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.

The association of von willebrand factor and its cleaving protease (ADAMTS13) with health behaviours in young black and white adults: the African-PREDICT study.

To reduce cardiovascular risks imposed by Von Willebrand factor (vWF) and ADAMTS13 from young ages, knowledge on health behaviours that may affect their concentrations is essential. We therefore determined whether circulating vWF antigen and ADAMTS13 associate with health behaviours. We included 1196 black and white healthy adults aged 20-30 years and used questionnaires for socio-economic, tobacco and alcohol use data. vWF:Ag was measured from citrated samples and ADAMTS13, cotinine and gamma-glutamyl transferase (GGT) from serum. Salt intake was estimated from 24-hour urine and body mass index (BMI) was calculated. Black adults had higher vWF:Ag and lower ADAMTS13 levels compared to whites (all p < 0.001). In multiple regression analyses in the total group, vWF:Ag associated positively with BMI (p = 0.037), while ADAMTS13 associated negatively with BMI (p = 0.016) and cotinine (p = 0.029); and positively with GGT (p = 0.002). When exploring within each ethnic group, vWF:Ag associated positively with estimated salt intake (p = 0.043) only in blacks. In whites, vWF:Ag associated positively with BMI (p = 0.023) while ADAMTS13 associated positively with GGT (p = 0.003) and negatively with cotinine (p = 0.041). Young black adults may have an increased thrombotic risk due to higher vWF and lower ADAMTS13. The ethnic-specific associations observed may have implications for public health initiatives to improve cardiovascular outcomes.

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.

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.

A biomarker of tissue damage, lactate dehydrogenase, is associated with fibulin-1 and oxidative stress in blacks: the SAfrEIC study.

CONTEXT: Extracellular matrix (ECM) remodeling and oxidative stress is present in hypertension and associated arterial stiffness, but little is known on the physiological link among lactate dehydrogenase (LDH), fibulin-1, and reactive oxygen species (ROS). OBJECTIVE: The objective of this study is to explore the link among a marker of tissue damage (LDH), fibulin-1 (as ECM biomarker), and ROS. METHODS: We included 316 black and 305 white South Africans and determined the above-mentioned biomarkers along with additional cardiometabolic risk factors. RESULTS: LDH associated positively with fibulin-1 (ß = 0.23; p < 0.001) and ROS (ß = 0.11; p = 0.30) in blacks only. CONCLUSION: Our finding suggests that increased circulating levels of LDH may be due to early ECM remodeling and oxidative stress in blacks that are subjected to detrimental and uncontrolled lifestyle risk factors.

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.

Characterization of the Renin-Angiotensin-Aldosterone System in Young Healthy Black Adults: The African Prospective Study on the Early Detection and Identification of Hypertension and Cardiovascular Disease (African-PREDICT Study).

[Figure: see text].

How to check whether a blood pressure monitor has been properly validated for accuracy.

Hypertension guidelines recommend that blood pressure (BP) should be measured using a monitor that has passed validation testing for accuracy. BP monitors that have not undergone rigorous validation testing can still be cleared by regulatory authorities for marketing and sale. This is the situation for most BP monitors worldwide. Thus, consumers (patients, health professionals, procurement officers, and general public) may unwittingly purchase BP monitors that are non-validated and more likely to be inaccurate. Without prior knowledge of these issues, it is extremely difficult for consumers to distinguish validated from non-validated BP monitors. For the above reasons, the aim of this paper is to provide consumers guidance on how to check whether a BP monitor has been properly validated for accuracy. The process involves making an online search of listings of BP monitors that have been assessed for validation status. Only those monitors that have been properly validated are recommended for BP measurement. There are numerous different online listings of BP monitors, several are country-specific and two are general (international) listings. Because monitors can be marketed using alternative model names in different countries, if a monitor is not found on one listing, it may be worthwhile cross-checking with a different listing. This information is widely relevant to anyone seeking to purchase a home, clinic, or ambulatory BP monitor, including individual consumers for use personally or policy makers and those procuring monitors for use in healthcare systems, and retailers looking to stock only validated BP monitors.

The African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT): Design, recruitment and initial examination.

BACKGROUND: Globally hypertension is stabilising, but in sub-Saharan Africa the incidence of hypertension remains on an increase. Although this might be attributed to poor healthcare and ineffective antihypertensive treatment, there is a limited understanding of population and individual-specific cardiovascular pathophysiology - necessary for effective prevention and treatment strategies in Africa. As there is a lack of longitudinal studies tracking the early pathophysiological development of hypertension in black populations, the African-PREDICT study was initiated. The purpose of this paper is to describe the detailed methodology and baseline cohort profile of the study. METHODS AND RESULTS: From 2013 to 2017, the study included 1202 black ( N = 606) and white ( N = 596) men and women (aged 20-30 years) from South Africa - screened to be healthy and clinic normotensive. At baseline, and each 5-year follow-up examination, detailed measures of health behaviours, cardiovascular profile and organ damage are taken. Also, comprehensive biological sampling for the 'omics' and biomarkers is performed. Overall, the baseline black and white cohort presented with similar ages, clinic and 24-hour blood pressures, but black adults had lower socioeconomic status and higher central systolic blood pressure than white individuals. CONCLUSIONS: The prospective African-PREDICT study in young black and white adults will contribute to a clear understanding of early cardiovascular disease development.

Ethnic differences regarding arterial stiffness of 6-8-year-old black and white boys.

OBJECTIVES: Vascular deterioration is suggested to occur earlier in black than white populations, thereby increasing their risk for developing hypertension. To establish whether this is the case, we compared different estimates of arterial stiffness in black and white children and investigated the links with body composition and advanced glycation end products (AGEs) as potential contributors. METHODS: We included 40 black and 41 white boys (aged 6-8 years) from similar schools and measured arterial stiffness [pulse wave velocity (PWV) in different arterial sections, systemic arterial compliance and carotid stiffness estimates], anthropometry as well as urinary pentosidine as a marker of AGEs. RESULTS: Black boys displayed increased PWV [carotid-to-radial (P = 0.002), carotid-to-femoral (P < 0.0001) and carotid-to-dorsalis pedis (P = 0.008)], DBP (P = 0.001) and carotid intima-media thickness (P = 0.007) than white boys. Despite higher pentosidine in black boys (P = 0.039), arterial stiffness indices did not correlate with pentosidine in any group. However, only in black boys, pentosidine correlated negatively with BMI (P = 0.015), BSA (P = 0.017), weight (P = 0.018), waist (P = 0.022) and hip circumference (P = 0.010). Arterial stiffness indices related inversely to body composition in white boys, but femoral PWV correlated inversely with BMI (r = -0.32; P = 0.049) in black boys. CONCLUSION: Already at very young ages (6-8 years), with a high proportion of prehypertension, black boys in our study have increased arterial stiffness in all sections of the arterial tree, along with higher DBP, carotid intima-media thickness and AGEs. This phenotype underlines the increasing trend of early-onset vascular aging among black populations.