No Association Between AGT Gene Polymorphisms with Hypertension in a South African Population.

Purpose: Hypertension is a leading cause of cardiovascular-related morbidity and mortality worldwide, with a prevalence increasing at an alarming rate in both middle- and low-income countries. Various environmental and genetic factors have been attributed to play a significant role in the increasing prevalence of hypertension. Single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene are reported to have a significant association with hypertension; however, there are limited studies done on South African populations. Therefore, this case-control study aimed to investigate the association between AGT SNPs (rs2004776, rs3789678, rs5051 and rs7079) with hypertension in a study population of isiXhosa-speaking participants from the Eastern Cape Province in South Africa. Materials and Methods: The SNPs were genotyped in 250 hypertensive cases and 237 normotensive controls, using TaqMan genotyping assays. Results: For the SNP rs2004776, the frequency of CC genotype (18.4%) and C allele (44%) in hypertensive cases showed no significant differences (p = 0.52, χ2 = 1.32), when compared to the normotensive control group (CC: 19.8% and C allele: 43%). Similar results were obtained for the genotypic and allelic frequencies between hypertensive cases and normotensive controls for rs3789678 (p = 0.88, χ2=0.26) and rs5051 (p = 0.57, χ2=1.12), and rs7079 (p = 0.33, χ2=2.23). These findings demonstrate that there were no significant associations between the SNPs rs2004776, rs3789678, rs7079, rs5051 with hypertension in our study population. Conclusion: These findings suggest that AGT gene polymorphisms are not associated with the development of hypertension in the studied population. The present study represents the first genetic report to investigate the AGT gene polymorphisms with hypertension in an isiXhosa-speaking South African population.

People living with HIV display increased anti-apolipoprotein A1 auto-antibodies, inflammation, and kynurenine metabolites: a case-control study.

Objective: This study aimed to study the relationship between auto-antibodies against apolipoprotein A1 (anti-apoA1 IgG), human immunodeficiency virus (HIV) infection, anti-retroviral therapy (ART), and the tryptophan pathways in HIV-related cardiovascular disease. Design: This case-control study conducted in South Africa consisted of control volunteers (n = 50), people living with HIV (PLWH) on ART (n = 50), and untreated PLWH (n = 44). Cardiovascular risk scores were determined, vascular measures were performed, and an extensive biochemical characterisation (routine, metabolomic, and inflammatory systemic profiles) was performed. Methods: Anti-apoA1 IgG levels were assessed by an in-house ELISA. Inflammatory biomarkers were measured with the Meso Scale Discovery® platform, and kynurenine pathway metabolites were assessed using targeted metabolomic profiling conducted by liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS). Results: Cardiovascular risk scores and vascular measures exhibited similarities across the three groups, while important differences were observed in systemic inflammatory and tryptophan pathways. Anti-apoA1 IgG seropositivity rates were 15%, 40%, and 70% in control volunteers, PLWH ART-treated, and PLWH ART-naïve, respectively. Circulating anti-apoA1 IgG levels were significantly negatively associated with CD4+ cell counts and positively associated with viremia and pro-inflammatory biomarkers (IFNγ, TNFα, MIPα, ICAM-1, VCAM-1). While circulating anti-apoA1 IgG levels were associated with increased levels of kynurenine in both control volunteers and PLWH, the kynurenine/tryptophan ratio was significantly increased in PLWH ART-treated. Conclusion: HIV infection increases the humoral response against apoA1, which is associated with established HIV severity criteria and kynurenine pathway activation.

Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort.

Introduction: Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan African populations are sparse. Methods: We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic. A second sample from the same patients was collected on day 7 of ICU admission. Patients were followed up until in-hospital death or hospital discharge. A custom-designed 52 biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between biomarkers and mortality based on pre-determined functional groups, and individual analytes. Results: Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines, chemokines, and acute phase reactants, as well as reduced levels of regulatory T cell cytokines. Interleukin (IL)-15 and IL-18 were elevated in those who died, and levels reduced over time in those who survived. Procalcitonin (PCT), C-reactive protein, Endothelin-1 and vascular cell adhesion molecule-1 were elevated in those who died. Discussion: These results show the pattern of dysregulation in critical COVID-19 in a Sub-Saharan African cohort. They suggest that fatal COVID-19 involved excessive activation of cytotoxic cells and the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome. Furthermore, superinfection and endothelial dysfunction with thrombosis might have contributed to mortality. HIV infection did not affect the outcome. A clinically relevant biosignature including PCT, pH and lymphocyte percentage on differential count, had an 84.8% sensitivity for mortality, and outperformed the Luminex-derived biosignature.

Recombinant Endostatin as a Potential Radiosensitizer in the Treatment of Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer, which is the leading cause of cancer-related deaths worldwide. Over the past decades, tumour angiogenesis has been intensely studied in the treatment of NSCLC due to its fundamental role in cancer progression. Several anti-angiogenic drugs, such as recombinant endostatin (RE), have been evaluated in several preclinical and clinical trials, with mixed and often disappointing results. However, there is currently an emerging interest in RE due to its ability to create a vascular normalization window, which could further improve treatment efficacy of the standard NSCLC treatment. This review provides an overview of preclinical and clinical studies that combined RE and radiotherapy for NSCLC treatment. Furthermore, it highlights the ongoing challenges that have to be overcome in order to maximize the benefit; as well as the potential advantage of combinations with particle therapy and immunotherapy, which are rapidly gaining momentum in the treatment landscape of NSCLC. Different angiogenic and immunosuppressive effects are observed between particle therapy and conventional X-ray radiotherapy. The combination of RE, particle therapy and immunotherapy presents a promising future therapeutic triad for NSCLC.

Concentrations of Efavirenz, Tenofovir, and Emtricitabine in Obesity: A Cross-Sectional Study.

BACKGROUND: Obesity is increasing worldwide including in people living with HIV (PLWH). Antiretroviral pharmacokinetic data in obesity are limited. OBJECTIVES: To measure antiretroviral drug concentrations in obese and nonobese PLWH treated with the fixed-dose combination of efavirenz-tenofovir-emtricitabine. To determine pharmacokinetic differences across indicators of obesity and their associated immunovirological outcomes. METHODS: We conducted a cross-sectional sample analysis of 2 cohort studies. We measured mid-dose efavirenz, 8-hydroxy-efavirenz, tenofovir, and emtricitabine concentrations. Antiretroviral drug concentrations were analyzed by body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). RESULTS: We performed a study of 213 participants: General obesity was detected in 20.4% using BMI and abdominal obesity in 53.6% using WC and 62.4% using WHR, respectively. The median concentrations of all antiretroviral drugs were lower among obese participants determined by BMI and WC, with efavirenz showing greater differences than tenofovir or emtricitabine. For BMI, results were most striking for efavirenz (1752.3 vs 2342.9 ng/mL, P = 0.002) with lower concentrations in obese participants. Using WC, efavirenz (1845.8 vs 2571.2 ng/mL, P < 0.001), tenofovir (65.8 vs 73.2 ng/mL, P = 0.036), and emtricitabine (159.5 vs 221.0 ng/mL, P = 0.005) concentrations were lower in obese participants. Eight-hydroxyefavirenz concentrations were similar in nonobese and obese participants for WC. Using WHR, the concentrations of all antiretroviral drugs were lower in the obese population, most strikingly for emtricitabine (173.5 vs 229.0 ng/mL, P = 0.015). There were no immunovirological associations. CONCLUSION: We found lower antiretroviral concentrations in all obese groups, most strikingly in participants with abdominal obesity determined by WC. Lower drug concentrations had no immunovirological associations.

Cardiovascular Profile of South African Adults with Low-Level Viremia during Antiretroviral Therapy.

Chronic inflammation is an HIV infection feature, contributing to elevated risk of cardiovascular disease among people with HIV, which can be induced by viral replication. A proportion of antiretroviral therapy (ART) recipients fail to achieve viral suppression, despite not meeting criteria for treatment failure, so-called low-level viremia (LLV). We investigated the relationship between LLV and an array of cardiovascular measures and biomarkers. South Africans with LLV (viral load = 50−999 copies/mL) and virological suppression (viral load <50 copies/mL) were selected from the EndoAfrica study (all receiving efavirenz-based ART) for cross-sectional comparison of vascular structure and function measures, as well as 21 plasma biomarkers related to cardiovascular risk and inflammation. Associations were investigated with univariate, multivariate, and binomial logistic regression analyses (having outcome measures above (cases) or below (controls) the 75th percentile). Among 208 participants, 95 (46%) had LLV, and 113 (54%) had viral suppression. The median age was 44 years, 73% were women, and the median ART duration was 4.5 years. Cardiovascular measures and biomarker levels were similar between these two categories. Cardiovascular function and structure measures were not associated with viremia status and having LLV did not increase the odds of having outcome measures above the 75th percentile. In this study among South African ART recipients, LLV did not associate with cardiovascular risk.

A systematic review exploring the significance of measuring epicardial fat thickness in correlation to B-type natriuretic peptide levels as prognostic and diagnostic markers in patients with or at risk of heart failure.

Emerging evidence suggests that epicardial fat thickness (EFT) may be a critical feature to understand cardiac health and determine the risk of heart failure. The current review critically assesses and discusses evidence on the efficiency of measuring EFT, in comparison to the well-known markers B-type natriuretic peptide (BNP) and its N-terminal fragment pro-B-type natriuretic peptide (NT-proBNP), as a prognostic and diagnostic approach in individuals with or at risk of heart failure. A systematic approach was undertaken to search major databases, PubMed, Scopus, Google Scholar and the Cochrane library to identify studies that quantified EFT and serum BNP/NT-proBNP levels in individuals with or at risk of heart failure. Twelve studies met the inclusion criteria and a total of 1983 participants were included in this systematic review. Evidence shows a clear association between increased EFT and elevated BNP/NT-proBNP levels in individuals with metabolic disease and suggests that both methods can be used for heart failure diagnosis and prognosis. However, due to the broad spectrum of challenges linked with measuring EFT, BNP/Pro-BNP is the predominant method used for heart failure diagnosis and prognosis in clinical practice. Nonetheless, measuring EFT provides a powerful and reproducible diagnostic tool for risk stratification and heart failure diagnosis and prognosis. Importantly, measuring EFT proves valuable to validate BNP/NT-proBNP levels to predict heart failure, especially due to its non-invasive nature.

Comparison of endothelial function and cardiometabolic profiles of people living with HIV in two South African regions: the EndoAfrica study.

BACKGROUND: People living with HIV (PLWH) are at risk for cardiovascular disease, but regional differences have not been studied in South Africa. We compared endothelial function and cardiometabolic markers in PLWH and HIV-free controls from two distinct South African regions. METHODS: We measured flow-mediated dilation (FMD), cardiometabolic, immunological and viral markers in age- and gender-matched PLWH on antiretroviral therapy (n = 100/group) and HIV-free participants (n = 50/group) in samples from cohort studies in the North West and Western Cape provinces. RESULTS: Endothelial function and cardiometabolic profiles were not worse in PLWH than in HIV-free individuals, and %FMD was not associated with cardiometabolic, viral or immunological markers. PLWH from the North West region had lower %FMD but overall better metabolic profiles. CONCLUSIONS: Ethnic, cultural and socio-economic differences need further investigation to understand the possible protective role of antiretroviral treatment on the vasculature and to direct region-specific HIV and AIDS guidelines in South Africa.

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.

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.

HIV and Antiretroviral Therapy Are Independently Associated with Cardiometabolic Variables and Cardiac Electrical Activity in Adults from the Western Cape Region of South Africa.

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 the Western 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 (ß: 0.333 (0.130-0.573); p = 0.002), and elevated alanine aminotransferase levels (ß: 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.

Mobility Deviations in Adults With Human Immunodeficiency Virus: A Cross-Sectional Assessment Using Gait Analysis, Functional Performance, and Self-Report.

BACKGROUND: Little is known about how human immunodeficiency virus (HIV) affects walking biomechanics, or about associations between HIV-related gait deviations, functional performance, and self-reported outcomes. This paper reports on (1) gait biomechanics and variability in people with HIV (PWH) and (2) associations with clinical tests, self-reported function, and falls. METHODS: A cross-sectional study tested consecutively sampled PWH (n = 50) and HIV-seronegative participants ([SNP] n = 50). Participants underwent 3-dimensional gait analysis, performed clinical tests (short walk and single leg stance tests with and without dual tasking, chair-rise tests, and a physical performance battery), and completed questionnaires about function and falls. Between-group comparisons were done using analysis of covariance. Linear correlations between gait variability, clinical tests, and patient-reported outcomes were established. RESULTS: People with HIV and SNP had comparable median ages (PWH = 36.6, interquartile range [IQR] = 32.0-45.6]; SNP = 31.1, IQR = 23.2-45.1). Compared with SNP, PWH walked slower (adjusted mean difference [MD] = -0.2 meters per second [m/s], 95% confidence interval [CI] = -0.3 to -0.1) with greater variability (adjusted MD = 14.7 variability score points, 95% CI = 9.9-19.5). Moreover, PWH were slower in five-times sit-to-stand (5STS) performance (adjusted MD = 1.9 seconds, 95% CI = 1.00-2.9). Significant deviations in hip kinematics (increased flexion; adjusted MDs = 2.4°-2.8°, P = .012-.016) and knee kinematics (reduced flexion; adjusted MDs = 2.3°-3.7°, P = .007-.027) were found in PWH during dual-task (DT) walking. The PWH's 5STS moderately correlated with larger gait variability (usual pace r = -0.5; dual task r = -0.6), poorer self-reported mobility (r = 0.4) and self-care function (r = 0.5), and fear of falling (P = .003). CONCLUSIONS: People with HIV presented with biomechanical deviations suggestive of a slowed and variable gait, especially under cognitive challenges. Five-times STS may be useful to screen for gait deviations in PWH.

Relationship between Endothelial Function, Antiretroviral Treatment and Cardiovascular Risk Factors in HIV Patients of African Descent in South Africa: A Cross-Sectional Study.

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 HIV-positive 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. Flow-mediated 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.

Cardiovascular effects of air pollution: current evidence from animal and human studies.

Air pollution is a global health concern. Particulate matter (PM)2.5, a component of ambient air pollution, has been identified by the World Health Organization as one of the pollutants that poses the greatest threat to public health. Cardiovascular health effects have been extensively documented, and these effects are still being researched to provide an overview of recent literature regarding air pollution-associated cardiovascular morbidity and mortality in humans. Additionally, potential mechanisms through which air pollutants affect the cardiovascular system are discussed based on human and additional animal studies. We used the strategy of a narrative review to summarize the scientific literature of studies that were published in the past 7 yr. Searches were carried out on PubMed and Web of Science using predefined search queries. We obtained an initial set of 800 publications that were filtered to 78 publications that were relevant to include in this review. Analysis of the literature showed significant associations between air pollution, especially PM2.5, and the risk of elevated blood pressure (BP), acute coronary syndrome, myocardial infarction (MI), cardiac arrhythmia, and heart failure (HF). Prominent mechanisms that underlie the adverse effects of air pollution include oxidative stress, systemic inflammation, endothelial dysfunction, autonomic imbalance, and thrombogenicity. The current review underscores the relevance of air pollution as a global health concern that affects cardiovascular health. More rigorous standards are needed to reduce the cardiovascular disease burden imposed by air pollution. Continued research on the health impact of air pollution is needed to provide further insight.

Vascular health assessment with flow-mediated dilatation and retinal image analysis: a pilot study in an adult population from Cape Town.

AIM: Flow-mediated dilatation (FMD) and retinal vascular analysis (RVA) may assist in predicting cardiovascular disease (CVD) but are poorly characterised in South Africa. We recorded baseline FMD and retinal vascular widths in healthy participants, and investigated associations with cardiovascular risk factors. METHODS: Endothelial function (measured with FMD), microvascular structure (evaluated via fundus image analysis) and major CVD risk factors were assessed in 66 participants from Cape Town. RESULTS: Median FMD% was 9.6%, with higher values in females. Mean retinal arteriolar and venular widths were ˜156 and ˜250 µm, respectively. FMD was not associated with CVD risk factors. Hypertension was associated with narrower retinal arterioles and venules. CONCLUSIONS: We report novel baseline FMD data in healthy South African adults from the Western Cape, and show that retinal microvascular calibres are associated with blood pressure. Our baseline FMD and RVA data could serve as a reference for future studies in South Africa.

HIV-related cardiovascular disease: any role for high-density lipoproteins?

The introduction of antiretroviral therapy (ART) has improved the life expectancy of patients infected with human immunodeficiency virus (HIV). However, this population is at an increased risk for noncommunicable diseases, including atherosclerotic cardiovascular disease (CVD). Both ART and viral infection may be potential contributors to the pathophysiology of HIV-related CVD. The mechanisms behind this remain unclear, but it is critical to delineate early biomarkers of cardiovascular risk in the HIV population. In this review, we postulate that potential biomarkers could include alterations to high-density lipoprotein (HDL). Indeed, recent data suggest that HIV and ART may induce structural changes of HDL, thus resulting in shifts in HDL subclass distribution and HDL functionality.

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.

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 18 months 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, gamma-glutamyltransferase 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.

Rooibos (Aspalathus linearis) protects against nicotineinduced vascular injury and oxidative stress in Wistar rats.

BACKGROUND: Rooibos (Aspalathus linearis) is an indigenous South African plant, traditionally used by the local population as a remedy against several ailments. More recently, rooibos was shown to exhibit potent antioxidant properties, attributed to its polyphenols. We assessed whether treatment with fermented rooibos (RF), unfermented rooibos (RUF) and melatonin (Mel), a well-documented antioxidant included for comparison, could counter the harmful vascular and pro-oxidant effects of nicotine. METHODS: Vascular function, antioxidant enzyme activity and lipid peroxidation were assessed in male adult rats treated with nicotine (5 mg/kg body weight/day) and 2% RF, 2% RUF or 4% Mel co-administration. Nitric oxide (NO) production and cell viability were measured in nicotine-exposed rat aortic endothelial cells (AECs) pre-treated with RF (0.015 mg/ml). RESULTS: Vascular studies showed that co-administration with RF or Mel exerted anti-contractile and pro-relaxation responses in aortic rings, and increased hepatic superoxide dismutase and catalase activity in nicotine-exposed animals. Co-treatment with Mel additionally decreased lipid peroxidation in nicotine-exposed rats. RUF exerted anti-contractile responses in aortic rings of nicotine-treated animals, while in nicotine-exposed AECs, RF pre-treatment increased intracellular NO levels. CONCLUSIONS: For the first time, we have shown that rooibos co-treatment exerted beneficial vascular effects in nicotine-exposed rats, and that this was associated with increased antioxidant enzyme activity.

Personal exposure to NO2 and benzene in the Cape Town region of South Africa is associated with shorter leukocyte telomere length in women.

Air pollution exposure is a major global health concern and has been associated with molecular aging. Unfortunately, the situation has not received much attention in the African region. The aim of this study was to investigate whether current personal ambient NO2 and benzene, toluene, ethyl-benzene and xylenes (ortho (o)-, meta (m)- and para (p)-xylene (BTEX) exposure is associated with leukocyte telomere length (LTL), a marker of molecular ageing, in apparently healthy women (mean ± SD age: 42.5 ± 13.4 years) residing in the Cape Town region of South Africa. The repeated measures study collected data from 61 women. Seven-day median (interquartile range (IQR)) personal NO2 and BTEX exposure levels were determined via compact passive diffusion samplers carried on the person prior to baseline (NO2: 14.2 (9.4-17.2) µg/m³; Benzene: 3.1 (2.1-5.3) µg/m³) and 6-month follow-up (NO2: 10.6 (6.6-13.6) µg/m³; Benzene: 2.2 (1.3-4.9) µg/m³) visits. LTL was measured at baseline and follow-up using a real-time PCR method. Multiple linear mixed model analyses (adjusting for age, body mass index, smoking, employment status, level of education and assessment visit) showed that each IQR increment increase in NO2 (7.0 µg/m³) and benzene (3.3 µg/m³) was associated with -7.30% (95% CI: -10.98 to -3.46%; p < 0.001) and -6.78% (95% CI: -11.88 to -1.39%; p = 0.015) difference in LTL, respectively. The magnitude of these effects of NO2 and benzene corresponds to the effect of an increase of 10.3- and 6.0-year in chronological age on LTL. Our study shows that personal exposures to NO2 and benzene are associated with molecular ageing as indicated by LTL in healthy women residing in the Cape Town region.

Fall History and Associated Factors Among Adults Living With HIV-1 in the Cape Winelands, South Africa: An Exploratory Investigation.

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.

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.

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.