Strategies of Modelling Incident Outcomes Using Cox Regression to Estimate the Population Attributable Risk.

When the Cox model is applied, some recommendations about the choice of the time metric and the model's structure are often disregarded along with the proportionality of risk assumption. Moreover, most of the published studies fail to frame the real impact of a risk factor in the target population. Our aim was to show how modelling strategies affected Cox model assumptions. Furthermore, we showed how the Cox modelling strategies affected the population attributable risk (PAR). Our work is based on data collected in the North-West Province, one of the two PURE study centres in South Africa. The Cox model was used to estimate the hazard ratio (HR) of mortality for all causes in relation to smoking, alcohol use, physical inactivity, and hypertension. Firstly, we used a Cox model with time to event as the underlying time variable. Secondly, we used a Cox model with age to event as the underlying time variable. Finally, the second model was implemented with age classes and sex as strata variables. Mutually adjusted models were also investigated. A statistical test to the multiplicative interaction term the exposures and the log transformed time to event metric was used to assess the proportionality of risk assumption. The model's fitting was investigated by means of the Akaike Information Criteria (AIC). Models with age as the underlying time variable with age and sex as strata variables had enhanced validity of the risk proportionality assumption and better fitting. The PAR for a specific modifiable risk factor can be defined more accurately in mutually adjusted models allowing better public health decisions. This is not necessarily true when correlated modifiable risk factors are considered.

Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. METHODS: In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men). INTERPRETATION: Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women. FUNDING: Funding sources are listed at the end of the Article.

Determining Underlying Mechanisms of Early Vascular Ageing by Clustered Analysis: The African-PREDICT Study.

OBJECTIVE: Identifying individuals at increased risk of early vascular ageing (EVA) is paramount to inform intervention and prevention strategies and curb the increasing burden of cardiovascular disease. METHODS: We stratified and phenotyped pre-screened young apparently healthy South African adults (20-30 yrs) (n=1,041) into vascular ageing profile groups based on carotid femoral pulse wave velocity (cfPWV) percentiles (healthy vascular ageing [HVA]; average vascular ageing [AVA] and EVA). We further compared various anthropometric, cardiovascular (CV), oxidative stress and lifestyle risk factors and determined factor scores to explore associations between CV measures and factor clusters to explore associations in those at risk of EVA. RESULTS: Young adults in the EVA group displayed marked phenotypic characteristics in terms of anthropometry, CV, and lifestyle risk factors, even though cfPWV were within healthy ranges. Blood pressure (brachial and central) and cfPWV were all incrementally higher across all three vascular ageing groups (p-trend ≤0.011). Hypertension, lifestyle risk factors such as self-reported smoking and alcohol consumption were all highest in the EVA group (p-trend ≤0.046). Additionally, in the EVA group only, cfPWV (adj. R2=0.028; ß=0.171; p=0.042) associated positively with Factor 2 (oxidative stress and antioxidant capacity). No associations existed between Factor 1 (basic lipids) and any anthropometric or CV measures (p>0.050). CONCLUSION: Young adults with higher cfPWV presented with a less favourable vascular profile and more unhealthy lifestyle behaviours compared to groups with lower cfPWV. In the EVA group, cfPWV positively associated with a cluster of oxidative stress and antioxidant capacity. Early lifestyle behaviours may have the ability to modify the balance between oxidants and antioxidants, potentially contributing to early onset arterial stiffness.

Obesity, blood pressure and retinal microvascular phenotype in a bi-ethnic cohort of young children.

BACKGROUND AND AIMS: Childhood obesity and high blood pressure (BP) are main determinants for cardiovascular disease development with regional and ethnic differences. Narrower arteriolar (CRAE) and wider venular (CRVE) retinal vessel diameters are sensitive markers of early vascular compromise in children. We aimed to compare retinal vessel diameters and investigate associations and odds ratios with body mass index (BMI) and BP in a multi-national/ethnic childhood study. METHODS: BMI, systolic (SBP) and diastolic BP (DBP) were screened in 929 black and white South African (SA) and 1171 Swiss children (aged 5-9 years). Retinal assessments were performed using a retinal vessel analyzer to determine CRAE and CRVE. RESULTS: Black SA children had wider CRVE compared to white SA and Swiss children (all p < 0.001). However, BMI or BP was not associated with CRVE in black SA children. Higher BMI and BP associated with narrower CRAE in all children, except for BMI in black SA children, in whom narrower CRAE was found for every unit increase in SBP (ß = -0.199 µm, p = 0.001) and DBP (ß = -0.312 µm, p < 0.001). Obesity (OR:1.38[1.01; 1.89]), hypertension (OR:1.90[1.53; 2.36]) and black ethnicity (OR:1.50[1.18; 1.92]) increased the likelihood for arteriolar narrowing. CONCLUSIONS: Black SA children presented with wider retinal venules compared to their white SA and Swiss peers, which was unexplained by conventional risk factors. The overall risk of arteriolar narrowing was driven by obesity, hypertension and ethnicity. Our findings indicate the importance to differentiate cardiovascular risk by microvascular phenotype in different populations and ethnicity early in life.

Age-related differences in the vascular function and structure of South Africans living with HIV.

Background: As the life expectancy of people living with the HIV increases because of antiretroviral treatment (ART), their risk for vascular co-morbidities and early vascular ageing (EVA) also increases. Objective: We aimed to investigate whether HIV infection relates to vascular structure and function in black South African adults and whether this relationship is age dependent. Method: This cross-sectional study carried out in urban and rural areas of North West province, South Africa, included 572 age- and sex-matched people living with HIV (PLWH) and without HIV. Participants from the EndoAfrica study and PURE study were stratified according to tertiles of age. Measures of vascular structure (carotid intima-media thickness) and function (carotid-femoral pulse wave velocity, central systolic blood pressure, central pulse pressure and pulse pressure amplification) were determined. Results: Blood pressure measures were lower in PLWH compared with their controls (all P ≤ 0.001), especially in the younger and middle-aged groups (all P ≤ 0.031), whilst vascular measures did not differ (all P ≥ 0.611). In multivariate linear regression analyses, vascular measures were not associated with a HIV- positive status in either the total or any of the age groups. Conclusion: Black South Africans living with HIV have a less adverse blood pressure profile than their counterparts without HIV. The HIV-positive status was not associated with measures of vascular structure or function in any age group. The results suggest that HIV does not contribute to EVA in this population; however, further longitudinal investigation is warranted.

Aldosterone and angiotensin II profiles in young black and white women using different hormonal contraceptives: the African-PREDICT study.

Exogenous estrogens and progestins may affect the components of the renin-angiotensin-aldosterone system (RAAS). Changes in ventricular blood volume are associated with increased secretion of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP), which may also be affected by hormonal contraceptives. In this study, we aimed to compare components of the RAAS and NT-proBNP between groups using different hormonal contraceptives, including the combination pill, the injection or implant, and controls (no contraception) in black and white women of fertile age (20 - 30 years). Secondly, we determined whether blood pressure and NT-proBNP are associated with the RAAS components. We included 397 black and white women not using contraceptives, 120 using the combination pill, and 103 receiving an injection/implant. RAAS Triple-A analysis was carried out with LC-MS/MS quantification, and blood pressure measurements (ABPM) taken over 24 h. We found that serum aldosterone was higher (475.7 vs. 249.2 pmol/L; p < 0.001) in the combination pill group than in the no contraception group of white women. The aldosterone-angiotensin II ratio (AA2) was higher (5.4 vs. 2.5; p < 0.001) in the combination pill group than in the no contraception group. In the black women using the combination pill, we found a borderline-positive and borderline-negative association between 24-h systolic blood pressure and NT-proBNP with equilibrium (eq) Ang II, respectively. In white women using the combination pill, only CRP contributed positively and independently to NT-proBNP. To conclude, activation of RAAS by different hormonal contraceptives may increase future risk for the development of hypertension in young black and white women.

Elevated blood pressure positively associates with alpha-1 microglobulin in prepubescent children: the ExAMIN Youth SA study.

OBJECTIVES AND METHODS: Hypertension is a growing health concern in childhood populations and individuals of African descent. As the kidneys play a significant role in blood pressure regulation, we compared alpha-1 microglobulin (A1M) as a marker of proximal tubular function between young healthy black and white children (n = 957; aged: 5-9 years) and explored its association with blood pressure. RESULTS: The black children had higher levels of A1M (P < 0.001) and higher DBP (P < 0.001) when compared with their white counterparts. In multiple regression analysis, SBP (adj. R2 = 0.173, ß = 0.151; P < 0.001) and DBP (adj. R2 = 0.110, ß = 0.179; P < 0.001) associated positively with A1M in the black children. In binary logistic regression, each standard deviation increase in A1M increased the odds of having elevated blood pressure by 28% (P = 0.002) in the black group, independent of age, sex, BMI z-score and body height. No significance was reached in the white children. CONCLUSION: Our findings highlight the importance of a marker of proximal tubular function, especially in children of black ethnicity, in the setting of elevated blood pressure. Early childhood screening for elevated blood pressure remains essential in order to promote primary prevention of hypertension and early onset kidney damage in children.

Comparing the associations of clinic vs. ambulatory blood pressure with subclinical organ damage in young healthy adults: the African-PREDICT study.

Raised blood pressure (BP) causes pathophysiological cardiovascular changes resulting in target organ damage. Although ambulatory and central BP relate more strongly to outcomes than clinical brachial BP in the elderly population, it is unknown which measure of BP is most strongly associated with markers of organ damage in younger populations. We compared the strength of associations between different BPs and measures of subclinical organ damage and investigated whether ethnic differences exist between these associations. The design was a cross-sectional analysis of the African-PREDICT study, including young black and white men and women (aged 20-30, N = 1202). We obtained clinic, ambulatory, and central BP readings, as well as measures of subclinical organ damage: central retinal arteriolar equivalent (CRAE) from fundus images, echocardiography to determine left ventricular mass index (LVMi), carotid intima media thickness (CIMT), carotid-femoral pulse wave velocity (PWV), and albumin-to-creatinine ratio (ACR) determined from spot urine samples. Overall, weak correlations were evident between CIMT, ACR, and BP, whereas CRAE, LVMi, and PWV correlated strongly with BP. In the total group, clinic brachial BP had stronger associations with CRAE, LVMi, and PWV (all p < 0.001) than ambulatory and central BP. Although the ethnic groups showed similar correlations between CRAE, LVMi, CIMT, and the various BPs, PWV correlated more strongly with ambulatory systolic BP (p < 0.001) in white participants. In young healthy adults, clinic brachial BP correlated more strongly with measures of early target organ damage than central or ambulatory BP. No differences were observed between correlations of BP and measures of target organ damage in the two ethnic groups.

Cross-Talk Between Large Artery Stiffness and Retinal Microvasculature in Children: The ExAMIN Youth SA Study.

Background: Cross-talk between the macro-and microvasculature is considered an important contributor to target organ damage. Previous findings were predominantly in adult populations and investigation into this mechanism in children may provide insight into the development of early adverse vascular changes. Whether any ethnic differences in cross-talk is evident, also remains to be determined. Objective: To determine whether retinal microvascular diameters are associated with large artery stiffness in young children and whether ethnic differences are evident. Materials and Methods: In this cross-sectional study, 730 black (n = 437) and white (n = 293) school children aged 5-9 years were included. Pulse wave velocity (PWV) was measured and the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) diameters were calculated from fundus images. The arterio-venous ratio (AVR) was subsequently calculated. Results: Pulse wave velocity was lower (p ≤ 0.001) in the black group when compared to the white group. The black group had a narrower CRAE, wider CRVE and lower AVR (all p < 0.001). Pulse wave velocity associated negatively with CRAE (r = -0.141, p = 0.003) and AVR (r = -0.185, p ≤ 0.001) in the black group only. A positive association between PWV and CRVE was seen in the black (r = 0.174, p ≤ 0.001) and white (r = 0.119, p = 0.043) group. Conclusion: Large artery stiffness is associated with retinal arterial narrowing and venular widening in children, suggesting cross-talk between the macro-and microvasculature. Ethnic differences in these associations are also evident. Our findings warrant further investigation into environmental and sociocultural risk factors contributing to premature cardiovascular disease development.

Associations of central and peripheral blood pressure with the renin-angiotensin-aldosterone system in healthy young adults: the African-PREDICT study.

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.

Vascular function and cardiovascular risk in a HIV infected and HIV free cohort of African ancestry: baseline profile, rationale and methods of the longitudinal EndoAfrica-NWU study.

BACKGROUND: People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world's largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. METHODS: In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. RESULTS: At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV. CONCLUSION: Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.

The Exercise, Arterial Modulation and Nutrition in Youth South Africa Study (ExAMIN Youth SA).

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. Trial registration: The study was retrospectively registered on ClinicalTrials.gov on 15 August 2019 (NCT04056377).

Ethnicity and Arterial Stiffness.

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.

Relation of the renin-angiotensin-aldosterone system with potential cardiac injury and remodelling: the SABPA study.

Purpose: The renin-angiotensin-aldosterone system (RAAS) plays an important role in maintaining hemodynamic homeostasis. Ethnic disparities exist regarding RAAS activity due to sympathetic activity and sodium-water retention, however the implications thereof on cardiac damage is unknown. This study investigated the associations of cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NTproBNP) and subclinical LVH with components of the RAAS (renin, aldosterone and aldosterone-to-renin ratio (ARR)) and copeptin in a black and white South African cohort.Materials and methods: The study population consisted of 305 participants (black = 139, white = 166) aged 20-62 years. Serum cTnT, NTproBNP, Cornell product, components of the RAAS (active renin, aldosterone and ARR) and copeptin were determined.Results: The black group had lower renin (p < 0.001) and higher ARR (p < 0.001), cTnT (p = 0.015) and Cornell product compared to whites (all p < 0.001). NTproBNP and copeptin were similar between the groups. After forward stepwise adjustments for multiple confounders, inverse associations of cTnT with renin (ß = -0.17, p = 0.018) and aldosterone (ß = -0.14, p = 0.048) as well as an inverse association between NTproBNP and aldosterone (ß = -0.25, p < 0.001) were observed in the white population only. In the black group cTnT associated positively with renin (ß = 0.16, p = 0.040) and copeptin (ß = 0.21, p = 0.020) and inversely with ARR (ß = -0.15, p = 0.047). Additionally, NTproBNP associated positively with copeptin (ß = 0.18, p = 0.045). No correlations were observed between the RAAS and Cornell product in any of the groups.Conclusions: Our findings suggest that RAAS, together with cardiac stress may function differently in cardiac damage and remodelling in the two ethnic groups; which may influence treatment in clinical practice.

A primary aldosteronism-like phenotype identified with the aldosterone-to-angiotensin II ratio in black men: the SABPA study.

INTRODUCTION: Black populations may be more likely to have primary aldosteronism (PA) due to adrenal hyperplasia or other forms of adrenal hyperactivity, with suppressed renin levels and high levels of aldosterone, which may contribute to the development of hypertension. METHODS: This sub-study involved 35 black men matched for age, gender and race, and aged 20-65 years, living in the North West Province of South Africa. RAAS triple-A analysis was carried out with LC-MS/MS quantification. Blood pressure, electrocardiography and other variables were determined with known methods. RESULTS: Hypertensive subjects with higher aldosterone levels showed an increased aldosterone-angiotensin II ratio (AA2 ratio) compared to the hypertensive subjects with low aldosterone levels (10.2 vs 3.0 pmol/l; p = 0.003). The serum potassium concentration was significantly lower in the high-aldosterone group and the serum sodium-potassium ratio was significantly higher compared to the low-aldosterone group (3.9 vs 4.5, p = 0.016, 34.8 vs 31.8, p = 0.032, respectively). Furthermore, aldosterone was positively associated with both left ventricular hypertrophy (Cornell product) (Spearman R = 0.560; p = 0.037) and kidney function [albumin-to-creatinine ratio (ACR) ] (Spearman R = 0.589, p = 0.021) in the hypertensive high-serum aldosterone group. CONCLUSIONS: The AA2 ratio, a novel screening test that is currently being validated for PA case detection, was used to identify a PA-like phenotype in black men. Excess aldosterone was associated with endothelial dysfunction and left ventricular hypertrophy, independent of blood pressure.

Is the cardiovascular health of South Africans today comparable with African Americans 45 years ago?

OBJECTIVES: Hypertension occurs frequently among black populations around the world. In the United States (US) health system, interventions since the 1960s resulted in improvements in hypertension awareness, management and control among African Americans. This is in stark contrast to current health systems in African countries. To objectively assess the current situation in South Africa, we compared the cardiovascular health status of African Americans from 1960 to 1980 to black South Africans from recent years, as there is potential to implement best practices from the US. We also reviewed the recent cardiovascular health changes of a South African population over 10 years. METHODS: Men and women were included from three studies performed in the United States (Evans County Heart Study; Charleston Heart Study; NHANES I and II) and one in South Africa (PURE, North West Province). We compared blood pressure (BP), BMI, cholesterol, diabetes and smoking status. RESULTS: Age-adjusted SBP and DBP of South African men were lower than US studies conducted from 1960 to 1971 (Evans County; Charleston; NHANES I; all P < 0.001) but similar to NHANES II (P = 0.987) conducted in 1976. South African women had lower SBP than all four of the US studies (all P < 0.001); their DBP was lower than Evans County and Charleston studies, but similar to NHANES I and II. Reviewing South African data, BMI increased steeply over 10 years in women (P < 0.001) but not men (P = 0.451). CONCLUSION: Blood pressure of South Africans is lower than African Americans from the 1960s, but comparable for 1970s to 1980s. With obesity of South African women rising sharply, escalating figures for hypertension and diabetes are anticipated.

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

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

Iron loading, alcohol and mortality: A prospective study.

BACKGROUND & AIMS: The relationship between total body iron and cardiovascular disease remains controversial and information absent in black sub-Saharan Africans in whom alcohol consumption tends to be high. The level of total body iron is tightly regulated, however this regulation is compromised by high alcohol intake causing iron loading. The aim of this study is to investigate total body iron, as represented by serum ferritin, and its interaction with measures of alcohol intake in predicting all-cause and cardiovascular mortality. METHODS: We followed health outcomes for a median of 9.22 years in 877 randomly selected HIV negative African women (mean age: 50.4 years). RESULTS: One hundred and five deaths occurred of which 40 were cardiovascular related. Ferritin averaged 84.0 (5th to 95th percentile interval, 7.5-533.3) ng/ml and due to the augmenting effect of inflammation, lowered to 75.3 (6.9-523.2) ng/ml after excluding 271 participants with high-sensitivity C-reactive protein (CRP) levels (above 8 mg/l). CRP increased by quartiles of ferritin in the total group (P trend = 0.002), but this relationship was absent after excluding the 271 participants with high CRP values (P trend = 0.10). Ferritin, gamma-glutamyl transferase and carbohydrate deficient transferrin (all P < 0.0001) were higher in drinkers compared to non-drinkers, but CRP was similar (P = 0.77). In multivariable-adjusted analyses, ferritin predicted both all-cause (hazard ratio, 2.08; 95% confidence interval, 1.62-2.68; P < 0.0001) and cardiovascular (1.94; 1.29-2.92; P = 0.002) mortality. In participants with CRP levels below or equal to 8 mg/l, the significant relationship remained between ferritin and all-cause (2.51; 1.81-3.49; P < 0.0001) and cardiovascular mortality (2.34; 1.45-3.76; P = 0.0005). In fully adjusted models, interactions existed between ferritin and gamma-glutamyl transferase, self-reported alcohol use and carbohydrate deficient transferrin in predicting all-cause (P ≤ 0.012) and cardiovascular mortality (P ≤ 0.003). CONCLUSIONS: Iron loading in African women predicted all-cause and cardiovascular mortality and the intake of alcohol seems mechanistically implicated.

Assessing tobacco use in an African population: Serum and urine cotinine cut-offs from South Africa.

BACKGROUND: Cotinine, a nicotine metabolite, is used to measure tobacco use and exposure, but recommended cut-offs to differentiate tobacco users from those exposed through the environment range from 3 to 58 ng/ml in serum, and 2.5 to 550 ng/ml in urine. Cut-offs may differ by ethnicity, sex and age. As data from adults in Africa are scarce, our aim was to evaluate cut-offs for serum and urine cotinine that best predict self-reported tobacco use in South African adults. METHODS: Two datasets were explored: African-PREDICT (n = 941 black and white healthy young adults, 20-30 years, serum cotinine); and WHO SAGE Wave 2 (n = 604 adults, 18-102 years, urine cotinine). Population specific cut-offs (ROC analyses) were compared with published cut-offs and self-reported tobacco use. RESULTS: Overall, 19% (293 of 1545) reported current tobacco use. The following cotinine cut-offs showed the highest sensitivity and specificity: serum ≥15 ng/ml in black and white men, and white women; serum ≥10 ng/ml in black women; urine ≥300 ng/ml for black, mixed ancestry, and older adults (50-plus years); urine ≥500 ng/ml for younger adults (18-49 years). Specificity was lower for urine than for serum cotinine. CONCLUSION: Our study suggests that a serum cotinine level of ≥15 ng/ml and a urine cotinine level of ≥300 ng/ml best distinguish current tobacco users from non-users generally in the South African adult population.

Pulse pressure amplification and its relationship with age in young, apparently healthy black and white adults: The African-PREDICT study.

BACKGROUND: Pulse pressure amplification (PPA), i.e. the amplification from central arteries to the periphery, is inversely related to arterial stiffness, organ damage and mortality. It is known that arterial stiffness is higher in black than white populations, but it is unclear if this is due to early vascular aging. We therefore investigated whether PPA declines earlier in young normotensive black South Africans, when compared to their white counterparts. METHODS: We included 875 black and white men and women from the African-PREDICT study (55% black, 41% men), aged 20-30years, with no prior diagnosis of chronic disease, screened for normotensive clinic blood pressure (BP). We determined supine central PP (cPP), and supine brachial systolic- and diastolic BP, from which brachial PP (bPP) was calculated. PPA was defined as the ratio of the amplitude of the PP between these distal and proximal locations (bPP/cPP). RESULTS: We found the mean PPA to be lower in black compared to white participants (1.43 vs. 1.46; P=0.013). In black adults PPA declined earlier with increasing age (P-trend<0.001), with a weak trend in whites (P=0.069) after adjustment for sex, socio-economic status, height, heart rate and mean arterial pressure. In multivariable-adjusted regression, we found an independent inverse association between PPA and age only in the black group (ß=-0.18, P=0.002). CONCLUSION: PPA declines earlier with age in normotensive black adults younger than 30years, exemplifying early vascular aging which may predispose black individuals to future cardiovascular outcomes.