiography at the end of the 10-week protocol. Organ mass was measured, and LDL concentration was determined from collected serum with ELISA. Ovariectomized rats were heavier than sham-operated rats overtime (211 ± 38 vs. 169 ± 22g; p <0.0001). Food intake and organ masses were greater in ovariectomized rats compared to the sham-operated rats. When normalized to body mass, the food intake and organ masses were lower than in the sham-operated rats. Ovariectomized rats had greater left ventricular (LV) end-diastolic diameter (5.1 ± 0.4 vs. 4.6 ± 0.6mm; p = 0.03) and LV end-systolic diameter (3.0 ± 0.5 vs. 2.4 ± 0.4mm; p = 0.004) than sham-operated rats. The ovariectomized rats also had reduced endocardial fractional shortening (41 ± 8 vs. 49 ± 4%) and LV ejection fraction (71 ± 10 vs. 80 ± 4%) (both p = 0.007) than sham-operated rats. The cardiometabolic parameters measured were similar between the CPS and control lighting rats, except for a greater water intake overtime (CPS: 29 ± 7.1 vs. ctr light: 26 ± 3.2ml/day; p = 0.048) and a reduced liver mass (CPS: 7.2 ± 0.6 vs. ctr light: 7.6 ± 0.8g; p = 0.03) in CPS rats. When normalized to body mass, sham-operated rats had a greater water intake than the ovariectomized rats. No interaction between ovariectomy and CPS was demonstrated. In conclusion, estrogen deficiency impairs systolic function in female SHR. However, circadian misalignment does not worsen the cardiometabolic parameters in female SHR. Because of their genetic predispositions, female SHR may already have abnormal circadian rhythms, illustrating the complex and multifaceted circadian regulation within this rat model
  • Thumbnail Image
    Item
    The impact of altitude on the prevalence and characteristics of Restless Legs Syndrome
    (University of the Witwatersrand, Johannesburg, 2023) Munian, Pariska
    Restless Legs Syndrome (RLS) is a neurological sensory disorder, characterised by the irresistible urge to move due to unpleasant, deep-seated paresthesias in the legs. The urge to move usually occurs in the evening, when an individual is at rest and the sensations experienced are alleviated with movement. The prevalence of RLS in a general population ranges from 2.5 to 10%, from studies across the globe. Differences in RLS prevalence have been noted between different ethnic groups, with individuals of European ancestry exhibiting greater prevalence of RLS compared to individuals of Asian and African ancestry. The aetiology of RLS is unclear; however, there is evidence of central nervous system iron dysregulation. Low partial pressure of oxygen at high altitude, which is a large distance above sea level, may exacerbate iron dysregulation which may account for the greater prevalence of RLS at high compared to low altitude, which is an area at sea level. However, the impact of altitude on the prevalence of RLS requires further investigation and is the aim of this study. To investigate the effect of altitude on the prevalence and characteristics of RLS, a questionnaire was administered to the general South African population at two altitudes: low altitude (Durban, South Africa) and higher altitude, (1753m above sea level, Johannesburg, South Africa). The survey was completed by 1291 participants (416 at low altitude and 875 at higher altitude). Using an online questionnaire, data were collected on demographic characteristics (including age, sex and ethnicity), the Cambridge-Hopkins RLS questionnaire (to assess the presence/absence of RLS), self-reported iron deficiency, subjective measures of sleep, measures of daytime sleepiness (using the Epworth Sleepiness Scale) and levels of fatigue (using the Fatigue Assessment Scale). RLS was significantly more prevalent at the higher altitude (n = 69, 7.9%) compared to low altitude (n = 20, 4.8%), which may be due to an increase in iron dysregualtion at high altitude, resulting from the low partial pressure of oxygen. Factors associated with RLS also were exacerbated at higher altitude; these include increased RLS severity (p = 0.003), increased daytime sleepiness (p = 0.04) and decreased self-reported iron levels (p = 0.03) in individuals with RLS at higher altitude compared with low altitude. RLS was less prevalent in individuals with African ancestry than in those with European ancestry at the higher altitude (p = 0.0025). However, RLS was more prevalent in individuals with African ancestry than in those with Indian ancestry at low altitude (p = 0.0004). My data therefore support that altitude appears relevant to the pathophysiology of RLS, with high altitude presenting as a risk factor for RLS and exacerbating some characteristics of RLS