Circulating cytokines and risk of developing hypertension: A systematic review and meta-analysis.

BACKGROUND: Immune responses play a significant role in hypertension, though the importance of key inflammatory mediators remains to be defined. We used a systematic literature review and meta-analysis to study the associations between key cytokines and incident hypertension. METHODS: We performed a systematic search of Pubmed/Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL), for peer-reviewed studies published up to August 2022. Incident hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg and/or the use of antihypertensive medications. Random effects meta-analyses were used to calculate pooled hazard ratios (HRs)/risk ratios (RRs) and 95% confidence intervals by cytokine levels (highest vs. lowest quartile). RESULTS: Only IL-6 and IL-1ß levels have evidence allowing for quantitative evaluation concerning the onset of hypertension. Six studies (10406 participants, 2932 incident cases) examined the association of IL-6 with incident hypertension. The highest versus lowest quartile of circulating IL-6 was associated with a significant HR/RR of hypertension (1.61, 95% CI: 1.00 to 2.60; I2 =87%). After adjusting for potential confounders, including body mass index (BMI), HR/RR was no longer significant (HR/RR: 1.24; 95% CI, 0.96 to 1.61; I2 = 56%). About IL-1ß, neither the crude (HR/RR: 1.03; 95% CI, 0.60 to 1.76; n = 2) nor multivariate analysis (HR/RR: 0.97, 95% CI, 0.60 to 1.56; n = 2) suggested a significant association with the risk of developing hypertension. CONCLUSIONS: A limited number of studies suggest that higher IL-6, but not IL-1ß, might be associated with the development of hypertension.

Comparing a range of potassium-enriched low sodium salt substitutes to common salt: Results of taste and visual tests in South African adults.

BACKGROUND AND AIMS: Potassium-enriched low sodium salt substitutes (LSSS), which replace a proportion of sodium chloride (NaCl) with potassium chloride (KCl), have been shown to reduce blood pressure and offer a potential solution to address the high burden of hypertension in South Africa. However, it is unknown which proportions of KCl in LSSS are acceptable. We compared the taste and visual acceptability of various LSSS in South African adults. METHODS AND RESULTS: Fifty-six adults underwent double-blind taste and visual tests of four LSSS (35%KCl/65%NaCl; 50%KCl/50%NaCl; 66%KCl/34%NaCl; 100%KCl) in comparison to 100%NaCl (common salt). Participants scored each product by taste ranking, taste perception and likeliness to use. Participants then visually inspected the five products and attempted to identify which was which. Almost half (45 %) of participants ranked the taste of 50%KCl/50 %NaCl as fantastic or really good. Furthermore, 62 % of participants liked and would be happy to use the 50 %KCl/50 %NaCl or felt this tasted like common salt. Only 12 % rated the 100%KCl highly for taste, and over half reported being unlikely to use this. Most participants (57.3 % and 36.4 %) were able to visually identify 100%NaCl and 100%KCl, while identification of other blends was generally poor. Responses were similar for 35%KCl/65%NaCl and 66%KCl/34%NaCl throughout. CONCLUSION: Our findings suggest that the taste of the 50%KCl salt substitute would be well tolerated by South African adults, most of which could not visually differentiate between this salt substitute and common salt.

Obesity, hypertension, and tobacco use associated with left ventricular remodeling and hypertrophy in South African women: Birth to Twenty Plus Cohort.

BACKGROUND: Left ventricular hypertrophy (LVH) is a marker of increased risk in developing future life-threatening cardiovascular disease (CVD), however, it is unclear how CVD risk factors, such as obesity, blood pressure (BP), and tobacco use, are associated with left ventricular (LV) remodeling and LVH in urban African populations. Therefore, we aimed to identify the prevalence of LVH as well as the health factors associated with LV remodeling and LVH, within black South African adult women and their pre-pubescent children. METHODS: Black female adults (n = 123; age: 29-68 years) and their children (n = 64; age: 4-10; 55% female) were recruited from the Birth to Twenty Plus Cohort in Soweto, South Africa. Tobacco and alcohol use, physical activity, presence of diabetes mellitus, heart disease, and medication were self-reported. Height, weight, and blood pressure were measured in triplicate to determine the prevalence of obesity and hypertension respectively. Echocardiography was used to assess LV mass at end-diastole, based on linear measurements, and indexed to body surface area to determine LVH. RESULTS: Hypertension and obesity prevalences were 35.8% and 59.3% for adults and 45.3% and 6.3% for children. Self-reported tobacco use in adults was 22.8%. LVH prevalence was 35.8% in adults (75% eccentric: 25% concentric), and 6.3% in children. Concentric remodeling was observed in 15.4% of adults, however, concentric remodeling was only found in one child. In adults, obesity [OR: 2.54 (1.07-6.02; p = 0.02)] and hypertension [3.39 (1.08-10.62; p = 0.04)] significantly increased the odds of LVH, specifically eccentric LVH, while concentric LVH was associated with self-reported tobacco use [OR: 4.58 (1.18-17.73; p = 0.03)]. Although no logistic regression was run within children, of the four children LVH, three had elevated blood pressure and the child with normal blood pressure was overweight. CONCLUSIONS: The association between obesity, hypertension, tobacco use, and LVH in adults, and the 6% prevalence of LVH in children, calls for stronger public health efforts to control risk factors and monitor children who are at risk.

Inflammation and salt in young adults: the African-PREDICT study.

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.

Distinct inflammatory mediator patterns in young black and white adults: The African-predict study.

OBJECTIVE: Inflammatory mediators have been implicated in the early stages of cardiovascular disease development, including hypertension. Since global reports reflect a higher hypertension prevalence in black than white populations, we hypothesise the involvement of specific inflammatory mediators. We therefore compared a detailed range of 22 inflammatory mediators between young black and white adults, and determined the relationship with blood pressure. APPROACH AND RESULTS: We included 1197 adults (20-30 years; 50% black; 52% female) with detailed ambulatory blood pressures. Blood samples were analysed for 22 inflammatory mediators. For pro-inflammatory mediators, the black adults had higher C-reactive protein, interferon-inducible T-cell alpha chemoattractant, macrophage inflammatory protein 3 alpha (all p ≤ 0.008), but lower interferon-gamma, interleukin (IL)-1ß, IL-8, IL-12, IL-17A, and tumour necrosis factor alpha (all p ≤ 0.048). For anti-inflammatory mediators the black group consistently had lower levels (IL-5, IL-10 and IL-13 (all p ≤ 0.012)), resulting in generally higher pro-to-anti-inflammatory ratios in black than white adults (p ≤ 0.001). In mediators with pro- and anti-inflammatory functions, the black group had lower granulocyte-macrophage colony-stimulating factor and IL-6 (both p ≤ 0.010). These patterns were confirmed after adjustment for age, sex and waist circumference, or when stratifying by hypertensive status, sex and socio-economic status. Multi-variable adjusted regression analyses and factor analysis yielded no relationship between inflammatory mediators and blood pressure in this young healthy population. CONCLUSIONS: Black and white ethnic groups each consistently presented with unique inflammatory mediator patterns regardless of blood pressure, sex or social class. No association with blood pressure was seen in either of the groups.

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

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

Acceptability and feasibility of home-based hypertension and physical activity screening by community health workers in an under-resourced community in South Africa.

Background: Low-middle-income countries (LMICs) face increasing burdens from non-communicable disease (NCDs) requiring primary care task shifting to community health workers (CHWs). This study explored community members' perceptions of NCD-focused, CHW-led home visits in a historically disadvantaged township of South Africa. Methods: Trained CHWs visited community member homes, performing blood pressure and physical activity (PA) screenings, followed by brief counselling and a satisfaction survey. Semi-structured interviews were conducted within 3 days of the visit to learn about their experiences. Results: CHWs visited 173 households, with 153 adult community members consenting to participate (88.4%). Participants reported that it was easy to understand CHW-delivered information (97%), their questions were answered well (100%), and they would request home service again (93%). Twenty-eight follow-up interviews revealed four main themes: 1) acceptance of CHW visits, 2) openness to counselling, 3) satisfaction with screening and a basic understanding of the results, and 4) receptiveness to the PA advice. Conclusion: Community members viewed CHW-led home visits as an acceptable and feasible method for providing NCD-focused healthcare services in an under-resourced community. Expanding primary care reach through CHWs offers more accessible and individualized care, reducing barriers for individuals in under-resourced communities to access support for NCD risk reduction.

Reliability, usability and identified need for home-based cardiometabolic health self-assessment during the COVID-19 pandemic in Soweto, South Africa.

A major obstacle to tackling the growing burden of chronic disease in South Africa is lack of testing, particularly where individuals face multiple barriers to accessing health services. We conducted a pilot study to evaluate a cardiometabolic self-measurement kit, including assessment of blood pressure, obesity and urine analysis, amongst adults in Soweto, South Africa. Participants (N = 94) were recruited by researchers during community health screening and were provided with a home test kit including a tablet with self-measurement instructions. The participants entered their results on the tablet and, on completion, the researcher immediately repeated the measurements. We interviewed 10% of participants to understand their experience and views of the kits. Concordance correlation coefficients ranged from 0.78 for waist circumference to 0.93 for height, while the overall percentage agreement ranged from 80.5% for both urine protein and urine glucose testing to 91.4% for the identification of central obesity (ratio of waist circumference to height of ≥ 0.5). Participants saw the need for self-testing and found the process for the most part simple, though urine testing and height self-assessment presented some challenges. This pilot study suggests that self-assessment at home has the potential to facilitate the identification of individuals at risk for cardiometabolic disease in low-income settings, adding to a growing body of evidence on the use of self-testing in disease prevention and detection. However, we would not recommend self-testing for urine glucose and protein without further study.

Prevalence and socio-structural determinants of tobacco exposure in young women: Data from the Healthy Trajectories Initiative (HeLTI) study in urban Soweto, South Africa.

BACKGROUND: Tobacco use is a major public health risk worldwide, which has increased on the African continent over the past 40 years. Socio-economic factors impact tobacco use and exposure, but little is known about the scope of this problem in young women living in an urban, historically disadvantaged township in contemporary South Africa. This study aimed to identify the prevalence of tobacco use in a cohort of young South African women using serum cotinine, and to assess the association between a number of socio-economic and social factors and tobacco use in this setting. METHODS: Secondary analysis was conducted on cross-sectional data from the Healthy Life Trajectories Initiative (HeLTI) study. Serum cotinine was measured and a cut-off of ≥ 10 ng/mL was classified as tobacco use. Household socio-economic, socio-demographic and health information were collected by an interviewer-administered questionnaire. RESULTS: Cotinine data was available for 1508 participants, of whom 29.2% (n = 441) had cotinine levels indicative of tobacco use. In regression analyses, moderate to severe socio-economic vulnerability (score 2-3 OR 1.66, p = 0.008; score ≥4: OR 1.63, p = 0.026) and multiparity (OR 1.74, p = 0.013) were associated with tobacco use. In addition, alcohol dependence (OR 3.07, p < 0.001) and drug use (OR 4.84, p < 0.001) were associated with tobacco use. CONCLUSION: Young women with multiple children, moderate to severe socio-economic vulnerability, and alcohol and drug use were identified as more likely to use tobacco, indicating the need for targeted anti-tobacco interventions to curb the impact of tobacco on the growing burden of noncommunicable diseases in this setting.

Paediatric Hypertension in Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: The burden of cardiovascular disease (CVD) and hypertension is rapidly increasing in low- and middle-income countries. This is evident not only in adults, but also in children. Recent estimates of prevalence in children are lacking, particularly in Africa. As such, we conducted a systematic review and meta-analysis to provide updated estimates of paediatric hypertension in Africa. METHODS: We searched PubMed and EBSCO to identify articles published from January 2017 to November 2020. Studies were assessed for quality. We combined results for meta-analyses using a random effects model (Freeman-Tukey arcsine transformation). Heterogeneity was quantified using the I2 statistic. FINDINGS: In the narrative synthesis of 53 studies, publication bias was low for 28, moderate for 24, and high for one study. Hypertension prevalence ranged substantially (0·2%-38·9%). Meta-analysis included 41 studies resulting in data on 52918 participants aged 3 to 19 years from ten countries. The pooled prevalence for hypertension (systolic/diastolic BP≥95th percentile) was 7·45% (95%CI 5·30-9·92, I2=98.96%), elevated blood pressure (BP, systolic/diastolic BP≥90th percentile and <95th percentile) 11·38% (95%CI 7·94-15·33, I2=98.97%) and combined hypertension/elevated BP 21·74% (95%CI 15·5-28·69, I2=99.48%). Participants categorized as overweight/with obesity had a higher prevalence of hypertension (18·5% [95%CI 10·2-28·5]) than those categorized as underweight/normal (1·0% [95%CI 0·1-2·6], 4·8% [95%CI 2·9-7·1], p<0·001). There were significant differences in hypertension prevalence when comparing BP measurement methods and classification guidelines. INTERPRETATION: Compared to a previous systematic review conducted in 2017, this study suggests a continued increase in prevalence of paediatric hypertension in Africa, and highlights the potential role of increasing overweight/obesity. FUNDING: This research was funded in part by the Wellcome Trust [Grant number:214082/Z/18/Z]. LJW and SAN are supported by the DSI-NRF Centre of Human Development at the University of the Witwatersrand.

Are cardiovascular health measures heritable across three generations of families in Soweto, South Africa? A cross-sectional analysis using the random family method.

OBJECTIVES: Cardiovascular disease is increasing in many low and middle-income countries, including those in Africa. To inform strategies for the prevention of cardiovascular disease in South Africa, we sought to determine the broad heritability of phenotypic markers of cardiovascular risk across three generations. DESIGN: A cross-sectional study conducted in a longitudinal family cohort. SETTING: Research unit within a tertiary hospital in a historically disadvantaged, large urban township of South Africa. PARTICIPANTS: 195 individuals from 65 biological families with all three generations including third-generation children aged 4-10 years were recruited from the longest running intergenerational cohort study in Africa, the Birth to Twenty Plus cohort. All adults (grandparents and parents) were female while children were male or female. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was heritability of blood pressure (BP; brachial and central pressures). Secondary outcomes were heritability of arterial stiffness (pulse wave velocity), carotid intima media thickness (cIMT) and left ventricular mass indexed to body surface area (LVMI). RESULTS: While no significant intergenerational relationships of BP or arterial stiffness were found, there were significant relationships in LVMI across all three generations (p<0.04), and in cIMT between grandparents and parents (p=0.0166). Heritability, the proportion of phenotypic trait variation attributable to genetics, was estimated from three common statistical methods and ranged from 23% to 44% for cIMT and from 21% to 39% for LVMI. CONCLUSIONS: Structural indicators of vascular health, which are strong markers of future clinical cardiovascular outcomes, transmit between generations within African families. Identification of these markers in parents may be useful to trigger assessments of preventable risk factors for cardiovascular disease in offspring.

Inflammation and hypertension development: A longitudinal analysis of the African-PREDICT study.

BACKGROUND: The role of inflammation in the development of hypertension remains incompletely understood. While single inflammatory mediators have been shown to associate with changes in blood pressure (ΔBP), the role of clusters of inflammatory mediators has been less comprehensively explored. We therefore determined whether individual or clusters of inflammatory mediators from a large biomarker panel were associated with ΔBP over 4.5 years, in young healthy adults. METHODS: We included 358 adults (white, n = 156; black, n = 202) with detailed information on ambulatory blood pressure (BP) at baseline and follow-up. Baseline blood samples were analysed for 22 inflammatory mediators using multiplexing technology. Principal component analysis was used to study associations between clusters of inflammatory mediators and ΔBP. RESULTS: In the total cohort in multivariable-adjusted regression analyses, percentage change in 24hr systolic BP associated positively with Factors 1 (Interferon-gamma, interleukin (IL)-4, IL-7, IL-10, IL-12, IL-17A, IL-21, IL-23, macrophage inflammatory protein (MIP)-1α, MIP-1ß, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF)) and 2 (IL-5, IL-6, IL-8, IL-13). Change in daytime systolic BP associated positively with Factors 1, 2 and 3 (C-Reactive protein, IL-1ß, IL-2, MIP-3α). Subgroup analysis found these findings were limited to white study participants. Numerous associations were present between individual inflammatory mediators (Interferon-gamma, GM-CSF, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-21, IL-23, MIP-1α and MIP-1ß) and ΔBP in the white but not black subgroups. CONCLUSION: We found independent relationships between numerous inflammatory mediators (individual and clusters) and ΔBP over 4.5 years. The relationship between inflammatory markers and ΔBP was only found in white participants. ClinicalTrials.gov (Identifier: NCT03292094)..

Dietary sodium intake and its relationship to adiposity in young black and white adults: The African-PREDICT study.

Obesity and salt intake are both established factors contributing to cardiovascular disease development. Recently, studies found a controversial positive relationship between dietary salt and obesity. Therefore, the authors investigated whether obesity-related measures are associated with 24-hour urinary sodium in a healthy biethnic population. The study included 761 adults (20-30 years) with complete 24-hour urinary sodium, anthropometry, and bioelectrical impedance measurements. In single regression analyses all obesity-related measures related positively with 24-hour urinary sodium (P ≤ .008). However, with multivariate adjustments for energy intake, accelerometery, age, sex, black and white ethnicity, and other covariates, only body surface area (BSA) remained independently associated with 24-hour urinary sodium (R2  = 0.72, ß = .05, P = .039). To conclude, we found a consistent and robust positive relationship between BSA and estimated salt intake - but not with traditional obesity measures such as body mass index (BMI). Further studies are needed to investigate body surface area and potentially, skin area, in salt handling.