Identifying a urinary peptidomics profile for hypertension in young adults: The African-PREDICT study: Urinary peptidomics and hypertension: Urinary peptidomics and hypertension.

Hypertension is one of the most important and complex risk factors for cardiovascular diseases (CVDs). By using urinary peptidomics analyses, we aimed to identify peptides associated with hypertension, building a framework for future research towards improved prediction and prevention of premature development of CVD. We included 78 hypertensive and 79 normotensive participants from the African-PREDICT study (aged 20-30 years), matched for sex (51% male) and ethnicity (49% black and 51% white). Urinary peptidomics data were acquired using capillary-electrophoresis-time-of-flight-mass-spectrometry. Hypertension-associated peptides were identified and combined into a support vector machine-based multidimensional classifier. When comparing the peptide data between the normotensive and hypertensive groups, 129 peptides were nominally differentially abundant (Wilcoxon p < 0.05). Nonetheless, only three peptides, all derived from collagen alpha-1(III), remained significantly different after rigorous adjustments for multiple comparisons. The 37 most significant peptides (all p ≤ 0.001) served as basis for the development of a classifier, with 20 peptides being combined into a unifying score, resulting in an AUC of 0.85 in the ROC analysis (p < 0.001), with 83% sensitivity at 80% specificity. Our study suggests potential value of urinary peptides in the classification of hypertension, which could enable earlier diagnosis and better understanding of the pathophysiology of hypertension and premature cardiovascular disease development.

The inflammatory score and cardiovascular risk in young adults with overweight or obesity: The African-PREDICT study.

OBJECTIVES: A complex relationship of adipokines and cytokines with cardiovascular risk motivates the use of an integrated approach to identify early signs of adiposity-related inflammation. We compared the inflammatory profiles, including an integrated inflammatory score, and cardiovascular profiles of young adults who are living with overweight and/or obesity (OW/OB). DESIGN AND METHODS: This cross-sectional study included 1194 men and women with a median age of 24.5 ± 3.12 years from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT). Participants were divided into approximate quartiles based on adiposity measures (body mass index, waist circumference, and waist-to-height ratio). We compared an integrated inflammatory score (including leptin, adiponectin, interleukin-6, interleukin-8, interleukin-10, and tumour necrosis factor-α) as well as the individual inflammatory markers, between extreme quartiles. We also compared blood pressure measures, left ventricular mass index, carotid-femoral pulse wave velocity, and carotid intima-media thickness between these groups. RESULTS: Individuals in the top quartile had worse inflammatory- and cardiovascular profiles as the integrated inflammatory score, leptin, interleukin-6, blood pressure measures, and left ventricular mass index were higher, while adiponectin was lower (all p ≤ 0.003). Unexpectedly, carotid-femoral pulse wave velocity was also lower (p < 0.001) in the top quartile. Exclusively in the top quartile, all adiposity measures related positively with the integrated inflammatory score and central systolic blood pressure (both r ≥ 0.24; p < 0.001), and negatively with interleukin-10 (all r ≤ -0.13; p < 0.03). Of these relationships, the correlations with the integrated inflammatory score were the strongest (p < 0.001). The percentage difference of being in the top quartile of all adiposity measures were higher for the inflammatory score (all ≥ 263 %), leptin (all ≥ 175 %), interleukin-6 (all ≥ 134 %), and tumour necrosis factor-α (all ≥ 26 %), and lower for adiponectin (all ≥ 57 %), interleukin-10 (all ≥ 9 %), and interleukin-8 (all ≥ 15 %) compared to being in the bottom quartile. CONCLUSION: The inflammatory score, as a comprehensive marker of adiposity-related inflammation, is strongly related to adiposity and may be an indication of early cardiovascular risk in young adults; however, further work is required to establish the clinical use thereof.

Markers of arterial stiffness and urinary metabolomics in young adults with early cardiovascular risk: the African-PREDICT study.

INTRODUCTION: Increased exposure to risk factors in the young and healthy contributes to arterial changes, which may be accompanied by an altered metabolism. OBJECTIVES: To increase our understanding of early metabolic alterations and how they associate with markers of arterial stiffness, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and in a control group without CVD risk factors. METHODS: We included healthy black and white women and men (N = 1202), aged 20-30 years with a detailed CVD risk factor profile, reflecting obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036) and the control group (N = 166). Markers of arterial stiffness, central systolic blood pressure (BP) and pulse wave velocity were measured. A targeted metabolomics approach was followed by measuring amino acids and acylcarnitines using a liquid chromatography-tandem mass spectrometry method. RESULTS: In the CVD risk group, central systolic BP (adjusted for age, sex, ethnicity) was negatively associated with histidine, arginine, asparagine, serine, glutamine, dimethylglycine, threonine, GABA, proline, methionine, pyroglutamic acid, aspartic acid, glutamic acid, branched chain amino acids (BCAAs) and butyrylcarnitine (all P ≤ 0.048). In the same group, pulse wave velocity (adjusted for age, sex, ethnicity, mean arterial pressure) was negatively associated with histidine, lysine, threonine, 2-aminoadipic acid, BCAAs and aromatic amino acids (AAAs) (all P ≤ 0.044). In the control group, central systolic BP was negatively associated with pyroglutamic acid, glutamic acid and dodecanoylcarnitine (all P ≤ 0.033). CONCLUSION: In a group with increased CVD risk, markers of arterial stiffness were negatively associated with metabolites related to AAA and BCAA as well as energy metabolism and oxidative stress. Our findings may suggest that metabolic adaptations may be at play in response to increased CVD risk to maintain cardiovascular integrity.

Using urinary metabolomics to identify metabolic pathways linked to cardiac structural alterations in young adults: The African-PREDICT study.

BACKGROUND AND AIMS: Risk factor exposure from young ages was shown to contribute to cardiovascular events - cardiac hypertrophy, which may be accompanied by an altered metabolism. To determine how early metabolic alterations associate with myocardial structural changes, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and a control group without CVD risk factors. METHODS AND RESULTS: We included healthy adults (N = 1202), aged 20-30 years, stratified based on risk factors, i.e., obesity, physical inactivity, elevated blood pressure (BP), hyperglycemia, dyslipidemia, low socio-economic status, smoking and excessive alcohol use - forming the CVD risk group (N = 1036) and the control group (N = 166). Relative wall thickness (RWT) and left ventricular mass index (LVMi) were measured using echocardiography. Targeted metabolomics data were obtained using a liquid chromatography-tandem mass spectrometry method. Clinic systolic BP, 24 h BP and RWT were higher in the CVD risk group compared to the control group (all P ≤ 0.031). Exclusively in the CVD risk group, RWT associated with creatine and dodecanoylcarnitine; while LVMi associated with glycine, serine, glutamine, threonine, alanine, citrulline, creatine, proline, pyroglutamic acid and glutamic acid (all P ≤ 0.040). Exclusively in the control group, LVMi associated with propionylcarnitine and butyrylcarnitine (all P ≤ 0.009). CONCLUSION: In young adults without CVD, but with CVD risk factors, LVMi and RWT associated with metabolites linked energy metabolism (shifting from solely fatty acid oxidation to glycolysis, with impaired creatine kinase activity) and oxidative stress. Our findings support early onset metabolic changes accompanying cardiac structural alterations due to lifestyle and behavioural risk factors.

Determining Underlying Mechanisms of Early Vascular Ageing by Clustered Analysis: The African-PREDICT Study.

OBJECTIVE: Identifying individuals at increased risk of early vascular ageing (EVA) is paramount to inform intervention and prevention strategies and curb the increasing burden of cardiovascular disease. METHODS: We stratified and phenotyped pre-screened young apparently healthy South African adults (20-30 yrs) (n=1,041) into vascular ageing profile groups based on carotid femoral pulse wave velocity (cfPWV) percentiles (healthy vascular ageing [HVA]; average vascular ageing [AVA] and EVA). We further compared various anthropometric, cardiovascular (CV), oxidative stress and lifestyle risk factors and determined factor scores to explore associations between CV measures and factor clusters to explore associations in those at risk of EVA. RESULTS: Young adults in the EVA group displayed marked phenotypic characteristics in terms of anthropometry, CV, and lifestyle risk factors, even though cfPWV were within healthy ranges. Blood pressure (brachial and central) and cfPWV were all incrementally higher across all three vascular ageing groups (p-trend ≤0.011). Hypertension, lifestyle risk factors such as self-reported smoking and alcohol consumption were all highest in the EVA group (p-trend ≤0.046). Additionally, in the EVA group only, cfPWV (adj. R2=0.028; ß=0.171; p=0.042) associated positively with Factor 2 (oxidative stress and antioxidant capacity). No associations existed between Factor 1 (basic lipids) and any anthropometric or CV measures (p>0.050). CONCLUSION: Young adults with higher cfPWV presented with a less favourable vascular profile and more unhealthy lifestyle behaviours compared to groups with lower cfPWV. In the EVA group, cfPWV positively associated with a cluster of oxidative stress and antioxidant capacity. Early lifestyle behaviours may have the ability to modify the balance between oxidants and antioxidants, potentially contributing to early onset arterial stiffness.

The renin-angiotensin-system and left ventricular mass in young adults: the African-PREDICT study.

PURPOSE: Raised blood pressure, with the renin-angiotensin system (RAS) as a central regulatory component, is one of the most important contributors to early development of left ventricular hypertrophy. Factors such as increased age, sex, black ethnicity and a low socio-economic status also contribute to left ventricular remodelling. To better understand early contributors to left ventricular mass, we investigated the relationship between left ventricular mass index (LVMi) and the components of the RAS in young healthy adults while considering ethnicity, sex and socio-economic status. MATERIALS AND METHODS: Black and white women and men (N = 1186) between the ages of 20-30 years were included. By using standard echocardiography, we determined LVMi. Ultra-pressure-liquid chromatography tandem-mass spectrometry (LC-MS/MS) was used to measure the RAS-fingerprint®. RESULTS: Components of the RAS such as plasma renin activity (PRA-S), angiotensin I (Ang I), angiotensin II (Ang II) and aldosterone were suppressed in the black compared to the white group (all p < 0.001). No associations between LVMi and the RAS were evident in the total, black or white groups. With additional grouping according to sex and socio-economic status, inverse associations between LVMi and PRA-S (ß= -0.168;  p = 0.017), Ang I (ß= -0.155; p = 0.028) and Ang II (ß= -0.172; p = 0.015) were found only in low socio-economic black women. CONCLUSION: Despite a suppressed RAS in the black compared to the white group, components of the RAS were not associated with LVMi in this young cohort. The low socio-economic black women of this study population may be vulnerable to future RAS-related increases in left ventricular mass.

Nitric oxide-related markers link inversely to blood pressure in black boys and men: the ASOS and African-PREDICT studies.

Nitric oxide plays an important role in maintaining endothelial function, while increased oxidative stress may lead to nitric oxide inactivation and cardiovascular disease. If nitric oxide biosynthesis/bioavailability is already suppressed early in life, it may potentially predispose an individual to the early development of cardiovascular disease. We therefore aimed to identify differences in nitric oxide-related markers (urinary nitrate, nitrite and the nitrate-to-nitrite ratio (UNOxR)) between young black and white individuals, and whether these markers are associated with blood pressure and carotid intima media thickness. We included black and white healthy boys (n = 80; aged 6-8 years) and men (n = 510; 20-30 years) and measured blood pressure and carotid intima media thickness, along with urinary biochemical markers including nitrate and nitrite. The black boys and men had lower nitrate and UNOxR (all p ≤ 0.003) than their white counterparts. In single and multiple regression analyses, we found an inverse association of diastolic blood pressure in the black boys (adj. R2 = 0.27; ß = -0.32; p = 0.030), and systolic blood pressure in black men (adj. R2 = 0.07; ß = -0.13; p = 0.036) with nitrate. Carotid intima media thickness associated inversely with UNOxR in the black men (adj. R2 = 0.02; ß = -0.14; p = 0.023), but not in the boys. Lower urinary nitrate in black boys and young men was associated negatively with blood pressure, suggesting that potentially lower nitric oxide bioavailability in young black individuals may contribute to hypertension development in later life.

Asymmetric dimethylarginine and L-homoarginine prospectively relate to carotid wall thickness in a South African cohort.

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

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.

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 [ß = 0.23; p = 0.036]) in black African women and with a macrovascular measure (24-hour PP [ß = -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 (ß = 0.23; p = 0.035), as well as with macrovascular measures (AIx, PP) in the black (ß = -0.25; p = 0.027) and white African men (ß = -0.22; p = 0.035), and black African women (ß = -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.

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.

Cardiovascular reactivity and oxidative stress in young and older adults: the African-PREDICT and SABPA studies.

Background: Oxidative stress and increased cardiovascular reactivity are associated with endothelial dysfunction and cardiovascular disease development. These factors along with early vascular compromise are more pronounced in black populations. We aimed to compare cardiovascular reactivity and investigate associations thereof with oxidative stress in two bi-ethnic cohorts (younger: 25.0 ± 3.19yrs; older: 44.7 ± 9.61yrs). Methods: Cardiovascular reactivity using the color-word conflict test was measured with the Finometer device. Oxidative stress markers included superoxide dismutase (SOD), γ-glutamyl transferase (γ-GT) and reactive oxygen species (ROS). Results: Black groups displayed greater cardiovascular responses to stress than white groups. In younger white participants, diastolic blood pressure (DBP) (ß = 0.31; p = 0.001) and mean arterial blood pressure (MAP) (ß = 0.28; p = 0.002) associated with ROS. In older black participants, DBP (ß = 0.23; p = 0.009), MAP (ß = 0.18; p = 0.033), stroke volume (ß = -0.20; p = 0.023) and arterial compliance (ß = -0.25; p = 0.005) associated with γ-GT. In older white participants, systolic blood pressure (ß = -0.20; p = 0.006) and MAP (ß = -0.19; p = 0.009) associated with SOD. Conclusions: In the older black group, cardiovascular reactivity associated with markers of glutathione metabolism, suggesting a possible compensatory up-regulation thereof in order to correct their heightened responses to stress. Independent of age, findings in the white groups support a regulatory role of ROS to maintain vascular tone during stress.

Morning Blood Pressure Surge Relates to Autonomic Neural Activity in Young Non-Dipping Adults: The African-PREDICT Study.

BACKGROUND: It is well established that an exaggerated morning blood pressure surge (MBPS) is associated with an increased risk for cardiovascular disease development in hypertensive individuals. However, in non-dipping individuals, a lower surge was reportedly associated with increased cardiovascular risk. Sympathetic nervous system activity is involved in 24-hour blood pressure fluctuations, including night-time dipping and the MBPS. To better understand this interaction, we investigated associations of MBPS with heart-rate variability and baroreceptor sensitivity in young healthy dippers and non-dippers. METHODS: We included black and white men and women (n=827), aged 20-30 years and determined the MBPS using two formulas: the sleep-trough and dynamic morning surge. For autonomic function we determined baroreceptor sensitivity and heart-rate variability. RESULTS: The majority of non-dippers in this population were black (70.4%), presenting lower sleep-trough and dynamic morning surge (all p<0.001). Heart-rate variability was comparable between dippers and non-dippers, whereas baroreceptor sensitivity was higher in non-dippers (p=0.021). Despite a suppressed MBPS profile in non-dippers, we found both sleep-trough (ß=-0.25; p=0.039) and dynamic morning surge (ß=-0.14; p=0.047) to be inversely and independently associated with 24-hour heart-rate variability (total power). These results were absent in dippers. CONCLUSIONS: In conclusion, we found a higher night-time blood pressure coupled with lower MBPS in young healthy non-dippers. Furthermore, this lower MBPS was independently and negatively associated with autonomic neural activity, suggesting increased autonomic function involvement in MBPS suppression of non-dippers. The predictive value of suppressed nocturnal dipping pattern should be investigated while taking autonomic neural activity into account.

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.

Change in renin, cardiovascular and inflammatory markers over three years in a black and white population: the SABPA study.

BACKGROUND: To investigate if percentage change (%∆) in renin over a 3 year follow-up is associated with %∆ in cardiovascular and inflammatory markers in a low renin bi-ethnic group. METHODS: Blood pressure, active renin, C-reactive protein and interleukin-6 levels of 73 black and 81 white teachers were measured at baseline and after 3 years. RESULTS: In the black group, %∆ renin was inversely associated with %∆ systolic blood pressure (ß = -0.27; p = 0.011). In the white group %∆ renin was inversely associated with %∆interleukin-6 (ß = -0.24; p = 0.005). CONCLUSIONS: These prospective results indicate that a decrease in renin over time is associated with an increase in blood pressure in a low renin black South African cohort.

Nitric oxide synthesis capacity, ambulatory blood pressure and end organ damage in a black and white population: the SABPA study.

Nitric oxide (NO) synthesis capacity is determined by the availability of substrate(s) such as L-arginine and the influence of nitric oxide synthase (NOS) inhibitors, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). These factors may be important in black South Africans with a very high prevalence of hypertension. We compared ambulatory blood pressure (BP), markers of end organ damage and NO synthesis capacity markers [L-arginine, L-homoarginine, L-citrulline, L-arginine:ADMA, ADMA, SDMA and dimethylarginine (DMA)], between black and white teachers (n = 390). Associations of nighttime BP and markers of end organ damage with NO synthesis capacity markers were also investigated. Although black men and women had higher BP and albumin-to-creatinine ratio (ACR) (all p < 0.001), they also had higher L-arginine, L-homoarginine, L-arginine:ADMA and lower SDMA and DMA levels (all p < 0.05). Only in white men ADMA concentrations associated positively with nighttime systolic blood pressure (R (2) = 0.20, ß = 0.26, p = 0.009), nighttime diastolic blood pressure (R (2) = 0.23, ß = 0.27, p = 0.007), carotid intima media thickness (cIMT) (R (2) = 0.36, ß = 0.22, p = 0.008) and ACR (R (2) = 0.14, ß = 0.32, p = 0.001). Our findings suggest that despite an adverse cardiovascular profile in blacks, their NO synthesis capacity profile seems favourable, and that other factors, such as NO inactivation, may prove to be more important.

Cardiovascular function is not associated with creatine kinase activity in a black African population: The SABPA study.

BACKGROUND: Higher creatine kinase (CK) activity is associated with the development of cardiovascular disease in black African populations. We compared CK activity and investigated associations of blood pressure with CK activity in black and white men as well as black and white women. METHODS: Ambulatory blood pressure, total peripheral resistance and pulse wave velocity of 197 black and 208 white participants were determined and serum CK activity was measured. RESULTS: Blood pressure and pulse wave velocity were higher in black men and women (all p < 0.001) when compared to their white counterparts. CK activity only varied between black and white women (75.9 U/l vs 62.8 U/l, p = 0.009), even after adjusting for age, body mass index and physical activity. Despite the worse cardiovascular profile of black men and women, and the higher CK activity in the black women, we were unable to link blood pressure, pulse wave velocity or total peripheral resistance with CK activity, in the black African population. In white men, total peripheral resistance was associated with CK activity (R (2) = 0.32; ß = 0.25; p = 0.009), whereas systolic blood pressure (R (2) = 0.46; ß = 0.17; p = 0.03) and pulse pressure (R (2) = 0.31; ß = 0.21; p = 0.01) were associated with CK activity in white women. CONCLUSIONS: The lack of associations in the black African population suggests that the link between a worse cardiovascular profile and CK activity may be overshadowed by other contributing factors. Whereas, the established link between cardiovascular function and CK activity in the white groups may be the result of enhanced smooth muscle cell contractility and/or attenuated nitric oxide synthesis capacity.

Ethnic-specific relationships between haemostatic and oxidative stress markers in black and white South Africans: The SABPA study.

Haemostatic- and oxidative stress markers are associated with increased cardiovascular risk. In the black population, evidence exists that both an imbalance in the haemostatic system and oxidative stress link with the development of hypertension. However, it is unclear whether these two risk components function independently or are related, specifically in the black population, who is known to have a high prevalence of stroke. We aimed to investigate associations between the haemostatic system and oxidative stress in black and white South Africans. We performed a cross-sectional study including 181 black (mean age, 44; 51.4% women) and 209 white (mean age, 45; 51.7% women) teachers. Several markers of the haemostatic- (von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1, d-dimer and clot lysis time) and oxidant-antioxidant (serum peroxides, total glutathione, glutathione peroxidase- and glutathione reductase activities) systems were measured. Along with a worsened cardiovascular profile, the black group had higher haemostatic-, inflammation- and oxidative stress markers as well as decreased glutathione peroxidase activity. In multiple regression analyses, fibrinogen was positively associated with serum peroxides (p < 0.001) in both ethnic groups. In the black population, we found negative associations of von Willebrand factor and clot lysis time with glutathione peroxidase activity (p ≤ 0.008), while a positive association existed between clot lysis time and serum peroxides (p = 0.011) in the white population. We conclude that in the black population, decreased GPx activity accompanies an altered haemostatic profile, while in the white population associations may suggest that serum peroxides impair fibrin clot lysis.

Twenty-four-hour ambulatory, but not clinic blood pressure associates with leptin in young adults with overweight or obesity: The African-PREDICT study.

Hypertension and obesity are known pro-inflammatory conditions, and limited studies explored various blood pressure modalities and inflammatory markers in young adults with overweight or obesity (OW/OB). We assessed the relationship of clinic and 24 h ambulatory blood pressure with an array of inflammatory markers in young adults with OW/OB. This cross-sectional study included women and men of Black and White ethnicity (n = 1194) with a median age of 24.5 ± 3.12 years. Participants were divided into normal weight and OW/OB groups according to body mass index. Clinic and 24 h ambulatory systolic and diastolic blood pressure were measured. Inflammatory markers included leptin, interleukin-6, interleukin-8, tumour necrosis factor-α, adiponectin, interleukin-10, and C-reactive protein. After adjustments for age, sex, and ethnicity, the OW/OB group had higher blood pressure and an overall worse inflammatory profile compared to the normal weight group (all p ≤ 0.024). In the OW/OB group, 24 h systolic (r = 0.22; p < 0.001) and diastolic blood pressure (r = 0.28; p < 0.001) correlated with leptin, independent of age, sex, and ethnicity. In fully adjusted regression models, 24 h systolic blood pressure (adj.R2 = 0.25; ß = 0.28; p = 0.035) and diastolic blood pressure (adj.R2 = 0.10; ß = 0.32; p = 0.034), associated with leptin in the OW/OB group and significance remained with additional adjustments for visceral adiposity index. Twenty-four-hour ambulatory, but not clinic blood pressure, is related to leptin in young adults with OW/OB. Leptin shows a stronger relationship with adiposity when compared to other inflammatory markers and may play a role in subcutaneous adiposity-related increased blood pressure.

A urinary peptidomics approach for early stages of cardiovascular disease risk: The African-PREDICT study.

Cardiovascular disease (CVD) affects individuals across the lifespan, with multiple cardiovascular (CV) risk factors increasingly present in young populations. The underlying mechanisms in early cardiovascular disease development are complex and still poorly understood. We therefore employed urinary proteomics as a novel approach to gain better insight into early CVD-related molecular pathways based on a CVD risk stratification approach. This study included 964 apparently healthy (no self-reported chronic illnesses, free from clinical symptoms of CVD) black and white men and women (aged 20-30 years old) from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT) study. Cardiovascular risk factors used for stratification included obesity, physical inactivity, tobacco use, high alcohol intake, hyperglycemia, dyslipidemia and hypertension. Participants were divided into low (0 risk factors), medium (1-2 risk factors) and high (≥3 risk factors) CV risk groups. We analyzed urinary peptidomics by capillary electrophoresis time-of-flight mass spectrometry. After adjusting for ethnicity, sex and age, 65 sequenced urinary peptides were differentially expressed between the CV risk groups (all q-values ≤ 0.01). These peptides included a lower abundance of collagen type I- and III-derived peptides in the high compared to the low CV risk group. With regard to noncollagen peptides, we found a lower abundance of alpha-1-antitrypsin fragments in the high compared to the low CV risk group (all q-values ≤ 0.01). Our findings indicate lower abundances of collagen types I and III in the high compared to the low CV risk group, suggesting potential early alterations in the CV extracellular matrix.

High prevalence but lack of awareness of hypertension in South Africa, particularly among men and young adults.

Cardiovascular disease (CVD) is a leading cause of death in South Africa (SA) and high blood pressure (BP) is the primary risk factor. However, hypertension prevalence is high, BP control is poor and CV events occur at a younger age than in Europe or America. Increasing screening, raising awareness and improving management of hypertension are critical to prevent CVD in SA. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension aimed at raising awareness of high BP. As part of the MMM campaign, in SA (2017, 2018, 2019 and 2021), BP measurements and a cross-sectional survey of volunteers aged ≥ 18years were performed. Of 11,320 individuals (age 36.6 ± 16.8years) screened, 29.7% had hypertension (systolic BP/diastolic BP ≥ 140/90 mmHg or antihypertensive medication use) and the prevalence was higher (p < 0.0001) in men (35.6%) than in women (26.3%). Of those with hypertension, only 54.3% were aware and 46.8% were receiving antihypertensive medication, and 53.7% of these had controlled BP. In men with hypertension, awareness (45.2%, treatment (38.2%) and controlled BP on antihypertensive medication (45.2%) were lower (p < 0.0001) than in women (awareness: 60.8%; treatment: 53.5%; controlled BP: 58.3%). In young participants (age < 40years), 15.6% had hypertension, 18.6% of these were on treatment but 76.0% were not aware, and only 57.7% had controlled BP. The high prevalence of hypertension, but low levels of awareness, treatment, and BP control in SA, especially in young adults and men, highlight the need for systematic BP screening programmes and improvements in education and management of hypertension.