The impact of endocrine disrupting compounds and carcinogens in wastewater: Implications for breast cancer.

The incidence of breast cancer is often associated with geographic variation which indicates that a person's surrounding environment can be an important etiological factor in cancer development. Environmental risk factors can include exposure to sewage- or wastewater, which consist of a complex mixture of pathogens, mutagens and carcinogens. Wastewater contains primarily carbonaceous, nitrogenous and phosphorus compounds, however it can also contain trace amounts of chemical pollutants including toxic metal cations, hydrocarbons and pesticides. More importantly, the contamination of drinking water by wastewater is a potential source of exposure to mammary carcinogens and endocrine disrupting compounds. Organic solvents and other pollutants often found in wastewater have been detected in various tissues, including breast and adipose tissues. Furthermore, these pollutants such as phenolic compounds in some detergents and plastics, as well as parabens and pesticides can mimic estrogen. High estrogen levels are a well-established risk factor for estrogen-receptor (ER) positive breast cancer. Therefore, exposure to wastewater is a risk factor for the initiation, progression and metastasis of breast cancer. Carcinogens present in wastewater can promote tumourigenesis through various mechanisms, including the formation of DNA adducts, gene mutations and oxidative stress. Lastly, the presence of endocrine disrupting compounds in wastewater can have negative implications for ER-positive breast cancers, where these molecules can activate ERα to promote cell proliferation, survival and metastasis. As such, strategies should be implemented to limit exposure, such as providing funding into treatment technologies and implementation of regulations that limit the production and use of these potentially harmful chemicals.

Noncommunicable Disease Conditions and HIV in Rural and Urban South Africa: 2005-2015.

Purpose: Hypertension, obesity, hyperlipidemia, and type 2 diabetes contribute primarily to noncommunicable disease deaths and together with human immunodeficiency virus contribute largely to mortality in South Africa. Our longitudinal study provides the necessary data and insights over a 10-year period to highlight the areas where improved management is required in urban and rural localities. Methods: This study included 536 rural and 387 urban Black participants aged 32 to 93 years from the North-West province, South Africa. Disease prevalence, treatment, and control were determined in 2005 and were re-evaluated in 2015. Multiple measures analyses were used to determine the trends of blood pressure and waist circumference. Results: The initial prevalence of hypertension was 53.2%, obesity was 23.6%, hyperlipidemia was 5.1%, diabetes was 2.9%, and human immunodeficiency virus was 10.7% in 2005. By 2015, the rural population had higher rates of hypertension (63.7% versus 58.5%) and lower rates diabetes (4.3% versus 7.9%) and hyperlipidemia (6.6% versus 18.0%) with similar obesity rates (41.7% versus 42.4%). The average blood pressure levels of urban hypertensives decreased (Ptrend<.001), whereas levels were maintained in the rural group (Ptrend=.52). In both locations, treatment and control rates increased from 2005 to 2015 for all conditions (all ≥6.7%), except for diabetes in which a decrease in control was observed. Waist circumference increased (Ptrend>.001) in both sex and locality groups over the 10-year period. Conclusion: Although average blood pressure of urban hypertensive individuals decreased, urgent measures focused on early identification, treatment, and control of the respective conditions should be implemented to decrease the burden of noncommunicable diseases.

The effect of HIF-1α inhibition in breast cancer cells prior to doxorubicin treatment under conditions of normoxia and hypoxia.

BACKGROUND: Oxygen deprivation is a key hallmark within solid tumours that contributes to breast-tumour pathophysiology. Under these conditions, neoplastic cells activate several genes, regulated by the HIF-1 transcription factor, which alters the tumour microenvironment to promote survival - including resistance to cell death in therapeutic attempts such as doxorubicin (Dox) treatment. METHODS: We investigated HIF-1ɑ as a therapeutic target to sensitize breast cancer cells to Dox treatment. Under both normoxic (21% O2) and hypoxic (∼0.1% O2) conditions, the HIF-1 inhibitor, 2-methoxyestradiol (2-ME), was investigated as an adjuvant for its ability to alter MCF-7 cell viability, apoptosis, autophagy and molecular pathways which are often associated with increased cell survival. RESULTS: Here we observed that an inverse relationship between HIF-1ɑ and apoptosis exists and that Dox promotes autophagy under hypoxic conditions. Although adjuvant therapy with 2-ME induced an antagonistic effect in breast cancer cells, upregulated HIF-1ɑ expression in a hypoxic environment promotes treatment resistance and this was attenuated once HIF-1ɑ gene expression was silenced. CONCLUSION: Therefore, highlighting the identification of possible hypoxia-targeting therapies for breast cancer patients can be beneficial by promoting more favourable treatment responses.

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.

Age-related differences in the vascular function and structure of South Africans living with HIV.

Background: As the life expectancy of people living with the HIV increases because of antiretroviral treatment (ART), their risk for vascular co-morbidities and early vascular ageing (EVA) also increases. Objective: We aimed to investigate whether HIV infection relates to vascular structure and function in black South African adults and whether this relationship is age dependent. Method: This cross-sectional study carried out in urban and rural areas of North West province, South Africa, included 572 age- and sex-matched people living with HIV (PLWH) and without HIV. Participants from the EndoAfrica study and PURE study were stratified according to tertiles of age. Measures of vascular structure (carotid intima-media thickness) and function (carotid-femoral pulse wave velocity, central systolic blood pressure, central pulse pressure and pulse pressure amplification) were determined. Results: Blood pressure measures were lower in PLWH compared with their controls (all P ≤ 0.001), especially in the younger and middle-aged groups (all P ≤ 0.031), whilst vascular measures did not differ (all P ≥ 0.611). In multivariate linear regression analyses, vascular measures were not associated with a HIV- positive status in either the total or any of the age groups. Conclusion: Black South Africans living with HIV have a less adverse blood pressure profile than their counterparts without HIV. The HIV-positive status was not associated with measures of vascular structure or function in any age group. The results suggest that HIV does not contribute to EVA in this population; however, further longitudinal investigation is warranted.

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.

Homoarginine and blood pressure: a 10-year prospective relationship in normotensives.

Nitric oxide plays a major role in the regulation of blood pressure, and impaired nitric oxide bioavailability contributes to the development of hypertension (HT). Various factors may contribute to nitric oxide bioavailability-including availability of the substrate for nitric oxide synthesis, L-arginine and its homolog L-homoarginine. We investigated whether blood pressure after 10 years associates with baseline L-homoarginine in participants who remained normotensive (NT) or developed HT, respectively. Data from the South African leg of the Prospective Urban and Rural Epidemiology study, performed in the North-West Province, were used. We investigated participants who either remained NT (N = 166) or who developed HT (N = 166) over 10 years. Blood pressure was measured with validated OMRON devices and serum L-homoarginine was analyzed with liquid chromatography-tandem mass spectrometry. L-homoarginine levels were similar at baseline (p = 0.39) and follow-up (p = 0.93) between NT and hypertensive groups. In the group that remained NT after 10 years, baseline L-homoarginine correlated positively with follow-up brachial systolic blood pressure (adj.R2 = 0.13; ß = 0.33; p = 0.001), brachial pulse pressure (adj.R2 = 0.15 ß = 0.40; p = 0.001), and central pulse pressure (adj.R2 = 0.20; ß = 0.30; p = 0.003). No significant associations were found in the group that developed HT after 10 years. We found a positive, independent association between blood pressure and L-homoarginine in a group that remained NT, but not in a group that developed HT after 10 years. This may suggest a protective role for L-homoarginine to maintain normal blood pressure, but only to a certain level. Once HT develops other factors may overshadow the protective effects of L-homoarginine.

The impact of mitochondria on cancer treatment resistance.

BACKGROUND: The ability of cancer cells to develop treatment resistance is one of the primary factors that prevent successful treatment. Although initially thought to be dysfunctional in cancer, mitochondria are significant players that mediate treatment resistance. Literature indicates that cancer cells reutilize their mitochondria to facilitate cancer progression and treatment resistance. However, the mechanisms by which the mitochondria promote treatment resistance have not yet been fully elucidated. CONCLUSIONS AND PERSPECTIVES: Here, we describe various means by which mitochondria can promote treatment resistance. For example, mutations in tricarboxylic acid (TCA) cycle enzymes, i.e., fumarate hydratase and isocitrate dehydrogenase, result in the accumulation of the oncometabolites fumarate and 2-hydroxyglutarate, respectively. These oncometabolites may promote treatment resistance by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, inhibiting the anti-tumor immune response, or promoting angiogenesis. Furthermore, stromal cells can donate intact mitochondria to cancer cells after therapy to restore mitochondrial functionality and facilitate treatment resistance. Targeting mitochondria is, therefore, a feasible strategy that may dampen treatment resistance. Analysis of tumoral DNA may also be used to guide treatment choices. It will indicate whether enzymatic mutations are present in the TCA cycle and, if so, whether the mutations or their downstream signaling pathways can be targeted. This may improve treatment outcomes by inhibiting treatment resistance or promoting the effectiveness of anti-angiogenic agents or immunotherapy.

L-homoarginine is associated with decreased cardiovascular- and all-cause mortality.

BACKGROUND: Increasing evidence suggests that L-homoarginine, an endogenous analogue of the amino acid L-arginine, may have beneficial effects on vascular homeostasis. We examined whether L-homoarginine is associated with 10-year risk of all-cause and cardiovascular mortality in a black South African population. METHODS: We included 669 black South African participants (mean age 59.5 years), 143 of whom died during the 10-year follow-up period. Mortality data were acquired via verbal autopsy. Plasma L-homoarginine (and other related markers) were analysed with liquid chromatography-tandem mass spectrometry. RESULTS: Survivors had higher L-homoarginine levels compared with nonsurvivors (1.25 µM vs. 0.89 µM; P < .001). Multivariable Cox regression analyses revealed that higher plasma L-homoarginine predicted a reduction in 10-year cardiovascular (hazard ratio [HR] per SD increment, 0.61; 95% CI 0.50 to 0.75) and all-cause (hazard ratio [HR] per SD increment, 0.59; 95% CI 0.41 to 0.84) mortality risk. CONCLUSION: Higher L-homoarginine levels are associated with reduced risk of 10-year cardiovascular and all-cause mortality. Regulation of L-homoarginine levels as a therapeutic target in the management of cardiovascular disease should be investigated.

Serum amyloid A and inflammasome activation: A link to breast cancer progression?

Breast cancer is the most frequently diagnosed cancer in women globally. Although there have been many significant advances made in the diagnosis and treatment of breast cancer, numerous unresolved challenges remain, which include prevention, early diagnosis, metastasis and recurrence. The role of inflammation in cancer development is well established and is believed to be one of the leading hallmarks of cancer progression. Recently, the role of the inflammasome, a cytosolic multiprotein complex, has received attention in different cancers. By contributing to the activation of inflammatory cytokines the inflammasome intensifies the inflammatory cascade. The inflammasome can be activated through several pathways, which include the binding of pattern associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs) to toll-like receptors (TLRs). Serum amyloid A (SAA), a non-specific acute-phase protein, can function as an endogenous DAMP by binding to pattern recognition receptors like TLRs on both breast cancer cells and cancer associated fibroblasts (CAFs). SAA can thus stimulate the production of IL-1ß, thereby creating a favourable inflammatory environment to support tumour growth. The aim of this review is to highlight the possible role of SAA as an endogenous DAMP in the tumour microenvironment (TME) thereby promoting breast cancer growth through the activation of the NLRP3 inflammasome.

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.

A comparative analysis of blood pressure in HIV-infected patients versus uninfected controls residing in Sub-Saharan Africa: a narrative review.

Elevated blood pressure (BP) is an important risk factor for cardiovascular disease and mortality in Sub-Saharan Africa (SSA). We reviewed the literature comparing BP in treated HIV-infected populations against untreated and/or uninfected controls from SSA. We conducted a narrative review through PubMed and EBSCO Discovery Service to determine estimates of raised BP and hypertension in HIV-infected patients versus untreated/uninfected controls (1 January 2005 to 31 July 2019 and 9 May 2020). We included 19 eligible studies that compared treated HIV-infected with untreated and/or uninfected controls. In studies comparing treated HIV-infected patients to uninfected controls, studies including 6882 (56.30%) and 21,819 (79.2%) participants reported lower BP and hypertension prevalence, respectively in HIV-infected patients; whereas studies including 753 (6.16%) and 3553 (12.9%) participants showed a higher BP and hypertension prevalence. Lastly, 4588 (37.54%) and 2180 (7.91%) participants showed no difference in BP and the prevalence of hypertension. When comparing BP of treated versus untreated HIV-infected patients, studies including 5757 (44.2%) patients reported lower BP in treated patients; while studies with 200 (1.53%) patients showed higher BP and 7073 (54.28%) showed no difference in BP. For hypertension status, studies with 4547 (74.5%) patients reported a lower prevalence of hypertension in treated patients; whereas studies with 598 (9.80%) patients showed higher prevalence; and 959 (15.7%) no difference in prevalence between treated versus untreated HIV-infected patients. In studies conducted in Sub-Saharan Africa, the majority of the findings indicate lower blood pressure and/or prevalence of hypertension in treated HIV-infected individuals compared to untreated and uninfected controls.

Asymmetric dimethylarginine and L-homoarginine prospectively relate to carotid wall thickness in a South African cohort.

BACKGROUND AND AIMS: The L-arginine derivatives asymmetric (ADMA) and symmetric dimethylarginine (SDMA), as well as L-homoarginine may have opposing effects in the pathogenesis of atherosclerosis. We aimed to investigate (i) 5-year changes in arginine derivatives, and (ii) the association between baseline arginine derivatives and follow-up measures of carotid wall thickness in South Africans. METHODS AND RESULTS: This study included men (n = 187) and women (n = 396) who took part in the 2010 and 2015 data collections of the South African arm of the Prospective Urban and Rural Epidemiology (PURE) study. Arginine derivatives were determined in plasma with liquid chromatography-tandem mass spectrometry. Carotid intima-media thickness (cIMT) and cross-sectional wall area (CSWA) were determined with B-mode ultrasonography. RESULTS: Mean values of arginine derivatives did not change over time. In the study group, follow-up cIMT (ß = - 0.10 p = 0.018) and CSWA (ß = - 0.12; p = 0.004) inversely associated with baseline L-homoarginine, and cIMT inversely associated with ADMA (ß = - 0.09; p = 0.033). In women, CSWA inversely associated with both ADMA (ß = - 0.11; p = 0.034) and L-homoarginine (ß = - 0.11; p = 0.024). No such associations were found in men. CONCLUSION: These results suggest that higher levels of L-homoarginine may play a protective role against vascular injury and delay progression of carotid wall thickening in this cohort. The role of ADMA in atherosclerosis deserves further investigation in this population.

A 10-year follow-up study of demographic and cardiometabolic factors in HIV-infected South Africans.

OBJECTIVES: Understanding of the interplay between human immunodeficiency virus (HIV) and cardiovascular disease, especially in Africa, is limited to evidence from longitudinal studies. Therefore the demographic profile and cardiometabolic, renal and liver function of an HIV-infected South African population were profiled from 2005 to 2015. METHODS: The study included 117 HIV-infected and 131 uninfected controls that were examined at baseline, five and 10 years. RESULTS: Mortality rate declined from 24% (2005-2010) to 0% (2010-2015) after the introduction of ART. Longitudinal increases in C-reactive protein (p = 0.002), alanine transaminase (p = 0.006) and gamma-glutamyl transferase (p = 0.046) levels and estimated glomerular filtration rate (p < 0.001) were seen only in the HIV-infected group. This group also showed increased high-density lipoprotein cholesterol (HDL-C) (p < 0.001) and total cholesterol (p < 0.001) levels and decreased triglyceride:HDL-C (p = 0.011) levels. Low-density lipoprotein cholesterol decreased in both groups (p < 0.001). CONCLUSIONS: Despite trajectories of deranged lipid and inflammatory profiles, the cardiometabolic disease risk seems stable in HIV-infected South Africans. Inflammation and renal and liver function warrant regular monitoring.

The paracrine effects of fibroblasts on Doxorubicin-treated breast cancer cells.

Breast cancer is frequently diagnosed in women and poses a major health problem throughout the world. Currently, the unresponsiveness of cancer cells to chemotherapeutics is a major concern. During chemotherapeutic treatment with Doxorubicin, neighbouring cells in the tumor microenvironment are also damaged. Depending on the concentration of Doxorubicin, apoptotic or senescent fibroblasts in the tumor microenvironment can then secrete a variety of bioactive molecules which promote tumor growth, metastasis and drug resistance. Mouse embryonic fibroblasts (MEFs) were treated with Doxorubicin to induce apoptosis and senescence respectively. Conditioned media was collected from the MEFs and was used to assess the paracrine effects between fibroblasts and E0771 murine breast cancer cells. Senescent fibroblasts significantly increased cell viability in E0771 cells following Doxorubicin treatment by activating Akt and ERK. Autophagy contributed to cancer cell death and not to treatment resistance in breast cancer cells. Our results highlight the complexity of the tumor microenvironment where chemotherapeutic agents such as Doxorubicin can induce significant changes fibroblasts which can affect tumor growth via the secretion of paracrine factors. Here we have demonstrated that those secreted paracrine factors enhance breast cancer growth and induce therapeutic resistance through the evasion of apoptotic cell death.

The African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT): Design, recruitment and initial examination.

BACKGROUND: Globally hypertension is stabilising, but in sub-Saharan Africa the incidence of hypertension remains on an increase. Although this might be attributed to poor healthcare and ineffective antihypertensive treatment, there is a limited understanding of population and individual-specific cardiovascular pathophysiology - necessary for effective prevention and treatment strategies in Africa. As there is a lack of longitudinal studies tracking the early pathophysiological development of hypertension in black populations, the African-PREDICT study was initiated. The purpose of this paper is to describe the detailed methodology and baseline cohort profile of the study. METHODS AND RESULTS: From 2013 to 2017, the study included 1202 black ( N = 606) and white ( N = 596) men and women (aged 20-30 years) from South Africa - screened to be healthy and clinic normotensive. At baseline, and each 5-year follow-up examination, detailed measures of health behaviours, cardiovascular profile and organ damage are taken. Also, comprehensive biological sampling for the 'omics' and biomarkers is performed. Overall, the baseline black and white cohort presented with similar ages, clinic and 24-hour blood pressures, but black adults had lower socioeconomic status and higher central systolic blood pressure than white individuals. CONCLUSIONS: The prospective African-PREDICT study in young black and white adults will contribute to a clear understanding of early cardiovascular disease development.

The metabolic syndrome and renal function in an African cohort infected with human immunodeficiency virus.

INTRODUCTION: The human immunodeficiency virus (HIV) is often accompanied by renal dysfunction. It is expected that metabolic syndrome (MetS) may exacerbate renal impairment. OBJECTIVE: We therefore determined the prevalence of MetS and the association thereof with renal function in a South African cohort infected with HIV. METHODS: We matched 114 HIV-infected (77.3% on antiretroviral therapy [ART] and 22.7% ART-naïve) and 114 HIV-uninfected individuals according to age, sex and locality. We examined cardiovascular, anthropometric and metabolic measurements and determined the MetS. Renal function was assessed using standardised procedures. RESULTS: The prevalence of MetS was lower in the HIV-infected individuals as compared to the uninfected individuals (28% vs. 44%, p = 0.013). The HIV-infected group presented with a lower body mass index (BMI) and waist circumference (WC) (all p < 0.001), as well as blood pressure (BP) (p ≤ 0.0021). The results were confirmed when comparing the HIV-infected group using ART (N = 85) and the HIV-uninfected group. When comparing the HIV-infected individuals with MetS to the HIV-uninfected individuals with MetS, no differences in BP were seen. With regard to renal function, the HIV-infected individuals with MetS (n = 32) had 43% higher urinary albumin-creatinine ratio (uACR) compared to the HIV-uninfected individuals with MetS, after adjusting for age, sex and WC (p = 0.032). None of the other renal function markers differed after adjustments for WC or BMI. CONCLUSION: The HIV-infected Africans with MetS had almost twofold higher uACR, despite the low prevalence of MetS, compared to their uninfected counterparts. The combination of HIV and MetS seemed to increase the risk for renal impairment.

HIV treatment is associated with a two-fold higher probability of raised triglycerides: Pooled Analyses in 21 023 individuals in sub-Saharan Africa.

BACKGROUND: Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations. METHODS: Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models. FINDINGS: Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51-2.77, I2=45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies. INTERPRETATION: Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.

Evaluating several biomarkers as predictors of aortic stiffness in young and older Africans, not consuming alcohol based on self-report.

AIMS: Black populations from sub-Saharan Africa have a high prevalence of cardiovascular disease, which places significant strain on public health systems. Aortic stiffness is a prominent risk factor for cardiovascular disease development. We reported earlier that excessive alcohol use predicts aortic stiffness. However, we require a better understanding of other biomarkers involved in stiffness development, beyond alcohol use. Therefore, we determined which biomarkers (metabolic, inflammatory, endothelial activation and oxidative stress) relate to aortic stiffness in young and older black South Africans, self-reporting no alcohol-use. METHODS: We included cross-sectional data from young (aged 24.7 ±â€¯3.24 years) black adults participating in the African Prospective study on the Early Detection and Identification of Cardiovascular Disease and Hypertension (African-PREDICT) study (N = 216), and five-year follow-up data from older (aged 61.6 ±â€¯9.77 years) black adults (N = 322) participating in the South African leg of the Prospective Urban and Rural Epidemiology study, conducted in the North West Province (PURE-SA-NWP). We excluded all participants self-reporting alcohol use. We determined biomarkers from blood samples, and measured carotid-femoral pulse wave velocity (PWV). RESULTS: Of all biomarkers investigated in multivariable-adjusted regression analyses, only plasma glucose (R2 = 0.24, ß = 0.21, p < 0.001) and glycated haemoglobin (R2 = 0.22, ß = 0.17, p = 0.002) independently predicted PWV five years later in older adults. We found no other associations in young or older black adults. CONCLUSION: Dysglycaemia independently predicted aortic stiffness after five years in older black adults. Life-course management of body weight and sugar intake are important in preventing early vascular ageing and subsequent cardiovascular disease development in Africa.

A health profile associated with excessive alcohol use independently predicts aortic stiffness over 10 years in black South Africans.

OBJECTIVE: Black populations exhibit higher arterial stiffness than whites and suffer a disproportionate burden of cardiovascular disease. It is therefore important to identify modifiable health behaviours predicting large artery stiffness in blacks. We examined whether traditional cardiovascular risk factors and health behaviours of black South Africans predict large artery stiffness 10 years later. METHODS: We included 650 HIV-free participants (32.8% men) and collected data in rural and urban areas of the North West Province in 2005 and 2015. We collected questionnaire data, anthropometry, blood pressure and determined cardiometabolic and inflammatory markers from blood samples. We measured carotid-femoral pulse wave velocity (PWV) at follow-up. RESULTS: A total of 25.3% of our population, aged 65 ±â€Š9.57 years, had a PWV exceeding 10 m/s. In multivariable-adjusted regression analyses, the strongest predictors of PWV were mean arterial pressure, age and heart rate (all P < 0.024). Urban locality (R = 0.31, ß = 0.12, P = 0.001), self-reported alcohol use (ß = 0.11, P = 0.018) and plasma glucose (ß = 0.08 P = 0.023) associated positively with PWV at follow-up. We found a negative association between PWV and BMI (ß = -0.15, P = 0.001), and no associations with sex, smoking, inflammatory markers, lipids, liver enzymes or antihypertensive medication. When replacing self-reported alcohol with gamma-glutamyltransferase, the latter associated positively with PWV (ß = 0.09, P = 0.023). CONCLUSION: A health profile associated with excessive alcohol use, including an urban setting, elevated plasma glucose and lower BMI predicts large artery stiffness independently of age and blood pressure in black South Africans over 10 years. This observation prompts urgent public health strategies to target alcohol overuse.