Aletta E. Schutte

Are behavioural risk factors to be blamed for the conversion from optimal blood pressure to hypertensive status in Black South Africans? A 5-year prospective study

BACKGROUNDnLongitudinal 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) (≤ 120/80 mm Hg), and their 5-year prediction for the development of hypertension.nnnMETHODSnThe Prospective Urban Rural Epidemiology study in the North West Province, South Africa, started in 2005 and included African volunteers (n = 1994; aged > 30 years) from a sample of 6000 randomly selected households in rural and urban areas.nnnRESULTSnAt baseline, 48% of the participants were hypertensive (≥ 140/90 mmHg). Those with optimal BP (n = 478) 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 0.94 cm (95% CI: 0.86-0.99)] and greater amount of γ-glutamyltransferase [0.74 U/l (95% CI: 0.62-0.88)] at baseline. The 5-year change in BP was independently explained by baseline γ-glutamyltransferase [R(2) = 0.23, β = 0.13 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 [β = 0.18 cm (95% CI: 0.05-0.24)] and CSWA. HIV infection was inversely associated with increased BP.nnnCONCLUSIONSnDuring 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.

Lipid abnormalities in a never-treated HIV-1 subtype C-infected African population.

Dyslipidemia has been documented worldwide among human immunodeficiency virus-infected (HIV) individuals and these changes are reminiscent of the metabolic syndrome (MetS). In South Africa, with the highest number of HIV infections worldwide, HIV-1 subtype C is prevalent, while HIV-1 subtype B (genetically different from C) prevails in Europe and the United States. We aimed to evaluate if HIV infection (subtype C) is associated with dyslipidemia, inflammation and the occurrence of the MetS in Africans. Three hundred newly diagnosed HIV-infected participants were compared to 300 age, gender, body mass index and locality matched uninfected controls. MetS was defined according to the Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) criteria. The HIV-infected group showed lower high density lipoprotein cholesterol (1.23 vs. 1.70xa0mmol/L) and low density lipoprotein cholesterol (2.60 vs. 2.80xa0mmol/L) and higher triglycerides (1.29 vs. 1.15xa0mmol/L), C-reactive protein (3.31 vs. 2.13xa0mg/L) and interleukin 6 (4.70 vs. 3.72xa0pg/L) levels compared to the uninfected group. No difference in the prevalence of the MetS was seen between the two groups (ATP III, 15.2 vs. 11.5%; IDF, 21.1 vs. 22.6%). This study shows that HIV-1 subtype C is associated with dyslipidemia, but not with a higher incidence of MetS in never antiretroviral-treated HIV-infected Africans.

Evaluation of waist-to-height ratio to predict 5 year cardiometabolic risk in sub-Saharan African adults

BACKGROUND AND AIMSnSimple, 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.nnnMETHODS AND RESULTSnBlack 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/m(2), men 20.9 ± 4.3 kg/m(2)); 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.nnnCONCLUSIONSnThe 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.

Self-reported alcohol intake is a better estimate of 5-year change in blood pressure than biochemical markers in low resource settings: the PURE study

Background: Despite criticism of self-reported alcohol intake, it is a valuable tool to screen for alcohol abuse as a risk factor for cardiovascular disease. We aimed to compare various self-reported estimates of alcohol use with &ggr;-glutamyltransferase (GGT) and percentage carbohydrate deficient transferrin (%CDT) considering their relationship with blood pressure changes (%BP) over a 5-year period in black South Africans. Method: We recruited 1994 participants and collected 5-year followed up data (Nu200a=u200a1246). Participants completed questionnaires on alcohol intake indicating their former and current alcohol use (‘yes’ response and ‘no’ if alcohol was never used). We assessed alcohol intake (in g) using a quantified food frequency questionnaire. We collected blood samples and measured GGT and %CDT. Brachial BP (bBP) was measured at baseline and follow-up and central BP (cBP) at follow-up only. Results: Self-reported alcohol intake was significantly associated with the 5-year change in bBP before and after adjusting for confounders (%bSBP: R2u200a=u200a0.263, &bgr;u200a=u200a0.06, Pu200a=u200a0.023; %bDBP: R2u200a=u200a0.326, &bgr;u200a=u200a0.08 Pu200a=u200a0.005), as well as cSBP (R2u200a=u200a0.286, &bgr;u200a=u200a0.09, Pu200a=u200a0.010) and central pulse pressure (R2u200a=u200a0.254, &bgr;u200a=u200a0.06, Pu200a=u200a0.020). GGT and %CDT correlated well with self-reported alcohol intake (ru200a=u200a0.44; Pu200a=u200a0.001; ru200a=u200a0.34 Pu200a=u200a0.001), but did not associate significantly with %bBP or cBP at follow-up. Conclusion: Self-reported alcohol use was strongly associated with a 5-year increase in BP in Africans with a low socio-economic status. This was not found for biochemical measures, GGT and %CDT. Self-reported alcohol intake could be an important measure to implement in primary healthcare settings in middle to low income countries, where honest reporting is expected.

Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?

Abstract 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.

Ethnic differences regarding arterial stiffness of 6-8-year-old black and white boys.

Objectives: Vascular deterioration is suggested to occur earlier in black than white populations, thereby increasing their risk for developing hypertension. To establish whether this is the case, we compared different estimates of arterial stiffness in black and white children and investigated the links with body composition and advanced glycation end products (AGEs) as potential contributors. Methods: We included 40 black and 41 white boys (aged 6‐8 years) from similar schools and measured arterial stiffness [pulse wave velocity (PWV) in different arterial sections, systemic arterial compliance and carotid stiffness estimates], anthropometry as well as urinary pentosidine as a marker of AGEs. Results: Black boys displayed increased PWV [carotid-to-radial (Pu200a=u200a0.002), carotid-to-femoral (Pu200a<u200a0.0001) and carotid-to-dorsalis pedis (Pu200a=u200a0.008)], DBP (Pu200a=u200a0.001) and carotid intima–media thickness (Pu200a=u200a0.007) than white boys. Despite higher pentosidine in black boys (Pu200a=u200a0.039), arterial stiffness indices did not correlate with pentosidine in any group. However, only in black boys, pentosidine correlated negatively with BMI (Pu200a=u200a0.015), BSA (Pu200a=u200a0.017), weight (Pu200a=u200a0.018), waist (Pu200a=u200a0.022) and hip circumference (Pu200a=u200a0.010). Arterial stiffness indices related inversely to body composition in white boys, but femoral PWV correlated inversely with BMI (ru200a=u200a−0.32; Pu200a=u200a0.049) in black boys. Conclusion: Already at very young ages (6‐8 years), with a high proportion of prehypertension, black boys in our study have increased arterial stiffness in all sections of the arterial tree, along with higher DBP, carotid intima–media thickness and AGEs. This phenotype underlines the increasing trend of early-onset vascular aging among black populations.

Soluble urokinase plasminogen activator receptor (suPAR) is associated with metabolic changes in HIV-1 infected Africans: a prospective study

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 3xa0years 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.

Cardiometabolic changes in treated versus never treated HIV-infected black South Africans: the PURE study.

BACKGROUNDnThe use of antiretroviral treatment is known to be accompanied by several negative health outcomes and may negatively affect a country such as South Africa, which is the most burdened by the human immunodeficiency virus (HIV) in the world. We aimed to determine whether receiving antiretroviral treatment changes the cardiometabolic profile of HIV-infected South Africans.nnnMETHODSnIn this sub-study, embedded in the Prospective Urban and Rural Epidemiology (PURE) study, we compared the cardiometabolic profile in a cohort of 66 treated and 71 never treated HIV-infected participants from the North-West province, South Africa. By using standard techniques, these participants cardiometabolic, biochemical and lifestyle variables were assessed in 2005 and 2010, respectively.nnnRESULTSnThe treated group showed a higher percentage change in pulse pressure (13.3%; p = 0.004), systolic blood pressure (4.5%; p = 0.029) and CD4 cell count (9.2%; p = 0.009) levels over five years. During follow-up (2010), lipid variables were worse in the treated group. Further, antiretroviral treatment was associated with the percentage change in pulse pressure (R(2) = 0.24; β = 0.19; p = 0.020).nnnCONCLUSIONSnWe concluded that Africans receiving antiretroviral treatment had a greater increase in pulse pressure and systolic blood pressure, as well as an unfavourable lipid profile when compared to never treated participants. Whether, in the long term, antiretroviral treatment will lead to increased arterial stiffness and/or accelerated atherosclerosis among this HIV-infected African population remains to be seen.

Cardiometabolic markers to identify cardiovascular disease risk in HIV-infected black South Africans

BACKGROUNDnThe 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.nnnOBJECTIVEnThis 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.nnnMETHODSnAnthropometric 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 Students t-tests were further employed to compare the means of risk factors on interval scales; for comparison of categorical risk factors between groups, chi2 tests were used.nnnRESULTSnA TG:HDL-C ratio > or = 1.49, TC:HDL-C ratio > or = 5.4 and an HDL-C level < or = 0.76 mmol/l indicated CVD risk in this cohort of patients living with HIV.nnnCONCLUSIONnThe 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.

Urinary albumin excretion from spot urine samples predict all-cause and stroke mortality in Africans.

BACKGROUNDnIncreased urinary albumin excretion reflects general vascular damage and predicts adverse cardiovascular and renal outcomes. Albuminuria can be determined from easily collected spot urine samples, especially in low-resource settings. However, no prognostic evidence exists for Africans.nnnMETHODSnWe followed clinical outcomes in 1,061 randomly selected non diabetic, human immunodeficiency virus (HIV)-negative Africans (mean age: 51.5 years; 62.0% women). Baseline urinary albumin-to-creatinine ratio was assessed from spot urine samples.nnnRESULTSnOver a median follow-up of 4.52 years, 132 deaths occurred, of which 47 were cardiovascular related. The urinary albumin-to-creatinine ratio averaged 6.1 μg/mg (5th to 95th percentile interval; 1.2-70.0). In multivariable-adjusted analyses, urinary albumin excretion predicted all-cause mortality (hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.07-1.48; P = 0.006), and a tendency existed for cardiovascular mortality (HR, 1.26; 95% CI, 0.97-1.63; P = 0.087), which seemed to be driven by fatal stroke (HR, 1.72; 95% CI, 1.17-2.54; P = 0.006) rather than cardiac mortality (HR, 0.67; 95% CI, 0.41-1.07; P = 0.094). The predictive value remained in 528 hypertensives for both all-cause (HR, 1.38; 95% CI, 1.13-1.69; P = 0.001) and cardiovascular (HR, 1.45; 95% CI, 1.07-1.96; P = 0.017) mortality, again driven by stroke. Our findings also remained significant after we excluded participants with macroalbuminuria, those on antihypertensive treatment, as well as participants who died within 1 year after enrollment.nnnCONCLUSIONnIn nondiabetic HIV-negative Africans, albuminuria predicts all-cause and stroke mortality.