Evidence that fibrinogen γ' regulates plasma clot structure and lysis and relationship to cardiovascular risk factors in black Africans.

Fibrinogen γ' is known to influence fibrin clot structure in purified experimental models, but little is known regarding its influence on clot structure in plasma. Furthermore, the environmental and biological factors that affect its concentration are poorly described. We analyzed fibrinogen γ', total fibrinogen concentration, and fibrin clot structure in 2010 apparently healthy black South Africans and related them to traditional cardiovascular disease (CVD) risk factors. Fibrinogen γ' generally increased with increasing fibrinogen concentration, but a decreased γ'/total fibrinogen ratio was found at the highest total fibrinogen concentrations. Clot maximum absorbance increased with total fibrinogen and fibrinogen γ', but decreased with γ'/total fibrinogen ratio. Clot lysis time showed a stronger relationship with fibrinogen γ' than with total fibrinogen, whereby increased fibrinogen γ' delayed clot lysis. CVD risk factors (excluding fibrinogen) explained 20% and 3%, respectively, of the variance in fibrinogen γ' and the γ'/total fibrinogen ratio, with C-reactive protein making the biggest contribution. More than 50% of the variance in fibrinogen γ' and γ'/total fibrinogen ratio is explained by factors other than total fibrinogen or other traditional CVD risk factors. Our data show that fibrinogen γ' modulates plasma clot structure and fibrinolysis and is also influenced by factors other than fibrinogen.

Common and rare single nucleotide polymorphisms in the LDLR gene are present in a black South African population and associate with low-density lipoprotein cholesterol levels.

The LDL receptor has an essential role in regulating plasma LDL-C levels. Genetic variation in the LDLR gene can be associated with either lower or moderately raised plasma levels of LDL-C, or may cause familial hypercholesterolemia. The prevalence of single-nucleotide polymorphisms (SNPs) in the LDLR in the black South African population is not known and therefore, we aimed to determine the genotypic variation of the LDLR in the study population as well as to define the association of the different genotypes with plasma LDL-C levels. A random selection of 1860 apparently healthy black South African volunteers aged 35-60 years was made in a cross-sectional study. Novel SNPs were identified in a subset of 30 individuals by means of automated sequencing before screening the entire cohort by means of the Illumina VeraCode GoldenGate Genotyping Assay on a BeadXpress Reader system. Twenty-five SNPs were genotyped, two of which were novel. A very rare SNP, rs17249141, in the promoter region was significantly associated with lower levels of LDL-C. Four other SNPs (rs2738447, rs14158, rs2738465 and rs3180023) were significantly associated with increased levels of LDL-C. We can conclude that some of the various SNPs identified do indeed associate with LDL-C levels.

The use of predefined diet quality scores in the context of CVD risk during urbanization in the South African Prospective Urban and Rural Epidemiological (PURE) study.

OBJECTIVE: Urbanization is generally associated with increased CVD risk and accompanying dietary changes. Little is known regarding the association between increased CVD risk and dietary changes using approaches such as diet quality. The relevance of predefined diet quality scores (DQS) in non-Western developing countries has not yet been established. DESIGN: The association between dietary intakes and CVD risk factors was investigated using two DQS, adapted to the black South African diet. Dietary intake data were collected using a quantitative FFQ. CVD risk was determined by analysing known CVD risk factors. SETTING: Urban and rural areas in North West Province, South Africa. SUBJECTS: Apparently healthy volunteers from the South African Prospective Urban and Rural Epidemiological (PURE) study population (n 1710). RESULTS: CVD risk factors were significantly increased in the urban participants, especially women. Urban men and women had significantly higher intakes of both macro- and micronutrients with macronutrient intakes well within the recommended CVD guidelines. While micronutrient intakes were generally higher in the urban groups than in the rural groups, intakes of selected micronutrients were low in both groups. Both DQS indicated improved diet quality in the urban groups and good agreement was shown between the scores, although they seemed to measure different aspects of diet quality. CONCLUSIONS: The apparent paradox between improved diet quality and increased CVD risk in the urban groups can be explained when interpreting the cut-offs used in the scores against the absolute intakes of individual nutrients. Predefined DQS as well as current guidelines for CVD prevention should be interpreted with caution in non-Western developing countries.

Effects of a multi-micronutrient-fortified beverage, with and without sugar, on growth and cognition in South African schoolchildren: a randomised, double-blind, controlled intervention.

Little is known about the effects of combined micronutrient and sugar consumption on growth and cognition. In the present study, we investigated the effects of micronutrients and sugar, alone and in combination, in a beverage on growth and cognition in schoolchildren. In a 2 × 2 factorial design, children (n 414, 6-11 years) were randomly allocated to consume beverages containing (1) micronutrients with sugar, (2) micronutrients with a non-nutritive sweetener, (3) no micronutrients with sugar or (4) no micronutrients with a non-nutritive sweetener for 8.5 months. Growth was assessed and cognition was tested using the Kaufman Assessment Battery for Children version II (KABC-II) subtests and the Hopkins Verbal Learning Test (HVLT). Micronutrients decreased the OR for Fe deficiency at the endpoint (OR 0.19; 95% CI 0.07, 0.53). Micronutrients increased KABC Atlantis (intervention effect: 0.76; 95% CI 0.10, 1.42) and HVLT Discrimination Index (1.00; 95% CI 0.01, 2.00) scores. Sugar increased KABC Atlantis (0.71; 95% CI 0.05, 1.37) and Rover (0.72; 95% CI 0.08, 1.35) scores and HVLT Recall 3 (0.94; 95% CI 0.15, 1.72). Significant micronutrient × sugar interaction effects on the Atlantis, Number recall, Rover and Discrimination Index scores indicated that micronutrients and sugar in combination attenuated the beneficial effects of micronutrients or sugar alone. Micronutrients or sugar alone had a lowering effect on weight-for-age z-scores relative to controls (micronutrients - 0.08; 95% CI - 0.15, - 0.01; sugar - 0.07; 95% CI - 0.14, - 0.002), but in combination, this effect was attenuated. The beverages with micronutrients or added sugar alone had a beneficial effect on cognition, which was attenuated when provided in combination.

Point-of-use micronutrient fortification: lessons learned in implementing a preschool-based pilot trial in South Africa.

This current pilot trial assessed the feasibility of implementing a point-of-use (PoU) micronutrient fortification in preschool settings. Preschool children (n = 151) aged 36-79 months were randomized into intervention (n = 76) and control (n = 75) groups, both receiving breakfast maize-porridge with added micronutrient or placebo powder for 52 school days. Process evaluation and early childhood development indicators were used to assess trial feasibility. Process evaluation results showed that the implementation components were feasible and could be delivered with high fidelity. The improvement in hemoglobin concentration in intervention and control groups were not significantly different (P = 0.250). There was medium likelihood for practical significance for the two global cognitive scores assessed: non-verbal index (intervention effects: 7.20; 95% confidence interval: 2.60, 11.81; P = 0.002, effect size: 0.55) and mental processing index (intervention effects: 2.73; 95% confidence interval: 0.25, 5.70; P = 0.072, effect size: 0.36) on the Kaufman Assessment Battery for Children, Second Edition. The lessons from this trial could help in planning/implementing future PoU micronutrient fortification trial among South African preschool children.

Glycaemic control improves fibrin network characteristics in type 2 diabetes - a purified fibrinogen model.

Diabetic subjects have been shown to have altered fibrin network structures. One proposed mechanism for this is non-enzymatic glycation of fibrinogen due to high blood glucose. We investigated whether glycaemic control would result in altered fibrin network structures due to decreased fibrinogen glycation. Twenty uncontrolled type 2 diabetic subjects were treated with insulin in order to achieve glycaemic control. Twenty age- and body mass index (BMI)-matched non-diabetic subjects were included as a reference group. Purified fibrinogen, isolated from plasma samples was used for analysis. There was a significant decrease in fibrinogen glycation (6.81 to 5.02 mol glucose/mol fibrinogen) with a corresponding decrease in rate of lateral aggregation (5.86 to 4.62) and increased permeability (2.45 to 2.85 x 10(-8) cm(2)) and lysis rate (3.08 to 3.27 microm/min) in the diabetic subjects after glycaemic control. These variables correlated with markers of glycaemic control. Fibrin clots of non-diabetic subjects had a significantly higher ratio of inelastic to elastic deformation than the diabetic subjects (0.10 vs. 0.09). Although there was no difference in median fiber diameter between diabetic and non-diabetic subjects, there was a small increase in the proportion of thicker fibers in the diabetic samples after glycaemic control. Results from SDS-PAGE indicated no detectable difference in factor XIIIa-crosslinking of fibrin clots between uncontrolled and controlled diabetic samples. Diabetic subjects may have altered fibrin network formation kinetics which contributes to decreased pore size and lysis rate of fibrin clots. Achievement of glycaemic control and decreased fibrinogen glycation level improves permeability and lysis rates in a purified fibrinogen model.

Glycation of fibrinogen in uncontrolled diabetic patients and the effects of glycaemic control on fibrinogen glycation.

INTRODUCTION: Evidence exists for a relationship between glycaemic control and macrovascular disease. Non-enzymatic glycation of proteins may explain this relationship in part. We investigated the effect of blood glucose control, under out-patient conditions, on fibrinogen glycation as well as the relationship between glycated fibrinogen and glycaemic control using a new sensitive method for the measurement of glycated fibrinogen. MATERIALS AND METHODS: Blood samples were taken from twenty subjects with uncontrolled Type 2 diabetes (HbA1c>7%) to determine the levels of glycation. The subjects were then treated with insulin in order to control blood glucose. Twenty age and BMI matched non-diabetic subjects were included as a reference group. RESULTS: The subjects with diabetes had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects (7.84 vs 3.89 mol glucose/mol fibrinogen; p<0.001). After control of blood glucose, fibrinogen glycation was reduced significantly in the subjects with diabetes (7.84 to 5.24 mol glucose/mol fibrinogen; p<0.0002). The change in glycation during the intervention correlated significantly with the change in capillary glucose in the diabetic group (r=0.6, p=0.005). Fibrinogen glycation was comparable to HbA1c in predicting glycaemic control (p=0.54). Fibrinogen glycation correlated best with the average fasting capillary glucose of the preceding 5-8 days (r=0.54, p=0.014). CONCLUSION: We conclude that glucose control under out-patient conditions decreases fibrinogen glycation in subjects with Type 2 diabetes and that glycated fibrinogen compares well with HbA1c in its relation to glycaemic control.

The effect of glycaemic control on fibrin network structure of type 2 diabetic subjects.

Diabetic subjects have been shown to have altered fibrin network structures. One possible cause may be fibrinogen glycation resulting in altered structure/function properties. We investigated the effect of glucose control on fibrinogen glycation and fibrin network structure in type 2 diabetes. Blood samples were taken from twenty uncontrolled diabetic subjects at baseline to determine the levels of fibrinogen glycation and fibrin network structures. The subjects were then treated with insulin until blood glucose control was achieved before end blood samples were taken. Twenty age- and BMI-matched non-diabetic subjects were included as a reference group. The diabetic subjects had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects (7.84 vs. 3.89 mol glucose / mol fibrinogen; p < 0.001). This was significantly reduced during the intervention (7.84 to 5.24 mol glucose / mol fibrinogen; p < 0.0002) in the diabetic group. Both groups had high mean fibrinogen concentrations (4.25 and 4.02 g/l, diabetic and non-diabetic subjects respectively). There was no difference in fibrinogen concentration, porosity, compaction and kinetics of clot formation between the diabetic subjects and non-diabetic subjects at baseline, nor were there any changes during the intervention despite the reduced fibrinogen glycation. Fibrin network characteristics correlated well with fibrinogen but not with any markers of glycaemic control. Improved glycaemic control resulted in decreased fibrinogen glycation but not fibrinogen concentration. It seems as though porosity, compaction and kinetics of clot formation are more related to fibrinogen concentration than fibrinogen glycation in this model.

Modulation of baroreflex sensitivity by walnuts versus cashew nuts in subjects with metabolic syndrome.

BACKGROUND: Impaired baroreflex sensitivity (BRS) is associated with cardiovascular diseases and the metabolic syndrome. Because lipid abnormalities have been associated with impaired BRS, this study aimed to determine whether diets known to improve the lipid profile, namely a diet high in polyunsaturated fatty acids (walnuts) or monounsaturated fatty acids (cashew nuts), would improve BRS in subjects with metabolic syndrome (MS). METHODS: A controlled feeding trial with a randomized, controlled, parallel study design was undertaken, which involved 62 subjects with MS. Subjects were stratified according to gender and age and were randomized into three groups receiving a control diet, or a diet high (20% energy) in walnuts or unsalted cashew nuts for 8 weeks while maintaining body weight. The BRS, C-reactive protein (CRP), and MS components were measured before and after the intervention. RESULTS: After the intervention, BRS in the walnut-fed study group decreased (P = .038) and that in the cashew-fed study group increased (P = .036), but the BRS in the control group did not change (P = .56). The percent change of the walnut versus cashew group differed (P = .019). Body mass index, waist circumference, blood pressure, high-density lipoprotein cholesterol, and triacylglycerol did not change. The fasting glucose concentrations of the cashew group increased (P = .03). CONCLUSIONS: The significant improvements in BRS obtained by a diet rich in cashew nuts underline the beneficial cardiovascular effects of nuts. However, the opposite result was obtained with a diet rich in walnuts. These significant changes observed might indicate that BRS is particularly sensitive and influenced by changes in diet without changes in obesity.

Regulation of tissue factor-induced coagulation and platelet aggregation in flowing whole blood.

Photochemically induced thrombosis (a thrombin-dependent process) was measured in rats treated with moderate doses of anticoagulants, but which appeared to be unchanged. We considered the possibility that platelet-inhibiting agents, which also indirectly inhibit coagulation, would act as more potent antithrombotic agents. Inhibitors used as such were prostaglandin E1 (PGE1), which elevates cyclic AMP levels, and the P2Y12 ADP-receptor antagonist, AR-C69931MX. Effects of these agents were investigated in an ex vivo model system, in which whole blood under coagulant conditions was perfused over fibrinogen at defined wall shear rate. Perfusion of blood (rat or human) in the presence of tissue factor resulted in deposition of activated platelets and subsequent aggregate formation, along with exposure of procoagulant phosphatidylserine (PS) on the platelet surface and formation of fibrin fibers. In the presence of PGE1 aggregation was completely inhibited, but platelet adhesion and PS exposure were only party reduced, while fibrin formation was hardly affected. Treatment with AR-C69931MX caused similar, but less complete effects. These results indicate that in tissue factor-triggered blood under conditions of flow: (i) the platelet procoagulant response is independent of aggregate formation; (ii) the platelet-inhibiting effect of PGE1 and AR-C69931MX is sufficient to suppress aggregation, but not platelet adhesion and coagulation. These platelet inhibitors thus maintain their aggregation-inhibiting effect at sites of thrombin formation.

Clustering of haemostatic variables and the effect of high cashew and walnut diets on these variables in metabolic syndrome patients.

We investigated the effect of a high walnut and cashew diet on haemostatic variables in people with the metabolic syndrome. Factor analysis was used to determine how the haemostatic variables cluster with other components of the metabolic syndrome and multiple regression to determine possible predictors. This randomized, control, parallel, controlled-feeding trial included 68 subjects who complied with the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol criteria. After a 3-week run-in following the control diet, subjects were divided into three groups receiving either walnuts or cashews (20 energy%) or a control diet for 8 weeks. The nut intervention had no significant effect on von Willebrand factor antigen, fibrinogen, factor VII coagulant activity, plasminogen activator inhibitor 1 activity, tissue plasminogen activator activity or thrombin activatable fibrinolysis inhibitor. Statistically, fibrinogen clustered with the body-mass-correlates and acute phase response factors, and factor VII coagulant activity clustered with high-density lipoprotein cholesterol (HDL-C). Tissue plasminogen activator activity, plasminogen activator inhibitor 1 activity and von Willebrand factor antigen clustered into a separate endothelial function factor. HDL-C and markers of obesity were the strongest predictors of the haemostatic variables. We conclude that high walnut and cashew diets did not influence haemostatic factors in this group of metabolic syndrome subjects. The HDL-C increase and weight loss may be the main focus of dietary intervention for the metabolic syndrome. Furthermore, diet composition may have only limited effects if weight loss is not achieved.

Educating and training a workforce for nutrition in a post-2015 world.

Nearly all countries in the world today are burdened with malnutrition, manifesting as undernutrition, micronutrient deficiencies, and/or overweight and obesity. Despite some progress, efforts to alleviate malnutrition are hampered by a shortage in number, skills, and geographic coverage, of a workforce for nutrition. Here, we report the findings of the Castel Gandolfo workshop, a convening of experts from diverse fields in March 2014 to consider how to develop the capacity of a global cadre of nutrition professionals for the post-2015 development era. Workshop participants identified several requirements for developing a workforce for nutrition, including an ability to work as part of a multisectoral team; communication, advocacy, and leadership skills to engage decision makers; and a set of technical skills to address future challenges for nutrition. Other opportunities were highlighted that could immediately contribute to capacity development, including the creation of a consortium to link global North and South universities, online training modules for middle managers, and practical, hands-on experiences for frontline nutrition workers. Institutional and organizational support is needed to enable workshop recommendations on education and training to be effectively implemented and sustained. The findings from the Castel Gandolfo workshop can contribute to the delivery of successful nutrition-relevant actions in the face of mounting external pressures and informing and attaining the forthcoming Sustainable Development Goals.

Effect of freeze-drying, freezing and frozen storage of blood plasma on fibrin network characteristics.

INTRODUCTION: We investigated the effect of freezing, freeze-drying and the duration of frozen storage of blood plasma on fibrin network characteristics of clots subsequently produced. MATERIALS AND METHODS: Fibrin network characteristics of clots made from freeze-dried and frozen plasma were compared to those made from fresh plasma. Freeze-dried pooled plasma was reconstituted and frozen each month for 4 months to describe the differences in fibrin networks that occur as a result of storage of the plasma over this period. RESULTS: Compared to freezing, freeze-drying of plasma had fewer undesirable effects on the fibrin network characteristics measured. Only the permeability of the clots from freeze-dried plasma was significantly less compared to the values of clots from the fresh plasma (p=0.005). Fibrinogen activity and mass-length ratio, compaction and fibrin content of the clots made from frozen plasma were, however, all significantly affected by freezing. Mass-length ratio and compaction showed a linear decrease and fibrin content a linear increase over a 4-month frozen storage period, thereby indicating that these variables were probably not stable. Large variation found in the data from each month indicates that there may be other factors, apart from storage time, that have a larger influence on these fibrin network characteristics, than frozen storage of plasma for 4 months. Storage of plasma in the freeze-dried form for 4 months resulted in a significant increase in fibrinogen (p=0.0004) but significant decrease in fibrin content (p=0.0002). CONCLUSIONS: Although the process of freeze-drying had fewer undesirable effects on the measured fibrin network characteristics compared to freezing, storage in both forms resulted in altered activity upon rehydration and thawing.

Fish oil inhibits photochemically induced thrombosis in the guinea pig in a dose dependent manner.

The dose-response effect of dietary fish oil was investigated in the photochemically induced thrombosis model in guinea pigs. In this arterial thrombosis model thrombus formation was evaluated by determination of different occlusion parameters (percentage of occlusion, area under the blood flow curve, time to first occlusion, spontaneous reflow). Sixty guinea pigs (7 weeks old) were randomly assigned to and fed a 40 energy % diet containing increasing amounts (0, 5.5, 17 and 36 energy %) of fish oil for four weeks. Arterial thrombosis was induced in the femoral artery by free radical damage and subsequent thrombus formation. Increasing fish oil concentrations in the diet were associated with a linear decrease (p<0.001) in the percentage of occlusion (calculated as a decrease in blood flow) and a linear increase in area under the blood flow curve/begin flow (p<0.001). The time to thrombus formation was not significantly prolonged in any group. However the frequency of animals in which complete occlusion of the femoral artery was not obtained during the thrombosis induction and subsequent observation period was higher in the groups receiving the two highest doses of fish oil. Spontaneous reflow correlated positively (p<0.013) with increasing dietary fish oil content. In conclusion, our data indicates that dietary fish oil inhibits photochemically induced thrombosis in this animal model of arterial thrombosis in a dose dependent manner.

The effect of red palm olein and refined palm olein on lipids and haemostatic factors in hyperfibrinogenaemic subjects.

Little is known about the physiological effects of red palm olein (RPO). The effects of red palm olein and palm olein (POL) compared to sunflower oil (SFO), on lipids, haemostatic factors and fibrin network characteristics in hyperfibrinogenaemic volunteers were investigated. Fifty-nine free-living, hyperfibrinogenaemic volunteers participated in this randomized, controlled, single blind parallel study. After a 4-week run-in, during which subjects received sunflower oil products, they were paired and randomly assigned to one of three intervention groups receiving products containing 25 g/day ( approximately 12% of total energy intake) of either red palm olein, palm olein or sunflower oil for another 4 weeks. Anthropometric measurements, blood samples and dietary intakes were measured before run-in, and before and after intervention. The differences in changes in total serum cholesterol response between palm olein and red palm olein (+0.59 vs. +0.18 mmol/l; p=0.053), and between palm olein and sunflower oil (+0.59 vs. -0.003 mmol/l; p < or =0.01) were significant. The low-density lipoprotein cholesterol (LDLC) response in the palm olein-and sunflower oil-groups also differed significantly (+0.42 vs. -0.11 mmol/l; p < or =0.01). Tissue plasminogen activator antigen (tPA(ag)) decreased significantly in the red palm olein group compared to the palm olein-and sunflower oil-groups. No effects were found in other haemostatic variables. Palm olein and red palm olein had no independent effect on fibrin network characteristics. In conclusion, compared to palm olein, red palm olein had less detrimental effects on the lipid profile and decreased tissue plasminogen activator antigen. Studies in larger groups are advised for confirmation of results, elucidation of mechanisms and effects of nonglyceride constituents of red palm oil (PO).

Sensitivity of the Finometer device in detecting acute and medium-term changes in cardiovascular function.

BACKGROUND: The Finometer (FMS, Finapres Measurement Systems, Arnhem, Netherlands), which is the improved successor of the Finapres (TNO Biomedical Instrumentation, Amsterdam, Netherlands), measures finger arterial blood pressure non-invasively and computes other cardiovascular parameters from the computed aortic-flow waveform. The usability of the Finometer would depend on whether it is sensitive enough to detect small cardiovascular changes. The aim was therefore to determine the sensitivity of the Finometer regarding acute and longer-term cardiovascular changes. DESIGN AND METHODS: The sensitivity of the Finometer regarding the acute effect of 200 mg caffeine was determined with a double-blind, placebo-controlled crossover study which included 38 young male subjects. Finometer recordings were performed during four occasions at fasting level and after 30 min of ingestion. To evaluate the sensitivity of the Finometer in recording longer-term effects of a daily dosage of 1000 mg vitamin C, 800 mg vitamin E and 10 mg folic acid, 14 young males took placebo and 17 took the vitamins for 12 weeks in a double-blind study. Two recordings were performed at baseline and two after 12 weeks. RESULTS: After caffeine ingestion significantly (P<0.05) higher systolic, diastolic and mean blood pressure values than resting values were obtained. The arterial compliance was significantly lower after caffeine ingestion, whereas heart rate, peripheral resistance, stroke volume and cardiac output did not change significantly. No differences were shown after intake of placebo. Concerning the effects of vitamin intake, the vitamin group indicated a significant decrease in systolic blood pressure (P=0.03) whereas the placebo group indicated no significant differences after 12 weeks. CONCLUSIONS: The results suggest that the improved Finometer might be a sensitive instrument in the recording of relative small acute and longer-term changes in cardiovascular function, but more studies are necessary before final conclusions can be drawn.

Cardiovascular effects of oral Supplementation of vitamin C, E and folic acid in young healthy males.

Numerous observational studies showed associations of antioxidants (vitamins C and E) and folate intake with a reduced risk of cardiovascular disease, but randomized controlled clinical trials have generally not supported this hypothesis. The objective of this study was to investigate the effects of a daily dosage of 1000 mg vitamin C, 800 mg vitamin E, and 10 mg folate on markers of vascular function in 31 young healthy male adults. Cardiovascular values after a 12-week vitamin (14 subjects) or placebo (17 subjects) intervention were compared to baseline values. Cardiovascular parameters (blood pressure, stroke volume, heart rate, cardiac output, vascular resistance, arterial compliance) were measured continuously after an overnight fast under controlled circumstances with a Finometer device. Our main finding was a significant decrease (p = 0.03) in systolic blood pressure in the experimental group. No statistically significant changes were observed within other cardiovascular variables of the experimental group, but possible beneficial decreases in diastolic blood pressure and increases in arterial compliance after 12 weeks of vitamin supplementation were indicated. In conclusion, beneficial effects of antioxidants and folate were observed probably because the supplementation was used by young healthy subjects under carefully controlled conditions.

In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time.

Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.

Plasma clot lysis time and its association with cardiovascular risk factors in black Africans.

Studies in populations of European descent show longer plasma clot lysis times (CLT) in patients with cardiovascular disease (CVD) than in controls. No data are available on the association between CVD risk factors and fibrinolytic potential in black Africans, a group undergoing rapid urbanisation with increased CVD prevalence. We investigated associations between known CVD risk factors and CLT in black Africans and whether CLTs differ between rural and urban participants in light of differences in CVD risk.Data from 1000 rural and 1000 urban apparently healthy black South Africans (35-60 years) were cross-sectionally analysed.Increased PAI-1(act), BMI, HbA1c, triglycerides, the metabolic syndrome, fibrinogen concentration, CRP, female sex and positive HIV status were associated with increased CLTs, while habitual alcohol consumption associated with decreased CLT. No differences in CLT were found between age and smoking categories, contraceptive use or hyper- and normotensive participants. Urban women had longer CLT than rural women while no differences were observed for men.CLT was associated with many known CVD risk factors in black Africans. Differences were however observed, compared to data from populations of European descent available in the literature, suggesting possible ethnic differences. The effect of urbanisation on CLT is influenced by traditional CVD risk factors and their prevalence in urban and rural communities.

Association between iron status and white blood cell counts in African schoolchildren of the North-West Province, South Africa.

Iron deficiency with or without anemia is associated with increased susceptibility to infection owing to impaired immune function; this study aimed to examine the associations between markers of iron status and white blood cell counts in African schoolchildren. This cross-sectional study is part of the larger BeForMi study done in the North-West province of South Africa. A total of 556 African schoolchildren (aged 7-10 years) were recruited from the three schools participating in the BeForMi multiple micronutrient intervention study. Demographic information of the children was obtained from their parents/caregivers/guardians in the language of choice using validated questionnaires. Anthropometric indices (weight and height), iron status parameters, hematological parameters (hemoglobin (Hb), red blood cell count (RBC), total and differential white blood cell counts) were measured using standard procedures. No significant gender differences were observed in most of the iron markers and hematological parameters except in C-reactive protein (CRP) (p=0.004) and eosinophils (p=0.042) which were higher in boys while RBC (p=0.018) and Hb (p=0.023) levels were higher in girls. No relationships were observed between the different iron markers and differential white blood cell counts. A positive correlation was observed between serum ferritin (SF) and CRP in girls only (r=0.336, p<0.01), and a positive correlation between SF and mean cell volume (MCV) in boys only (r=0.197, p<0.01). In both genders, no correlations were observed between the different iron markers and the differential white blood cell counts. The study revealed no associations between iron status and differential white blood cell counts in children that participated in the BeForMi study calling for more studies to be done in the area of the significance of iron supplementation in healthy children.