Differences in calculated body fat percentage estimated from published equations based on bioelectric impedance analysis in healthy young South African adults.

Background: Adult overweight and obesity, in addition to the intake of saturated fat and total serum cholesterol must be monitored as biological risk factors for non-communicable diseases (NCDs). Bioelectric impedance analysis (BIA) provides data on body fat for use in epidemiological settings. However, optimized equations should be used to calculate percentage body fat (%BF). The purpose of this study was to assess the differences between %BF calculated using different published BIA equations and %BF measured by BIA in young South African adults. Design and methods: In this observational study, differences in calculated %BF were assessed, with different BIA equations retrieved from the literature used in 1128 healthy young adults aged 20-30 years. The %BF (measured by BIA) was compared between equations, between Black and White men and women, respectively. Results: The results showed statistically significant differences in the %BF calculated from published BIA equations when used in young South African adults (χ² = 946, χ² = 2528, χ² = 2088, respectively, p < 0.0001). In Black and White men and women, respectively, %BF levels were significantly higher when calculated by equations, than when measured by BIA (p < 0.0001). Conclusion: There seem to be large discrepancies in estimating %BF by BIA equations and these values cannot be used interchangeably for young South African adults. A South African age, ethnicity and sex-specific BIA equation needs to be developed to accurately estimate %BF in young South African adults.

Association of the metabolic syndrome with PAI 1act and clot lysis time over a 10-year follow up in an African population.

BACKGROUND AND AIMS: The association between the metabolic syndrome (MetS) and plasminogen activator inhibitor-1 (PAI-1) has been well established in cross-sectional studies. It is less clear whether this translates into decreased clot lysis rates and very little information is available on non-European populations. Little is known regarding prospective associations and whether clot lysis progressively worsens in MetS individuals over time. We determined the prospective association of MetS with PAI-1 activity (PAI-1act) and clot lysis time (CLT) over a 10-year period. METHODS AND RESULTS: As many as 2010 African men and women aged ≥30 years were stratified according to MetS status and number of MetS criteria (0-5). We also determined the contribution of the PAI-1 4G/5G polymorphism to these associations and identified which MetS criteria had the strongest associations with PAI-1act and CLT. Both PAI-1act and CLT remained consistently elevated in individuals with MetS throughout the 10-year period. PAI-1act and CLT did not increase more over time in MetS individuals than in controls. The 4G/5G genotype did not influence the association of PAI-1act or clot lysis with MetS. Increased waist circumference, increased triglycerides and decreased HDL-C were the main predictors of PAI-1act and CLT. CONCLUSIONS: Black South Africans with MetS had increased PAI-1act and longer CLTs than individuals without MetS. The inhibited clot lysis in MetS did, however, not deteriorate over time compared to controls. Of the MetS criteria, obesity and altered lipids were the main predictors of PAI-1act and CLT and are thus potential targets for prevention strategies to decrease thrombotic risk.

Associations Between 25-Hydroxyvitamin D and Total and γ' Fibrinogen and Plasma Clot Properties and Gene Interactions in a Group of Healthy Black South African Women.

The role of 25-hydroxyvitamin D [25(OH)D] in reducing the risk of cardiovascular disease (CVD) has been recognized, but the mechanisms involved are unclear. Researchers have discovered a link between vitamin D and fibrinogen. Until now, data on the relationship between vitamin D and the γ' splice variant of fibrinogen and fibrin clot characteristics remain unexplored. In this study, 25(OH)D, total and γ' fibrinogen, as well as turbidimetrically determined plasma clot properties, were quantified, and fibrinogen and FXIII SNPs were genotyped in 660 Black, apparently healthy South African women. Alarmingly, 16 and 45% of the women presented with deficient and insufficient 25(OH)D, respectively. Total fibrinogen and maximum absorbance (as a measure of clot density) correlated inversely, whereas γ' fibrinogen correlated positively with 25(OH)D. γ' fibrinogen increased whereas maximum absorbance decreased over the deficient, insufficient, and sufficient 25(OH)D categories before and after adjustment for confounders. 25(OH)D modulated the association of the SNPs regarding fibrinogen concentration and clot structure/properties, but did not stand after correction for false discovery rate. Because only weak relationships were detected, the clinical significance of the findings are questionable and remain to be determined. However, we recommend vitamin D fortification and supplementation to reduce the high prevalence of this micronutrient deficiency and possibly to improve fibrinogen and plasma clot structure if the relationships are indeed clinically significant. There is a need for large cohort studies to demonstrate the relationship between vitamin D and cardiovascular and inflammatory risk factors as well as to uncover the molecular mechanisms responsible.

The Metabolic Profiles of Metabolically Healthy Obese and Metabolically Unhealthy Obese South African Adults over 10 Years.

Obesity is associated with an increased cardiometabolic risk, but some individuals maintain metabolically healthy obesity (MHO). The aims were to follow a cohort of black South African adults over a period of 10 years to determine the proportion of the group that maintained MHO over 10 years, and to compare the metabolic profiles of the metabolically healthy and metabolically unhealthy groups after the follow-up period. The participants were South African men (n = 275) and women (n = 642) from the North West province. The prevalence of obesity and the metabolic syndrome increased significantly. About half of the metabolically healthy obese (MHO) adults maintained MHO over 10 years, while 46% of the women and 43% of men became metabolically unhealthy overweight/obese (MUO) at the end of the study. The metabolic profiles of these MHO adults were similar to those of the metabolically healthy normal weight (MHNW) group in terms of most metabolic syndrome criteria, but they were more insulin resistant; their CRP, fibrinogen, and PAI-1act were higher and HDL-cholesterol was lower than the MHNW group. Although the metabolic profiles of the MUO group were less favourable than those of their counterparts, MHO is a transient state and is associated with increased cardiometabolic risk.

Lifestyle Influences Changes in Fibrin Clot Properties Over a 10-Year Period on a Population Level.

Case-control and observational studies have provided a plausible mechanistic link between clot structure and thrombosis. We aimed to identify lifestyle, demographic, biochemical, and genetic factors that influence changes in total fibrinogen concentration and clot properties over a 10-year period in 2,010 black South Africans. Clot properties were assessed with turbidimetry and included lag time, slope, maximum absorbance, and clot lysis time. Linear mixed models with restricted maximum likelihood were used to determine whether (1) outcome variables changed over the 10-year period; (2) demographic and lifestyle variables, biochemical variables, and fibrinogen single-nucleotide polymorphisms influenced the change in outcome variables over the 10-year period; and (3) there was an interaction between the exposures and time in predicting the outcomes. A procoagulant risk score was furthermore created, and multinomial logistic regression was used to determine the exposures that were associated with the different risk score categories. In this population setting, female gender, obesity, poor glycemic control, increased low-density lipoprotein cholesterol, and decreased high-density lipoprotein cholesterol contributed to the enhanced progression to prothrombotic clot properties with increasing age. Alcohol consumption on the other hand, offered a protective effect. The above evidence suggest that the appropriate lifestyle changes can improve fibrin clot properties on a population level, decreasing cardiovascular disease risk and thus alleviate the strain on the medical health care system.

Automated Fiber Diameter and Porosity Measurements of Plasma Clots in Scanning Electron Microscopy Images.

Scanning Electron Microscopy (SEM) is a powerful, high-resolution imaging technique widely used to analyze the structure of fibrin networks. Currently, structural features, such as fiber diameter, length, density, and porosity, are mostly analyzed manually, which is tedious and may introduce user bias. A reliable, automated structural image analysis method would mitigate these drawbacks. We evaluated the performance of DiameterJ (an ImageJ plug-in) for analyzing fibrin fiber diameter by comparing automated DiameterJ outputs with manual diameter measurements in four SEM data sets with different imaging parameters. We also investigated correlations between biophysical fibrin clot properties and diameter, and between clot permeability and DiameterJ-determined clot porosity. Several of the 24 DiameterJ algorithms returned diameter values that highly correlated with and closely matched the values of the manual measurements. However, optimal performance was dependent on the pixel size of the images-best results were obtained for images with a pixel size of 8-10 nm (13-16 pixels/fiber). Larger or smaller pixels resulted in an over- or underestimation of diameter values, respectively. The correlation between clot permeability and DiameterJ-determined clot porosity was modest, likely because it is difficult to establish the correct image depth of field in this analysis. In conclusion, several DiameterJ algorithms (M6, M5, T3) perform well for diameter determination from SEM images, given the appropriate imaging conditions (13-16 pixels/fiber). Determining fibrin clot porosity via DiameterJ is challenging.

Certain Associations Between Iron Biomarkers and Total and γ' Fibrinogen and Plasma Clot Properties Are Mediated by Fibrinogen Genotypes.

Introduction: Evidence for the relationship between body iron and cardiovascular disease (CVD) is inconsistent and mechanisms involved remain poorly understood. Therefore, we first investigated whether there are linear or non-linear relationships between iron status and total and γ' fibrinogen as well as plasma fibrin clot properties and, second, determined whether there are interactions with iron biomarkers and fibrinogen and FXIII single nucleotide polymorphisms (SNPs) in relation to fibrinogen concentration and functionality. Methods: In this cross-sectional analysis of 2,010 apparently healthy Black South Africans we quantified total and γ' fibrinogen, serum iron, ferritin and transferrin using standardized methods and calculated transferrin saturation (TS). Clot architecture and lysis were explored with a global analytical turbidity assay. The SNPs were determined through an Illumina BeadXpress® platform. Results: Total, but not %γ', fibrinogen negatively correlated with serum iron concentrations, although both decreased over iron tertiles. %γ' fibrinogen correlated negatively with transferrin and decreased over the transferrin tertiles. A weak negative association between total fibrinogen and TS was detected with fibrinogen decreasing over the TS tertiles and categories based on TS. Lag time correlated positively with transferrin and increased over transferrin tertiles, when adjusting for fibrinogen. Before adjusting for fibrinogen, lag time was shorter in those with adequate iron status based on TS than other iron subcategories. Clot lysis time (CLT) negatively correlated with ferritin and was longer in the first than in the third ferritin tertile. Among iron status categories based on ferritin, only CLT differed and was longer in those with adequate iron than with iron-overload. CLT negatively correlated with TS, albeit weakly, shortened over the TS tertiles and was shorter in those with adequate iron based on TS categories. Interactions were observed between FGB SNPs and some of the markers of iron status investigated, in relation to the clot properties with the most prominent associations detected in homozygous carriers of the variant alleles for whom increased iron status was more beneficial than for those harboring the wild-type alleles. Iron modulated the influence of the SNPs so that for the majority iron was beneficial in respect of clot properties, but even more so for a minority group harboring specific variant alleles. Conclusion: This is the first large-scale epidemiological study to relate fibrinogen concentration and functionality to markers of iron status and to take genetic factors into consideration. We have detected a relationship between iron biomarkers and fibrinogen as well as clot characteristics that are influenced by the genetic make-up of an individual.

Fibrinogen and Fibrin.

Fibrinogen is a large glycoprotein, synthesized primarily in the liver. With a normal plasma concentration of 1.5-3.5 g/L, fibrinogen is the most abundant blood coagulation factor. The final stage of blood clot formation is the conversion of soluble fibrinogen to insoluble fibrin, the polymeric scaffold for blood clots that stop bleeding (a protective reaction called hemostasis) or obstruct blood vessels (pathological thrombosis). Fibrin is a viscoelastic polymer and the structural and mechanical properties of the fibrin scaffold determine its effectiveness in hemostasis and the development and outcome of thrombotic complications. Fibrin polymerization comprises a number of consecutive reactions, each affecting the ultimate 3D porous network structure. The physical properties of fibrin clots are determined by structural features at the individual fibrin molecule, fibrin fiber, network, and whole clot levels and are among the most important functional characteristics, enabling the blood clot to withstand arterial blood flow, platelet-driven clot contraction, and other dynamic forces. This chapter describes the molecular structure of fibrinogen, the conversion of fibrinogen to fibrin, the mechanical properties of fibrin as well as its structural origins and lastly provides evidence for the role of altered fibrin clot properties in both thrombosis and bleeding.

Mechanical and Physical Behavior of Fibrin Clot Formation and Lysis in Combined Oral Contraceptive Users.

Combined oral contraceptives (COCs) are commonly prescribed and increase the risk of venous thromboembolism (VTE). We have previously found that two COCs, both containing drospirenone (DRSP) and ethinyl estradiol (EE), cause spontaneous fibrin formation in whole blood. The aim of this study was, therefore, to use platelet-poor plasma (PPP) from the same cohort of DRSP/EE users to determine the impact of these COCs on the fibrin component, specifically the fibrin clot viscoelasticity, turbidimetry, and biophysical traits. PPP from 25 females per test group and a control group (n = 25) were analyzed using thromboelastography (TEG), turbidimetry, and scanning electron microscopy. The results highlight abnormal fibrin clot formation, lysis, and architecture; DRSP/20EE showed the greatest effect. DRSP/EE use increased the fibrin fiber diameter and showed dense matted clots. Only when the influence of COCs on the structural properties and behavior of fibrin fibers during thrombus formation and lysis is better understood are we able to predict and prevent coagulopathies associated with these synthetic hormones. Clinical practitioners should take this into consideration for female patients that either have comorbidities, which could burden the coagulation system, or may be exposed to external factors that could increase their risk for VTE.