Browsing by Author "Strijdom, Hans"

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    Ambient air pollution and health in Sub-Saharan Africa : current evidence, perspectives and a call to action
    (Elsevier, 2019) Katoto, Patrick D. M. C.; Byamungu, Liliane; Brand, Amanda S.; Mokaya, Jolynne; Strijdom, Hans; Goswami, Nandu; De Boever, Patrick; Nawrot, Tim S.; Nemery, Benoit
    Background: People from low- and middle-income countries are disproportionately affected by the global burden of adverse health effects caused by ambient air pollution (AAP). However, data from Sub-Saharan Africa (SSA) are still scarce. We systematically reviewed the literature to describe the existing knowledge on AAP and health outcomes in SSA. Methods: We searched PubMed, Medline-OVID, EMBASE and Scopus databases to identify studies of AAP and health outcomes published up to November 15, 2017. We used a systematic review approach to critically analyze and summarize levels of outdoor air pollutants, and data on health effects associated with AAP. We excluded occupational and indoor exposure studies. Results: We identified 60 articles, with 37 only describing levels of AAP and 23 assessing the association between air pollution and health outcomes. Most studies (75%) addressing the relation between AAP and disease were cross-sectional. In general, exposure data were only obtained for selected cities in the framework of temporary international collaborative research initiatives without structural long-term continuation. Measurements of AAP revealed 10–20 fold higher levels than WHO standards. Of the 23 studies reporting health effects, 14 originated from South Africa, and most countries within SSA contributed no data at all. No studies, except from South Africa, were based on reliable morbidity or mortality statistics at regional or country level. The majority of studies investigated self-reported respiratory symptoms. Children and the elderly were found to be more susceptible to AAP. Conclusion: AAP and its negative health effects have been understudied in SSA compared with other continents. The limited direct measurements of air pollutants indicate that AAP in SAA cities is high compared with international standards. Efforts are needed to monitor AAP in African cities, to identify its main sources, and to reduce adverse health effects by enforcing legislation.
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    Cardiovascular risk and endothelial function in people living with HIV/AIDS: design of the multi-site, longitudinal EndoAfrica study in the Western Cape Province of South Africa
    (BioMed Central, 2017-01-07) Strijdom, Hans; De Boever, Patrick; Walzl, Gerhard; Essop, M. Faadiel; Nawrot, Tim S.; Webster, Ingrid; Westcott, Corli; Mashele, Nyiko; Everson, Frans; Malherbe, Stephanus T.; Stanley, Kim; Kessler, Harald H.; Stelzl, Evelyn; Goswami, Nandu
    Background: There is growing evidence of an interaction between HIV-infection, anti-retroviral therapy (ART) and cardiovascular diseases (CVD). Epidemiological studies in Europe and North America have been observing a shift towards an increased incidence of coronary heart disease and acute myocardial infarctions in HIV-infected populations compared to the general population even after adjusting for traditional cardiovascular risk factors. Despite South Africa (and sub-Saharan Africa, SSA) being regarded as the epicentre of the global HIV epidemic, very little is known about the prevalence of cardiovascular risk factors and precursors of vascular disease in HIV-infected populations in this region. The knowledge gap is further widened by the paucity of data from prospective studies. We present the rationale, objectives and key methodological features of the EndoAfrica study, which aims to determine whether HIVinfection and ART are associated with altered cardiovascular risk and changes in vascular endothelial structure and function in adults living in the Western Cape Province of South Africa. Methods: In this longitudinal study, comprehensive cardiovascular assessments of HIV-negative and HIV-positive (with and without ART) study participants are performed by clinical and biochemical screening for traditional cardiovascular risk factors and biomarkers of CVD. Vascular and endothelial function is determined by brachial artery flow-mediated dilatation (FMD), carotid-intima-thickness (IMT) measurements and quantitative retinal blood vessel analyses, complemented by vascular endothelial biomarker assays. Finally, we aim to statistically determine whether HIVinfection and/or ART are associated with increased cardiovascular risk and vascular endothelial dysfunction, and determine whether there is progression/regression in these endpoints 18 months after the baseline assessments. Discussion: The EndoAfrica study provides a unique opportunity to recruit a cohort of HIV-infected patients and HIVnegative controls who will be comprehensively and longitudinally assessed for cardiovascular risk and disease profile with vascular endothelial function as a potentially important intermediate cardiovascular phenotype. To our knowledge, it is the first time that such a systematic study has been established in the context of SSA and South Africa.
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    Fall history and associated factors among adults living with HIV-1 in the Cape Winelands, South Africa : an exploratory investigation
    (Oxford University Press, 2019) Berner, Karina; Strijdom, Hans; Essop, M. Faadiel; Webster, Ingrid; Morris, Linzette; Louw, Quinette
    Background. People with HIV-1 (PWH) exhibit a high fall incidence and increased fracture risk. As little is known about fall frequency and associated factors in PWH residing in lower-middle-income countries (LMIC), we investigated fall frequency, bone quality, and factors associated with fall history in a South African cohort. Methods. Fifty PWH without obvious predisposing factors for mobility impairments attending 2 public primary care clinics in the Western Cape region participated. Demographic, clinical, and physical performance data were collected. Falls were assessed retrospectively over 12 months. Mobility and balance were evaluated using a physical performance battery. Bone mineral density was screened using quantitative ultrasound (QUS). Associations between variables and falls grouping were analyzed using chi-square tests, t tests, and Mann-Whitney U tests, and effect sizes (ES) were calculated. Results. Thirty-four percent of PWH (median age, 36.6 years) reported falling during the past year, and 41.2% of fallers reported multiple falls. Fallers had more mobility problems (P = .013), higher fear of falling (P = .007), higher fracture history (P = .003), worse balance performance (P < .001), higher proportions of detectable viral loads (P = .021), and poorer bone quality (P = .040). Differences were of medium to large ES. Conclusions. This exploratory study is the first to show that relatively young South African PWH without obvious predisposing factors for gait and balance impairments experience falls. The observed fall-associated factors warrant further research using larger samples and longitudinal designs to ascertain fall predictors within this population.
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    Fenofibrate protects endothelial cells against the harmful effects of TNF-alpha
    (South African Heart Association, 2017) Westcott, Corli; Genis, Amanda; Mthethwa, Mashudu; Graham, Roxanne; Van Vuuren, Derick; Huisamen, Barbara; Strijdom, Hans
    Introduction: Fenofibrate exerts pleiotropic effects on endothelial cells (ECs) by, amongst others, increasing nitric oxide (NO) production. We aimed to investigate fenofi brate’s putative beneficial actions in healthy or TNF-alpha-induced dysfunctional ECs. Methods: Fenofi brate-induced pro-vasodilatory responses were assessed in aortic rings (50 - 125μM; 30min) with and without L-NMMA (100μM). Rat cardiac microvascular ECs were treated with fenofibrate (30 and 50μM; 1h). In the pre-treatment experiments, fenofibrate (50μM) was administered one hour before TNFalpha treatment (20ng/ml; 24h). NO-production (DAF-2/DA or Griess assay), mitochondrial ROS-production (MitoSox™), cell viability (propidium iodide staining), and changes in the expression/phosphorylation of critical endothelial proteins were measured by Western blotting. Results: Fenofibrate increased NO-production ˜2-fold in healthy ECs (p<0.05 vs. vehicle). A ˜23% pro-vasodilatory response was induced in aortic rings, which was reversed by L-NMMA (p<0.05 vs. fenofibrate). Fenofibrate pretreatment ameliorated TNF-alpha-induced endothelial dysfunction by reversing the loss of NO, improving oxidative stress, restoring cell viability and preventing caspase-3 activation. Protective effects were underpinned by ˜47% and ˜49% up-regulation of activated eNOS and AMP-kinase, respectively (p<0.05 vs. TNFalpha). Conclusions: Fenofibrate protects TNF-alpha-induced dysfunctional ECs via up-regulated eNOS-NO, reduced oxidative stress and improved cell viability. These novel findings warrant further investigations to explore the potential use of fenofibrate as an anti-endothelial dysfunction therapeutic agent.
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    Highly active antiretroviral therapy alters sperm parameters and testicular antioxidant status in diet-induced obese rats
    (Korean Society of Toxicology, 2018) Oyeyipo, Ibukun P.; Skosana, Bongekile T.; Everson, Frans P.; Strijdom, Hans; Du Plessis, Stefan S.
    The efficacy of highly active antiretroviral therapy (HAART) has led to an increase demand for therapeutic use, thereby necessitating investigation into drug toxicity. This study was designed to investigate the in vivo effects of HAART on sperm parameters and testicular oxidative stress in lean and obese rats. Wistar rats (males, n = 40, weighing 180~200 g) were assigned randomly into 4 groups and treated accordingly for 16 weeks as follows: Control (C): lean group fed with standard rat chow; Diet induced obesity (DIO): obese animals fed a high caloric diet; C + ART: lean animals treated with HAART; DIO + ART: obese animals treated with HAART. An antiretroviral drug combination of Tenofovir, Emtricitabine and Efavirenz at a dose of 17, 26 and 50 mg/kg/day was administered for the latter 6 weeks via jelly cube feeding. At the end of the experimental period, sperm analysis was performed on sperm collected from the caudal epididymis, while the testis was homogenized for antioxidant enzyme and lipid peroxidation assays. Results showed that HAART significantly decreased sperm motility (p < 0.05) in both lean and obese animals, and viability (p < 0.05) in the DIO group. Testicular glutathione, catalase and superoxide dismutase were significantly decreased (p < 0.05), while Thiobarbituric acid reactive substances (TBARS) levels were significantly increased (p < 0.05) when the DIO+ART group was compared to Control group. Thus, the decreased sperm qualities associated with HAART might be as a result of increased testicular oxidative stress prominent in obese animals.
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    HIV and antiretroviral therapy are independently associated with cardiometabolic variables and cardiac electrical activity in adults from the Western Cape Region of South Africa
    (MDPI, 2021-09) Williams, Cassidy; Kamau, Festus M.; Everson, Frans; Kgokane, Boipelo; De Boever, Patrick; Goswami, Nandu; Webster, Ingrid; Strijdom, Hans
    Cardiovascular-related complications are on the rise in people with HIV/AIDS (PWH); however, the relationship among HIV and antiretroviral therapy (ART)-related parameters, cardiovascular risk, and cardiac electrical activity in PWH remain poorly studied, especially in sub-Saharan African populations. We investigated whether HIV and ART are associated with cardiometabolic and cardiac electrical activity in PWH from Worcester in theWestern Cape Province, South Africa. This was a cross-sectional study with HIV-negative (HIV�����, n = 24) and HIV-positive on ART (HIV+/ART+, n = 63) participants. We obtained demographic, lifestyle, and medical history data and performed anthropometric, clinical assessments, and blood/urine biochemistry. We performed multiple stepwise linear regression analyses to determine independent associations among HIV, ART, cardiometabolic, and electrocardiographic (ECG) variables. HIV+/ART+ independently associated with a lower body mass index (p = 0.004), elevated gamma-glutamyl transferase levels ( : 0.333 (0.130–0.573); p = 0.002), and elevated alanine aminotransferase levels ( : 0.427 (0.224–0.629); p < 0.001) compared to HIV�����. Use of second-line ART was positively associated with high-sensitivity C-reactive protein (p = 0.002). Although ECG parameters did not differ between HIV����� and HIV+/ART+, viral load positively associated with p-wave duration (0.306 (0.018–0.594); p = 0.038), and longer HIV duration ( 5 years) with ST-interval (0.270 (0.003–0.537); p = 0.047) after adjusting for confounding factors. Our findings suggest that HIV and ART are associated with mixed effects on this population’s cardiometabolic profile and cardiac electrical activity, underpinning the importance of cardiovascular risk monitoring in PWH.
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    Hypoxia and the heart : the role of nitric oxide in cardiac myocytes and endothelial cells
    (Stellenbosch : University of Stellenbosch, 2007-03) Strijdom, Hans; Lochner, Amanda; Moolman, Johan; University of Stellenbosch. Faculty of Health Sciences. Dept. of Biomedical Sciences. Medical Physiology.
    Nitric oxide (NO) is a major signaling molecule in the heart with various biological effects. The putative role of NO as a cardioprotective agent against ischaemiareperfusion injury and in ischaemic preconditioning (IP) has made it one of the fastest growing fields in basic cardiovascular research. However, NO may also be associated with harmful effects, especially when released in excessive amounts. Little is known about the relative contributions to NO-production by the cardiac microvascular endothelial cells (CMECs) and the adjacent cardiomyocytes. Furthermore, the respective roles of endothelial NOS (eNOS) and inducible NOS (iNOS) are not well characterized in these cell types, particularly in hypoxia. In order to gain a better understanding of the role of NO in the hypoxic/ischaemic heart, the aims of this study were to: (1) develop an isolated cardiomyocyte model in which hypoxia and early IP can be induced and the role of NO assessed; (2) measure NOproduction in cardiomyocytes and CMECs under baseline and hypoxic conditions; and (3) evaluate the expression, regulation and activation of eNOS and iNOS in cardiomyocytes and CMECs (baseline and hypoxia) and establish the relationship with NO-production under these conditions. Cardiomyocytes isolated from adult rat hearts and commercially purchased rat CMECs were used as cell models.
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    Personal NO2 and volatile organic compounds exposure levels are associated with markers of cardiovascular risk in women in the Cape Town region of South Africa
    (MDPI, 2019) Everson, Frans; De Boever, Patrick; Nawrot, Tim S.; Goswami, Nandu; Mthethwa, Mashudu; Webster, Ingrid; Martens, Dries S.; Mashele, Nyiko; Charania, Sana; Kamau, Festus; Strijdom, Hans
    ENGLISH ABSTRACT: Exposure to ambient NO2 and benzene, toluene ethyl-benzene and m+p- and o-xylenes (BTEX) is associated with adverse cardiovascular effects, but limited information is available on the effects of personal exposure to these compounds in South African populations. This 6-month follow-up study aims to determine 7-day personal ambient NO2 and BTEX exposure levels via compact passive diffusion samplers in female participants from Cape Town, and investigate whether exposure levels are associated with cardiovascular risk markers. Overall, the measured air pollutant exposure levels were lower compared to international standards. NO2 was positively associated with systolic and diastolic blood pressure (SBP and DBP), and inversely associated with the central retinal venular equivalent (CRVE) and mean baseline brachial artery diameter. o-xylene was associated with DBP and benzene was strongly associated with carotid intima media thickness (cIMT). Our findings showed that personal air pollution exposure, even at relatively low levels, was associated with several markers of cardiovascular risk in women residing in the Cape Town region.
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    Physical exercise potentially targets epicardial adipose tissue to reduce cardiovascular disease risk in patients with metabolic diseases : oxidative stress and inflammation emerge as major therapeutic targets
    (MDPI, 2021-11-04) Nyawo, Thembeka A.; Pheiffer, Carmen; Mazibuko-Mbeje, Sithandiwe E; Mthembu, Sinenhlanhla X. H.; Nyambuya, Tawanda M.; Nkambule, Bongani B.; Sadie-Van Gijsen, Hanel; Strijdom, Hans; Tiano, Luca; Dludla, Phiwayinkosi V.
    ENGLISH ABSTRACT: Excess epicardial adiposity, within a state of obesity and metabolic syndrome, is emerging as an important risk factor for the development of cardiovascular diseases (CVDs). Accordingly, increased epicardial fat thickness (EFT) implicates the exacerbation of pathological mechanisms involving oxidative stress and inflammation within the heart, which may accelerate the development of CVDs. This explains increased interest in targeting EFT reduction to attenuate the detrimental effects of oxidative stress and inflammation within the setting of metabolic syndrome. Here, we critically discuss clinical and preclinical evidence on the impact of physical exercise on EFT in correlation with reduced CVD risk within a setting of metabolic disease. This review also brings a unique perspective on the implications of oxidative stress and inflammation as major pathological consequences that link increased EFT to accelerated CVD risk in conditions of metabolic disease.
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    Relationship between Endothelial Function, Antiretroviral Treatment and Cardiovascular Risk Factors in HIV Patients of African Descent in South Africa: A Cross-Sectional Study
    (MDPI, 2021-01-20) Nkeh-Chungag, Benedicta N.; Goswami, Nandu; Engwa, Godwill A.; Sewani-Rusike, Constance R.; Mbombela, Vuyolwethu; Webster, Ingrid; De Boever, Patrick; Kessler, Harald H.; Stelzl, Evelyn; Strijdom, Hans
    Limited information on the effect of antiretroviral treatment (ART) on vascular function in South Africans of African descent living with human immunodeficiency virus (HIV) is available. The relationship between ART, vascular function and cardiovascular risk factors in South Africans of African ancestry with HIV was therefore studied. This cross-sectional study recruited 146 HIVpositive individuals on ART (HIV+ART+), 163 HIV-positive individuals not on ART (HIV+ART�����) and 171 individuals without HIV (HIV�����) in Mthatha, Eastern Cape Province of South Africa. Flowmediated dilation (FMD) test was performed to assess endothelial function. Anthropometry and blood pressure parameters were measured. Lipid profile, glycaemic indices, serum creatinine as well as CD4 count and viral load were assayed in blood. Urinary albumin to creatinine ratio (ACR) was determined as a marker of cardiovascular risk. Obesity and albuminuria were positively associated with HIV, and HIV+ART+ participants had significantly higher HDL cholesterol. Dyslipidaemia markers were significantly higher in hypertensive HIV+ART+ participants compared with the controls (HIV+ART����� and HIV����� participants). FMD was not different between HIV+ART+ participants and the controls. Moreover, HIV+ART+ participants with higher FMD showed lower total cholesterol and LDL cholesterol comparable to that of HIV����� and HIV+ART����� participants. A positive relationship between FMD and CD4 count was observed in HIV+ART+ participants. In conclusion, antiretroviral treatment was associated with cardiovascular risk factors, particularly dyslipidaemia, in hypertensive South Africans of African ancestry with HIV. Although, ART was not associated with endothelial dysfunction, flow-mediated dilatation was positively associated with CD4 count in HIV-positive participants on ART.
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    Treatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese rats
    (Public Library of Science, 2018-12-05) Everson, Frans; Genis, Amanda; Ogundipe, Temitope; De Boever, Patrick; Goswami, Nandu; Lochner, Amanda; Blackhurst, Dee; Strijdom, Hans
    HIV-infection, certain antiretroviral drug classes, especially protease inhibitors (PI), and obesity are associated with increased ischaemic heart disease (IHD) risk. However, the effect of PI-free fixed dose combination (FDC) antiretroviral therapy (ART) on hearts exposed to ischaemia-reperfusion injury (I/R) is unknown, particularly in obesity. This is becoming relevant as World Health Organisation guidelines recommend a FDC ART containing (non-) nucleoside reverse transcriptase inhibitors (tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV)) as first-line HIV treatment. Additionally, obesity rates are rising in HIV-infected populations, not only in ART-experienced individuals, but also at the time of ART initiation, which may further increase the risk of IHD. Therefore, we investigated the effects of PI-free FDC ART in myocardial I/R-exposed hearts from obese rats. Obesity was induced in male wistar rats via a 16-week high calorie diet. At week 10, treatment with a FDC ART drug containing TDF/FTC/EFV was initiated. Biometric and metabolic parameters, as well as myocardial functional recovery and infract size (IS), and myocardial signalling proteins following I/R were assessed after 16 weeks. Obese rats presented with increased body and intraperitoneal fat mass, elevated triglyceride and TBARS levels, whilst the hearts responded to I/R with impaired functional performance and increased IS. The FDC ART treatment did not alter biometric and metabolic parameters in obese rats. In a novel finding, ART protected obese hearts against I/R as shown by improved functional performance and smaller IS vs. untreated obese hearts. Cardioprotection was underscored by increased myocardial phosphorylated endothelial nitric oxide synthase (eNOS) and reduced AMP-kinase levels. In conclusion, these results demonstrate for the first time, that 6-weeks treatment of obese rats with a FDC ART drug specifically containing TDF/FTC/EFV conferred cardioprotection against I/R. The FDC ART-induced cardioprotection was seemingly unrelated to metabolic changes, but rather due to direct cardiac mechanisms including the up-regulation of myocardial eNOS.
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    Vascular function and cardiovascular risk in a HIV infected and HIV free cohort of African ancestry : baseline profile, rationale and methods of the longitudinal EndoAfrica-NWU study
    (BioMed Central, 2020-07-03) Fourie, Carla M. T.; Botha-Le Roux, Shani; Smith, Wayne; Schutte, Aletta E.; Breet, Yolandi; Mels, Carina M. C.; Gafane-Matemane, Lebo F.; Lammertyn, Leandi; Uys, Lisa; Burger, Adele; Joseph, Jitcy S.; Goswami, Nandu; De Boever, Patrick; Strijdom, Hans
    Background: People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world’s largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. Methods: In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. Results: At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gammaglutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV. Conclusion: Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.