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The endogenous Na+/K+-ATPase inhibitor, marinobufagenin (MBG), strongly associates with salt intake and a greater left ventricular mass index (LVMi) in humans and was shown to promote cardiac fibrosis and hypertrophy in animals. The adverse effects of MBG on cardiac remodeling may be exacerbated with obesity, due to an increased sensitivity of Na+/K+-ATPase to MBG. This study determined whether MBG is related to the change in LVMi over time in adults with a body mass index (BMI) ≥30 kg/m2 (obese) and <30 kg/m2 (non-obese). The study followed 275 healthy participants (aged 20–30 years) from the African-Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT) study over 4.5 years. At baseline, we measured 24 h urine MBG excretion. MBG levels were positively associated with salt intake. LVMi was determined by two-dimensional echocardiography at baseline and after >4.5 years. With multivariate adjusted analyses in obese adults (N = 56), we found a positive association of follow-up LVMi (Adjusted (Adj.) R2 = 0.35; Std. β = 0.311; p = 0.007) and percentage change in LVMi (Adj. R2 = 0.40; Std. β = 0.336; p = 0.003) with baseline MBG excretion. No association of LVMi (Adj. R2 = 0.37; p = 0.85) or percentage change in LVMi (Adj. R2 = 0.19; p = 0.68) with MBG excretion was evident in normal weight adults (N = 123). These findings suggest that obese adults may be more sensitive to the adverse cardiac effects of MBG and provide new insight into the potential role of dietary salt, by way of MBG, in the pathogenesis of cardiac remodeling in obese individuals

Hypertension is common in black populations and is known to be associated with low nitric oxide (NO) bioavailability. We compared plasma and urinary NO-related markers and plasma creatine kinase (CK) levels between young healthy black and white adults along with the associations of these markers with the urinary albumin-to-creatinine ratio (uACR), which is a surrogate marker of endothelial and kidney function. We included 1105 participants (20–30 years). We measured the uACR, plasma CK, plasma and urinary arginine, homoarginine, asymmetric (ADMA) and symmetric dimethylarginine (SDMA), urinary ornithine/citrulline, nitrate and nitrite, and malondialdehyde (MDA). In addition, the urinary nitrate-to-nitrite ratio (UNOxR) was calculated and used as a measure of circulating NO bioavailability. The uACR was comparable between the groups, yet the black group had lower urinary nitrate (by −15%) and UNOxR values (by −18%) (both p ≤ 0.001), higher plasma (by +9.6%) and urinary (by +5.9%) arginine (both p ≤ 0.004), higher plasma (by +13%) and urinary (by +3.7%) ADMA (both p ≤ 0.033), and higher CK (by +9.5%) and MDA (by +19%) (both p < 0.001) compared with white adults. Plasma and urinary homoarginine were similar between the groups. In the multiple regression analysis, we confirmed the inverse associations of the uACR with both plasma (adj. R2 = 0.066; β = −0.209; p = 0.005) and urinary (adj. R2 = 0.066; β = −0.149; p = 0.010) homoarginine and with the UNOxR (adj. R2 = 0.060; β = −0.122; p = 0.031) in the black group only. The overall less favorable NO profile and higher CK and MDA levels in the black cohort along with the adverse associations with the uACR may reflect the vulnerability of this cohort to the early development of hypertension

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

Background and aims Increased left ventricular mass is an independent predictor for cardiovascular events, and shown to be higher in black than white populations. To gain a better understanding of early factors contributing to increased left ventricular mass in young black adults, we investigated metabolomic profiles, identified and compared metabolites that associated with left ventricular mass index in healthy black and white adults. Methods and results We included normotensive black and white participants from the African-PREDICT study, with data on urinary metabolomics and echocardiography. Urinary metabolites were measured using three different analytical platforms. Univariate statistical analyses, including independent t-test (adjusted for multiple comparisons), effect size (d ≥ 0.3) and single regression analyses were used to identify metabolites. When comparing the black and white groups, the black group had higher central systolic blood pressure (p > 0.005), whereas left ventricular mass index was similar between the groups (p = 0.97). Three from a total of 192 metabolites were identified to be more abundant (p < 0.046) and inversely associated with left ventricular mass index in the black group only: hydroxyproline (β = −0.22; p = 0.045), glycine (β = −0.20; p = 0.049) and trimethylamine (β = −0.21; p = 0.037). Conclusion Higher urinary levels of hydroxyproline, glycine and trimethylamine were inversely associated with left ventricular mass index in the black adults only. Hydroxyproline and glycine are important in maintaining healthy collagen turnover and stability in the heart. Our results may reflect an increase in collagen biosynthesis and collagen deposition in the left ventricle due to higher central systolic blood pressure in the black population

Background Physical inactivity contributes significantly to the development of obesity‐related cardiovascular disease. Adiposity may lead to reduced heart rate variability (HRV), whereas increased physical activity (PA) has the potential to improve autonomic activity. These associations remain largely unexplored in healthy individuals. We therefore investigated whether adiposity and physical activity (PA) are associated with reduced heart rate variability (HRV) in young adults. Materials and methods We examined 403 black and 461 white healthy adults (aged 20‐30 years) for HRV, including standard deviation of normal RR intervals (SDNN) and root mean square of successive differences (RMSSD). We measured adiposity, PA levels and blood pressure (BP). Body mass index (BMI) of ≥ 30 kg/m2 indicated obesity. Results Participants with obesity had lower mean HRV than normal weight (SDNN [95% CI]; 138 [131‐145]s vs 161 [158‐165]ms), where those with the highest PA had higher SDNN (164 [160‐169]ms) and RMSSD (51 [49‐53]ms) than the least active individuals (150 [146‐155]s) and 46 [44‐48]ms)(all P < .01). BMI, waist circumference and body fat associated with lower SDNN (P < .001). With each unit increase of vigorous PA, a favourable higher RMSSD was found (P < .05). One unit increase in diastolic BP was associated with decreased SDNN and RMSSD (P < .001). These findings remained significant in multivariable‐adjusted analyses. Conclusions Adiposity and low PA associated independently with depressed autonomic activity in young healthy adults. Sympathovagal imbalance seems to already contribute to elevated diastolic BP at young ages. Our study supports population‐based prevention programmes in young adults, improving PA and healthy diet, to curb the development of cardiovascular disease

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 (β = 0.076; p = 0.027), age (β = 0.096; p = 0.006), low socio-economic status (β = −0.12; p = 0.003), physical inactivity (β = −0.18; p < 0.0001), tumour necrosis factor-alpha (β = 0.28; p < 0.0001) and cotinine (β = 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

Proteinic arginine dimethylation (PADiMe) is a major post-translational modification. Proteolysis of asymmetric and symmetric PADiMe products releases asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), respectively, two endogenous atherogenic substances. SDMA, ADMA, and its major metabolite dimethylamine (DMA) are eliminated by the kidney. The urinary concentrations of DMA+ADMA, SDMA, and DMA+ADMA+SDMA are useful measures of the whole-body asymmetric and symmetric PADiMe, respectively. Urinary (DMA+ADMA)/SDMA is an index of the asymmetric to symmetric PADiMe balance. In two bi-ethnic studies, the ASOS (39 black boys, 41 white boys) and the African-PREDICT (292 black young men, 281 white young men) studies, we investigated whether ethnicity is a major determinant of PADiMe, and whether PADiMe is associated with blood pressure and ethnicity-dependent growth and inflammatory factors, including HDL. DMA, ADMA, and SDMA were measured in spot urine samples by gas chromatography–mass spectrometry, and their excretion was corrected for creatinine excretion. In black boys, creatinine-corrected DMA, DMA+ADMA, and DMA+ADMA+SDMA concentrations were lower by 11.7%, 9.5%, and 7.6% (all p < 0.05), respectively, compared to the white boys, and 3.4%, 2.0%, and 1.8% lower (all p < 0.05), respectively, in black compared to white men. (DMA+ADMA)/SDMA did not differ between black boys and black men, but was higher in white boys compared to white men. ADMA did not differ between black and white boys, or between black and white men. Creatinine-corrected SDMA excretion was lower in black boys compared to white boys (by 8%) and to white men (by 3.1%). None of the PADiMe indices were associated with blood pressure in either study. IGF-binding protein 3 correlated inversely with all PADiMe indices in the black men only. Our study showed that asymmetric proteinic arginine dimethylation is higher in white boys than in black boys, and that this difference disappears in adu

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

Several life-threatening complications can develop in the ascending aorta, which include dissection or rupture of an aortic aneurysm. Those at high risk of developing such complications can be categorised according to the types of thoracic aneurysms. Older individuals (age >59 years), and especially men, with atherosclerotic disease including hypertension are vulnerable to develop supravalvular aortic aneurysms (above the sinuses of Valsalva).1 Aortic root (AR) aneurysms occur mostly in younger individuals (age <50 years) and affect men and women equally.1,2 In addition, AR aneurysms are believed to be of idiopathic origin, but often occur in specific conditions such as Marfan’s syndrome, Ehler Danlos syndrome, bicuspid valve connective tissue disorders or in rare bacterial infections of the endocardium.3 The echocardiographic measurement of the AR diameter remains a clinical marker of aortic root dilation (ARD). A dilated ascending aorta of 50 mm or greater is considered a risk factor for dissection or aortic rupture.4

Background: The impact of a sedentary and unhealthy lifestyle on cardiovascular health is well-documented, however the current obesity and hypertension trends among children is concerning. The ExAMIN Youth SA study aims to investigate the impact of lifestyle behaviors (physical fitness/activity, dietary intake and psychosocial factors) involved in early vascular aging among South African children. Methods: This study is an analytical, multidisciplinary, observational cohort study in a school-based setting. We aim to phenotype a cohort of ∼1,000 primary school children (black and white boys and girls between ages 5–9 years) based on current clinical childhood conditions including hypertension and obesity. The primary phenotype is large artery stiffness and retinal microvascular diameters, both biomarkers of early vascular aging. The risk factors and mediators of early vascular aging and also responsible for the clinical conditions include physical inactivity, unhealthy diet, and life stress. Additionally, urinalysis and salivary analyses will be performed to identify biomarkers related to the pathophysiology of early vascular aging. Discussion: In line with the growing prevalence of obesity and hypertension responsible for the development of early vascular aging from childhood to adulthood, this study will address the critical areas in which we observe unfavorable arterial modulation related to dietary behaviors, physical inactivity, and early life stress. Implementation of novel biological markers may further contribute to our understanding of early cardiovascular adaptations in childhood, and aid in the development of primary prevention programs

The New Investigators Committee (NIC) of the International Society of Hypertension (ISH) is a dynamic group of junior doctors and scientists, actively involved in various society activities. This report highlights the events (scientific meetings and summer schools) and activities (social media, mentorship and networking) during 2019 including May Measurement Month and collaborative efforts with the ISH Women in Hypertension Research Committee (WiHRC). The ISH NIC is proud to sponsor awards for outstanding work by junior and emerging researchers at hypertension conferences and also provides opportunities to showcase their work on our social media features such as ‘Our Fellows Work’ and the New Investigator Spotlight of the month. In 2020, the ISH NIC aims to promote women in leadership roles and to foster strong collaborations with and between society committees and other scientific organizations

Oxidative stress and inflammation has been implicated in arterial stiffness, and hypertension development. Oxidative stress may interfere with normal vascular function by inactivation of NO and/or the production of endothelin-1. Limited information exists regarding the link of NO and endothelin-1 with oxidative stress markers in black South Africans, a population known for early vascular compromise and increasing prevalence of hypertension. Our objective was to compare variables implicated in vascular function namely NO metabolites, endothelium-1 and markers of inflammation and oxidative stress in a biethnic South African population. We also investigated the association of endothelin-1 with markers of oxidative stress implicated in arterial stiffness and endothelial function as well as if an increase in endothelin-1 levels over time predict a change in markers implicated in vascular function

Corrigendum to: May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension [Eur Heart J 2019;40:2006–2017]. In the original version of this article, a small number of the MMM Investigators were missing or recorded incorrectly, and an author's affiliation was incorrect. This has now been corrected online and in print. The authors apologise for the error.

The World Health Organization (WHO) has set a global target to reduce physical inactivity by 10% by 2025,1 but according to a pooled analysis of 1.9 million participants during 2001 to 2016, the progress of the WHO target is “not on track”.2 This analysis indicated a prevalence of 28% of adults, or approximately 1.4 billion people worldwide, to be physically inactive.2 Sedentary behaviour and poor physical fitness are described as major modifiable risk factors and also implicated in cardiovascular disease morbidity and mortality.3 The enormous adversity of physical inactivity on the human body ranges from increased oxidative stress, proinflammation, subcutaneous and visceral adiposity, high blood pressure and subsequently type 2 diabetes mellitus, to coronary artery disease, heart failure, stroke as well as various cancers and mental disorders.4

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

Early cardiovascular disease (CVD) onset can be inflicted by familial cardiovascular and lifestyle risk factors. We aimed to compare phenotypic characteristics and explore associations between oxidative stress and vascular function in boys stratified by maternal cardiovascular and lifestyle risk. We included 40 Black and 41 White boys (ages 6–8 years), along with the biological mother of each child. The study population was divided into two groups (nonmaternal risk vs. maternal risk) according to maternal risk predetermined by their selfreported cardiovascular and lifestyle risk factors. Pulse wave velocity (PWV) was measured at various sites and blood pressures were recorded. Urine samples were collected for analyses of thiobarbituric acid-reactive substances (TBARS), 8-hydroxy-2-deoxy guanosine (8-OHdG), albumin, and creatinine. Higher levels of urinary albumin to creatinine ratio (uACR) were found in the maternal risk group compared to the nonmaternal risk group (p = .038). Multiple regression analysis in the maternal risk group revealed diastolic blood pressure (R2 = 0.159; β = 0.293; p = .050), carotid femoral PWV (R2 = 0.158; β = 0.297; p = .038) and carotid dorsalis pedis PWV (adj R2 = 0.322; β = 0.505; p < .001) to be positively associated with TBARS, while an inverse association of uACR (R2 = 0.161; β = −0.261; p = .046) with TBARS was observed. Also, in the maternal risk group, independent associations of DBP (R2 = 0.273; β = 0.289; p = .040) and uACR (R2 = 0.283; β = 0.268; p = .027) with 8-OHdG were indicated. In boys, as young as 6 years of age, oxidative stress related to arterial stiffness and diastolic blood pressure was observed. This association was only evident in boys with linked maternal lifestyle and cardiovascular risk factors, suggesting potential family-related early onset of cardiovascular risk

Background Oestradiol has a protective effect on coronary artery health in women but the effect it has on men, is controversial. A translational approach was followed to assess whether sex hormone levels are associated with silent myocardial ischemia (SMI) and hypertension risk over a 3 year period. Methods Participants included 89 Black and 91 White men (aged 21–63 years) participating in both phases of the Sympathetic activity and Ambulatory Blood Pressure in Africans prospective study. Fasting blood samples, ambulatory blood pressure and 2-lead ECG recordings were obtained. Results No difference in the levels of the various baseline serum T fractions between the two ethnic groups occurred. Oestradiol of the Black men increased by 54.2% compared to a decrease of 24.1% in the White men. Changes in total oestradiol (adjusted R2 = 0.33, β = − 0.31, p = 0.023) and free oestradiol (adjusted R2 = 0.34, β = − 0.33, p = 0.019) were inversely associated with changes in SMI in the Black men but not in White men. Baseline serum nitric oxide metabolites were inversely associated with ΔSMI in the Blacks only (adjusted R2 = 0.33, β = − 0.28, p = 0.047). Chronic SMI was associated with 24 h hypertension in Blacks [cut point 1.5 events: Area under the curve 0.71 (95% CI: 0.60, 0.82); p = 0.006; with sensitivity/specificity 44%/94%]. Conclusions Chronic SMI events facilitated future ischemic heart disease in Black men. Up-regulated free oestradiol seems to be involved in the protection of the heart against SMI and hypertension risk in Black but not in White men. A similar protective role for testosterone could however not be shown

Background Hypertensive heart disease is a rising concern, especially among black South African women. As high sensitivity cardiac troponin T (cTnT) is a marker of cardiomyocyte damage, we determined the potential link of (i) systemic endothelial dysfunction (reflected by urinary albumin-to-creatinine ratio), (ii) large artery stiffness, (iii) cardiac volume load (estimated by the N-terminal prohormone B-type natriuretic peptide (Nt-proBNP)), and (iv) ECG left ventricular hypertrophy in post-menopausal black women. Methods In 121 (50 normotensive and 71 hypertensive) black women (mean age: 60.6 years), basic cardiovascular assessments including blood pressure and ECG were performed, along with plasma and urinary biomarkers including cTnT. Results The cTnT levels (p=0.049) along with Nt-proBNP (p=0.003), pulse pressure (p<0.0001) and the Cornell product (p=0.030) were higher in hypertensive than normotensive women. Only in hypertensive women, was cTnT independently associated with urinary albumin-to-creatinine ratio (β=0.25; p=0.019), pulse pressure (β=0.31; p=0.019), Nt-proBNP (β=0.47; p<0.0001) and Cornell product (β=0.31; p=0.018). An independent association between albumin-to-creatinine ratio and cTnT was also evident in normotensive women (β=0.34; p=0.037). Conclusion We found cTnT to be a useful marker in an elderly black population relating to several measures of cardiovascular deterioration – from subclinical endothelial dysfunction to left ventricular hypertrophy

"Background: Oestradiol has a protective effect on coronary artery health in women but the effect it has on men, is controversial. A translational approach was followed to assess whether sex hormone levels are associated with silent myocardial ischemia (SMI) and hypertension risk over a 3 year period. Methods: Participants included 89 Black and 91White men (aged 21 – 63years) participating in bothphases of the Sympathetic activity and Ambulatory Blood Pressure in Africans prospective study. Fasting blood samples, ambu- latory blood pressure and 2-lead ECG recordings were obtained. Results: No difference in the levels of the various baseline serum T fractions between the two ethnic groups occurred. Oestradiol of the Black men increased by 54.2% comparedto a decrease of24.1% in the White men.Changes in total oestradiol (adjusted R2=0.33, β = − 0.31, p = 0.023) and free oestradiol (adjusted R2=0.34, β = − 0.33, p = 0.019) were inversely associated with changes in SMI in the Black men but not in White men. Baseline serum nitric oxide metabolites were inversely associated with Δ SMI in the Blacks only (adjusted R2=0.33, β = − 0.28, p = 0.047). Chronic SMI was associated with 24 h hypertension in Blacks [cut point 1.5 events: Area under the curve 0.71 (95% CI: 0.60, 0.82); p = 0.006; with sensitivity/specificity 44%/94%]. Conclusions: Chronic SMI events facilitated future ischemic heart disease in Black men. Up-regulated free oestradiol seems to be involved in the protection of the heart against SMI and hypertension risk in Black but not in White men. A similar protective role for testosterone could however not be shown."

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the human immunodeficiency virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa.

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

Background Fibulin-1 and soluble urokinase-type plasminogen activator receptor (suPAR) emerged as mediators in the development of sclerotic disease. SuPAR along with C-reactive protein (CRP) and albumin delineate inflammatory processes associated with extracellular matrix turnover in atherosclerosis. We explored the independent relationship of fibulin-1 with these inflammatory markers in a bi-ethnic South African population. Methods This study included 290 Africans (men: n = 130 and women: n = 160) and 343 sex- and age-matched Caucasians (men: n = 160 and women: n = 183). Serum fibulin-1, suPAR, CRP and albumin levels were measured along with conventional cardiovascular and metabolic variables. Results In both single and age-adjusted regression analyses, fibulin-1 correlated with both suPAR and albumin in African men and with suPAR in Caucasian men. These findings were absent in women. In multivariate regression analysis, these associations were confirmed in African men (R$^2$ = 0.22; β=0.329; p < 0.001) and Caucasian men (R$^2$ = 0.14; β=0.234; p = 0.008). Fibulin-1 independently associated positively with suPAR in all men, but inversely with albumin in African men only. Conclusions These results are indicating the presence of potential subclinical inflammation (suPAR) within the extracellular matrix of endothelial tissue, contributing to the potential onset of cardiac fibrosis or vascular sclerosis among these South African men with lower albumin levels

Evidence of the relationship between left ventricular hypertrophy and urinary albumin excretion is contradictory and limited in black adults in whom hypertensive heart disease is common. We aimed to investigate the relationship between subclinical left ventricular hypertrophy and albuminuria in non diabetic hypertensive blacks. Urinary albumin to creatinine ratio (UACR) was determined from 8 hour overnight urine collection. We recorded ambulatory blood pressure and 12 lead electrocardiogram "during a typical working day. Cornell product (P ¼ .002), UACR (P ¼ .042), 24 hour systolic pressure (P < .0001), and 24 hour pulse pressure (P < .0001) were higher in the hypertensive group. Cornell product was associated with UACR in single (r ¼ 0.25; P ¼ .012), partial (P trend ¼ .002), and multiple regression (b ¼ 0.326; P ¼ .0005) analyses in the hypertensive group only, even below the threshold for microalbuminuria and independent of 24 hour systolic pressure. Urinary albumin excretion is associated with subclinical left ventricular hypertrophy in non diabetic hypertensive blacks and may be a useful marker of early cardiovascular disease in blacks. J Am Soc Hypertens 2015;9(2):115 122. 2015 American Society of Hypertension.

Various studies indicate a relationship between increased oxidative stress and hypertension, resulting in increased DNA damage and consequent excretion of 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG). The aim of this study was to compare urinary 8-oxodG levels in African and Caucasian men and to investigate the association between ambulatory blood pressure (BP) and pulse pressure (PP) with 8-oxodG in these groups. We included 98 African and 92 Caucasian men in the study and determined their ambulatory BP and PP. Biochemical analyses included, urinary 8-oxodG, reactive oxygen species (ROS) (measured as serum peroxides), ferric reducing antioxidant power (FRAP), total glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) activity. The African men had significantly higher systolic (SBP) and diastolic blood pressure (DBP) (both p < 0.001). Assessment of the oxidative stress markers indicated significantly lower 8-oxodG levels (p < 0.001) in the African group. The African men also had significantly higher ROS (p = 0.002) with concomitant lower FRAP (p < 0.001), while their GSH levels (p = 0.013) and GR activity (p < 0.001) were significantly higher. Single and partial regression analyses indicated a negative association between urinary 8-oxodG levels with SBP, DBP and PP only in African men. These associations were confirmed in multiple regression analyses (SBP: R$^2$ = 0.41; β = −0.25; p = 0.002, DBP: R$^2$ = 0.30; β = −0.21; p = 0.022, PP: R$^2$ = 0.30; β = −0.19; p = 0.03). Our results revealed significantly lower urinary 8-oxodG in African men, accompanied by a negative association with BP and PP. We propose that this may indicate a dose-response relationship in which increased oxidative stress may play a central role in the up-regulation of antioxidant defence and DNA repair mechanisms

Background and aims Simple, low-cost central obesity measures may help identify individuals with increased cardiometabolic disease risk, although it is unclear which measures perform best in African adults. We aimed to: 1) cross-sectionally compare the accuracy of existing waist-to-height ratio (WHtR) and waist circumference (WC) thresholds to identify individuals with hypertension, pre-diabetes, or dyslipidaemia; 2) identify optimal WC and WHtR thresholds to detect CVD risk in this African population; and 3) assess which measure best predicts 5-year CVD risk. Methods and results Black South Africans (577 men, 942 women, aged >30years) were recruited by random household selection from four North West Province communities. Demographic and anthropometric measures were taken. Recommended diagnostic thresholds (WC > 80 cm for women, >94 cm for men; WHtR > 0.5) were evaluated to predict blood pressure, fasting blood glucose, lipids, and glycated haemoglobin measured at baseline and 5 year follow up. Women were significantly more overweight than men at baseline (mean body mass index (BMI) women 27.3 ± 7.4 kg/m2, men 20.9 ± 4.3 kg/m2); median WC women 81.9 cm (interquartile range 61–103), men 74.7 cm (63–87 cm), all P < 0.001). In women, both WC and WHtR significantly predicted all cardiometabolic risk factors after 5 years. In men, even after adjusting WC threshold based on ROC analysis, WHtR better predicted overall 5-year risk. Neither measure predicted hypertension in men. Conclusions The WHtR threshold of >0.5 appears to be more consistently supported and may provide a better predictor of future cardiometabolic risk in sub-Saharan Africa. •Obesity & CVD are increasing rapidly in Africa.•Low cost measures are needed to find those at risk.•Debate continues on the optimum Waist Circumference threshold for African adults.•Waist-to-height ratio predicts current & future CVD risk in South-African adults.•There is greater global agreement on the WHtR threshold (>0.5) for ris

Background: Fibulin-1, a circulating extracellular matrix glycoprotein, has been associated with arterial disease and elevated N-terminal prohormone B-type natriuretic peptide (NT-proBNP) in diabetes. Soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation, has been associated with subclinical atherosclerosis. Therefore, we aimed to explore the interplay between these biomarkers and mild to moderate aortic valve stenosis (AS). Methods: In 374 patients with mild to moderate AS, we investigated the relationship of fibulin-1 with NT-proBNP, levels ofsuPAR and the degree of AS at baseline and after one and four years of treatment with Simvastatin 40 mg and Ezetimibe 10 mg or placebo. Results: During treatment, fibulin-1 became more closely associated with NT-proBNP (byear0= 0.10, p = 0.08, byear1= 0.16, p = 0.005, byear4= 0.22, p,0.001) and suPAR (byear0= 0.05, p = 0.34, byear1= 0.16, p = 0.006, byear4 = 0.13, p = 0.03) at the expense of the association to aortic valve area index (AVAI) (byear0=20.14, p = 0.005, byear1=20.08, p = 0.11, byear4=20.06, p = 0.22) independently of age, gender, creatinine, and serum aspartate aminotransferase (Adj.R year02= 0.19, Adj.R year12= 0.22, Adj.R year42= 0.27). Fibulin-1 was unrelated to aortic regurgitation, left ventricular mass, and ejection fraction. In patients with baseline AVAI, 0.58 cm 2/m2(median value), fibulin-1 was more closely associated to NT-proBNP(byear0= 0.25, byear1= 0.21, byear4= .22, all p, 0.01), and suPAR (byear0= 0.09, p = 0.26, byear1 = 0.23, byear4= 0.21, both p, 0.01) independently of age, gender, AST and treatment allocation. Conclusions: Increased levels of fibulin-1 were independently associated with higher levels of suPAR and NT-proBNP especially in patients with lower AVAI, suggesting that fibulin-1 may be an early marker of AS as well as cardiac fibrosis secondarily to elevated left ventricular hemodynamic load

The prevalence of hypertension in sub-Saharan Africa is increasing rapidly, and treatment remains challenging. Although the use of l-carnitine in treatment has received much attention, studies reporting on physiological l-carnitine levels in hypertensives are limited. Our aim was to determine physiological levels of l-carnitine and acylcarnitines in African and Caucasian men, and to investigate associations between ambulatory blood pressure (BP) and carnitine levels. Participants included 101 African and 101 Caucasian teachers. Ambulatory BP measurements were conducted, and l-carnitine and acylcarnitine levels determined. African men showed significantly higher systolic BP (p < 0.001), diastolic BP (p < 0.001) and l-carnitine levels (p = 0.01). In both ethnic groups, partial regression analyses revealed a positive association between BP and l-carnitine, although in Caucasians it was with systolic (r = 0.20, p = 0.045), and in Africans with diastolic BP (r = 0.23, p = 0.023). After adjusting for confounders, an independent positive association between systolic (R 2 = 0.37, β = 0.12, p = 0.041) and diastolic BP (R 2 = 0.39, β = 0.14, p = 0.018) and l-carnitine and long-chain acylcarnitines (R 2 = 0.38, β = 0.17, p = 0.005 and R 2 = 0.39, β = 0.15, p = 0.011) were found, independent of ethnicity. Physiological l-carnitine levels were not only higher in Africans than in Caucasians but also above the expected reference range. Despite promising results on l-carnitine (and its short-chain derivatives) in hypertension treatment regimens, our findings paradoxically show that elevated BP is significantly associated with higher physiological l-carnitine and long-chain acylcarnitine levels.

Background: Low testosterone, acute and chronic stress and hypercoagulation are all associated with hypertension and hypertension-related diseases. The interaction between these factors and future risk for coronary artery disease in Africans has not been fully elucidated. In this study, associations of testosterone, acute cardiovascular and coagulation stress responses with fibrinogen and von Willebrand factor in African and Caucasian men in a South African cohort were investigated. Methods: Cardiovascular variables were studied by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum-, salivary testosterone and citrate coagulation markers were obtained from venous blood samples. Acute mental stress responses were evoked with the Stroop test. Results: The African group demonstrated a higher cardiovascular risk compared to Caucasian men with elevated blood pressure, low-grade inflammation, chronic hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress responses were demonstrated in African males. In multiple regression analyses, higher circulating levels of fibrinogen and VWF in Africans were associated with a low T environment (R2 0.24–0.28; p ≤ 0.01), but only circulating fibrinogen in Caucasians. Regarding endothelial function, a low testosterone environment and a profile of augmented α-adrenergic acute mental stress responses (diastolic BP, D-dimer and testosterone) were associated with circulating VWF levels in Africans (Adj R2 0.24; p b 0.05). Conclusions: An interdependence between acute mental stress, salivary testosterone, D-dimer and vascular responses existed in African males in their association with circulating VWF but no interdependence of the independent variables occurred with fibrinogen levels.

Objective and design: This cross-sectional study aimed to investigate associations between a marker of cardiac strain, the N-terminal prohormone B-type natriuretic peptide (NT-proBNP), and inflammation as reflected by either a conventional or novel inflammatory marker in a bi-ethnic South African cohort. Methods and subjects: We measured NT-proBNP, C-reactive protein (CRP) and plasma-soluble urokinase plasminogen activator receptor (suPAR) levels along with conventional biomarkers in black (n = 117) and white (n = 116) men. Results: NT-proBNP, CRP and suPAR levels were higher in black compared to white men. NT-proBNP was significantly associated with both CRP (r = 0.38; p = 0.001) and suPAR (r = 0.42; p,0.001) in black men only. After full adjustment in multiple regression analyses, the above associations of NT-proBNP with CRP (b = 0.199; p = 0.018) and suPAR (b = 0.257; p,0.01) were confirmed in black men. Conclusion: These results suggest that a low-grade inflammatory state as reflected by both a conventional and novel marker of inflammation may contribute to higher cardiovascular risk as reflected by the associations obtained with a marker of cardiac strain in black South African men

Background This study compared NT-proBNP levels and the association with cardiovascular markers between Africans and Caucasians from South Africa. Methods This cross-sectional study involved 201 Africans and 255 Caucasians from the North West province, South Africa. Serum NT-proBNP concentrations, blood pressure, pulse wave velocity and arterial compliance were measured. Results NT-proBNP levels were significantly higher (P < 0.001) in Africans than Caucasians, also after adjusting for gender, body mass index (BMI) and pulse wave velocity (P = 0.008). This significant difference became borderline significant after adjusting for systolic blood pressure (SBP) (P = 0.060), and non-significant after adjusting for arterial compliance (P = 0.35). In single regression, a significant positive correlation of NT-proBNP with SBP (r = 0.26; P < 0.001) and pulse pressure (PP) (r = 0.28; P < 0.001) were shown for Africans only. After multiple adjustments, the associations of NT-proBNP with SBP and PP remained significant in Africans (SBP: β = 0.187, P < 0.01; PP: β = 0.234, P < 0.001), with no significant associations in Caucasians. Conclusions NT-proBNP levels were higher in Africans than Caucasians, independently of BMI and gender. This difference was partly driven by higher SBP and lower arterial compliance in Africans. NT-proBNP was persistently associated with SBP and PP in Africans, but not in Caucasians. These associations may suggest early vascular changes contributing to cardiac alterations in Africans.

Objectives The N-terminal prohormone B-type natriuretic peptide (NT-proBNP) is involved in the regulation of volume load and secreted when systemic cardiac overload occurs. Fibulin-1 on the other hand is a component of many extracellular matrix proteins including those present in atherosclerotic lesions, expressed in elastin-containing fibres of blood vessels, and also in the heart. Due to an alarming prevalence of hypertensive heart disease in black South Africans, we investigated the associations of NT-proBNP with fibulin-1 and markers of arterial stiffness in Africans and Caucasians. Methods We included 231 Africans and 238 Caucasians from South Africa aged 22–77 years. Serum NT-proBNP and fibulin-1 levels were determined, and arterial compliance and pulse wave velocity were measured. Results Africans had significantly higher blood pressure and NT-proBNP levels than Caucasians and African men had higher fibulin-1 levels than Caucasian men. In single regression analysis, NT-proBNP was significantly associated with fibulin-1 in African men and Caucasian women. NT-proBNP correlated negatively with arterial compliance in all groups except Caucasian women. After partial adjustments, the association between NT-proBNP and fibulin-1 strengthened in African men only. After full adjustment in multiple regression analysis, the association of NT-proBNP with fibulin-1 was confirmed in African men (R2 = 0.41; β = 0.26; p < 0.01) and also in younger women (R2 = 0.34; β = 0.251; p = 0.012). Conclusions Only Africans indicated a significant independent association between NT-proBNP and fibulin-1, suggesting that cardiovascular alterations are already present in this relatively young African population as opposed to Caucasians.

Many mechanisms, including oxidative stress, contribute to hypertension. This study investigated the possible associations between oxidative stress, blood pressure and arterial stiffness in black South Africans. Ambulatory blood pressure measurements were taken for 101 black South African men and 99 women. The stiffness indices included ambulatory arterial stiffness index (AASI) and pulse pressure (PP). Reactive oxygen species (ROS) levels (Po0.0001) were higher in the African women compared with men. ROS levels were also higher in hypertensive compared with normotensive men. The 24h systolic blood pressure (SBP; Po0.01), 24 h diastolic blood pressure (DBP; Po0.0001) and pulse wave velocity (PWV; Po0.01) were significantly higher in African men compared with women. There were unadjusted positive associations of 24 h SBP (r¼0.33; P¼0.001), 24 h DBP (r¼0.26; P¼0.008) and 24 h PP (r¼0.29; P¼0.003) with ROS in African men only. A positive association between AASI and ROS existed only in hypertensive men (r¼0.27; P¼0.035), but became nonsignificant (B¼0.0014; P¼0.14) after adjustments. Adjusted, positive associations of 24h SBP (B¼0.181; P¼0.018) and 24h PP (B¼0.086; P¼0.050) with ROS were again only evident in African men. ROS is positively associated with SBP and PP in African men, suggesting that increased ROS levels may contribute to hypertension in this population group.

Background: Hypertension and increased blood glucose are associated with subclinical kidney damage, atherosclerosis and with low testosterone values. Low testosterone in men is often accompanied by increased levels of estradiol. Objectives and methods: In this study, the association between estradiol, subclinical kidney damage and atherosclerosis in African and white men in a South African cohort was investigated. Cardiovascular variables were studied by means of B-mode ultrasound and ambulatory blood pressure (BP) monitoring. The sex hormones and other biochemical values were measured from fasting venous blood and overnight urine samples. The ethnic groups were stratified into low and high testosterone groups by means of median split. Results: The low testosterone African group demonstrated a higher cardiovascular risk compared with the low testosterone white men with 91% being hypertensive and having increased albumin-to-creatinine ratio (ACR), left carotid intima–media thickness (L-CIMTf) and estradiol-to-testosterone ratio. In the low-testosterone African men, estradiol explained 33% of the variance in ACR, whereas the estradiol-to-testosterone ratio explained 22% of the variance in L-CIMTf, respectively. Estradiol-to-testosterone ratio was positively associated with ACR in the low testosterone whites. Conclusion: We conclude that increased levels of estradiol may play a role in the development of subclinical kidney damage in both African and white men as well as atherosclerosis in low-testosterone African men.

OBJECTIVE: The N-terminal prohormone B-type natriuretic peptide (NT-proBNP) is a reliable marker of cardiac strain. In hypertensive heart disease, NT-proBNP levels increase and may lose its protective function. Simultaneously, the vasculature is also subject to hemodynamic stress, resulting in vascular matrix remodeling and stiffening which contribute to further cardiac alterations. Alkaline phosphatase (ALP) is a marker of osteoblast activity and is involved in vascular calcification. We explored the link between NT-proBNP and ALP in Black and Caucasian African men. DESIGN AND MAIN OUTCOME MEASURES: This study included 128 Black (mean age, 41.1 years) and 118 Caucasian (mean age, 36.4 years) men. Conventional measurements were acquired along with serum NT-proBNP and ALP. RESULTS: NT-proBNP correlated positively with ALP (r=0.29; p<0.001) in Black Africans, but inversely in Caucasians (r=-0.20; p=0.024). After minimal adjustment (age, body mass index, systolic blood pressure and arterial compliance), the positive significant correlation of NT-proBNP with ALP remained in Black men (r=0.225; p=0.014), whereas significance was lost in Caucasian men. Multiple regression analyses confirmed the independent association of NT-proBNP with ALP in Black men (R2=0.37; beta=0.248; p=0.005), as well as in younger Black men (R2=0.26; beta=0.375; p<0.001; n=96), with no significance in Caucasians. CONCLUSIONS: NT-proBNP is independently and positively associated with ALP in Black African men. This was however not evident in Caucasian men. These results suggest that African men are susceptible to potential early vascular calcification and may develop increased cardiac afterload prematurely.