Kidney dysfunction: prevalence and associated risk factors in a community-based study from the North West Province of South Africa.

BACKGROUND: Globally, the World Health Organization ranks chronic kidney disease (CKD) as one of the top 10 causes of mortality. In South Africa, where noncommunicable diseases have become leading causes of mortality, the true population prevalence of CKD is unknown and associated risk factors remain understudied. This study aimed to describe the prevalence of kidney dysfunction and associated risk factors in a community from the North West province of South Africa. METHODS: This cross-sectional study included 1999 participants older than 30 years. Kidney dysfunction was defined as (i) estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2, or (ii) urine albuminuria-to-creatinine ratio (uACR) ≥ 3.0 mg/mmol, or a combination (i and ii). Risk factors included age, sex, urban/rural locality, body mass index (BMI), blood pressure (BP), lipid profile, haemoglobin A1c (HbA1C), C-reactive protein (CRP), gamma-glutamyl transferase (GGT), tobacco use, and HIV status. RESULTS: Mean age of participants was 48 (42;56) years, and 655/1999 (33%) had eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol. Compared to those with normal kidney function, participants with eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol were older, female, had higher measures of adiposity, systolic, diastolic, and mean arterial blood pressure, serum lipids and C-reactive protein (CRP) (all p ≤ 0.024). In multiple regression analyses eGFR was associated with systolic BP (ß = 0.11) and HIV infection (ß = -0.09), and albuminuria was associated with elevated CRP (ß = 0.12) and HIV infection (ß = 0.11) (all p < 0.026). In both groups (individuals with and without kidney dysfunction respectively), eGFR was associated with age (ß = -0.29, ß = -0.49), male sex (ß = 0.35, ß = 0.28), BMI (ß = -0.12, ß = -0.09), low-density/high-density lipoprotein cholesterol ratio (ß = -0.17, ß = -0.09) and CRP (ß = 0.10, ß = 0.09) (all p < 0.005); and uACR was associated with female sex (ß = 0.10, ß = -0.14), urban locality (ß = -0.11, ß = -0.08), BMI (ß = -0.11, ß-0.11), and systolic BP (ß = 0.27, ß = 0.14) (all p < 0.017). CONCLUSION: In this study from the North West province, South Africa, eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol was prevalent and associated with modifiable risk factors. The findings may inform screening strategies for kidney disease prevention, focusing on women, obesity, blood pressure control, dyslipidaemia, identifying and treating inflammation, and HIV diagnosis and treatment.

The Relationship of Circulating Homocysteine with Fibrinogen, Blood Pressure, and Other Cardiovascular Measures in African Adolescents.

OBJECTIVES: To evaluate the associations between homocysteine (Hcy) and cardiovascular health in South African adolescents. STUDY DESIGN: Circulating Hcy concentrations of 172 South African adolescents (105 girls, ages 13 to <18 years) were measured. Anthropometric and cardiovascular factors were also included and cross-sectionally analyzed through general linear models. RESULTS: Hcy correlated positively with body weight (P = .03; after adjusting for multiple testing, it was not regarded as significant) and muscle mass (P = .01), but negatively with fibrinogen concentrations (P = .001). Across Hcy tertiles, blood pressure produced approximating U-shaped curves, with differences between the middle and upper tertiles (all P < .02). Forty percent of the adolescents had elevated blood pressure, of whom 37% fell in the lowest and 38% in the highest Hcy tertiles. Hcy differed between the sexes (with boys having higher Hcy), but not between subgroups based on puberty, weight, stunting, smoking, or alcohol consumption. CONCLUSIONS: Both high and low Hcy could be early contributing risk factors to cardiovascular health. The associations between Hcy and blood pressure suggest that dietary and lifestyle manipulation, to achieve the optimal range of Hcy, may be beneficial in preventing Hcy-related hypertension in adulthood. The inverse relationship between Hcy and fibrinogen remains to be clarified.

The association of von willebrand factor and its cleaving protease (ADAMTS13) with health behaviours in young black and white adults: the African-PREDICT study.

To reduce cardiovascular risks imposed by Von Willebrand factor (vWF) and ADAMTS13 from young ages, knowledge on health behaviours that may affect their concentrations is essential. We therefore determined whether circulating vWF antigen and ADAMTS13 associate with health behaviours. We included 1196 black and white healthy adults aged 20-30 years and used questionnaires for socio-economic, tobacco and alcohol use data. vWF:Ag was measured from citrated samples and ADAMTS13, cotinine and gamma-glutamyl transferase (GGT) from serum. Salt intake was estimated from 24-hour urine and body mass index (BMI) was calculated. Black adults had higher vWF:Ag and lower ADAMTS13 levels compared to whites (all p < 0.001). In multiple regression analyses in the total group, vWF:Ag associated positively with BMI (p = 0.037), while ADAMTS13 associated negatively with BMI (p = 0.016) and cotinine (p = 0.029); and positively with GGT (p = 0.002). When exploring within each ethnic group, vWF:Ag associated positively with estimated salt intake (p = 0.043) only in blacks. In whites, vWF:Ag associated positively with BMI (p = 0.023) while ADAMTS13 associated positively with GGT (p = 0.003) and negatively with cotinine (p = 0.041). Young black adults may have an increased thrombotic risk due to higher vWF and lower ADAMTS13. The ethnic-specific associations observed may have implications for public health initiatives to improve cardiovascular outcomes.

Retinal vessel caliber and caliber responses in true normotensive black and white adults: The African-PREDICT study.

PURPOSE: Globally, a detrimental shift in cardiovascular disease risk factors and a higher mortality level are reported in some black populations. The retinal microvasculature provides early insight into the pathogenesis of systemic vascular diseases, but it is unclear whether retinal vessel calibers and acute retinal vessel functional responses differ between young healthy black and white adults. METHODS: We included 112 black and 143 white healthy normotensive adults (20-30 years). Retinal vessel calibers (central retinal artery and vein equivalent (CRAE and CRVE)) were calculated from retinal images and vessel caliber responses to flicker light induced provocation (FLIP) were determined. Additionally, ambulatory blood pressure (BP), anthropometry and blood samples were collected. RESULTS: The groups displayed similar 24 h BP profiles and anthropometry (all p > .24). Black participants demonstrated a smaller CRAE (158 ±â€¯11 vs. 164 ±â€¯11 MU, p < .001) compared to the white group, whereas CRVE was similar (p = .57). In response to FLIP, artery maximal dilation was greater in the black vs. white group (5.6 ±â€¯2.1 vs. 3.3 ±â€¯1.8%; p < .001). CONCLUSIONS: Already at a young age, healthy black adults showed narrower retinal arteries relative to the white population. Follow-up studies are underway to show if this will be related to increased risk for hypertension development. The reason for the larger vessel dilation responses to FLIP in the black population is unclear and warrants further investigation.

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.

Leptin and the Retinal Microvasculature in Young Black and White Adults: The African-PREDICT Study.

BACKGROUND: Leptin is a vasoactive peptide that has been linked to diseases associated with macrovascular deterioration. What is still uncertain is its involvement in the microvasculature. Since microvascular changes are presumed to precede macrovascular deterioration, we examined whether measures of the retinal microvasculature are associated with leptin in healthy, young Black and White individuals. METHOD: We included 283 Black and 289 White men and women (aged 20-30 years). We determined serum leptin, calculated central retinal artery and vein equivalents and arterio-venous ratio. We also measured retinal vessel responses to light flicker provocation. RESULTS: Black men were leaner and had lower leptin than White men, whereas Black women had increased adiposity and leptin compared to White women (all p<0.001). Black groups had narrower retinal arteries, and greater maximum arteriolar and venular dilations in response to light flicker than the White groups (p<0.001). Arterio-venous ratio associated negatively with leptin (all p≤0.044) in all groups (except Black women), but was lost upon adjustment for body mass index and other covariates. We found an inverse association between maximal venular dilation and leptin only in Black men in single and multiple regression analyses (Std ß= -0.22; R2=0.05; p=0.035). No associations were found between other retinal measures with leptin in the other groups. CONCLUSION: We found an independent, negative association between retinal vein dilation with leptin in healthy, young Black men, suggesting a potential detrimental role for leptin in regulating microvascular responses in a population group known to be at greater risk of cardiovascular disease development.

Leptin and the vasculature in young adults: The African-PREDICT study.

BACKGROUND AND AIM: Information regarding the effect of leptin on the vasculature in young healthy adults at risk for cardiovascular disease development is limited. We therefore examined the associations between measures of subclinical atherosclerosis (carotid intima-media thickness, carotid cross-sectional wall area), large artery stiffness (pulse wave velocity) and a measure of endothelial dysfunction (von Willebrand factor [vWF]) with leptin in young healthy men and women. METHODS: In a cross-sectional study in South Africa involving 820 normotensive individuals (337 men and 483 women) aged 20-30 years, we measured carotid intima-media thickness, carotid cross-sectional wall area, pulse wave velocity, vWF from citrated plasma and leptin from serum. RESULTS: Despite sevenfold higher leptin in women than men (P < 0.001), only in young healthy men, we observed negative, independent associations between measures of carotid wall thickness (carotid intima-media thickness: R2  = 0.05; ß = -0.20; P = 0.036; carotid cross-sectional wall area: R2  = 0.05; ß = -0.20; P = 0.035) with leptin in multivariable-adjusted regression analyses. When reviewing these associations across body mass index categories, we found an association to be evident only in overweight men (carotid intima-media thickness: R2  = 0.15; ß = -0.41; P = 0.007; carotid cross-sectional wall area: R2  = 0.21; ß = -0.47; P = 0.002). No association was observed in the women or between pulse wave velocity and vWF with leptin. CONCLUSION: In young healthy men, we found a beneficial inverse association between measures of carotid wall thickness and circulating leptin, thereby supporting a potential vascular protective role of leptin.

BDNF increases associated with constant troponin T levels and may protect against poor cognitive interference control: The SABPA prospective study.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) modulates brain health and cognition, which can interfere with executive cognitive function. BDNF was implicated with microcirculatory ischaemia and may reflect cardiomyocyte injury. We aimed to determine whether prospective changes (%Δ) in BDNF and cardiac troponin T (cTnT) will be associated with executive cognitive function in a bi-ethnic cohort. DESIGN: A prospective investigation was conducted over a three-year period in a bi-ethnic sex cohort (N = 338; aged 20-65 years) from South Africa. Fasting serum samples for BDNF and cTnT were obtained. The STROOP-color-word conflict test (CWT) was applied to assess executive cognitive function at baseline. RESULTS: In Blacks, BDNF (P < 0.001) increased over the three-year period while cTnT did not change. In contrast, in Whites, BDNF and cTnT decreased over three years. In Black men, no change in cTnT was associated with increased ΔBDNF (ß = 0.25; 95% CI 0.05-0.45; P = 0.02). In the Black men, constant cTnT levels were inversely associated with executive cognitive function (ß = -0.33; 95% CI -0.53 to -0.12; P = 0.003). Three-year increases in BDNF increased the likelihood for chronic lower cTnT levels at a pre-established cut-point of <4.2 ng/L [OR = 2.35 (1.12-4.94), P = 0.02]. The above associations were not found in the White sex groups. CONCLUSIONS: Central neural control mechanisms may have upregulated BDNF in Black men as a way to protect against myocardial stress progression and to possibly improve processes related to cognitive interference control. High-sensitive cTnT levels may act as an early predictor of disturbed neural control mechanisms.

Leptin and its Relation to Autonomic Activity, Endothelial Cell Activation and Blood Pressure in a Young Black and White Population: The African-PREDICT study.

An increasing prevalence of obesity-related hypertension is observed in the youth and may have severe consequences for future cardiovascular disease development. Previous studies portrayed leptin as a potential factor involved in obesity-related hypertension development. In order to understand leptin's contributions to early cardiovascular deterioration, we investigated leptin and its associations with measures of autonomic activity, endothelial activation, and blood pressure in young healthy black and white men and women. We included 820 participants (aged 20-30 years) and determined serum leptin and endothelial cellular adhesion molecules. We measured 24-h blood pressure, heart rate, and heart rate variability components. In multivariate-adjusted regression analyses, we found consistent associations between markers of autonomic activity (such as 24-h heart rate, day and night-time heart rate as well as heart rate variability total power) and leptin in both white (all p≤0.001) and black men (all p≤0.040). These findings were absent or less prominent in women, despite their almost 10-fold higher leptin levels than men. Only in white men, 24-h diastolic blood pressure was associated with leptin (Std ß=0.37; p=0.006). This association was found to be partly mediated by autonomic activity (24-h heart rate variability total power). No independent associations were observed between leptin and markers of endothelial cell activation, irrespective of race or gender. Leptin's independent association with autonomic neural activity in a young apparently healthy population suggests an early influence of leptin on autonomic function and future blood pressure elevation especially in men.

Ethnic-specific relationships between haemostatic and oxidative stress markers in black and white South Africans: The SABPA study.

Haemostatic- and oxidative stress markers are associated with increased cardiovascular risk. In the black population, evidence exists that both an imbalance in the haemostatic system and oxidative stress link with the development of hypertension. However, it is unclear whether these two risk components function independently or are related, specifically in the black population, who is known to have a high prevalence of stroke. We aimed to investigate associations between the haemostatic system and oxidative stress in black and white South Africans. We performed a cross-sectional study including 181 black (mean age, 44; 51.4% women) and 209 white (mean age, 45; 51.7% women) teachers. Several markers of the haemostatic- (von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1, d-dimer and clot lysis time) and oxidant-antioxidant (serum peroxides, total glutathione, glutathione peroxidase- and glutathione reductase activities) systems were measured. Along with a worsened cardiovascular profile, the black group had higher haemostatic-, inflammation- and oxidative stress markers as well as decreased glutathione peroxidase activity. In multiple regression analyses, fibrinogen was positively associated with serum peroxides (p < 0.001) in both ethnic groups. In the black population, we found negative associations of von Willebrand factor and clot lysis time with glutathione peroxidase activity (p ≤ 0.008), while a positive association existed between clot lysis time and serum peroxides (p = 0.011) in the white population. We conclude that in the black population, decreased GPx activity accompanies an altered haemostatic profile, while in the white population associations may suggest that serum peroxides impair fibrin clot lysis.

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.

H-Type Hypertension among Black South Africans and the Relationship between Homocysteine, Its Genetic Determinants and Estimates of Vascular Function.

Elevated homocysteine (Hcy) increases cardiovascular disease (CVD) risk. Our objective was to emphasize Hcy's contribution in hypertension and CVD management by determining H-type hypertension (hypertension with Hcy ≥ 10 µmol/L) and associations between Hcy, blood pressure (BP) and estimates of vascular function among Black South Africans. We included 1995 adults (63% female). Plasma Hcy and cardiovascular measures (systolic and diastolic BP (SBP, DBP), pulse pressure, heart rate (HR), carotid-radialis pulse wave velocity (cr-PWV), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1) were quantified. Five Hcy-related polymorphisms (cystathionine ß-synthase (CBS 844ins68, T833C, G9276A); methylenetetrahydrofolate reductase (MTHFR C677T) and methionine synthase (MTR A2756G)) were genotyped. Hcy was >10 µmol/L in 41% (n = 762), and of the 47% (n = 951) hypertensives, 45% (n = 425) presented with H-type. Hcy was higher in hypertensives vs. normotensives (9.86 vs. 8.78 µmol/L, p < 0.0001, effect size 0.56) and correlated positively with SBP, DBP, cr-PWV and ICAM-1 (r > 0.19, p < 0.0001). Over Hcy quartiles, SBP, DBP, HR, cr-PWV and ICAM-1 increased progressively (all p-trends ≤ 0.001). In multiple regression models, Hcy contributed to the variance of SBP, DBP, HR, cr-PWV and ICAM-1. H-type hypertensives also had the lowest MTHFR 677 CC frequency (p = 0.03). Hcy is positively and independently associated with markers of vascular function and raised BP.

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.

Aldosterone and angiotensin II profiles in young black and white women using different hormonal contraceptives: the African-PREDICT study.

Exogenous estrogens and progestins may affect the components of the renin-angiotensin-aldosterone system (RAAS). Changes in ventricular blood volume are associated with increased secretion of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP), which may also be affected by hormonal contraceptives. In this study, we aimed to compare components of the RAAS and NT-proBNP between groups using different hormonal contraceptives, including the combination pill, the injection or implant, and controls (no contraception) in black and white women of fertile age (20 - 30 years). Secondly, we determined whether blood pressure and NT-proBNP are associated with the RAAS components. We included 397 black and white women not using contraceptives, 120 using the combination pill, and 103 receiving an injection/implant. RAAS Triple-A analysis was carried out with LC-MS/MS quantification, and blood pressure measurements (ABPM) taken over 24 h. We found that serum aldosterone was higher (475.7 vs. 249.2 pmol/L; p < 0.001) in the combination pill group than in the no contraception group of white women. The aldosterone-angiotensin II ratio (AA2) was higher (5.4 vs. 2.5; p < 0.001) in the combination pill group than in the no contraception group. In the black women using the combination pill, we found a borderline-positive and borderline-negative association between 24-h systolic blood pressure and NT-proBNP with equilibrium (eq) Ang II, respectively. In white women using the combination pill, only CRP contributed positively and independently to NT-proBNP. To conclude, activation of RAAS by different hormonal contraceptives may increase future risk for the development of hypertension in young black and white women.

Associations of cholesterol and glucose with cardiovascular dysfunction in black Africans: the SABPA study.

The aim was to determine whether blood glucose or cholesterol is the more prominent contributor to cardiovascular dysfunction in 101 African men and 99 African women. We measured ambulatory daytime blood pressure (BP), carotid intima-media thickness (CIMT), and determined blood glucose and lipids in serum. High-density lipoprotein cholesterol (HDL) (p = 0.002) and HDL: total cholesterol (HDL:TC) (p ≤ 0.001) were significantly lower, while serum glucose (p ≤ 0.001) was significantly higher in men. In single, partial, and multiple regression analysis, BP correlated positively with blood glucose in men. Furthermore, CIMT (B = -0.50; p = 0.009) correlated negatively with HDL:TC in men. While in women CIMT (B = 0.346; p = 0.015) correlated positively with glucose. In conclusion, subclinical atherosclerosis is significantly related to an unfavorable HDL profile in men, whereas in women, this link is stronger with fasting glucose.

Exploring biomarkers associated with deteriorating vascular health using a targeted proteomics chip: The SABPA study.

ABSTRACT: In this observational study, by the use of a multiplex proteomic platform, we aimed to explore associations between 92 targeted proteins involved in cardiovascular disease and/or inflammation, and phenotypes of deteriorating vascular health, with regards to ethnicity.Proteomic profiling (92 proteins) was carried out in 362 participants from the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study of black and white African school teachers (mean age 44.7 ±â€Š9.9 years, 51.9% women, 44.5% Black Africans, 9.9% with known cardiovascular disease). Three proteins with <15% of samples below detectable limits were excluded from analyses. Associations between multiple proteins and prevalence of hypertension as well as vascular health [Carotid intima-media thickness (cIMT) and pulse wave velocity (PWV)] measures were explored using Bonferroni-corrected regression models.Bonferroni-corrected significant associations between 89 proteins and vascular health markers were further adjusted for clinically relevant co-variates. Hypertension was associated with growth differentiation factor 15 (GDF-15) and C-X-C motif chemokine 16 (CXCL16). cIMT was associated with carboxypeptidase A1 (CPA1), C-C motif chemokine 15 (CCL15), chitinase-3-like protein 1 (CHI3L1), scavenger receptor cysteine-rich type 1 protein M130 (CD163) and osteoprotegerin, whereas PWV was associated with GDF15, E-selectin, CPA1, fatty acid-binding protein 4 (FABP4), CXCL16, carboxypeptidase B (CPB1), and tissue-type plasminogen activator. Upon entering ethnicity into the models, the associations between PWV and CPA1, CPB1, GDF-15, FABP4, CXCL16, and between cIMT and CCL-15, remained significant.Using a multiplex proteomic approach, we linked phenotypes of vascular health with several proteins. Novel associations were found between hypertension, PWV or cIMT and proteins linked to inflammatory response, chemotaxis, coagulation or proteolysis. Further, we could reveal whether the associations were ethnicity-dependent or not.

A demographic approach to assess elevated blood pressure and obesity in prepubescent children: the ExAMIN Youth South Africa study.

BACKGROUND: Obesity and hypertension prevalence among children are a concern, with limited evidence available on sex and ethnic differences in childhood blood pressure. We aimed to determine the number of children with hypertension and obesity to identify unique adiposity and blood pressure characteristics by sex and ethnicity, and to estimate the odds of having elevated blood pressure with increasing adiposity. METHODS: We included 1062 healthy children (5-9 years of age) in an observational school-based study in South Africa. Pediatric validated automated devices were used to measure brachial blood pressure and performed pulse wave analysis to assess central hemodynamics. Standard anthropometry was carried out to determine body composition and demographic questionnaires were completed. RESULTS: Almost 20% of children were overweight/obese and 14.1% had elevated blood pressure or hypertension (22.8%). Ethnic differences included greater adiposity in white compared with black children (all P < 0.0001), but higher DBP and total vascular resistance in black compared with white children (both P < 0.05). DBP and total vascular resistance were also higher in girls than boys (both P < 0.01). A 51-60% increased risk of developing elevated blood pressure was observed for 1SD (standard deviation) increase of sex-specific BMI [1.60 (1.4-1.8); P < 0.0001] and waist/height ratio [1.51 (1.3-1.7); P < 0.0001]. CONCLUSION: Unique sex and ethnic differences in body composition and blood pressure exist in prepubescent children, with overweight/obesity increasing the risk of elevated blood pressure. Our findings support primary prevention strategies to combat the growing burden of hypertension and obesity-related diseases in youth. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov (NCT04056377).

Vascular Structure and Inflammation in a South African Population: The SABPA Study.

BACKGROUND AND OBJECTIVE: Inflammation plays a role in the early onset of cardiovascular disease. However, longitudinal studies on this topic, especially in South African populations, are scant. We explored whether early changes in vascular structure are associated with changes in inflammation. METHODS: We investigated 303 South African teachers aged 20-65 years at two intervals, three years apart. Standardised methods were used to determine carotid intima-media thickness (IMT) and cross-sectional wall area (CSWA) as measures of vascular structure, as well as the inflammatory markers soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein (CRP) and interleukin-6 (IL-6) at baseline and follow-up. RESULTS: IMT and CSWA were higher, while CRP was lower at follow-up than at baseline. After adjusting for confounding factors, percent change in IMT was inversely associated with percent change in suPAR (ß = -0.12, p = 0.036; adjusted R2 = 0.16) only, and only in the highest tertile of percent change in suPAR (r = -0.31; p = 0.002). CONCLUSION: The early structural changes observed are not related to higher inflammatory levels in this South African population. Future studies are needed to investigate the possible protective effect of suPAR on early changes in vascular structure, especially with the focus on cardiovascular disease prevention.

Retinal microvasculature and masked hypertension in young adults: the African-PREDICT study.

Masked hypertension is known to induce microvascular complications. However, it is unclear whether early microvascular changes are already occurring in young, otherwise healthy adults. We therefore investigated whether retinal microvascular calibers and acute responses to a flicker stimulus are related to masked hypertension. We used the baseline data of 889 participants aged 20-30 years who were taking part in the African Prospective study on the Early Detection and Identification of Cardiovascular Disease and Hypertension. Clinic and 24-h ambulatory blood pressure were measured. The central retinal artery equivalent (CRAE) and central retinal vein equivalent were calculated from fundus images, and retinal vessel dilation was determined in response to flicker light-induced provocation. A smaller CRAE was observed in those with masked hypertension vs. those with normotension (157.1 vs. 161.2 measuring units, P < 0.001). In forward multivariable-adjusted regression analysis, only CRAE was negatively related to masked hypertension [adjusted R2 = 0.267, ß = -0.097 (95% CI = -0.165; -0.029), P = 0.005], but other retinal microvascular parameters were not associated with masked hypertension. In multivariable logistic regression analyses, masked hypertension [OR = 2.333, (95% CI = 1.316; 4.241), P = 0.004] was associated with a narrower CRAE. In young healthy adults, masked hypertension was associated with retinal arteriolar narrowing, thereby reflecting early microvascular alterations known to predict cardiovascular outcomes in later life.

The Exercise, Arterial Modulation and Nutrition in Youth South Africa Study (ExAMIN Youth SA).

Background: The impact of a sedentary and unhealthy lifestyle on cardiovascular health is well-documented, however the current obesity and hypertension trends among children is concerning. The ExAMIN Youth SA study aims to investigate the impact of lifestyle behaviors (physical fitness/activity, dietary intake and psychosocial factors) involved in early vascular aging among South African children. Methods: This study is an analytical, multidisciplinary, observational cohort study in a school-based setting. We aim to phenotype a cohort of ~1,000 primary school children (black and white boys and girls between ages 5-9 years) based on current clinical childhood conditions including hypertension and obesity. The primary phenotype is large artery stiffness and retinal microvascular diameters, both biomarkers of early vascular aging. The risk factors and mediators of early vascular aging and also responsible for the clinical conditions include physical inactivity, unhealthy diet, and life stress. Additionally, urinalysis and salivary analyses will be performed to identify biomarkers related to the pathophysiology of early vascular aging. Discussion: In line with the growing prevalence of obesity and hypertension responsible for the development of early vascular aging from childhood to adulthood, this study will address the critical areas in which we observe unfavorable arterial modulation related to dietary behaviors, physical inactivity, and early life stress. Implementation of novel biological markers may further contribute to our understanding of early cardiovascular adaptations in childhood, and aid in the development of primary prevention programs. Trial registration: The study was retrospectively registered on ClinicalTrials.gov on 15 August 2019 (NCT04056377).