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Aim: Marinobufagenin (MBG), a cardiotonic steroid and a natriuretic hormone, is elevated in response to high salt diet consumption. In animal models salt intake stimulates adrenocortical MBG secretion via increased angiotensin II, sympathetic activity and aldosterone. No evidence in humans exists to suggest the involvement of the angiotensinergic-sympatho-excitatory pathway in MBG production. We investigated whether MBG is related to indices of autonomic activity in men and women. Methods: This cross-sectional study included 680 black and white, men and women from the African-PREDICT study (aged 20–30 years). Continuous 24 hr ECG recordings were used to obtain low and high frequency (LF, HF) heart rate variability (HRV). We measured 24 hr urinary MBG excretion and serum aldosterone. Results: We found a positive association of MBG excretion with estimated salt intake (P < 0.001) and aldosterone (P < 0.001) in women and men. In women only, a positive relationship was evident between MBG excretion and LF HRV in multivariate adjusted regression analyses (Adj. R2 = 0.33; β = 0.11; P = 0.030). In men, MBG excretion associated positively with HF HRV in similar regression analyses (R2 = 0.36; β = 0.12; P = 0.034). Sex-specific results were corroborated only in blacks, namely, a positive association of MBG excretion with LF HRV in black women (R2 = 0.38; β = 0.13; P = 0.036), and negative association with HF HRV in black men (R2 = 0.40; β = 0.18; P = 0.045). No relationships were evident in white women (P = 0.58) or men (P = 0.27). Conclusion: Our findings in this human cohort support suggested mechanisms whereby MBG is elevated as a result of increased salt intake, including autonomic activity, previously demonstrated in Dahl salt-sensitive hypertension

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

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

Background Leptin is a vasoactive peptide that has been linked to diseases associated with macrovascular deterioration. What is still uncertain is its involvement in the microvasculature. Since microvascular changes are presumed to precede macrovascular deterioration, we examined whether measures of the retinal microvasculature are associated with leptin in healthy, young Black and White individuals. Method We included 283 Black and 289 White men and women (aged 20–30 years). We determined serum leptin, calculated central retinal artery and vein equivalents and arterio-venous ratio. We also measured retinal vessel responses to light flicker provocation. Results Black men were leaner and had lower leptin than White men, whereas Black women had increased adiposity and leptin compared to White women (all p<0.001). Black groups had narrower retinal arteries, and greater maximum arteriolar and venular dilations in response to light flicker than the White groups (p<0.001). Arterio-venous ratio associated negatively with leptin (all p≤0.044) in all groups (except Black women), but was lost upon adjustment for body mass index and other covariates. We found an inverse association between maximal venular dilation and leptin only in Black men in single and multiple regression analyses (Std β= -0.22; R 2=0.05; p=0.035). No associations were found between other retinal measures with leptin in the other groups. Conclusion We found an independent, negative association between retinal vein dilation with leptin in healthy, young Black men, suggesting a potential detrimental role for leptin in regulating microvascular responses in a population group known to be at greater risk of cardiovascular disease development

Masked hypertension is known to induce microvascular complications. However, it is unclear whether early microvascular changes are already occurring in young, otherwise healthy adults. We therefore investigated whether retinal microvascular calibers and acute responses to a flicker stimulus are related to masked hypertension. We used the baseline data of 889 participants aged 20–30 years who were taking part in the African Prospective study on the Early Detection and Identification of Cardiovascular Disease and Hypertension. Clinic and 24-h ambulatory blood pressure were measured. The central retinal artery equivalent (CRAE) and central retinal vein equivalent were calculated from fundus images, and retinal vessel dilation was determined in response to flicker light-induced provocation. A smaller CRAE was observed in those with masked hypertension vs. those with normotension (157.1 vs. 161.2 measuring units, P < 0.001). In forward multivariable-adjusted regression analysis, only CRAE was negatively related to masked hypertension [adjusted R2 = 0.267, β = −0.097 (95% CI = −0.165; −0.029), P = 0.005], but other retinal microvascular parameters were not associated with masked hypertension. In multivariable logistic regression analyses, masked hypertension [OR = 2.333, (95% CI = 1.316; 4.241), P = 0.004] was associated with a narrower CRAE. In young healthy adults, masked hypertension was associated with retinal arteriolar narrowing, thereby reflecting early microvascular alterations known to predict cardiovascular outcomes in later life

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

Mounting evidence supports the central role of oxidative stress and inflammation in obesity and the development of hypertension. However, most studies focusing on the non-enzymatic antioxidants, such as uric acid and bilirubin, and their relationship with obesity and hypertension were done in older populations with overt cardiovascular disease. The aim of this study was therefore to compare measures of cardiovascular function (blood pressure and arterial stiffness) and non-enzymatic antioxidants (uric acid and bilirubin) between young healthy lean and overweight/obese men and women and to investigate the link between these variables. We grouped 967 men and women (aged 20–30 years) according to body mass index (BMI) categories (lean BMI < 25 kg/m2; overweight/obese BMI ≥ 25 kg/m2). Cardiovascular measurements included 24 h blood pressure and carotid-femoral pulse wave velocity. Serum samples were used to analyse uric acid and bilirubin. Women and men with a BMI ≥ 25 kg/m2 displayed higher 24 h blood pressure (P < 0.001) and uric acid (P ≤ 0.014) than their lean counterparts; lean women showed higher bilirubin (P < 0.001). In multi-variable adjusted regression analyses we found that 24 h systolic blood pressure was independently associated with uric acid (R2 = 0.10; β = 0.19; P = 0.017) only in overweight/obese women. In lean women a negative association of 24 h systolic blood pressure with bilirubin (R2 = 0.03; β = −0.14; P = 0.018) was found. No associations were found in men. In conclusion, we found adverse associations between blood pressure and uric acid in young healthy women with increased adiposity, but not in lean women or men

Suppressed nighttime blood pressure dipping is associated with salt sensitivity and may increase the hemodynamic load on the microvasculature. The mechanism remains unknown whereby salt sensitivity may increase the cardiovascular risk of non-dippers. Marinobufagenin, a novel steroidal biomarker, is associated with salt sensitivity and other cardiovascular risk factors independent of blood pressure. The authors investigated whether microvascular function in non-dippers is associated with marinobufagenin. The authors included 220 dippers and 154 non-dippers (aged 20-30 years) from the African-PREDICT study, with complete 24-hour urinary marinobufagenin and sodium data. The authors determined dipping status using 24-hour blood pressure monitoring and defined nighttime non-dipping <10%. The authors measured microvascular reactivity as retinal artery dilation in response to light flicker provocation. Young healthy non-dippers and dippers presented with similar peak retinal artery dilation, urinary sodium, and MBG excretion (P > .05). However, only in non-dippers did peak retinal artery dilation relate negatively to marinobufagenin excretion after single (r = -0.20; P = .012), partial (r = -0.23; P = .004), and multivariate-adjusted regression analyses (Adj. R2 = 0.34; β = -0.26; P < .001). The authors also noted a relationship between peak artery dilation and estimated salt intake (Adj. R2 = 0.30; β = -0.14; P = .051), but it was lost upon inclusion of marinobufagenin (Adj. R2 = 0.33; β = -0.015; P = .86). No relationship between microvascular reactivity and marinobufagenin was evident in dippers (P = .77). Marinobufagenin, representing salt sensitivity, may be involved in early microvascular functional changes in young non-dippers and thus contributes to the development of hypertension and cardiovascular disease later in life

High salt (sodium chloride) intake raises blood pressure and increases the risk of developing hypertension, a major risk factor for cardiovascular disease. Little is known about salt intake in Nepal, and no study has estimated salt consumption from 24‐hour urinary sodium excretion. Participants (n = 451) were recruited from the Community‐Based Management of Non‐Communicable Diseases in Nepal (COBIN) cohort in 2018. Salt intake was estimated by analyzing 24‐hour urinary sodium excretion. Multivariate linear regression was used to estimate differences in salt intake. The mean (±SD) age and salt intake were 49.6 (±9.8) years and 13.3 (±4.7) g/person/d, respectively. Higher salt intake was significantly associated with male gender (β for female = −2.4; 95% CI: −3.3, −1.4) and younger age (β10 years = −1.4; 95% CI: −1.4, −0.5) and higher BMI (β = 0.1; 95% CI: 0.0, 0.2). A significant association was also found between increase in systolic blood pressure and higher salt intake (β = 0.3; 95% CI: 0.0, 0.7). While 55% reported that they consumed just the right amount of salt, 98% were consuming more than the WHO recommended salt amount (<5 g/person/d). Daily salt intake in this population was over twice the limit recommended by the WHO, suggesting a substantial need to reduce salt intake in this population. It also supports the need of global initiatives such as WHO's Global Hearts Initiative SHAKE technical package and Resolves to Save Lives for sodium reduction in low‐ and middle‐income countries like Nepal

Purpose Globally, a detrimental shift in cardiovascular disease risk factors and a higher mortality level are reported in some black populations. The retinal microvasculature provides early insight into the pathogenesis of systemic vascular diseases, but it is unclear whether retinal vessel calibers and acute retinal vessel functional responses differ between young healthy black and white adults. Methods We included 112 black and 143 white healthy normotensive adults (20–30 years). Retinal vessel calibers (central retinal artery and vein equivalent (CRAE and CRVE)) were calculated from retinal images and vessel caliber responses to flicker light induced provocation (FLIP) were determined. Additionally, ambulatory blood pressure (BP), anthropometry and blood samples were collected. Results The groups displayed similar 24 h BP profiles and anthropometry (all p > .24). Black participants demonstrated a smaller CRAE (158 ± 11 vs. 164 ± 11 MU, p < .001) compared to the white group, whereas CRVE was similar (p = .57). In response to FLIP, artery maximal dilation was greater in the black vs. white group (5.6 ± 2.1 vs. 3.3 ± 1.8%; p < .001). Conclusions Already at a young age, healthy black adults showed narrower retinal arteries relative to the white population. Follow-up studies are underway to show if this will be related to increased risk for hypertension development. The reason for the larger vessel dilation responses to FLIP in the black population is unclear and warrants further investigation

Background and aims The association between plasminogen activator inhibitor-1 (PAI-1) and blood pressure is well established, but it is debatable whether raised PAI-1 levels precede or result from raised blood pressure. Furthermore, it is unclear whether this association already exists in the absence of overt hypertension and to what degree it is influenced by health behaviours. Our aim was to investigate the association of 24 h blood pressure with PAI-1 activity (PAI-1act) in a young, healthy cohort, and to assess the influence of alcohol consumption and smoking on these associations. Methods and results Healthy black and white men and women (aged 20–30 years, n = 1156) were cross-sectionally analysed. Statistical analysis was performed first split by ethnicity and sex and then by alcohol consumption and smoking. Regression analyses adjusted for age revealed positive associations of 24 h blood pressure with PAI-1act in most groups (p < 0.05). In multivariate-adjusted analyses, significance was lost in all groups except black men, who also had higher monocyte chemoattractant protein-1 (MCP-1) and von Willebrand factor antigen (vWFag) compared to white men (both p < 0.001). Analyses in black men, split by self-reported alcohol use and smoking, revealed 24 h blood pressure-PAI-1act associations only in alcohol users (24 h SBP [B = 4.22, p < 0.001], DBP [B = 2.04, p = 0.015] and PP [B = 2.18, p = 0.013]) and smokers (24 h SBP [B = 6.10, p < 0.001] and PP [B = 4.33, p = 0.001]). Conclusion Our findings support a positive association between 24 h blood pressure and PAI-1, particularly in individuals with higher MCP-1 and vWFag levels. Furthermore, smoking and alcohol consumption play an important role in modifying the association between blood pressure and PAI-1.

Given a global focus on salt reduction efforts to reduce cardiovascular risk, it is important to obtain accurate measures of salt intake on a population level. This study determined firstly whether adjustment for intra-individual variation in urinary sodium (Na) excretion using three repeated 24 h collections affects daily estimates and whether the use of repeated spot urine samples results in better prediction of 24 h Na compared to a single collection. Twenty three community-dwelling men and women from South Africa (mean age 59.7 years (SD = 15.6)) participating in the World Health Organization Study on global AGEing and adult health (WHO-SAGE) Wave 3 study collected 24 h and spot early morning urine samples over three consecutive days to assess urinary Na excretion. INTERSALT, Tanaka, and Kawasaki prediction equations, with either average or adjusted spot Na values, were used to estimate 24 h Na and compared these against measured 24 h urinary Na. Adjustment was performed by using the ratio of between-person (sb) and total (sobs) variability obtained from repeated measures analysis of variance. Sensitivity of the equations to predict daily urinary Na values below 5 g salt equivalent was calculated. The sb/sobs for urinary Na using three repeated samples for spot and 24 h samples were 0.706 and 0.798, respectively. Correction using analysis of variance for 3 × 24 h collections resulted in contraction of the upper end of the distribution curve (90th centile: 157 to 136 mmoL/day; 95th centile: 220 to 178 mmoL/day). All three prediction equations grossly over-estimated 24 h urinary Na excretion, regardless of whether a single spot urine or repeated collections corrected for intra-individual variation were used. Sensitivity of equations to detect salt intake equivalent values of ≤5 g/day was 13% for INTERSALT, while the other two equations had zero sensitivity. Correcting for intra-individual variability in Na excretion using three 24 h urine collections contracted th

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

Background Excessive alcohol use is the third leading cause of mortality in the United States, where alcohol use consistently increased over the last decades. This trend is currently maintained, despite regulatory policies aimed to counteract it. While the increased health risks resulting from alcohol use are evident, some open questions regarding alcohol use and its consequences in the US population remain. Objectives The current work aims to evaluate the relation between alcohol consumption trends over a period of 15 y with all-cause and cause-specific mortality. In addition, we evaluate the adequacy of the current alcohol recommended limits according to the 2015–2020 US Dietary Guidelines for Americans (USDGA). Methods This was a prospective population-based study defined by the NHANES conducted over the period 1999–2014 linked to US mortality registry in 2015. Results The sample, composed of 34,672 participants, was observed for a median period of 7.8 y, totaling 282,855 person-years. In the present sample, 4,303 deaths were observed. Alcohol use increased during the period 1999–2014. Alcohol use above the current US recommendations was associated with increased all-cause and cause-specific mortality risk, ranging from 39% to 126%. A proportion of these deaths, ranging from 19% to 26%, could be theoretically prevented if US citizens followed current guidelines, and 13% of all-cause deaths in men could be avoided if the current US guidelines for women (1 standard drink/d) were applied to them. Conclusions The present study provides evidence in support of limiting alcohol intake in adherence to the USDGA recommendations

Background & aims Uncertainty still exists on the impact of low to moderate consumption of different drink types on population health. We therefore investigated the associations of different drink types in the form of beer/cider, champagne/white wine, red wine and spirits with various health outcomes. Methods Over 500,000 participants were recruited to the UK Biobank cohort. Alcohol consumption was self-reported as pints beer/cider, glasses champagne/white wine, glasses of red wine, and measures of spirits per week. We followed health outcomes for a median of 7.02 years and reported all-cause mortality, cardiovascular events, ischemic heart disease, cerebrovascular events, and cancer. Results In continuous analysis after excluding non-drinkers, beer/cider and spirits intake associated with an increased risk for all-cause mortality (beer/cider: hazard ratio, 1.56; 95% confidence interval, 1.45–1.68; spirits: 1.47; 1.35–1.60), cardiovascular events (beer/cider: 1.25; 1.17–1.33; spirits: 1.25; 1.16–1.36), ischemic heart disease (beer/cider:1.12; 0.99–1.26 [P = 0.056]; spirits: 1.17; 1.02–1.35), cerebrovascular disease (beer/cider: 1.63; 1.32–2.02; spirits: 1.59; 1.25–2.02) and cancer (beer/cider: 1.14; 1.05–1.24; spirits: 1.14; 1.03–1.26), while both champagne/white wine and red wine associated with a decreased risk for ischemic heart disease only (champagne/white wine: 0.84; 0.72–0.98; red wine: 0.88; 0.77–0.99). Conclusions Our findings do not support the notion that alcohol from any drink type is beneficial to health. Consuming low levels of beer/cider and spirits already associated with an increased risk for all health outcomes, while wine showed opposite protective relationships only with ischemic heart disease

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

Objective: Our study aims to evaluate hypertensive case management in South Africa's public health sector using simulated patients. Method: Our study describes interactions between hypertensive simulated patients and primary healthcare workers at 39 public sector healthcare facilities in two metropolitan centres in the Eastern and Western Cape Provinces of South Africa. Our analysis focus on 97 interactions where our eight simulated patients tested within range for stage 1 hypertension, that is with SBP 140–159 mmHg and/or DBP 90–99 mmHg. For this subset, we describe how healthcare workers communicated the outcome of the blood pressure test, and whether they follow government guidelines on risk assessment and lifestyle advice. Results: Healthcare workers highlighted the risks associated with hypertension in one out of three cases and stressed the importance of regular monitoring of blood pressure in less than half of cases. Hypertensive patients received advice on all six lifestyle risk factors in 8% of cases. 39% of patients received no lifestyle advice at all. In one out of four cases, hypertensive patients left the facility without a hypertension diagnosis and with no prospect of a follow-up visit. Conclusion: Simulated patients can assess the quality of hypertension case management, yielding granular and comprehensive information that can help mobilize resources to improve care. The management of hypertension patients in South African public healthcare facilities is critically insufficient. Given that hypertension is responsible for a rising share of deaths in South Africa and many of these deaths are preventable, urgent intervention is needed

The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organisation for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP

The home blood pressure monitoring (HBPM) method that measures blood pressure during sleep hours was reported to be comparable to ambulatory blood pressure monitoring (ABPM) in measuring nighttime blood pressure and detecting nocturnal hypertension. The aim of this study was to directly compare the prognostic power of nocturnal hypertension detected by HBPM versus ABPM for predicting future cardiovascular events. We analyzed nighttime blood pressure (measured by HBPM and ABPM) data of 1005 participants who were included in the J-HOP study (Japan Morning Surge-Home Blood Pressure). During a follow-up period of 7.6±3.4 years, 80 cardiovascular disease events occurred. The majority (91.8%) of our study population were hypertensive, and 80.7% of participants were using antihypertensive medication. Nighttime home systolic blood pressure (SBP) was higher compared to nighttime ambulatory SBP (123.0±14.6 versus 120.3±14.4 mm Hg, P<0.001). Nocturnal hypertension was defined as nighttime home or ambulatory SBP of ≥120 mm Hg. The number of participants with nocturnal hypertension defined by HBPM and ABPM was 564 (56.1%) and 469 (46.7%), respectively. Nocturnal hypertension defined by HBPM was associated with increased risk of future cardiovascular events: total cardiovascular events (coronary artery disease and stroke events; 1.78 [1.00–3.15]) and stroke (2.65 [1.14–6.20]), independent of office SBP. These results were absent with nocturnal hypertension defined by ABPM. This is the first comparison prospective study illustrating that uncontrolled nocturnal hypertension defined by HBPM (independent of office SBP) is a predictor of future cardiovascular events

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

Context and Purpose of This Guideline Statement of Remit To align with its mission to reduce the global burden of raised blood pressure (BP), the International Society of Hypertension (ISH) has developed worldwide practice guidelines for the management of hypertension in adults, aged 18 years and older. The ISH Guidelines Committee extracted evidence-based content presented in recently published extensively reviewed guidelines and tailored and standards of care in a practical format that is easy-to-use particularly in low, but also in high resource settings – by clinicians, but also nurses and community health workers, as appropriate. Although distinction between low and high resource settings often refers to high (HIC) and low- and middle-income countries (LMIC), it is well established that in HIC there are areas with low resource settings, and vice versa. Herein optimal care refers to evidence-based standard of care articulated in recent guidelines1,2 and summarized here, whereas standards recognize that standards would not always be possible. Hence essential standards refer to minimum standards of care. To allow specification of essential standards of care for low resource settings, the Committee was often confronted with the limitation or absence in clinical evidence, and thus applied expert opinion

Globally, raised blood pressure is the leading risk factor accountable for over 10.4 million deaths per year.1 The cardiovascular consequences of hypertension are devastating, which is why raised blood pressure requires aggressive confrontation. It is therefore disturbing that the number of adults with raised blood pressure increased over the past four decades from 594 million to 1.13 billion in 2015—due to population growth and aging.2 But all regions in the world were not affected equally. For instance, the high‐income Asia Pacific region indicated some of the highest global blood pressures in the 1970s, but it is also this region that showed the largest decreases in systolic blood pressure of 3.2 mm Hg per decade for women, and 2.4 mm Hg per decade for men.2 In contrast to these decreases, blood pressure seems to have increased in populations from east and southeast Asia, as well as south Asia—with south Asia presenting with the highest mean blood pressures in 2015.2

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Though Ghana has high hypertension prevalence, the country lacks current national salt consumption data required to build and enhance advocacy for salt reduction. We explored the characteristics of a randomly selected sub sample that had valid urine collection, along with matched survey, anthropometric and BP data (n = 839, mean age = 60y), from the World Health Organization’s Study on global AGEing and adult health (WHO-SAGE), Ghana Wave 3, n = 3053). We also investigated the relationship between salt intake and blood pressure (BP) among the cohort. BP was measured in triplicate and 24 h urine was collected for the determination of urinary sodium (Na), potassium (K), creatinine (Cr) and iodine levels. Hypertension prevalence was 44.3%. Median salt intake was 8.3 g/day, higher in women compared to men (8.6, interquartile range (IQR) 7.5 g/day vs 7.5, IQR 7.4 g/day, p < 0.01), younger participants (18–49 y) compared to older ones (50+ y) (9.7, IQR 7.9 g/day vs 8.1, IQR 7.1 g/day, p < 0.01) and those with higher Body Mass Index (BMI) (> 30 kg/m2) compared to a healthy BMI (18.5–24.9 kg/m2) (10.04, IQR 5.1 g/day vs 6.2, IQR 5.6 g/day, p < 0.01). More than three quarters (77%, n = 647) of participants had salt intakes above the WHO maximum recommendation of 5 g/d, and nearly two thirds (65%, n = 548) had daily K intakes below the recommended level of 90 mmol. Dietary sodium to potassium (Na: K) ratios above 2 mmol/mmol were positively associated with increasing BP with age. Population-based interventions to reduce salt intake and increase K consumption are needed

Background After its outbreak in China, the novel COronaVIrus Disease 19 is spreading across the globe. It is an emergency the world has never seen before. Main text The attention of health systems is mainly focused on COronaVIrus Disease 19 patients and on the risk that intensive care units might be overwhelmed by the serious pulmonary complications. Different countries are also attempting to establish infection prevention and control strategies which proved effective in China where the outbreak was initially reported. We reflect on important lessons to be learnt from different countries. The effects that infection prevention and control strategies, such as social distancing or isolation, can have on the care of millions of patients with non-communicable diseases, who may be indirectly affected, have not been taken into consideration so much. Conclusions When dealing with COronaVIrus Disease 19, policy makers and healthcare personnel should consider the indirect effects on the treatment of non-communicable diseases

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 coronavirus disease 2019 (COVID-19) pandemic not only changed our day-to-day lives abruptly, but it also forced the global scientific community to reevaluate everything that we thought we knew

This study investigated associations of brachial and central blood pressure (BP) with detailed renin-angiotensin-aldosterone system (RAAS) components in a healthy young population stratified according to ethnicity and sex. We included healthy black men (n = 285) and women (n = 304) and white men (n = 278) and women (n = 305) aged 20–30 years old. We derived central systolic BP (cSBP), measured clinic and 24-h systolic and diastolic BP. Aldosterone and equilibrium angiotensin levels were assessed and used for calculating angiotensin-derived markers for plasma renin activity (PRA-S, Angiotensin I + Angiotensin II), angiotensin-converting enzyme (ACE-S, Angiotensin II/Angiotensin I), and two markers for adrenal effects of angiotensin II, the aldosterone-to-renin ratio (ARR-S, Aldosterone/PRA-S) and the aldosterone-to-angiotensin II-ratio (AA2-R, Aldosterone/Angiotensin II). Young black men and women presented with lower RAAS components and higher cSBP compared to their white counterparts (all p ≤ 0.001). In multivariable-adjusted regression analyses, positive associations of cSBP with ARR-S and AA2-R and negative associations with PRA-S and angiotensin II were found for black women (all p ≤ 0.001); this pattern was also observed for 24-h and clinic BP (p ≤ 0.045). A similar trend of RAAS associations was present in black men but only for clinic BP (all p ≤ 0.047). In white men, negative associations between clinic SBP and PRA-S, angiotensin II and aldosterone were detected (all p ≤ 0.048). No associations were observed in white women. Positive associations of central and peripheral BP with the ratio of aldosterone to PRA-S and angiotensin II only in healthy, young black adults suggest that relative aldosterone excess may contribute to early hypertension development in this group

Summary Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO’s Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries’ health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO’s GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of

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

Cardiovascular diseases are the major cause of morbidity and mortality worldwide. They develop over long periods of time, and are typically caused by multiple factors, and interaction with the environment. Proteomics allows simultaneous quantification of multiple protein markers in a biosample, and therefore offers opportunities for precise individual definition of risk profiles, prediction, and diagnosis of disease. Proteomic biomarkers can also be used for monitoring of disease progression, and response to therapy. The large amount of information that can be obtained from comprehensive studies of the proteome naturally feeds into concepts of precision medicine, and has the potential not only to target preventative and therapeutic strategies to individual patients, but also to identify new therapeutic principles. In this chapter we will provide an overview of proteomic techniques, and how they can be applied in cardiovascular medicine

CVD is the most common chronic condition and the highest cause of mortality in the USA. The aim of the present work was to investigate diet and sedentary behaviour in relation to mortality in US CVD survivors. The National Health and Nutrition Examination Surveys conducted between 1999 and 2014 linked to the US mortality registry updated to 2015 were investigated. Multivariate adjusted Cox regression was used to derive mortality hazards in relation to sedentary behaviour and nutrient intake. A multiplicative and additive interaction analysis was conducted to evaluate how sedentariness and diet influence mortality in US CVD survivors. A sample of 2473 participants followed for a median period of 5·6 years resulted in 761 deaths, and 199 deaths were due to CVD. A monotone increasing relationship between time spent in sedentary activities and mortality risk was observed for all-cause and CVD mortality (hazard ratio (HR) = 1·20, 95 % CI 1·09, 1·31 and HR = 1·19, 95 % CI 1·00, 1·67, respectively). Inverse mortality risks in the range of 22–34 % were observed when comparing the highest with the lowest tertile of dietary fibre, vitamin A, carotene, riboflavin and vitamin C. Sedentariness below 360 min/d and dietary fibre and vitamin intake above the median interact on an additive scale influencing positively all-cause and CVD mortality risk. Reduced sedentariness in combination with a varied diet rich in dietary fibre and vitamins appears to be a useful strategy to reduce all-cause and CVD mortality in US CVD survivors

The 2020 ISH Global Hypertension Practice Guidelines [1] include a detailed list of lifestyle modifications with varying levels of evidence for the reduction of blood pressure and cardiovascular risk. We listed some novel and inexpensive approaches, such as Transcendental Meditation, to purposefully broaden interventions that could be employed in low and high resource settings. We thank Drs Schneider, Salerno and Brook for their noteworthy correspondence emphasizing the importance of this inclusion as a useful intervention to lower cardiovascular risk [2]. The authors correctly highlight that we only cited one systematic review to support this intervention, and that there is a broader range of evidence that require citation. We not only appreciate this notion but also wish to reiterate our statement in the guidelines that the Guidelines Committee did not perform a detailed systematic literature review for the purpose of writing the guidelines, but mostly extracted evidence from recently published guidelines. This was done with the purpose to produce short and practical guidelines

DNA methylation data can be used to estimate proportions of leukocyte subsets retrospectively, when directly measured cell counts are unavailable. The methylation-derived neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratios (mdNLRs and mdLMRs) have proven to be particularly useful as indicators of systemic inflammation. As with directly measured NLRs and LMRs, these methylation-derived ratios have been used as prognostic markers for cancer, although little is known about them in relation to other disorders with inflammatory components, such as cardiovascular disease (CVD). Recently, methylation of five genomic cytosine-phosphate-guanine sites (CpGs) was suggested as proxies for mdNLRs, potentially providing a cost-effective alternative when whole-genome methylation data are not available. This study compares seven methylation-derived inflammatory markers (mdNLR, mdLMR, and individual CpG sites) with five conventionally used protein-based inflammatory markers (C-reactive protein, interleukins 6 and 10, tumor-necrosis factor alpha, and interferon-gamma) and a protein-based inflammation score, in their associations with cardiovascular function (CVF) and risk. We found that markers of CVF were more strongly associated with methylation-derived than protein-based markers. In addition, the protein-based and methylation-derived inflammatory markers complemented rather than proxied one another in their contribution to the variance in CVF. There were no strong correlations between the methylation and protein markers either. Therefore, the methylation markers could offer unique information on the inflammatory process and are not just surrogate markers for inflammatory proteins. Although the five CpGs mirrored the mdNLR well in their capacity as proxies, they contributed to CVF above and beyond the mdNLR, suggesting possible added functional relevance. We conclude that methylation-derived indicators of inflammation enable individuals with increased CVD risk to be identifi

Repeated 24-hour urine collection is considered to be the gold standard for assessing salt intake. This is often impractical in large-population studies, especially in low–middle-income countries. Equations to estimate 24-hour urinary salt excretion from a spot urine sample have been developed, but have not been widely validated in African populations. This study aimed to systematically assess the validity of four existing equations to predict 24-hour urinary sodium excretion (24UNa) from spot urine samples in a nationally representative sample of South Africans. Spot and 24-hour urine samples were collected in a subsample (n = 438) of participants from the World Health Organisation Study on global AGEing and adult health (SAGE) Wave 2 in South Africa in 2015. Measured 24UNa values were compared with predicted 24UNa values from the Kawasaki, Tanaka, INTERSALT and Mage equations using Bland–Altman plots. In this subsample (mean age 52.8 ± 16.4 years; body mass index 30.2 ± 8.2 kg/m2; 76% female; 73% black African; 42% hypertensive), all four equations produced a significantly different population estimate compared with the measured median value of 6.7 g salt/day (IQR 4.4–10.5). Although INTERSALT underestimated salt intake (−3.77 g/d; −1.64 to −7.09), the other equations overestimated by 1.28 g/d (−3.52; 1.97), 6.24 g/d (2.22; 9.45), and 17.18 g/d (8.42; 31.96) for Tanaka, Kawasaki, and Mage, respectively. Bland–Altman curves indicated unacceptably wide levels of agreement. Use of these equations to estimate population level salt intake from spot urine samples in South Africans is not recommended

Objectives: Understanding of the interplay between human immunodeficiency virus (HIV) and cardiovascular disease, especially in Africa, is limited to evidence from longitudinal studies. Therefore the demographic profile and cardiometabolic, renal and liver function of an HIV-infected South African population were profiled from 2005 to 2015. Methods: The study included 117 HIV-infected and 131 uninfected controls that were examined at baseline, five and 10 years. Results: Mortality rate declined from 24% (2005–2010) to 0% (2010–2015) after the introduction of ART. Longitudinal increases in C-reactive protein (p = 0.002), alanine transaminase (p = 0.006) and gamma-glutamyl transferase (p = 0.046) levels and estimated glomerular filtration rate (p < 0.001) were seen only in the HIV-infected group. This group also showed increased high-density lipoprotein cholesterol (HDL-C) (p < 0.001) and total cholesterol (p < 0.001) levels and decreased triglyceride:HDL-C (p = 0.011) levels. Low-density lipoprotein cholesterol decreased in both groups (p < 0.001). Conclusion: Despite trajectories of deranged lipid and inflammatory profiles, the cardiometabolic disease risk seems stable in HIV-infected South Africans. Inflammation and renal and liver function warrant regular monitoring

Elevated blood pressure (BP), or hypertension, is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and acting as a stimulus to improving screening programmes worldwide. In the United Kingdom (UK) nearly 1 in 5 people, and in the Republic of Ireland (RoI) 3 out of 10, have hypertension, of which a large proportion remains undiagnosed. 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 analysis followed a standardized protocol. Screenings sites in hospitals, universities, shopping centres, workplaces, sports clubs, community centres, GP practices, and pharmacies were set up across the UK and RoI as part of this initiative. Seven thousand seven hundred and fourteen individuals were screened during MMM17. After multiple imputation, 3099 (40.3%) had hypertension. Of individuals not receiving antihypertensive medication, 1406 (23.4%) were hypertensive. Of individuals receiving antihypertensive medication, 682 (40.5%) had uncontrolled BP. MMM17 was the largest BP screening campaign ever undertaken in the UK and RoI. These data prove for the first time that a relatively inexpensive, volunteer based, convenience sampling of screening BP in the community identified two out of five individuals as hypertensive, with one in four not receiving treatment. Of major concern is that these data demonstrate that of those individuals receiving treatment, two out of five still did not have controlled BP

Key Messages About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke). There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring. Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated. Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks. Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care. Urgent sustained action is needed is needed for effective public polcies and health system changes to prevent and control hypertension

Blood pressure (BP) measurement, a technique first described over a century ago, is an essential component of clinical care and critical for the detection and management of hypertension.1 Accordingly, the ramifications of inaccurate BP measurement, which is a per‐ sistent and pervasive problem worldwide, are profound.2 Assuming a global prevalence of hypertension of 1.4 billion,3 a 5‐mmHg error in BP measurement has been estimated to result in the incorrect classification of hypertension status in at least 84 million individ‐ uals worldwide.4 In addition, incorrect classification has important ramifications for individual patients, whether it leads to misdiagno‐ sis and inappropriate prescribing of antihypertensive drugs, or to lack of recognition of an clinical condition that can cause devastat‐ ing cardiovascular consequences. The continued rise in the global prevalence of hypertension has made work related to optimizing BP measurement even more critical, and notwithstanding similar initia‐ tives that have been conducted or are ongoing, additional efforts to improve BP measurement on a global scale are clearly needed.5

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.

Background: South Africa has the largest population of human immunodefciency virus (HIV) infected patients on antiretroviral therapy (ART) realising the benefts of increased life expectancy. However, this population may be susceptible to cardiovascular disease (CVD) development, due to the chronic consequences of a lifestyle-related combination of risk factors, HIV infection and ART. We predicted a 10-year cardiovascular mortality risk in an HIV-infected population on long-term ART, based on their observed metabolic risk factor profle. Methods: We extracted data from hospital medical charts for 384 randomly selected HIV-infected patients aged ≥30 years. We defned metabolic syndrome (MetS) subcomponents using the International Diabetes Federation defnition. A validated non-laboratory-based model for predicting a 10-year CVD mortality risk was applied and categorised into fve levels, with the thresholds ranging from very low-risk (<5%) to very high-risk scores (>30%). Results: Among the 384 patients, with a mean (± standard deviation) age of 42.90±8.20 years, the proportion of patients that were overweight/obese was 53.3%, where 50.9% had low high-density lipoprotein (HDL) cholesterol and 21 (17.5%) had metabolic syndrome. A total of 144 patients with complete data allowed a defnitive prediction of a 10-year CVD mortality risk. 52% (95% CI 44–60) of the patients were stratifed to very low risk (<5%) compared to 8% (95% CI 4–13) that were at a very high risk (>30%) of 10-year CVD mortality. The CVD risk grows with increasing age (years), 57.82±6.27 among very high risk and 37.52±4.50; p<0.001 in very low risk patients. Adjusting for age and analysing CVD risk mortality as a continuous risk score, increasing duration of HIV infection (p=0.002) and ART (p=0.007) were signifcantly associated with increased predicted 10 year CVD mortality risk. However, there was no association between these factors and categorised CVD mortality risk as per recommended scoring thresholds.

Nutritional transition in Africa is linked with increased blood pressure (BP). We examined 10-year fatty acid status and longitudinal associations between individual long-chain polyunsaturated fatty acids (PUFA), BP and status of hypertension (≥140/90 mmHg and/or medication use) in black South Africans. We included 300 adults (>30 years) participating in the Prospective Urban Rural Epidemiology study, and analysed data from three consecutive examinations (2005, 2010 and 2015 study years). Fatty acids in plasma phospholipids were analysed by gas chromatography-mass spectrometry. We applied sequential linear mixed models for continuous outcomes and generalized mixed models for the hypertension outcome, in the complete sample and separately in urban and rural subjects. Mean baseline systolic/diastolic BP was 137/89 mmHg. Ten-year hypertension status increased among rural (48.6% to 68.6%, p = 0.001) and tended to decrease among urban subjects (67.5% to 61.9%, p = 0.253). Regardless of urbanisation, n-6 PUFA increased and eicosapentaenoic acid (EPA, C20:5 n-3) decreased over the 10-years. Subjects in the highest tertile of arachidonic acid (C20:4 n-6) had 3.81 mmHg lower systolic (95% confidence interval (CI): −7.07, −0.54) and 3.82 mmHg lower diastolic BP (DBP) (95% CI: −5.70, −1.95) compared to the reference tertile, irrespective of lifestyle and clinical confounders. Similarly, osbond acid (C22:5 n-6) was inversely associated with DBP. Over the 10-years, subjects in the highest EPA tertile presented with +2.92 and +1.94 mmHg higher SBP and DBP, respectively, and with 1.46 higher odds of being hypertensive. In black South African adults, individual plasma n-6 PUFA were inversely associated with BP, whereas EPA was adversely associated with hypertension, supporting implementation of dietary fat quality in national cardiovascular primary prevention strategies

Objectives: Plasminogen activator inhibitor-1 (PAI-1) has consistently shown positive associations with blood pressure (BP). Whether elevations in PAI-1 levels precede or result from raised BP is still under debate and data on prospective studies are limited. Hence, we investigated the prospective associations of PAI-1 and the 4G/5G polymorphism with brachial and central BP and pulse pressure (PP) over a 10-year period. Methods: Black South Africans aged 30 years and older were included. Baseline data collection commenced in 2005 (n = 2010) with follow-up data collection in 2010 (n = 1288) and 2015 (n = 926). Plasma PAI-1 activity (PAI-1act), 4G/5G polymorphism genotyping, waist circumference and BP measurements were performed and analysed using sequential regression and mixed models. Results: In multivariable adjusted analyses, PAI-1act and the 4G/4G (vs. the 5G/5G) genotype increased the odds of developing hypertension in the total group [1.04 (1.01; 1.08) and 1.82 (1.07; 3.12) respectively]. Furthermore, PAI-1act was prospectively associated with brachial SBP (r = 0.0815) and PP (r = 0.0832) in the total group, and with central PP in women (r = 0.1125; all P < 0.05). Addition of waist circumference to the models either decreased or nullified the contribution of PAI-1act to BP and hypertension development. Conclusion: PAI-1act and the 4G/4G (vs. the 5G/5G) genotype increased the odds of developing hypertension. Furthermore, PAI-1act associated prospectively with both brachial and central BP. These associations were mediated in part by central adiposity. The study supports the hypothesis that PAI-1 also contributes to hypertension development rather than solely being a consequence thereof

Background Suboptimal diet is an important preventable risk factor for non-communicable diseases (NCDs); however, its impact on the burden of NCDs has not been systematically evaluated. This study aimed to evaluate the consumption of major foods and nutrients across 195 countries and to quantify the impact of their suboptimal intake on NCD mortality and morbidity. Methods By use of a comparative risk assessment approach, we estimated the proportion of disease-specific burden attributable to each dietary risk factor (also referred to as population attributable fraction) among adults aged 25 years or older. The main inputs to this analysis included the intake of each dietary factor, the effect size of the dietary factor on disease endpoint, and the level of intake associated with the lowest risk of mortality. Then, by use of diseasespecific population attributable fractions, mortality, and disability-adjusted life-years (DALYs), we calculated the number of deaths and DALYs attributable to diet for each disease outcome. Findings In 2017, 11 million (95% uncertainty interval [UI] 10–12) deaths and 255 million (234–274) DALYs were attributable to dietary risk factors. High intake of sodium (3 million [1–5] deaths and 70 million [34–118] DALYs), low intake of whole grains (3 million [2–4] deaths and 82 million [59–109] DALYs), and low intake of fruits (2 million [1–4] deaths and 65 million [41–92] DALYs) were the leading dietary risk factors for deaths and DALYs globally and in many countries. Dietary data were from mixed sources and were not available for all countries, increasing the statistical uncertainty of our estimates. Interpretation This study provides a comprehensive picture of the potential impact of suboptimal diet on NCD mortality and morbidity, highlighting the need for improving diet across nations. Our findings will inform implementation of evidence-based dietary interventions and provide a platform for evaluation of their impact on human health annuall

Purpose: Elevated blood pressure is a well‐documented risk factor for cardiovascular disease and mortality in Sub‐Saharan Africa (SSA). With SSA also affected by high Human Immunodeficiency Virus (HIV) infection rates, it remains controversial whether the HIV‐infected population has a higher cardiovascular risk than the general population. We, therefore reviewed the literature comparing blood pressure estimates in treated HIV‐infected populations against untreated and/or uninfected controls from SSA. Methods: We conducted a narrative review through PubMed and EBSCO Discovery Service (EDS) to determine the estimates of raised blood pressure and hypertension in the HIV‐infected individuals versus uninfected controls (01 January 2005 to 11 November 2018). Results: After review, we included 14 eligible studies from six countries including 26,302 participants that compared treated HIV‐infected, versus untreated and uninfected controls. Studies involving 24,696 participants reported lower blood pressure and/or prevalence of hypertension in treated HIV‐infected patients compared to uninfected controls. Studies comprising of 3,536 participants reported higher blood pressure and hypertension prevalence in the treated HIV‐infected group than uninfected counterparts, whereas studies with 6,379 participants showed no difference in blood pressure and/or prevalence of hypertension. When comparing HIV patients with and without antiretroviral treatment, studies with 10,304 patients showed treated patients to have lower blood pressure and/or prevalence of hypertension, one study indicated higher blood pressure and/or prevalence of hypertension and studies with 5,806 patients showed no difference in blood pressure and/or prevalence of hypertension than untreated infected patients. Conclusion: The majority of the findings in this review indicate lower or similar blood pressure and/or prevalence of hypertension in treated HIV‐infected individuals compared to untreated and uninfected co

Background Stroke is a leading cause of mortality and disability worldwide and the economic costs of treatment and post-stroke care are substantial. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic, comparable method of quantifying health loss by disease, age, sex, year, and location to provide information to health systems and policy makers on more than 300 causes of disease and injury, including stroke. The results presented here are the estimates of burden due to overall stroke and ischaemic and haemorrhagic stroke from GBD 2016. Methods We report estimates and corresponding uncertainty intervals (UIs), from 1990 to 2016, for incidence, prevalence, deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). DALYs were generated by summing YLLs and YLDs. Cause-specific mortality was estimated using an ensemble modelling process with vital registration and verbal autopsy data as inputs. Non-fatal estimates were generated using Bayesian meta-regression incorporating data from registries, scientific literature, administrative records, and surveys. The Socio-demographic Index (SDI), a summary indicator generated using educational attainment, lagged distributed income, and total fertility rate, was used to group countries into quintiles. Findings In 2016, there were 5·5 million (95% UI 5·3 to 5·7) deaths and 116·4 million (111·4 to 121·4) DALYs due to stroke. The global age-standardised mortality rate decreased by 36·2% (−39·3 to −33·6) from 1990 to 2016, with decreases in all SDI quintiles. Over the same period, the global age-standardised DALY rate declined by 34·2% (−37·2 to −31·5), also with decreases in all SDI quintiles. There were 13·7 million (12·7 to 14·7) new stroke cases in 2016. Global age-standardised incidence declined by 8·1% (−10·7 to −5·5) from 1990 to 2016 and decreased in all SDI quintiles except the middle SDI group. There were 80·1 million (74·1 to 86·