Although conventional lipids (high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), total cholesterol (TC) and triglycerides (TG)) are therapeutic targets to manage and prevent atherosclerotic cardiovascular disease (CVD), apolipoprotein (Apo) levels have sparked interest for their potential to improve CVD risk prediction. This study explored the relationships of traditional CVD risk factors with conventional lipids, as well as ApoA1, ApoB and its ratio (ApoB: ApoA1) in South African adults of African ancestry. This study included 1697 adults (aged 29 to 94) from the Prospective Urban Rural Epidemiology (PURE) study. The CVD risk markers included body mass index (BMI), physical activity index, tobacco use, dietary fat intake, γ-glutamyl transferase (γGT) and glycated haemoglobin (HbA1C). Conventional lipids were measured in serum samples using standard methodology, while ApoA1 and ApoB were measured using a multiplex magnetic bead immunoassay. Stratified into tertiles of conventional lipid and Apo levels, trends emerged across multiple CVD risk markers, including BMI, tobacco use, fat intake, γGT and HbA1C levels. Higher tertiles of LDLC, TC, TG, ApoB and ApoB: ApoA1, along with the lowest tertiles of HDLC and ApoA1 exhibited higher prevalence of Type II diabetes mellitus (all p ≤ 0.024) and overweight or obesity (all except for TC, p ≤ 0.024). HDLC was negatively associated and LDLC, TC, and TG were positively associated with BMI (all p < 0.001) and HbA1C (all except for TC, p ≤ 0.005). Similarly, ApoA1 associated negatively with BMI (β=-0.067 (-0.125; -0.010), p = 0.022) and HbA1C (β=-0.071 (-0.122; -0.020), p = 0.007), while ApoB associated positively with BMI (β = 0.168 (0.117; 0.218), p < 0.001). The ApoB: ApoA1 showed positive associations with BMI (β = 0.213 (0.163; 0.263), p < 0.001) and HbA1C (β = 0.123 (0.074; 0.172), p < 0.001). In South African adults of African ancestry, ApoA1, ApoB and ApoB: ApoA1 levels are associated with various established CVD risk markers and suggests that these apolipoproteins may provide additional mechanistic insights beyond the conventional lipids to understand the aetiology of early cardiometabolic disease development.

In children reduced baroreceptor sensitivity (BRS) has been linked to obesity but not blood pressure (BP). Offspring of hypertensive parents have reduced BRS, with possibly increasing risk for hypertension development and kidney dysfunction. This study aimed to explore the relationships between BRS, kidney function, familial cardiovascular-and lifestyle risk in prepubescent boys with varying BP levels. We included 40 Black and 41 White boys (aged 6–8 years). Anthropometric measurements included calculated body mass index (BMI) and sex-and-age specific BMI z-scores (BMIz). Demographic data was collected with questionnaires and included information on familial cardiovascular-and lifestyle risk. Cardiovascular measures were resting BP and Finometer monitoring for BRS calculation. Kidney function was assessed using urinary albumin-to-creatinine ratio (uACR). Stratification was based on normal or elevated BP status. The elevated BP group had more Black boys (n = 37; 65.5%; p = 0.003). Notably, BRS (p = 0.56) and uACR (p = 0.92) were comparable between normal and elevated BP groups. In the normal BP group, single, partial and fully adjusted models revealed an inverse association between BRS and uACR (β = −0.38; p = 0.009). In the elevated BP group, BRS associated with familial risk (β = −0.52; p = 0.002), BMIz (β = 0.36; p = 0.020) and Black ethnicity (β = −0.37; p = 0.024), yet no association was evident between BRS and uACR. A cardioprotective relationship exists between BRS and kidney function in boys with normal BP. In boys with elevated BP, a positive familial cardiovascular-and lifestyle risk, adiposity and Black ethnicity seems to contribute to cardiovascular disease risk via a relationship with lower BRS.

Objectives:Greater vulnerability of Black vs. White individuals to cardiovascular disease (CVD) and chronic kidney disease (CKD) is well charted in the United States, but studies involving sub-Saharan blacks are scarce.Methods:Baseline data (2021-2024) were collected in 168 sub-Saharan Blacks and 93 European Whites in an ongoing clinical trial (NCT04299529), using standardized patient selection criteria. Data included clinical and biochemical risk factors, ECG and echocardiographic traits, Framingham CVD risk, CKD grades (KDIGO 2024), self-assessed symptoms (WHO questionnaire), and urinary proteomic profiles predictive of left ventricular dysfunction (LVD) and CKD, HF1, and CKD273, respectively. Racial comparisons rested on unadjusted and multivariable-adjusted analyses.Results:Despite being younger (60.4 vs. 68.3 years), blacks had a worse risk profile, as evidenced by higher diabetes prevalence, higher BMI, faster heart rate, unfavourable serum cholesterol fractions, lower estimated glomerular filtration rate, microalbuminuria, and sedentary lifestyle. This resulted in blacks having higher 10-year CVD risk, higher heart age (index of vascular ageing with chronological age as reference), and a worse CKD grades. In both races, CKD273 increased with CKD grade, but CKD273 and HF1 were not different by race. These observations were robust in subgroup and adjusted analyses.Conclusion:This study did not differentiate host (genetic, molecular, and pathogenic) from environmental drivers of disease. Nonetheless, the findings call for a multipronged and comprehensive implementation of innovative health policies in sub-Saharan countries. Education, research, empowerment of stakeholders, and international learned societies connecting experts from a wide array of disciplines should vigorously sustain this effort.

OBJECTIVE:Hypertension and kidney disease share common pathophysiological pathways involved in endothelial dysfunction including increased oxidative stress and chronic inflammation. The precise early-stage mechanisms associated with nephron-specific kidney injury remain unclear. We aimed to explore associations of kidney function biomarkers with markers representing these mechanisms in young adults stratified by blood pressure status [according to 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines]. METHODS:We cross-sectionally analysed 1055 adults. Kidney biomarkers included estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (uACR), alpha-1 microglobulin (uA1M), neutrophil gelatinase-associated lipocalin (uNGAL), uromodulin (uUMOD) and CKD273 classifier. Markers of oxidative stress [gamma-glutamyl transferase (GGT); malondialdehyde (MDA)], inflammation [interleukin 6 (IL-6); C-reactive protein (CRP); fibrinogen] and endothelial function [soluble intercellular adhesion molecule-1; soluble vascular cell adhesion molecule-1 (sVCAM-1); von Willebrand factor antigen (vWF ag ); monocyte chemoattractant protein-1 (MCP-1); plasminogen activator inhibitor-1 activity (PAI-1 act ); urinary nitrate-to-nitrite ratio] were analysed. RESULTS:Individuals in the hypertensive group (mean age 24.8 years; 73.2% men; 39% Black) had higher GGT, CRP, IL-6, MCP-1 and PAI-1 act levels (all P  ≤ 0.024) compared to their normotensive counterparts. In individuals with hypertension, eGFR associated negatively and uNGAL positively with IL-6, while uA1M associated positively with PAI-1 act (all P  ≤ 0.047). In the same group, UMOD associated positively with fibrinogen and CKD273 classifier negatively with MCP-1 (all P  ≤ 0.021). In contrast, eGFR associated positively with MDA and negatively with GGT, CKD273 classifier associated positively with GGT, sVCAM-1 and vWF ag , and uACR associated negatively with CRP (all P  ≤ 0.033) in normotensives. CONCLUSION:In young adults, mechanisms linked to early nephron-specific kidney injury biomarkers differ according to blood pressure status.

BACKGROUND: Aortic pulse wave velocity (PWV) is an indicator of vascular aging and has proven to be effective in adult cardiovascular risk assessment. To use it in young people to identify those who may be at increased cardiovascular disease risk, reference values need to be determined. The Youth Vascular Consortium is a large, international database which was established to investigate vascular aging in youth. Using data from the Youth Vascular Consortium, this study aimed to develop reference values for aortic PWV in healthy young people. METHODS: This is a retrospective, multicenter study. Data on demographics, anthropometric, biochemical, and vascular aging measures from participants aged 1 year to 40 years were harmonized. Generalized additive models were used to derive percentile curves for PWV and predicted percentiles at years of age were reported by sex, continent, and device. RESULTS: Data from 19 930 participants (mean age=17 years, 51% female, 71% European), classified as healthy based on blood pressure, body mass index, serum glucose, and cholesterol levels, were included to construct the reference values. Six devices were used to assess aortic PWV (29% SphygmoCor). Device-specific percentile curves for aortic PWV were constructed, and an increasing trend was identified for both sexes with age. CONCLUSIONS: This study provided reference values for aortic PWV assessed with 6 devices for healthy young people by age and sex. These percentiles may be applied clinically to identify youth with impaired vascular aging and, thus, those who may be at risk of developing overt cardiovascular disease in the future.

INTRODUCTION:Hypertension is a leading risk factor of global morbidity and mortality. Reports indicate a rise in mortality linked to blood pressure (BP) levels exceeding 115/75 mmHg. Even with hypertension management based on redefined guidelines, many young individuals with early signs of target organ injury (TOI) may still go undetected AIM : We determined the most accurate diagnostic criteria of hypertension (using the 2017 ACC/AHA and the 2023 ESC/ESH guidelines) for detecting an increased risk of early vascular aging (EVA). We additionally estimated the effects of the guidelines' definitions on the distribution of BP phenotypes and risk of EVA. METHODS:A total of 1026 men and women (aged 20-30 years) were included. The primary data collected included office- and ambulatory blood pressure (ABPM) measurement, and carotid-femoral pulse wave velocity (PWV). The upper 25th percentile of PWV was regarded as having an increased risk of EVA. The frequencies of hypertension and BP phenotypes were calculated according to both guidelines and correlated with TOI by multiple linear regression. Receiver operating characteristic (ROC) curves were constructed to determine the best BP threshold for detecting increased risk of EVA. RESULTS:Pulse wave velocity was associated with all pathological BP phenotypes (SHT, WCHT and MHT), based on the ESC/ESH and with SHT and WCHT based on the ACC/AHA criteria (all p<0.024). CONCLUSION:The ESC/ESH criteria, but not the ACC/AHA criteria, is sensitive to identify all BP phenotypes. The lower thresholds advised by the ACC/AHA guidelines however seem to favour early detection of increased risk for EVA.

BACKGROUND:Glomerular filtration rate (eGFR) derived from serum creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys) by race-free equations are recommended staging chronic kidney disease (CKD). The current study aimed to compare these race-free eGFR equations for screening for low-grade CKD in Blacks and non-Blacks and to evaluate their association with mortality. METHODS:Race-free eGFR equations were evaluated in four studies with specific inclusion criteria based on the original research goals: African-PREDICT (341/380 healthy Black/White South Africans), FLEMENGHO (709 White community-dwelling Flemish), NHANES (1760/7931 Black and non-Black adult Americans), and 401 Black African patients hospitalised in Mbuji Mayi, Democratic Republic of Congo. The intraclass correlation coefficient and Bland and Altman statistics were used to assess consistency between eGFR equations and multivariable logistic or Cox regression to evaluate their association with mortality. RESULTS:Intraindividual discordance between eGFRs was larger in Black than non-Black NHANES and African-PREDICT participants. In NHANES, eGFRcr-cys was greater than eGFRcr, but smaller than eGFRcys, and replacing eGFRcr-cys by eGFRcr moved 25% Blacks and 15% non-Blacks to a higher (worse) eGFR KDIGO stage. In African-PREDICT and FLEMENGO, half of the measured creatinine clearance to eGFR ratios fell outside the expected 1.1-1.2 band. In NHANES, multivariable hazard ratios for total and cardiovascular mortality in relation to CKD grade were all lower than unity for grade-1 CKD and greater than unity for grade ≥3 (p < 0.0001) without any racial difference (0.11≤p ≤ 0.98). These NHANES findings were consistent, if CKD stage was replaced by eGFR and in subgroup analyses. Whereas eGFRcys and eGFRcr-cys refined models, eGFRcr did not. CONCLUSIONS:The NHANES mortality outcomes support the use of eGFRcys and eGFRcr-cys. However, large intraindividual variability between eGFR estimates may lead to KDIGO eGFR stage misclassification and calls for caution in the opportunistic or systematic screening for CKD in asymptomatic individuals with prevention as objective.

The growing burden of cardiovascular diseases has become a significant concern in both adult and youth populations. Urinary biomarkers of kidney function could provide useful insights that may aid in the early identification of individuals at higher risk of adverse cardiovascular outcomes. This systematic review aimed to assess associations between urinary biomarkers of kidney function and different measures of cardiovascular health. PubMed, Scopus, and EBSCOhost were searched for articles published between January 2018 and December 2023. Studies exploring associations between urinary kidney biomarkers (alpha-1 microglobulin (uA1M), neutrophil gelatinase-associated lipocalin (uNGAL), uromodulin (uUMOD) and CKD273 classifier) and measures of cardiovascular health (blood pressure and markers of target organ damage) were included. We identified 1186 articles, with 22 studies eligible for inclusion. Among 12 studies reporting associations between uA1M and measures of cardiovascular health, six studies indicated positive associations with office blood pressure and three studies observed associations with different markers of target organ damage. Out of the nine studies that explored the link between uUMOD and cardiovascular health parameters, four found negative associations between uUMOD and blood pressure. With regard to uNGAL, only two out of the seven studies analysed reported varying associations with blood pressure, while neither of the two studies focusing on CKD273 observed any statistically significant results. Biomarkers of kidney tubule function, represented by uA1M and uUMOD, are relevant in the setting of cardiovascular health and should be assessed for utilisation in clinical practice to identify adverse cardiovascular outcomes at an early stage allowing for timely intervention.

BACKGROUND AND AIMS:A fibre rich diet is linked to a healthier cardiometabolic profile and may promote fatty acid oxidation to lower acylcarnitine accumulation. This study aimed to determine whether total dietary fibre intake was related to cardiometabolic risk markers as well as acylcarnitine levels in apparently healthy adults, which concurrently may be related to blood pressure (BP). METHODS AND RESULTS:This study included 983 adults from the African-PREDICT study (aged 24 ± 3 years). Total fibre intake was determined using 24-hr dietary recalls, and 24-hr ambulatory BP was measured. Acylcarnitines were analysed in spot urine samples using liquid chromatography-tandem mass spectrometry-based metabolomics. Lower dietary fibre intake was related to a higher waist circumference (WC) and body mass index (BMI) as well as higher total cholesterol, low-density lipoprotein-cholesterol (LDL-C), triglycerides, Apo-lipoprotein-B, C-reactive protein (CRP), free carnitine, and short-chain acylcarnitine (C2-, C4- and C5-carnitine) levels (all p trend <0.05). Concurrently, all traditional cardiometabolic risk markers (WC, BMI, total cholesterol, LDL-C, triglycerides, Apo-B, and CRP) correlated positively with 24-hr BP. In multiple regression analyses, 24-hr SBP was associated with WC (β = 0.44; p < 0.001) and total energy intake (β = 0.096; p = 0.002), while 24-hr DBP was associated with WC (β = 0.283; p < 0.001), triglyceride levels (β = 0.085 p = 0.008), dietary fibre intake (β = -0.120; p < 0.001) and total energy intake (β = 0.128; p < 0.001). There was no relationship between acylcarnitine levels and 24-hr BP. CONCLUSION:We demonstrate that participants consuming a higher fibre diet had a more favourable metabolic profile than those consuming a low fibre diet, which was ultimately associated with lower BP.

Cardiovascular risk factors are known to contribute to cardiovascular disease (CVD) development by inducing endothelial activation, increasing oxidative stress and pro-inflammation. The early interaction between these pathways and individual cardiovascular (CV) risk factors is poorly understood. We profiled a range of circulating endothelial function, oxidative stress and inflammatory biomarkers and explored their associations with individual CV risk factors in young (20–30 years, n = 1196) adults without self-reported chronic conditions or medication use. Participants were stratified into CV risk factor groups based on blood pressure, anthropometrical measurements, biochemical analyses and questionnaire data. We identified several differences in biomarker levels between control (without any CV risk factors) and individual CV risk factor groups and confirmed independent associations of these biomarkers with individual risk factors (all p < 0.05). Greater central adiposity was mainly associated with a pro-inflammatory profile (interleukin-6, C-reactive protein and fibrinogen), but also with endothelial activation and oxidative stress (plasminogen activator inhibitor-1 and reactive oxygen species). High low-density lipoprotein cholesterol levels and alcohol use were associated with endothelial activation (P-selectin), while smoking, low high-density lipoprotein cholesterol levels and alcohol use were related to markers of inflammation (growth differentiation factor-15 and monocyte chemoattractant protein-1). Glycated hemoglobin levels and blood pressure were positively associated with glutathione reductase activity, while blood pressure also associated positively with interleukin-10 levels. Our data provides insight into the initial underlying mechanisms associated with early CVD development in young individuals exposed to different cardiovascular risk factors.

AbstractThe exposure to modifiable risk factors at young ages have been linked to premature fatal and non-fatal cardiovascular and kidney outcomes. The use of urinary metabolomics has shown strong predictability of kidney function and cardiovascular disease (CVD). We therefore determined the associations between estimated glomerular filtration rate (eGFR) and urinary metabolites in young adults with and without CVD risk factors. Apparently healthy Black and White sexes were included (aged 20–30 years) and categorised by the presence or absence of risk factors, i.e., obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036), CVD risk clusters (i.e. presenting with 1 CVD risk factor (N = 344), 2 CVD risk factors (N = 360) and 3 + CVD risk factors (N = 332)) and the control group (N = 166). eGFR was calculated with CKD-EPI equations. A targeted metabolomics approach using liquid chromatography-tandem mass spectrometry was used to measure amino acids and acylcarnitines. Lower cystatin C-based eGFR were indicated in the CVD risk group, 2 and 3 + CVD risk clusters compared to the control group (all P ≤ 0.033). In the CVD risk group, eGFR associated positively with histidine, lysine, asparagine, glycine, serine, glutamine, dimethylglycine, threonine, alanine, creatine, cystine, methionine, tyrosine, pyroglutamic acid, leucine/isoleucine, aspartic acid, tryptophan, glutamic acid, free carnitine, acetylcarnitine, propionylcarnitine, isovalerylcarnitine, octanoylcarnitine and decanoylcarnitine (all P ≤ 0.044), with similar results found in the CVD risk clusters, particularly the 2 CVD risk cluster. eGFR was positively associated with metabolites linked to aromatic amino acid and branched-chain amino acid metabolism, energy metabolism and oxidative stress. These findings may indicate altered reabsorption of these metabolites or altered metabolic regulation to preserve renal health in the setting of CVD risk factors at this young age without established CVD.

Introduction:Single-nucleotide polymorphisms (SNPs) in the UMOD -PDILT genetic locus are associated with chronic kidney disease (CKD) in European populations, through their effect on urinary uromodulin (uUMOD) levels. The genetic and nongenetic factors associated with uUMOD in African populations remain unknown. Methods:Clinical parameters, 3 selected UMOD-PDILT SNPs and uUMOD levels were obtained in 1202 young Black and White adults from the African-PREDICT study and 1943 middle aged Black adults from the PURE-NWP-SA study, 2 cross-sectional, observational studies. Results:Absolute uUMOD and uUMOD/creatinine levels were lower in Black participants compared to White participants. The prime CKD-risk allele at rs12917707 was more prevalent in Black individuals, with strikingly more risk allele homozygotes compared to White individuals. Haplotype analysis of the UMOD-PDILT locus predicted more recombination events and linkage disequilibrium (LD) fragmentation in Black individuals. Multivariate testing and sensitivity analysis showed that higher uUMOD/creatinine associated specifically with risk alleles at rs12917707 and rs12446492 in White participants and with higher serum renin and lower urine albumin-to-creatinine ratio in Black participants, with a significant interaction of ethnicity on the relationship between all 3 SNPs and uUMOD/creatinine. The multiple regression model explained a greater percentage of the variance of uUMOD/creatinine in White adults compared to Black adults (23% vs. 8%). Conclusion:We evidenced ethnic differences in clinical and genetic determinants of uUMOD levels, in particular an interaction of ethnicity on the relationship between CKD-risk SNPs and uUMOD. These differences should be considered when analyzing the role of uromodulin in kidney function, interpreting genome-wide association studies (GWAS), and precision medicine recommendations.

This sub-study of the African Prospective Study on the Early Detection and Identification of Cardiovascular Disease and Hypertension (African-PREDICT) explored possible early psychological predictors of change in blood pressure. In a sample of normotensive at baseline black and white South Africans ( n = 105; mean age at baseline 24.93), this study investigated the relationship between personality traits, coping strategies, and 24-hour ambulatory blood pressure measured at baseline and 5-year follow-up. Another aim was to investigate a possible mediating effect of coping strategies on the relationship between personality traits and change in blood pressure. Extraversion, agreeableness, openness, and problem-solving skills were identified as possible protective factors against cardiovascular risk, confirming previous research in this regard. However, the effect of these was different for gender and ethnic subgroups. Preconditions for a possible mediation role for coping in the relationship between personality and change in blood pressure were not met. Future research should further explore gender and ethnic differences in the relationship between personality, coping, and cardiovascular health.

Blacks are more prone to salt-sensitive hypertension than Whites. This cross-sectional analysis of a multi-ethnic cohort aimed to search for proteins potentially involved in the susceptibility to salt sensitivity, hypertension, and hypertension-related complications. The study included individuals enrolled in African Prospective Study on the Early Detection and Identification of Cardiovascular Disease and Hypertension (African-PREDICT), Flemish Study of the Environment, Genes and Health Outcomes (FLEMENGHO), Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers (PROVALID)-Austria, and Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform Trial (UPRIGHT-HTM). Sequenced urinary peptides detectable in 70% of participants allowed the identification of parental proteins and were compared between Blacks and Whites. Of 513 urinary peptides, 300 had significantly different levels among healthy Black ( n  = 476) and White ( n  = 483) South Africans sharing the same environment. Analyses contrasting 582 Blacks versus 1731 Whites, and Sub-Saharan Blacks versus European Whites replicated the findings. COL4A1, COL4A2, FGA, PROC, MGP, MYOCD, FYXD2, and UMOD were identified as the most likely candidates underlying the racially different susceptibility to salt sensitivity, hypertension, and related complications. Enriched pathways included hemostasis, platelet activity, collagens, biology of the extracellular matrix, and protein digestion and absorption. Our study suggests that MGP and MYOCD being involved in cardiovascular function, FGA and PROC in coagulation, FYXD2 and UMOD in salt homeostasis, and COL4A1 and COL4A2 as major components of the glomerular basement membrane are among the many proteins potentially incriminated in the higher susceptibility of Blacks compared to Whites to salt sensitivity, hypertension, and its complication. Nevertheless, these eight proteins and their associated pathways deserve further exploration in molecular and human studies as potential targets for intervention to reduce the excess risk of hypertension and cardiovascular complications in Blacks versus Whites.

ABSTRACTBiomarkers of kidney function, including glomerular, tubular, and fibrotic markers, have been associated with blood pressure in elderly populations and individuals with kidney and cardiovascular diseases. However, limited information is available in young adults. In this study, we compared levels of several kidney function biomarkers between normotensive and hypertensive young adults and explored the associations of these biomarkers with blood pressure within these groups. In this cross‐sectional assessment, twenty‐four‐hour (24‐h) blood pressure measurements of 1055 participants (mean age = 24.6 years) were used to classify hypertension as per the 2018 ESC/ESH guidelines. Biomarkers of kidney function included estimated glomerular filtration rate, urinary albumin, alpha‐1 microglobulin (uA1M), neutrophil gelatinase‐associated lipocalin (uNGAL), uromodulin (uUMOD), and the CKD273 classifier. All urinary biomarkers, except for the CKD273 classifier, were standardized for urinary creatinine (Cr). In the hypertensive group (61.0% White; 73.2% men), urinary albumin‐to‐creatinine ratio (uACR), uNGAL/Cr and uUMOD/Cr were lower than the normotensive group. In multiple regression analyses, 24‐h systolic blood pressure (SBP) (β = 0.14; p = 0.042), 24‐h diastolic blood pressure (DBP) (β = 0.14; p = 0.040), and 24‐h mean arterial pressure (MAP) (β = 0.16; p = 0.020) associated positively with uA1M/Cr in the hypertensive group, while 24‐h MAP positively associated with uACR (β = 0.17; p = 0.017). In exploratory factor analysis, positive associations of 24‐h DBP and 24‐h MAP with a factor pattern including tubular biomarkers were observed in the hypertensive group (24‐h DBP: β = 0.18; p = 0.026, 24‐h MAP: β = 0.17; p = 0.032). In the setting of hypertension, high perfusion pressure in the kidneys may play a role in the development of proximal tubule damage and promote early deterioration in kidney function in young adults.Trial Registration: ClinicalTrials.gov identifier: NCT03292094

The contrasting relationships of plant and animal protein intake with blood pressure (BP) may be partially attributed to the differential non-protein (e.g., saturated fat and fibre) and amino acid (AA) compositions. This study determined whether animal and plant protein intake were related to differential metabolomic profiles associated with BP. This study included 1008 adults from the African-PREDICT study (aged 20–30 years). Protein intake was determined using 24-h dietary recalls. Twenty-four-hour ambulatory BP was measured. Amino acids and acylcarnitines were analysed in spot urine samples using liquid chromatography-tandem mass spectrometry-based metabolomics. Participants with a low plant, high animal protein intake had higher SBP (by 3 mmHg, p = 0.011) than those with high plant, low animal protein intake (low-risk group). We found that the relationships of plant and animal protein intake with 24-h SBP were partially mediated by BMI and saturated fat intake, which were independently associated with SBP. Protein intake was therefore not related to SBP in multiple regression analysis after adjusting for confounders. In the low-risk group, methionine (Std. β = −0.217; p = 0.034), glutamic acid (Std. β = −0.220; p = 0.031), glycine (Std. β = −0.234; p = 0.025), and proline (Std. β = −0.266; p = 0.010) were inversely related to SBP, and beta-alanine (Std. β = −0.277; p = 0.020) to DBP. Ultimately a diet high in animal and low in plant protein intake may contribute to higher BP by means of increased BMI and saturated fat intake. Conversely, higher levels of urinary AAs observed in adults consuming a plant rich diet may contribute to lower BP.

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 in-flammatory score (including leptin, adiponectin, interleukin-6, interleukin-8, interleukin-10, and tumour ne-crosis factor-alpha) 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-alpha (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.

Background and Aims: Hypertension is one of the most important and complex risk factors for cardiovascular diseases. Identifying biomarkers in hypertension may lead to better strategies to understand the development of hypertension. Biomarker discovery through the use of peptidomics may also provide essential information for the prediction and prevention of premature CVD development. Methods and Results: We included 78 hypertensive (based on 24-hour ambulatory blood pressure) and 79 normotensive age (20–30-years old), sex and ethnicity (62% black and 48% white) matched participants from the African-PREDICT study. Urinary peptidomics were analysed with capillary electrophoresis time-of-flight mass spectrometry. Hypertension-specific peptide profiles were combined into a single summary multidimensional classifier. When comparing the peptide data between the normotensive and hypertensive groups, 354 peptides were nominally differentially expressed (Wilcoxon p-value less than 0.05). Nonetheless, only three peptides (ID10000 (SHANK1), ID8939 (unsequenced) and ID6841 (unsequenced)) remained significant after rigorous adjustments for multiple comparisons (maxT test) and were more abundant in the hypertensive compared to the normotensive group (all p-value less than 0.001). Furthermore, the 15 nominally most significant peptides (all p-value less than or equal to 0.0013) were combined into a unifying score which differed significantly between the groups (p-value less than 0.001) but had an insufficient prediction capability for hypertension. Conclusion: Apart from differential expression of single peptides in hypertensive adults, including ID10000 (SHANK1), no unifying urinary hypertension peptidomics profile was identified with a sufficient prediction capability. Our findings suggest that a downstream multimarker approach cannot reliably represent a complex multifactorial condition such as hypertension.

Increased arterial stiffness is related to early vascular aging and is an independent predictor for cardiovascular disease and mortality. Molecular mechanisms underlying increased arterial stiffness are largely unexplored, especially at the proteome level. We aimed to explore the relationship between pulse wave velocity and urinary proteomics. We included 919 apparently healthy (no chronic illnesses) Black and White men and women (equally distributed) between 20 and 30 years from the African-PREDICT study. Capillary electrophoresis time-of-flight mass spectrometry was used to analyze the urinary proteome. We measured the carotid-femoral pulse wave velocity to estimate arterial stiffness. In the total group, pulse wave velocity correlated positively with collagen-derived peptides including collagen types I, II, III, IV, V, and IX and inversely with collagen type XI (adjusted for mean arterial pressure). Regarding noncollagen-derived peptides, pulse wave velocity positively correlated with polymeric immunoglobulin receptor peptides (n = 2) (all q-value ≤0.05). In multivariable adjusted analyses, pulse wave velocity associated positively and independently with seven urinary peptides (collagen type I, n = 5) (all p-value ≤0.05). We found significant positive and independent associations between pulse wave velocity and the collagen type I-derived peptides, suggesting that dysregulation of collagen type I in the extracellular matrix scaffold could lead to early onset of increased arterial stiffness.