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.

Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153 152 middle-aged individuals.

AIMS: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine antithrombotic use and clinical outcomes. METHODS AND RESULTS: Baseline ECGs were collected in 153 152 middle-aged participants (ages 35-70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow-up of 7.4 years) were available in one cohort. Cross-sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China, and Southeast Asia (270-360 cases per 100 000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100 000 persons) (P < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs) (P < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received antithrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke [hazard ratio (HR) 2.29; 95% confidence interval (CI) 1.49-3.52] and death (HR 2.97; 95% CI 2.25-3.93); with similar rates in different countries grouped by income level. CONCLUSIONS: Large variations in AF prevalence occur in different regions and countries grouped by income level, but this is only partially explained by traditional AF risk factors. Antithrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.

Retinal microvasculature and masked hypertension in young adults: the African-PREDICT study.

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, ß = -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.

Drink types unmask the health risks associated with alcohol intake - Prospective evidence from the general population.

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.

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.

Retinal vessel caliber and caliber responses in true normotensive black and white adults: The African-PREDICT study.

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 ±â€¯11 vs. 164 ±â€¯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 ±â€¯2.1 vs. 3.3 ±â€¯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.

Three-year change in oxidative stress markers is linked to target organ damage in black and white men: the SABPA study.

Oxidative stress is implicated in hypertension, carotid wall thickening, and renal dysfunction. Oxidative stress is linked to cardiovascular pathology in the black South African individuals who have a high prevalence of hypertension and early vascular aging. However, there are limited data relating changes in oxidative stress with vascular and renal deterioration over time. We aimed to investigate whether changes in oxidative stress over 3 years are associated with target organ damage in black (N = 89) and white (N = 91) men. Carotid intima-media thickness was measured using the SonoSite Micromaxx ultrasound system, and cross-sectional wall area (CSWA) was calculated. The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula. The percentage change (%∆) in oxidative stress markers was calculated and included reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR). Over 3 years, black men exhibited decreased ROS, SOD, and GR, while white men revealed decreased SOD and GPx. Black men displayed positive associations of CSWA with %∆ ROS (ß = 0.28; p = 0.017) and %∆ SOD (ß = 0.24; p = 0.047). White men displayed a negative association of CSWA with %∆ SOD (ß = -0.22; p = 0.042) and positive associations of eGFR with %∆ GPx (ß = 0.33; p = 0.001) and %∆ GR (ß = 0.39; p < 0.001). In white men, the association of CSWA with decreased SOD activity suggests oxidative-stress-related carotid remodeling, while associations of eGFR with the glutathione system suggests a postponement of microvascular deterioration. In black men, associations of oxidative stress markers with CSWA suggest that a sufficiently functioning antioxidant system may delay target organ damage.

Cardiovascular reactivity and oxidative stress in young and older adults: the African-PREDICT and SABPA studies.

Background: Oxidative stress and increased cardiovascular reactivity are associated with endothelial dysfunction and cardiovascular disease development. These factors along with early vascular compromise are more pronounced in black populations. We aimed to compare cardiovascular reactivity and investigate associations thereof with oxidative stress in two bi-ethnic cohorts (younger: 25.0 ± 3.19yrs; older: 44.7 ± 9.61yrs). Methods: Cardiovascular reactivity using the color-word conflict test was measured with the Finometer device. Oxidative stress markers included superoxide dismutase (SOD), γ-glutamyl transferase (γ-GT) and reactive oxygen species (ROS). Results: Black groups displayed greater cardiovascular responses to stress than white groups. In younger white participants, diastolic blood pressure (DBP) (ß = 0.31; p = 0.001) and mean arterial blood pressure (MAP) (ß = 0.28; p = 0.002) associated with ROS. In older black participants, DBP (ß = 0.23; p = 0.009), MAP (ß = 0.18; p = 0.033), stroke volume (ß = -0.20; p = 0.023) and arterial compliance (ß = -0.25; p = 0.005) associated with γ-GT. In older white participants, systolic blood pressure (ß = -0.20; p = 0.006) and MAP (ß = -0.19; p = 0.009) associated with SOD. Conclusions: In the older black group, cardiovascular reactivity associated with markers of glutathione metabolism, suggesting a possible compensatory up-regulation thereof in order to correct their heightened responses to stress. Independent of age, findings in the white groups support a regulatory role of ROS to maintain vascular tone during stress.

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.

The relation of blood pressure and carotid intima-media thickness with the glutathione cycle in a young bi-ethnic population: the African-PREDICT study.

Oxidative stress has been implicated in the development of hypertension, arterial stiffness and atherosclerosis. Optimal functioning of the enzymatic antioxidant system is central to prevent increased oxidative stress and its consequences. We aimed to investigate the relationships of ambulatory blood pressure and carotid intima-media thickness with enzyme activities of the glutathione cycle in 396 young, black and white South Africans of the African-PREDICT study. Ambulatory blood pressure and carotid intima-media thickness were measured and glutathione peroxidase and glutathione reductase activities were analyzed. Black participants had higher reactive oxygen species (men: p = 0.019; women: borderline p = 0.064) and total glutathione (both p < 0.001), but lower glutathione peroxidase activity and total antioxidant status (all p < 0.001). In black men, ambulatory pulse pressure was negatively associated with glutathione peroxidase activity (R2 = 0.19; ß = -0.25; p = 0.06). Black and white women displayed positive associations of ambulatory systolic blood pressure (black: R2 = 0.25; ß = 0.21; p = 0.048; white: R2 = 0.44; ß = 0.18; p = 0.016) with glutathione reductase activity, whereas white men displayed a positive association of ambulatory pulse pressure with glutathione reductase activity (R2 = 0.25; ß = 0.29; p = 0.01). The lower glutathione peroxidase activity and total antioxidant status, the higher reactive oxygen species, as well as the negative association between ambulatory pulse pressure and glutathione peroxidase activity in the black men suggest that oxidative stress may be associated with early vascular changes in this group. In the other three groups, the positive associations of blood pressure with glutathione reductase activity suggest a possible role for adequate glutathione reductase activity in preventing or delaying the development of hypertension.

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.

The association of endothelin-1 with markers of oxidative stress in a biethnic South African cohort: the SABPA study.

Both endothelin-1 and oxidative stress have important roles in the development of cardiovascular diseases such as hypertension and atherosclerosis. Limited information is available on the interaction between oxidative stress, the glutathione system and endothelin-1 in humans. We aimed to investigate the association of endothelin-1 with markers of oxidative stress and the antioxidant capacity in a biethnic South African cohort. This cross-sectional study included 195 black and 198 white South Africans. Serum endothelin-1 levels and oxidative stress-related markers such as reactive oxygen species (measured as serum peroxides), glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase were measured. In single, partial and multiple regression analyses endothelin-1 correlated positively with glutathione reductase activity (adj. R2=0.10; ß=0.232; P=0.020) and negatively with antihypertension medication (P=0.02) and tended to correlate with glutathione reductase-to-glutathione peroxidase ratio (adj. R2=0.10; ß=0.19; P=0.057) in black men. In white men, endothelin-1 correlated positively with ROS (adj. R2=0.09; ß=0.26; P=0.01) and negatively with glutathione peroxidase activity (adj. R2=0.05; ß=-0.23; P=0.02). In black women, endothelin-1 correlated negatively with total glutathione (adj. R2=0.22; ß=-0.214; P=0.026). Endothelin-1 may contribute to glutathione reductase upregulation through increased reactive oxygen species production mediated via endothelin-1 in black men. In white men, we observed a negative association between glutathione peroxidase and endothelin-1, describing the expected physiological relationship between endothelin-1 and reactive oxygen species. Higher total glutathione levels may act as a counter-regulatory mechanism to protect against oxidative vascular damage attributed by endothelin-1 in black women.

Carotid characteristics of black South Africans with five-year sustained hypertension.

INTRODUCTION: An important feature of hypertension is a reduction in large artery distensibility, which may be due to structural and functional adaptations. Black populations are particularly prone to the development of hypertension. We therefore compared the carotid characteristics between five-year sustained hypertensive and normotensive black South Africans, and investigated how carotid characteristics relate to cardiometabolic risk factors, inflammation, endothelial activation and health behaviours. METHODS: We included HIV-free black South Africans who were either consistently hypertensive (n = 351) or normotensive (n = 241) from 2005 to 2010. We assessed carotid characteristics, including intima-media thickness (IMT), distensibility and lumen diameter with B-mode ultrasound, and calculated Young's elastic modulus, cross-sectional wall area and beta-stiffness index. We measured the carotid dorsalis pedis pulse-wave velocity, brachial and central systolic blood pressure (cSBP) and determined metabolic, inflammatory and endothelial activation markers from blood samples. Health behaviours were reported in questionnaires. RESULTS: The hypertensive group presented with higher brachial and central blood pressure, thicker IMT and stiffer carotid arteries (all p < 0.001). However, after adjustment for cSBP but not mean arterial pressure (MAP), all significant differences in carotid characteristics were lost. The carotid thickness measurements did not differ after adjustment for MAP. After adjustment, metabolic, inflammatory and endothelial activation markers did not differ between the two groups. CONCLUSION: Our results suggest that besides structural changes, functional adaptations are also involved in deterioration of the carotid wall characteristics of hypertensive black South Africans. These results highlight the importance of proper hypertension control in Africa.

Lung function, inflammation and cardiovascular mortality in Africans.

BACKGROUND: The link between impaired lung function and cardiovascular outcome is well established in European and American populations. It is possible that this association may be driven by a systemic spillover of inflammation occurring within the lungs. As several studies have found an increased level of inflammatory markers in African populations, we aimed to establish the contribution of lung function in predicting all-cause and cardiovascular mortality in Africans, whilst taking inflammatory markers into account. DESIGN: We followed 1442 black South Africans from the North West Province participating in the South African leg of the Prospective Urban and Rural Epidemiology (PURE) study, over a five-year period. Spirometry, cardiovascular and metabolic measures were performed, and cardiovascular mortality as well as all-cause mortality used as endpoints. RESULTS: In univariate Cox regression models, both forced expiratory volume in 1-s (FEV1 ) and forced vital capacity (FVC) predicted all-cause (P = 0·022; P < 0·001) and cardiovascular mortality (P = 0·004; P < 0·001). In multivariate adjusted standardized Cox regression analyses, only FVC predicted cardiovascular mortality independent of several covariates (hazard ratio, 0·57 [0·35-0·94]), including C-reactive protein (CRP). When CRP was replaced by interleukin-6 in the model, the significance of FVC was lost (hazard ratio, 0·85 [0·55-1·30]). CONCLUSION: FVC, but not FEV1 , is a strong predictor of both all-cause and CV mortality in black South Africans, which may be mediated by inflammation.

Attenuated IGF-1 predicts all-cause and cardiovascular mortality in a Black population: A five-year prospective study.

BACKGROUND: Inconsistent findings are reported on whether insulin-like growth factor-1 (IGF-1) is protective or harmful in predicting hypertension, carotid wall thickness and mortality. We determined the five-year prognostic value of IGF-1 for these outcomes in a large Black population prone to hypertension and cardiovascular disease. DESIGN: A longitudinal study as part of the PURE (Prospective Urban and Rural Epidemiology) study, North West Province, South Africa. METHODS: We measured IGF-1 and IGF binding protein-3 (IGFBP-3) in 1038 HIV-uninfected participants (age range 32-94 years) and assessed blood pressure, carotid intima-media thickness and mortality. RESULTS: Over five years 116 deaths occurred. Baseline IGF-1 was similar in survivors and non-survivors (p = 0.50), but tended to be higher in survivors upon adjustment for IGFBP-3 and covariates (p = 0.061). Normotensives and hypertensives (p = 0.072), and those with carotid intima-media thickness < 0.9 mm and ≥ 0.9 mm also displayed similar baseline IGF-1 (p = 0.55). Multivariable-adjusted Cox-regression indicated high IGF-1 predicting lower risk for all-cause mortality (hazard ratio 0.45; 0.23-0.88) and cardiovascular mortality (hazard ratio 0.26; 0.08-0.83) when also adjusting for IGFBP-3. When including normo- and hypertensives at baseline, high IGF-1 was related to normotension at follow-up (hazard ratio 0.68; 0.49-0.95). We found no association with carotid intima-media thickness (hazard ratio 0.59; 0.31-1.14). CONCLUSION: In a Black South African population with low socio-economic status and harmful health behaviours, we found a protective independent association between IGF-1 and hypertension, cardiovascular and all-cause mortality, with no association with carotid wall thickness.

Cardiovascular function is not associated with creatine kinase activity in a black African population: The SABPA study.

BACKGROUND: Higher creatine kinase (CK) activity is associated with the development of cardiovascular disease in black African populations. We compared CK activity and investigated associations of blood pressure with CK activity in black and white men as well as black and white women. METHODS: Ambulatory blood pressure, total peripheral resistance and pulse wave velocity of 197 black and 208 white participants were determined and serum CK activity was measured. RESULTS: Blood pressure and pulse wave velocity were higher in black men and women (all p < 0.001) when compared to their white counterparts. CK activity only varied between black and white women (75.9 U/l vs 62.8 U/l, p = 0.009), even after adjusting for age, body mass index and physical activity. Despite the worse cardiovascular profile of black men and women, and the higher CK activity in the black women, we were unable to link blood pressure, pulse wave velocity or total peripheral resistance with CK activity, in the black African population. In white men, total peripheral resistance was associated with CK activity (R (2) = 0.32; ß = 0.25; p = 0.009), whereas systolic blood pressure (R (2) = 0.46; ß = 0.17; p = 0.03) and pulse pressure (R (2) = 0.31; ß = 0.21; p = 0.01) were associated with CK activity in white women. CONCLUSIONS: The lack of associations in the black African population suggests that the link between a worse cardiovascular profile and CK activity may be overshadowed by other contributing factors. Whereas, the established link between cardiovascular function and CK activity in the white groups may be the result of enhanced smooth muscle cell contractility and/or attenuated nitric oxide synthesis capacity.

Antioxidant enzyme activity is associated with blood pressure and carotid intima media thickness in black men and women: The SABPA study.

In the urbanized black population of South Africa, oxidative stress may play a crucial role in the development of hypertension. Since oxidative stress may result from impaired antioxidant capacity we aimed to investigate antioxidant enzyme activity as well as its associations with vascular function and structure in a bi-ethnic population. Participants included 409 subjects almost equally stratified by ethnicity and sex. Blood pressure and carotid intima media thickness (cIMT) were measured and glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) enzyme activities were determined. GR activity was significantly higher in black men (7.71 nmol/min/ml vs 2.23 nmol/min/ml) and women (6.46 nmol/min/ml vs 2.86 nmol/min/ml) (p < 0.001) when compared to their white counterparts. In black women, GPx activity was significantly lower (p < 0.001) when compared to white women (31.9 nmol/min/ml vs 37.1 nmol/min/ml). In black men, cIMT was positively and independently associated with GR activity (R(2) = 0.30; ß = 0.18; p = 0.048). In black women, systolic blood pressure (R(2) = 0.21; ß = -0.24; p = 0.014), diastolic blood pressure (R(2) = 0.11; ß = -0.20; p = 0.044) and mean arterial pressure (R(2) = 0.20; ß = -0.31; p = 0.002) were inversely associated with GPx activity. No associations were found in the white groups. The positive association between GR activity and cIMT in black men may be the result of a compensatory response to prevent arterial remodelling. The inverse association between GPx activity and blood pressure in black women may indicate a role for decreased GPx activity in hypertension development in this population.

The relationship of nitric oxide synthesis capacity, oxidative stress, and albumin-to-creatinine ratio in black and white men: the SABPA study.

Inadequate substrate availability and increased nitric oxide synthase inhibitor levels attenuate nitric oxide (NO) synthesis, whereas increased vascular oxidative stress may lead to inactivation of NO. We compared markers of NO synthesis capacity and oxidative stress in a bi-ethnic male population. Inter-relationships of ambulatory blood pressure and urinary albumin-to-creatinine ratio with NO synthesis capacity and oxidative stress markers were investigated. NO synthesis capacity markers (L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)) and oxidative stress markers (serum peroxides, total glutathione, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase) were measured. Black men displayed higher blood pressure and albumin-to-creatinine ratio (all p < 0.001), while NO synthesis capacity was more favorable (higher L-arginine and lower ADMA (p ≤ 0.003)). Antioxidant enzyme activities were similar except for the redox status markers (GR activity and GR/GPx ratio), which were upregulated in black men (p < 0.001). In black men, ADMA was inversely related to GPx activity (R (2) = 0.15; ß = -0.20; p = 0.050) and GPx/SOD ratio (R (2) = 0.24; ß = -0.37; p < 0.001), but none of these markers related to blood pressure or albumin-to-creatinine ratio. In white men, albumin-to-creatinine ratio was positively associated with ADMA (R (2) = 0.18; ß = 0.39; p < 0.001) while ADMA was inversely related to GR activity (R (2) = 0.26; ß = -0.29; p = 0.002) and GR/GPx ratio (R (2) = 0.25; ß = -0.28; p = 0.003). Black men with elevated blood pressure and albumin-to-creatinine ratio displayed a favorable NO synthesis capacity. This may be counteracted by increased inactivation of NO, although it was not linked to vascular or renal phenotypes. In white men, reduced NO synthesis capacity may lower NO bio-availability, thereby influencing the albumin-to-creatinine ratio.