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.

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.

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.

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.

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.

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

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, chi2 tests were used. RESULTS: A 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. 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.

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

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/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. 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.

Compromised bioavailable IGF-1 of black men relates favourably to ambulatory blood pressure: The SABPA study.

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 (R(2) = 0.24; ß = -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 (R(2) = 0.42; ß = -0.17; p = 0.039) prior to adjustment for γ-glutamyl transferase (R(2) = 0.45; ß = -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.

Attenuated NOx responses and myocardial ischemia, a possible risk for structural vascular disease in African men: the SABPA study.

Chronically elevated blood pressure has been associated with impaired NO-mediated vasodilation and structural vascular disease risk. This study aimed to determine whether significant associations exist regarding NO metabolite (NOx) responses, cardiovascular function and structural vascular disease in a cohort of African and Caucasian men. The study included 81 African and 94 Caucasian male teachers stratified via median splits into low and high NOx ethnic groups. Ambulatory blood pressure, electrocardiogram monitoring and ultrasound carotid intima-media thickness (CIMT) images were obtained. Cardiovascular measurements and fasting blood for NOx responses were measured during rest and on challenging the cardiovascular system with the Stroop colour-word conflict test. African men displayed significantly higher resting NOx as well as higher number of 24 h silent ischemic events than their Caucasian counterparts. Low NOx African men displayed enhanced α-adrenergic and ECG ST segment depression acute mental stress responses as well as 24 h silent ischemic events associated with CIMT (adjusted R(2) = 0.47; ß = 0.25; confidence interval (CI) = 0.13, 0.41). African men demonstrated a vulnerable cardiovascular profile. Novel findings revealed α-adrenergic-driven blood pressure responses and less NO bioavailability during acute stress. The association between myocardial ischemia and CIMT in this group emphasized their risk for future coronary artery disease and cerebrovascular events.

Chronic distress and acute vascular stress responses associated with ambulatory blood pressure in low-testosterone African men: the SABPA Study.

It is known that low testosterone (T) and high cortisol levels are associated with hypertension as well as with chronic stress, linking stress with elevated blood pressure (BP). However, the association between acute stress-, chronic stress responses and BP is not clear in Africans. Therefore, we examined the association between cortisol, psychological distress and BP responses in low- and high-T male subgroups. Beat-to-beat and ambulatory blood pressure (ABPM) and electrocardiogram measures were obtained. Serum samples were collected and analyzed for sex hormones and cortisol. Chronic psychological distress was verified with the General Health Questionnaire and acute stress with the cold pressor test. More chronic psychological distress was observed in both low- and high-T Africans compared with the Caucasians. The low-T Africans tended to have more ischemic events (P=0.06) and ABPM values (P⩽0.01) than any of the other groups. Both chronic distress (cortisol) and acute stress (total peripheral resistance cold pressor responses) were associated with ABPM in the low-T African group. Acute and chronic stress may contribute to increased BP in low-T African men. Their cortisol and vascular responses supported a tendency for ischemia, increasing their risk for coronary artery disease.

The link between vascular deterioration and branched chain amino acids in a population with high glycated haemoglobin: the SABPA study.

Globally the prevalence of non-communicable diseases, such as hypertension and type 2 diabetes, are escalating. Metabolomic studies indicated that circulating branched chain amino acids (BCAAs) are associated with insulin resistance, coronary artery disease and increased risk for cardiovascular events. We aimed to extend the current understanding of the cardiovascular risk associated with BCAAs. We explored whether BCAAs are related to markers of cardiovascular disease in a bi-ethnic population and whether this relationship was influenced by chronic hyperglycaemia. We included 200 African and 209 Caucasian participants, and determined their ambulatory blood pressure and carotid intima-media thickness (cIMT). We analysed blood samples for glycated haemoglobin (HbA1c) and BCAAs. Participants were stratified into two groups according to their HbA1c value using the median cut-off value of 5.6%. Ambulatory BP, cIMT and BCAAs were significantly higher (all p < 0.001) in the high HbA1c group. Single regression analyses indicated significant positive associations of ambulatory blood pressure and cIMT with BCAAs (all p < 0.05) in both the groups. These associations between ambulatory systolic blood pressure (SBP) (r = 0.16, p = 0.035) and cIMT (r = 0.22, p = 0.004) with BCAAs remained in the high HbA1c group after adjusting for age, gender, ethnicity and body mass index (BMI) and were confirmed in multiple regression analyses (ambulatory SBP: R (2) = 0.17, ß = 0.21, p = 0.005 and cIMT: R (2) = 0.30, ß = 0.19, p = 0.003). Our results demonstrate that BCAAs are independently related to ambulatory BP and cIMT in individuals with high HbA1c levels and suggest that potential cardiovascular deterioration accompany the rise in BCAAs in conditions of hyperglycaemia.

A comparison of the association between glomerular filtration and L-arginine status in HIV-infected and uninfected African men: the SAfrEIC study.

Hypertension, a major risk factor for cardiovascular disease worldwide, is increasing significantly in urbanised South Africans. Impaired glomerular filtration is a potential contributor to hypertension. Although HIV infection is widespread, little is known regarding its contribution to diminished estimated glomerular filtration rate (eGFR) and, in turn, hypertension in Africans. We compared eGFRs and cardiovascular profiles of newly identified HIV infected African men (N=53) not yet undergoing anti-retroviral therapy, and uninfected African men of similar age and anthropometry. The aim of the study was to determine whether eGFR is diminished in treatment naive HIV infected individuals and whether eGFR is associated with a potential modulator of hypertension, namely serum L-arginine. Cardiovascular risk factor profiles of HIV infected and uninfected men were similar. In men with healthy eGFRs >90 ml min(-1) per 1.73 m(2), eGFR was significantly lower with HIV infection (114 (90; 147)) compared with that in uninfected men: (120 (91; 168)), P=0.043. Despite the absence of clinically-diagnosed renal dysfunction, eGFR associated significantly with serum L-arginine only in HIV infected men (R(2)=0.277, ß=-0.299, P=0.034), whereas L-arginine did not stay in the model for uninfected men. This difference suggests that the fate of L-arginine as a substrate for nitric oxide generation may be altered in HIV infected individuals. Subsequently this is likely to escalate endothelial dysfunction, contributing to later hypertension and cardiovascular disease. Our findings show that while glomerular filtration rate is not associated with L-arginine in uninfected men, it is diminished and significantly negatively associated with serum L-arginine in HIV infected men.

Defensive coping facilitates higher blood pressure and early sub-clinical structural vascular disease via alterations in heart rate variability: the SABPA study.

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 and-HRV 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 time-domain 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. R(2) = 0.34; ß = -0.24; p = 0.08) and vagal-impaired heart rate responses (RMSSD: adj. R(2) = 0.28; ß = -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.

Defensive active coping facilitates chronic hyperglycaemia and endothelial dysfunction in African men: the SABPA study.

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.

Alkaline phosphatase and arterial structure and function in hypertensive African men: the SABPA study.

BACKGROUND: Vascular calcification is believed to be due to the conversion of vascular smooth muscle cells into osteoblast-like cells and is associated with mortality. Since hypertension and related mortality in Africans is a concern, we investigated associations between a marker of osteoblastic activity, alkaline phosphatase (ALP), and measures of arterial structure and function in hypertensive African men. METHODS: This study included 79 participants. We conducted 24h ambulatory blood pressure and carotid intima-media thickness (cIMT) measurements. cIMT was obtained with an intra-observer variability of 0.04 mm and the cross-sectional wall area (CSWA) was calculated. ALP was measured in serum. RESULTS: ALP was within its reference range (101.6 vs. 30.0-120.0 U/L), however cIMT was higher when this group was stratified and compared to gender and age-specific reference values. In univariate and partial regressions, and confirmed with multiple regression analyses, 24h systolic blood pressure (ß=0.289, p=0.018), 24h pulse pressure (ß=0.387, p=0.002), but not 24h diastolic blood pressure (ß=0.073, p=0.58), were positively associated with ALP. In addition, mean cIMT (ß=0.322, p=0.006) and CSWA (ß=0.285, p=0.013) also correlated positively with ALP after adjusting for significant covariates, and after excluding participants with diabetes, renal dysfunction or a HIV positive status. CONCLUSION: Serum alkaline phosphatase is adversely associated with measures of arterial structure and function in hypertensive African men.