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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 (R2 = 0.24; β = −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 (R2 = 0.42; β = −0.17; p = 0.039) prior to adjustment for γ-glutamyl transferase (R2 = 0.45; β = −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.

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: R2 = 0.17, β = 0.21, p = 0.005 and cIMT: R2 = 0.30, β = 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.

The renin–angiotensin–aldosterone system can be activated by sympathetic nervous input and is thought to have an important role in the prevalence of hypertension and cardiovascular risk in black Africans. We examined (1) the association between plasma renin responses to mental stress and a marker of sub-clinical atherosclerosis; and (2) associations between resting renin and 24-h ambulatory blood pressure. Participants were 143 urbanized black African men and women (43.1±7.7 years) drawn from a study of Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA). After an overnight fast, participants completed the Stroop mental stress task. Blood samples were drawn during baseline and 10 min after the task to assess the concentration of active renin in plasma. Blood pressure assessments included continuous Finometer measures during the stress testing and 24-h ambulatory monitoring. Carotid intima–media thickness (CIMT) was measured using high-resolution ultrasound. Approximately 50% of the sample responded to the task with an increase in renin concentration. Multiple linear regression analysis revealed an association between the renin stress response and CIMT (β=0.024, 95% confidence interval, 0.004–0.043), after adjustment for conventional risk factors, blood pressure stress responses and basal levels of renin activity (R2 for model=0.37). In addition, resting renin was inversely associated with ambulatory blood pressure. In summary, heightened release of renin during a laboratory mental stressor was associated with a marker of sub-clinical atherosclerosis; thus, it may be a potential mechanism in explaining the increased burden of cardiovascular disease in urbanized black Africans. http://dx.doi.org/10.1038/jhh.2010.82

Severe underweight may be a risk factor for hypertension in developing countries, although the manner whereby this occurs is unknown. Leptin is known to exert both beneficial and detrimental vascular effects, and is predictive of poor cardiovascular outcome at high levels, but also at low levels. We explored the relationship between blood pressure and leptin in black men from South Africa with a body mass index (BMI) in the underweight to normal range. We included 113 African men (BMI≤25 kg/m 2 ) and took anthropometric, biochemical and cardiovascular measures. The blood pressure-leptin relationship was then investigated along quintiles of leptin and within BMI stratified median split (20 kg/m 2 ) groups. Blood pressure increased across leptin quintiles 1–3 (p for trend≤0.040), whereas no relationship was observed along quintiles 3 to 5 (p for trend≥0.14) (adjusted for age and waist circumference). Blood pressure was similar in the two BMI median split groups (p≥0.083). In the low BMI group only, blood pressure associated positively with leptin following unadjusted, partial, and full adjustment (systolic blood pressure and diastolic blood pressure: R 2 =0.20–0.27, β=0.32–0.34, p≤0.009). Decreasing leptin levels are not likely to contribute to hypertension prevalence in the underweight. Rather, in African men with a BMI≤20 kg/m 2 , low leptin levels are positively and independently associated with elevated blood pressure, which is not seen at higher BMI (20–25 kg/m 2 ). Our findings suggest a differential concentration dependent vascular effect of leptin in underweight and normal weight African men.

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, χ 2 tests were used. Results . A TG:HDL-C ratio ≥1.49, TC:HDL-C ratio ≥5.4 and an HDL-C level ≤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.

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; β = −0.25; p = 0.002, DBP: R$^2$ = 0.30; β = −0.21; p = 0.022, PP: R$^2$ = 0.30; β = −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

Twenty-four hour urinary albumin excretion reflects general endothelial damage, relates to arterial stiffness, and predicts adverse health outcomes. Albumin determined from easily collected spot urine samples is also predictive. No prognostic evidence for albumin excretion from any means of urine collection exists for Africans. We followed health outcomes in 1061 randomly selected non-diabetic, HIV negative Africans (mean age: 51.5 years; 62.0% women). We determined the baseline urinary albumin-to-creatinine ratio from spot urine samples. Over a median follow-up of 4.52 years, 132 deaths occurred of which 47 were cardiovascular-related. The urinary albumin-to-creatinine ratio averaged 0.68 (5th to 95th percentile interval; 0.13, 4.54 mg/mmol). In multivariable-adjusted analyses, albumin excretion predicted all-cause mortality (hazard ratio, 1.26; 95% confidence interval, 1.07, 1.48; P=0.006), and a tendency existed for cardiovascular (1.26; 0.97, 1.63; P=0.087) mortality, which seemed driven by stroke (1.72; 1.17, 2.54; P=0.006) and not cardiac mortality (0.67; 0.41, 1.07; P=0.094). The predictive value remained in 528 hypertensives for both all-cause (1.38; 1.13, 1.69; P=0.001) and cardiovascular mortality (1.45; 1.07, 1.96; P=0.017), but again driven by stroke. Our findings remained significant after excluding participants with macroalbuminuria and those on anti-hypertensive treatment. In conclusion, in non-diabetic HIV-negative Africans, albumin excretion from spot urine samples predicts all-cause and stroke mortality.

Background: Hypertension and increased blood glucose are associated with subclinical kidney damage, atherosclerosis and with low testosterone values. Low testosterone in men is often accompanied by increased levels of estradiol. Objectives and methods: In this study, the association between estradiol, subclinical kidney damage and atherosclerosis in African and white men in a South African cohort was investigated. Cardiovascular variables were studied by means of B-mode ultrasound and ambulatory blood pressure (BP) monitoring. The sex hormones and other biochemical values were measured from fasting venous blood and overnight urine samples. The ethnic groups were stratified into low and high testosterone groups by means of median split. Results: The low testosterone African group demonstrated a higher cardiovascular risk compared with the low testosterone white men with 91% being hypertensive and having increased albumin-to-creatinine ratio (ACR), left carotid intima–media thickness (L-CIMTf) and estradiol-to-testosterone ratio. In the low-testosterone African men, estradiol explained 33% of the variance in ACR, whereas the estradiol-to-testosterone ratio explained 22% of the variance in L-CIMTf, respectively. Estradiol-to-testosterone ratio was positively associated with ACR in the low testosterone whites. Conclusion: We conclude that increased levels of estradiol may play a role in the development of subclinical kidney damage in both African and white men as well as atherosclerosis in low-testosterone African men. http://dx.doi.org/10.1097/HJH.0b013e3283599bb5

The aetiology for an increasing incidence of hypertensive cardiovascular disease amongst Africans in southern Africa is unclear. Hypertension may be induced by inadequate release of L-arginine-derived nitric oxide impairing vascular tone regulation. In addition, asymmetric dimethylarginine (ADMA) is associated with cardiovascular disease. We compared profiles of L-arginine in African and Caucasian men of similar age with cardiovascular risk factors. We studied 163 Caucasian and 132 African men, respectively, (20 to 70 years) measuring serum L-arginine, ADMA, creatinine, urea, symmetric dimethylarginine (SDMA) and blood pressure. L-arginine levels were significantly lower, whereas blood pressure and pulse wave velocity were significantly higher in African men. Simple linear regression showed ADMA more strongly associated with L-arginine in Caucasians (r=0.59 vs 0.19), whereas association of SDMA with L-arginine was significant only in Caucasians (r=0.43 vs 0.001). The stronger association of L-arginine with ADMA in Caucasian men was confirmed by multiple regression analysis (β=0.46 vs 0.25). Our findings show that the relationship of cardiovascular risk factors with serum L-arginine and some of its catabolites is different in African and Caucasian men and that this may be associated with a relatively higher prevalence of hypertension in African men. http://www.nature.com/jhh/journal/v26/n12/pdf/jhh2011103a.pdf http://dx.doi.org/10.1038/jhh.2011.103

Background Dissociation between behavioural defensive active coping (AC) control albeit physiological "loss of control" responses was associated with silent ischaemia and structural wall abnormalities in African men. Whether it applies to structural alterations and endothelial dysfunction is uncertain. We therefore aimed to determine AC ethnic-gender specific receiver operating characteristic (ROC) carotid intima media far wall (CIMTf) cut points best associated with 24-h BP, -silent ischaemia and glycated haemoglobin (HbA1c). Methods Participants included African and Caucasians (N=317) without pre-existing stroke or atrial fibrillation, aged 45±9years. The Coping Strategy Indicator was used to measure AC. Ultrasound CIMTf, ambulatory BP, silent ischaemia and fasting blood samples were obtained. Results Between 69 and 77% of AC African men showed above normal diastolic BP and HbA1c levels compared to 44–48% of AC Caucasian men. In AC African women, 41–60% showed above normal BP, silent ischaemia and HbA1c levels compared to 17–44% of their Caucasian counterparts. ROC curve analyses, detecting optimal CIMTf cut points, ranged between 0.57 and 0.65mm (BP) and 0.71 and 0.74mm (silent ischaemia) in AC ethnic-gender groups. Only HbA1C (>5.7%), with a sensitivity/specificity 47%/74%, after controlling for confounders, predicted structural alterations at an optimal cut point of 0.69mm in AC African men (OR 4.5; 95% CI 2.93–18.73). Conclusion Novel findings of behavioural resilience were apparent in the AC African female despite a high prevalence of risk markers. In AC males, chronic hyperglycaemia facilitated endothelial dysfunction, i.e. a physiological "loss of control" and susceptibility to stroke risk.