Four-oil intravenous lipid emulsion effect on plasma fatty acid composition, inflammatory markers and clinical outcomes in acutely ill patients: A randomised control trial (Foil fact).

BACKGROUND AND AIMS: Data in critically ill patients on the effect of intravenous lipid emulsions (LEs), containing omega-3 polyunsaturated fatty acids (PUFAs), in parenteral nutrition (PN) are scarce and conflicting. This study compared the effects of a four-oil LE (30% soybean oil, 30% medium-chain triglycerides, 25% olive oil and 15% fish oil (FO)) (SMOFlipid®) to those of a 100% soybean oil-based LE in critically ill adult intensive care unit (ICU) patients. METHODS: In this double-blind, randomised study, patients (n = 75) predicted to need PN for more than 5 days were randomised to receive either a four-oil LE (Study Group (SG)) or a 100% soybean oil LE (Control Group (CG)). Isocaloric, isonitrogenous PN was administered continuously for 5 days. FO was provided at a dose of 0.09-0.22 g/kg body weight. Measurements included biochemical parameters and sequential organ failure assessment (SOFA) score daily and plasma total phospholipid fatty acids (FAs) and cytokine levels on days 1, 3, 6. Days on mechanical ventilation, length of stay and mortality were also recorded. ANOVA was used to compare response variables between the two groups over the time and Pearson correlation was used to measure relationships between continuous variables. RESULTS: 68 patients completed the study (n = 35 SG, n = 33 CG), with male predominance (66% SG, 56% CG). Average age was 60.8 ± 13.9 years (SG) versus 55.7 ± 14.8 (CG) (p = 0.143). The majority were surgical admissions (85% SG versus 91% CG) followed by medical. Plasma phospholipid oleic acid (p = 0.022) and alpha-linolenic acid (p<0.0005) increased in both groups. In the SG, plasma phospholipid EPA and DHA increased (both p<0.001), whereas the omega-6:omega-3 PUFA (n-6:n-3 PUFA) ratio decreased (p < 0.001). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin decreased in both treatment groups. Considering only the change from day 1 to day 6 there was a bigger decrease in AST, ALT and bilirubin levels in the SG. Concentrations of TNF-α decreased from day 1 to day 6 in the SG, whereas they increased in the CG, but the change was not statistically significant (p = 0.112). A significant negative correlation was found between EPA provision on day 3 and the SOFA score (r = -0.4047, p = 0.018). Days on mechanical ventilation (1.24 ± 0.83 days in SG versus 0.88 ± 1.63 days in CG, p = 0.385) and ICU LOS (9.5 ± 7.09 days in SG versus 10.7 ± 7.6 days in CG, p = 0.490) were not different between groups. CONCLUSION: PN containing a four-oil LE increased plasma EPA and DHA, decreased n-6:n-3 PUFA ratio, and was safe and well tolerated. The negative relationship between day 3 EPA and SOFA score seems promising, but EPA intake and effects may have been diluted by enteral nutrition which was started in more than half of patients on day 4. There was no significant difference in terms of other biochemical measurements, SOFA score, length of ICU stay and mortality. More research is needed in this patient population, particularly regarding dose, duration and timing of FO and the effects on clinical outcomes.

Cultural coping as a risk for depression and hypertension: the SABPA prospective study.

OBJECTIVE: In past studies, a lack of social support has been associated with cardiovascular disease (CVD) risk, particularly in black Africans. However, whether or not coping strategies have beneficial effects on blood pressure (BP) and emotional well-being is not clear. We therefore assessed the relationship between BP levels, depression and coping strategies. METHODS: A prospective bi-ethnic cohort followed 359 black and white South African school teachers (aged 20-65 years) over a three-year period. Data on ambulatory 24-hour blood pressure, depression, coping strategies (defensiveness, social support, avoidance) and culture-specific coping scores (cognitive/emotional debriefing, spiritual-, collectivistic and ritualcentred) were obtained. RESULTS: Over three years, chronic depression (38 vs 19%) and hypertension (68 vs 35%) were apparent in blacks ( d-values > 0.3) as opposed to whites. In both groups, depression was accompanied by more avoidance (loss-of-control) coping. Consistent spiritual and increasing collectivistic coping were apparent in whites. Over time, increasing defensiveness (OR 1.08, p ≤ 0.05) and ritual coping (OR 1.27, p ≤ 0.01; d-values > 0.5), predicted chronic depression in blacks. The change in their symptoms of depression predicted 24-hour hypertension (OR 1.11, p = 0.04). No similar associations existed in whites. CONCLUSIONS: Blacks showed increasing defensiveness and ritual- and spiritual-centred coping in an attempt to combat chronic depression, which may be costly, as reflected by their chronic hypertensive status. Whites showed consistent spiritual- centred coping while utilising avoidance or loss-of-control coping, with a trend of seeking less social support or isolation as a coping mechanism. During counselling of depressed patients with hypertension, the beneficial effects of social support and spiritual coping may be of great importance.

Asymmetric dimethylarginine and symmetric dimethylarginine prospectively relates to carotid wall thickening in black men: the SABPA study.

The relationship of both asymmetric (ADMA) and symmetric (SDMA) dimethylarginine with carotid wall thickness is inconclusive especially among black populations. We aimed to compare carotid intima media thickness (cIMT) and dimethylarginine levels in 75 black and 91 white men at baseline and after a 3-year follow-up, and to investigate associations of percentage change in cIMT with percentage change in dimethylarginine levels (ADMA and SDMA). Plasma levels of ADMA and SDMA were determined with a liquid chromatography mass spectrometry method and B-mode ultrasonography was used to determine the cIMT at baseline and follow-up. In black men, mean cIMT (p = 0.79) and ADMA levels (p = 0.67) remained the same, but SDMA levels were lower (p < 0.001) when comparing baseline and follow-up. In white men, cIMT increased (p < 0.001), but both mean ADMA and SDMA levels decreased (p < 0.001) over time. In black men, percentage change in cIMT was positively associated with percentage change in ADMA (R 2 = 0.49; ß = 0.46; p < 0.001) and percentage change in SDMA (R 2 = 0.46; ß = 0.41; p < 0.001). These associations were absent in the white men. Despite lower mean SDMA and similar ADMA and cIMT in black men, percentage change in cIMT was independently associated with percentage change in ADMA and percentage change in SDMA. These results suggest an important role for ADMA and SDMA lowering strategies to delay carotid wall thickening, especially in black populations prone to the development of cardiovascular disease.

Recent advances in understanding hypertension development in sub-Saharan Africa.

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the human immunodeficiency virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies and

The association between seven-day objectively measured habitual physical activity and 24 h ambulatory blood pressure: the SABPA study.

Few studies have examined objective physical activity in relation to 24 h ambulatory blood pressure (BP). We aimed to assess the association of 7-day objectively measured habitual physical activity with ambulatory BP in a sample of African and Caucasian school teachers (n=216, age 49.7 years) from the sympathetic activity and blood pressure in Africans prospective cohort study. Hypertension (ambulatory systolic BP⩾130 and/or diastolic BP⩾80 mm Hg) was prevalent in 53.2% of the sample, particularly in black Africans. The hypertensive group spent significantly more awake time in sedentary activity (51.5% vs 40.8% of waking hours, P=0.001), as well as doing less light- (34.1% vs 38.9%, P=0.043) and moderate-intensity (14.0% vs 19.7%, P=0.032) activities compared with normotensives, respectively. In covariate adjusted models, light-intensity activity time was associated with lower 24 h and daytime ambulatory systolic BP (ß=-0.15, 95% confidence interval (CI): -0.26, -0.05, P=0.004; ß=-0.14, CI: -0.24, -0.03, P=0.011) and diastolic BP (ß=-0.14, CI: -0.25, -0.03, P=0.015; ß=-0.13, CI: -0.24, -0.01, P=0.030), as well as resting systolic BP (ß=-0.13, CI: -0.24, -0.01, P=0.028). Sedentary time was associated only with 24 h systolic BP (ß=0.12; CI: 0.01, 0.22), which was largely driven by night-time recordings. Participants in the upper sedentary tertile were more likely to be 'non-dippers' (odds ratio=2.11, 95% CI: 0.99, 4.46, P=0.052) compared with the lowest sedentary tertile. There were no associations between moderate to vigorous activity and BP. In conclusion, objectively assessed daily light physical activity was associated with ambulatory BP in a mixed ethnic sample.

Quantification of systemic renin-angiotensin system peptides of hypertensive black and white African men established from the RAS-Fingerprint®.

OBJECTIVE: The objective of this study was to make use of a quantitative and qualitative approach comparing the systemic renin-angiotensin system (RAS) of hypertensive black and white African men by using RAS equilibrium analysis. MATERIALS AND METHODS: This sub-study involved 23 black (n = 15) and white (n = 8) hypertensive men aged 39.5-41 years, living in the North West Province of South Africa. The RAS-Fingerprinting was determined with LC-MS/MS quantification of angiotensin peptides. Blood pressure and other variables were determined with known methods. RESULTS: The main finding of this study was the significant lower Ang I (<5.0 and 45.1 pg/ml; p = 0.005) and Ang II (15.6 and 123.9 pg/ml; p ⩽ 0.001) encountered in the hypertensive black African men compared to their white counterparts. Levels of Ang 1-5 (downstream metabolite of Ang 1-7) (1.8 and 3.0 pg/ml), were detected in black and white hypertensive men, respectively. CONCLUSIONS: The observed differences between circulating RAS components, which are reflected via equilibrium angiotensin levels, point to a distinctive molecular regulation of the RAAS in the two study cohorts. The increased peripheral resistance observed in hypertensive black individuals might take over a dominant role in control of blood pressure in this study population. A novel highly sensitive LC-MS/MS method resolved the issue of peptide recovery variations during sample preparation by using internal standards for each individual angiotensin metabolite.

Tactical damage control resuscitation in austere military environments.

BACKGROUND: Despite the early uses of tourniquets and haemostatic dressings, blood loss still accounts for the vast majority of preventable deaths on the battlefield. Over the last few years, progress has been made in the management of such injuries, especially with the use of damage control resuscitation concepts. The early application of these procedures, on the field, may constitute the best opportunity to improve survival from combat injury during remote operations. DATA SOURCES: Currently available literature relating to trauma-induced coagulopathy treatment and far-forward transfusion was identified by searches of electronic databases. The level of evidence and methodology of the research were reviewed for each article. The appropriateness for field utilisation of each medication was then discussed to take into account the characteristics of remote military operations. CONCLUSIONS: In tactical situations, in association with haemostatic procedures (tourniquet, suture, etc), tranexamic acid should be the first medication used according to the current guidelines. The use of fibrinogen concentrate should also be considered for patients in haemorrhagic shock, especially if point-of-care (POC) testing of haemostasis or shock severity is available. If POC evaluation is not available, it seems reasonable to still administer this treatment after clinical assessment, particularly if the evacuation is delayed. In this situation, lyophilised plasma may also be given as a resuscitation fluid while respecting permissive hypotension. Whole blood transfusion in the field deserves special attention. In addition to the aforementioned treatments, if the field care is prolonged, whole blood transfusion must be considered if it does not delay the evacuation.

Low immune cell ARA and high plasma 12-HETE and 17-HDHA in iron-deficient South African school children with allergy.

Allergy has been associated with altered fatty acid and inflammatory status. In this cross-sectional study of 321 rural iron deficient (ID) South African children (aged 6-11 years), a subsample (n=111) of children with parent-reported allergy data were divided into an allergic (n=30) and non-allergic (n=81) group and compared. PBMC arachidonic acid (ARA; P=0.010) and the PBMC ARA to dihomo-gamma-linolenic acid (DGLA) ratio (P=0.035) were lower in the allergic children. Plasma 12-hydroxyeicosatetraenoic acid and 17-hydroxydocosahexaenoic acid (17-HDHA) were higher (P=0.040 and 0.020, respectively) in the allergic group. Thus, a fatty acid composition and lipid mediator levels indicative of increased release of ARA from PBMC membranes, increased inflammation as well as the resolving thereof, were associated with parent-reported allergy symptoms. This study used baseline data of an intervention study which was registered at clinicaltrials.gov as NCT01092377.

Iron and a mixture of DHA and EPA supplementation, alone and in combination, affect bioactive lipid signalling and morbidity of iron deficient South African school children in a two-by-two randomised controlled trial.

We recently reported that iron supplementation increased respiratory morbidity in iron deficient South African children. This increase, however, was attenuated when iron was provided in combination with a mixture of DHA/EPA. To explore potential underlying mechanisms, we examined the effects of iron and DHA/EPA, alone and in combination, on plasma lipid-derived immune modulator concentrations and related gene expression in peripheral blood mononuclear cells (PBMC). DHA/EPA decreased inflammatory 12-hydroxyeicosatetraenoic acid and tended to increase anti-inflammatory and pro-resolving 17-hydroxydocosahexaenoic acid (17-HDHA), while iron decreased 17-HDHA. However, in combination with iron, the anti-inflammatory effect of DHA/EPA was maintained. These biochemical changes may explain the prevention of iron-induced respiratory morbidity that we observed when iron was supplemented in combination with DHA/EPA during the 8.5 month randomised controlled trial and might lead to a safer approach of delivering iron supplementation. The study was registered at clinicaltrials.gov as NCT01092377.

Attenuated brain-derived neurotrophic factor and hypertrophic remodelling: the SABPA study.

Brain-derived neurotrophic factor (BDNF) has been linked to neurological pathologies, but its role in cardiometabolic disturbances is limited. We aimed to assess the association between serum BDNF levels and structural endothelial dysfunction (ED) as determined by cross-sectional wall area (CSWA) and albumin/creatinine ratio (ACR) in black Africans. Ambulatory blood pressure (BP) and ultrasound CSWA values were obtained from 82 males and 90 females. Fasting blood and 8 h overnight urine samples were collected to determine serum BDNF and cardiometabolic risk markers, that is, glycated haemoglobin (HbA1c), lipids, inflammation and ACR. BDNF median split × gender interaction effects for structural ED justified stratification of BDNF into low and high (⩽/>1.37 ng ml(-1)) gender groups. BDNF values (0.86-1.98 ng ml(-1)) were substantially lower than reference ranges (6.97-42.6 ng ml(-1)) in the African gender cohort, independent of age and body mass index. No relationship was revealed between BDNF and renal function and was opposed by an inverse relationship between BDNF and CSWA (r=-0.17; P=0.03) in the African cohort. Linear regression analyses revealed a positive relationship between systolic BP and structural remodelling in the total cohort and low-BDNF gender groups. In the high-BDNF females, HbA1C was associated with structural remodelling. Attenuated or possible downregulated BDNF levels were associated with hypertrophic remodelling, and may be a compensatory mechanism for the higher BP in Africans. In addition, metabolic risk and hypertrophic remodelling in women with high BDNF underpin different underlying mechanisms for impaired neurotrophin homeostasis in men and women.

Leukocyte telomere length and hemostatic factors in a South African cohort: the SABPA Study.

BACKGROUND: Incident atherothrombotic disease is predicted by leukocyte telomere length, a marker of biological age, and hemostatic factor levels, indicating a hypercoagulable state. We hypothesized that shorter telomeres are associated with elevated circulating levels of hemostatic factors. METHODS: We examined 171 South African (black) and 182 Caucasian (white) schoolteachers (mean age ± standard deviation, 48.5 ± 9.0 years; 50.4% women). Levels of fibrinogen, von Willebrand factor antigen (VWF:Ag), D-dimer and plasminogen activator inhibitor-1 antigen (PAI-1:Ag) were measured in plasma, and values were log-transformed before analysis. Relative average telomere length (content of telomere PCR product/content of human ß-globin PCR product ratio, i.e. telomere/single-copy gene ratio) was assessed with multiplex quantitative real-time PCRs. Multivariate analyses included demographics, metabolic factors, health behavior, and medication. RESULTS: Africans had shorter mean telomere length (0.82, 95% confidence interval [CI] 0.79-0.86 vs. 1.07, 95% CI 1.04-1.10) and higher fibrinogen (B = 0.085, 95% CI 0.061-0.109) and PAI-1:Ag (B = 0.255, 95% CI 0.206-0.303) levels, but lower VWF:Ag levels (B = - 0.059, 95% CI - 0.089 to - 0.028), than Caucasians. Shorter telomeres were associated with higher fibrinogen (B = - 0.045, 95% CI - 0.088 to - 0.001), VWF:Ag (B = - 0.137, 95% CI - 0.193 to - 0.081) and D-dimer (B = - 0.201, 95% CI - 0.377 to - 0.025) levels, conditional on ethnicity. An interaction emerged between ethnicity and telomere length for VWF:Ag level; that is, shorter telomeres were associated with higher VWF:Ag levels in Caucasians (B = - 0.170, 95% CI - 0.232 to - 0.108) but not in Africans. CONCLUSIONS: Shorter telomeres were associated with increased levels of several hemostatic factors after adjustment for confounding variables, whereby ethnicity partially moderated this effect. A relationship between accelerated biological aging and hypercoagulability might contribute to the risk of premature atherothrombotic events.

8-Oxo-7,8-dihydro-2'-deoxyguanosine, reactive oxygen species and ambulatory blood pressure in African and Caucasian men: the SABPA study.

Various studies indicate a relationship between increased oxidative stress and hypertension, resulting in increased DNA damage and consequent excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). The aim of this study was to compare urinary 8-oxodG levels in African and Caucasian men and to investigate the association between ambulatory blood pressure (BP) and pulse pressure (PP) with 8-oxodG in these groups. We included 98 African and 92 Caucasian men in the study and determined their ambulatory BP and PP. Biochemical analyses included, urinary 8-oxodG, reactive oxygen species (ROS) (measured as serum peroxides), ferric reducing antioxidant power (FRAP), total glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) activity. The African men had significantly higher systolic (SBP) and diastolic blood pressure (DBP) (both p < 0.001). Assessment of the oxidative stress markers indicated significantly lower 8-oxodG levels (p < 0.001) in the African group. The African men also had significantly higher ROS (p = 0.002) with concomitant lower FRAP (p < 0.001), while their GSH levels (p = 0.013) and GR activity (p < 0.001) were significantly higher. Single and partial regression analyses indicated a negative association between urinary 8-oxodG levels with SBP, DBP and PP only in African men. These associations were confirmed in multiple regression analyses (SBP: R(2) = 0.41; ß = -0.25; p = 0.002, DBP: R(2) = 0.30; ß = -0.21; p = 0.022, PP: R(2) = 0.30; ß = -0.19; p = 0.03). Our results revealed significantly lower urinary 8-oxodG in African men, accompanied by a negative association with BP and PP. We propose that this may indicate a dose-response relationship in which increased oxidative stress may play a central role in the up-regulation of antioxidant defence and DNA repair mechanisms.

Cardiometabolic markers to identify cardiovascular disease risk in HIV-infected black South Africans.

BACKGROUND: The prevalence of HIV is the highest in sub-Saharan Africa; South Africa (SA) is one of the most affected countries with the highest number of adults living with HIV infection in the world. Besides the traditional risk factors for cardiovascular disease (CVD) in the general population, in people living with HIV there are specific factors - chronic inflammation, metabolic changes associated with the infection, therapy, and lipodystrophy - that potentially increase the risk for developing CVD. OBJECTIVE: This study proposes a screening discriminant model to identify the most important risk factors for the development of CVD in a cohort of 140 HIV-infected black Africans from the North West Province, SA. METHODS: Anthropometric measures, systolic blood pressure, diastolic blood pressure and the carotid-dorsalis pedis pulse wave velocity were determined. Blood was analysed to determine the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, triglycerides (TGs) and glucose. Partial least squares discriminant analysis was performed as a supervised pattern recognition method. Independent Student's t-tests were further employed to compare the means of risk factors on interval scales; for comparison of categorical risk factors between groups, chi2 tests were used. RESULTS: A TG:HDL-C ratio > or = 1.49, TC:HDL-C ratio > or = 5.4 and an HDL-C level < or = 0.76 mmol/l indicated CVD risk in this cohort of patients living with HIV. CONCLUSION: The results have important health implications for black Africans living with HIV as these lipid levels may be a useful indicator of the risk for CVD.

Compromised bioavailable IGF-1 of black men relates favourably to ambulatory blood pressure: The SABPA study.

OBJECTIVES: Insulin-like growth factor-1 (IGF-1) has potent endothelial-protective, anti-platelet and anti-thrombotic activities, and also exerts mitogenic and proliferatory actions on vascular smooth muscle cells. Conflicting reports exist regarding the role of IGF-1 in vascular protection and atherogenesis. We therefore investigated the relationships of ambulatory blood pressure (BP) and carotid intima-media thickness (cIMT) with a range of components of the IGF-1 axis in a bi-ethnic population. METHODS: We included black (N = 86) and white (N = 101) men and measured growth hormone, total IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), and pregnancy-associated plasma protein-A (PAPP-A) levels. RESULTS: Ambulatory BP was almost 10 mmHg higher in black men (137/88 mmHg versus 128/80 mmHg; both p < 0.001), accompanied by an adverse profile of the IGF-axis for all measured components (all p < 0.01), including reduced bioavailable IGF-1 (IGF-1/IGFBP-3; p = 0.006) and tissue IGF-1 accessibility index as represented by IGF-1.PAPP-A/IGFBP-3 (p < 0.001). Single, partial and multiple regression analyses confirmed an independent inverse association between ambulatory systolic BP and bioavailable IGF-1 in black men (R(2) = 0.24; ß = -0.22; p = 0.035). cIMT was similar in the ethnic groups (p = 0.34), and was negatively associated with bioavailable IGF-1 in white men (R(2) = 0.42; ß = -0.17; p = 0.039) prior to adjustment for γ-glutamyl transferase (R(2) = 0.45; ß = -0.10; p = 0.25). CONCLUSION: Ambulatory systolic BP is inversely related to bioavailable IGF-1 in black men who displayed low IGF-1 concentrations. An inverse relation was found between cIMT and IGF-1 in white men, which disappeared after correction for γ-glutamyl transferase - opposing reports of a detrimental role of IGF-1 in the early stages of atherogenesis.

Attenuated NOx responses and myocardial ischemia, a possible risk for structural vascular disease in African men: the SABPA study.

Chronically elevated blood pressure has been associated with impaired NO-mediated vasodilation and structural vascular disease risk. This study aimed to determine whether significant associations exist regarding NO metabolite (NOx) responses, cardiovascular function and structural vascular disease in a cohort of African and Caucasian men. The study included 81 African and 94 Caucasian male teachers stratified via median splits into low and high NOx ethnic groups. Ambulatory blood pressure, electrocardiogram monitoring and ultrasound carotid intima-media thickness (CIMT) images were obtained. Cardiovascular measurements and fasting blood for NOx responses were measured during rest and on challenging the cardiovascular system with the Stroop colour-word conflict test. African men displayed significantly higher resting NOx as well as higher number of 24 h silent ischemic events than their Caucasian counterparts. Low NOx African men displayed enhanced α-adrenergic and ECG ST segment depression acute mental stress responses as well as 24 h silent ischemic events associated with CIMT (adjusted R(2) = 0.47; ß = 0.25; confidence interval (CI) = 0.13, 0.41). African men demonstrated a vulnerable cardiovascular profile. Novel findings revealed α-adrenergic-driven blood pressure responses and less NO bioavailability during acute stress. The association between myocardial ischemia and CIMT in this group emphasized their risk for future coronary artery disease and cerebrovascular events.

Chronic distress and acute vascular stress responses associated with ambulatory blood pressure in low-testosterone African men: the SABPA Study.

It is known that low testosterone (T) and high cortisol levels are associated with hypertension as well as with chronic stress, linking stress with elevated blood pressure (BP). However, the association between acute stress-, chronic stress responses and BP is not clear in Africans. Therefore, we examined the association between cortisol, psychological distress and BP responses in low- and high-T male subgroups. Beat-to-beat and ambulatory blood pressure (ABPM) and electrocardiogram measures were obtained. Serum samples were collected and analyzed for sex hormones and cortisol. Chronic psychological distress was verified with the General Health Questionnaire and acute stress with the cold pressor test. More chronic psychological distress was observed in both low- and high-T Africans compared with the Caucasians. The low-T Africans tended to have more ischemic events (P=0.06) and ABPM values (P⩽0.01) than any of the other groups. Both chronic distress (cortisol) and acute stress (total peripheral resistance cold pressor responses) were associated with ABPM in the low-T African group. Acute and chronic stress may contribute to increased BP in low-T African men. Their cortisol and vascular responses supported a tendency for ischemia, increasing their risk for coronary artery disease.

The link between vascular deterioration and branched chain amino acids in a population with high glycated haemoglobin: the SABPA study.

Globally the prevalence of non-communicable diseases, such as hypertension and type 2 diabetes, are escalating. Metabolomic studies indicated that circulating branched chain amino acids (BCAAs) are associated with insulin resistance, coronary artery disease and increased risk for cardiovascular events. We aimed to extend the current understanding of the cardiovascular risk associated with BCAAs. We explored whether BCAAs are related to markers of cardiovascular disease in a bi-ethnic population and whether this relationship was influenced by chronic hyperglycaemia. We included 200 African and 209 Caucasian participants, and determined their ambulatory blood pressure and carotid intima-media thickness (cIMT). We analysed blood samples for glycated haemoglobin (HbA1c) and BCAAs. Participants were stratified into two groups according to their HbA1c value using the median cut-off value of 5.6%. Ambulatory BP, cIMT and BCAAs were significantly higher (all p < 0.001) in the high HbA1c group. Single regression analyses indicated significant positive associations of ambulatory blood pressure and cIMT with BCAAs (all p < 0.05) in both the groups. These associations between ambulatory systolic blood pressure (SBP) (r = 0.16, p = 0.035) and cIMT (r = 0.22, p = 0.004) with BCAAs remained in the high HbA1c group after adjusting for age, gender, ethnicity and body mass index (BMI) and were confirmed in multiple regression analyses (ambulatory SBP: R (2) = 0.17, ß = 0.21, p = 0.005 and cIMT: R (2) = 0.30, ß = 0.19, p = 0.003). Our results demonstrate that BCAAs are independently related to ambulatory BP and cIMT in individuals with high HbA1c levels and suggest that potential cardiovascular deterioration accompany the rise in BCAAs in conditions of hyperglycaemia.

Procoagulant reactivity to laboratory acute mental stress in Africans and Caucasians, and its relation to depressive symptoms: the SABPA study.

The risk of cardiovascular disease is dramatically increasing in Africans (black). The prothrombotic stress response contributes to atherothrombotic disease and is modulated by depressive symptoms. We examined coagulation reactivity to acute mental stress and its relation to psychological well-being in Africans relative to Caucasians (white). A total of 102 African and 165 Caucasian school teachers underwent the Stroop Color-Word Conflict test. Circulating levels of von Willebrand factor (VWF) antigen, fibrinogen, and D-dimer were measured before and after the Stroop. Cardiovascular reactivity measures were also obtained. All participants completed the Patient Health Questionnaire-9 and the General Health Questionnaire-28 for the assessment of depressive symptoms and total psychological distress, respectively. After controlling for covariates, resting levels of VWF, fibrinogen, and D-dimer were higher in Africans than in Caucasians (all p-values ≤0.006). Depressive symptoms and psychological distress were not significantly associated with resting coagulation measures. Stress reactivity in VWF (p<0.001) and fibrinogen (p=0.016), but not in D-dimer (p=0.27), were decreased in Africans relative to Caucasians with Africans showing greater reactivity of total peripheral resistance (p=0.017). Depressive symptoms, but not general psychological distress, were associated with greater VWF increase (p=0.029) and greater fibrinogen decrease (p=0.030) in Africans relative to Caucasians. In conclusion, Africans showed greater hypercoagulability at rest but diminished procoagulant reactivity to acute mental stress when compared with Caucasians. Ethnic differences in the vascular adrenergic stress response might partially explain this finding. Depressive symptoms were associated with exaggerated VWF reactivity in Africans relative to Caucasians. The clinical implications of these findings for Africans need further study.

Structural vascular disease in Africans: Performance of ethnic-specific waist circumference cut points using logistic regression and neural network analyses: The SABPA study.

A recently proposed model for waist circumference cut points (RPWC), driven by increased blood pressure, was demonstrated in an African population. We therefore aimed to validate the RPWC by comparing the RPWC and the Joint Statement Consensus (JSC) models via Logistic Regression (LR) and Neural Networks (NN) analyses. Urban African gender groups (N=171) were stratified according to the JSC and RPWC cut point models. Ultrasound carotid intima media thickness (CIMT), blood pressure (BP) and fasting bloods (glucose, high density lipoprotein (HDL) and triglycerides) were obtained in a well-controlled setting. The RPWC male model (LR ROC AUC: 0.71, NN ROC AUC: 0.71) was practically equal to the JSC model (LR ROC AUC: 0.71, NN ROC AUC: 0.69) to predict structural vascular -disease. Similarly, the female RPWC model (LR ROC AUC: 0.84, NN ROC AUC: 0.82) and JSC model (LR ROC AUC: 0.82, NN ROC AUC: 0.81) equally predicted CIMT as surrogate marker for structural vascular disease. Odds ratios supported validity where prediction of CIMT revealed -clinical -significance, well over 1, for both the JSC and RPWC models in African males and females (OR 3.75-13.98). In conclusion, the proposed RPWC model was substantially validated utilizing linear and non-linear analyses. We therefore propose ethnic-specific WC cut points (African males, ≥90 cm; -females, ≥98 cm) to predict a surrogate marker for structural vascular disease.

Defensive coping facilitates higher blood pressure and early sub-clinical structural vascular disease via alterations in heart rate variability: the SABPA study.

OBJECTIVES: Defensive coping (AC) responses in urban African males have been associated with vascular responsiveness, partly explaining autonomic nervous system dysfunction. We therefore aimed to assess whether AC responses facilitate higher blood pressure and early sub-clinical structural vascular disease via alterations in frequency- and time-domain heart rate variability (HRV) responses. METHODS: We included 355 African and Caucasian men and women without pre-existing atrial fibrillation, aged 45 ± 9 years. Significant interaction on main effects (coping × ethnicity × gender) for left carotid intima media thickness far wall (L-CIMTf) and cross sectional wall area values necessitated selection of AC responders above mean via the Coping Strategy Indicator. We collected B-mode ultrasound L-CIMTf, ambulatory BP and-HRV data. Overnight fasting blood was obtained. RESULTS: Overall, Africans and AC Africans, mostly men, revealed a poorer lifestyle profile, higher prevalence of hypertensive status, disturbed sympathovagal balance and depressed HRV temporal and geometric patterns compared to the Caucasians (P ≤ 0.05). Moderately depressed non-linear and time-domain HRV (SDNN <100 ms) was prevalent in 28% of Africans compared to 11% of Caucasians. A similar trend was shown for the AC African participants (32%) compared to Caucasians (16%). Only depressed HRV time-domain (SDNN: adj. R(2) = 0.34; ß = -0.24; p = 0.08) and vagal-impaired heart rate responses (RMSSD: adj. R(2) = 0.28; ß = -0.28; p < 0.05) were associated with higher blood pressure and early structural vascular changes in AC African men. CONCLUSION: Defensive coping facilitated autonomic nervous system dysfunction, which was associated with higher blood pressure and sub-clinical structural vascular disease in an African male cohort.