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

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

Purpose: Elevated blood pressure is a well‐documented risk factor for cardiovascular disease and mortality in Sub‐Saharan Africa (SSA). With SSA also affected by high Human Immunodeficiency Virus (HIV) infection rates, it remains controversial whether the HIV‐infected population has a higher cardiovascular risk than the general population. We, therefore reviewed the literature comparing blood pressure estimates in treated HIV‐infected populations against untreated and/or uninfected controls from SSA. Methods: We conducted a narrative review through PubMed and EBSCO Discovery Service (EDS) to determine the estimates of raised blood pressure and hypertension in the HIV‐infected individuals versus uninfected controls (01 January 2005 to 11 November 2018). Results: After review, we included 14 eligible studies from six countries including 26,302 participants that compared treated HIV‐infected, versus untreated and uninfected controls. Studies involving 24,696 participants reported lower blood pressure and/or prevalence of hypertension in treated HIV‐infected patients compared to uninfected controls. Studies comprising of 3,536 participants reported higher blood pressure and hypertension prevalence in the treated HIV‐infected group than uninfected counterparts, whereas studies with 6,379 participants showed no difference in blood pressure and/or prevalence of hypertension. When comparing HIV patients with and without antiretroviral treatment, studies with 10,304 patients showed treated patients to have lower blood pressure and/or prevalence of hypertension, one study indicated higher blood pressure and/or prevalence of hypertension and studies with 5,806 patients showed no difference in blood pressure and/or prevalence of hypertension than untreated infected patients. Conclusion: The majority of the findings in this review indicate lower or similar blood pressure and/or prevalence of hypertension in treated HIV‐infected individuals compared to untreated and uninfected co

BACKGROUND: Waist circumference (WC) thresholds derived from western populations continue to be used in sub-Saharan Africa (SSA) despite increasing evidence of ethnic variation in the association between adiposity and cardiometabolic disease and availability of data from African populations. We aimed to derive a SSA-specific optimal WC cut-point for identifying individuals at increased cardiometabolic risk. METHODS: We used individual level cross-sectional data on 24 181 participants aged ⩾15 years from 17 studies conducted between 1990 and 2014 in eight countries in SSA. Receiver operating characteristic curves were used to derive optimal WC cutpoints for detecting the presence of at least two components of metabolic syndrome (MS), excluding WC. RESULTS: The optimal WC cut-point was 81.2 cm (95% CI 78.5–83.8 cm) and 81.0 cm (95% CI 79.2–82.8 cm) for men and women, respectively, with comparable accuracy in men and women. Sensitivity was higher in women (64%, 95% CI 63–65) than in men (53%, 95% CI 51–55), and increased with the prevalence of obesity. Having WC above the derived cut-point was associated with a twofold probability of having at least two components of MS (age-adjusted odds ratio 2.6, 95% CI 2.4–2.9, for men and 2.2, 95% CI 2.0–2.3, for women). CONCLUSION: The optimal WC cut-point for identifying men at increased cardiometabolic risk is lower (⩾81.2 cm) than current guidelines (⩾94.0 cm) recommend, and similar to that in women in SSA. Prospective studies are needed to confirm these cut-points based on cardiometabolic outcomes

Objective: Black populations exhibit higher arterial stiffness than whites and suffer a disproportionate burden of cardiovascular disease. It is therefore important to identify modifiable health behaviours predicting large artery stiffness in blacks. We examined whether traditional cardiovascular risk factors and health behaviours of black South Africans predict large artery stiffness 10 years later. Methods: We included 650 HIV-free participants (32.8% men) and collected data in rural and urban areas of the North West Province in 2005 and 2015. We collected questionnaire data, anthropometry, blood pressure and determined cardiometabolic and inflammatory markers from blood samples. We measured carotid–femoral pulse wave velocity (PWV) at follow-up. Results: A total of 25.3% of our population, aged 65 ± 9.57 years, had a PWV exceeding 10 m/s. In multivariable-adjusted regression analyses, the strongest predictors of PWV were mean arterial pressure, age and heart rate (all P < 0.024). Urban locality (R2 = 0.31, β = 0.12, P = 0.001), self-reported alcohol use (β = 0.11, P = 0.018) and plasma glucose (β = 0.08 P = 0.023) associated positively with PWV at follow-up. We found a negative association between PWV and BMI (β = −0.15, P = 0.001), and no associations with sex, smoking, inflammatory markers, lipids, liver enzymes or antihypertensive medication. When replacing self-reported alcohol with gamma-glutamyltransferase, the latter associated positively with PWV (β = 0.09, P = 0.023). Conclusion: A health profile associated with excessive alcohol use, including an urban setting, elevated plasma glucose and lower BMI predicts large artery stiffness independently of age and blood pressure in black South Africans over 10 years. This observation prompts urgent public health strategies to target alcohol overus

Background Hypertensive heart disease is a rising concern, especially among black South African women. As high sensitivity cardiac troponin T (cTnT) is a marker of cardiomyocyte damage, we determined the potential link of (i) systemic endothelial dysfunction (reflected by urinary albumin-to-creatinine ratio), (ii) large artery stiffness, (iii) cardiac volume load (estimated by the N-terminal prohormone B-type natriuretic peptide (Nt-proBNP)), and (iv) ECG left ventricular hypertrophy in post-menopausal black women. Methods In 121 (50 normotensive and 71 hypertensive) black women (mean age: 60.6 years), basic cardiovascular assessments including blood pressure and ECG were performed, along with plasma and urinary biomarkers including cTnT. Results The cTnT levels (p=0.049) along with Nt-proBNP (p=0.003), pulse pressure (p<0.0001) and the Cornell product (p=0.030) were higher in hypertensive than normotensive women. Only in hypertensive women, was cTnT independently associated with urinary albumin-to-creatinine ratio (β=0.25; p=0.019), pulse pressure (β=0.31; p=0.019), Nt-proBNP (β=0.47; p<0.0001) and Cornell product (β=0.31; p=0.018). An independent association between albumin-to-creatinine ratio and cTnT was also evident in normotensive women (β=0.34; p=0.037). Conclusion We found cTnT to be a useful marker in an elderly black population relating to several measures of cardiovascular deterioration – from subclinical endothelial dysfunction to left ventricular hypertrophy

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the human immunodeficiency virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa.

Introduction: An important feature of hypertension is a reduction in large artery distensibility, which may be due to structural and functional adaptations. Black populations are particularly prone to the development of hypertension. We therefore compared the carotid characteristics between fiveyear sustained hypertensive and normotensive black South Africans, and investigated how carotid characteristics relate to cardiometabolic risk factors, inflammation, endothelial activation and health behaviours. Methods: We included HIV-free black South Africans who were either consistently hypertensive (n = 351) or normotensive (n = 241) from 2005 to 2010. We assessed carotid characteristics, including intima–media thickness (IMT), distensibility and lumen diameter with B-mode ultrasound, and calculated Young’s elastic modulus, cross-sectional wall area and beta-stiffness index. We measured the carotid dorsalis pedis pulse-wave velocity, brachial and central systolic blood pressure (cSBP) and determined metabolic, inflammatory and endothelial activation markers from blood samples. Health behaviours were reported in questionnaires. Results: The hypertensive group presented with higher brachial and central blood pressure, thicker IMT and stiffer carotid arteries (all p < 0.001). However, after adjustment for cSBP but not mean arterial pressure (MAP), all significant differences in carotid characteristics were lost. The carotid thickness measurements did not differ after adjustment for MAP. After adjustment, metabolic, inflammatory and endothelial activation markers did not differ between the two groups. Conclusion: Our results suggest that besides structural changes, functional adaptations are also involved in deterioration of the carotid wall characteristics of hypertensive black South Africans. These results highlight the importance of proper hypertension control in Africa

Background: Tenofovir disoproxil fumarate (TDF) has been associated with kidney tubular dysfunction and reduced renal function. Limited studies were performed in Europe and Asia that related plasma tenofovir (TFV) concentration with renal function; no such studies to date have been performed on Africans. Objective: To investigate the correlation between plasma tenofovir (TFV) concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART). These markers were also compared to a HIV-uninfected control group. Methods: HIV-infected women (n = 30) on TDF-based ART were matched with 30 controls for age and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR), creatinine clearance (CrCl), serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Stepwise regression, Mann–Whitney test, unpaired and paired t-tests were applied in the statistical analyses. Results: TFV concentration was independently associated with albuminuria (adjusted r2 = 0.339; p = 0.001) in HIV-infected women. In the adjusted (weight) analysis, eGFR (p = 0.038), CrCl (p = 0.032) and albuminuria (p = 0.048) were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR (p < 0.001) and CrCl (p = 0.008) increased from baseline to follow-up in HIV-infected women. Conclusion: Plasma TFV concentration was associated with increased albuminuria in HIVinfected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation

The role the human immunodeficiency virus (HIV) and antiretroviral treatment on endothelial activation, and the subsequent relationship with cardiovascular disease, is not well understood. We investigated endothelial activation, inflammatory and cardiometabolic profiles, and measures of vascular structure and function of 66 antiretroviral treated (ART), 78 never-treated (no-ART) HIV infected and 165 HIV free Africans. Methods Blood samples were obtained for biochemical analysis and blood pressure, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) measurements were performed. Results The HIV infection duration was at least five years and the treatment 2.86 ± 0.13 years. The intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) levels were elevated in the HIV infected groups compared to the controls. The odds of higher adhesion molecule levels were increased when HIV infected (especially in the no-ART group); OR no-ART vs. no-HIV: ICAM 3.92 (2.2–7.0); VCAM 16.2 (7.5–35). ICAM and VCAM associated with HIV status and interleukin-6 (IL-6) in the total group (all p < 0.01). In both HIV infected groups VCAM associated inversely with CD4 counts (no-ART: β = −0.28, p = 0.01; ART: β = −0.22, p = 0.07) and TC (no-ART: β = −0.36, p < 0.01; ART: β = −0.27, p = 0.03). The ART group had an unfavourable lipid profile compared to the no-ART group. The inflammatory markers (C-reactive protein (CRP) and IL-6), PWV and IMT did not differ between the three groups. Conclusion HIV infected Africans showed endothelial activation when compared to HIV free controls. The endothelial activation was not accompanied by increased inflammation (as measured with CRP and IL-6), arterial stiffness or sub-clinical atherosclerosis.

Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker that links inflammation with cardiovascular risk. "However, studies linking suPAR and hypertension are scant. First, we determined whether baseline suPAR is elevated in" "normotensive black South Africans who developed hypertension over 5 years, compared with those who remained normotensive; and second, whether hypertension is associated with suPAR. This substudy is embedded in the South African leg of the Prospective Urban and Rural Epidemiology study, performed in the North West Province. We investigated 429 normotensive individuals, of which 191 developed hypertension and 238 remained normotensive over 5 years. We determined suPAR from plasma (ethylenediaminetetraacetic acid) samples with the suPARnostic ELISA Kit and blood pressure with an OMRON HEM–757 device. Despite similar mean baseline suPAR levels (P=0.43), suPAR increased more in the group that developed hypertension compared with those who remained normotensive (14.2% vs. 6.94%; P=0.007). Five–year percentage change in systolic blood pressure correlated positively (r=0.23; P=0.002) and associated independently with baseline suPAR (?=0.14; P=0.043), only in participants who developed hypertension. Participants were 1.41 times more likely (P=0.015) to develop hypertension with 1 s.d. increase in percentage change in suPAR levels over 5 years. Change in systolic blood pressure was associated with baseline suPAR in hypertensive participants and change in suPAR with hypertensive status. This study highlights the need for more research on the role of suPAR in hypertension and cardiovascular disease development in black South" Africans.

Evidence of the relationship between left ventricular hypertrophy and urinary albumin excretion is contradictory and limited in black adults in whom hypertensive heart disease is common. We aimed to investigate the relationship between subclinical left ventricular hypertrophy and albuminuria in non diabetic hypertensive blacks. Urinary albumin to creatinine ratio (UACR) was determined from 8 hour overnight urine collection. We recorded ambulatory blood pressure and 12 lead electrocardiogram "during a typical working day. Cornell product (P ¼ .002), UACR (P ¼ .042), 24 hour systolic pressure (P < .0001), and 24 hour pulse pressure (P < .0001) were higher in the hypertensive group. Cornell product was associated with UACR in single (r ¼ 0.25; P ¼ .012), partial (P trend ¼ .002), and multiple regression (b ¼ 0.326; P ¼ .0005) analyses in the hypertensive group only, even below the threshold for microalbuminuria and independent of 24 hour systolic pressure. Urinary albumin excretion is associated with subclinical left ventricular hypertrophy in non diabetic hypertensive blacks and may be a useful marker of early cardiovascular disease in blacks. J Am Soc Hypertens 2015;9(2):115 122. 2015 American Society of Hypertension.

Background: Elevated inflammatory markers such as C–reactive protein (CRP) and interleukin–6 (IL–6) are wellknown risk factors for cardiovascular mortality. The less familiar marker, soluble urokinase plasminogen activator receptor (suPAR), is known to predict cancer, infections and all–cause mortality. We determined whether suPAR, CRP and IL–6 are predictive of both all–cause and cardiovascular mortality in a black population, highly burdened by cardiovascular disease and HIV infection." "Methods:We included 1425 black South Africans, of which 208 died within five years after baseline data collection. EDTA plasma biomarker levelswere determined, while all–cause and cardiovascular mortality were used as endpoints." "Results: At baseline suPAR, CRP and IL–6 were higher in non–survivors than in survivors (P b 0.001). SuPAR (HR 1.27, 95% CI 1.09 1.48), IL–6 (HR 1.49, 95% CI 1.24 1.78) and CRP (HR 1.39, 95% CI 1.17 1.65) predicted allcause mortality,while only suPAR (HR 1.40, 95% CI 1.04 1.87) and IL–6 (HR 1.61, 95% CI 1.10 2.35) predicted cardiovascular mortality. The prognostic value of suPAR was independent of IL–6 and CRP (P ? 0.015)." "Conclusion: SuPAR predicted both all–cause and cardiovascular mortality, independent of traditional risk factors, HIV and other inflammatory markers, underlining the prognostic value of suPAR in a black population.

Alarming increases in the incidence of hypertension in many low– and middle–income countries are related to alcohol overuse. It is unclear whether alcohol overuse is a symptom of psychological distress. The authors assessed psychological "distress in Africans and its relationship with a 5–year change in blood pressure (BP), independent of alcohol intake. The authors followed 107 Africans with optimal BP (?120/80 mm Hg) (aged 35 75 years) over 5 years. Alcohol intake (self–report and serum c–glutamyl transferase) and nonspecific psychological distress (Kessler Screening Scale for Psychological Distress [K6]) were assessed. The K6 predicted hypertension development (P=.019), and its individual component nervous increased a participant s risk two–fold to become hypertensive (hazard ratio, 2.00 [1.23 3.26]). By entering K6 and c–glutamyl transferase into multivariable–adjusted regression models for change in systolic BP, both were independently associated with change in systolic BP. Psychological distress and scoring high on being nervous predicted the development of hypertension over 5 years, independent of alcohol intake.

Background. The prevalence of HIV is the highest in sub-Saharan Africa; South Africa (SA) is one of the most affected countries with the highest number of adults living with HIV infection in the world. Besides the traditional risk factors for cardiovascular disease (CVD) in the general population, in people living with HIV there are specific factors – chronic inflammation, metabolic changes associated with the infection, therapy, and lipodystrophy – that potentially increase the risk for developing CVD. Objective. This study proposes a screening discriminant model to identify the most important risk factors for the development of CVD in a cohort of 140 HIV-infected black Africans from the North West Province, SA. Methods. Anthropometric measures, systolic blood pressure, diastolic blood pressure and the carotid-dorsalis pedis pulse wave velocity were determined. Blood was analysed to determine the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, triglycerides (TGs) and glucose. Partial least squares discriminant analysis was performed as a supervised pattern recognition method. Independent Student’s t-tests were further employed to compare the means of risk factors on interval scales; for comparison of categorical risk factors between groups, χ2 tests were used. Results. A TG:HDL-C ratio ≥1.49, TC:HDL-C ratio ≥5.4 and an HDL-C level ≤0.76mmol/l indicated CVD risk in this cohort of patients living with HIV. Conclusion. The results have important health implications for black Africans living with HIV as these lipid levels may be a useful indicator of the risk for CVD

Various studies indicate a relationship between increased oxidative stress and hypertension, resulting in increased DNA damage and consequent excretion of 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG). The aim of this study was to compare urinary 8-oxodG levels in African and Caucasian men and to investigate the association between ambulatory blood pressure (BP) and pulse pressure (PP) with 8-oxodG in these groups. We included 98 African and 92 Caucasian men in the study and determined their ambulatory BP and PP. Biochemical analyses included, urinary 8-oxodG, reactive oxygen species (ROS) (measured as serum peroxides), ferric reducing antioxidant power (FRAP), total glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) activity. The African men had significantly higher systolic (SBP) and diastolic blood pressure (DBP) (both p < 0.001). Assessment of the oxidative stress markers indicated significantly lower 8-oxodG levels (p < 0.001) in the African group. The African men also had significantly higher ROS (p = 0.002) with concomitant lower FRAP (p < 0.001), while their GSH levels (p = 0.013) and GR activity (p < 0.001) were significantly higher. Single and partial regression analyses indicated a negative association between urinary 8-oxodG levels with SBP, DBP and PP only in African men. These associations were confirmed in multiple regression analyses (SBP: R$^2$ = 0.41; β = −0.25; p = 0.002, DBP: R$^2$ = 0.30; β = −0.21; p = 0.022, PP: R$^2$ = 0.30; β = −0.19; p = 0.03). Our results revealed significantly lower urinary 8-oxodG in African men, accompanied by a negative association with BP and PP. We propose that this may indicate a dose-response relationship in which increased oxidative stress may play a central role in the up-regulation of antioxidant defence and DNA repair mechanisms

Objectives Insulin-like growth factor-1 (IGF-1) has potent endothelial-protective, anti-platelet and anti-thrombotic activities, and also exerts mitogenic and proliferatory actions on vascular smooth muscle cells. Conflicting reports exist regarding the role of IGF-1 in vascular protection and atherogenesis. We therefore investigated the relationships of ambulatory blood pressure (BP) and carotid intima-media thickness (cIMT) with a range of components of the IGF-1 axis in a bi-ethnic population. Methods We included black (N = 86) and white (N = 101) men and measured growth hormone, total IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), and pregnancy-associated plasma protein-A (PAPP-A) levels. Results Ambulatory BP was almost 10 mmHg higher in black men (137/88 mmHg versus 128/80 mmHg; both p < 0.001), accompanied by an adverse profile of the IGF-axis for all measured components (all p < 0.01), including reduced bioavailable IGF-1 (IGF-1/IGFBP-3; p = 0.006) and tissue IGF-1 accessibility index as represented by IGF-1.PAPP-A/IGFBP-3 (p < 0.001). Single, partial and multiple regression analyses confirmed an independent inverse association between ambulatory systolic BP and bioavailable IGF-1 in black men (R2 = 0.24; β = −0.22; p = 0.035). cIMT was similar in the ethnic groups (p = 0.34), and was negatively associated with bioavailable IGF-1 in white men (R2 = 0.42; β = −0.17; p = 0.039) prior to adjustment for γ-glutamyl transferase (R2 = 0.45; β = −0.10; p = 0.25). Conclusion Ambulatory systolic BP is inversely related to bioavailable IGF-1 in black men who displayed low IGF-1 concentrations. An inverse relation was found between cIMT and IGF-1 in white men, which disappeared after correction for γ-glutamyl transferase – opposing reports of a detrimental role of IGF-1 in the early stages of atherogenesis.

Background: Soluble urokinase plasminogen activator receptor (suPAR), a novel indicator of low-grade inflammation, is associated with cardiovascular disease and mortality in the general population, while an unhealthy lifestyle influences inflammatory status. We aimed to explore the relationship of suPAR with lifestyle and cardiometabolic risk factors in a black South African population. Design: This cross-sectional study includes 1068 men and women (56.4±10.1 years) from the North West province who took part in the South African leg of the Prospective Urban and Rural Epidemiology (PURE) study in 2010. Captured data included a detailed lifestyle profile (tobacco use, alcohol consumption, physical activity, psychological and dietary intake status), biochemical analyses (suPAR, C-reactive protein (CRP), glucose and lipids), as well as cardiovascular and anthropometric measurements. Results: In exploratory analyses, we observed positive relationships between suPAR and lifestyle factors, such as tobacco use (P-trend <0.001), both alcohol consumption (P-trend=0.001) and γ-glutamyl transferase (GGT) (P-trend <0.001) and unemployment (P-trend=0.002). suPAR and CRP correlated significantly (r=0.23; P<0.001). These relationships were confirmed in multiple regression analyses as suPAR independently associated with tobacco use (β=0.13; P<0.001), GGT (β=0.24; P<0.001) and unemployment (β=0.07; P=0.039). suPAR did not associate with the cardiometabolic factors glucose, lipids, blood pressure or measures of adiposity. Conclusion: suPAR was independently associated with unhealthy lifestyle behaviours, but not with cardiometabolic risk factors suggesting that suPAR, as known predictor of cardiovascular disease and mortality, is augmented by modifiable cardiovascular risk factors. These findings emphasise the need for a healthy lifestyle to decrease the burden of cardiovascular disease in Africans.

Background and aims Simple, low-cost central obesity measures may help identify individuals with increased cardiometabolic disease risk, although it is unclear which measures perform best in African adults. We aimed to: 1) cross-sectionally compare the accuracy of existing waist-to-height ratio (WHtR) and waist circumference (WC) thresholds to identify individuals with hypertension, pre-diabetes, or dyslipidaemia; 2) identify optimal WC and WHtR thresholds to detect CVD risk in this African population; and 3) assess which measure best predicts 5-year CVD risk. Methods and results Black South Africans (577 men, 942 women, aged >30years) were recruited by random household selection from four North West Province communities. Demographic and anthropometric measures were taken. Recommended diagnostic thresholds (WC > 80 cm for women, >94 cm for men; WHtR > 0.5) were evaluated to predict blood pressure, fasting blood glucose, lipids, and glycated haemoglobin measured at baseline and 5 year follow up. Women were significantly more overweight than men at baseline (mean body mass index (BMI) women 27.3 ± 7.4 kg/m2, men 20.9 ± 4.3 kg/m2); median WC women 81.9 cm (interquartile range 61–103), men 74.7 cm (63–87 cm), all P < 0.001). In women, both WC and WHtR significantly predicted all cardiometabolic risk factors after 5 years. In men, even after adjusting WC threshold based on ROC analysis, WHtR better predicted overall 5-year risk. Neither measure predicted hypertension in men. Conclusions The WHtR threshold of >0.5 appears to be more consistently supported and may provide a better predictor of future cardiometabolic risk in sub-Saharan Africa. •Obesity & CVD are increasing rapidly in Africa.•Low cost measures are needed to find those at risk.•Debate continues on the optimum Waist Circumference threshold for African adults.•Waist-to-height ratio predicts current & future CVD risk in South-African adults.•There is greater global agreement on the WHtR threshold (>0.5) for ris

The prevalence of hypertension in sub-Saharan Africa is increasing rapidly, and treatment remains challenging. Although the use of l-carnitine in treatment has received much attention, studies reporting on physiological l-carnitine levels in hypertensives are limited. Our aim was to determine physiological levels of l-carnitine and acylcarnitines in African and Caucasian men, and to investigate associations between ambulatory blood pressure (BP) and carnitine levels. Participants included 101 African and 101 Caucasian teachers. Ambulatory BP measurements were conducted, and l-carnitine and acylcarnitine levels determined. African men showed significantly higher systolic BP (p < 0.001), diastolic BP (p < 0.001) and l-carnitine levels (p = 0.01). In both ethnic groups, partial regression analyses revealed a positive association between BP and l-carnitine, although in Caucasians it was with systolic (r = 0.20, p = 0.045), and in Africans with diastolic BP (r = 0.23, p = 0.023). After adjusting for confounders, an independent positive association between systolic (R 2 = 0.37, β = 0.12, p = 0.041) and diastolic BP (R 2 = 0.39, β = 0.14, p = 0.018) and l-carnitine and long-chain acylcarnitines (R 2 = 0.38, β = 0.17, p = 0.005 and R 2 = 0.39, β = 0.15, p = 0.011) were found, independent of ethnicity. Physiological l-carnitine levels were not only higher in Africans than in Caucasians but also above the expected reference range. Despite promising results on l-carnitine (and its short-chain derivatives) in hypertension treatment regimens, our findings paradoxically show that elevated BP is significantly associated with higher physiological l-carnitine and long-chain acylcarnitine levels.

Background: Dissociation between behavioural defensive active coping (AC) control albeit physiological “loss of control” responses was associated with silent ischaemia and structural wall abnormalities in African men. Whether it applies to structural alterations and endothelial dysfunction is uncertain. We therefore aimed to determine AC ethnic-gender specific receiver operating characteristic (ROC) carotid intima media far wall (CIMTf) cut points best associated with 24-h BP, -silent ischaemia and glycated haemoglobin (HbA1c). Methods: Participants included African and Caucasians (N=317) without pre-existing stroke or atrial fibrillation, aged 45±9 years. The Coping Strategy Indicator was used to measure AC. Ultrasound CIMTf, ambulatory BP, silent ischaemia and fasting blood samples were obtained. Results: Between 69 and 77% of AC African men showed above normal diastolic BP and HbA1c levels compared to 44–48% of AC Caucasian men. In AC African women, 41–60% showed above normal BP, silent ischaemia and HbA1c levels compared to 17–44% of their Caucasian counterparts. ROC curve analyses, detecting optimal CIMTf cut points, ranged between 0.57 and 0.65 mm (BP) and 0.71 and 0.74 mm (silent ischaemia) in AC ethnic-gender groups. Only HbA1C (>5.7%), with a sensitivity/specificity 47%/74%, after controlling for confounders, predicted structural alterations at an optimal cut point of 0.69 mm in AC African men (OR 4.5; 95% CI 2.93–18.73). Conclusion: Novel findings of behavioural resilience were apparent in the AC African female despite a high prevalence of risk markers. In AC males, chronic hyperglycaemia facilitated endothelial dysfunction, i.e. a physiological “loss of control” and susceptibility to stroke risk.

Objectives: Defensive coping (AC) responses in urban African males have been associated with vascular responsiveness, partly explaining autonomic nervous system dysfunction. We therefore aimed to assess whether AC responses facilitate higher blood pressure and early sub-clinical structural vascular disease via alterations in frequency- and time-domain heart rate variability (HRV) responses. Methods:We included 355 African and Caucasian men and women without pre-existing atrial fibrillation, aged 45 9 years. Significant interaction on main effects (coping ethnicity gender) for left carotid intima media thickness far wall (L-CIMTf) and cross sectional wall area values necessitated selection of AC responders above mean via the Coping Strategy Indicator. We collected B-mode ultrasound L-CIMTf, ambulatory BP andeHRV data. Overnight fasting blood was obtained. Results: Overall, Africans and AC Africans, mostly men, revealed a poorer lifestyle profile, higher prevalence of hypertensive status, disturbed sympathovagal balance and depressed HRV temporal and geometric patterns compared to the Caucasians (P 0.05). Moderately depressed non-linear and timedomain HRV (SDNN <100 ms) was prevalent in 28% of Africans compared to 11% of Caucasians. A similar trend was shown for the AC African participants (32%) compared to Caucasians (16%). Only depressed HRV time-domain (SDNN: adj. R2 ¼ 0.34; b ¼ 0.24; p ¼ 0.08) and vagal-impaired heart rate responses (RMSSD: adj. R2 ¼ 0.28; b ¼ 0.28; p < 0.05) were associated with higher blood pressure and early structural vascular changes in AC African men. Conclusion: Defensive coping facilitated autonomic nervous system dysfunction, which was associated with higher blood pressure and sub-clinical structural vascular disease in an African male cohort.

High susceptibility of the African population to develop cardiovascular disease obliges us to investigate possible contributing risk factors. Our aim was to determine whether low 25(OH)D status is associated with increased blood pressure and carotid-radial pulse wave velocity in black South African women. We studied 291 urban women (mean age: 57.5669.00 yrs.). 25(OH)D status was determined by serum 25(OH)D levels. Women were stratified into sufficient (.30 ng/ ml), and insufficient/deficient (,30 ng/ml) groups. Cardiovascular variables were compared between groups. Women with low 25(OH)D levels had significantly higher SBP (150.8627.1 vs. 137.6621.0), DBP (94.7614.5 vs. 89.3612.3) and PP (53.15(50.7;55.7) vs. 46.3(29.4;84.6)) compared to women with sufficient levels. No significant difference was observed with regards to c-rPWV. ANCOVA analyses still revealed significant differences between the two groups with regards to SBP, DBP as well as PP. Partial correlations revealed significant inverse association between SBP and 25(OH)D (p = .04;r =2.12). Women with low 25(OH)D levels were ,2 times more likely to have high SBP (95% CI: 3.23;1.05). To conclude, women with deficient/insufficient 25(OH)D had significantly higher SBP compared to women with a sufficient 25(OH) status

Background: Defensive active coping responses (being-in-control, acceptance of the stressor as reality) have been associated with vascular hyper-responsiveness in urban Africans. However, the association between active coping responses, blood pressure (BP), and ECG-derived left-ventricular hypertrophy (LVH) responses is unknown. Objectives and methods: Associations between BP, silent ischaemia and ECG Cornell product LVH were assessed in 161 African and Caucasian men with active coping responses identified by the Amirkhan Coping Strategy Indicator. BP, ECG and silent ischaemia data were obtained from 24-h ambulatory monitoring. Beat-to-beat BP was continuously recorded during stress testing and fasting resting blood samples obtained for biochemical analyses. Results: Enhanced ß-adrenergic central cardiac responses were evident in active coping Caucasians as opposed to a predomination of α-adrenergic vascular responses in active coping Africans. Active coping African men displayed higher 24-h BP and prevalence of silent ischaemia events compared to the Caucasian men. Regression analyses revealed that α-adrenergic responses were associated with silent ischaemic events, adjusted R2 0.21 [ß 1.07, 95% confidence interval (CI) 0.29–1.85] and that ischaemic events predicted LVH in active coping Africans (adjusted R2 0.12, ß 0.35, 95% CI 0.11–0.59). Receiver-operated characteristic (ROC) analyses indicated a defensive pathway cut point of 16 in Africans as opposed to 32 in Caucasians predicting silent ischaemia with sensitivity/specificity 100/96%. Conclusions: A defensive pathway revealed disturbed vascular function showing dissociation between behavioural and physiological ß-adrenergic active coping responses in Africans. Vascular responsiveness facilitated silent ischaemia events and structural LVH changes which potentially explain the increased risk for incident ischaemic stroke in black Africans.

Aim. Serum γ-glutamyltransferase (GGT) is increasingly regarded as a marker of vascular function. However, the usefulness of this marker is in dispute. Gender and ethnic differences, as well as the serum level range where correlations with vascular function will emerge, may complicate the usefulness of GGT. The aim is to compare correlations with markers of vascular function between African and Caucasian groups. Methods. This cross-sectional target population study involved four groups of African and Caucasian men and women of 100 participants each. Fasting lipids, GGT, C-reactive protein (CRP), reactive oxygen species, and glycosylated hemoglobin (HbA1c) were determined as well as blood pressure, carotid intima-media thickness (CIMT), and left ventricular hypertrophy. Results. γ-Glutamyltransferase levels were significantly higher in Africans compared with Caucasians and also higher in men than in women. γ-Glutamyltransferase correlated with triglycerides in all four groups and after adjusting the correlations sustained in the male groups but disappeared in women. Correlations existed between GGT and blood pressure, except for the African women. After adjustments, CIMT correlated with GGT in Caucasian men (r = 0.29; P < .01). Glycosylated hemoglobin was associated with GGT in Caucasian women (r = 0.26; P = .01) as well as CRP (r = 0.36; P < .01). When the groups were divided into low and high GGT groups by median split, most of the correlations disappeared in the high GGT groups. Conclusions. Gender and ethnic-specific associations occurred regarding GGT and variables associated with cardiovascular function. With high levels of GGT the correlations diminished. The usefulness of GGT as a marker of vascular dysfunction seems limited.

The aetiology for an increasing incidence of hypertensive cardiovascular disease amongst Africans in southern Africa is unclear. Hypertension may be induced by inadequate release of L-arginine-derived nitric oxide impairing vascular tone regulation. In addition, asymmetric dimethylarginine (ADMA) is associated with cardiovascular disease. We compared profiles of L-arginine in African and Caucasian men of similar age with cardiovascular risk factors. We studied 163 Caucasian and 132 African men, respectively, (20 to 70 years) measuring serum L-arginine, ADMA, creatinine, urea, symmetric dimethylarginine (SDMA) and blood pressure. L-arginine levels were significantly lower, whereas blood pressure and pulse wave velocity were significantly higher in African men. Simple linear regression showed ADMA more strongly associated with L-arginine in Caucasians (r=0.59 vs 0.19), whereas association of SDMA with L-arginine was significant only in Caucasians (r=0.43 vs 0.001). The stronger association of L-arginine with ADMA in Caucasian men was confirmed by multiple regression analysis (β=0.46 vs 0.25). Our findings show that the relationship of cardiovascular risk factors with serum L-arginine and some of its catabolites is different in African and Caucasian men and that this may be associated with a relatively higher prevalence of hypertension in African men.

Many mechanisms, including oxidative stress, contribute to hypertension. This study investigated the possible associations between oxidative stress, blood pressure and arterial stiffness in black South Africans. Ambulatory blood pressure measurements were taken for 101 black South African men and 99 women. The stiffness indices included ambulatory arterial stiffness index (AASI) and pulse pressure (PP). Reactive oxygen species (ROS) levels (Po0.0001) were higher in the African women compared with men. ROS levels were also higher in hypertensive compared with normotensive men. The 24h systolic blood pressure (SBP; Po0.01), 24 h diastolic blood pressure (DBP; Po0.0001) and pulse wave velocity (PWV; Po0.01) were significantly higher in African men compared with women. There were unadjusted positive associations of 24 h SBP (r¼0.33; P¼0.001), 24 h DBP (r¼0.26; P¼0.008) and 24 h PP (r¼0.29; P¼0.003) with ROS in African men only. A positive association between AASI and ROS existed only in hypertensive men (r¼0.27; P¼0.035), but became nonsignificant (B¼0.0014; P¼0.14) after adjustments. Adjusted, positive associations of 24h SBP (B¼0.181; P¼0.018) and 24h PP (B¼0.086; P¼0.050) with ROS were again only evident in African men. ROS is positively associated with SBP and PP in African men, suggesting that increased ROS levels may contribute to hypertension in this population group.

Background: Hypertension and increased blood glucose are associated with subclinical kidney damage, atherosclerosis and with low testosterone values. Low testosterone in men is often accompanied by increased levels of estradiol. Objectives and methods: In this study, the association between estradiol, subclinical kidney damage and atherosclerosis in African and white men in a South African cohort was investigated. Cardiovascular variables were studied by means of B-mode ultrasound and ambulatory blood pressure (BP) monitoring. The sex hormones and other biochemical values were measured from fasting venous blood and overnight urine samples. The ethnic groups were stratified into low and high testosterone groups by means of median split. Results: The low testosterone African group demonstrated a higher cardiovascular risk compared with the low testosterone white men with 91% being hypertensive and having increased albumin-to-creatinine ratio (ACR), left carotid intima–media thickness (L-CIMTf) and estradiol-to-testosterone ratio. In the low-testosterone African men, estradiol explained 33% of the variance in ACR, whereas the estradiol-to-testosterone ratio explained 22% of the variance in L-CIMTf, respectively. Estradiol-to-testosterone ratio was positively associated with ACR in the low testosterone whites. Conclusion: We conclude that increased levels of estradiol may play a role in the development of subclinical kidney damage in both African and white men as well as atherosclerosis in low-testosterone African men.

Background Longitudinal cohort studies in sub-Saharan Africa are urgently needed to understand cardiovascular disease development. We, therefore, explored health behaviours and conventional risk factors of African individuals with optimal blood pressure (BP) (4120/80mm Hg), and their 5-year prediction for the development of hypertension. Methods The Prospective Urban Rural Epidemiology study in the North West Province, South Africa, started in 2005 and included African volunteers (n¼1994; aged430 years) from a sample of 6000 randomly selected households in rural and urban areas. Results At baseline, 48% of the participants were hypertensive (5140/ 90 mmHg). Those with optimal BP (n¼478) were followed at a success rate of 70% for 5 years (213 normotensive, 68 hypertensive, 57 deceased). Africans that became hypertensive smoked more than the normotensive individuals (68.2% vs 49.8%), and they also had a greater waist circumference [ratio of geometric means of 0.94cm (95% CI: 0.86–0.99)] and greater amount of g-glutamyltransferase [0.74 U/l (95% CI: 0.62–0.88)] at baseline. The 5-year change in BP was independently explained by baseline g-glutamyltransferase [R2¼0.23, b¼0.13 U/l (95% CI: 0.01–0.19)]. Alcohol intake also predicted central systolic BP and carotid cross-sectional wall area (CSWA) at follow-up. Waist circumference was another predictor of BP changes [b¼0.18 cm (95% CI: 0.05–0.24)] and CSWA. HIV infection was inversely associated with increased BP. Conclusions During the 5 years, 24% of Africans with optimal BP developed hypertension. The surge in hypertension in Africa is largely explained by modifiable risk factors. Public health strategies should focus aggressively on lifestyle to prevent a catastrophic burden on the national health system.

Soluble urokinase plasminogen activator receptor (suPAR) is associated with inflammation and may predict lipodystrophy and dysmetabolism in human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy. We aimed to assess firstly, whether suPAR levels are elevated in treated and untreated HIV-1-infected Africans compared to uninfected controls at baseline and at a 3-year follow-up, and secondly whether suPAR levels are correlated with cardiovascular and/or metabolic changes. SuPAR, cardiovascular, and metabolic variables were assessed and the percentage change was determined. HIV-1-infected black South Africans had significantly higher suPAR levels than uninfected controls at baseline and at follow-up 3 years later. However, only the treated HIV-1-infected participants showed an increase in suPAR levels at follow-up. The treated group also showed signs of lipodystrophy and their baseline suPAR levels correlated positively with an increased waist circumference. This study indicates that suPAR levels increase and that baseline suPAR is associated with an increase in abdominal fat distribution in HIV-infected black Africans on antiretroviral therapy.

Recent evidence suggests that low-grade urinary albumin excretion is a marker of early general attenuation of vascular function, but studies are limited to Caucasian population groups. We compared low-grade urinary albumin excretion (<3.5 mg mmol−1 or 30 μg mg−1) between non-diabetic African (aged, 41.7 years; n=70) and Caucasian (aged, 44.6 years; n=91) men and ethnic-specific associations thereof with arterial stiffness and ambulatory blood pressure. The albumin-to-creatinine ratio (ACR) was determined from an 8 h overnight urine collection. We recorded ambulatory blood pressure over 24 h during a typical workday and the carotid–dorsalis pedis pulse wave velocity measured the next morning after a controlled overnight stay. ACR was higher in Africans compared with Caucasians (P<0.001), also after adjusting for 24 h systolic blood pressure, diastolic blood pressure and hypertension prevalence (P<0.001) or when grouped by similar 24 h mean arterial pressures (P<0.01 for all categories). Daytime (P=0.002) and night time (P< 0.001) systolic and daytime (P<0.001) and night time (P<0.001) diastolic blood pressures were higher in Africans compared with Caucasians, but no differences existed for daytime and night time pulse pressure and pulse wave velocity. In African men only, after adjustment for covariates, night time systolic blood pressure (β=0.347; P=0.003), diastolic blood pressure (β=0.298; P=0.010) and mean arterial pressure (β=0.331; P=0.004) correlated positively with ACR. In addition, daytime (β=0.265; P=0.032) and night time (β=0.258; P=0.038) pulse pressure as well as pulse wave velocity (β=0.271; P=0.032) correlated positively with ACR. In conclusion, arterial stiffness and ambulatory blood pressure are already associated with low-grade albuminuria in non-diabetic African men with normal kidney function.

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.

The prognostic significance of blood pressure (BP) variability has lately enjoyed considerable attention. The need for early markers of cardiovascular dysfunction is imperative in black South Africans who have a significant risk for cardiovascular disease. We therefore compared 24-h BP variability with various traditional and advanced BP measurements, regarding their association with sub-clinical organ damage in black and white South Africans. The study included 409 African and Caucasian teachers aged 25–60 yrs. We measured office BP, 1-min continuous (finger) BP, ambulatory BP, BP reactivity and determined weighted 24-h BP variability. Albumin-to-creatinine ratio, Cornell product and carotid cross-sectional wall area (CSWA) were measures of organ damage. Africans had higher 24-h BP, BP variability, BP reactivity and sub-clinical organ damage (P<0.001). Correlations of BP variability with organ damage were overall weak when compared with other BP measurements. In normotensive groups, we found an independent association of 24-h systolic BP (SBP) variability with Cornell product only in Africans (r=0.37; P=0.01), confirmed in multiple regression models, with 24-h SBP included in the model. Only in hypertensive Caucasians, a significant correlation between CSWA and 24-h SBP variability was evident (r=0.30; P=0.01), although CSWA indicated stronger correlations with office or 24-h SBP than 24-h SBP variability. To conclude, 24-h SBP variability could potentially be an effective measure for the early detection of normotensive Africans at increased risk for the development of cardiovascular complications. Its usefulness based on associations with target organ damage in hypertensive groups seems to be less than traditional office or 24-h BP measurements.

Conventional and behavioral risk factors explain differences in sub-clinical vascular disease between black and Caucasian South Africans: The SABPA study Objectives: There is an emerging burden of cardiovascular disease among urban black Africans in South Africa, which has been largely explained by the transition from traditional African lifestyles to more westernized behavior. We examined the role of health behaviors in explaining the excess burden of sub clinical vascular disease seen in black Africans compared to Caucasians. Methods: This was a cross-sectional study, comprising of urban African teachers (n = 192 black, 206 Caucasian) working for one of the four Kenneth Kaunda Education districts in the North West Province, South Africa. Conventional cardiovascular risk factors, 24 h ambulatory blood pressure and objectively measured physical activity (Actical® accelerometers), smoking (confirmed by serum cotinine), and alcohol (serum gamma glutamyl transferase) were assessed. The main outcome was a marker of sub-clinical vascular disease, mean carotid intima media thickness (mCIMT), measured using high resolution ultrasound. Results: Compared with Caucasians, the black Africans demonstrated higher mCIMT (age and sex adjusted ˇ = 0.044, 95% CI, 0.024–0.064 mm). The blacks also had higher 24 h systolic and diastolic blood pressure, triglycerides, adiposity, and C-reactive protein. In addition, blacks were less physically active (790.0 kcal/dvs 947.3 kcal/d, p < 0.001), more likely to smoke (25% vs 16.3%, p = 0.002), and demonstrated higher alcohol abuse (gamma glutamyl transferase, 66.6_/L vs 27.2_/L, p < 0.001) compared with Caucasians. The difference in mCIMT between blacks and Caucasians was attenuated by 34% when conventional risk factors were added to the model and a further 18% when health behaviors were included. Conclusion: There is an excess burden of sub clinical vascular disease seen in black Africans compared to Caucasians, which can be largely explaine

Background: The Omron HEM-9000AI is the first automated tonometer to provide an estimate of central SBP (cSBP), which is considered to be more predictive of cardiovascular events than brachial pressure. However, considerable differences between the cSBP estimate of Omron and that of SphygmoCor have been reported, but not explained. This study assesses the sources of differences between both cSBP estimates and provides a handle on which estimate is closest to reality. Method: For this purpose, aortic cSBP derived from calibrated carotid SBP was used as device- and algorithm-independent reference. Radial, brachial and carotid applanation tonometry were performed in 143 black South Africans, aged 39–91 years. Each individual was measured with an Omron HEM-9000AI and a SphygmoCor. Results: When using both devices as advocated by their manufacturers, the corresponding cSBP estimates correlated strongly (r = 0.99, P < 0.001), but the Omron estimate was 18.8 (4.3) mmHg higher than the SphygmoCor estimate. Aortic SBP was in between both estimates: 11.7 (5.5) mmHg lower than cSBP-Omron and 7.1 (5.0) mmHg higher than cSBP-SphygmoCor. Alternative calibration of the radial SphygmoCor-curves with radial instead of brachial pressures yielded a cSBP that was 3.0 (4.2) mmHg lower than aortic SBP. The shape of the recorded pressure waves was similar in both devices: less than 5% of the observed cSBP difference was caused by differences in wave shape. Conclusion: The results from this study demonstrate that the considerable difference between the central pressure estimates of Omron HEM-9000AI and SphygmoCor is due to algorithm differences, and suggest that the overestimation by Omron HEM-9000AI is larger than the underestimation by SphygmoCor.

The chronic infection status suffered by HIV-infected individuals promotes chronic arterial inflammation and injury, which leads to dysfunction of the endothelium, atherosclerosis and thrombosis. Although HIV-1 subtype C is prevalent in South Africa and accounts for almost a third of the infections worldwide, this subtype differs genetically from HIV-1 subtype B on which the majority of studies have been done. The objective of this study was to assess whether newly identified, never-treated, HIV-1-infected South African participants showed signs of endothelial dysfunction, accelerated atherosclerosis and increased blood coagulation. We compared 300 newly diagnosed (never antiretroviral-treated) HIV-infected participants to 300 age-, gender-, body mass index- and locality-matched uninfected controls. Levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, interleukin-6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), fibrinogen and plasminogen activator inhibitor-1 (PAI-1), and carotid radialis pulse wave velocity (cr-PWV) were determined. The HIV-infected participants showed lower HDL-C and higher IL-6, CRP, ICAM-1 and VCAM-1 levels compared to the uninfected controls. No differences in fibrinogen and PAI-1 levels were detected. A continuous positive trend of increasing age with cr-PWV was detected in the HIV-infected group. Our findings suggest inflammatory injury of the endothelium, pointing to endothelial dysfunction of never-treated HIV-1-infected South Africans of African ancestry. Although no indication of a prothrombotic state could be detected, there was an indication of accelerated vascular aging and probable early atherosclerosis in the older HIV-infected participants.

Objective Adipokines contribute directly to the coexistence of insulin resistance and endothelial dysfunction. Most studies focus on a single adipokine. We therefore investigated the independent relationships of leptin, adiponectin, tumor necrosis factor-α, resistin and visfatin, as well as the gut hormone ghrelin with blood pressure and insulin resistance. Secondly we evaluated the interrelationships of adipokines and ghrelin in concert with various cardiometabolic markers. Methods and Results Caucasian women (N = 115) with varying levels of obesity (aged 31.3 ± 9.18 years) were included. Significant correlations of leptin, adiponectin, ghrelin and visfatin with mean arterial pressure (p < 0.05) disappeared after adjustment for age, body mass index and waist circumference. But significant correlations with insulin resistance (HOMA) (for leptin, adiponectin and ghrelin) remained significant after adjustments. Factor analyses yielded five factors, but two main clusters, namely a metabolic syndrome cluster (including leptin, adiponectin and ghrelin) and a vascular atherosclerotic cluster (including tumor necrosis factor-α, visfatin and resistin). Conclusion Factor analyses identified patterns which indicate specific roles of the various adipokines. Leptin, adiponectin and ghrelin were more closely related to insulin resistance and central obesity as core components of the metabolic syndrome. Visfatin, tumor necrosis factor-α and resistin seem to direct their effects onto the vascular system possibly by means of mechanisms such as inflammation, vasoconstriction and coagulation

Objectives: Low serum IGF-I is an independent risk factor for diabetes and cardiovascular disease. These noncommunicable diseases are extremely common in urban black South Africans, but their IGF-I concentration is unknown. We aimed to compare serum IGF-I concentrations of African and Caucasian people, investigate their age-related IGF-I decline, and determine whether IGF-I could account, at least in part, for the high prevalence of noncommunicable diseases in black Africans. Research Design and Methods: This cross-sectional study involved 211 African and 316 Caucasian men and women (aged 20–70 yr). Fasting glucose, insulin, lipids, albumin, creatinine, liver enzymes, cotinine, high-sensitivity C-reactive protein, reactive oxygen species, IGF-I, blood pressure (BP), and pulse wave velocity were determined. Results: IGF-I was lower in Africans (P < 0.001) and in both ethnicities declined significantly by age quartiles (P < 0.001). In African men and women, IGF-I declined significantly from age quartile 1 to 2 (r = −0.65, P < 0.001), not seen in young Caucasian men and women (r = −0.08, P = 0.45; r = −0.10, P = 0.34). This was confirmed after adjustment for BP, insulin resistance, high-sensitivity C-reactive protein, cotinine, γ-glutamyl transferase, and reactive oxygen species. Only young Africans showed significant negative correlations of IGF-I with BP, pulse wave velocity, and high-density lipoprotein cholesterol. Conclusions: Africans presented lower IGF-I levels than Caucasians due to an accelerated decline in serum IGF-I concentration prior to 40 yr of age. Strong associations of low serum IGF-I with blood pressure and arterial stiffness in young Africans suggest that the loss of cardiometabolic protection by IGF-I could predispose them to earlier disease onset

Objective Alarming increases in hypertension and type 2 diabetes among Africans accentuate the need to identify factors that could serve as targets for prevention or treatment. In Caucasian populations, asymmetric dimethylarginine (ADMA), the predominant endogenous nitric oxide synthase inhibitor, is associated with cardiovascular disease and insulin resistance (IR). ADMA's counterpart, symmetric dimethylarginine (SDMA), originally thought to be inert, was recently also linked with cardiovascular risk. Since little information regarding ADMA or SDMA is available for Africans, our aim was to explore the relationships of ADMA and SDMA with measures of arterial stiffness and IR in Africans and Caucasians from South Africa. Methods The study consisted of 235 nonsmoking, nondiabetic, nonobese, human immunodeficiency virus-uninfected Africans (n=64) and Caucasians (n=171), aged 20–70 years. We measured blood pressure, pulse wave velocity, ADMA, SDMA, and IR (homeostasis model assessment, HOMA). Results African and Caucasian men had similar ADMA and SDMA, whereas Caucasian women had higher ADMA and SDMA than African women (P<0.05). African men and Caucasian women indicated strong correlations of ADMA with arterial stiffness (r=0.47, P=0.021; r=0.26, P=0.008), confirmed in multivariate analyses. Caucasian participants showed negative associations between SDMA and HOMA, being strongest in the men (r=−0.41; P=0.002). Conclusion Our results indicate that ADMA is independently associated with vascular dysfunction in African men and Caucasian women. A strong, independent negative association of SDMA with IR was found only in Caucasian participants. The molecular explanation for this is unclear, but these findings motivate experimental studies that could shed more light on these relationships

Sub-Saharan Africans face an increasing burden of hypertension. Although controversial, recent experimental evidence strongly suggests that serum calcium contributes to elevated blood pressure through increased vascular resistance. We investigated the associations of 24-h blood pressure and cardiovascular reactivity with serum calcium in African men stratified by age. The study consisted of 50 younger (median age: 38 years) and 49 older (median age: 49 years) participants. We measured 24-h ambulatory blood pressure with a mean successful inflation rate of 72.6%. Total peripheral resistance and stroke volume reactivity were obtained using a Finometer device during application of the Stroop color and word conflict test. Total serum calcium was adjusted for serum albumin. Results showed that serum calcium levels were similar between the younger and older groups. However, in the younger group, 24-h systolic blood pressure, 24-h diastolic blood pressure and total peripheral resistance reactivity correlated positively, whereas stroke volume reactivity correlated negatively with serum calcium in single and multiple regression analyses (systolic blood pressure: B=34.99, P=0.017; diastolic blood pressure: B=34.93, P<0.001; total peripheral resistance reactivity: B=65.44, P=0.048; stroke volume reactivity: B=−45.40, P=0.017). No associations were evident in the older African men. In conclusion, 24-h ambulatory systolic and diastolic blood pressures are positively associated with serum calcium in African men younger than 43 years. The blood pressure–serum calcium relationship seems to be mediated through increased vascular resistance during stress

Background: Sub-Saharan Africans face an increasing burden of hypertension and related cardiac and cerebrovascular morbidity and mortality, making the identification of factors leading to early vascular abnormalities imperative. Methods: We investigated the possible influence of the antioxidant glutathione (GSH) on early subclinical atherosclerosis in 63 hypertensive (aged 45.2 years) and 34 normotensive (aged 38.9 years; P < 0.001) nondiabetic African men. We measured ambulatory daytime systolic and diastolic blood pressure (SBP, DBP) as well as daytime mean arterial pressure (MAP), carotid intima-media thickness (CIMT), and calculated the cross-sectional wall area.We determined the reduced form of GSH in whole blood and blood glucose in serum. Results: Blood glucose (110 vs. 92 mg/dl; P < 0.001) and CIMT (0.75 vs. 0.61 mm; P < 0.001) were higher in hypertensives compared to normotensives. No significant difference existed for GSH. Associations in normotensives suggested the hypotensive effect of GSH after single (SBP: r = ―0.35,P ≤ 0.05; DBP: r=-0.37, P ≤ 0.05; MAP: r=-0.38, P ≤ 0.05) and multiple (SBP: B = ―0.015, P < 0.05; DBP: B = ―0.011, P < 0.05; MAP: B = ―0.012, P < 0.05) regression analyses. In hypertensives, CIMT (B = ―0.00027, P < 0.01) and cross-sectional wall area (CSWA) (B = ―0.0066, P < 0.05) correlated negatively with GSH.These findings were consistent after excluding 10 human immunodeficiency virus (HIV)-positive hypertensive subjects. Conclusions: In hypertensive African men, CIMT is negatively associated with GSH, suggesting a possible contributory role of attenuated GSH levels in the development of subclinical atherosclerosis.

The literature shows an increase in endothelin-1 with increased levels of erythrocytes. There are also indications that inflammation and elevated endothelin-1 levels interact with erythropoiesis. In this study, the association of erythrocytes and endothelin-1 in women of different ethnicities was investigated. Blood pressure, vascular resistance, and C-reactive protein (P = 0.09) were significantly higher in the African women (n = 102) compared to the Caucasian women (n = 115), while arterial compliance was significantly lower in the African women with no significant differences for endothelin-1. In single, partial, and multiple regression analyses, there was a significant positive correlation between the red blood cell count and log endothelin-1 in the Caucasians while in the Africans there was a weak negative correlation. This is an indication that endothelin-1 might interfere with erythrocyte production in Africans with higher levels of inflammation.

BACKGROUND: The increasing prevalence of hypertension and vascular-related morbidity and mortality among Africans emphasizes the need to identify markers for the early detection of vascular disease. Caucasian-based studies demonstrate that the von Willebrand factor (vWf) is a useful marker of vascular dysfunction. We investigated whether associations between this marker and markers of cardiovascular function in Caucasian women are comparable with African women. METHODS: The study consisted of apparently healthy African (n = 99) and Caucasian (n = 114) women (mean age, 31.0 years), individually matched for age and body mass index. We measured blood pressure and arterial compliance noninvasively, and vWf in serum. We assessed univariate and multivariate-adjusted associations of blood pressure and arterial compliance with vWf. RESULTS: Although no ethnic difference existed for mean vWf levels, Caucasian and African women showed opposite associations of blood pressure and arterial compliance with vWf after single, partial, and multiple regression analyses. In Caucasians, after full adjustment, systolic (beta = +0.179; P < 0.05) and diastolic (beta = +0.190; P < 0.05) blood pressure correlated positively and arterial compliance negatively (beta = -0.197; P < 0.01) with vWf. Conversely, in Africans, systolic blood pressure correlated weakly, but negatively (beta = -0.168; P = 0.059) with vWf. However, this opposite tendency seemed due to the confounding influence of the depot medroxyprogesterone acetate (DMPA) contraceptive injection and, although >99% power existed, significance disappeared after excluding these subjects (beta = -0.071; P = 0.46). CONCLUSIONS: Associations of vWf with blood pressure and arterial compliance were not comparable between Caucasian and African women, suggesting that the vWf may not be a useful marker of vascular alterations in African women.

Background: The prevalence of hypertension among Black adults in South Africa is high. Because cardiovascular reactivity can be used to predict hypertension in later life, we attempted to determine whether cardiac and vascular responses to a task in Black South African children influence their cardiovascular parameters. Design: This study was embedded in the Transition and Health during Urbanization in South Africa in Children study, which studied the health status of children. During the study, cardiovascular reactivity was determined with a hand dynamometer in 670 Black African children. Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, and Windkessel compliance of the arterial system were obtained by means of the Finapres (finger arterial pressure) apparatus and the Fast Modelflow software program. Anthropometric measurements were performed according to standard methods. Cardiac and vascular responders were classified with a regression-based approach. Results: Cardiac responders had higher stroke volume; a trend to higher cardiac output; lower diastolic blood pressure; and a tendency toward lower systolic blood pressure, heart rate, and total peripheral resistance. Vascular responders showed no significant changes in cardiovascular parameters when responders and nonresponders were compared. Conclusions: Cardiac responders had higher stroke volume and a trend toward higher cardiac output, which may be an early indication of hypertension