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1.
J Nutr ; 154(2): 435-445, 2024 02.
Article in English | MEDLINE | ID: mdl-38110181

ABSTRACT

BACKGROUND: Low-potassium intake is associated with a higher risk of type 2 diabetes and hypertension. Both conditions occur more frequently in Black populations, who also consume less potassium-rich foods. OBJECTIVES: Using metabolomics to identify dysregulated metabolic pathways associated with low-potassium excretion may procure more accurate entry points for nutritional prevention and intervention for type 2 diabetes and hypertension. METHODS: A total of 440 White and 350 Black adults from the African-PREDICT study (aged 20-30 y) were included. Twenty-four-hour blood pressure (BP) was measured. Potassium, sodium, and fasting glucose concentrations were analyzed in 24-h urine and plasma samples. Liquid chromatography-tandem mass spectrometry-based metabolomics included the analyses of amino acids and acylcarnitines in spot urine samples. RESULTS: Black participants had lower urinary potassium concentrations than Whites (36.6 compared with 51.1 mmol/d; P < 0.001). In White but not Black adults, urinary potassium correlated positively with 2-aminoadipic acid (2-AAA) (r = 0.176), C3-[propionyl]carnitine (r = 0.137), C4-[butyryl]carnitine (r = 0.169) and C5-[isovaleryl]carnitine (r = 0.167) in unadjusted and 2-AAA (r = 0.158) and C4-carnitine (r = 0.160) in adjusted analyses (all P < 0.05 and q < 0.05). Elevated C0-, C3-, and C5-carnitine in turn were positively associated with systolic BP (Black and White groups), diastolic BP (Black group), and glucose (White group) (all P < 0.05). CONCLUSIONS: Racial differences are an important consideration when investigating nutrient-metabolite relationships and the role thereof in cardiovascular disease. Only in White adults did urinary potassium associate with 2-AAA and short-chain acylcarnitines. These metabolites were positively related to BP and fasting plasma glucose concentrations. In White adults, the metabolomic profiles related to potassium excretion may contribute to BP regulation and glucose homeostasis. This trial was registered at clinicaltrials.gov as NCT03292094.


Subject(s)
Carnitine , Diabetes Mellitus, Type 2 , Hypertension , Adult , Humans , Blood Pressure/physiology , Carnitine/analogs & derivatives , Homeostasis , Hypertension/urine , Potassium/urine
2.
BMC Endocr Disord ; 24(1): 213, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39390433

ABSTRACT

BACKGROUND: The use of non-invasive risk scores to detect undiagnosed type 2 diabetes (T2D) ensures the restriction of invasive and costly blood tests to those most likely to be diagnosed with the disease. This study assessed and compared the performance of the African Diabetes Risk Score (ADRS) with three other diabetes risk prediction models for identifying screen-detected diabetes based on fasting plasma glucose (FPG) or glycated haemoglobin (HBA1c). METHODS: Age, sex, waist circumference, body mass index, blood pressure, history of diabetes and physical activity levels from the SA-NW-PURE study were used to externally validate the ADRS and other established risk prediction models. Discrimination was assessed and compared using C-statistics and nonparametric methods. Calibration was assessed using calibration plots, before and after recalibration. RESULTS: Nine hundred and thirty-seven participants were included; 14% had prevalent undiagnosed T2D according to FPG and 26% according to HbA1c. Discrimination was acceptable and was mostly similar between models for both diagnostic measures. The C-statistics for diagnosis by FPG ranged from 0.69 for the Simplified FINDRISC model to 0.77 for the ADRS model and 0.77 for the Simplified FINDRISC model to 0.79 for the ADRS model for diagnosis by HbA1c. Calibration ranged from acceptable to good, though over- and underestimation were present. All models improved significantly following recalibration. CONCLUSIONS: The models performed comparably, with the ADRS offering a non-invasive way to identify up to 79% of cases. Based on its ease of use and performance, the ADRS is recommended for screening for T2D in certain Black population groups in South Africa. HbA1c as a means of diagnosis also showed comparable performance with FPG. Therefore, further validation studies can potentially use HbA1c as the standard to compare to.


Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Fasting , Glycated Hemoglobin , Humans , Male , Female , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Middle Aged , Glycated Hemoglobin/analysis , Blood Glucose/analysis , South Africa/epidemiology , Fasting/blood , Black People/statistics & numerical data , Adult , Risk Assessment/methods , Risk Factors , Aged , Biomarkers/blood , Prognosis , African People
3.
Nutr Metab Cardiovasc Dis ; 33(3): 592-601, 2023 03.
Article in English | MEDLINE | ID: mdl-36646603

ABSTRACT

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.


Subject(s)
Metabolic Syndrome , Adult , Female , Humans , Male , Cross-Sectional Studies , Fibrin Clot Lysis Time , Follow-Up Studies , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Metabolic Syndrome/genetics , Plasminogen Activator Inhibitor 1/genetics
4.
Subcell Biochem ; 96: 471-501, 2021.
Article in English | MEDLINE | ID: mdl-33252741

ABSTRACT

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.


Subject(s)
Blood Coagulation , Fibrin , Fibrinogen , Thrombosis , Hemostasis , Humans , Polymerization
5.
J Pediatr ; 234: 158-163.e2, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33775664

ABSTRACT

OBJECTIVES: To evaluate the associations between homocysteine (Hcy) and cardiovascular health in South African adolescents. STUDY DESIGN: Circulating Hcy concentrations of 172 South African adolescents (105 girls, ages 13 to <18 years) were measured. Anthropometric and cardiovascular factors were also included and cross-sectionally analyzed through general linear models. RESULTS: Hcy correlated positively with body weight (P = .03; after adjusting for multiple testing, it was not regarded as significant) and muscle mass (P = .01), but negatively with fibrinogen concentrations (P = .001). Across Hcy tertiles, blood pressure produced approximating U-shaped curves, with differences between the middle and upper tertiles (all P < .02). Forty percent of the adolescents had elevated blood pressure, of whom 37% fell in the lowest and 38% in the highest Hcy tertiles. Hcy differed between the sexes (with boys having higher Hcy), but not between subgroups based on puberty, weight, stunting, smoking, or alcohol consumption. CONCLUSIONS: Both high and low Hcy could be early contributing risk factors to cardiovascular health. The associations between Hcy and blood pressure suggest that dietary and lifestyle manipulation, to achieve the optimal range of Hcy, may be beneficial in preventing Hcy-related hypertension in adulthood. The inverse relationship between Hcy and fibrinogen remains to be clarified.


Subject(s)
Heart Disease Risk Factors , Homocysteine/blood , Adolescent , Biomarkers/blood , Black People , Body Mass Index , Cross-Sectional Studies , Female , Humans , Male , South Africa
6.
Microvasc Res ; 137: 104180, 2021 09.
Article in English | MEDLINE | ID: mdl-34015274

ABSTRACT

AIMS: Plasminogen activator inhibitor-1 (PAI-1), traditionally associated with fibrinolysis, is increasingly implicated in impaired vascular function. However, studies on its association with microvascular function are limited to the cutaneous and coronary microvascular beds in older and diseased individuals. To better understand its potential involvement in the early stages of disease development, we investigated the associations of retinal vasodilatory responses to flicker light with PAI-1 activity (PAI-1act) in young and healthy individuals. METHODS: We included healthy Black and White women and men (n = 518; aged 20-30 years), and measured plasma PAI-1act and retinal vasodilatory responses to flicker light provocation. We also collected demographic and lifestyle data, measured blood pressure, anthropometry, blood lipids, inflammatory and other biomarkers. RESULTS: In multivariate regression analyses, maximal retinal venular dilation associated independently and inversely with PAI-1act (adj. R2 = 0.11; ß = -0.15; p = 0.001) in the total group. In exploratory subgroup analyses, this association remained in White women (adj. R2 = 0.07; ß = -0.23; p = 0.005), and was more robust with younger age and lower blood pressure and in non-smokers, but also with greater central adiposity, higher low-density lipoprotein cholesterol and inflammation (all p < 0.05). CONCLUSIONS: Our data suggest that in young individuals, PAI-1 may already be associated with subclinical microvascular dysfunction.


Subject(s)
Plasminogen Activator Inhibitor 1/blood , Retinal Vessels/physiology , Vasodilation , Venules/physiology , Adult , Age Factors , Biomarkers/blood , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/physiopathology , Cross-Sectional Studies , Female , Healthy Volunteers , Humans , Light , Male , Photic Stimulation , Predictive Value of Tests , Risk Factors , South Africa , Young Adult
7.
Nutr Metab Cardiovasc Dis ; 31(7): 2023-2032, 2021 06 30.
Article in English | MEDLINE | ID: mdl-33975737

ABSTRACT

BACKGROUND AND AIMS: Obesity is associated with an increasing prevalence of cardiovascular diseases in Africa, but some obese individuals maintain cardiometabolic health. The aims were to track metabolically healthy overweight or obesity (MHO) over 10 years in African adults and to identify factors associated with a transition to metabolically unhealthy overweight or obesity (MUO). METHODS AND RESULTS: The participants were the South African cohort of the international Prospective Urban and Rural Epidemiological study. From the baseline data of 1937 adults, 649 women and 274 men were followed for 10 years. The combined overweight and obesity prevalence of men (19.2%-23.8%, p = .02) and women (58%-64.7%, p < .001), and the prevalence of the metabolic syndrome in all participants (25.4%-40.2%, p < .001) increased significantly. More than a quarter (26.2%) of the women and 10.9% of men were MHO at baseline, 11.4% of women and 5.1% of men maintained MHO over 10 years, while similar proportions (12.3% of women, 4.7% of men) transitioned to MUO. Female sex, age, and total fat intake were positively associated with a transition to MUO over 10 years, while physical activity was negatively associated with the transition. HIV positive participants were more likely to be MHO at follow-up than their HIV negative counterparts. CONCLUSIONS: One in two black adults with BMI ≥25 kg/m2 maintained MHO over 10 years, while a similar proportion transitioned into MUO. Interventions should focus on lower fat intakes and higher physical activity to prevent the transition to MUO.


Subject(s)
Adiposity/ethnology , Black People , Life Style/ethnology , Metabolic Syndrome/ethnology , Obesity, Metabolically Benign/ethnology , Adult , Aged , Cardiometabolic Risk Factors , Dietary Fats/adverse effects , Disease Progression , Exercise , Female , Humans , Male , Metabolic Syndrome/diagnosis , Metabolic Syndrome/physiopathology , Middle Aged , Obesity, Metabolically Benign/diagnosis , Obesity, Metabolically Benign/physiopathology , Prevalence , Prognosis , Prospective Studies , Risk Assessment , Rural Health , Sedentary Behavior/ethnology , South Africa/epidemiology , Time Factors , Urban Health
8.
Public Health Nutr ; : 1-13, 2021 Dec 27.
Article in English | MEDLINE | ID: mdl-34955112

ABSTRACT

OBJECTIVE: To quantify the inflammatory potential of the diet of rural and urban Black South Africans using an adapted energy-adjusted dietary inflammatory index (AE-DII) and to investigate its relationship with inflammatory and cardio-metabolic disease risk markers. Dietary inflammatory potential has not been investigated in African populations. DESIGN: Cross-sectional investigation. SETTING: Rural and urban sites in the North West province of South Africa. PARTICIPANTS: 1885 randomly selected, apparently healthy Black South Africans older than 30 years. RESULTS: AE-DII scores ranged from -3·71 to +5·08 with a mean of +0·37. AE-DII scores were significantly higher in men (0·47 ± 1·19) than in women (0·32 ± 1·29), and in rural (0·55 ± 1·29) than urban participants (0·21 ± 1·19). Apart from its dietary constituents, AE-DII scores are primarily associated with age, rural-urban status and education. Contrary to the literature, alcohol consumption was positively associated with AE-DII scores. Of the four tested inflammatory and thirteen cardio-metabolic biomarkers, the AE-DII was only significantly negatively associated with albumin and HDL cholesterol, and positively with waist circumference and fasting glucose, upon full adjustment. CONCLUSION: Rural men consumed the most pro-inflammatory diet, and urban women the least pro-inflammatory diet. The diet of the participants was not overtly pro- or anti-inflammatory and was not associated with measured inflammatory markers. The inflammatory potential of alcohol at different levels of intake requires further research. Understanding dietary inflammatory potential in the context of food insecurity, unhealthy lifestyle practices and lack of dietary variety remains limited.

9.
Br J Nutr ; 124(12): 1329-1337, 2020 12 28.
Article in English | MEDLINE | ID: mdl-32600485

ABSTRACT

CVD is the most common chronic condition and the highest cause of mortality in the USA. The aim of the present work was to investigate diet and sedentary behaviour in relation to mortality in US CVD survivors. The National Health and Nutrition Examination Surveys conducted between 1999 and 2014 linked to the US mortality registry updated to 2015 were investigated. Multivariate adjusted Cox regression was used to derive mortality hazards in relation to sedentary behaviour and nutrient intake. A multiplicative and additive interaction analysis was conducted to evaluate how sedentariness and diet influence mortality in US CVD survivors. A sample of 2473 participants followed for a median period of 5·6 years resulted in 761 deaths, and 199 deaths were due to CVD. A monotone increasing relationship between time spent in sedentary activities and mortality risk was observed for all-cause and CVD mortality (hazard ratio (HR) = 1·20, 95 % CI 1·09, 1·31 and HR = 1·19, 95 % CI 1·00, 1·67, respectively). Inverse mortality risks in the range of 22-34 % were observed when comparing the highest with the lowest tertile of dietary fibre, vitamin A, carotene, riboflavin and vitamin C. Sedentariness below 360 min/d and dietary fibre and vitamin intake above the median interact on an additive scale influencing positively all-cause and CVD mortality risk. Reduced sedentariness in combination with a varied diet rich in dietary fibre and vitamins appears to be a useful strategy to reduce all-cause and CVD mortality in US CVD survivors.


Subject(s)
Cardiovascular Diseases/mortality , Diet/mortality , Nutrition Surveys/statistics & numerical data , Registries/statistics & numerical data , Sedentary Behavior , Adult , Aged , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , United States/epidemiology
10.
Thromb J ; 18(1): 35, 2020 Nov 30.
Article in English | MEDLINE | ID: mdl-33292263

ABSTRACT

BACKGROUND: Alcohol consumption is associated with haemostasis and so may influence cardiovascular conditions. It is unknown whether the association of alcohol with total and γ' fibrinogen concentrations, as well as clot structure, are modulated by fibrinogen and factor (F) XIII single nucleotide polymorphisms (SNPs). METHODS: Total fibrinogen, γ' fibrinogen and clot properties of 2010 healthy Africans residing in South Africa were measured in relation to alcohol intake as well as its markers - gamma-glutamyltransferase (GGT), percentage carbohydrate deficient transferrin (%CDT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Fourteen fibrinogen and two SNPs in the FXIII gene were genotyped to determine their influence. RESULTS: Alcohol intake and its markers correlated negatively with fibrinogen and clot lysis time (CLT) as well as with most of the clot properties. Percentage γ' fibrinogen correlated positively with AST and negatively with alcohol intake. We then stratified for alcohol intake and found inverse associations between γ' fibrinogen and both %CDT and GGT-CDT in consumers, but the positive association with AST remained only in abstainers. Alcohol intake and its markers modulated the influence of fibrinogen SNPs on total fibrinogen concentrations and the fibrinogen SNPs as well as an FXIII SNP on clot density (all p < 0.004). CONCLUSION/S: We show for the first time that some individuals harbour certain genotypes that, in combination with alcohol consumption, might predispose or protect them from haemostatic factors that might lead to the development of cardiovascular disease. Studies are needed to clarify the mechanisms related to the interplay between alcohol and the gene variants observed here.

11.
Nutr Metab Cardiovasc Dis ; 30(11): 2063-2071, 2020 10 30.
Article in English | MEDLINE | ID: mdl-32811735

ABSTRACT

BACKGROUND AND AIMS: The association between plasminogen activator inhibitor-1 (PAI-1) and blood pressure is well established, but it is debatable whether raised PAI-1 levels precede or result from raised blood pressure. Furthermore, it is unclear whether this association already exists in the absence of overt hypertension and to what degree it is influenced by health behaviours. Our aim was to investigate the association of 24 h blood pressure with PAI-1 activity (PAI-1act) in a young, healthy cohort, and to assess the influence of alcohol consumption and smoking on these associations. METHODS AND RESULTS: Healthy black and white men and women (aged 20-30 years, n = 1156) were cross-sectionally analysed. Statistical analysis was performed first split by ethnicity and sex and then by alcohol consumption and smoking. Regression analyses adjusted for age revealed positive associations of 24 h blood pressure with PAI-1act in most groups (p < 0.05). In multivariate-adjusted analyses, significance was lost in all groups except black men, who also had higher monocyte chemoattractant protein-1 (MCP-1) and von Willebrand factor antigen (vWFag) compared to white men (both p < 0.001). Analyses in black men, split by self-reported alcohol use and smoking, revealed 24 h blood pressure-PAI-1act associations only in alcohol users (24 h SBP [B = 4.22, p < 0.001], DBP [B = 2.04, p = 0.015] and PP [B = 2.18, p = 0.013]) and smokers (24 h SBP [B = 6.10, p < 0.001] and PP [B = 4.33, p = 0.001]). CONCLUSION: Our findings support a positive association between 24 h blood pressure and PAI-1, particularly in individuals with higher MCP-1 and vWFag levels. Furthermore, smoking and alcohol consumption play an important role in modifying the association between blood pressure and PAI-1.


Subject(s)
Alcohol Drinking/adverse effects , Black People , Blood Pressure , Plasminogen Activator Inhibitor 1/blood , Smoking/adverse effects , Time Factors , White People , Adult , Age Factors , Alcohol Drinking/blood , Alcohol Drinking/ethnology , Alcohol Drinking/physiopathology , Biomarkers/blood , Chemokine CCL2/blood , Circadian Rhythm , Cross-Sectional Studies , Female , Heart Disease Risk Factors , Humans , Male , Prospective Studies , Race Factors , Sex Factors , Smoking/blood , Smoking/ethnology , Smoking/physiopathology , South Africa/epidemiology , Young Adult , von Willebrand Factor/analysis
12.
Biophys J ; 110(6): 1400-10, 2016 Mar 29.
Article in English | MEDLINE | ID: mdl-27028649

ABSTRACT

The major structural component of a blood clot is a mesh of fibrin fibers. Our goal was to determine whether fibrinogen glycation and fibrin fiber diameter have an effect on the mechanical properties of single fibrin fibers. We used a combined atomic force microscopy/fluorescence microscopy technique to determine the mechanical properties of individual fibrin fibers formed from blood plasma. Blood samples were taken from uncontrolled diabetic patients as well as age-, gender-, and body-mass-index-matched healthy individuals. The patients then underwent treatment to control blood glucose levels before end blood samples were taken. The fibrinogen glycation of the diabetic patients was reduced from 8.8 to 5.0 mol glucose/mol fibrinogen, and the healthy individuals had a mean fibrinogen glycation of 4.0 mol glucose/mol fibrinogen. We found that fibrinogen glycation had no significant systematic effect on single-fiber modulus, extensibility, or stress relaxation times. However, we did find that the fiber modulus, Y, strongly decreases with increasing fiber diameter, D, as Y∝D(-1.6). Thin fibers can be 100 times stiffer than thick fibers. This is unusual because the modulus is a material constant and should not depend on the sample dimensions (diameter) for homogeneous materials. Our finding, therefore, implies that fibrin fibers do not have a homogeneous cross section of uniformly connected protofibrils, as is commonly thought. Instead, the density of protofibril connections, ρPb, strongly decreases with increasing diameter, as ρPb∝D(-1.6). Thin fibers are denser and/or have more strongly connected protofibrils than thick fibers. This implies that it is easier to dissolve clots that consist of fewer thick fibers than those that consist of many thin fibers, which is consistent with experimental and clinical observations.


Subject(s)
Fibrin/chemistry , Fibrinogen/chemistry , Adult , Aged , Biomechanical Phenomena , Crystallography, X-Ray , Elastic Modulus , Female , Glycosylation , Humans , Middle Aged , Viscoelastic Substances
13.
Br J Haematol ; 168(1): 102-12, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25156046

ABSTRACT

Inter-ethnic variation in fibrinogen levels is hypothesized to be the result of differences in genetic background. No information is available regarding the contribution of genetics to fibrinogen γ' in Africans. Only limited information is available regarding the interaction between genotypes and total and γ' fibrinogen concentration in determining fibrin clot properties. Our aim was to investigate the effect of polymorphisms in the fibrinogen and Factor XIII genes on total and γ' fibrinogen and clot properties (turbidimetry) in 2010 black Africans as well as to determine their interactions. Significant associations were observed between rs1049636 (FGG gene), with total fibrinogen levels and between rs2070011 (FGA promoter area) and fibrinogen γ' levels. Significant associations were observed between single nucleotide polymorphisms (SNPs) in the FGA (rs2070011), FGB (rs1800787) and FGG (rs1049636) genes and fibre size. Significant interactions were found between total and/or γ' fibrinogen levels and SNPs in the FGA (rs2070011), FGB (rs2227385, rs1800787, rs1800788, rs4220) and F13A1 genes (rs5985) in determining clot properties. The different SNPs influenced the relationships between total and γ' fibrinogen levels with clot properties in opposing directions. Genetic influences may be ethnic-specific and should not only focus on fibrinogen concentration, but also on functionality in determining its role in CVD.


Subject(s)
Black People/genetics , Blood Coagulation/genetics , Fibrin/metabolism , Fibrinogen/genetics , Fibrinogen/metabolism , Polymorphism, Genetic , Adult , Alleles , Female , Gene Frequency , Gene-Environment Interaction , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Prospective Studies
14.
Blood ; 121(16): 3254-60, 2013 Apr 18.
Article in English | MEDLINE | ID: mdl-23422752

ABSTRACT

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.


Subject(s)
Cardiovascular Diseases/blood , Fibrin/metabolism , Fibrinogen/metabolism , Fibrinogens, Abnormal/metabolism , Fibrinolysis , Adult , Aged , Black People , C-Reactive Protein/metabolism , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/metabolism , Cohort Studies , Female , Fibrin/chemistry , Fibrin Clot Lysis Time , Humans , Male , Middle Aged , Regression Analysis , Risk Factors , South Africa/epidemiology
15.
Clin Exp Hypertens ; 37(6): 511-7, 2015.
Article in English | MEDLINE | ID: mdl-25919704

ABSTRACT

Haemostatic- and oxidative stress markers are associated with increased cardiovascular risk. In the black population, evidence exists that both an imbalance in the haemostatic system and oxidative stress link with the development of hypertension. However, it is unclear whether these two risk components function independently or are related, specifically in the black population, who is known to have a high prevalence of stroke. We aimed to investigate associations between the haemostatic system and oxidative stress in black and white South Africans. We performed a cross-sectional study including 181 black (mean age, 44; 51.4% women) and 209 white (mean age, 45; 51.7% women) teachers. Several markers of the haemostatic- (von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1, d-dimer and clot lysis time) and oxidant-antioxidant (serum peroxides, total glutathione, glutathione peroxidase- and glutathione reductase activities) systems were measured. Along with a worsened cardiovascular profile, the black group had higher haemostatic-, inflammation- and oxidative stress markers as well as decreased glutathione peroxidase activity. In multiple regression analyses, fibrinogen was positively associated with serum peroxides (p < 0.001) in both ethnic groups. In the black population, we found negative associations of von Willebrand factor and clot lysis time with glutathione peroxidase activity (p ≤ 0.008), while a positive association existed between clot lysis time and serum peroxides (p = 0.011) in the white population. We conclude that in the black population, decreased GPx activity accompanies an altered haemostatic profile, while in the white population associations may suggest that serum peroxides impair fibrin clot lysis.


Subject(s)
Black People/ethnology , Cardiovascular Diseases/ethnology , Hemostasis/physiology , Oxidative Stress/physiology , White People/ethnology , Adult , Biomarkers/blood , Cardiovascular Diseases/blood , Cross-Sectional Studies , Female , Humans , Inflammation , Male , Middle Aged , Plasminogen Activator Inhibitor 1 , Risk Factors , South Africa/epidemiology , Stroke
16.
Public Health Nutr ; 17(8): 1706-16, 2014 Aug.
Article in English | MEDLINE | ID: mdl-23952977

ABSTRACT

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.


Subject(s)
Cardiovascular Diseases/etiology , Diet/adverse effects , Feeding Behavior , Nutrition Assessment , Nutrition Policy , Urban Population , Urbanization , Adult , Diet/standards , Energy Intake , Female , Humans , Male , Micronutrients/administration & dosage , Reference Values , Risk Factors , Sex Factors , South Africa , Surveys and Questionnaires
17.
PLoS One ; 19(6): e0305826, 2024.
Article in English | MEDLINE | ID: mdl-38917149

ABSTRACT

BACKGROUND: Human immunodeficiency virus (HIV) and antiretroviral treatment (ART) are both associated with hypercoagulability. Altered clot properties could be a potential mechanism thereof. We aimed to investigate the association of HIV and ART, with fibrinogen and plasma clot properties in a group of Black South Africans. METHODS: At baseline, 151 newly diagnosed people living with HIV (PLWH) and 176 controls were recruited. Some PLWH subsequently commenced with ARTs (n = 70) while others remained ART-naïve (n = 81). Fibrinogen and clot properties (turbidity assay) were investigated from baseline to 5-year follow-up. A sub-group of 21 women (n = 10 ART-treated; n = 11 ART-naïve) with HIV was systematically selected and matched with 12 controls, and additional clot properties (rheometry, permeability and fibre diameter) were investigated. RESULTS: Fibrinogen was lower in the HIV groups compared to the controls, while % γ' fibrinogen was higher. PLWH had shorter lag times and lower maximum absorbance than the controls (p<0.05). Their CLTs on the other hand were longer. Most variables increased over time in all groups, but differences in the degree of change over time was observed for lag time (p = 0.024) and permeability (p = 0.03). Participants who commenced with ART had a tendency of delayed clot formation (p = 0.08) and increased clot permeability (p = 0.005). CONCLUSION: PLWH had lower total fibrinogen concentration and formed less dense clots. They also formed clots that were more difficult to lyse, which likely not resulted from altered clot properties. ART use (NNRTI's) had a moderately protective effect, delaying clot formation, and increasing clot permeability.


Subject(s)
Black People , Blood Coagulation , Fibrinogen , HIV Infections , Humans , Female , HIV Infections/drug therapy , South Africa/epidemiology , Adult , Fibrinogen/metabolism , Fibrinogen/analysis , Male , Blood Coagulation/drug effects , Middle Aged , Case-Control Studies , African People
18.
Int J Lab Hematol ; 46(1): 20-32, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37984807

ABSTRACT

This guidance was prepared on behalf of the International Council for Standardisation in Haematology (ICSH) by an international working group of clinicians and scientists. The document focuses on tests and assays used for the assessment of fibrinogen function, particularly in the scenario of bleeding disorders. Thrombin clotting time (TT) is used as a screening test in some laboratories and also has some utility when direct anticoagulants are in use. The Clauss fibrinogen assay remains the method of choice for the assessment of fibrinogen function, but there are some situations where the results may be misleading. Prothrombin time derived fibrinogen assays are frequently used, but should be interpreted with caution; the results are not interchangeable between different methods and fibrinogen can be overestimated in certain clinical scenarios. Viscoelastic point of care methods may be helpful in emergency situations, while Reptilase time (and similar tests) are useful combined with TT in distinguishing heparin contamination of samples (i.e., if an incorrect blood draw is suspected) and the presence of direct thrombin inhibitors. Fibrinogen antigen assays should be used in the investigation of functional fibrinogen abnormalities; fibrinogen antigen and genetic testing are recommended in the confirmation of congenital fibrinogen disorders. The following recommendations for fibrinogen function assessment are based on published literature and expert opinion and should supplement local regulations and standards.


Subject(s)
Blood Coagulation Disorders , Hematology , Hemostatics , Humans , Thrombin Time , Thrombin , Blood Coagulation Tests/methods , Fibrinogen/analysis
19.
J Clin Lipidol ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39306544

ABSTRACT

BACKGROUND: Case-control, intervention and laboratory studies have demonstrated a link between apolipoprotein B-containing lipoproteins and clot structure and thrombosis. There is, however, limited evidence on population level. OBJECTIVES: We determined the cross-sectional relationship between lipoprotein(a) (Lp(a)), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) with fibrinogen and plasma clot properties in 1 462 Black South Africans, a population with higher fibrinogen and Lp(a) levels compared with individuals of European descent. METHODS: Data were obtained from participants in the South African arm of the Prospective Urban and Rural Epidemiology study. Clot properties analysed included lag time, slope, maximum absorbance, and clot lysis time (turbidity). Lp(a) was measured in nM using particle-enhanced immunoturbidimetry. General linear models (GLM) were used to determine the associations between ApoB and ApoB-containing lipoproteins with fibrinogen and plasma clot properties. Stepwise regression was used to determine contributors to clot properties and Lp(a) variance. RESULTS: GLM and regression results combined, indicated fibrinogen concentration and rate of clot formation (slope) had the strongest association with Lp(a); clot density associated positively with both Lp(a) and LDL-C; time to clot formation associated negatively with ApoB; and CLT demonstrated strong positive associations with both ApoB and LDL-C, while its association with Lp(a) was fibrinogen concentration dependent. CONCLUSION: These findings suggest that ApoB and the lipoproteins carrying it contribute to prothrombotic clot properties in Africans on epidemiological level and highlight potential novel prothrombotic roles for these (apo)lipoproteins to be considered for the development of targeted therapeutic approaches to address thrombotic conditions related to clot properties.

20.
Hypertens Res ; 47(9): 2456-2470, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38965426

ABSTRACT

The contrasting relationships of plant and animal protein intake with blood pressure (BP) may be partially attributed to the differential non-protein (e.g., saturated fat and fibre) and amino acid (AA) compositions. This study determined whether animal and plant protein intake were related to differential metabolomic profiles associated with BP. This study included 1008 adults from the African-PREDICT study (aged 20-30 years). Protein intake was determined using 24-h dietary recalls. Twenty-four-hour ambulatory BP was measured. Amino acids and acylcarnitines were analysed in spot urine samples using liquid chromatography-tandem mass spectrometry-based metabolomics. Participants with a low plant, high animal protein intake had higher SBP (by 3 mmHg, p = 0.011) than those with high plant, low animal protein intake (low-risk group). We found that the relationships of plant and animal protein intake with 24-h SBP were partially mediated by BMI and saturated fat intake, which were independently associated with SBP. Protein intake was therefore not related to SBP in multiple regression analysis after adjusting for confounders. In the low-risk group, methionine (Std. ß = -0.217; p = 0.034), glutamic acid (Std. ß = -0.220; p = 0.031), glycine (Std. ß = -0.234; p = 0.025), and proline (Std. ß = -0.266; p = 0.010) were inversely related to SBP, and beta-alanine (Std. ß = -0.277; p = 0.020) to DBP. Ultimately a diet high in animal and low in plant protein intake may contribute to higher BP by means of increased BMI and saturated fat intake. Conversely, higher levels of urinary AAs observed in adults consuming a plant rich diet may contribute to lower BP.


Subject(s)
Blood Pressure , Metabolomics , Humans , Male , Adult , Female , Blood Pressure/physiology , Young Adult , Plant Proteins, Dietary , Amino Acids/urine , Animal Proteins, Dietary/urine , Carnitine/urine , Carnitine/analogs & derivatives , Dietary Proteins
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