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

Plasma renin and cardiovascular responses to the cold pressor test differ in black and white populations: The SABPA study.

Low plasma renin levels and augmented cardiovascular reactivity to stress are common in blacks and have been linked to the development of hypertension in this population. We (i) compared cardiovascular and plasma renin reactivity to a cold pressor test between a black and white population; and (ii) investigated the associations between cardiovascular and plasma renin reactivity within the black and white populations. Our population consisted of 153 black and 188 white men and women (age range, 20-65 years). We measured blood pressure (BP), heart rate (HR), stroke volume (SV), total peripheral resistance (TPR), Windkessel arterial compliance, and determined plasma renin levels at rest and during the cold pressor test. Reactivity was calculated for each participant as the percentage change from the resting value. We found lower renin and elevated BP in blacks compared with whites at rest and during stress (both, P<0.001). During stress, HR increased more in blacks (P<0.001), whereas SV (P<0.001) and arterial compliance (P=0.013) decreased more in blacks compared with whites. TPR reactivity was positively associated with renin reactivity in blacks only (ß=0.17; P=0.041), while in whites diastolic BP reactivity was positively associated with renin reactivity (ß=0.21; P=0.005). Although blacks had suppressed renin levels at rest and during acute stress, vascular resistance reactivity associated positively with renin reactivity only in the black population. These results suggest that low renin levels in blacks during rest and stress are linked to increased peripheral vascular responses to stress, which may contribute to elevated BP in blacks.

Bioavailable IGF-1 and its Relation to the Metabolic Syndrome in a Bi-Ethnic Population of Men and Women.

Insulin-like growth factor 1 (IGF-1), an insulin sensitivity and vasculoprotective factor, associates negatively with the metabolic syndrome. However, IGF-1 is reduced by factors such as inflammation, oxidative stress and liver dysfunction. We investigated the relationship between bioavailable IGF-1 and the number of metabolic syndrome components and determined whether this relationship is independent of inflammation, oxidative stress and gamma glutamyl transferase (γ-GT; a marker of liver dysfunction). This study included 907 black and white participants stratified by sex (aged 43.0±11.8 years). Among them 63 participants had fasting glucose levels of ≥+7.0+mmol/l and/or used diabetes medication. Via standard methods we determined waist circumference, fasting glucose, triglycerides, high-density lipoprotein cholesterol and blood pressure. We also determined high-sensitivity C-reactive protein (CRP), reactive oxygen species (ROS), γ-GT, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3). IGF-1/IGFBP-3 was used as an estimate of bioavailable IGF-1. Total IGF-1 was similar between men and women (p=0.10), however, bioavailable IGF-1 was lower in women (p<0.001). In multivariate-adjusted analyses, IGF-1/IGFBP-3 was inversely associated with the number of metabolic syndrome components in both sexes (men: ß=- 0.11; p=0.013 and women: ß=- 0.17; p=0.003). Upon inclusion of ROS, γ-GT and CRP, significance was lost. In patients without diabetes, the results for men changed marginally, but were consistent for women. We found an inverse association between bioavailable IGF-1 and the number of metabolic syndrome components. But the relationship was dependent on oxidative stress, liver dysfunction and inflammation, suggesting underlying processes by which the metabolic syndrome attenuates IGF-1.

Leptin relates to prolonged cardiovascular recovery after acute stress in Africans: The SABPA study.

BACKGROUND AND AIMS: Heightened cardiovascular reactivity and delayed recovery to stress are associated with an increased risk of cardiovascular disease. Africans, who are more prone to develop hypertension, show greater cardiovascular reactivity to stress. However, causal factors underlying individual and ethnic differences in stress reactivity and recovery remain largely unexplored. Leptin, which is known for its sympatho-activating effects, is higher in Africans compared to Caucasians for any given body mass index. We compared how cardiovascular reactivity and recovery relate to leptin in African (n = 200) and Caucasian (n = 209) teachers. METHODS AND RESULTS: We measured leptin in serum and cardiovascular baseline and reactivity continuously with the Finometer device during the cold pressor test for 1 min, and recovery at intervals of 1, 3 and 5 min. Africans had higher body mass index, leptin and blood pressure (all P < 0.001). After full adjustment in multiple regression analyses, associations were seen mainly at the 5 min recovery interval. In Africans, cardiac output reactivity (ß = -0.335; P = 0.0018) and arterial compliance- (ß = -0.241; P = 0.048) associated negatively and total peripheral resistance- (ß = 0.227; P = 0.047) positively with leptin. In Caucasians, diastolic blood pressure correlated positively with leptin (ß = 0.200; P = 0.015). CONCLUSION: In Africans, higher circulating leptin levels associated with prolonged cardiovascular recovery after exposure to stress which could explain their increased vulnerability to hypertension development.

Bioavailable IGF-1 and its relationship with endothelial damage in a bi-ethnic population: The SABPA study.

INTRODUCTION: Insulin-like growth factor-1 (IGF-1) has vasculoprotective effects and can directly oppose endothelial dysfunction in several ways. To improve our understanding on the potential contribution of reduced IGF-1 to the development of vascular endothelial damage, we investigated the link between bioavailable IGF-1 and von Willebrand factor (vWF) as a marker of endothelial damage. We performed this study in black South African school teachers, known to be prone to hypertension. MATERIALS AND METHODS: From the larger Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study we included 179 black and 207 white non-diabetic men and women (aged 44.5 ± 9.96 years). We measured ambulatory blood pressure and determined IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3) and vWF antigen from blood samples. We used the molar IGF-1/IGFBP-3 ratio as an estimate of bioavailable IGF-1. RESULTS: Black individuals presented higher blood pressure and vWFag and lower IGF-1 than the white group (all p < 0.001). In multivariate-adjusted analyses, vWFag was inversely associated with IGF-1 (R(2) = 0.18; ß = -0.17; p = 0.044) and IGF-1/IGFBP-3 (R(2) = 0.18; ß = -0.17; p = 0.030) in blacks, with no associations in whites. Since IGF-1 is attenuated and vWFag elevated in diabetes, we included patients with diabetes (n = 38) and the aforementioned associations found in blacks remained robust. CONCLUSION: The inverse association between bioavailable IGF-1 and vWF in black South Africans suggests that suppressed IGF-1 may result in endothelial damage independent of traditional risk factors.

Leptin is positively associated with blood pressure in african men with a low body mass index: the SAfrEIC study.

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, ß=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.

Large artery stiffness and carotid intima-media thickness in relation to markers of calcium and bone mineral metabolism in African women older than 46 years.

Vascular calcification and cardiovascular diseases have been associated with altered bone metabolism. We explored the relationships of arterial pressures and carotid intima-media thickness (CIMT) with parathyroid hormone, 25-hydroxycholecalciferol and their ratio (PTH:25(OH)D3) as well as a marker of bone resorption (CTX) in lean and overweight/obese African women. A population of 434 African women older than 46 years was divided into lean and overweight/obese groups. We assessed brachial blood pressure, central pulse pressure (cPP) and CIMT, and determined PTH, 25(OH)D3 and CTX concentrations. Overweight/obese women had elevated PTH and PTH:25(OH)D3 compared with lean women (both P<0.001), whereas lean women had higher CTX (P<0.001). Single, partial and multiple regression analyses indicated that, in lean women CIMT was independently associated with PTH:25(OH)D3 (R(2)=0.22; ß=0.26; P=0.003), whereas in obese women cPP was associated with both PTH:25(OH)D3 (R2=0.20; ß=0.17; P=0.017) and CTX (R2=0.20; ß=0.17; P=0.025). In conclusion, we found that in African women with increased adiposity, cPP (as a surrogate measure of arterial stiffness), was positively associated with alterations in bone metabolism and calciotropic hormones, whereas CIMT of lean women was positively associated with PTH:25(OH)D3. Our results suggest that alterations in bone and calcium metabolism may contribute to arterial calcification in older African women.

Circadian rhythm and day to day variability of serum potassium concentration: a pilot study.

BACKGROUND: Hyperkalemia is a common and life-threatening complication frequently seen in patients with acute kidney injury, end-stage renal disease and chronic heart failure. Cardiac arrest and ventricular fibrillation are possible consequences. Biosensors are currently being developed to measure serum potassium under ambulatory conditions and trigger an alarm if the potassium concentration exceeds normal limits. Only few studies exist on the circadian rhythm of potassium; and its dependence on age and kidney function is less clear. METHODS: Our observational monocentric exploratory study included 30 subjects of which 15 had impaired renal function (RF) (GFR <60 ml/min/1.73 m(2)). Subjects were further categorized into three age groups: 18-39 years (N normal RF = 5, N impaired RF = 4), 40-59 years (N normal RF = 5, N impaired RF = 6), 60-80 years (N normal RF = 5, N impaired RF = 5). Serum potassium levels were measured every 2 h during a 24 h period and repeated once after 2, 4, or 6 days. RESULTS: In the 15 subjects with normal RF, the lowest mean potassium level (3.96 ± 0.14 mmol/l) was observed at 9 p.m. and the greatest (4.23 ± 0.23 mmol/l) at 1 p.m. In patients with impaired RF the lowest mean potassium level (4.20 ± 0.32 mmol/l) was observed at 9 p.m. and the highest (4.57 ± 0.46 mmol/l) at 3 p.m. The range between the mean of minimum and maximum was greater in patients with impaired RF (0.71 ± 0.45 mmol/l) than in subjects with normal RF (0.53 ± 0.14 mmol/l) [p < 0.001]. No difference in the circadian rhythm was found between the first and second examination. CONCLUSION: Our results indicate that patients with normal and impaired RF have comparable circadian patterns of serum potassium concentrations, but higher fluctuations in patients with impaired RF. These results have clinical relevance for developing an automatic biosensor to measure the potassium concentration in blood under ambulatory conditions in patients at high risk for potassium fluctuations.

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.

Relationship of coagulation and fibrinolytic variables with arterial structure and function in Africans.

INTRODUCTION: Although both coagulation and fibrinolysis are associated with cardiovascular disease (CVD) the underlying nature and pathways of many of these associations are still unclear. Our aim was to determine which of the current or 5-year prior levels of total fibrinogen, fibrinogen γ', plasminogen activator inhibitor-1 (PAI-1act) and global fibrinolytic potential were the stronger determinant of arterial structure and function. MATERIALS AND METHODS: This prospective study consisted of 2010 Africans over the age of 35 years with 5-year follow-up data available for 1288 participants. Cardiovascular measurements included arterial stiffness, blood pressure and carotid intima media thickness. RESULTS: Fibrinogen γ' showed stronger associations with blood pressure than total fibrinogen also in the presence of other CVD risk factors. PAI-1act was positively associated with blood pressure both cross-sectionally and prospectively, with the longitudinal association being the stronger determinant, also after adjustment for known CVD risk factors. Clot lysis time (CLT) was positively associated, both prospectively and cross-sectionally, with intima media thickness and negatively with markers of arterial stiffness but not after adjustment for known CVD risk factors. CONCLUSIONS: Fibrinogen γ' was more strongly associated with CVD function than total fibrinogen. PAI-1act was significantly associated with blood pressure with changes in PAI-1 levels preceding changes in blood pressure. Different mechanisms may be at play determining arterial wall stiffness/thickening and blood pressure as observed from the opposing associations with PAI-1act and CLT. CLT was not independently related to cardiovascular measures as its associations were weakened in the presence of other known CVD risk factors.

Evaluation of waist-to-height ratio to predict 5 year cardiometabolic risk in sub-Saharan African adults.

BACKGROUND AND AIMS: Simple, low-cost central obesity measures may help identify individuals with increased cardiometabolic disease risk, although it is unclear which measures perform best in African adults. We aimed to: 1) cross-sectionally compare the accuracy of existing waist-to-height ratio (WHtR) and waist circumference (WC) thresholds to identify individuals with hypertension, pre-diabetes, or dyslipidaemia; 2) identify optimal WC and WHtR thresholds to detect CVD risk in this African population; and 3) assess which measure best predicts 5-year CVD risk. METHODS AND RESULTS: Black South Africans (577 men, 942 women, aged >30years) were recruited by random household selection from four North West Province communities. Demographic and anthropometric measures were taken. Recommended diagnostic thresholds (WC > 80 cm for women, >94 cm for men; WHtR > 0.5) were evaluated to predict blood pressure, fasting blood glucose, lipids, and glycated haemoglobin measured at baseline and 5 year follow up. Women were significantly more overweight than men at baseline (mean body mass index (BMI) women 27.3 ± 7.4 kg/m(2), men 20.9 ± 4.3 kg/m(2)); median WC women 81.9 cm (interquartile range 61-103), men 74.7 cm (63-87 cm), all P < 0.001). In women, both WC and WHtR significantly predicted all cardiometabolic risk factors after 5 years. In men, even after adjusting WC threshold based on ROC analysis, WHtR better predicted overall 5-year risk. Neither measure predicted hypertension in men. CONCLUSIONS: The WHtR threshold of >0.5 appears to be more consistently supported and may provide a better predictor of future cardiometabolic risk in sub-Saharan Africa.

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.

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.

A comparison of the association between glomerular filtration and L-arginine status in HIV-infected and uninfected African men: the SAfrEIC study.

Hypertension, a major risk factor for cardiovascular disease worldwide, is increasing significantly in urbanised South Africans. Impaired glomerular filtration is a potential contributor to hypertension. Although HIV infection is widespread, little is known regarding its contribution to diminished estimated glomerular filtration rate (eGFR) and, in turn, hypertension in Africans. We compared eGFRs and cardiovascular profiles of newly identified HIV infected African men (N=53) not yet undergoing anti-retroviral therapy, and uninfected African men of similar age and anthropometry. The aim of the study was to determine whether eGFR is diminished in treatment naive HIV infected individuals and whether eGFR is associated with a potential modulator of hypertension, namely serum L-arginine. Cardiovascular risk factor profiles of HIV infected and uninfected men were similar. In men with healthy eGFRs >90 ml min(-1) per 1.73 m(2), eGFR was significantly lower with HIV infection (114 (90; 147)) compared with that in uninfected men: (120 (91; 168)), P=0.043. Despite the absence of clinically-diagnosed renal dysfunction, eGFR associated significantly with serum L-arginine only in HIV infected men (R(2)=0.277, ß=-0.299, P=0.034), whereas L-arginine did not stay in the model for uninfected men. This difference suggests that the fate of L-arginine as a substrate for nitric oxide generation may be altered in HIV infected individuals. Subsequently this is likely to escalate endothelial dysfunction, contributing to later hypertension and cardiovascular disease. Our findings show that while glomerular filtration rate is not associated with L-arginine in uninfected men, it is diminished and significantly negatively associated with serum L-arginine in HIV infected men.

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.

Double product and end-organ damage in African and Caucasian men: the SABPA study.

BACKGROUND: Increasing urbanisation in sub-Saharan African countries is causing a rapid increase in cardiovascular disease. Evidence suggests that Africans have higher blood pressures and a higher prevalence of hypertension-related cardiovascular morbidity and mortality, compared to Caucasians. We investigated double product (systolic blood pressure × heart rate), a substantial measure of cardiac workload, as a possible cardiovascular risk factor in African and Caucasian men. MATERIAL AND METHODS: The study consisted of 101 urbanised African and 101 Caucasian male school teachers. We measured 24h ambulatory blood pressure and the carotid cross-sectional wall area, and determined left ventricular hypertrophy electrocardiographically by means of the Cornell product. Urinary albumin and creatinine were analysed to obtain the albumin-to-creatinine ratio. RESULTS: Africans had higher 24h, daytime and nighttime systolic- and diastolic blood pressure, heart rate and resultant double product compared to the Caucasians. In addition, markers of end-organ damage, albumin-to-creatinine ratio and left ventricular hypertrophy were higher in the Africans while cross-sectional wall area did not differ. In Africans after single partial and multiple regression analysis, 24h systolic blood pressure, but not double product or heart rate, correlated positively with markers of end-organ damage (cross-sectional wall area: ß=0.398, P=0.005; left ventricular hypertrophy: ß=0.455, P<0.001; albumin-to-creatinine ratio: ß=0.280, P=0.012). No associations were evident in Caucasian men. CONCLUSIONS: Double product may not be a good marker of increased cardiovascular risk when compared to systolic blood pressure in African and Caucasian men.

Defensive active coping facilitates chronic hyperglycaemia and endothelial dysfunction in African men: the SABPA study.

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 ± 9 years. 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 0.65 mm (BP) and 0.71 and 0.74 mm (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 0.69 mm 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.