Optimal waist-to-height ratio values for cardiometabolic risk screening in an ethnically diverse sample of South African urban and rural school boys and girls.

BACKGROUND: The proposed waist-to-height ratio (WHtR) cut-off of 0.5 is less optimal for cardiometabolic risk screening in children in many settings. The purpose of this study was to determine the optimal WHtR for children from South Africa, and investigate variations by gender, ethnicity and residence in the achieved value. METHODS: Metabolic syndrome (MetS) components were measured in 1272 randomly selected learners, aged 10-16 years, comprising of 446 black Africans, 696 mixed-ancestry and 130 Caucasians. The Youden's index and the closest-top-left (CTL) point approaches were used to derive WHtR cut-offs for diagnosing any two MetS components, excluding the waist circumference. RESULTS: The two approaches yielded similar cut-off in girls, 0.465 (sensitivity 50.0, specificity 69.5), but two different values in boys, 0.455 (42.9, 88.4) and 0.425 (60.3, 67.7) based on the Youden's index and the CTL point, respectively. Furthermore, WHtR cut-off values derived differed substantially amongst the regions and ethnic groups investigated, whereby the highest cut-off was observed in semi-rural and white children, respectively, Youden's index0.505 (31.6, 87.1) and CTL point 0.475 (44.4, 75.9). CONCLUSION: The WHtR cut-off of 0.5 is less accurate for screening cardiovascular risk in South African children. The optimal value in this setting is likely gender and ethnicity-specific and sensitive to urbanization.

Chronic kidney diseases in mixed ancestry south African populations: prevalence, determinants and concordance between kidney function estimators.

BACKGROUND: Population-based data on the burden of chronic kidney disease (CKD) in sub-Saharan Africa is still very limited. We assessed the prevalence and determinants of CKD, and evaluated the concordance of commonly advocated estimators of glomerular filtration rate (eGFR) in a mixed ancestry population from South Africa. METHODS: Participants were a population-based sample of adults selected from the Bellville-South community in the metropolitan city of Cape Town. eGFR was based on the Cockroft-Gault (CG), Modification of Diet in Kidney Disease (MDRD) and CKD Epidemiology Collaboration (CKD-EPI) equations (with and without adjustment for ethnicity). Kidney function staging used the Kidney Disease Outcome Quality Initiative (KDOQI) classification. Logistic regressions and kappa statistic were used to investigate determinants of CKD and assess the agreement between different estimators. RESULTS: The crude prevalence of CKD stage 3-5 was 14.8% for Cockcroft-Gault, 7.6% and 23.9% respectively for the MDRD with and without ethnicity correction, and 7.4% and 17.3% for the CKD-EPI equations with and without ethnicity correction. The highest agreement between GFR estimators was between MDRD and CKD-EPI equations, both with ethnicity correction, Kappa 0.91 (95% CI: 0.86-0.95), correlation coefficient 0.95 (95% CI: 0.94-0.96). In multivariable logistic regression models, sex, age and known hypertension were consistently associated with CKD stage 3-5 across the 5 estimators. CONCLUSIONS: The prevalence of CKD stages greater than 3 is the highest reported in Africa. This study provides evidence for support of the CKD-EPI equation for eGFR reporting and CKD classification.

Associations of MC3R polymorphisms with physical activity in South African adolescents.

BACKGROUND: There is evidence demonstrating that the contribution of sedentary behavior and effect of physical activity on metabolic phenotypes is mediated by polymorphisms in genes. METHODS: The type and frequency of physical activity was assessed by means of structured questionnaires in 1555 South African school learners. Anthropometric measurements, blood pressure, fasting blood glucose and lipids were measured using standard procedures. The effect of different types and frequency of physical activity on obesity-related traits was assessed in relation to MC3R T6K and V81I genotypes in 430 of the learners. RESULTS: Levels of total cholesterol were significantly lower in learners carrying the MC3R T6K and V81I minor alleles, after adjusting for age, race, gender, and each specific physical activity category. An activity-by-genotype interaction was also detected: learners heterozygous for the V81I polymorphism and performed house chores often had reduced total cholesterol. Though no association was observed between frequency of physical activity and BMI, television viewing was significantly associated with an increase in height, weight and marginally with waist circumference. CONCLUSION: Our findings suggest that physical activity even in the form of house chores has a positive effect on metabolic traits and this effect is further enhanced in the presence of MC3R polymorphisms.

The growing importance of PON1 in cardiovascular health: a review.

The wide acceptance of the oxidation theory of atherogenesis has prompted attention to antioxidant mechanisms, particularly the prevention of lipid oxidation by high-density lipoprotein-associated proteins like paraoxonase 1 (PON1) enzyme. PON1 is a calcium-dependent enzyme that has interested toxicologists since its discovery as an organophosphate hydrolase. There is a growing interest in the enzyme's importance in cardiovascular health prompted by evidence that it may have a role in lipid metabolism and the development of atherosclerosis via its antioxidant effects. PON1 is capable of hydrolyzing homocysteine thiolactone, a metabolite of homocysteine that can impair protein function leading to endothelial dysfunction and vascular damage. Although this lactonase activity has been suggested to be PON1's native activity, the enzyme's specific physiological role and substrate remain unclear. In this review, we summarize developments in the field of PON1 research relating to cardiovascular health, and highlight those that perhaps warrant further research.

Assessment of Epstein-Barr virus in blood from patients with multiple sclerosis.

Viruses such as Epstein-Barr virus (EBV) which can establish latent infections in the central nervous system or the immune system have been associated with chronic neurological disorders, including multiple sclerosis. Results vary, therefore the aim of this study was to investigate the presence of EBV using both viral DNA and antibody screening techniques, using PCR and ELISA assays respectively, to evaluate viral presence in blood from control subjects and patients with multiple sclerosis. Viral gene sequences for latent proteins EBNA-1 and LMP-1 and lytic gene BamH1-W were present equally in both patients and controls (<7%). Anti-EBV-VCA IgG positive cases were present in >99% of all study subjects, and anti-EBV-VCA IgG immune status ratio showed a near-significant positive correlation with the EDSS in patients with multiple sclerosis. In contrast, Anti-EBV-VCA IgM positive cases were significantly increased in patients (controls: 23.3%; patients; 41.9%; P = 0.046). The IgM to IgG immune status ratio was near-significantly higher in patients with relapse episodes in the year preceding blood sampling (P = 0.058). Results from this and previous studies have shown higher prevalence rates for EBV evaluating anti-EBV IgM positive cases against viral DNA positive cases. Also, IgM, an innate immune response, showed an association with relapse episodes, suggesting viral re-activation as a contributing factor to these relapses.

Peripheral blood mononuclear cell membrane fluidity and disease outcome in patients with multiple sclerosis.

Immune cell membrane lipids are important determinants of membrane fluidity, eicosanoid production and phagocytosis and fatty acid metabolic abnormalities have been reported in immune cells from patients with multiple sclerosis. The aim of this study was to investigate the relationship between peripheral blood mononuclear cell membrane fluidity, permeability status, and disease outcome as measured by the Kurtzke expanded disability status scale. Phospholipids, fatty acids and cholesterol composition in peripheral blood mononuclear cells from 26 patients diagnosed with multiple sclerosis and 25 healthy control subjects were determined by colorimetric assay, gas chromatography and enzymatic assays, respectively. Membrane fluidity was calculated according to previously established formulae and correlated with C-reactive protein and the Kurtzke expanded disability status scale. There were no significant differences in membrane lipids in peripheral blood mononuclear cells from patients and controls. However, correlation studies showed lipid metabolic abnormalities, which were reflected in significant correlations between membrane fluidity as measured by both its fatty acid and phospholipid compositions, and the functional system scores. C-reactive protein showed positive correlations with phosphatidylcholine, phosphatidylserine, phosphatidylinositol and total phospholipids in membranes from control subjects. Metabolic abnormalities, as well as correlations between membrane fluidity and the functional system scores, suggested the involvement of these immune cell membranes in the disease progression. Furthermore, the changed relationship between membrane phospholipids and C-reactive protein, which has been shown to correlate with infectious episodes and clinical relapse, could be an indication of immune cell dysfunction in patients with multiple sclerosis.

Distribution and association of hs-CRP with cardiovascular risk variables of metabolic syndrome in adolescent learners.

OBJECTIVE: Metabolic syndrome (MetS) and its associated cardiovascular risk are on the increase in children. High-sensitivity C-reactive protein (hs-CRP) has emerged as a useful marker for inflammation associated with atherosclerosis and cardiovascular disease. Our aim was to determine the distribution of hs-CRP in an effort to identify the MetS variable that is critical in modulating plasma CRP levels in a population of South African adolescents. DESIGN: A cross-sectional analytical study design was used for this investigation, where the dependent and independent variables were measured simultaneously. METHODS: Anthropometric variables, blood pressure, fasting blood glucose and lipids were performed on 324 consenting learners aged 15-18 years from three different ethnic groups (Black, White and Coloured). The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) for ages 15-18 year olds was used to define MetS. RESULTS: The prevalence of MetS and obesity was 3.7% and 7.1%, respectively. The hs-CRP levels were significantly higher in subjects with a waist-circumference greater than the 90th percentile (p < 0.01) and in obese learners with MetS, but was lower in adolescents with normal weight and MetS. Median hs-CRP levels increased with an increasing number of metabolic abnormalities and exceeded 3 mg/L in 19% of adolescents. Gender and ethnic differences were observed. CONCLUSION: Our findings suggest that obesity and waist circumference appear to be major mediators of hs-CRP levels in South African adolescents.

HbA1c of 6.5% to diagnose diabetes mellitus -- does it work for us? -- the Bellville South Africa study.

BACKGROUND: HbA1c has been the gold standard for glycaemic control follow-up for decades. In 2009, a level of 6.5% (48 mmol/mol) was proposed as diagnostic for diabetes. We test this cut-off in our community. METHODS: Participants (946) from a community-based study were screened for diabetes using either a fasting blood glucose or oral glucose tolerance test (OFTT). The HbA1c cut-off of 6.5% was tested for each group. A receiver operator characteristic (ROC) curve for both groups was generated to establish an optimal cut-off. RESULTS: Our study included 224 (23.7%) males and 722 (76.3%) females. Using fasting blood glucose alone, 117 (14%) were diagnosed with diabetes--50% had an HbA1c value of ≥6.5% (48 mmol/mol). Using an OGTT, 147 (18%) were diagnosed with diabetes--46% had an HbA1c value of ≥6.5% (48 mmol/mol). ROC curves found a level of 6.1% (43 mmol/mol) to be optimal in both groups (AUC 0.85 and 0.82 respectively). The sensitivities were 80% and 75% and the specificities 77% and 78% respectively. CONCLUSIONS: A cut off of 6.5% (48 mmol/mol) is a good diagnostic tool with its high specificity; however the low sensitivity limits its use. We found a level of 6.1% (43 mmol/mol) to be optimal. This emphasizes the need for evidenced based values to be established in various population groups.

Red blood cell membrane fluidity in the etiology of multiple sclerosis.

Organisms adjust the order, or fluidity, of their cellular membranes in response to changes in their physiochemical environment by adjusting the lipid composition of their membranes. We investigated membrane fluidity using the phospholipid, fatty acid and cholesterol content of red blood cells (RBCs) from multiple sclerosis (MS) patients and correlated this with C-reactive protein (CRP) as well as with the severity of neurological outcome as measured by the Kurtzke Expanded Disability Status Scale (EDSS) and its Functional System Scores. The study group consisted of 31 patients with MS and 30 healthy control subjects. Phospholipids were determined using a colorimetric assay, fatty acids by gas chromatography, cholesterol by an enzymatic assay and CRP by a Beckman nephelometer. Cell membrane fluidity was calculated according to previously established formulae. RBC membrane fluidity as measured by the saturated to polyunsaturated fatty acid ratio was higher in patients than in controls (P = 0.04). The phosphatidylethanolamine saturated to polyunsaturated fatty acid ratio showed highly significant positive correlations with the EDSS and CRP < 5 microg/ml. CRP showed significant inverse correlations with the saturated nature but positive correlations with the ordered-crystalline-phase to liquid-crystalline-phase lipid ratio. In this study we show that membrane fluidity as measured by the relationship between membrane fatty acids, phospholipids and cholesterol is closely interrelated with inflammation and disease outcome in patients with MS. In conclusion, our findings suggest that the membrane lipid composition of patients with MS and, consequently, membrane fluidity are altered, which seems to be influenced by the inflammatory status.