Alcohol - The myth of cardiovascular protection.

BACKGROUND & AIMS: To investigate potential biases that exist in available epidemiological evidence resulting in negative associations or underestimation of cardiovascular (CV) risk associated with alcohol consumption. METHODS: UK Biobank involved baseline data collection from 22 assessment centres across the United Kingdom. The cohort consisted of 333 259 alcohol consumers and 21 710 never drinkers. Participants were followed up for a median 6.9 years capturing incident fatal and non-fatal CV events, ischemic heart disease and cerebrovascular disease. Alcohol intake was reported as grams/week. RESULTS: Using never drinkers as reference, alcohol from all drink types combined (hazard ratios ranging between 0.61 and 0.74), beer/cider (0.70-0.80) and spirits combined, and all wines combined (0.66-0.77) associated with a reduced risk for all outcome measures (all CV events, ischaemic heart disease, cerebrovascular disease). In continuous analysis, alcohol captured from all drink types combined (hazard ratio, 1.08, 95% confidence interval, 1.01-1.14), and beer/cider and spirits combined (1.24, 1.17-1.31) associated with an increased risk for overall CV events, however hazard ratios were stronger for beer/cider and spirits (P < 0.0001). Wine associated with a reduced risk for overall CV events (0.92, 0.86-0.98) and ischemic heart disease (0.75, 0.67-0.84). This negative relationship with overall CV events was lost after excluding ischemic heart disease events (1.00, 0.93-1.08), while the positive association of alcohol captured from beer/cider and spirits remained significant (1.30, 1.22-1.40). This positive association with overall CV events was present even when consuming less than 14 units per week. CONCLUSIONS: Avoiding potential biases prevents underestimation of cardiovascular risk and indicates that consuming up to 14 units per week also associated with increased CV risk in the general population.

Association of red and processed meat consumption with cardiovascular morbidity and mortality in participants with and without obesity: A prospective cohort study.

OBJECTIVE: There is increasing evidence that red and processed meat consumption is associated with increased risk of cardiovascular (CV) disease. However, little literature reported the association among people with obesity versus those without obesity. We sought to investigate this using the UK Biobank data. METHODS: In this large prospective population-based cohort study, the red and processed meat consumption was assessed through the UK Biobank touch-screen questionnaire at baseline. The estimated hazards ratios (HRs) with 95% confidence intervals (CIs) were obtained from the Cox proportional hazard models to assess the association between red and processed meat consumption and the risk of CV death, cerebrovascular, and ischemic heart diseases in participants with and without obesity. RESULTS: Of 428,070 participants, 100,175 (23.4%) were obese with the mean age of 56 (SD: 7.9) years old and 54% were female. Participants without obesity, the mean age was 56 (SD: 5.2) years old and 55% were female. The overall median follow-up was 7.2 (IQR: 6.5-7.8) years. red and processed meat consumption had increased risk of CV death (HR (95%CI):1.04 (1.01-1.08) per week serve for participants with obesity and 1.04 (1.02-1.07) for those without obesity) after adjusted for age, sex, ethnicity, education, smoking and alcohol status and overall health. The moderate positive association between red and processed meat consumption and ischemic heart disease was only observed in participants without obesity (HR (95%CI): 1.15 (1.00-1.31) for the highest versus lowest terciles of red and processed meat consumption). No association was found with cerebrovascular disease in the participants regardless of obesity. CONCLUSIONS: Consumption frequency of red and processed meat is associated with higher risk of CV death regardless of obesity. The risk of ischemic heart disease associated with red and processed meat consumption may be higher in participants without obesity. Further studies are needed to understand the full extent of the mechanism of the association.

Associations of weight changes with all-cause, cancer and cardiovascular mortality: A prospective cohort study.

Objectives: Previous studies suggest that changes in body weight can lead to an increased risk of mortality in the general population, although the results are controversial. The current study sought to investigate this association further using data from the UK Biobank. Study design: This is a large prospective population-based cohort study. Data were derived from the UK Biobank, with the initial assessments commencing between 2006 and 2010. Methods: Proportional hazard models were used to assess the association between self-reported weight change and risk of all-cause, cancer and cardiovascular mortality. The effect of gender was also investigated. Results: Of 433,829 participants with data for self-reported weight change, the mean age was 56 (standard deviation [SD]: 8.1) years and 55% were female. In total, 55% of participants reported no weight change, 28% gained weight, 15% lost weight, 2% did not know and 0.1% preferred not to give an answer. The median follow-up was 7.1 (interquartile range [IQR]: 6.4-7.8) years. Compared with participants with no weight change, those with weight loss had an increased risk of all-cause mortality (adjusted hazard ratio [HR] 1.25, 95% confident interval [CI] 1.18-1.32), cancer death (HR 1.17, 95% CI 1.08-1.27) and cardiovascular death (HR 1.26, 95% CI 1.12-1.43). Similarly, participants reporting weight gain also had an increased risk of all-cause mortality (HR 1.08, 95% CI 1.02-1.13), cancer death (HR 1.14, 95% CI 1.07-1.22) and cardiovascular death (HR 1.27, 95% CI 1.14-1.42). Participants who had a response 'do not know' or 'prefer not to answer' showed an increased risk of all-cause and cardiovascular mortality, particularly in men. Conclusions: The results of this study highlight the importance of maintaining a stable weight in middle-aged adults. Further studies are needed to understand the pathophysiology of weight change and its effects on mortality.

Diet and sedentary behaviour in relation to mortality in US adults with a cardiovascular condition: results from the National Health and Nutrition Examination Survey linked to the US mortality registry.

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

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.

Trends in alcohol consumption in relation to cause-specific and all-cause mortality in the United States: a report from the NHANES linked to the US mortality registry.

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

Aldosterone and renin in relation to surrogate measures of sympathetic activity: the SABPA study.

INTRODUCTION: Hypertension, particularly in black populations, is often accompanied by augmented sympathetic nervous system activity and suppressed renin activity, indicative of possible blood pressure (BP) dysregulation. The potential role of the interrelationship between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system in the context of low-renin conditions is unclear. We therefore explored whether surrogate measures of sympathetic activity [noradrenaline, 24-hour heart rate (HR) and percentage (%) dipping of night-time HR] relate to renin, aldosterone and aldosterone-to-renin ratio (ARR) in black and white South Africans. METHODS: We included black (n = 127) and white (n = 179) males and females aged 20-63 years. We measured 24-hour BP and HR, and calculated night-time dipping. We determined renin and aldosterone levels in plasma and calculated ARR. Noradrenaline and creatinine levels were determined in urine and the noradrenaline:creatinine ratio was calculated. RESULTS: More blacks had low renin levels (80.3%) compared to whites (58.7%) (p < 0.001). In univariate and after multivariate analyses the following significant associations were evident in only the black group: HR dipping was associated negatively with aldosterone level (ß = -0.18, p = 0.024) and ARR (ß = -0.20, p = 0.011), while 24-hour HR was associated positively with renin level (ß = 0.20, p = 0.024). Additionally, there was a borderline significant positive association between noradrenaline:creatinine ratio and aldosterone level (ß = 0.19, p = 0.051). CONCLUSIONS: The observed associations between surrogate measures of sympathetic nervous system activity and components of the RAAS in the black group suggest that the adverse effects of aldosterone and its ratio to renin on the cardiovascular system may be coupled to the effects of the sympathetic nervous system.

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.

Muscle mass measures and incident osteoporosis in a large cohort of postmenopausal women.

BACKGROUND: Despite several muscle mass measures being used in the current definitions of sarcopenia, their usefulness is uncertain because of limited data on their association with health outcomes. The aim of the study was to compare the performance of different muscle mass measures for predicting incident osteoporosis in postmenopausal women. METHODS: This study included data from 149 166 participants (aged 60.3 ± 5.5 years) as part of the UK Biobank cohort. Body composition was assessed using bioelectrical impedance. The muscle mass measures included were total body skeletal muscle mass (SMM) and appendicular SMM (aSMM) divided by height squared (ht2 ), derived residuals, SMM, SMM adjusted for body mass (SMM/bm × 100), and aSMM normalized for body mass index (aSMM/BMI). Diagnoses of the events were confirmed by primary care physicians and coded according to the World Health Organization's International Classification of Diseases 10th Revision (ICD-10: M80-M82). RESULTS: Over a median follow-up of 6.75 (5th to 95th percentile interval, 1.53 to 8.37) years, 394 newly diagnosed cases of osteoporosis occurred, with 40 (10.2%) cases being associated with a pathological fracture. SMM/ht2 , aSMM/ht2 residual, and SMM were lower in postmenopausal women with osteoporosis compared with women without (all P < 0.0001), while SMM/bm × 100 (P = 0.003), but not aSMM/BMI (P = 0.59), was higher in the osteoporosis group. The unadjusted rates of osteoporosis increased with decreasing quintiles for SMM/ht2 , aSMM/ht2 , residuals, and SMM (all P trend <0.0001), while the incidence of osteoporosis increased with increasing SMM/bm × 100 (P trend =0.001), but not for aSMM/BMI (P = 0.45). After minimally adjusting for age and after full adjustment, SMM/ht2 , aSMM/ht2 , and SMM were the only measure that consistently predicted osteoporosis in the total group of postmenopausal women [hazard ratio (HR) 0.65-0.67, all P ≤ 0.0001], in lean women (HR 0.62-0.68; all P ≤ 0.001), and women with increased adiposity (HR 0.64-0.68; all P ≤ 0.01). In fully adjusted models, the changes in the R2 statistic were 13.4%, 11.6%, and 15.3% for the SMM/ht2 (aSMM/ht2 ), residual, and SMM, but only 4.9% and 1.3% for SMM/bm × 100 and aSMM/BMI. CONCLUSIONS: Muscle mass measures adjusted for height only (SMM/ht2 , aSMM/ht2 ) appear to be better muscle-relevant risk factors for incident osteoporosis in postmenopausal women, including when stratified into lean participants and participants with increased adiposity.

Cross-sectional associations of active transport, employment status and objectively measured physical activity: analyses from the National Health and Nutrition Examination Survey.

BACKGROUND: To investigate associations between active transport, employment status and objectively measured moderate-to-vigorous physical activity (MVPA) in a representative sample of US adults. METHODS: Cross-sectional analyses of data from the National Health and Nutrition Examination Survey. A total of 5180 adults (50.2 years old, 49.0% men) were classified by levels of active transportation and employment status. Outcome measure was weekly time spent in MVPA as recorded by the Actigraph accelerometer. Associations between active transport, employment status and objectively measured MVPA were examined using multivariable linear regression models adjusted for age, body mass index, race and ethnicity, education level, marital status, smoking status, working hour duration (among the employed only) and self-reported leisure time physical activity. RESULTS: Patterns of active transport were similar between the employed (n=2897) and unemployed (n=2283), such that 76.0% employed and 77.5% unemployed engaged in no active transport. For employed adults, those engaging in high levels of active transport (≥90 min/week) had higher amount of MVPA than those who did not engage in active transport. This translated to 40.8 (95% CI 15.7 to 65.9) additional minutes MVPA per week in men and 57.9 (95% CI 32.1 to 83.7) additional minutes MVPA per week in women. Among the unemployed adults, higher levels of active transport were associated with more MVPA among men (44.8 min/week MVPA, 95% CI 9.2 to 80.5) only. CONCLUSIONS: Findings from the present study support interventions to promote active transport to increase population level physical activity. Additional strategies are likely required to promote physical activity among unemployed women.

Liver enzymes are not directly involved in atrial fibrillation: a prospective cohort study.

BACKGROUND: Epidemiological evidence proposes the direct involvement of the liver enzymes in atrial fibrillation. These relationships are controversial and mechanistically unclear. As part of the British Regional Heart Study, we investigated whether change in liver enzymes over time associates with atrial fibrillation in men initially free of this heart condition. MATERIALS AND METHODS: We prospectively investigated change (delta) in liver enzymes and new-onset atrial fibrillation in a representative sample of 1428 men aged 60-79 years. RESULTS: Mean follow-up was 12·3 years, after which 108 new atrial fibrillation cases were identified. The liver enzymes did not differ at baseline or follow-up, except for gamma-glutamyl transferase which was higher at follow-up in men who developed atrial fibrillation compared to those who did not (P < 0·0001). Change in GGT was greater in men who developed AF than those who did not (+6·12 vs. -2·60 U/L, P = 0·036). N-terminal pro-brain natriuretic peptide (baseline and follow-up, P < 0·0001) and total bilirubin (follow-up only, P < 0·0001) were also higher in men who developed atrial fibrillation while serum haemoglobin was similar at baseline and follow-up (P ≥ 0·74). Atrial fibrillation was associated with change in gamma-glutamyl transferase (OR, 1·18; 95% CI, 1·01-1·37) after multiple adjustments and exclusions. However, after adjusting for baseline (P = 0·088) or change (P = 0·40) in N-terminal pro-brain natriuretic peptide, the association between atrial fibrillation and change in gamma-glutamyl transferase was lost. CONCLUSION: The direct relationship between atrial fibrillation and liver enzymes is absent and depends, at least in part, on the progression of heart failure as captured by N-terminal pro-brain natriuretic peptide.

IGF-1 and NT-proBNP in a black and white population: The SABPA study.

BACKGROUND: Black populations exhibit lower concentrations of the cardioprotective peptide, insulin-like growth factor-1 (IGF-1), and are more prone to develop hypertensive heart disease than whites. We therefore determined whether lower IGF-1 in black individuals relates to a marker of cardiac overload and systolic dysfunction, namely N-terminal prohormone B-type natriuretic peptide (NT-proBNP). MATERIALS AND METHODS: We included 160 black and 195 white nondiabetic South African men and women (aged 44·4 ± 9·81 years) and measured ambulatory blood pressure, NT-proBNP, IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3). RESULTS: Although the black group presented elevated ambulatory blood pressure accompanied by lower IGF-1 compared to the white group (all P < 0·001), we found similar NT-proBNP concentrations (P = 0·72). Furthermore, in blacks we found a link between NT-proBNP and systolic blood pressure (SBP) (R(2) = 0·37; ß = 0·28; P < 0·001), but not with IGF-1. In the white group, NT-proBNP was inversely associated with IGF-1 (R(2) = 0·39; ß = -0·22; P < 0·001) after adjusting for covariates and potential confounders. As IGF-1 is attenuated in diabetes, we added the initially excluded patients with diabetes (n = 38), and the aforementioned associations remained robust. CONCLUSION: Contrary to the white group, we found no association between NT-proBNP and IGF-1 in black adults. Our findings suggest that SBP and other factors may play a greater contributory role in cardiac pathology in blacks.

Retinal vessel caliber and its relationship with nocturnal blood pressure dipping status: the SABPA study.

Adverse changes in retinal microvasculature caliber are associated with incident hypertension, coronary heart disease and stroke. The absence of a nocturnal dipping in arterial pressure may induce changes throughout the vascular tree, including the retinal microvasculature, but the later link is not sufficiently studied. We explored the relationship between retinal vessel caliber and dipping status in a group of black and white teachers. The study included black (n=68) and white (n=81) men (24-66 years) from the SABPA study. We measured 24 h ambulatory blood pressure and the percentage mean arterial pressure dipping(%MAPdip) was calculated as (diurnal MAP-nocturnal MAP)/diurnal MAP × 100. Retinal images were captured and the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) calculated. Black men demonstrated higher diurnal and nocturnal MAP (P⩽0.001) and a lesser %MAPdip compared with white men (P=0.047). When stratified by dipping status, black non-dippers (n=33) revealed an increased CRVE (P<0.001) compared with their dipper counterparts (n=35). In black men, CRVE was negatively (R2=0.38, ß=-0.47, P<0.001) associated with %MAPdip independent of 24 h MAP or nocturnal MAP. CRVE also associated negatively with dipping status as a dichotomized variable (R2=0.29, ß=-0.32, P=0.006), independent of 24 h MAP. These associations were absent in the white men. In conclusion, in this group of black men, a non-dipping blood pressure profile was associated with a larger CRVE, suggesting microvascular deterioration due to the absence of nocturnal dipping in blood pressure. This may add to our understanding of the stroke risk in black populations.

Vitamin K Dependent Protection of Renal Function in Multi-ethnic Population Studies.

BACKGROUND: Following activation by vitamin K (VK), matrix Gla protein (MGP) inhibits arterial calcification, but its role in preserving renal function remains unknown. METHODS: In 1166 white Flemish (mean age, 38.2 years) and 714 South Africans (49.2% black; 40.6 years), we correlated estimated glomerular filtration (eGFR [CKD-EPI formula]) and stage of chronic kidney disease (CKD [KDOQI stages 2-3]) with inactive desphospho-uncarboxylated MGP (dp-ucMGP), using multivariable linear and logistic regression. RESULTS: Among Flemish and white and black Africans, between-group differences in eGFR (90, 100 and 122 mL/min/1.73 m(2)), dp-ucMGP (3.7, 6.5 and 3.2 µg/L), and CKD prevalence (53.5, 28.7 and 10.5%) were significant, but associations of eGFR with dp-ucMGP did not differ among ethnicities (P ≥ 0.075). For a doubling of dp-ucMGP, eGFR decreased by 1.5 (P = 0.023), 1.0 (P = 0.56), 2.8 (P = 0.0012) and 2.1 (P < 0.0001) mL/min/1.73 m(2) in Flemish, white Africans, black Africans and all participants combined; the odds ratios for moving up one CKD stage were 1.17 (P = 0.033), 1.03 (P = 0.87), 1.29 (P = 0.12) and 1.17 (P = 0.011), respectively. INTERPRETATION: In the general population, eGFR decreases and CKD risk increases with higher dp-ucMGP, a marker of VK deficiency. These findings highlight the possibility that VK supplementation might promote renal health.

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 in Low-Income South African Adults.

While South Africa has one of the highest hypertension rates globally, there are few data on masked hypertension (MHT) and white-coat hypertension (WCHT). This study measured the frequency of MHT and WCHT in low-income (<$500 US per month) South African adults, evaluating cardiovascular risk by arterial stiffness. Participants (n=101, 50% male; mean age 39.4±9.7 years) were recruited from a large North-West Province employer. Clinic and 24-hour blood pressure (BP) and pulse wave analysis were recorded. Clinic BP identified 18% of patients as hypertensive, while 24-hour BP showed that 63% of patients were hypertensive. The frequency of MHT was high (33 of 81, 41%) with only one case of WCHT. In comparison to those with normal clinic and 24-hour BP, augmentation index and pulse wave velocity were significantly higher in those with hypertensive 24-hour BP irrespective of clinic BP, indicating that, in this group, masked and sustained hypertension carry a similar elevated cardiovascular risk.

Retinal vessel calibres and haemostasis in black and white South Africans: the SABPA study.

OBJECTIVES: Retinal arteriolar narrowing associates with hypertension development and indicates increased cardiovascular risk. Evidence on whether the retinal vessel calibres are related to the haemostatic system is limited, especially in the black hypertension-prone population with a high stroke incidence. We therefore investigated the relationships between haemostatic markers and retinal vessel calibres. METHODS: We performed a cross-sectional study involving 170 black (mean age, 58 years; 44% women) and 189 white (mean age, 49 years; 52% women) teachers, and determined ambulatory blood pressure, haemostatic factors (fibrinogen, von Willebrand factor, D-dimer, plasminogen activator inhibitor-1 and clot lysis time) and retinal vessel calibres (central retinal artery and vein equivalent). The black and white groups were stratified by median split of the retinal arteriolar calibre. RESULTS: Both ethnic groups with a smaller arteriolar calibre had higher SBP and narrower venular calibres. In the black population, the central retinal vein equivalent was positively (ß = 0.293; P = 0.024) associated with fibrinogen, whereas in the white population, the central retinal artery equivalent (ß = -0.256; P = 0.016) was negatively and central retinal vein equivalent (ß = 0.234; P = 0.021) positively associated with von Willebrand factor. Furthermore, clot lysis time was negatively associated with the central retinal artery equivalent (ß = -0.390; P = 0.014) in the black group and positively associated with the central retinal vein equivalent (ß = 0.275; P = 0.008) in the white group. CONCLUSION: Relationships between markers of haemostasis and the retinal vessel calibres exist, and vary between ethnicities. Haemostatic alterations are linked to early retinal microvascular changes, and future studies should investigate whether it translates into an elevated stroke risk.

Ethnic-specific relationships between haemostatic and oxidative stress markers in black and white South Africans: The SABPA study.

Haemostatic- and oxidative stress markers are associated with increased cardiovascular risk. In the black population, evidence exists that both an imbalance in the haemostatic system and oxidative stress link with the development of hypertension. However, it is unclear whether these two risk components function independently or are related, specifically in the black population, who is known to have a high prevalence of stroke. We aimed to investigate associations between the haemostatic system and oxidative stress in black and white South Africans. We performed a cross-sectional study including 181 black (mean age, 44; 51.4% women) and 209 white (mean age, 45; 51.7% women) teachers. Several markers of the haemostatic- (von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1, d-dimer and clot lysis time) and oxidant-antioxidant (serum peroxides, total glutathione, glutathione peroxidase- and glutathione reductase activities) systems were measured. Along with a worsened cardiovascular profile, the black group had higher haemostatic-, inflammation- and oxidative stress markers as well as decreased glutathione peroxidase activity. In multiple regression analyses, fibrinogen was positively associated with serum peroxides (p < 0.001) in both ethnic groups. In the black population, we found negative associations of von Willebrand factor and clot lysis time with glutathione peroxidase activity (p ≤ 0.008), while a positive association existed between clot lysis time and serum peroxides (p = 0.011) in the white population. We conclude that in the black population, decreased GPx activity accompanies an altered haemostatic profile, while in the white population associations may suggest that serum peroxides impair fibrin clot lysis.