Recent Submissions

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    The association of measures of the micro- and macro-vasculature with selenium and GPx activity in a young bi-ethnic population: The African-PREDICT study
    (Taylor and Francis, 2019-03-01) Swart, R; Schutte, A.E; van Rooyen, J.M; Smith, W; Mels, C.M.C
    Objective: Selenium plays an important physiological role as component for antioxidant selenoproteins such as glutathione peroxidase (GPx). Since oxidative stress contributes to hypertension development, it is likely that selenium deficiency may contribute to the burden of cardiovascular disease. To better understand the involvement of selenium and GPx in the early development of cardiovascular disease, we investigated in young, healthy black and white African men and women whether measures of the micro- and macrovasculature are related to selenium and GPx activity. Methods: In young adults (N = 394; aged 20–30 years) we determined serum selenium, GPx activity, microvascular measures (central retinal artery equivalent, central retinal vein equivalent, arteriolar-to-venular ratio [AVR], and estimated glomerular filtration rate [eGFR]), and macrovascular measures (pulse wave velocity, 24-hour pulse pressure [PP] and augmentation index [Aix]). Results: In multivariable-adjusted regression analyses, there were vasculoprotective associations between serum selenium and a microvascular measure (AVR [β = 0.23; p = 0.036]) in black African women and with a macrovascular measure (24-hour PP [β = −0.15; p = 0.048]) in white African women. In turn, GPx activity also showed a protective association with a microvascular measure (eGFR) in white African men (β = 0.23; p = 0.035), as well as with macrovascular measures (AIx, PP) in the black (β = −0.25; p = 0.027) and white African men (β = −0.22; p = 0.035), and black African women (β = −0.32; p = 0.001). Conclusions: Collectively the findings suggest a protective role for the micronutrient selenium and GPx on both the micro- and macrovasculature in a young, healthy bi-ethnic population.
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    Central systolic pressure and a nonessential amino acid metabolomics profile: The African prospective study on the early detection and identification of cardiovascular disease and hypertension
    (Wolters Kluwer, 2019-06) Mels, C.M; Delles, C; Louw, R; Schutte, A.E
    Objectives: Early-life exposures to cardiovascular risk factors may manifest as early vascular ageing, a phenomenon to which black populations are more prone. The metabolome provides insight into the current state and regulation of physiological processes and was used to investigate the early molecular determinants of arterial stiffness. Methods: Black (N = 80) and white (N = 80) men and women (aged 20-30 years, clinic blood pressure <140 and 90 mmHg) across the arterial stiffness spectrum were included. Carotid-femoral pulse wave velocity, central SBP (cSBP) and central pulse pressure (cPP) were measured. NMR spectroscopy, liquid chromatography tandem mass spectrometry and gas chromatography-time of flight-mass spectrometry methods produced metabolomic data. Results: Differences (d ≥ 0.3) in 34 metabolites between black and white groups were found (adjusted for multiple comparisons). Only cSBP were higher in the black group (P = 0.003). Lower dietary protein intake (P < 0.001), but higher urinary nonessential amino acid levels were found in the black group (q ≤ 0.05). In multivariable-adjusted regression models cSBP and cPP inversely correlated with various nonessential amino acids, but only in black adults. These include associations of cSBP with 4-hydroxyproline (β = -0.24; P = 0.042), alanine: (β = -0.29; P = 0.015), glutamine (β = -0.25; P = 0.028), glycine (β = -0.26; P = 0.027), histidine (β = -0.30; P = 0.009), serine (β = -0.29; P = 0.012), and associations of cPP with alanine (β = -0.31; P = 0.005) and serine (β = -0.26; P = 0.019). Conclusion: These amino acids play pivotal roles in collagen metabolism, glucose metabolism and oxidative stress and this ethnic-specific finding suggests that biosynthesis of nonessential amino acids may be upregulated to protect the vasculature against the onset of early vascular deterioration.
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    Aldosterone and renin in relation to surrogate measures of sympathetic activity: the SABPA study
    (Sabinet, 2019-01-22) Gafane-Matemane, L.F; van Rooyen, J. M; Schutte, R; Schutte, A.E
    Introduction: Hypertension, particularly in black populations, is often accompanied by augmented sympathetic nervous system activity and suppressed renin activity, indicative of possible blood pressure (BP) dysregulation. The potential role of the interrelationship between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system in the context of low-renin conditions is unclear. We therefore explored whether surrogate measures of sympathetic activity [noradrenaline, 24-hour heart rate (HR) and percentage (%) dipping of night-time HR] relate to renin, aldosterone and aldosterone-to-renin ratio (ARR) in black and white South Africans. Methods: We included black (n = 127) and white (n = 179) males and females aged 20-63 years. We measured 24-hour BP and HR, and calculated night-time dipping. We determined renin and aldosterone levels in plasma and calculated ARR. Noradrenaline and creatinine levels were determined in urine and the noradrenaline:creatinine ratio was calculated. Results: More blacks had low renin levels (80.3%) compared to whites (58.7%) (p < 0.001). In univariate and after multivariate analyses the following significant associations were evident in only the black group: HR dipping was associated negatively with aldosterone level (β = -0.18, p = 0.024) and ARR (β = -0.20, p = 0.011), while 24-hour HR was associated positively with renin level (β = 0.20, p = 0.024). Additionally, there was a borderline significant positive association between noradrenaline:creatinine ratio and aldosterone level (β = 0.19, p = 0.051). Conclusions: The observed associations between surrogate measures of sympathetic nervous system activity and components of the RAAS in the black group suggest that the adverse effects of aldosterone and its ratio to renin on the cardiovascular system may be coupled to the effects of the sympathetic nervous system.
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    The African prospective study on the early detection and identification of cardiovascular disease and Hypertension (African-PREDICT): Design, recruitment and initial examination
    (SABINET, 2019-01-22) Schutte, A.E; Gona, P.N; Delles, C; Uys, A.S; Burger, A; Mels, C.Mc; Kruger, R; Smith, W; Fourie, C.Mt; Botha, S; Lammertyn, L; van Rooyen, J.M; Gafane-Matemane, L.F; Mokwatsi, G.G; Breet, Y; Kruger, H.S; Zyl, T.V; Pieters, M; Zandberg, L; Louw, R; Moss, S.J; Khumalo, I.P; Huisman, H.W
    Introduction: Hypertension, particularly in black populations, is often accompanied by augmented sympathetic nervous system activity and suppressed renin activity, indicative of possible blood pressure (BP) dysregulation. The potential role of the interrelationship between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system in the context of low-renin conditions is unclear. We therefore explored whether surrogate measures of sympathetic activity [noradrenaline, 24-hour heart rate (HR) and percentage (%) dipping of night-time HR] relate to renin, aldosterone and aldosterone-to-renin ratio (ARR) in black and white South Africans. Methods: We included black (n = 127) and white (n = 179) males and females aged 20-63 years. We measured 24-hour BP and HR, and calculated night-time dipping. We determined renin and aldosterone levels in plasma and calculated ARR. Noradrenaline and creatinine levels were determined in urine and the noradrenaline:creatinine ratio was calculated. Results: More blacks had low renin levels (80.3%) compared to whites (58.7%) (p < 0.001). In univariate and after multivariate analyses the following significant associations were evident in only the black group: HR dipping was associated negatively with aldosterone level (β = -0.18, p = 0.024) and ARR (β = -0.20, p = 0.011), while 24-hour HR was associated positively with renin level (β = 0.20, p = 0.024). Additionally, there was a borderline significant positive association between noradrenaline:creatinine ratio and aldosterone level (β = 0.19, p = 0.051). Conclusions: The observed associations between surrogate measures of sympathetic nervous system activity and components of the RAAS in the black group suggest that the adverse effects of aldosterone and its ratio to renin on the cardiovascular system may be coupled to the effects of the sympathetic nervous system.
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    Autonomic activity and its relationship with the endogenous cardiotonic steroid marinobufagenin: The African-PREDICT study
    (Taylor and Francis, 2019-01-07) Strauss, M; Smith, W; Wei, W; Fedorova, O.V; Schutte, A.E
    Aim: Marinobufagenin (MBG), a cardiotonic steroid and a natriuretic hormone, is elevated in response to high salt diet consumption. In animal models salt intake stimulates adrenocortical MBG secretion via increased angiotensin II, sympathetic activity and aldosterone. No evidence in humans exists to suggest the involvement of the angiotensinergic-sympatho-excitatory pathway in MBG production. We investigated whether MBG is related to indices of autonomic activity in men and women. Methods: This cross-sectional study included 680 black and white, men and women from the African-PREDICT study (aged 20-30 years). Continuous 24 hr ECG recordings were used to obtain low and high frequency (LF, HF) heart rate variability (HRV). We measured 24 hr urinary MBG excretion and serum aldosterone. Results: We found a positive association of MBG excretion with estimated salt intake (P < 0.001) and aldosterone (P < 0.001) in women and men. In women only, a positive relationship was evident between MBG excretion and LF HRV in multivariate adjusted regression analyses (Adj. R 2 = 0.33; β = 0.11; P = 0.030). In men, MBG excretion associated positively with HF HRV in similar regression analyses (R 2 = 0.36; β = 0.12; P = 0.034). Sex-specific results were corroborated only in blacks, namely, a positive association of MBG excretion with LF HRV in black women (R 2 = 0.38; β = 0.13; P = 0.036), and negative association with HF HRV in black men (R 2 = 0.40; β = 0.18; P = 0.045). No relationships were evident in white women (P = 0.58) or men (P = 0.27). Conclusion: Our findings in this human cohort support suggested mechanisms whereby MBG is elevated as a result of increased salt intake, including autonomic activity, previously demonstrated in Dahl salt-sensitive hypertension.

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