Publications by authors named "Nigel J Crowther"

80 Publications

Adiposity Phenotypes and Subclinical Atherosclerosis in Adults from Sub-Saharan Africa: An H3Africa AWI-Gen Study.

Glob Heart 2021 Mar 19;16(1):19. Epub 2021 Mar 19.

Department of Chemical Pathology, National Health Laboratory Service, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, ZA.

Background: Obesity and adipose tissue distribution contribute to an increased risk of cardiovascular disease (CVD) by promoting atherosclerosis. This association has been poorly studied in sub-Saharan Africa (SSA) despite the rising prevalence of cardiovascular disease.

Objectives: We determined the association between various adiposity phenotypes and carotid intima-media thickness (CIMT), a proxy of subclinical atherosclerosis, in a large SSA population.

Methods: A population-based cross-sectional study was performed from 2013-2016 in Burkina Faso, Ghana, Kenya and South Africa. Body mass index (BMI), waist (WC), hip circumferences (HC), visceral (VAT) and subcutaneous adipose tissue (SCAT) using B-mode ultrasound were measured. Ultrasonography of left and right far wall CIMT of the common carotid artery was used as an indicator of subclinical atherosclerosis. Individual participant data meta-analyses were used to determine the associations between adiposity phenotypes and CIMT in the pooled sample while adjusted multivariable linear regression analyses were used for site specific analyses.

Results: Data were obtained from 9,010 adults (50.3% women and a mean age of 50± 6years). Men had higher levels of visceral fat than women while women had higher BMI, waist and hip circumference and subcutaneous fat than men at all sites except Burkina Faso. In the pooled analyses, BMI (β-value [95% CIs]: 19.5 [16.8, 22.3] μm) showed the strongest relationship with CIMT followed by VAT (5.86 [4.65, 7.07] μm), SCAT (5.00 [2.85, 7.15] μm), WC (1.27 [1.09, 1.44] μm) and HC (1.23 [1.04, 1.42] μm). Stronger associations were observed in men than in women.

Conclusion: Obesity within SSA will likely result in higher levels of atherosclerosis and promote the occurrence of cardio- and cerebrovascular events, especially in males, unless addressed through primary prevention of obesity in both rural and urban communities across Africa. The inverse association of VAT with CIMT in Burkina Faso and Ghana requires further investigation.

Highlights: All adiposity phenotypes were positively associated with common carotid intima-media thickness (CIMT) in the entire cohort (pooled analyses).BMI had the strongest association with CIMT compared to other phenotypes.The magnitude of association between adiposity phenotypes and CIMT was higher in men than in women.Subcutaneous adipose tissue was inversely associated with CIMT only in women.An unexpected finding was the inverse association of visceral adipose tissue with CIMT in Burkina Faso and Ghana.
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http://dx.doi.org/10.5334/gh.863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977036PMC
March 2021

Endothelial Dysfunction as a Primary Consequence of SARS-CoV-2 Infection.

Adv Exp Med Biol 2021 ;1321:33-43

Department of Chemical Pathology, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa.

A number of different viral species are known to have effects on the endothelium. These include dengue, Ebola, Marburg, Lassa fever, yellow fever and influenza viruses, cytomegalovirus and coronaviruses. There are currently seven human endemic coronaviruses, all of which cause respiratory diseases and bind to receptors found within the endothelium. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) is highly infectious. Like its predecessor, SARS-CoV, it binds to angiotensin-converting enzyme-2 (ACE-2), which is expressed in many cell types, particularly in the lung, including endothelial cells. The initiation of a cytokine storm by the virus along with infection of endothelial cells leads to apoptosis and structural and functional changes that attenuate vascular integrity in many organs including the lungs, heart, liver and kidney. Endothelial damage also enhances the coagulation pathway leading to thrombus formation in major vessels and capillaries. Infection with SARS-CoV-2 has an adverse outcome for individuals with particular comorbid diseases, e.g. hypertension, obesity, type 2 diabetes and cardiovascular disease. It is possible that this is due to the presence of pre-existing endothelial dysfunction and systemic inflammation in subjects with these diseases. Therapies for COVID-19 that target the endothelium, the inflammatory response and the coagulation pathway are currently under trial.
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http://dx.doi.org/10.1007/978-3-030-59261-5_3DOI Listing
March 2021

Poor cardiovascular health is associated with subclinical atherosclerosis in apparently healthy sub-Saharan African populations: an H3Africa AWI-Gen study.

BMC Med 2021 Feb 10;19(1):30. Epub 2021 Feb 10.

Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Background: The cardiovascular health index (CVHI) introduced by the American Heart Association is a valid, accessible, simple, and translatable metric for monitoring cardiovascular health in a population. Components of the CVHI include the following seven cardiovascular risk factors (often captured as life's simple 7): smoking, dietary intake, physical activity, body mass index, blood pressure, glucose, and total cholesterol. We sought to expand the evidence for its utility to under-studied populations in sub-Saharan Africa, by determining its association with common carotid intima-media thickness (CIMT).

Methods: We conducted a cross-sectional study involving 9011 participants drawn from Burkina Faso, Ghana, Kenya, and South Africa. We assessed established classical cardiovascular risk factors and measured carotid intima-media thickness of the left and right common carotid arteries using B-mode ultrasonography. Adjusted multilevel mixed-effect linear regression was used to determine the association of CVHI with common CIMT. In the combined population, an individual participant data meta-analyses random-effects was used to conduct pooled comparative sub-group analyses for differences between countries, sex, and socio-economic status.

Results: The mean age of the study population was 51 ± 7 years and 51% were women, with a mean common CIMT of 637 ± 117 μm and CVHI score of 10.3 ± 2.0. Inverse associations were found between CVHI and common CIMT (β-coefficients [95% confidence interval]: Burkina Faso, - 6.51 [- 9.83, - 3.20] μm; Ghana, - 5.42 [- 8.90, - 1.95]; Kenya, - 6.58 [- 9.05, - 4.10]; and South Africa, - 7.85 [- 9.65, - 6.05]). Inverse relations were observed for women (- 4.44 [- 6.23, - 2.65]) and men (- 6.27 [- 7.91, - 4.64]) in the pooled sample. Smoking (p < 0.001), physical activity (p < 0.001), and hyperglycemia (p < 0.001) were related to CIMT in women only, while blood pressure and obesity were related to CIMT in both women and men (p < 0.001).

Conclusion: This large pan-African population study demonstrates that CVHI is a strong marker of subclinical atherosclerosis, measured by common CIMT and importantly demonstrates that primary prevention of atherosclerotic cardiovascular disease in this understudied population should target physical activity, smoking, obesity, hypertension, and hyperglycemia.
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http://dx.doi.org/10.1186/s12916-021-01909-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874493PMC
February 2021

Estimating the burden of cardiovascular risk in community dwellers over 40 years old in South Africa, Kenya, Burkina Faso and Ghana.

BMJ Glob Health 2021 Jan;6(1)

MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.

Introduction: Cardiovascular disease (CVD) risk factors are increasing in sub-Saharan Africa. The impact of these risk factors on future CVD outcomes and burden is poorly understood. We examined the magnitude of modifiable risk factors, estimated future CVD risk and compared results between three commonly used 10-year CVD risk factor algorithms and their variants in four African countries.

Methods: In the Africa-Wits-INDEPTH partnership for Genomic studies (the AWI-Gen Study), 10 349 randomly sampled individuals aged 40-60 years from six sites participated in a survey, with blood pressure, blood glucose and lipid levels measured. Using these data, 10-year CVD risk estimates using Framingham, Globorisk and WHO-CVD and their office-based variants were generated. Differences in future CVD risk and results by algorithm are described using kappa and coefficients to examine agreement and correlations, respectively.

Results: The 10-year CVD risk across all participants in all sites varied from 2.6% (95% CI: 1.6% to 4.1%) using the WHO-CVD lab algorithm to 6.5% (95% CI: 3.7% to 11.4%) using the Framingham office algorithm, with substantial differences in risk between sites. The highest risk was in South African settings (in urban Soweto: 8.9% (IQR: 5.3-15.3)). Agreement between algorithms was low to moderate (kappa from 0.03 to 0.55) and correlations ranged between 0.28 and 0.70. Depending on the algorithm used, those at high risk (defined as risk of 10-year CVD event >20%) who were under treatment for a modifiable risk factor ranged from 19.2% to 33.9%, with substantial variation by both sex and site.

Conclusion: The African sites in this study are at different stages of an ongoing epidemiological transition as evidenced by both risk factor levels and estimated 10-year CVD risk. There is low correlation and disparate levels of population risk, predicted by different risk algorithms, within sites. Validating existing risk algorithms or designing context-specific 10-year CVD risk algorithms is essential for accurately defining population risk and targeting national policies and individual CVD treatment on the African continent.
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http://dx.doi.org/10.1136/bmjgh-2020-003499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825268PMC
January 2021

Nutrient Patterns and Body Composition Parameters of Black South African Women.

Nutrients 2020 Dec 22;13(1). Epub 2020 Dec 22.

SAMRC/Wits Developmental Pathways for Health Research Unit (DPHRU), Faculty of Health Sciences, University of the Witwatersrand and Johannesburg, Johannesburg 2198, South Africa.

Obesity is more prevalent in black South African women than men. However, little is known about the nutrient patterns associated with body composition indices in black African women. Principle Component Analysis (PCA) was applied to 25 nutrients derived from quantified food frequency questionnaires (QFFQs) in 498 middle aged black South African women. Three nutrient patterns, the plant driven, animal driven and Vitamin C, sugar and potassium driven nutrient patterns, accounted for 59% of the variance of nutrient intake. Linear models of the body composition parameters as outcome variables indicated that a standard deviation increase in the animal driven nutrient pattern was significantly associated with increases in body mass index (BMI) (1.29 kg·m (95% CI, 0.54-2.04; = 0.001), subcutaneous adipose tissue (SAT) (26.30 cm (7.97-44.63); = 0.005), visceral adipose tissue (VAT) (9.88 cm (5.13-14.63); < 0.001), VAT/SAT ratio (0.01 (0.00-0.02); = 0.018), whole body fat mass index (0.74 kg·m (0.25-1.22); = 0.003), and whole body lean mass index (0.53 kg·m (0.23-0.83); = 0.001). An increase in plant driven nutrient pattern was significantly associated with an increase in SAT of 20.45 cm (0.47-40.43); = 0.045. This study demonstrates that animal driven nutrient pattern, characterised by the consumption of more animal protein and fat nutrients, similar to the western diet is associated with increased body fat and lean mass.
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http://dx.doi.org/10.3390/nu13010006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822018PMC
December 2020

A Polymorphism in the Gene Encoding the Insulin Receptor Binding Protein ENPP-1 Is Associated with Decreased Glomerular Filtration Rate in an Under-Investigated Indigenous African Population.

Kidney Blood Press Res 2020 3;45(6):1009-1017. Epub 2020 Dec 3.

Department of Chemical Pathology, University of the Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa.

Introduction: The C allele of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP-1) rs1044498 polymorphism has previously been associated with increased binding of ENPP-1 to the insulin receptor (IR), resulting in decreased IR signalling and enhanced insulin resistance. It has also been associated with reduced kidney function in participants with diabetes of predominantly European and Asian descent. The association of this polymorphism with kidney disease in healthy Black South African participants has yet to be ascertained.

Objective: This study, therefore, aimed to determine whether the K121Q polymorphism is associated with estimated glomerular filtration rate (eGFR) in a Black South African cohort.

Methods: Black South African participants (n = 348) from an existing cohort with known eGFR levels were genotyped for the K121Q polymorphism using PCR-RFLP and assessed for any statistical association between genotype and kidney function.

Results: Individuals with the A allele had significantly lower eGFR levels than individuals with the CC genotype (86.52 ± 18.95 vs. 93.29 ± 23.55 mL/min; p = 0.022). The association of the A allele with lower eGFR levels remained after controlling for sex, blood pressure, insulin resistance, age, smoking, thyroid-stimulating hormone, insulin-like growth factor-1, and BMI (R2 = 0.030, p < 0.001).

Conclusion: The rs1044498 A allele was significantly associated with lower eGFR levels in a cohort of apparently healthy Black South Africans, through an unknown mechanism that was independent of insulin resistance. It is possible that the rs1044498 polymorphism affects kidney function by altering the role of ENPP-1 in endothelial wound healing, podocyte signalling, or oxidative stress. Thus, the presence of this polymorphism may predispose individuals to a greater risk of CKD even in the absence of diabetes.
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http://dx.doi.org/10.1159/000511213DOI Listing
December 2020

Candidate Gene Analysis Reveals Strong Association of Variants With High Density Lipoprotein Cholesterol and Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-Study.

Front Genet 2020 30;11:456661. Epub 2020 Oct 30.

Navrongo Health Research Centre, Navrongo, Ghana.

Variations in lipid levels are attributed partly to genetic factors. Genome-wide association studies (GWASs) mainly performed in European, African American and Asian cohorts have identified variants associated with LDL-C, HDL-C, total cholesterol (TC) and triglycerides (TG), but few studies have been performed in sub-Saharan Africans. This study evaluated the effect of single nucleotide variants (SNVs) in eight candidate loci (, , , , , , , and ) on lipid levels among 1855 Ghanaian adults. All lipid levels were measured directly using an automated analyser. DNA was extracted and genotyped using the H3Africa SNV array. Linear regression models were used to test the association between SNVs and log-transformed lipid levels, adjusting for sex, age and waist circumference. In addition Bonferroni correction was performed to account for multiple testing. Several variants of , , , and (MAF > 0.05) were associated with HDL-C, LDL-C and TC levels at < 0.05. The lead variants for association with HDL-C were rs17231520 in (β = 0.139, < 0.0001) and rs1109166 in (β = -0.044, = 0.028). Lower LDL-C levels were associated with an intronic variant in (rs11806638 [β = -0.055, = 0.027]) and increased TC was associated with a variant in (rs854558 [β = 0.040, = 0.020]). functional analyses indicated that these variants likely influence gene function through their effect on gene transcription. We replicated a strong association between variants and HDL-C and between variant and LDL-C in West Africans, with two potentially functional variants and identified three novel variants in linkage disequilibrium in which were associated with increasing TC levels in Ghanaians.
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http://dx.doi.org/10.3389/fgene.2020.456661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661969PMC
October 2020

Branched-chain and aromatic amino acids and cardiometabolic risk in Black African and Asian Indian populations.

Metabolomics 2020 10 8;16(10):108. Epub 2020 Oct 8.

Department of Chemical Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Introduction: Studies have shown that systemic levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are elevated in cardiometabolic diseases (CMDs) in populations resident in high income countries. However, little is known about the association of BCAAs and AAAs with metabolic syndrome and its components in Asian Indian (AI) and Black African (BA) populations.

Objective: The aim of this study was to describe the association of BCAAs and AAAs with the metabolic syndrome, its individual components and insulin resistance in AI and BA populations.

Methods: Serum samples collected from AI (n = 349) and BA (n = 369) subjects were used to measure levels of BCAAs and AAAs by ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Anthropometric, demographic and cardiometabolic variables were measured in all subjects.

Results: The sum of BCAAs and AAAs was higher in AIs compared to BAs. The BCAAs and AAAs were positively associated with insulin resistance, metabolic syndrome and its individual components. This was particularly the case for AI subjects, in unadjusted regression models. However, these associations were non-significant after adjusting for co-variates, particularly visceral adipose tissue (VAT). Triglyceride levels were significantly associated with valine and leucine levels in BAs even after adjustment for co-variates. Lastly, we found that fasting circulatory BCAA and AAA levels are strongly correlated with VAT in both populations.

Conclusion: This study identified specific associations of serum valine and leucine levels with triglycerides in BAs. The association of amino acids with CMDs was observed in AIs, but was found to be the result of confounding by VAT. Further studies are required to determine whether BCAAs and AAAs are aetiological factors in CMDs and how VAT modulates their serum levels.
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http://dx.doi.org/10.1007/s11306-020-01734-7DOI Listing
October 2020

Blood Pressure Indices and Associated Risk Factors in a Rural West African Adult Population: Insights from an AWI-Gen Substudy in Ghana.

Int J Hypertens 2020 26;2020:4549031. Epub 2020 Apr 26.

Navrongo Health Research Centre, Navrongo, Ghana.

Systolic (SBP) and diastolic blood pressure (DBP) are commonly used for cardiovascular disease (CVD) risk prediction, and pulse pressure (PP) and mean arterial blood pressure (MAP) can provide additional information. It is therefore important to understand the factors associated with these cardiovascular risk markers. This cross-sectional study involved 1839 men and women aged 40-60 years. Data on SBP, DBP, MAP, PP, sociodemography, lifestyle, anthropometry, and lipids were collected. Gender-stratified linear regression analyses were performed to determine the association between log-transformed blood pressure indices and the study variables. Age was associated with all measured blood pressure indices ( < 0.001) among men and women. Men had higher SBP (=0.007) and PP ( < 0.001) than women. Nankana ethnicity was associated with higher PP levels ( < 0.005) in the total population. Vendor meal consumption among women was associated with higher PP levels ( < 0.05). Fruit intake among men was associated with lower PP levels ( < 0.05). Currently unmarried women had higher SBP ( < 0.005), DBP ( < 0.05), MAP ( < 0.005), and PP ( < 0.005) than currently married women. Pesticide exposure was negatively associated with SBP ( < 0.005), DBP ( < 0.005), MAP ( < 0.005), and PP ( < 0.05) among women. Increased subcutaneous fat was associated with DBP ( < 0.005) and MAP ( < 0.05) among women. Among men, hip circumference was associated with higher DBP and MAP ( < 0.05 for both associations), subcutaneous fat associated with higher SBP ( < 0.005), DBP ( < 0.001), and MAP ( < 0.001) and visceral fat was associated with higher PP ( < 0.05). In the total population, visceral fat was associated with higher DBP ( < 0.05) and MAP ( < 0.001). High-density lipoprotein cholesterol was positively associated with SBP ( < 0.005), DBP ( < 0.005), and MAP ( < 0.001) for women and positively associated with SBP, DBP, and MAP ( < 0.001 for all three) and PP ( < 0.05) for men. The association of blood pressure indices with modifiable risk factors suggests that targeted health interventions may reduce CVD risk in this population.
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http://dx.doi.org/10.1155/2020/4549031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201512PMC
April 2020

Cardiovascular disease risk in an urban African population: a cross-sectional analysis on the role of HIV and antiretroviral treatment.

Retrovirology 2019 12 3;16(1):37. Epub 2019 Dec 3.

Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.

Background: Life expectancy is increasing in the HIV-positive population and age-related non-communicable diseases, such as cardiovascular disease, (CVD) are seen more frequently. This study investigated to what extent HIV and antiretroviral therapy (ART) is associated with CVD risk in an urban African population.

Methods: A cross-sectional study was performed in Johannesburg, South Africa, between July 2016 and November 2017. Both HIV-positive adults (ART-naïve, or on first- or second-line ART), as well as age and sex matched HIV-negative controls who were family or friends of the HIV-positive participants were included. Data were collected on demographics, cardiovascular risk factors, HIV-related characteristics, carotid intima-media thickness (CIMT) and carotid distensibility. The association between HIV, ART and CIMT and distensibility was analysed with linear regression models, adjusting for age, gender and CVD risk factors.

Results: The study included 548 participants, 337 (62%) females, age 38.3 ± 9.5 years of whom 104 (19.0%) were HIV-positive, ART-naïve; 94 (17.2%) were on first-line ART; 197 (35.9%) were on second-line ART; and 153 (27.9%) were HIV-negative. Participants on second-line ART had higher CIMT and lower distensibility compared to the other groups (p < 0.001). After adjustment for age, these outcomes were similar between groups. Further adjustment for CVD and HIV-related factors did not alter the findings.

Conclusion: Neither HIV nor ART was associated with CIMT or carotid distensibility in this urban African population. Longitudinal studies are needed to fully understand the relationship between HIV and CVD across different populations.
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http://dx.doi.org/10.1186/s12977-019-0497-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889610PMC
December 2019

Cognitive function and cardiometabolic disease risk factors in rural South Africa: baseline evidence from the HAALSI study.

BMC Public Health 2019 Nov 27;19(1):1579. Epub 2019 Nov 27.

MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.

Background: Evidence on cognitive function in older South Africans is limited, with few population-based studies. We aimed to estimate baseline associations between cognitive function and cardiometabolic disease risk factors in rural South Africa.

Methods: We use baseline data from "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa" (HAALSI), a population-based study of adults aged 40 and above in rural South Africa in 2015. Cognitive function was measured using measures of time orientation, immediate and delayed recall, and numeracy adapted from the Health and Retirement Study cognitive battery (overall total cognitive score range 0-26). We used multiple linear regression to estimate associations between cardiometabolic risk factors (including BMI, hypertension, dyslipidemia, diabetes, history of stroke, alcohol frequency, and smoking status) and the overall cognitive function score, adjusted for potential confounders.

Results: In multivariable-adjusted analyses (n = 3018; male = 1520; female = 1498; median age 59 (interquartile range 50-67)), cardiometabolic risk factors associated with lower cognitive function scores included: diabetes (b = - 1.11 [95% confidence interval: - 2.01, - 0.20] for controlled diabetes vs. no diabetes); underweight BMI (b = - 0.87 [CI: - 1.48, - 0.26] vs. normal BMI); and current and past smoking history compared to never smokers. Factors associated with higher cognitive function scores included: obese BMI (b = 0.74 [CI: 0.39, 1.10] vs. normal BMI); and controlled hypertension (b = 0.53 [CI: 0.11, 0.96] vs. normotensive).

Conclusions: We provide an important baseline from rural South Africa on the associations between cardiometabolic disease risk factors and cognitive function in an older, rural South African population using standardized clinical measurements and cut-offs and widely used cognitive assessments. Future studies are needed to clarify temporal associations as well as patterns between the onset and duration of cardiometabolic conditions and cognitive function. As the South African population ages, effective management of cardiometabolic risk factors may be key to lasting cognitive health.
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http://dx.doi.org/10.1186/s12889-019-7938-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882146PMC
November 2019

Kidney damage and associated risk factors in rural and urban sub-Saharan Africa (AWI-Gen): a cross-sectional population study.

Lancet Glob Health 2019 12;7(12):e1632-e1643

Division of Human Genetics, National Health Laboratory Service and University of Witwatersrand, Johannesburg, South Africa; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Background: Rapid epidemiological health transitions occurring in vulnerable populations in Africa that have an existing burden of infectious and non-communicable diseases predict an increased risk and consequent prevalence of kidney disease. However, few studies have characterised the true burden of kidney damage and associated risk factors in Africans. We investigated the prevalence of markers for kidney damage and known risk factors in rural and urban settings in sub-Saharan Africa.

Methods: In this cross-sectional population study (Africa Wits-International Network for the Demographic Evaluation of Populations and their Health Partnership for Genomic Studies [AWI-Gen]), we recruited unrelated adult participants aged 40-60 years from four rural community research sites (Nanoro, Burkina Faso; Navrongo, Ghana; Agincourt and Dikgale, South Africa), and two urban community research sites (Nairobi, Kenya; and Soweto, South Africa). Participants were identified and selected using random sampling frames already in use at each site. Participants completed a lifestyle and medical history questionnaire, had anthropometric and blood pressure measurements taken, and blood and urine samples were collected. Markers of kidney damage were defined as low estimated glomerular filtration rate (eGFR; <60 mL/min per 1·73 m), presence of albuminuria (urine albumin creatinine ratio >3 mg/mmol); or chronic kidney disease (low eGFR or albuminuria, or both). We calculated age-adjusted prevalence of chronic kidney disease, low eGFR, and albuminuria by site and sex and used logistic regression models to assess risk factors of kidney damage.

Findings: Between August, 2013, and August, 2016, we recruited 10 702 participants, of whom 8110 were analysable. 4120 (50·8%) of analysable participants were male, with a mean age of 49·9 years (SD 5·8). Age-standardised population prevalence was 2·4% (95% CI 2·1-2·8) for low eGFR, 9·2% (8·4-10·0) for albuminuria, and 10·7% (9·9-11·7) for chronic kidney disease, with higher prevalences in South African sites than in west African sites (14·0% [11·9-16·4] in Agincourt vs 6·6% [5·5-7·9] in Nanoro). Women had a higher prevalence of chronic kidney disease (12·0% [10·8-13·2] vs 9·5% [8·3-10·8]) and low eGFR (3·0% [2·6-3·6] vs 1·7% [1·3-2·3]) than did men, with no sex-specific differences for albuminuria (9·9% [8·8-11·0] vs 8·4% [7·3-9·7]). Risk factors for kidney damage were older age (relative risk 1·04, 95% CI 1·03-1·05; p<0·0001), hypertension (1·97, 1·68-2·30; p<0·0001), diabetes (2·22, 1·76-2·78; p<0·0001), and HIV (1·65, 1·36-1·99; p<0·0001); whereas male sex was protective (0·85, 0·73-0·98; p=0·02).

Interpretation: Regional differences in prevalence and risks of chronic kidney disease in sub-Saharan Africa relate in part to varying stages of sociodemographic and epidemiological health transitions across the area. Public health policy should focus on integrated strategies for screening, prevention, and risk factor management in the broader non-communicable disease and infectious diseases framework.

Funding: National Human Genome Research Institute, Office of the Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, the Office of AIDS Research, and National Institute of Diabetes and Digestive and Kidney Diseases, all of the National Institutes of Health, and the South African Department of Science and Technology.
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http://dx.doi.org/10.1016/S2214-109X(19)30443-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033368PMC
December 2019

Epigenetic modification of the pentose phosphate pathway and the IGF-axis in women with gestational diabetes mellitus.

Epigenomics 2019 09 4;11(12):1371-1385. Epub 2019 Oct 4.

Division of Human Genetics, National Health Laboratory Service and the School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.

Gestational diabetes mellitus (GDM) has been linked with adverse long-term health outcomes for the fetus and mother. These effects may be mediated by epigenetic modifications. Genome-wide RNA sequencing was performed in placental tissue and maternal blood in six GDM and six non-GDM pregnancies. Promoter region DNA methylation was examined for selected genes and correlated with gene expression to examine an epigenetic modulator mechanism. Reductions of mRNA expression and increases in promoter methylation were observed for in GDM women, and for genes encoding IGF-binding proteins in GDM-exposed placenta. GDM involves epigenetic attenuation of , which may lead to hyperglycemia and oxidative stress, and the IGF-axis, which may modulate fetal macrosomia.
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http://dx.doi.org/10.2217/epi-2018-0206DOI Listing
September 2019

Relationship of Visceral Fat and Adipokines with Cardiometabolic Diseases in Psoriasis.

Acta Derm Venereol 2019 Dec;99(13):1218-1223

Internal Medicine, Chris Hani Baragwanath Academic Hospital, 2013 Johannesburg, South Africa.

As part of a larger cross-sectional, case-control study on cardiometabolic diseases in psoriasis this study investigated the association of visceral fat and serum adipokines with psoriasis and cardiometabolic diseases. A total of 103 patients with psoriasis and 98 controls, matched for body mass index, ethnicity and sex, were recruited over 15 months. Abdominal visceral fat was measured by computerized tomo-graphy. Logistic regression analysis revealed that visceral fat was associated with psoriasis (odds ratio (95% confidence interval): 1.56 (1.15, 2.11)), hyper-triglyceridaemia (1.67 (1.22, 2.28)), low high-density lipoprotein (1.63 (1.19, 2.22)) and type 2 diabetes (1.77 (1.24, 2.54)), (p < 0.005 for all). These respective associations were linked to serum interleukin-6, adiponectin, tumour necrosis factor and insulin resistance. Psoriasis was associated with type 2 diabetes (7.94 (2.64, 23.9)), independent of visceral fat. These data suggest that visceral fat and its mediators play a key role in psoriasis-associated cardiometabolic diseases. Psoriasis itself is associated with an increased risk of type 2 diabetes.
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http://dx.doi.org/10.2340/00015555-3327DOI Listing
December 2019

Growth curve modelling to determine distinct BMI trajectory groups in HIV-positive adults on antiretroviral therapy in South Africa.

AIDS 2019 11;33(13):2049-2059

Department of Global Health, Boston University School of Public Health, Boston, Massachusetts, USA.

Objective: Obesity is a major long-term concern in HIV-positive patients due to the pathogenic link between obesity and noncommunicable chronic diseases (NCDs). We aim to characterize changes in BMI over time on antiretroviral therapy (ART) and investigate the association between weight gain and survival in South Africa.

Design And Methods: A prospective cohort study among HIV-positive adults on first-line ART between April 2004 and 2015 in Johannesburg, South Africa. We used latent-class growth modelling (adjusted for age, sex and CD4 cell count) to identify groups of individuals with similar patterns of change in BMI over time.

Results: Eleven thousand, two hundred and sixty-three patients were included. The best fit model involved two linear and two quadratic trajectories. Thirty-five percent of patients were categorized into group one (mean BMI at ART initiation, 20.4 kg/m; mean BMI after 8 years of follow-up, 20.9 kg/m), 38% into group two (24.5-26.2 kg/m), 21% into group three (29.5-32.6 kg/m) and 6% into group four (36.5-40.0 kg/m). Over the 8 years of follow-up, 6% of our cohort went down in BMI standard category, while 45% went up. The largest increase occurred in the first 12 months on ART. In years 2 through 8, we saw a more gradual increase in BMI.

Conclusion: The largest gain in BMI in HIV patients occurred in the first year on ART. During follow-up, over 50% of our population changed BMI categories putting them at an increased risk for NCDs. Consistent counselling on nutritional and lifestyle changes could help improve ART patients' long-term health outcomes.
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http://dx.doi.org/10.1097/QAD.0000000000002302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939155PMC
November 2019

Tissue non-specific alkaline phosphatase mediates the accumulation of cholesterol esters in the murine Y1 adrenal cortex cell line.

Ann Anat 2020 Jan 26;227:151420. Epub 2019 Sep 26.

Department of Chemical Pathology, University of the Witwatersrand Faculty of Health Sciences, National Health Laboratory Service, School of Pathology, Johannesburg, South Africa.

Background: Cholesterol esters (CEs) accumulate in the cells of the adrenal cortex and are used for the synthesis of steroid hormones. The full molecular pathways involved in mediating the accumulation of CEs within the adrenal cortex are yet to be elucidated. Tissue non-specific alkaline phosphatase (TNAP) is needed for intracellular lipid accumulation of triglycerides in adipocytes and is also expressed in the cortical cells of the adrenal gland. Therefore we aimed to determine if TNAP is needed for the accumulation of CEs within the murine Y1 adrenal cortex cell line.

Methods: Y1 cells were induced to accumulate lipids. Lipid accumulation and TNAP activity and expression were determined throughout intracellular lipid accumulation. The location of TNAP within the cell was determined through immunohistochemical analysis. Lipid accumulation in the cells was associated with a rise in TNAP activity and TNAP was localised to lipid droplets within the Y1 cells. Inhibition of TNAP with a specific inhibitor (levamisole) resulted in the cessation of CE accumulation.

Discussion And Conclusions: These data demonstrate that TNAP plays a role in the control of lipid accumulation in this adrenal cortex cell line. Therefore, in both triglyceride and CE storing cell types TNAP would seem to be essential for intra-cellular lipid storage.
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http://dx.doi.org/10.1016/j.aanat.2019.151420DOI Listing
January 2020

Classical Cardiovascular Risk Factors and HIV are Associated With Carotid Intima-Media Thickness in Adults From Sub-Saharan Africa: Findings From H3Africa AWI-Gen Study.

J Am Heart Assoc 2019 07 13;8(14):e011506. Epub 2019 Jul 13.

9 Department of Chemical Pathology National Health Laboratory Services (NHLS) Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa.

Background Studies on the determinants of carotid intima-media thickness ( CIMT ), a marker of sub-clinical atherosclerosis, mostly come from white, Asian, and diasporan black populations. We present CIMT data from sub-Saharan Africa, which is experiencing a rising burden of cardiovascular diseases and infectious diseases. Methods and Results The H3 (Human Hereditary and Health) in Africa's AWI-Gen (African-Wits-INDEPTH partnership for Genomic) study is a cross-sectional study conducted in adults aged 40 to 60 years from Burkina Faso, Kenya, Ghana, and South Africa. Cardiovascular disease risk and ultrasonography of the CIMT of right and left common carotids were measured. Multivariable linear and mixed-effect multilevel regression modeling was applied to determine factors related to CIMT. Data included 8872 adults (50.8% men), mean age of 50±6 years with age- and sex-adjusted mean (±SE) CIMT of 640±123μm. Participants from Ghana and Burkina Faso had higher CIMT compared with other sites. Age (β = 6.77, 95%CI [6.34-7.19]), body mass index (17.6[12.5-22.8]), systolic blood pressure (7.52[6.21-8.83]), low-density lipoprotein cholesterol (5.08[2.10-8.06]) and men (10.3[4.75- 15.9]) were associated with higher CIMT. Smoking was associated with higher CIMT in men. High-density lipoprotein cholesterol (-12.2 [-17.9- -6.41]), alcohol consumption (-13.5 [-19.1--7.91]) and HIV (-8.86 [-15.7--2.03]) were inversely associated with CIMT. Conclusions Given the rising prevalence of cardiovascular diseases risk factors in sub-Saharan Africa, atherosclerotic diseases may become a major pan-African epidemic unless preventive measures are taken particularly for prevention of hypertension, obesity, and smoking. HIV -specific studies are needed to fully understand the association between HIV and CIMT in sub-Saharan Africa.
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http://dx.doi.org/10.1161/JAHA.118.011506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662137PMC
July 2019

Deciphering Endothelial Dysfunction in the HIV-Infected Population.

Adv Exp Med Biol 2019 ;1134:193-215

Department of Chemical Pathology, University of the Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa.

Cardiovascular disease (CVD), as a possible consequence of endothelial dysfunction, is prevalent among HIV-infected patients despite successful administration of antiretroviral drugs. This warrants the routine clinical assessment of endothelial function in HIV-positive patients to circumvent potential CVD events. Several different non-invasive strategies have been employed to assess endothelial function in clinical research studies yielding inconsistencies among these reports. This review summarises the different techniques used for assessing endothelial function, with a focus on proposed blood-based biomarkers, such as endothelial leukocyte adhesion molecule-1 (E-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), TNF-α, interleukin 6 (IL6) and soluble thrombomodulin (sTM). The identification of suitable blood-based biomarkers, especially those that can be measured using a point-of-care device, would be more applicable in under-resourced countries where the prevalence of HIV is high.
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http://dx.doi.org/10.1007/978-3-030-12668-1_11DOI Listing
August 2019

High burden of the metabolic syndrome and its component disorders in South Africans with psoriasis.

Int J Dermatol 2019 May 19;58(5):557-562. Epub 2018 Dec 19.

Department of Internal Medicine, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Background: Psoriasis is associated with cardiometabolic diseases (CMDs) in Caucasians, but no data is available from sub-Saharan populations on either CMD prevalence or psoriasis risk factors. Our aim was to investigate the prevalence of CMDs in a predominantly non-Caucasian cohort of South Africans with psoriasis and to determine the principal risk factors associated with psoriasis.

Methods: This was a cross-sectional case-control study of adult psoriasis patients (n = 103) and controls (n = 98), comparing sociodemographic, anthropometric, clinical, and biochemical characteristics. The groups were matched for gender, ethnicity, and body mass index (BMI).

Results: The prevalence of metabolic syndrome (MetS) (52.4% vs. 33.7%; P = 0.007), type 2 diabetes (T2D) (25.2% vs. 4.1%; P < 0.0001), and hypertension (70.9% vs. 46.6%; P = 0.001) were all higher in the psoriasis group. High-sensitivity CRP was higher in psoriasis patients than controls (4.70 (2.00, 10.9) vs. 2.00 (1.10, 4.80) ng/ml; P < 0.0005). Multivariable logistic regression analysis showed that severe psoriasis was independently associated with MetS (odds ratio [95% CIs]: 4.42 [1.72, 11.4]; P = 0.002), T2D (11.3 [3.07, 41.3]; P = 0.0002), and hypertension (2.48 [0.97, 6.32]; P = 0.05), whilst for psoriasis the principal risk factors were smoking (3.87 [1.97, 7.63]; P < 0.0001) and hsCRP (1.05 [1.00, 1.10]; P = 0.029), with completion of high school (0.23 [0.11, 0.48]; P < 0.0001) being protective.

Conclusions: In this population, psoriasis is characterized by a high burden of CMDs, particularly in those subjects with severe psoriasis. Inflammation plays a role in the etiology of psoriasis, whilst smoking and poor education further increase disease risk.
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http://dx.doi.org/10.1111/ijd.14348DOI Listing
May 2019

The Use of 3T3-L1 Murine Preadipocytes as a Model of Adipogenesis.

Methods Mol Biol 2019 ;1916:263-272

Department of Chemical Pathology, National Health Laboratory Service, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

The 3T3-L1 murine preadipocyte cell line is a commonly used tool for analysis of the subcellular pathways involved in preadipocytic cell differentiation (a process also commonly known as adipogenesis). The major characteristic of adipogenesis is the intracellular accumulation of membrane-bound lipid droplets. Here, we describe methods used for the culture and transformation of these preadipocytes into mature adipocytes and quantification of intracellular lipid accumulation using the lipid specific dye, Oil Red O.
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http://dx.doi.org/10.1007/978-1-4939-8994-2_25DOI Listing
June 2019

Sociodemographic, socioeconomic, clinical and behavioural predictors of body mass index vary by sex in rural South African adults-findings from the AWI-Gen study.

Glob Health Action 2018 ;11(sup2):1549436

a MRC/Wits Rural Public Health and Health Transitions Research Unit, School of Public Health, Faculty of Health Sciences , University of the Witwatersrand , Johannesburg , South Africa.

Background: Despite increasing obesity in South African adults, data on the prevalence and determinants of body mass index (BMI) from rural communities, home to a significant proportion of the population, are scarce.

Objectives: To investigate overall and sex-specific determinants of BMI in a rural adult South African population undergoing rapid social and epidemiological transitions.

Methods: Baseline cross-sectional demographic, socioeconomic, anthropometric, clinical and behavioural data were collected between 2015 and 2016 from 1388 individuals aged 40-60 years and resident in the Agincourt sub-district of Mpumalanga province, a setting typical of rural northeast South Africa. A Health and Socio-Demographic Surveillance System (HDSS) underpins the sub-district and contributes to the Africa Wits-INDEPTH partnership for Genomic Studies (AWI-Gen). Linear regression was used to investigate univariate associations between log-transformed BMI and individual variables and multiple linear regression was used to investigate independent predictors of BMI overall and in sex-stratified analyses.

Results: Median BMI was significantly higher in females (28.7 kg/m[95% CI 24.2-33.2] vs 23.0 kg/m[95% CI 20.3-26.8];p < 0.001) with male sex associated with 17% lower BMI. In sex-stratified multiple linear regression models, compared to those never married, BMI was 7% higher in currently married males and 6% in currently married females. Current smoking in men and former smoking in women were associated with reductions in BMI of 13% and 26% respectively, compared with non-smokers. Higher educational attainment in women and higher socioeconomic status in men were both associated with higher BMI, while being HIV-positive and alcohol consumption in women were associated lower BMI.

Conclusions: Female sex strongly predicts higher BMI in this rural African population. While some predictors of higher BMI differ by sex, married individuals in both sexes had a higher BMI, suggesting that, in addition to developing sex-specific interventions to combat overweight and obesity, targeting married couples may result in reduction in population BMI.
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http://dx.doi.org/10.1080/16549716.2018.1549436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282437PMC
June 2019

The prevalence of gastroesophageal reflux disease in an adult, South African black population, and the association with obesity.

Minerva Gastroenterol Dietol 2019 Jun 27;65(2):100-106. Epub 2018 Nov 27.

Department of Chemical Pathology, National Health Laboratory Service, University of the Witwatersrand Medical School, Johannesburg, South Africa.

Background: The aim of the study was to determine the prevalence of gastroesophageal reflux disease (GERD) in a black population in South Africa and to determine if there was any association with obesity.

Methods: A sample of 312 black subjects was randomly selected and interviewed with a structured questionnaire (GerdQ) consisting of six questions translated into English and two of the most commonly used African languages (Zulu and Xhosa). This question-based symptom score for the diagnosis of GERD has been validated previously. Additional information about age, gender, smoking and alcohol was also obtained. All participants underwent anthropometric measurements.

Results: The prevalence of GERD was more common in black females (22.9%) than black males (4.1%; P<0.0005) and in females there was no association of GERD with waist circumference, age, smoking or alcohol intake. However, the prevalence of GERD was higher in the second compared to the first quartile of Body Mass Index (BMI) (31.4% versus 11.45; P<0.05) but fell in quartiles 3 (28.6%) and 4 (20.1%).

Conclusions: GERD is more common in black females than males and in the former group its prevalence rose with increasing BMI and then decreases at BMIs exceeding 33.1. The reason for the gender differences and the inverted 'U' shaped relationship between GERD and BMI are not known and require further investigation.
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http://dx.doi.org/10.23736/S1121-421X.18.02495-9DOI Listing
June 2019

The burden of dyslipidaemia and factors associated with lipid levels among adults in rural northern Ghana: An AWI-Gen sub-study.

PLoS One 2018 28;13(11):e0206326. Epub 2018 Nov 28.

Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Dyslipidaemia is a primary risk factor for cardiometabolic disease, causing over 17 million deaths globally in 2015. However, the burden of dyslipidaemia and factors associated with lipid levels remain unknown in many rural African populations. Therefore, this study evaluated the association of socio-demographic, anthropometric and behavioural factors with lipid levels in rural Ghana. The prevalence of hypercholesterolaemia, hypertriglyceridaemia and elevated LDL-C in the total population of 1839 (846 men and 993 women) was 4.02%, 2.12%, and 5.55% respectively and did not differ between genders. The prevalence of low HDL-C levels was 60.30% and differed (p = 0.005) between men (56.86%) and women (63.24%). Subcutaneous abdominal fat was associated with TC (β = 0.067, p = 0.015) and TG (β = 0.137, p<0.001) among women and LDL-C (β = 0.139, p = 0.006) and TC (β = 0.071, p = 0.048) among men. Body mass index was associated with TC (β = 0.010, p = 0.043) among men while waist circumference was associated with LDL-C (β = 0.116, p<0.001) and TG (β = 0.094, p<0.001) among women. Hip circumference was negatively associated (β = -0.053, p = 0.043) while visceral fat was positively associated with TG (β = 0.033, p = 0.022) among women. Socioeconomic status, education, being unmarried and employment were associated with HDL-C (β = 0.081, p = 0.004), LDL-C (β = 0.095, p = 0.004) and TG (β = 0.095, p = 0.001) all among women, and TC (β = 0.070, p = 0.010) among men, respectively. Nankana women had lower TC (β = -0.069, p = 0.001), and men lower TG levels (β = -0.084, p = 0.008) than the other ethnic groups. Tobacco smoking (β = 0.066, p = 0.024) and alcohol intake (β = 0.084, p = 0.001) were associated with HDL-C levels among men and women respectively. Further studies are required to investigate whether high prevalence of low HDL-C levels in this population presents with any adverse cardiovascular disease outcomes. Associations of education, employment and adiposity with lipid levels suggest that future societal advances and increases in the prevalence of obesity may lead to associated adverse health consequences. Monitoring and interventions are required to limit these effects.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206326PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261546PMC
April 2019

Gender differences in sociodemographic and behavioural factors associated with BMI in an adult population in rural Burkina Faso - an AWI-Gen sub-study.

Glob Health Action 2018 ;11(sup2):1527557

a Institut de Recherche en Sciences de la Santé, Clinical Research Unit of Nanoro (IRSS/CRUN) , Nanoro , Burkina Faso.

Background: The global health transition is linked with an increased burden of non-communicable diseases with cardiovascular diseases leading the epidemic. In sub-Saharan Africa (SSA), the prevalence of obesity has increased during the past decades and there is a need to investigate the associated driving factors. In Burkina Faso obesity remains low, especially in rural areas. In this study we recruited middle-aged adults, as part of a larger study on genetic and environmental contributions to cardiometabolic disease among Africans.

Objectives: To investigate the distribution of BMI and prevalence of obesity in a cross-sectional population-based study and to determine the sociodemographic and behavioural correlates with BMI.

Methods: Participants (N = 2,076) were recruited from the Nanoro Health and Demographic Surveillance System area and were aged 40-60 years. We applied hierarchical modelling to identify factors associated with BMI and structural equation modelling to identify mediated effects of sociodemographic and behavioural variables on BMI.

Results: Data are presented on 2,076 participants (49.9% female). Men had significantly higher BMI than women with medians of 21.1 (19.2 - 23.4) vs 19.8 (18.1 - 21.6) (p < 0.001), and there were significantly more underweight women compared to men (31.0% vs 17.4%) (p < 0.001). More men were overweight and obese than women (11.9% vs 5.2% and 2.2% vs 1.4%). Socioeconomic status was the major contributor to increased BMI for men, and education was the main contributor in women. Tobacco smoking and chewing, and problematic alcohol consumption were associated with a decrease in BMI in men and women.

Conclusion: Overweight and obesity are relatively low among adults in rural Burkina Faso, and men had a higher median BMI than women. Behavioural factors, including tobacco use and alcohol consumption, contributed to a decrease in BMI, whereas socioeconomic status and education (which were both generally low in this community) contributed to an increase in BMI.
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http://dx.doi.org/10.1080/16549716.2018.1527557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197018PMC
June 2019

Prevalence, incidence, predictors, treatment, and control of hypertension among HIV-positive adults on antiretroviral treatment in public sector treatment programs in South Africa.

PLoS One 2018 3;13(10):e0204020. Epub 2018 Oct 3.

Department of Global Health, Boston University School of Public Health, Boston, United States of America.

Background: One of the key risk factors for cardiovascular disease is hypertension. Hypertension, which leads to heart attacks and strokes, already affects one billion people worldwide, making it a global public health issue. Incidence and prevalence of the condition is on the rise in low- and middle-income countries, with the biggest increase in sub-Saharan Africa and South Africa at the forefront. We examined the prevalence, incidence, predictors, treatment, and control of hypertension among HIV-positive patients on ART in a large South African observational cohort.

Methods: We conducted a prospective study of ART naïve adults initiating ART at a public sector HIV clinic in South Africa between April 2004-2017. Patients with diagnosed hypertension at ART initiation were excluded from the incidence analysis. Log-binomial regression was used to estimate predictors of hypertension at ART initiation, while competing risks regression was used to evaluate the relationship between predictors of incident hypertension, accounting for death as a competing risk.

Results: Among 77,696 eligible patients, 22.0% had prevalent hypertension at ART initiation. Of the remaining patients with no hypertension at ART initiation, 8,125 incident hypertension cases were diagnosed over the period of follow-up, corresponding to an incident rate of 5.4 per 100 person-years (95% confidence interval (CI): 5.3-5.6). We found patients ≥40 years of age and patients with a body mass index (BMI) ≥25kg/m2 were at increased risk of both prevalent and incident hypertension. Male patients and those with pre-hypertension at ART initiation had increased hazards of hypertension over the period of follow-up. When assessing the choice of antiretroviral drug in first-line ART, patients initiated on nevirapine were at 27% increased risk of developing hypertension compared to those initiated on efavirenz, while patients who initiated on either zidovudine or stavudine had a 40% increased risk of developing hypertension compared to patients initiated on tenofovir. Patientswith poorer health status at ART initiation (i.e. WHO III/IV stage, low CD4 count, low hemoglobin levels and low BMI) had a decrease risk of prevalent hypertension. We found an inverse relationship in patients with a CD4 count <50 cells/mm3 at ART initiation who had a 25% increased risk of incident hypertension compared to those with a CD4 count ≥350 cells/mm3.

Conclusion: Over 20% of patients in our cohort had hypertension at ART initiation, and 13% of those with normal blood pressure at ART initiation developed hypertension while on ART. Older patients, males, those on nevirapine, zidovudine or stavudine, and those who are overweight/obese should be targeted for frequent blood pressure monitoring and the identification of other cardiovascular risk factors to encourage lifestyle modifications. Additionally, these groups should be offered pharmaceutical therapy to help prevent myocardial infarction, heart failure, stroke, and kidney disease. Further research is needed to determine the level of access and adherence to pharmaceutical treatment for hypertension in this population. Additionally, an HIV-negative comparison population is needed to assess the association of the HIV virus itself with hypertension.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204020PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169897PMC
April 2019

Genomic and environmental risk factors for cardiometabolic diseases in Africa: methods used for Phase 1 of the AWI-Gen population cross-sectional study.

Glob Health Action 2018 ;11(sup2):1507133

a Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences , University of the Witwatersrand , Johannesburg, South Africa.

There is an alarming tide of cardiovascular and metabolic disease (CMD) sweeping across Africa. This may be a result of an increasingly urbanized lifestyle characterized by the growing consumption of processed and calorie-dense food, combined with physical inactivity and more sedentary behaviour. While the link between lifestyle and public health has been extensively studied in Caucasian and African American populations, few studies have been conducted in Africa. This paper describes the detailed methods for Phase 1 of the AWI-Gen study that were used to capture phenotype data and assess the associated risk factors and end points for CMD in persons over the age of 40 years in sub-Saharan Africa (SSA). We developed a population-based cross-sectional study of disease burden and phenotype in Africans, across six centres in SSA. These centres are in West Africa (Nanoro, Burkina Faso, and Navrongo, Ghana), in East Africa (Nairobi, Kenya) and in South Africa (Agincourt, Dikgale and Soweto). A total of 10,702 individuals between the ages of 40 and 60 years were recruited into the study across the six centres, plus an additional 1021 participants over the age of 60 years from the Agincourt centre. We collected socio-demographic, anthropometric, medical history, diet, physical activity, fat distribution and alcohol/tobacco consumption data from participants. Blood samples were collected for disease-related biomarker assays, and genomic DNA extraction for genome-wide association studies. Urine samples were collected to assess kidney function. The study provides base-line data for the development of a series of cohorts with a second wave of data collection in Phase 2 of the study. These data will provide valuable insights into the genetic and environmental influences on CMD on the African continent.
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http://dx.doi.org/10.1080/16549716.2018.1507133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161608PMC
June 2019

Demographic, socio-economic and behavioural correlates of BMI in middle-aged black men and women from urban Johannesburg, South Africa.

Glob Health Action 2018 ;11(sup2):1448250

a MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences , University of the Witwatersrand , Johannesburg , South Africa.

Background: There is a high and increasing prevalence of overweight and obesity in South Africans of all ages. Risk factors associated with overweight and obesity must be identified to provide targets for intervention.

Objective: To identify the demographic, socio-economic and behavioural factors associated with body mass index (BMI) in middle-aged black South African men and women.

Methods: Data on demographic and socio-economic factors were collected via questionnaire on 1027 men and 1008 women from Soweto Johannesburg, South Africa. Weight and height were measured and BMI was determined. Behavioural factors included tobacco use and consumption of alcohol, and physical activity data were collected using the Global Physical Activity Questionnaire. Menopausal status was determined for the women, and HIV status was available for 93.6% of the men and 39.9% of the women.

Results: Significantly more women were overweight or obese than men (87.9 vs. 44.9%). Smoking prevalence (current or former) and minutes spent in moderate to vigorous intensity physical activity was significantly different between the sexes (both p < 0.0001). In the final hierarchical model, marital status (+ married/cohabiting), household asset score (+), current smoking (-), moderate to vigorous physical activity (-) and HIV status (- HIV infected) significantly contributed to 26% of the variance in BMI in the men. In the women, home language (Tswana-speaking compared to Zulu-speaking), marital status (+ unmarried/cohabiting), education (-), current smoking (-) and HIV status (- HIV infected) significantly contributed to 14% of the variance in BMI.

Conclusions: The sex difference in BMI and the prevalence of overweight and obesity between black South African men and women from Soweto, as well as the sex-specific associations with various demographic, socio-economic and behavioural factors, highlight the need for more tailored interventions to slow down the obesity epidemic.
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http://dx.doi.org/10.1080/16549716.2018.1448250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084500PMC
November 2018

Genetic variants in SEC16B are associated with body composition in black South Africans.

Nutr Diabetes 2018 07 19;8(1):43. Epub 2018 Jul 19.

Division of Human Genetics, School of Pathology, Faculty of Health Sciences, National Health Laboratory Service & University of the Witwatersrand, Johannesburg, South Africa.

Objective: The latest genome-wide association studies of obesity-related traits have identified several genetic loci contributing to body composition (BC). These findings have not been robustly replicated in African populations, therefore, this study aimed to assess whether European BC-associated gene loci played a similar role in a South African black population.

Methods: A replication and fine-mapping study was performed in participants from the Birth to Twenty cohort (N = 1,926) using the Metabochip. Measurements included body mass index (BMI), waist and hip circumference, waist-to-hip ratio (WHR), total fat mass, total lean mass and percentage fat mass (PFM).

Results: SNPs in several gene loci, including SEC16B (P <  9.48 × 10), NEGR1 (P < 1.64 × 10), FTO (P < 2.91 × 10), TMEM18 (P < 2.27 × 10), and WARS2 (P < 3.25 × 10) were similarly associated (albeit not at array-wide signficance (P ≤ 6.7 × 10) with various phenotypes including fat mass, PFM, WHR linked to BC in this African cohort, however the associations were driven by different sentinel SNPs. More importantly, DXA-derived BC measures revealed stronger genetic associations than simple anthropometric measures. Association signals generated in this study were shared by European and African populations, as well as unique to this African cohort. Moreover, sophisticated estimates like DXA measures enabled an enhanced characterisation of genetic associations for BC traits.

Conclusion: Results from this study suggest that in-depth genomic studies in larger African cohorts may reveal novel SNPs for body composition and adiposity, which will provide greater insight into the aetiology of obesity.
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http://dx.doi.org/10.1038/s41387-018-0050-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053407PMC
July 2018

Socio-demographic and behavioural determinants of body mass index among an adult population in rural Northern Ghana: the AWI-Gen study.

Glob Health Action 2018 ;11(sup2):1467588

a Navrongo Health Research Centre (NHRC) , Navrongo , Ghana.

Background: Obesity and associated cardiometabolic diseases are increasing in urban sub-Saharan Africa due to a complex epidemiological and nutritional transition. Related data on rural communities is scarce.

Objectives: The study characterized the socio-demographic and behavioural factors influencing body mass index (BMI) among adults in rural Northern Ghana Methods: A population-based cross-sectional study involving adults aged 40-60 years residing in the Kassena-Nankana districts was undertaken. Demographic, socio-economic and behavioural data were collected along with measures of anthropometry. We determined factors associated with BMI among women and men.

Results: A total of 2014 adults were studied. The median age was 51 (IQR 45-57) years and 54% were women. The prevalence of overweight/obesity was higher among women than men (18.4% vs. 7.2%; p < 0.001), whilst underweight was more prevalent in men (18.3% vs. 13.1%; p = 0.001). Participants with the highest level of education and a high household socio-economic status had higher BMIs than those in the lowest strata in both men (β = 0.074, p = 0.028 and β = 0.072, p < 0.001, respectively) and women (β = 0.174, p = 0.001 and β = 0.109, p < 0.001, respectively). Men (β = -0.050; p < 0.001) and women (β = -0.073; p < 0.001) of the Nankana ethnic group had a lower BMI than the Kassena ethnic group. Among men, alcohol consumption (β = -0.021; p = 0.001) and smoking (β = -0.216; p < 0.001) were associated with lower BMI. Smokeless tobacco was associated with lower BMI among women. Pesticide exposure was associated with higher BMI (β = 0.022; p = 0.022) among men.

Conclusion: Age, sex, ethno-linguistic group and prevailing socio-demographic and behavioural factors within this rural community in Northern Ghana influence BMI. The observed positive association between pesticide use and BMI warrants further investigation.
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http://dx.doi.org/10.1080/16549716.2018.1467588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041816PMC
November 2018