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.

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.

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.

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.

Activity and side effects of imatinib in patients with gastrointestinal stromal tumors: data from a German multicenter trial.

Gastrointestinal stromal tumors (GIST) are mesenchymal tumors that in the past were classified as leiomyosarcomas or leiomyomas not responding to standard sarcoma chemotherapy. In several phase I and II trials the efficacy and safety of imatinib was shown before the largest trial ever performed in a single sarcoma entity revealed response rates (CR/PR) of 52 %. This multicenter phase II trial presented here was performed to open access to imatinib for patients with unresectable or metastastatic GIST when the EORTC 62005 trial had been closed before imatinib was approved in Germany. It was designed to follow the best clinical response and to assess the efficacy, safety and tolerability of imatinib 400mg/d in patients with unresectable or metastatic gastrointestinal stromal tumor. - 95 patients were treated in this trial with Imatinib 400mg/d. Four patients (4.6 %) attained a complete response and 26 patients (29.9%) a partial response to imatinib treatment. Forty-one patients (47.1 %) revealed a stable disease and 16 patients (18.4 %) had a progressive disease. - Of the progressive patients 22% showed a partial response and 67 % showed stable disease after escalating the dose to 800 mg. According to SWOG tumor response classification, 66 patients (70%) were free of progression within the first year of treatment. - Seventy-one patients (74.7%) experienced adverse events or severe adverse events with a suspected relationship to the study drug. Among these, the most common were nausea (n=27 patients, 28.4 %), eyelid edema and peripheral edema in 23 patients each (24.2 %), diarrhea in 20 patients (21.1 %), muscle cramps in 15 patients (15.8 %) and fatigue in 13 patients (13.7 %). - Imatinib 400 mg/d led to disease stabilisation in 81,6% of patients with unresectable or metastatic malignant GIST. Thirty-four percent of patients attained a tumor remission (partial or complete response). The safety profile of imatinib based on adverse event assessment is favorable. Imatinib is generally well tolerated in patients with gastrointestinal stromal tumors.

Classifying Africans with the metabolic syndrome.

This study was aimed to compare prevalences of the metabolic syndrome in Africans using five definitions as proposed by the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR), the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel (ATPIII)], the American College of Endocrinology (ACE), and the International Diabetes Federation (IDF). A further objective was to identify difficulties in classifying Africans with the metabolic syndrome and to suggest specific areas where criteria adjustments for identifying Africans should be made. A case-case-control cross-sectional study involved 102 urban African women. Except for microalbumin data, all data necessary for classification of the metabolic syndrome were collected, including fasting and 2-h glucose and insulin, anthropometric measurements, blood pressure, and lipids. The metabolic syndrome prevalences ranged from 5.4% (EGIR), 15.7% (ATPIII), >or=19.4% (WHO), 24.8% (IDF) to 25.5% (ACE). Only 2.9% (n=3) had a triglyceride level >or=1.69 mmol/l, but 58.8% (n=60) had a HDL-level <1.29 mmol/l, whereas 27% (n=26) were insulin resistant, 22.3% (n=21), had a blood pressure >or=140/90 or used hypertension medication. It seems as if the classification of hypertension, insulin resistance and hyperglycemia might have been adequate, but body composition and dyslipidemia criteria need adjustment for Africans. Since neither definition seems completely suitable for Africans it is suggested that clinical emphasis should rather be on treating any specific cardiovascular disease risk factor that is present, than on diagnosing a patient with the metabolic syndrome.

Should obesity be blamed for the high prevalence rates of hypertension in black South African women?

Hypertension is highly prevalent in South Africa, resulting in high stroke mortality rates. Since obesity is very common among South African women, it is likely that obesity contributes to the hypertension prevalence. The aims were to determine whether black African women have higher blood pressures (BPs) than Caucasian women, and whether obesity is related to their cardiovascular risk. African (N=102) and Caucasian (N=115) women, matched for age and body mass index, were included. Correlations between obesity (total body fat, abdominal obesity and peripheral fat) and cardiovascular risk markers (haemodynamic parameters, lipids, inflammatory markers, prothrombotic factors, adipokines, HOMA-IR (homoeostasis model assessment insulin resistance)) were compared between the ethnic groups (adjusted for age, smoking, alcohol and physical activity). Comparisons between low- and high-BP groups were also made for each ethnic group. Results showed that African women had higher BP (P<0.01) with increased peripheral vascular resistance. Surprisingly, African women showed significantly weaker correlations between obesity measures and cardiovascular risk markers when compared to Caucasian women (specifically systolic BP, arterial resistance, cardiac output, fibrinogen, plasminogen activator inhibitor-1, leptin and resistin). Interestingly, the latter risk markers were also not significantly different between low- and high-BP African groups. African women, however, presented significant correlations of obesity with triglycerides, C-reactive protein and HOMA that were comparable to the Caucasian women. Although urban African women have higher BP than Caucasians, their obesity levels are weakly related to traditional cardiovascular risk factors compared to Caucasian women. The results, however, suggest a link with the development of insulin resistance.

Genetic polymorphisms of beta2- and beta3-adrenergic receptor genes associated with characteristics of the metabolic syndrome in black South African women.

BACKGROUND: Genetic variation in the beta2 (ADRB2) and beta3 (ADRB3) adrenergic receptor genes are associated with obesity and insulin resistance. To further elucidate the role of these genes in the pathophysiology of obesity the present study investigated associations between certain polymorphisms in ADRB2 and ADRB3 and parameters of carbohydrate and lipid metabolism in a population of African origin. MATERIAL AND METHODS: Data of 102 black South African women obtained in the POWIRS (Profile of Obese Women with the Insulin Resistance Syndrome) study were used. Endpoint measurements included several anthropometric variables, resting blood pressure, plasma glucose, insulin, free fatty acids (FFA), ghrelin, leptin and lipids, and insulin resistance as estimated by the homeostasis model assessment (HOMA-IR) index. Polymorphisms were analyzed via PCR based methods. RESULTS: The percentage body fat was significantly lower (p< or =0.05) and the FFA significantly higher (p< or =0.05) in lean subjects (BMI< or =25 kg/m2) with the Glu27 variant allele compared to subjects with the Gln27 wildtype allele of the ADRB2 gene. In contrast, the variant allele of the ADRB2 gene was significantly positive associated (p< or =0.05) with the HOMA-IR-index in overweight black African women (BMI>25 kg/m2). No significant differences in parameters of the metabolic syndrome were apparent between subjects with the wildtype and variant alleles in the ADRB3 gene. CONCLUSION: The presence of the Glu27 and Arg64 polymorphisms of the ADRB2 and ADRB3 genes are not directly related to indices of the metabolic syndrome.

Arterial structure and function and environmental exposure to cadmium.

OBJECTIVES: Few studies have addressed the effect of cadmium toxicity on arterial properties. METHODS: We investigated the possible association of 24 h urinary cadmium excretion (an index of lifetime exposure) with measures of arterial function in a randomly selected population sample (n = 557) from two rural areas with low and high environmental exposure to cadmium. RESULTS: 24 h urinary cadmium excretion was significantly higher in the high compared with the low exposure group (p<0.001). Even though systolic (p = 0.42), diastolic (p = 0.14) and mean arterial pressure (p = 0.68) did not differ between the high and low exposure groups, aortic pulse wave velocity (p = 0.008), brachial pulse pressure (p = 0.026) and femoral pulse pressure (p = 0.008) were significantly lower in the high exposure group. Additionally, femoral distensibility (p<0.001) and compliance (p = 0.001) were significantly higher with high exposure. Across quartiles of 24 h urinary cadmium excretion (adjusted for sex and age), brachial (p for trend = 0.015) and femoral (p for trend = 0.018) pulse pressure significantly decreased and femoral distensibility (p for trend = 0.008) and compliance (p for trend = 0.007) significantly increased with higher cadmium excretion. After full adjustment, the partial regression coefficients confirmed these associations. Pulse wave velocity (beta = -0.79+/-0.27; p = 0.004) and carotid (beta = -4.20+/-1.51; p = 0.006), brachial (beta = -5.43+/-1.41; p = 0.001) and femoral (beta = -4.72+/-1.74; p = 0.007) pulse pressures correlated negatively, whereas femoral compliance (beta = 0.11+/-0.05; p = 0.016) and distensibility (beta = 1.70+/-0.70; p = 0.014) correlated positively with cadmium excretion. CONCLUSION: Increased cadmium body burden is associated with lower aortic pulse wave velocity, lower pulse pressure throughout the arterial system, and higher femoral distensibility.

A comparison of uric acid levels in Black African vs Caucasian women from South Africa: the POWIRS study.

OBJECTIVES: Elevated levels of uric acid are often associated with cardiometabolic risk factors. The aim of this study was to determine whether uric acid levels differ between African and Caucasian women and whether uric acid is associated with cardiometabolic risk factors within the two ethnic groups. METHODS: Women from African (N=102) and Caucasian (N=115) descent were recruited and their uric acid levels measured. Anthropometric measurements included height (stature), weight, and waist circumference. Correlations between uric acid and cardiometabolic variables within each ethnic group were also determined. RESULTS: African women had significantly lower levels of uric acid (P<.01) and significantly higher levels of blood pressure (P=.05) compared to the Caucasian women. There was a significant increase in blood pressure from the lower to higher uric acid tertiles in the African women. Uric acid strongly correlated with waist circumference in both ethnic groups. CONCLUSIONS: Despite their higher blood pressure, the African women had lower uric acid levels, yet they showed a significant increase in blood pressure from a low uric acid tertile to high uric acid tertile, which was not noticeable in the Caucasian women. A possible explanation is a lower waist circumference in African women compared to Caucasian women.

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

Inflammation, obesity and cardiovascular function in African and Caucasian women from South Africa: the POWIRS study.

The integrated relationship between inflammation, obesity and cardiovascular disease is currently a subject of much research interest. These specific relationships, however, have not been studied in-depth in South African population groups in order to determine the role of ethnicity. It is known that Africans, compared to Caucasians, suffer from a high prevalence of hypertension. It was therefore hypothesized that the levels of inflammatory markers (high-sensitivity C-reactive protein (hsCRP), fibrinogen and leptin) are higher in Africans compared to Caucasians and are notably associated with cardiovascular dysfunction in Africans. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index (BMI), were recruited. Leptin, hsCRP, fibrinogen and lipid levels, waist circumference (WC), BMI, systolic and diastolic blood pressure, cardiac output (CO), total peripheral resistance (TPR) and Windkessel compliance were measured. Results showed that the levels of leptin, hsCRP and fibrinogen were significantly higher (P<0.05) in the African women. The inflammatory markers correlated strongly with cardiovascular parameters, age and obesity (BMI, WC) in both groups, but after adjusting for age and obesity, none of the correlations were significant anymore. Multiple regression analyses (with leptin, hsCRP or fibrinogen as dependent variable) showed that only leptin levels of African women were explained by cardiovascular parameters (BP, TPR and CO). In conclusion, even though African women had significantly higher leptin, hsCRP, fibrinogen and blood pressure levels than Caucasian women, no cardiovascular parameters explained the variation in the inflammatory markers (except for leptin levels of African women).

The influence of testosterone on blood pressure and risk factors for cardiovascular disease in a black South African population.

OBJECTIVES: Traditionally high testosterone levels have been thought to have a detrimental effect on lipid profiles. Recently, reports have shown that testosterone has a beneficial effect on lipid profiles. On the other hand, androgens may increase blood pressure via the renin-angiotensin system. The aim of this study was to determine whether the level of testosterone is increased in hypertensive subjects or if other cardiovascular risk factors are altered with increased levels of testosterone in the Black population of South Africa. METHODS: For this study, 536 male and 666 female Black subjects were included. The subjects were divided into hypertensive and normotensive groups and high and low testosterone groups. Resting blood pressure was recorded with a finger arterial pressure device. Blood sampling and biochemical analyses were done by using standardized methods. RESULTS: The levels of testosterone in the hypertensive males and females were significantly higher compared to the normotensives. In the male high testosterone group, the level of triglyceride was significantly lower, while the high-density lipoprotein cholesterol level was significantly higher. In the female high testosterone group, systolic blood pressure, cortisol level, and renin activity were significantly higher. CONCLUSION: In the males, we found beneficial effects of testosterone, which may explain the reported lower incidence of atheroma. However, the testosterone level is also higher with hypertension. The elevated levels of systolic blood pressure and renin activity that were found in the female group with high testosterone levels may be an indication of the role of the renin-angiotensin system in this regard.

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.

Leptin is independently associated with systolic blood pressure, pulse pressure and arterial compliance in hypertensive African women with increased adiposity: the POWIRS study.

High leptin levels are often observed in human obesity and are implicated in obesity-related hypertension. Leptin levels have been found to be higher in hypertensive obese African-American women compared to normotensive African-American women, but a direct association between leptin and blood pressure could not be obtained. Additionally, increased adiposity has been associated with higher aortic stiffness in obese African-American women, but leptin was not included in the study. The effects of leptin on cardiovascular function in African women have not yet been determined. We hypothesised that leptin is directly associated with blood pressure and decreased arterial compliance and that leptin levels are significantly higher in hypertensive overweight/obese African women compared to normotensive overweight/obese African women. A case-case control study was performed which included 98 African women. The subjects were divided into lean normotensive (lean NT), overweight/obese normotensive (OW/OB NT) and overweight/obese hypertensive (OW/OB HT). The Finometer apparatus was used to obtain a more elaborate cardiovascular profile. Serum leptin and insulin levels as well as the HOMA-IR index were determined. Various anthropometric measures were obtained. Leptin levels were elevated (P < or = 0.05) in the OW/OB NT and HT groups compared to the lean NT group, but were similar in the OW/OB NT and HT groups. After adjusting for obesity, insulin resistance, hyperinsulinaemia and age, a direct positive correlation was obtained between leptin and systolic blood pressure (SBP) (P < or = 0.05; r = 0.68) in the OW/OB HT group. Additionally, leptin also correlated negatively with arterial compliance (P< or = 0.05; r = -0.76) and positively with pulse pressure (P < or = 0.05; r = 0.71) in the OW/OB HT group. In conclusion, even though leptin levels were the same in OW/OB HT and NT African women, leptin was directly and positively associated with SBP and pulse pressure and negatively with C(W) only in OW/OB HT African women, independent of obesity, insulin-resistance, hyperinsulinaemia and age.

Leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans.

The comparison of the associations between chronically elevated leptin levels and cardiovascular function in obese Africans and Caucasians has not yet been determined. Therefore, the aim of this study was to compare leptin's associations with cardiovascular function in obese African and obese Caucasian women to determine whether leptin's associations differ between these two groups. This study consisted of two case-case control studies. The first study included a sample of 102 apparently healthy African women and the second, 115 apparently healthy Caucasian women. All lean and obese subjects were selected from each study. The Finometer apparatus was used to obtain a more elaborate cardiovascular profile. Serum leptin levels, insulin levels and the lipid profile were determined. Stroke volume (SV) and cardiac output (CO) were significantly (P< or =0.01) elevated in both obese African and Caucasian groups compared to their lean controls. Total peripheral resistance (TPR) was significantly decreased and arterial compliance (C(W)) significantly increased in both obese African and Caucasian groups. In the obese Caucasian group, diastolic blood pressure (DBP) was significantly (P< or =0.01) lower, SV and C(W) significantly higher (P< or =0.01) and TPR significantly lower compared to the age, body mass index (BMI), and leptin-matched obese African group. After adjusting for age and BMI, leptin correlated negatively with DBP (P< or =0.05; r=-0.33) and TPR (P< or =0.05; r=-0.36) in the obese Caucasian group, but not in the obese African group. Even though leptin levels were similar in obese African and Caucasian women, leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans.

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.

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.