Metabolomic Insights on Potassium Excretion, Blood Pressure, and Glucose Homeostasis: The African-PREDICT Study.

BACKGROUND: Low-potassium intake is associated with a higher risk of type 2 diabetes and hypertension. Both conditions occur more frequently in Black populations, who also consume less potassium-rich foods. OBJECTIVES: Using metabolomics to identify dysregulated metabolic pathways associated with low-potassium excretion may procure more accurate entry points for nutritional prevention and intervention for type 2 diabetes and hypertension. METHODS: A total of 440 White and 350 Black adults from the African-PREDICT study (aged 20-30 y) were included. Twenty-four-hour blood pressure (BP) was measured. Potassium, sodium, and fasting glucose concentrations were analyzed in 24-h urine and plasma samples. Liquid chromatography-tandem mass spectrometry-based metabolomics included the analyses of amino acids and acylcarnitines in spot urine samples. RESULTS: Black participants had lower urinary potassium concentrations than Whites (36.6 compared with 51.1 mmol/d; P < 0.001). In White but not Black adults, urinary potassium correlated positively with 2-aminoadipic acid (2-AAA) (r = 0.176), C3-[propionyl]carnitine (r = 0.137), C4-[butyryl]carnitine (r = 0.169) and C5-[isovaleryl]carnitine (r = 0.167) in unadjusted and 2-AAA (r = 0.158) and C4-carnitine (r = 0.160) in adjusted analyses (all P < 0.05 and q < 0.05). Elevated C0-, C3-, and C5-carnitine in turn were positively associated with systolic BP (Black and White groups), diastolic BP (Black group), and glucose (White group) (all P < 0.05). CONCLUSIONS: Racial differences are an important consideration when investigating nutrient-metabolite relationships and the role thereof in cardiovascular disease. Only in White adults did urinary potassium associate with 2-AAA and short-chain acylcarnitines. These metabolites were positively related to BP and fasting plasma glucose concentrations. In White adults, the metabolomic profiles related to potassium excretion may contribute to BP regulation and glucose homeostasis. This trial was registered at clinicaltrials.gov as NCT03292094.

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.

Early vascular ageing phenotypes and urinary targeted metabolomics in children and young adults: the ExAMIN Youth SA and African-PREDICT studies.

Some individuals are susceptible to accelerated biological ageing, resulting in premature alterations in arterial structure and function. Identifying early-onset vascular ageing characterised by arterial stiffening is vital for intervention and preventive strategies. We stratified and phenotyped healthy children (5-9 yrs) and young adults (20-30 yrs) into their vascular ageing extremes established by carotid-femoral pulse wave velocity (cfPWV) percentiles (i.e., healthy vascular ageing (HVA) and early vascular ageing (EVA)). We compared anthropometric, cardiovascular, and metabolomic profiles and explored associations between cfPWV and urinary metabolites. Children and adults in the EVA groups displayed higher levels of adiposity, cardiovascular, and lifestyle risk factors (adults only) (all p ≤ 0.018). In adults, several urinary metabolites were lower in the EVA group (all q ≤ 0.039) when compared to the HVA group, with no differences observed in children. In multiple regression analysis (adults only), we found inverse associations between cfPWV with histidine (adj. R2 = 0.038; ß = -0.192; p = 0.013) and beta-alanine (adj. R2 = 0.034; ß = -0.181; p = 0.019) in the EVA group, but with arginine (adj. R2 = 0.021; ß = -0.160; p = 0.024) in the HVA group. The inverse associations of beta-alanine and histidine with cfPWV in the EVA group is suggestive that asymptomatic young adults who present with an altered metabolomic and less desired cardiovascular profile in combination with unfavourable lifestyle behaviours may be predisposed to early-onset vascular ageing. Taken together, screening on both a phenotypic and metabolic level may prove important in the early detection, prevention, and intervention of advanced biological ageing.

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.

Kidney dysfunction: prevalence and associated risk factors in a community-based study from the North West Province of South Africa.

BACKGROUND: Globally, the World Health Organization ranks chronic kidney disease (CKD) as one of the top 10 causes of mortality. In South Africa, where noncommunicable diseases have become leading causes of mortality, the true population prevalence of CKD is unknown and associated risk factors remain understudied. This study aimed to describe the prevalence of kidney dysfunction and associated risk factors in a community from the North West province of South Africa. METHODS: This cross-sectional study included 1999 participants older than 30 years. Kidney dysfunction was defined as (i) estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2, or (ii) urine albuminuria-to-creatinine ratio (uACR) ≥ 3.0 mg/mmol, or a combination (i and ii). Risk factors included age, sex, urban/rural locality, body mass index (BMI), blood pressure (BP), lipid profile, haemoglobin A1c (HbA1C), C-reactive protein (CRP), gamma-glutamyl transferase (GGT), tobacco use, and HIV status. RESULTS: Mean age of participants was 48 (42;56) years, and 655/1999 (33%) had eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol. Compared to those with normal kidney function, participants with eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol were older, female, had higher measures of adiposity, systolic, diastolic, and mean arterial blood pressure, serum lipids and C-reactive protein (CRP) (all p ≤ 0.024). In multiple regression analyses eGFR was associated with systolic BP (ß = 0.11) and HIV infection (ß = -0.09), and albuminuria was associated with elevated CRP (ß = 0.12) and HIV infection (ß = 0.11) (all p < 0.026). In both groups (individuals with and without kidney dysfunction respectively), eGFR was associated with age (ß = -0.29, ß = -0.49), male sex (ß = 0.35, ß = 0.28), BMI (ß = -0.12, ß = -0.09), low-density/high-density lipoprotein cholesterol ratio (ß = -0.17, ß = -0.09) and CRP (ß = 0.10, ß = 0.09) (all p < 0.005); and uACR was associated with female sex (ß = 0.10, ß = -0.14), urban locality (ß = -0.11, ß = -0.08), BMI (ß = -0.11, ß-0.11), and systolic BP (ß = 0.27, ß = 0.14) (all p < 0.017). CONCLUSION: In this study from the North West province, South Africa, eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol was prevalent and associated with modifiable risk factors. The findings may inform screening strategies for kidney disease prevention, focusing on women, obesity, blood pressure control, dyslipidaemia, identifying and treating inflammation, and HIV diagnosis and treatment.

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.

Growth differentiating factor-15 and adiposity in young adults: The African-PREDICT study.

BACKGROUND AND AIMS: Circulating growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that increases in older individuals with established cardiovascular disease (CVD) and obesity. To address potential targets in primary prevention, we aimed to determine whether body weight, waist circumference, waist/height ratio, body mass index (BMI), body surface area (BSA) and leptin associate with GDF-15 in young underweight, lean and overweight/obese (ow/ob) adults. METHODS AND RESULTS: We included 1189 adults aged 20-30 years. We grouped participants as underweight (BMI ≤ 18 kg/m2, n = 59), lean (BMI > 18 kg/m2 and ≤25 kg/m2; n = 616) or ow/ob (BMI ≥ 25 kg/m2; n = 514) and determined serum GDF-15 and leptin levels. Body composition measurements, leptin and blood pressure readings were higher in the ow/ob group compared to the underweight and lean groups (all p < 0.0001). GDF-15 was higher in the underweight group compared to the lean and combined ow/ob groups (p = 0.041), and higher in obese (BMI ≥ 30 kg/m2) compared to overweight (p = 0.002) individuals. In multiple regression analysis, we found positive associations (all p ≤ 0.020) of body weight (adj. R2 = 0.398; ß = 0.11), waist circumference (adj. R2 = 0.271; ß = 0.11), waist/height ratio (adj. R2 = 0.168; ß = 0.14), BMI (adj. R2 = 0.263; ß = 0.14), BSA (adj. R2 = 0.508; ß = 0.083) and leptin (adj. R2 = 0.622; ß = 0.10) with GDF-15 in the ow/ob group. However, waist circumference (adj. R2 = 0.536; ß = -0.45), waist/height ratio (adj. R2 = 0.471; ß = -0.51) and leptin (adj. R2 = 434; ß = -0.25) associated inversely with GDF-15 in the underweight group (all p < 0.050). CONCLUSION: Our findings may suggest that in young adults with either underweight or excess adiposity, increased GDF-15 levels may contribute to the development of future cardiovascular health risks associated with pro-inflammation.

Ethnicity and Arterial Stiffness.

Early vascular aging reflects increased arterial stiffness of central blood vessels at young chronological ages and powerfully predicts cardiovascular events and mortality, independent of routine brachial blood pressure and other risk factors. Since ethnic disparities exist in routine blood pressure, in hypertension and cardiovascular outcomes, this review evaluates major studies comparing arterial stiffness through the life course between different ethnic groups or races (which have no biological definition)-in children, adolescents, young, and middle-aged adults and the very elderly. Most report that compared with white European-origin samples, populations of black African descent have increased central arterial stiffness throughout different life stages, as well as a more rapid increase in arterial stiffness at young ages. Exceptions may include African Caribbean origin people in Europe. Differences in vascular structure and function are clearest, where obesity, socioeconomic, and psychosocial factors are most marked. Few studies evaluate a wider spectrum of ethnic groups or factors contributing to these ethnic disparities. Genetic effects are not obvious; maternal risk and intergenerational studies are scarce. Nevertheless, across all ethnic groups, for given levels of blood pressure and age, some people have stiffer central arteries than others. These individuals are most at risk of vascular events and mortality and, therefore, may benefit from early, as yet untested, preventive action and treatment.

Racial differences of early vascular aging in children and adolescents.

The prevalence of non-communicable disease (NCDs) is rising globally, with a large burden recorded in sub-Saharan countries and populations of black race/ethnicity. Accelerated vascular deterioration, otherwise known as early vascular aging (EVA), is the underlying factor for highly prevalent NCDs such as hypertension. The etiology of EVA is multifactorial with a central component being arterial stiffness with subsequent development of hypertension and cardiovascular complications. Although arterial stiffness develops with increasing age, many children and adolescents are subjected to the premature development of arterial stiffness, due to genetic or epigenetic predispositions, lifestyle and behavioral risk factors, and early life programming. Race/ethnic differences in pediatric populations have also been reported with higher aortic stiffness in black (African American) compared with age-matched white (European American) counterparts independent of blood pressure, body mass index, or socioeconomic status. With known evidence of race/ethnic differences in EVA, the pathophysiological mechanisms underlying graded differences in the programming of EVA are still sparse and rarely explored. This educational review aims to address the early life determinants of EVA in children and adolescents with a particular focus on racial or ethnic differences.

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.

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.

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.

Growth differentiating factor-15 and its association with traditional cardiovascular risk factors: The African-PREDICT study.

BACKGROUND AND AIMS: Growth differentiating factor-15 (GDF-15) is a stress-induced and cardio-protective cytokine, reported to be influenced by a number of cardiovascular risk factors. In older adults, GDF-15 associated with age, black ethnicity and smoking. It is important to determine if GDF-15 could potentially be used as an early marker of cardiovascular disease, especially in young populations. We investigated whether GDF-15 associated with traditional cardiovascular risk factors (age, sex, ethnicity, blood pressure (BP), socio-economic status, waist-to-hip ratio, cholesterol, physical inactivity, smoking and alcohol use) in young apparently healthy adults. METHODS AND RESULTS: We included 1189 black and white participants (aged between 20 and 30 years). Questionnaires were used to collect demographic and physical activity data. We measured serum GDF-15, and performed 24-h ambulatory BP and pulse wave analysis. The following risk factors increased with increasing GDF-15 quartiles: age, black ethnicity, central systolic BP, 24-h diastolic BP, tumour necrosis factor-alpha, lipids, cotinine, smoking and alcohol use (all p trend ≤ 0.013). Socio-economic status and physical activity (p trend ≤ 0.014) were the lowest in the highest quartile. In multi-variable adjusted regression analyses GDF-15 associated with central systolic BP (ß = 0.076; p = 0.027), age (ß = 0.096; p = 0.006), low socio-economic status (ß = -0.12; p = 0.003), physical inactivity (ß = -0.18; p < 0.0001), tumour necrosis factor-alpha (ß = 0.28; p < 0.0001) and cotinine (ß = 0.12; p < 0.0001). CONCLUSION: In young adults, GDF-15 associated independently with multiple traditional cardiovascular risk factors including higher central systolic blood pressure, older age, lower socio-economic status, physical inactivity, inflammation and smoking. These results suggest that GDF-15 is a promising biomarker for early identification of cardiovascular risk.

Relation of the renin-angiotensin-aldosterone system with potential cardiac injury and remodelling: the SABPA study.

Purpose: The renin-angiotensin-aldosterone system (RAAS) plays an important role in maintaining hemodynamic homeostasis. Ethnic disparities exist regarding RAAS activity due to sympathetic activity and sodium-water retention, however the implications thereof on cardiac damage is unknown. This study investigated the associations of cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NTproBNP) and subclinical LVH with components of the RAAS (renin, aldosterone and aldosterone-to-renin ratio (ARR)) and copeptin in a black and white South African cohort.Materials and methods: The study population consisted of 305 participants (black = 139, white = 166) aged 20-62 years. Serum cTnT, NTproBNP, Cornell product, components of the RAAS (active renin, aldosterone and ARR) and copeptin were determined.Results: The black group had lower renin (p < 0.001) and higher ARR (p < 0.001), cTnT (p = 0.015) and Cornell product compared to whites (all p < 0.001). NTproBNP and copeptin were similar between the groups. After forward stepwise adjustments for multiple confounders, inverse associations of cTnT with renin (ß = -0.17, p = 0.018) and aldosterone (ß = -0.14, p = 0.048) as well as an inverse association between NTproBNP and aldosterone (ß = -0.25, p < 0.001) were observed in the white population only. In the black group cTnT associated positively with renin (ß = 0.16, p = 0.040) and copeptin (ß = 0.21, p = 0.020) and inversely with ARR (ß = -0.15, p = 0.047). Additionally, NTproBNP associated positively with copeptin (ß = 0.18, p = 0.045). No correlations were observed between the RAAS and Cornell product in any of the groups.Conclusions: Our findings suggest that RAAS, together with cardiac stress may function differently in cardiac damage and remodelling in the two ethnic groups; which may influence treatment in clinical practice.

May Measurement Month 2018: an analysis of blood pressure screening results in South Africa.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension (ISH) aimed at raising awareness of high BP and acting as a temporary solution to the lack of screening programmes worldwide. As part of MMM, screening in South Africa in 2017 revealed that 24.5% of adults (mean age = 31 years) have hypertension and only half of those with hypertension had controlled BP. These data highlight the need for continued screening and awareness campaigns. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2018. Blood pressure measurements, the definition of hypertension and statistical analyses followed the MMM protocol. The sites screened were general populations and university campuses in preference to hospitals and clinics, aiming to raise awareness and allow access to screening to those less likely to be aware of their BP. In total, 2965 individuals (age 40.5 ± 18.2 years) were screened. After multiple imputation for missing BP readings, 34.6% had hypertension, only 56.7% of those with hypertension were aware, 21.2% of those not receiving treatment for hypertension were hypertensive, and a large proportion (42.5%) of individuals receiving antihypertensive medication had uncontrolled BP. These results suggest that opportunistic screening campaigns can identify significant numbers with undiagnosed and uncontrolled hypertension. The high proportions of individuals with undiagnosed and treated uncontrolled hypertension highlight the need for hypertension awareness campaigns and more rigorous management of hypertension.

May Measurement Month 2017: an analysis of blood pressure screening results in South Africa-Sub-Saharan Africa.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension (ISH) aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programs worldwide. A surveillance study in 2016 in South Africa revealed that 45% of adults have hypertension and only 6-9% of men and women respectively had controlled BP on medication, highlighting the need for regular screening and awareness campaigns. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Blood pressure measurement, the definition of hypertension, and statistical analyses followed the MMM protocol. The sites screened were primarily university campuses and general populations in preference to hospitals and clinics, aiming to raise awareness and allow access to screening in those less likely to be aware of their BP. In total, 3250 individuals (mean age 31.0 ± 13.3 years) were screened. After multiple imputation for missing BP readings, 795 (24.5%) had hypertension. Of individuals not receiving antihypertensive medication, 459 (15.7%) were hypertensive, and 157 (46.9%) of individuals receiving antihypertensive medication had uncontrolled BP. These results suggest that opportunistic screening campaigns can identify significant numbers with undiagnosed and uncontrolled hypertension, even amongst the fairly young. The high proportions of individuals with undiagnosed and treated uncontrolled hypertension, highlight the need for campaigns to increase hypertension awareness and control.

Hypertension in sub-Saharan Africa: the current profile, recent advances, gaps, and priorities.

Recent global and regional reports consistently confirm the high and increasing prevalence of hypertension in sub-Saharan Africa (SSA), with poor detection, treatment, and control rates. This narrative review summarises the burden of hypertension in SSA and recent findings from community-based hypertension management strategies. We further outline prominent risk factors according to recent data and associated underlying mechanisms for hypertension development. An extensive review of literature showed that most countries have reported on the prevalence of hypertension during 2017-2023, despite limitations linked to the lack of nationally representative studies, heterogeneity of sampling and data collection methods. Task-shifting approaches that assign roles to model patients and community health workers reported improved linkage to healthcare services and adherence to medication, with inconsistent findings on blood pressure (BP)-lowering effects over time. The regularly reported risk factors include unhealthy diet, sedentary lifestyle, increased adiposity and underweight, ageing, level of education, and/or income as well as psychosocial factors. Newer data on the pathophysiological mechanisms leading to hypertension and potential areas of intervention are reported from children and adults and include, among others, salt-handling and volume overload, endothelial function, BP dipping patterns and the role of human immunodeficiency virus . To conclude, significant strides have been made in data reporting from SSA on the burden of hypertension in the region as well as biomarker research to improve understanding and identification of areas of intervention. However, gaps remain on linkage between knowledge generation, translation, and implementation research. Coordinated studies addressing both discovery science and public health are crucial to curb hypertension development and improve management in SSA.

Community-Based Strategies to Improve Health-Related Outcomes in People Living With Hypertension in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

Background: Individuals living with hypertension are at an increased risk of cardiovascular- and cerebrovascular-related outcomes. Interventions implemented at the community level to improve hypertension control are considered useful to prevent cardiovascular and cerebrovascular events; however, systematic evaluation of such community level interventions among patients living in low- and middle-income countries (LMICs) is scarce. Methods: Nine databases were searched for randomized controlled trials (RCTs) and cluster randomized control trials (cRCTs) implementing community level interventions in adults with hypertension in LMICs. Studies were included based on explicit focus on blood pressure control. Quality assessment was done using the Revised Cochrane Risk of Bias tool for randomized trials (ROBS 2). Results were presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Fixed-effect meta-analyses were conducted for studies that reported continuous outcome measures. Results: We identified and screened 7125 articles. Eighteen studies, 7 RCTs and 11 cRCTs were included in the analysis. The overall summary effect of blood pressure control was significant, risk ratio = 1.48 (95%CI = 1.40-1.57, n = 12). Risk ratio for RCTs was 1.68 (95%CI = 1.40-2.01, n = 5), for cRCTs risk ratio = 1.46 (95%CI = 1.32-1.61, n = 7). For studies that reported individual data for the multicomponent interventions, the risk ratio was 1.27 (95% CI = 1.04-1.54, n = 3). Discussion: Community-based strategies are relevant in addressing the burden of hypertension in LMICs. Community-based interventions can help decentralize hypertension care in LMIC and address the access to care gap without diminishing the quality of hypertension control.