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.

L-homoarginine is associated with decreased cardiovascular- and all-cause mortality.

BACKGROUND: Increasing evidence suggests that L-homoarginine, an endogenous analogue of the amino acid L-arginine, may have beneficial effects on vascular homeostasis. We examined whether L-homoarginine is associated with 10-year risk of all-cause and cardiovascular mortality in a black South African population. METHODS: We included 669 black South African participants (mean age 59.5 years), 143 of whom died during the 10-year follow-up period. Mortality data were acquired via verbal autopsy. Plasma L-homoarginine (and other related markers) were analysed with liquid chromatography-tandem mass spectrometry. RESULTS: Survivors had higher L-homoarginine levels compared with nonsurvivors (1.25 µM vs. 0.89 µM; P < .001). Multivariable Cox regression analyses revealed that higher plasma L-homoarginine predicted a reduction in 10-year cardiovascular (hazard ratio [HR] per SD increment, 0.61; 95% CI 0.50 to 0.75) and all-cause (hazard ratio [HR] per SD increment, 0.59; 95% CI 0.41 to 0.84) mortality risk. CONCLUSION: Higher L-homoarginine levels are associated with reduced risk of 10-year cardiovascular and all-cause mortality. Regulation of L-homoarginine levels as a therapeutic target in the management of cardiovascular disease should be investigated.

Inflammation and salt in young adults: the African-PREDICT study.

PURPOSE: Low-grade inflammation and a diet high in salt are both established risk factors for cardiovascular disease. High potassium (K+) intake was found to counter increase in blood pressure due to high salt intake and may potentially also have protective anti-inflammatory effects. To better understand these interactions under normal physiological conditions, we investigated the relationships between 22 inflammatory mediators with 24-h urinary K+ in young healthy adults stratified by low, medium and high salt intake (salt tertiles). We stratified by ethnicity due to potential salt sensitivity in black populations. METHODS: In 991 healthy black (N = 457) and white (N = 534) adults, aged 20-30 years, with complete data for 24-h urinary sodium and K+, we analysed blood samples for 22 inflammatory mediators. RESULTS: We found no differences in inflammatory mediators between low-, mid- and high-sodium tertiles in either the black or white groups. In multivariable-adjusted regression analyses in white adults, we found only in the lowest salt tertile that K+ associated negatively with pro-inflammatory mediators, namely interferon gamma, interleukin (IL) -7, IL-12, IL-17A, IL-23 and tumour necrosis factor alpha (all p ≤ 0.046). In the black population, we found no independent associations between K+ and any inflammatory mediator. CONCLUSION: In healthy white adults, 24-h urinary K+ associated independently and negatively with specific pro-inflammatory mediators, but only in those with a daily salt intake less than 6.31 g, suggesting K+ to play a protective, anti-inflammatory role in a low-sodium environment. No similar associations were found in young healthy black adults.

Lifestyle factors associated with the transition from healthy to unhealthy adiposity among black South African adults over 10 years.

BACKGROUND AND AIMS: Obesity is associated with an increasing prevalence of cardiovascular diseases in Africa, but some obese individuals maintain cardiometabolic health. The aims were to track metabolically healthy overweight or obesity (MHO) over 10 years in African adults and to identify factors associated with a transition to metabolically unhealthy overweight or obesity (MUO). METHODS AND RESULTS: The participants were the South African cohort of the international Prospective Urban and Rural Epidemiological study. From the baseline data of 1937 adults, 649 women and 274 men were followed for 10 years. The combined overweight and obesity prevalence of men (19.2%-23.8%, p = .02) and women (58%-64.7%, p < .001), and the prevalence of the metabolic syndrome in all participants (25.4%-40.2%, p < .001) increased significantly. More than a quarter (26.2%) of the women and 10.9% of men were MHO at baseline, 11.4% of women and 5.1% of men maintained MHO over 10 years, while similar proportions (12.3% of women, 4.7% of men) transitioned to MUO. Female sex, age, and total fat intake were positively associated with a transition to MUO over 10 years, while physical activity was negatively associated with the transition. HIV positive participants were more likely to be MHO at follow-up than their HIV negative counterparts. CONCLUSIONS: One in two black adults with BMI ≥25 kg/m2 maintained MHO over 10 years, while a similar proportion transitioned into MUO. Interventions should focus on lower fat intakes and higher physical activity to prevent the transition to MUO.

Potassium excretion and blood pressure are associated with heart rate variability in healthy black adults: The African-PREDICT study.

BACKGROUND AND AIMS: Heart rate variability (HRV) is a main determinant of autonomic function and related to the development of hypertension and cardiovascular (CV) disease. Hypertension develops in black populations at an earlier age, which could be due to differences in the autonomic nervous system activity and sodium/potassium handling in black and white populations. We investigated whether HRV is associated with 24 h urinary sodium and potassium excretion and blood pressure (BP) in a young bi-ethnic cohort. METHODS AND RESULTS: We examined 423 black and 483 white healthy adults (aged 24.5 ± 3.1 years) for 24 h HRV, including standard deviation of normal RR intervals (SDNN) reflecting autonomic variations over time, and root mean square of successive differences (RMSSD) reflecting parasympathetic activity. We measured 24 h urinary sodium and potassium concentration and BP. The black group had lower SDNN and potassium excretion as well as higher RMSSD, sodium and Na/k ratio compared to the white group (all p < 0.05). Only in black individuals, urinary potassium excretion was independently and negatively associated with SDNN (ß[95% CI];-0.26[-0.50;-0.02]ms) and RMSSD (-0.14[-0.27;-0.01]ms, p < 0.05). One unit increase in sodium/potassium (Na/K) ratio was associated with higher SDNN (ß[95% CI]; 3.04[0.89; 5.19]ms) and RMSSD (1.60[0.41; 2.78]ms) in the black cohort only (both p < 0.001). In both groups elevated 24 h diastolic BP was associated with lower RMSSD (p < 0.05). CONCLUSION: Lower potassium excretion and higher Na/K ratio related independently to higher HRV in young and healthy black adults. A better ethnic-specific understanding of sodium and potassium handling is required as part of preventive cardiology, especially in black individuals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03292094; URL: https://clinicaltrials.gov/ct2/show/NCT03292094.

Von Willebrand factor, its cleaving protease (ADAMTS13), and inflammation in young adults: The African-PREDICT study.

BACKGROUND: The role of inflammation in the early development of vascular dysfunction remains complex. Interleukin-6 (IL-6) and C-reactive protein (CRP) can cause an acute imbalance in the von Willebrand factor (vWF)-ADAMTS13 interaction, indicating a possible link between markers of haemostasis and low-grade inflammation. To better understand these inter-relationships in the early phases of disease development, we investigated whether vWF and ADAMTS13 associate with the pro-inflammatory markers, IL-6 and CRP in healthy young adults. We considered the role of blood types, sex and race on these relationships. METHODS: In healthy black and white men and women (n = 1113; 24 ± 5 years; no previous diagnosis or medication use for chronic diseases) we analysed von Willebrand factor antigen (vWFag), ADAMTS13, IL-6 and CRP, and grouped blood types as non-O (A, B and AB) and O. Covariates included socioeconomic status, age, estimated glomerular filtration rate, 24-hour systolic blood pressure, waist circumference, glucose, total cholesterol, platelet count, γ-glutamyl transferase and total energy expenditure. RESULTS: In the total group, vWFag was highest in the third tertile of both IL-6 and CRP (p ≤ 0.014), while ADAMTS13 was lowest in the third compared to the first IL-6 tertile (p = 0.006). In multivariate regression, vWFag associated positively with IL-6 (Adj R2 = 0.169; ß = 0.123; p = 0.001) and CRP (Adj R2 = 0.163; ß=0.094; p = 0.019) in the total group, in the O blood group (all p ≤ 0.051) and white men (all p ≤ 0.035). ADAMTS13 associated negatively with IL-6 (Adj R2 = 0.053; ß = -0.154; p = 0.015) and CRP (Adj R2 = 0.055; ß = -0.177; p = 0.009), only in the O blood group. CONCLUSIONS: Markers of haemostasis associated independently with low-grade inflammation in the O type blood group and white men. An interplay between the haemostatic and inflammatory systems may already exist in young healthy adults and is dependent on blood groups, sex and race. This extends our understanding on the role of inflammation in the early development of vascular dysfunction prior to cardiovascular compromise.

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.

Vascular function and cardiovascular risk in a HIV infected and HIV free cohort of African ancestry: baseline profile, rationale and methods of the longitudinal EndoAfrica-NWU study.

BACKGROUND: People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world's largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. METHODS: In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. RESULTS: At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV. CONCLUSION: Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.

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.

Obesity, blood pressure and retinal microvascular phenotype in a bi-ethnic cohort of young children.

BACKGROUND AND AIMS: Childhood obesity and high blood pressure (BP) are main determinants for cardiovascular disease development with regional and ethnic differences. Narrower arteriolar (CRAE) and wider venular (CRVE) retinal vessel diameters are sensitive markers of early vascular compromise in children. We aimed to compare retinal vessel diameters and investigate associations and odds ratios with body mass index (BMI) and BP in a multi-national/ethnic childhood study. METHODS: BMI, systolic (SBP) and diastolic BP (DBP) were screened in 929 black and white South African (SA) and 1171 Swiss children (aged 5-9 years). Retinal assessments were performed using a retinal vessel analyzer to determine CRAE and CRVE. RESULTS: Black SA children had wider CRVE compared to white SA and Swiss children (all p < 0.001). However, BMI or BP was not associated with CRVE in black SA children. Higher BMI and BP associated with narrower CRAE in all children, except for BMI in black SA children, in whom narrower CRAE was found for every unit increase in SBP (ß = -0.199 µm, p = 0.001) and DBP (ß = -0.312 µm, p < 0.001). Obesity (OR:1.38[1.01; 1.89]), hypertension (OR:1.90[1.53; 2.36]) and black ethnicity (OR:1.50[1.18; 1.92]) increased the likelihood for arteriolar narrowing. CONCLUSIONS: Black SA children presented with wider retinal venules compared to their white SA and Swiss peers, which was unexplained by conventional risk factors. The overall risk of arteriolar narrowing was driven by obesity, hypertension and ethnicity. Our findings indicate the importance to differentiate cardiovascular risk by microvascular phenotype in different populations and ethnicity early in life.

Homoarginine and blood pressure: a 10-year prospective relationship in normotensives.

Nitric oxide plays a major role in the regulation of blood pressure, and impaired nitric oxide bioavailability contributes to the development of hypertension (HT). Various factors may contribute to nitric oxide bioavailability-including availability of the substrate for nitric oxide synthesis, L-arginine and its homolog L-homoarginine. We investigated whether blood pressure after 10 years associates with baseline L-homoarginine in participants who remained normotensive (NT) or developed HT, respectively. Data from the South African leg of the Prospective Urban and Rural Epidemiology study, performed in the North-West Province, were used. We investigated participants who either remained NT (N = 166) or who developed HT (N = 166) over 10 years. Blood pressure was measured with validated OMRON devices and serum L-homoarginine was analyzed with liquid chromatography-tandem mass spectrometry. L-homoarginine levels were similar at baseline (p = 0.39) and follow-up (p = 0.93) between NT and hypertensive groups. In the group that remained NT after 10 years, baseline L-homoarginine correlated positively with follow-up brachial systolic blood pressure (adj.R2 = 0.13; ß = 0.33; p = 0.001), brachial pulse pressure (adj.R2 = 0.15 ß = 0.40; p = 0.001), and central pulse pressure (adj.R2 = 0.20; ß = 0.30; p = 0.003). No significant associations were found in the group that developed HT after 10 years. We found a positive, independent association between blood pressure and L-homoarginine in a group that remained NT, but not in a group that developed HT after 10 years. This may suggest a protective role for L-homoarginine to maintain normal blood pressure, but only to a certain level. Once HT develops other factors may overshadow the protective effects of L-homoarginine.

Comparison of endothelial function and cardiometabolic profiles of people living with HIV in two South African regions: the EndoAfrica study.

BACKGROUND: People living with HIV (PLWH) are at risk for cardiovascular disease, but regional differences have not been studied in South Africa. We compared endothelial function and cardiometabolic markers in PLWH and HIV-free controls from two distinct South African regions. METHODS: We measured flow-mediated dilation (FMD), cardiometabolic, immunological and viral markers in age- and gender-matched PLWH on antiretroviral therapy (n = 100/group) and HIV-free participants (n = 50/group) in samples from cohort studies in the North West and Western Cape provinces. RESULTS: Endothelial function and cardiometabolic profiles were not worse in PLWH than in HIV-free individuals, and %FMD was not associated with cardiometabolic, viral or immunological markers. PLWH from the North West region had lower %FMD but overall better metabolic profiles. CONCLUSIONS: Ethnic, cultural and socio-economic differences need further investigation to understand the possible protective role of antiretroviral treatment on the vasculature and to direct region-specific HIV and AIDS guidelines in South Africa.

Prognostic values of modifiable risk factors for cardiovascular events in South African health promotion.

BACKGROUND: Cardiovascular diseases (CVDs) are increasing at an alarming rate among the South African population. This study aimed to determine the prognostic value of modifiable CVD risk factors for fatal and non-fatal events to inform cardiovascular health promotion practices in the South African public health system. METHODS: Data was collected from individuals participating in the South African leg of a multi-national prospective cohort study. Binary logistic regression was applied to estimate odds of total, non-fatal and fatal cardiovascular events. RESULTS: Binary logistic regression analyses identified age as a predictor of non-fatal and fatal CV events, with ORs of 1.87 to 3.21, respectively. Hypertension increased the odd of suffering a non-fatal CV event by almost two and a half (OR = 2.47; 95% CI = 1.26, 4.85). Moreover, being physically active reduced the odd of non-fatal CVD events by 38% (OR = 0.62; 95% CI = 0.46, 0.83 for 1 Standard deviation increase of the weighted physical activity index score (WPA)). On the one hand, gamma-glutamyltransferase (GGT) was associated with a higher fatal cardiovascular disease risk OR = 2.45 (95% CI = 1.36, 4.42) for a standard deviation increase. CONCLUSIONS: Elevated blood pressure, GGT, and physical activity have significant prognostic values for fatal or non-fatal CV events. These findings emphasise the importance of highlighting hypertension and physical activity when planning cardiovascular health education and intervention programmes for this population, with attention to the monitoring of GGT.

Cardiovascular Profile of South African Adults with Low-Level Viremia during Antiretroviral Therapy.

Chronic inflammation is an HIV infection feature, contributing to elevated risk of cardiovascular disease among people with HIV, which can be induced by viral replication. A proportion of antiretroviral therapy (ART) recipients fail to achieve viral suppression, despite not meeting criteria for treatment failure, so-called low-level viremia (LLV). We investigated the relationship between LLV and an array of cardiovascular measures and biomarkers. South Africans with LLV (viral load = 50−999 copies/mL) and virological suppression (viral load <50 copies/mL) were selected from the EndoAfrica study (all receiving efavirenz-based ART) for cross-sectional comparison of vascular structure and function measures, as well as 21 plasma biomarkers related to cardiovascular risk and inflammation. Associations were investigated with univariate, multivariate, and binomial logistic regression analyses (having outcome measures above (cases) or below (controls) the 75th percentile). Among 208 participants, 95 (46%) had LLV, and 113 (54%) had viral suppression. The median age was 44 years, 73% were women, and the median ART duration was 4.5 years. Cardiovascular measures and biomarker levels were similar between these two categories. Cardiovascular function and structure measures were not associated with viremia status and having LLV did not increase the odds of having outcome measures above the 75th percentile. In this study among South African ART recipients, LLV did not associate with cardiovascular risk.

Cardiorespiratory Fitness, Blood Pressure and Ethnicity Are Related to Salivary Cortisol Responses after an Exercise Test in Children: The ExAMIN Youth SA Study.

BACKGROUND: Childhood elevated circulatory stress mediators such as cortisol seem to play an important role in the development of hypertension and metabolic disorders later in life. Little is known about the association of body composition, cardiorespiratory fitness (CRF), blood pressure (BP) and ethnicity with cortisol reactivity in young children. METHODS: In this cross-sectional study, 324 black and 227 white school children (aged 7.4 ± 1.0 years) were screened for salivary cortisol reactivity, body mass index, BP and CRF (shuttle run) by standardised assessments for children. RESULTS: Children in the lower cortisol reactivity percentile (<25th) had a higher heart rate (87.0 ± 12.9 bpm) and a lower CRF (3.1 ± 1.3 stages) compared to children in the upper (>25th) percentile (86.2 ± 11.5 bpm and 3.5 ± 1.7 stages, respectively). At baseline, children of black ethnicity had a higher cortisol level (p < 0.001). Immediately before the exercise test, no associations of obesity, BP, CRF and ethnicity with cortisol levels were found. In analysis of covariance (ANCOVA) we found that low CRF, high BP and black ethnicity were independently associated with lower cortisol reactivity by performing the shuttle run test (p < 0.01). CONCLUSION: Low CRF and high BP were associated with lower cortisol reactivity after a cardiorespiratory exercise test. Black children showed a lower cortisol reactivity which may contribute to the earlier onset of hypertension reported in black compared to white populations. Primary prevention programs need to focus on improving physical fitness to reduce the growing prevalence of cardiometabolic disorders during childhood.

Cross-Talk Between Large Artery Stiffness and Retinal Microvasculature in Children: The ExAMIN Youth SA Study.

Background: Cross-talk between the macro-and microvasculature is considered an important contributor to target organ damage. Previous findings were predominantly in adult populations and investigation into this mechanism in children may provide insight into the development of early adverse vascular changes. Whether any ethnic differences in cross-talk is evident, also remains to be determined. Objective: To determine whether retinal microvascular diameters are associated with large artery stiffness in young children and whether ethnic differences are evident. Materials and Methods: In this cross-sectional study, 730 black (n = 437) and white (n = 293) school children aged 5-9 years were included. Pulse wave velocity (PWV) was measured and the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) diameters were calculated from fundus images. The arterio-venous ratio (AVR) was subsequently calculated. Results: Pulse wave velocity was lower (p ≤ 0.001) in the black group when compared to the white group. The black group had a narrower CRAE, wider CRVE and lower AVR (all p < 0.001). Pulse wave velocity associated negatively with CRAE (r = -0.141, p = 0.003) and AVR (r = -0.185, p ≤ 0.001) in the black group only. A positive association between PWV and CRVE was seen in the black (r = 0.174, p ≤ 0.001) and white (r = 0.119, p = 0.043) group. Conclusion: Large artery stiffness is associated with retinal arterial narrowing and venular widening in children, suggesting cross-talk between the macro-and microvasculature. Ethnic differences in these associations are also evident. Our findings warrant further investigation into environmental and sociocultural risk factors contributing to premature cardiovascular disease development.

Blood pressure and nitric oxide synthesis capacity in physically active and inactive groups: the SABPA study.

Physical activity affects the vasculature through mechanisms related to nitric oxide bioavailability, oxidative stress, and inflammation; with endothelial function at the centre of this triad. In a South African setting, with the prevalence of hypertension and physical inactivity being alarmingly high, we aimed to investigate relationships of vascular function with markers of oxidative stress, inflammation and nitric oxide synthesis capacity in physically active and inactive groups. Based on the 2010 World Health Organisation guidelines, black and white school teachers were divided into physically active (n = 84) and physically inactive (n = 132) groups. Twenty-four-hour blood pressure (24 h BP), total peripheral resistance and Windkessel compliance were measured. Markers of oxidative stress, inflammation and nitric oxide synthesis capacity were analysed. Windkessel compliance (p = 0.041) and homoarginine (p = 0.006) were higher in the physically active group. In the same group, 24 h diastolic BP associated with total glutathione (ß = 0.17; p = 0.056), and 24 h BP (systolic blood pressure: ß = 0.23, p = 0.006; diastolic blood pressure: ß = 0.22, p = 0.019) associated with homoarginine. In the physically inactive group, 24 h BP (systolic blood pressure: ß = 0.26, p < 0.001; diastolic blood pressure: ß = 0.23, p = 0.007) associated with symmetric dimethylarginine (SDMA). These associations were independent of inflammation. Despite only reaching moderate physical activity levels, vascular function and nitric oxide synthesis capacity were more favourable in the physically active population compared to the physically inactive population. These results may suggest that even moderate physical activity could increase nitric oxide synthesis capacity, which in turn may mitigate the development of cardiovascular disease in this population.

Vascular Structure and Inflammation in a South African Population: The SABPA Study.

BACKGROUND AND OBJECTIVE: Inflammation plays a role in the early onset of cardiovascular disease. However, longitudinal studies on this topic, especially in South African populations, are scant. We explored whether early changes in vascular structure are associated with changes in inflammation. METHODS: We investigated 303 South African teachers aged 20-65 years at two intervals, three years apart. Standardised methods were used to determine carotid intima-media thickness (IMT) and cross-sectional wall area (CSWA) as measures of vascular structure, as well as the inflammatory markers soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein (CRP) and interleukin-6 (IL-6) at baseline and follow-up. RESULTS: IMT and CSWA were higher, while CRP was lower at follow-up than at baseline. After adjusting for confounding factors, percent change in IMT was inversely associated with percent change in suPAR (ß = -0.12, p = 0.036; adjusted R2 = 0.16) only, and only in the highest tertile of percent change in suPAR (r = -0.31; p = 0.002). CONCLUSION: The early structural changes observed are not related to higher inflammatory levels in this South African population. Future studies are needed to investigate the possible protective effect of suPAR on early changes in vascular structure, especially with the focus on cardiovascular disease prevention.

Inflammation and hypertension development: A longitudinal analysis of the African-PREDICT study.

BACKGROUND: The role of inflammation in the development of hypertension remains incompletely understood. While single inflammatory mediators have been shown to associate with changes in blood pressure (ΔBP), the role of clusters of inflammatory mediators has been less comprehensively explored. We therefore determined whether individual or clusters of inflammatory mediators from a large biomarker panel were associated with ΔBP over 4.5 years, in young healthy adults. METHODS: We included 358 adults (white, n = 156; black, n = 202) with detailed information on ambulatory blood pressure (BP) at baseline and follow-up. Baseline blood samples were analysed for 22 inflammatory mediators using multiplexing technology. Principal component analysis was used to study associations between clusters of inflammatory mediators and ΔBP. RESULTS: In the total cohort in multivariable-adjusted regression analyses, percentage change in 24hr systolic BP associated positively with Factors 1 (Interferon-gamma, interleukin (IL)-4, IL-7, IL-10, IL-12, IL-17A, IL-21, IL-23, macrophage inflammatory protein (MIP)-1α, MIP-1ß, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF)) and 2 (IL-5, IL-6, IL-8, IL-13). Change in daytime systolic BP associated positively with Factors 1, 2 and 3 (C-Reactive protein, IL-1ß, IL-2, MIP-3α). Subgroup analysis found these findings were limited to white study participants. Numerous associations were present between individual inflammatory mediators (Interferon-gamma, GM-CSF, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-21, IL-23, MIP-1α and MIP-1ß) and ΔBP in the white but not black subgroups. CONCLUSION: We found independent relationships between numerous inflammatory mediators (individual and clusters) and ΔBP over 4.5 years. The relationship between inflammatory markers and ΔBP was only found in white participants. ClinicalTrials.gov (Identifier: NCT03292094)..