Estimating the changing burden of disease attributable to high systolic blood pressure in South Africa for 2000, 2006 and 2012.

BACKGROUND: Ongoing quantification of trends in high blood pressure and the consequent disease impact are crucial for monitoring and decision-making. This is particularly relevant in South Africa (SA) where hypertension is well-established. OBJECTIVE: To quantify the burden of disease related to high systolic blood pressure (SBP) in SA for 2000, 2006 and 2012, and describe age, sex and population group differences. METHODS: Using a comparative risk assessment methodology, the disease burden attributable to raised SBP was estimated according to age, se, and population group for adults aged ≥25 years in SA in the years 2000, 2006 and 2012. We conducted a meta-regression on data from nine national surveys (N=124 350) to estimate the mean and standard deviation of SBP for the selected years (1998 - 2017). Population attributable fractions were calculated from the estimated SBP distribution and relative risk, corrected for regression dilution bias for selected health outcomes associated with a raised SBP, above a theoretical minimum of 110 - 115 mmHg. The attributable burden was calculated based on the estimated total number of deaths and disability-adjusted life years (DALYs). RESULTS: Mean SBP (mmHg) between 2000 and 2012 showed a slight increase for adults aged ≥25 years (127.3 - 128.3 for men; 124.5 - 125.2 for women), with a more noticeable increase in the prevalence of hypertension (31% - 39% in men; 34% - 40% in women). In both men and women, age-standardised rates (ASRs) for deaths and DALYs associated with raised SBP increased between 2000 and 2006 and then decreased in 2012. In 2000 and 2012, for men, the death ASR (339/100 000 v. 334/100 000) and DALYs (5 542/100 000 v. 5 423/100 000) were similar, whereas for women the death ASR decreased (318/100 000 v. 277/100 000) as did age-standardised DALYs (5 405/100 000 v. 4 778/100 000). In 2012, high SBP caused an estimated 62 314 deaths (95% uncertainty interval 62 519 - 63 608), accounting for 12.4% of all deaths. Stroke (haemorrhagic and ischaemic), hypertensive heart disease and ischaemic heart disease accounted for >80% of the disease burden attributable to raised SBP over the period. CONCLUSION: From 2000 to 2012, a stable mean SBP was found despite an increase in hypertension prevalence, ascribed to an improvement in the treatment of hypertension. Nevertheless, the high mortality burden attributable to high SBP underscores the need for improved care for hypertension and cardiovascular diseases, particularly stroke, to prevent morbidity and mortality.

Estimating the changing burden of disease attributable to high sodium intake in South Africa for 2000, 2006 and 2012.

BACKGROUND: Elevated sodium consumption is associated with increased blood pressure, a major risk factor for cardiovascular and chronic kidney disease. OBJECTIVES: To quantify the deaths and disability-adjusted life years (DALYs) attributed to high sodium intake in persons aged ≥25 years in South Africa (SA) for 2000, 2006 and 2012. METHODS: Comparative risk assessment (CRA) methodology was used and population attributable fractions (PAFs) of high sodium intake, mediated through high blood pressure (BP), for cardiovascular and chronic kidney disease were estimated. This was done by taking the difference between the PAF for elevated systolic BP (SBP) based on the estimated SBP level in the population and the PAF based on the estimated SBP that would result if sodium intake levels were reduced to the theoretical minimum risk exposure level (1 g/day) according to population group and hypertension categories. A meta-regression based on data from nine national surveys conducted between 1998 and 2017 was used to estimate the prevalence of hypertension by age, sex and population group. Relative risks identified from international literature were used and the difference in PAFs was applied to local burden estimates from the second South African National Burden of Disease Study. Age-standardised rates were calculated using World Health Organization (WHO) standard population weights. The attributable burden was also estimated for 2012 using an alternative target of 2 g/day proposed in the National Strategic Plan for the Prevention and Control of Non-communicable Diseases (NSP). RESULTS: High sodium intake as mediated through high SBP was estimated to cause 8 071 (95% uncertainty interval (UI) 6 542 - 15 474) deaths in 2012, a drop from 9 574 (95% UI 8 158 - 16 526) in 2006 and 8 431 (95% UI 6 972 - 14 511) in 2000. In 2012, ischaemic heart disease caused the highest number of deaths in persons (n=1 832), followed by haemorrhagic stroke (n=1 771), ischaemic stroke (n=1 484) and then hypertensive heart disease (n=1 230). Ischaemic heart disease was the highest contributor to deaths for males (27%), whereas for females it was haemorrhagic stroke (23%). In 2012, 1.5% (95% UI 1.3 - 2.9) of total deaths and 0.7% (95% UI 0.6 - 1.2) of total DALYs were attributed to high sodium intake. If the NSP target of <2 g/day sodium intake had been achieved in 2012, ~2 943 deaths and 48 870 DALYs would have been averted. CONCLUSION: Despite a slight decreasing trend since 2006, high sodium intake mediated through raised BP accounted for a sizeable burden of disease in 2012. Realising SA's target to reduce sodium intake remains a priority, and progress requires systematic monitoring and evaluation.

Arterial structure and function in Africans with HIV for > 5 years: longitudinal relationship with endothelial activation and cardiovascular risk markers.

OBJECTIVES: We aimed to determine whether people with human immunodeficiency virus (PWHIV) have increased measures of arterial injury [carotid intima-media thickness (cIMT)] and large artery stiffness [carotid-femoral pulse wave velocity (cfPWV)] when compared with their counterparts without HIV, and whether baseline markers of endothelial activation and cardiovascular risk are associated with cIMT and cfPWV after 5 years. METHODS: We matched 126 PWHIV from North West Province, South Africa, to 126 without HIV according to age, sex and locality. Cardiovascular risk and endothelial function markers [soluble intracellular adhesion molecule (ICAM-1) and soluble vascular cell adhesion molecule (VCAM-1)] were measured at baseline and cIMT and cfPWV at follow-up. RESULTS: This study included 21.4% men. The use of antiretroviral therapy (ART) increased from 44.1% at baseline to 81.4% at follow-up. At follow-up, cIMT (P = 0.90) and cfPWV (P = 0.35) were similar in the groups. Despite elevated ICAM-1 and VCAM-1 in the PWHIV (all P < 0.001) at baseline, these markers did not associate with cIMT and cfPWV after 5 years. In multivariable-adjusted regression analysis, cIMT associated positively with age (ß = 0.31, P = 0.002) and triglyceride: high-density lipoprotein-cholesterol (ß = 0.23, P = 0.016) in PWHIV. Mean arterial pressure (MAP) (ß = 0.28, P = 0.010) associated positively with cfPWV in the PWHIV. In the people without HIV, sex (ß = 0.31, P = 0.004) and glycated haemoglobin (HbA1c) (ß = 0.24, P = 0.026) associated with cIMT while age (ß = 0.17, P = 0.049), sex (ß = 0.29, P = 0.003), MAP (ß = 0.31, P = 0.001) and HbA1c (ß = 0.21, P = 0.041) associated positively with cfPWV. CONCLUSIONS: Measures of arterial structure and function were similar in Africans with HIV and their age, sex and locality matched controls. Traditional cardiovascular risk markers rather than elevated endothelial activation at baseline were independently associated with cIMT and cfPWV over 5 years.

[Features of antihypertensive therapy and real-world prescription of selective imidazoline receptor agonists in Russia vs other countries: STRAIGHT study data analysis].

Analysis of routine clinical practice of hypertensive patient management represents one of the important tools in the search for further ways to minimize hypertension-associated cardiovascular and renal adverse outcomes. AIM: To compare the strategies for hypertension management and features of clinical use of I1-imidazoline receptor (I1-IR) agonists in the Russian Federation and other countries where the STRAIGHT (Selective imidazoline receptor agonists Treatment Recommendation and Action In Global management of HyperTension) study was conducted. MATERIALS AND METHODS: It was a cross-sectional online study involving physicians of various specializations. The study was conducted from January 18 to July 1, 2019, in seven countries with a high rate of I1-IR agonist prescription, including Russia. RESULTS: A total of 125 (4.5%) responders filled out the survey in the Russian Federation, which was somewhat lower than in other countries (6.8%). The participants were mostly general practitioners (54.0%) and cardiologists (42.0%), while in other countries greater diversity was seen. Most Russian physicians (83.0%) seemed to rely on national clinical guidelines in their routine practice, while in other countries the US guidelines were more popular (66.0%). The majority of responders stated that they took into account the traditional risk factors of hypertension when initiating the therapy; every second responder noted if sleep apnea was present. Awareness of I1-IR agonists, their prescription rate and their preference were higher in Russia. The main reported benefits of I1-IR agonists were their efficacy, including in resistant hypertension, and their metabolic effects (in Russia). Most participants preferred I1-IR agonists as third-line therapy (65.0% in Russia vs 60.0% in other countries) and in combination with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blockers (ARB) (55.0% in Russia vs 54.0% in other countries). Compared to responders from other countries, Russian physicians prescribe I1-IR agonists as first-line (15.0% vs 5.0%) and second-line (48.0% vs 21.0%) therapy more often. CONCLUSION: Russian physicians were the most aware of I1-IR agonists and tended to prescribe drugs of this class for hypertension management more often, and I1-IR agonist combination with ACEi was preferable compared to physician responders from other countries. Antihypertensive efficacy and metabolic effects were reported as the major benefits of I1-IR agonist therapy.

Selenium and large artery structure and function: a 10-year prospective study.

PURPOSE: Despite selenium's beneficial effects in counteracting oxidative stress, inflammation, and vascular endothelial dysfunction, controversial results exist regarding the long-term associations between selenium and atherosclerosis, arterial stiffness, and hypertension. We investigated in normal and selenium-deficient groups (and the total group), whether serum selenium relates to measures of large artery structure and function over 10 years. METHODS: This longitudinal study included black adults from rural and urban areas in South Africa. Serum selenium and blood pressure were measured at baseline (N = 987). At follow-up, carotid intima media thickness (IMT), cross-sectional wall area (CSWA), carotid-femoral pulse wave velocity (c-fPWV), and blood pressure were measured (N = 718). Selenium deficiency was classified as serum levels < 8 µg/100 ml. RESULTS: In multivariable-adjusted regression analyses performed in the normal selenium group, c-fPWV after 10 years was negatively associated with baseline selenium (ß = - 0.09; p = 0.016). In the normal selenium group, baseline (but not 10 years) blood pressure also associated negatively with baseline selenium (ß = - 0.09; p = 0.007). Both IMT (ß = 0.12; p = 0.001) and CSWA (ß = 0.10; p = 0.003) after 10 years associated positively with baseline selenium in the total, normal, and selenium-deficient groups. CONCLUSION: We found a long-term vascular protective association of selenium on arterial stiffness and blood pressure in Africans with normal selenium levels, supporting the notion that selenium fulfills a vascular protective role. In contrast, we found a potential detrimental association between selenium and carotid wall thickness, particularly evident in individuals within the highest quartile of serum selenium.

Serum selenium levels, the selenoprotein glutathione peroxidase and vascular protection: The SABPA study.

Selenium is an important co-factor for the optimal functioning of the antioxidant enzyme, glutathione peroxidase (GPx). Studies investigating the associations of selenium with blood pressure (BP) and hemodynamic measures are sparse. This study investigated whether 24h blood pressure, vascular resistance, arterial compliance and arterial stiffness relate to both serum selenium and GPx activity. In this cross-sectional study selenium levels, GPx activity, ambulatory blood pressure and arterial stiffness of 200 black and 209 white school teachers from South Africa were measured. Serum selenium levels were significantly lower in black compared to white teachers (p<0.001), independent of sex. One in 10 black men and one in five black women were selenium deficient (<8µg/100ml). Only in white men inverse independent associations of 24h systolic BP (ß=-0.19; p=0.039) and 24h diastolic BP (ß=-0.21; p=0.029) with selenium were found. In the same group, an inverse association between carotid-dorsalis pedis pulse wave velocity (cd-PWV) and GPx activity (ß=-0.23; p=0.017) were also found. To conclude, lower serum selenium levels in black populations from the same geographical region as their white counterparts may impact on the loss of the vasculoprotective effects of selenium and selenoproteins such as GPx.

Deriving an optimal threshold of waist circumference for detecting cardiometabolic risk in sub-Saharan Africa.

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 cut-points 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.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.240.

Asymmetric dimethylarginine and symmetric dimethylarginine prospectively relates to carotid wall thickening in black men: the SABPA study.

The relationship of both asymmetric (ADMA) and symmetric (SDMA) dimethylarginine with carotid wall thickness is inconclusive especially among black populations. We aimed to compare carotid intima media thickness (cIMT) and dimethylarginine levels in 75 black and 91 white men at baseline and after a 3-year follow-up, and to investigate associations of percentage change in cIMT with percentage change in dimethylarginine levels (ADMA and SDMA). Plasma levels of ADMA and SDMA were determined with a liquid chromatography mass spectrometry method and B-mode ultrasonography was used to determine the cIMT at baseline and follow-up. In black men, mean cIMT (p = 0.79) and ADMA levels (p = 0.67) remained the same, but SDMA levels were lower (p < 0.001) when comparing baseline and follow-up. In white men, cIMT increased (p < 0.001), but both mean ADMA and SDMA levels decreased (p < 0.001) over time. In black men, percentage change in cIMT was positively associated with percentage change in ADMA (R 2 = 0.49; ß = 0.46; p < 0.001) and percentage change in SDMA (R 2 = 0.46; ß = 0.41; p < 0.001). These associations were absent in the white men. Despite lower mean SDMA and similar ADMA and cIMT in black men, percentage change in cIMT was independently associated with percentage change in ADMA and percentage change in SDMA. These results suggest an important role for ADMA and SDMA lowering strategies to delay carotid wall thickening, especially in black populations prone to the development of cardiovascular disease.

Associations between dietary salt, potassium and blood pressure in South African adults: WHO SAGE Wave 2 Salt & Tobacco.

BACKGROUND & AIMS: In June 2016, South Africa implemented legislation mandating maximum sodium levels in a range of processed foods with a goal of reducing population salt intake and disease burden from hypertension. Our aim was to explore the relationship between salt and blood pressure (BP) in a subsample of the World Health Organization Study on global AGEing and adult health (SAGE) Wave 2 before implementation of legislation in South Africa. METHODS & RESULTS: Blood pressure (BP) was measured in triplicate (n = 2722; median age 56 years; 33% male) and 24-h urine collected in a nested subsample (n = 526) for sodium, potassium and creatinine analysis. Hypertension prevalence was 55% in older adults (50-plus years) and 28% in younger adults (18-49 years). Median salt intake (6.8 g/day) was higher in younger than older adults (8.6 g vs 6.1 g/day; p < 0.001), and in urban compared to rural populations (7.0 g vs 6.0 g/day; p = 0.033). Overall, 69% of participants had salt intakes above 5 g/day. Potassium intakes were generally low (median 35 mmol/day) with significantly lower intakes in rural areas and older adults. Overall, 91% of adults failed to meet the daily potassium recommendation of 90 mmol/d. Salt intakes above 5 g/day, and to a greater extent, a dietary sodium-to-potassium (Na:K) ratio above 2 mmol/mmol, were associated with significantly steeper regression slopes of BP with age. CONCLUSION: These preliminary results indicate that high dietary Na:K ratio may lead to a greater increase in BP and hypertension risk with age. Interventions to increase potassium intakes alongside sodium reduction initiatives may be warranted.

Recent advances in understanding hypertension development in sub-Saharan Africa.

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

Cardiac Troponin T as Early Marker of Subclinical Cardiovascular Deterioration in Black Hypertensive Women.

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 (ß=0.25; p=0.019), pulse pressure (ß=0.31; p=0.019), Nt-proBNP (ß=0.47; p<0.0001) and Cornell product (ß=0.31; p=0.018). An independent association between albumin-to-creatinine ratio and cTnT was also evident in normotensive women (ß=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.

Quantification of systemic renin-angiotensin system peptides of hypertensive black and white African men established from the RAS-Fingerprint®.

OBJECTIVE: The objective of this study was to make use of a quantitative and qualitative approach comparing the systemic renin-angiotensin system (RAS) of hypertensive black and white African men by using RAS equilibrium analysis. MATERIALS AND METHODS: This sub-study involved 23 black (n = 15) and white (n = 8) hypertensive men aged 39.5-41 years, living in the North West Province of South Africa. The RAS-Fingerprinting was determined with LC-MS/MS quantification of angiotensin peptides. Blood pressure and other variables were determined with known methods. RESULTS: The main finding of this study was the significant lower Ang I (<5.0 and 45.1 pg/ml; p = 0.005) and Ang II (15.6 and 123.9 pg/ml; p ⩽ 0.001) encountered in the hypertensive black African men compared to their white counterparts. Levels of Ang 1-5 (downstream metabolite of Ang 1-7) (1.8 and 3.0 pg/ml), were detected in black and white hypertensive men, respectively. CONCLUSIONS: The observed differences between circulating RAS components, which are reflected via equilibrium angiotensin levels, point to a distinctive molecular regulation of the RAAS in the two study cohorts. The increased peripheral resistance observed in hypertensive black individuals might take over a dominant role in control of blood pressure in this study population. A novel highly sensitive LC-MS/MS method resolved the issue of peptide recovery variations during sample preparation by using internal standards for each individual angiotensin metabolite.

Plasma renin and cardiovascular responses to the cold pressor test differ in black and white populations: The SABPA study.

Low plasma renin levels and augmented cardiovascular reactivity to stress are common in blacks and have been linked to the development of hypertension in this population. We (i) compared cardiovascular and plasma renin reactivity to a cold pressor test between a black and white population; and (ii) investigated the associations between cardiovascular and plasma renin reactivity within the black and white populations. Our population consisted of 153 black and 188 white men and women (age range, 20-65 years). We measured blood pressure (BP), heart rate (HR), stroke volume (SV), total peripheral resistance (TPR), Windkessel arterial compliance, and determined plasma renin levels at rest and during the cold pressor test. Reactivity was calculated for each participant as the percentage change from the resting value. We found lower renin and elevated BP in blacks compared with whites at rest and during stress (both, P<0.001). During stress, HR increased more in blacks (P<0.001), whereas SV (P<0.001) and arterial compliance (P=0.013) decreased more in blacks compared with whites. TPR reactivity was positively associated with renin reactivity in blacks only (ß=0.17; P=0.041), while in whites diastolic BP reactivity was positively associated with renin reactivity (ß=0.21; P=0.005). Although blacks had suppressed renin levels at rest and during acute stress, vascular resistance reactivity associated positively with renin reactivity only in the black population. These results suggest that low renin levels in blacks during rest and stress are linked to increased peripheral vascular responses to stress, which may contribute to elevated BP in blacks.

Bioavailable IGF-1 and its Relation to the Metabolic Syndrome in a Bi-Ethnic Population of Men and Women.

Insulin-like growth factor 1 (IGF-1), an insulin sensitivity and vasculoprotective factor, associates negatively with the metabolic syndrome. However, IGF-1 is reduced by factors such as inflammation, oxidative stress and liver dysfunction. We investigated the relationship between bioavailable IGF-1 and the number of metabolic syndrome components and determined whether this relationship is independent of inflammation, oxidative stress and gamma glutamyl transferase (γ-GT; a marker of liver dysfunction). This study included 907 black and white participants stratified by sex (aged 43.0±11.8 years). Among them 63 participants had fasting glucose levels of ≥+7.0+mmol/l and/or used diabetes medication. Via standard methods we determined waist circumference, fasting glucose, triglycerides, high-density lipoprotein cholesterol and blood pressure. We also determined high-sensitivity C-reactive protein (CRP), reactive oxygen species (ROS), γ-GT, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3). IGF-1/IGFBP-3 was used as an estimate of bioavailable IGF-1. Total IGF-1 was similar between men and women (p=0.10), however, bioavailable IGF-1 was lower in women (p<0.001). In multivariate-adjusted analyses, IGF-1/IGFBP-3 was inversely associated with the number of metabolic syndrome components in both sexes (men: ß=- 0.11; p=0.013 and women: ß=- 0.17; p=0.003). Upon inclusion of ROS, γ-GT and CRP, significance was lost. In patients without diabetes, the results for men changed marginally, but were consistent for women. We found an inverse association between bioavailable IGF-1 and the number of metabolic syndrome components. But the relationship was dependent on oxidative stress, liver dysfunction and inflammation, suggesting underlying processes by which the metabolic syndrome attenuates IGF-1.

Leptin relates to prolonged cardiovascular recovery after acute stress in Africans: The SABPA study.

BACKGROUND AND AIMS: Heightened cardiovascular reactivity and delayed recovery to stress are associated with an increased risk of cardiovascular disease. Africans, who are more prone to develop hypertension, show greater cardiovascular reactivity to stress. However, causal factors underlying individual and ethnic differences in stress reactivity and recovery remain largely unexplored. Leptin, which is known for its sympatho-activating effects, is higher in Africans compared to Caucasians for any given body mass index. We compared how cardiovascular reactivity and recovery relate to leptin in African (n = 200) and Caucasian (n = 209) teachers. METHODS AND RESULTS: We measured leptin in serum and cardiovascular baseline and reactivity continuously with the Finometer device during the cold pressor test for 1 min, and recovery at intervals of 1, 3 and 5 min. Africans had higher body mass index, leptin and blood pressure (all P < 0.001). After full adjustment in multiple regression analyses, associations were seen mainly at the 5 min recovery interval. In Africans, cardiac output reactivity (ß = -0.335; P = 0.0018) and arterial compliance- (ß = -0.241; P = 0.048) associated negatively and total peripheral resistance- (ß = 0.227; P = 0.047) positively with leptin. In Caucasians, diastolic blood pressure correlated positively with leptin (ß = 0.200; P = 0.015). CONCLUSION: In Africans, higher circulating leptin levels associated with prolonged cardiovascular recovery after exposure to stress which could explain their increased vulnerability to hypertension development.

Bioavailable IGF-1 and its relationship with endothelial damage in a bi-ethnic population: The SABPA study.

INTRODUCTION: Insulin-like growth factor-1 (IGF-1) has vasculoprotective effects and can directly oppose endothelial dysfunction in several ways. To improve our understanding on the potential contribution of reduced IGF-1 to the development of vascular endothelial damage, we investigated the link between bioavailable IGF-1 and von Willebrand factor (vWF) as a marker of endothelial damage. We performed this study in black South African school teachers, known to be prone to hypertension. MATERIALS AND METHODS: From the larger Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study we included 179 black and 207 white non-diabetic men and women (aged 44.5 ± 9.96 years). We measured ambulatory blood pressure and determined IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3) and vWF antigen from blood samples. We used the molar IGF-1/IGFBP-3 ratio as an estimate of bioavailable IGF-1. RESULTS: Black individuals presented higher blood pressure and vWFag and lower IGF-1 than the white group (all p < 0.001). In multivariate-adjusted analyses, vWFag was inversely associated with IGF-1 (R(2) = 0.18; ß = -0.17; p = 0.044) and IGF-1/IGFBP-3 (R(2) = 0.18; ß = -0.17; p = 0.030) in blacks, with no associations in whites. Since IGF-1 is attenuated and vWFag elevated in diabetes, we included patients with diabetes (n = 38) and the aforementioned associations found in blacks remained robust. CONCLUSION: The inverse association between bioavailable IGF-1 and vWF in black South Africans suggests that suppressed IGF-1 may result in endothelial damage independent of traditional risk factors.

Endothelial activation and cardiometabolic profiles of treated and never-treated HIV infected Africans.

OBJECTIVE: 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: ß=-0.28, p=0.01; ART: ß=-0.22, p=0.07) and TC (no-ART: ß=-0.36, p<0.01; ART: ß=-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.

Leptin is positively associated with blood pressure in african men with a low body mass index: the SAfrEIC study.

Severe underweight may be a risk factor for hypertension in developing countries, although the manner whereby this occurs is unknown. Leptin is known to exert both beneficial and detrimental vascular effects, and is predictive of poor cardiovascular outcome at high levels, but also at low levels. We explored the relationship between blood pressure and leptin in black men from South Africa with a body mass index (BMI) in the underweight to normal range. We included 113 African men (BMI≤25 kg/m(2)) and took anthropometric, biochemical and cardiovascular measures. The blood pressure-leptin relationship was then investigated along quintiles of leptin and within BMI stratified median split (20 kg/m(2)) groups. Blood pressure increased across leptin quintiles 1-3 (p for trend≤0.040), whereas no relationship was observed along quintiles 3 to 5 (p for trend≥0.14) (adjusted for age and waist circumference). Blood pressure was similar in the two BMI median split groups (p≥0.083). In the low BMI group only, blood pressure associated positively with leptin following unadjusted, partial, and full adjustment (systolic blood pressure and diastolic blood pressure: R(2)=0.20-0.27, ß=0.32-0.34, p≤0.009). Decreasing leptin levels are not likely to contribute to hypertension prevalence in the underweight. Rather, in African men with a BMI≤20 kg/m(2), low leptin levels are positively and independently associated with elevated blood pressure, which is not seen at higher BMI (20-25 kg/m(2)). Our findings suggest a differential concentration dependent vascular effect of leptin in underweight and normal weight African men.

Large artery stiffness and carotid intima-media thickness in relation to markers of calcium and bone mineral metabolism in African women older than 46 years.

Vascular calcification and cardiovascular diseases have been associated with altered bone metabolism. We explored the relationships of arterial pressures and carotid intima-media thickness (CIMT) with parathyroid hormone, 25-hydroxycholecalciferol and their ratio (PTH:25(OH)D3) as well as a marker of bone resorption (CTX) in lean and overweight/obese African women. A population of 434 African women older than 46 years was divided into lean and overweight/obese groups. We assessed brachial blood pressure, central pulse pressure (cPP) and CIMT, and determined PTH, 25(OH)D3 and CTX concentrations. Overweight/obese women had elevated PTH and PTH:25(OH)D3 compared with lean women (both P<0.001), whereas lean women had higher CTX (P<0.001). Single, partial and multiple regression analyses indicated that, in lean women CIMT was independently associated with PTH:25(OH)D3 (R(2)=0.22; ß=0.26; P=0.003), whereas in obese women cPP was associated with both PTH:25(OH)D3 (R2=0.20; ß=0.17; P=0.017) and CTX (R2=0.20; ß=0.17; P=0.025). In conclusion, we found that in African women with increased adiposity, cPP (as a surrogate measure of arterial stiffness), was positively associated with alterations in bone metabolism and calciotropic hormones, whereas CIMT of lean women was positively associated with PTH:25(OH)D3. Our results suggest that alterations in bone and calcium metabolism may contribute to arterial calcification in older African women.

8-Oxo-7,8-dihydro-2'-deoxyguanosine, reactive oxygen species and ambulatory blood pressure in African and Caucasian men: the SABPA study.

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; ß = -0.25; p = 0.002, DBP: R(2) = 0.30; ß = -0.21; p = 0.022, PP: R(2) = 0.30; ß = -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.