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.

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.

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.

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.

Masked hypertension and its associated cardiovascular risk in young individuals: the African-PREDICT study.

Hypertension prevalence is increasing globally, yet little is known about the occurrence of masked hypertension (MHT) in young, sub-Saharan African adults, and how it relates to elevated cardiovascular risk. The African-PREDICT study (recruitment based on normotensive clinic blood pressure (BP)) determined the frequency of MHT and its relationship with arterial stiffness and biochemical markers of inflammation and endothelial activation. We included men and women (n=352), 20-30 years, screened for normotensive clinic BP (54% white, 40% men). Clinic BP, ambulatory blood pressure monitoring (ABPM), central systolic pressure, aortic pulse wave velocity (aPWV), augmentation index, anthropometry, physical activity and biochemical markers of cardiovascular risk were assessed (lipids, glucose, insulin, markers of endothelial activation and inflammation). Eighteen percent of the study population had MHT (60% white, 68% men). Those with MHT had increased adiposity, clinic-, ABPM- (24-h, day and night) and central-BP (within normal ranges), heart rate, aPWV and biochemical markers of cardiovascular risk, compared with normotensives (all P<0.05). Using multivariable adjusted odds ratios, we found that MHT was associated with increased likelihood for higher aPWV (odds ratio (OR)=1.567, P=0.010), insulin (OR=1.499, P=0.049), monocyte chemoattractant protein-1 (OR=1.499, P=0.026), vascular cellular adhesion molecule (OR=1.409, P=0.042) and C-reactive protein (OR=1.440, P=0.044). In a young adult (supposedly healthy) cohort, the occurrence of MHT is alarming, especially since MHT further demonstrated elevated cardiovascular risk via increased adiposity, arterial stiffness, endothelial activation and inflammation. Detection of MHT is crucial to increase awareness of elevated cardiovascular risk, and to ensure the required lifestyle and/or pharmaceutical interventions.

Inflammation as Possible Mediator for the Relationship Between Lung and Arterial Function.

INTRODUCTION: Reduced lung function is associated with a risk for the development of cardiovascular disease. This association may be due to chronic inflammation which is often present in those with reduced lung function. PURPOSE: We investigated the possible role of systemic inflammation as the mediator between lung function and arterial stiffness in 1534 black South Africans. METHODS: Spirometric data including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained. C-reactive protein (CRP), interleukin-6 (IL-6), blood pressure (BP) and carotid-radial pulse wave velocity (PWV) were determined. RESULTS: In multivariable-adjusted models, an independent inverse association was found between IL-6 and FEV1 (ß = -0.20, p < 0.001) and FVC (ß = -0.18, p < 0.001). Similar results were found for CRP. PWV was inversely associated with FEV1 (ß = -0.06, p = 0.037). No association was found between inflammatory markers, BP or PWV. CONCLUSION: Reduced lung function was associated with increased inflammation and arterial stiffness. The lack of association between arterial stiffness and inflammatory markers suggests that inflammation may not be the mediating link between lung and vascular function in this population.

South African and international reference values for lung function and its relationship with blood pressure in Africans.

BACKGROUND: In South Africa respiratory diseases are highly prevalent, with cardiovascular disease being a manifestation. However, international reference values for lung function are commonly used, which may not be appropriate to correctly identify reduced lung function. An inverse relationship exists between lung function and blood pressure (BP) but is not investigated extensively in black South Africans. METHODS: We included 2010 Africans from the PURE (Prospective Urban Rural Epidemiology) study (aged > 35 years) in the North West Province. Spirometry was performed and predicted values for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were calculated from South African, European and United States prediction equations. RESULTS: With the exception of the European predicted values, all other predicted mean FEV1 and FVC were above 80%. South African reference values displayed the highest percentages of the predicted values for FEV1 and FVC (87.9 and 99.7%, respectively.) BP increased from quintiles five to one for both FEV1 and FVC, (p for trend <0.001). After adjustment the differences remained (p<0.05). CONCLUSIONS: South African reference values yielded higher percentages of predicted FEV1 and FVC values than European and US equations suggesting that South African prediction equations may be more useful when investigating lung function in black South Africans. Elevated BP is related to reduced lung function, highlighting the importance in managing both respiratory- and cardiovascular disease.

Cornell product relates to albuminuria in hypertensive black adults independently of blood pressure: the SABPA study.

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