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.

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.

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.

Asymmetric dimethylarginine is associated with parameters of glucose metabolism in Caucasian but not in African women from South Africa.

AIM: Ethnic differences in obesity and obesity related disorders prompted us to search for possible contributors. The impact of the novel cardiovascular risk factor asymmetric dimethylarginine (ADMA) has been never determined in the African population. The present observational study aimed to compare ADMA levels between healthy African (102) and Caucasian women (115) from South Africa, and its impact on glucose metabolism. METHODS: All participants underwent an oral glucose tolerance test with measurements of glucose, insulin, C-peptide, proinsulin and free fatty acids before and after 30, 60, 90, 120 minutes. Fasting serum ADMA was measured by ELISA assay and obesity was determined by anthropometry. RESULTS: Serum ADMA did not differ between the ethnic groups. After stratification according to ADMA quartiles Caucasian women in the upper quartile had significantly higher body mass index and waist circumference as well as elevated insulin resistance, insulin, C-peptide and proinsulin levels with no differences in serum glucose compared to women in the lowest quartile. There was a significant stronger postchallenge insulin response in Caucasian women of the upper quartile. No differences were found in African women. CONCLUSIONS: Despite similar ADMA levels in both ethnic groups ADMA was positively correlated with parameters of glucose metabolism in the Caucasian but not in the African women from South Africa.

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.

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.

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.

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.

A biochemical analysis of the effects of arachidonic acid on sarcoplasmic reticulum function.

Discontinuous sucrose gradients were used to determine the degree of association between arachidonic acid and sarcoplasmic reticulum vesicle membranes. Fraction analyses showed that arachidonic acid migrated to a different region of the sucrose gradient in the presence of sarcoplasmic reticulum membranes. This could suggest that arachidonic acid was complexed into the membranes. Arrhenius curves representing the temperature dependency of Ca2+-Mg2+-ATPase activity and calcium uptake in the presence and absence of arachidonic acid were constructed. The activation energy for ATPase did not change significantly due to the presence of arachidonic acid. The curve representing control calcium uptake did not show a discontinuity. However, the curve representing calcium uptake in the presence of arachidonic acid showed discontinuities at 18 degrees C and 21 degrees C. Activation energy increased sharply between these temperatures. The results suggest that arachidonic acid reached the critical micellar concentration between these temperatures. Enthalpy decreased in the presence of arachidonic acid. This observation could suggest a transition of the protein-phospholipid complex to a less rigid state since decreased order in the membrane would decrease the energy barrier for activation of ATPase.

Validation of the Finometer device for measurement of blood pressure in black women.

The improved Finapres apparatus, known as the Finometer, measures finger blood pressure noninvasively on a beat-to-beat basis and gives waveform measurements similar to intra-arterial recordings. The Finometer measures brachial pressure and corrects for finger pressure accordingly. It also corrects for the hydrostatic height of the finger with respect to the heart level. The objective was to validate the Finometer according to the revised British Hypertension Society (BHS) protocol and the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). We carried out a main validation test using a subject group of 102 black women, which was also divided into smaller groups, namely 24 hypertensives, 25 obese normotensive and 35 lean normotensive women. Finometer and mercury sphygmomanometer blood pressure (BP) measurements were taken early in the morning before breakfast, after the subjects stayed overnight in a research unit. Within the whole subject group, the Finometer satisfied the AAMI criteria for accuracy and achieved an overall A/B grading according to the BHS criteria. The sphygmomanometer measurements were 128+/-20/78+/-12 mmHg compared to 130+/-20/78+/-11 mmHg for the Finometer. The average differences between the mercury sphygmomanometer and Finometer readings for systolic and diastolic BP were, respectively, -1.83+/-6.8 and 0.88+/-7.5. Systolic readings of the Finometer device differed by less than 5 mmHg for 64%, by less than 10 mmHg for 86% and differed by less than 15 mmHg for 96% of all readings. A total of 63% of all diastolic readings of the Finometer by less than 5 mmHg, 85% by less than 10 mmHg and 94% of all readings differed by less than 15 mmHg. On the basis of these results, the Finometer device satisfied the validation criteria of AAMI and received an A/B grading according to the BHS protocol. It can therefore be recommended for measurements in the clinical set-up and for research purposes.

Prolactin, testosterone and cortisol as possible markers of changes in cardiovascular function associated with urbanization.

People living in large informal settlements in South Africa showed a significant increase in cardio/cerebrovascular disease. This study was undertaken to compare the cardiovascular and endocrine parameters of urbanized and rural black female and males. The hormone levels such as prolactin, cortisol and testosterone may also change with urbanization and could make a contribution to the high rate of hypertension. For this study, 1202 black subjects were selected from 37 randomly selected rural and urbanized settlements. Resting blood pressure was recorded with a Finapres apparatus. Cardiac output, stroke volume, heart rate, total peripheral vascular resistance and compliance had been obtained with the Fast Modelflow software program. An acute laboratory stressor (hand dynamometer exercise) was applied to challenge the cardiovascular system and the measurements were repeated. Blood sampling was done and hormone levels were determined by biochemical analyses. For females, significant lower levels of cortisol were found in the urban strata in comparison with the rural strata. The testosterone levels were significantly lower and the prolactin levels significantly higher for females in the informal settlements compared with the rural strata. It is noticeable that most cardiovascular parameters showed the highest changes with the application of the stressor in the informal settlement strata and the lowest in people living on farms for both male and female. The prolactin levels in males are significantly higher in the informal settlement stratum. Subjects living in informal settlements showed a noticeable endocrine pattern of ongoing stress that can be associated with changes in the cardiovascular parameters with urbanization. This can partly explain the reported high rate of cardio/cerbrovascular disease in black South Africans living in informal settlements.

Dietary risk markers that contribute to the aetiology of hypertension in black South African children: the THUSA BANA study.

Although clinical hypertension occurs less frequently in children than in adults, ample evidence supports the concept that the roots of essential hypertension extend back to childhood. Since little is available in the literature on causal dietary factors of hypertension in children, this study hypothesised that certain dietary factors can be identified as risk markers that might contribute to the aetiology of hypertension in black children. Children aged 10-15 years were randomly selected from 30 schools in the North West Province from 2000 to 2001. These children comprised 321 black males and 373 females from rural to urbanised communities, of which 40 male and 79 female subjects were identified with high-normal to hypertensive blood pressure. Blood pressure was measured with a Finapres apparatus and data were analysed with the Fast Modelflo software program to provide systolic, diastolic and mean blood pressure. A 24-h dietary recall questionnaire and weight and height measurements were taken. In a stepwise regression analysis, the following variables were significantly associated (P < or = 0.05) with blood pressure parameters of hypertensive males: biotin, folic acid, pantothenic acid, zinc and magnesium. Energy, biotin and vitamin A intakes were significantly associated with blood pressure parameters of hypertensive females. No significant dietary markers were indicated for any of the normotensive groups. Dietary intakes of all of these nutrients were well below the dietary reference intakes. In conclusion, the dietary results coupled with the cardiovascular parameters of this study identified folic acid and biotin as risk markers that could contribute to the aetiology of hypertension in black persons. The low intakes of these nutrients, among others, is a matter of serious concern, as is the increasing tendency towards urbanisation.

Cardiovascular reactivity in Black South-African males of different age groups: the influence of urbanization.

OBJECTIVE: Blacks in an urban environment seem to be more vulnerable to excessive increases in blood pressure during daily life events. This greater cardiovascular reactivity during acute stress situations in urban Blacks may lead to the development of hypertension in their later lives. Because Blacks in South Africa are involved in a massive process of urbanization, which may lead to chronic diseases of lifestyle like hypertension and diabetes, this study was undertaken to compare the cardiovascular reactivity patterns of urbanized and rural Black males in the North-West province of South Africa. DESIGN: Two hundred twenty-three Black males of different age groups, Group 1: younger than 25 years of age; Group 2: between 25 and 44 years of age; and Group 3: 45 years of age and older. Participants were randomly selected from rural and urbanized settlements. METHODS: After resting blood pressure was recorded with a Finapres apparatus, and cardiac output, stroke volume, heart rate, and total peripheral vascular resistance had been obtained, an acute laboratory stressor (hand dynamometer exercise) was applied and the above measurements repeated. RESULTS: The SBP, DBP, and MAP increased 28% and 42% in both the rural and the urbanized groups. There was a shift from a central reactivity pattern (increased cardiac output) in the young rural group (< 25 years) to a peripheral reactivity pattern (increased total peripheral resistance) in the > or = 45 years old urbanized males after applying the stressor. CONCLUSIONS: Cardiovascular reactivity differs between Black males from a rural area compared to urbanized Black males. The urbanized males > or = 45 years of age were at a higher risk of developing cardiovascular disease because their total peripheral resistance reactivity increased the most during application of the stressor.

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.

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.

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.