The association of endothelin-1 with markers of oxidative stress in a biethnic South African cohort: the SABPA study.

Both endothelin-1 and oxidative stress have important roles in the development of cardiovascular diseases such as hypertension and atherosclerosis. Limited information is available on the interaction between oxidative stress, the glutathione system and endothelin-1 in humans. We aimed to investigate the association of endothelin-1 with markers of oxidative stress and the antioxidant capacity in a biethnic South African cohort. This cross-sectional study included 195 black and 198 white South Africans. Serum endothelin-1 levels and oxidative stress-related markers such as reactive oxygen species (measured as serum peroxides), glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase were measured. In single, partial and multiple regression analyses endothelin-1 correlated positively with glutathione reductase activity (adj. R2=0.10; ß=0.232; P=0.020) and negatively with antihypertension medication (P=0.02) and tended to correlate with glutathione reductase-to-glutathione peroxidase ratio (adj. R2=0.10; ß=0.19; P=0.057) in black men. In white men, endothelin-1 correlated positively with ROS (adj. R2=0.09; ß=0.26; P=0.01) and negatively with glutathione peroxidase activity (adj. R2=0.05; ß=-0.23; P=0.02). In black women, endothelin-1 correlated negatively with total glutathione (adj. R2=0.22; ß=-0.214; P=0.026). Endothelin-1 may contribute to glutathione reductase upregulation through increased reactive oxygen species production mediated via endothelin-1 in black men. In white men, we observed a negative association between glutathione peroxidase and endothelin-1, describing the expected physiological relationship between endothelin-1 and reactive oxygen species. Higher total glutathione levels may act as a counter-regulatory mechanism to protect against oxidative vascular damage attributed by endothelin-1 in black women.

Low BMI is inversely associated with arterial stiffness in Africans.

In low socio-economic status communities in South Africa, African men showed a low BMI. Data on the effect of low BMI on cardiovascular function are scant. The present study aimed to assess the associations between low BMI and markers of cardiovascular function such as pulse wave velocity (PWV) and blood pressure in Africans aged 35-65 years, with low socio-economic status. The study population (n 496) was stratified into a low-BMI group with BMI ≤ 20 kg/m² and a normal-BMI group with BMI >20 kg/m² and ≤ 25 kg/m². Blood pressure (Omron HEM-757) and PWV (Complior SP; Artech-Medical) was determined. Africans with low BMI showed an increased arterial stiffness with significantly higher PWV compared with the normal-BMI group (men: P= 0.001; women: P= 0.026), which remained after adjustment. In men with low BMI, PWV correlated negatively with BMI before (r -0.204; P= 0.012) and after (r -0.200; P= 0.020) adjustment. Forward stepwise regression analyses indicated a negative association between PWV and BMI in African men. A J-curve was evident suggesting a detrimental effect of low BMI on cardiovascular function in Africans. A low BMI may contribute to the high prevalence of cardiovascular-related morbidity and mortality within a developing country.

The Association of Endothelin-1 with Markers of Arterial Stiffness in Black South African Women: The SABPA Study.

Background. Limited data exist regarding endothelin-1 (ET-1), a vasoactive contributor in vascular tone, in a population subjected to early vascular deterioration. We compared ET-1 levels and explored its association with markers of arterial stiffness in black and white South Africans. Methodology. This cross-sectional substudy included 195 black (men: n = 99; women: n = 95) and 197 white (men: n = 99; women: n = 98) South Africans. Serum ET-1 levels were measured as well as markers of arterial stiffness (blood pressure, pulse wave velocity, and arterial compliance). ET-1 levels were higher in black men and white women compared to their counterparts after adjusting for C-reactive protein. In both single and partial (adjusting for body mass index and gamma glutamyl transferase) regression analyses ET-1 correlated with age, interleukin-6, high density lipoprotein cholesterol, systolic blood pressure, pulse pressure, and pulse wave velocity in black women. In multivariate regression analyses the independent association of ET-1 with systolic blood pressure (Adj. R (2) = 0.13; ß = 0.28, p < 0.01) and pulse pressure (Adj. R (2) = 0.11; ß = 0.27, p < 0.01) was confirmed in black women only. ET-1 additionally associated with interleukin-6 in black women (p < 0.01). Conclusion. Our result suggests that ET-1 and its link with subclinical arteriosclerosis are potentially driven by low-grade inflammation as depicted by the association with interleukin-6 in the black female cohort.

The usefulness of γ-glutamyltransferase as a marker of cardiovascular function in Africans and Caucasians: the SABPA study.

AIM: Serum γ-glutamyltransferase (GGT) is increasingly regarded as a marker of vascular function. However, the usefulness of this marker is in dispute. Gender and ethnic differences, as well as the serum level range where correlations with vascular function will emerge, may complicate the usefulness of GGT. The aim is to compare correlations with markers of vascular function between African and Caucasian groups. METHODS: This cross-sectional target population study involved four groups of African and Caucasian men and women of 100 participants each. Fasting lipids, GGT, C-reactive protein (CRP), reactive oxygen species, and glycosylated hemoglobin (HbA1c) were determined as well as blood pressure, carotid intima-media thickness (CIMT), and left ventricular hypertrophy. RESULTS: γ-Glutamyltransferase levels were significantly higher in Africans compared with Caucasians and also higher in men than in women. γ-Glutamyltransferase correlated with triglycerides in all four groups and after adjusting the correlations sustained in the male groups but disappeared in women. Correlations existed between GGT and blood pressure, except for the African women. After adjustments, CIMT correlated with GGT in Caucasian men (r = 0.29; P < .01). Glycosylated hemoglobin was associated with GGT in Caucasian women (r = 0.26; P = .01) as well as CRP (r = 0.36; P < .01). When the groups were divided into low and high GGT groups by median split, most of the correlations disappeared in the high GGT groups. CONCLUSIONS: Gender and ethnic-specific associations occurred regarding GGT and variables associated with cardiovascular function. With high levels of GGT the correlations diminished. The usefulness of GGT as a marker of vascular dysfunction seems limited.

Adipokines and cardiometabolic function: How are they interlinked?

OBJECTIVE: Adipokines contribute directly to the coexistence of insulin resistance and endothelial dysfunction. Most studies focus on a single adipokine. We therefore investigated the independent relationships of leptin, adiponectin, tumor necrosis factor-alpha, resistin and visfatin, as well as the gut hormone ghrelin with blood pressure and insulin resistance. Secondly we evaluated the interrelationships of adipokines and ghrelin in concert with various cardiometabolic markers. METHODS AND RESULTS: Caucasian women (N=115) with varying levels of obesity (aged 31.3 + or - 9.18 years) were included. Significant correlations of leptin, adiponectin, ghrelin and visfatin with mean arterial pressure (p<0.05) disappeared after adjustment for age, body mass index and waist circumference. But significant correlations with insulin resistance (HOMA) (for leptin, adiponectin and ghrelin) remained significant after adjustments. Factor analyses yielded five factors, but two main clusters, namely a metabolic syndrome cluster (including leptin, adiponectin and ghrelin) and a vascular atherosclerotic cluster (including tumor necrosis factor-alpha, visfatin and resistin). CONCLUSION: Factor analyses identified patterns which indicate specific roles of the various adipokines. Leptin, adiponectin and ghrelin were more closely related to insulin resistance and central obesity as core components of the metabolic syndrome. Visfatin, tumor necrosis factor-alpha and resistin seem to direct their effects onto the vascular system possibly by means of mechanisms such as inflammation, vasoconstriction and coagulation.

Aging influences the level and functions of fasting plasma ghrelin levels: the POWIRS-Study.

OBJECTIVE: Ghrelin, known for its orexigenic activity, also have functions such as vasodilation and a growth hormone releasing action. It is uncertain whether these functions change with increasing age. This study aimed to determine whether ghrelin levels differ between young and older women with different levels of obesity; and secondly whether the associations of ghrelin with metabolic syndrome (MS) components, adipocytokines, coagulation factors, and cortisol change with increasing age. METHODS AND RESULTS: Caucasian women (N=107) were divided into young (19-29 years) and older groups (30-56 years). Fasting ghrelin, leptin, adiponectin, glucose, insulin, cortisol, fibrinogen and plasminogen activator inhibitor-1 (PAI-1) levels were determined. Blood pressure (BP), body mass index and waist circumferences were measured. Older lean women showed lower levels of ghrelin (p<0.05) than young lean women, with no differences regarding BP, obesity, lipids, adipokines or insulin resistance (IR). Ghrelin levels of older women remained constant with increasing obesity, but younger women showed significantly reduced ghrelin levels in obese groups. Only younger women showed significant correlations between ghrelin and leptin, adiponectin, fibrinogen and PAI-1 (adjusted for age, obesity and menstrual phase), whereas both age groups showed significant correlations with IR. In younger women factor analysis grouped ghrelin with coagulation factors and all MS components. In older women ghrelin was absent from the MS cluster, but was associated with lower BP, cortisol and IR. CONCLUSIONS: Ghrelin levels were not significantly elevated in lean older women, and did not change with increased obesity in older women--as were observed in younger women. The functions of ghrelin also seem to change with increased age since only in young women ghrelin was associated with obesity, coagulation factors and leptin.

Specific coping strategies of Africans during urbanization: comparing cardiovascular responses and perception of health data.

Specific coping mechanisms of Africans during urbanization were compared to and correlated with cardiovascular responses and perception of health data. Subjects included men (N=286) and women (N=360). The COPE questionnaire classified subjects as active (AC) or passive (PC) copers and the General Health Questionnaire measured subjective perception of health. The Finapres recorded blood pressure continuously before and during application of a handgrip test. Analyses adjusting for age, body mass index and resting cardiovascular data revealed that AC rural subjects showed predominantly cardiac responses and PC rural subjects predominantly vascular responses. All urbanized African men and women showed higher resting blood pressure, vascular responsiveness and hypertension prevalences than their rural counterparts. All rural AC subjects, especially women, and all urban PC subjects, especially men, reported a poorer perception of health. In conclusion, subjects with a PC style showed a predominantly vascular response in rural and urban areas whereas subjects with an AC style seem to shift from a predominant cardiac output response to a predominant vascular resistance response when moving from a rural to an urban area.

Coping mechanisms, perception of health and cardiovascular dysfunction in Africans.

The purpose of this study was to compare active and passive coping strategies of Africans with perception of own health and cardiovascular data. The subjects included 236 apparently healthy Africans (men=109; women=127). The COPE questionnaire was adapted, translated and validated for Africans. Scores on reliable sub-scales were used to classify men and women into more active coping (AC) and more passive coping (PC) subgroups. The General Health Questionnaire measured subjective perception of health. Blood pressure was recorded before and during application of the handgrip test, using the Finapres, a continuous non-invasive blood pressure monitor. Plasma renin activity (PRA) values, measured with radio immuno assay, were compared to blood pressure variables. Analyses of co-variance, adjusted for resting values and age, indicated that PC men responded with a larger increase in total peripheral resistance (TPR) (p=0.006), larger decrease in stroke volume (p=0.07), smaller increase in cardiac output (p=0.09) and larger increases in PRA resting (p=0.04) and reactivity (p< or =0.05) values. PC subjects reported a more negative perception of health than AC subjects. Young PC women presented greater hypertension prevalence rates (p< or =0.01) than AC women. In conclusion, all AC and PC subjects reacted with increased vascular reactivity on the handgrip test. PC men presented enhanced vascular reactivity, PRA and perception of poorer health values.

Associations between arterial compliance and anthropometry of children from four ethnic groups in south africa: the THUSA BANA Study.

AIM: To investigate whether associations and differences exist regarding the arterial compliance, dietary intake and anthropometric parameters of children of four different ethnic groups in South Africa. STUDY DESIGN: In this study, 1244 children from four ethnic groups, aged 10-15 years, were randomly selected from five regions of the North West Province. Blood pressure was measured with a Finapres apparatus and analysed to obtain systemic arterial compliance. Measurements were done to obtain body mass index (BMI), waist-to-hip ratio and percentage body fat. Dietary intake was determined with a 24-h dietary recall questionnaire. RESULTS: The black and mixed-origin subjects indicated the lowest values (p < or = 0.05) for BMI, percentage body fat, and dietary intake, whereas the white and Indian subjects showed significantly higher values than the other ethnic groups. The white and Indian children had significantly higher arterial compliance than the black and mixed-origin children at all ages from 10 to 15 years. Compliance showed significant correlations with all anthropometric parameters. CONCLUSION: Since black and mixed-origin children have the highest prevalence of undernutrition and stunted growth, it is suggested that parental undernutrition and inadequate nutrition in early life, associated with lower arterial compliance, may lead to the onset of adult hypertension.