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-1act, 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

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-1 act 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-1 act 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

The clinical relevance of altered fibrinogen packaging in the presence of 17β-estradiol and progesterone

BACKGROUND : The effect of endogenous hormone concentrations, specifically 17β-estradiol and progesterone, on fibrin network formation has not been established. OBJECTIVES : It is essential to understand natural hormone mechanisms since these hormones are still present in circulation while hormonal contraceptives, which are associated with increased risk of venous thromboembolism, are used. METHODS : Due to the fact that these hormones are known to increase hypercoagulability and the prothrombotic state scanning electron microscopy (SEM), atomic force microscopy (AFM), thromboelastography (TEG) and turbidimetry were employed to investigate the morphology, surface roughness, viscoelastic properties and formation and lysis of fibrin. RESULTS : 17β-estradiol and progesterone showed hypercoagulable viscoelastic properties and decreased the diameter and surface roughness of fibrin while increasing dense matted deposit occurrence. Our results suggest that the additional burden of hormonal load, together with the presence of endogenous estrogen and progesterone, may result in a prothrombotic and hypercoagulable state in females with an inflammatory predisposition. CONCLUSION : Our results are of clinical importance when considering hormones as either pathological agent or therapeutic intervention as will be assessed in future investigation.Swanepoel received funding from the National Research Foundation (NRF) of South Africa and Pretorius received funding from the Medical Research Council (MRC) of South Africa.http://www.elsevier.com/locate/thromres2017-10-31hb2016Physiolog

Global fibrinolytic potential of black South Africans in the North West Province

Thesis (PhD (Nutrition))--North-West University, Potchefstroom Campus, 2013.INTRODUCTION AND AIM - The prevalence of cardiovascular disease (CVD) has increased significantly in the black South African population in recent years. Early in the development of CVD, atherosclerotic plaques form in the vessel wall. When this plaque becomes unstable and ruptures, the coagulation cascade is activated and a blood clot forms. The function of this clot is to stop bleeding. However, it cannot remain in the vasculature indefinitely and has to be lysed again. The ability of the body to lyse clots can be measured with global fibrinolytic potential (GFP) assays and expressed as lysis time. Increased clot lysis time (CLT) has been shown to be significantly associated with various CVD risk factors and CVD events in Caucasian populations while very little information is available for other ethnicities. In this study we investigated plasma GFP and its relation to CVD risk factors in a large black African population. We also determined the effect of three polymorphisms in the promoter area of the plasminogen activator inhibitor-1 (PAI-1) gene on PAI-1act (activity) levels (a main determinant of CLT) and CLT, together with gene-environment interactions and the effect of urbanisation on these interactions. PARTICIPANTS AND METHODS Apparently healthy men and women between the ages of 35 and 65 years were recruited to take part in the South African arm of the Prospective Urban and Rural Epidemiology (PURE) study. Approximately 1000 rural and 1000 urban black African individuals participated. Data and samples were collected during a 12-week collection period in 2005 for cross-sectional analysis. RESULTS - Increased PAI-1act levels, body mass index (BMI), glycosylated haemoglobin (HbA1c), triglycerides, fibrinogen concentration, C-reactive protein, female sex, positive HIV-status and the metabolic syndrome were all associated with prolonged CLTs, while increased habitual alcohol consumption was associated with shorter CLTs. Urban-rural differences for CLT existed in women only. This is likely due to the larger extent of rural-urban differences in other CVD risk factors observed in women compared to what was observed in men. Of the CVD risk factors measured, PAI-1 explained the largest proportion of the variance in CLT (27%). Owing to the important role PAI-1act plays in CLT, we investigated three polymorphisms in the PAI-1 gene promoter area (the 4G/5G polymorphism, the novel SNP C428T and SNP G429A (previously identified)), and the influence of these polymorphisms on PAI-1act levels and CLT. The frequency of the 5G allele was high (0.85) in comparison with previously reported literature. PAI-1act increased significantly across genotypes in the urban (5G/5G: 3.84 U/ml; 4G/5G: 4.85 U/ml; 4G/4G: 5.96 U/ml p=0.009) but not the rural subgroup, while CLT did not differ. We found significant interactions 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. Direct relationships with PAI-1act or CLT were not found for the C428T and G429A polymorphisms; they did, however, influence associations 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. CONCLUSION - CLT associated with many of the same CVD risk factors described in the literature for Caucasian populations, but also with other risk factors. Rural-urban differences in CLT are dependent on the association of CLT with other CVD risk factors in the rural-urban setting. Genetic polymorphisms of the PAI-1 gene did not directly influence CLT, despite influencing PAI-1act. The main contributor to PAI-1act variance, however, was (central) obesity. 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, were significantly influenced by urbanisation.Doctora

The association between alcohol consumption, PAI-1 activity and fibrinogen concentration in black South Africans

Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2010.INTRODUCTION AND AIM: The prevalence of cardiovascular disease(CVD) is increasing in the black South African population. At increased levels, plasminogen activator inhibitor type-1 (PAI-1) and fibrinogen, which are two of the best known haemostatic risk factors, may increase the risk of CVD. Fibrinogen concentrations have been shown to be higher, and PAI-1 levels to be significantly lower, in black South African populations than in Caucasians. Alcohol consumption has been shown to influence the risk of CVD, amongst others, through effects on haemostasis. Cross-sectional epidemiological studies indicate that moderate amounts of alcohol seem to correlate negatively with fibrinogen, while PAI-1 levels seem to increase with heavy alcohol consumption. However, these studies were conducted in Caucasian populations and, owing to differences between black Africans and Caucasians in absolute fibrinogen and PAI-1 levels, the question arises whether these risk factors will associate with habitual alcohol consumption in black Africans in the same way as they do in Caucasians. In the present study, we investigated the association between alcohol consumption, fibrinogen concentration and PAI-1act, as well as the influence of gender urbanisation, waist circumference, body mass index (BMI), triglyceride concentration and the 4G/5G polymorphism (the last two for PAI-1) on this association in the South African Prospective Urban and Rural Epidemiological (PURE) study population. PARTICIPANTS AND METHODS: Approximately 1000 rural and 1000 urban, apparently healthy, black men and women aged 35-60 years participated in the South African arm of the international PURE study. Over a twelve-week period in 2005, habitual alcohol consumption (g/day) was determined by quantitative food frequency questionnaires administered by trained fieldworkers, and blood samples and anthropometrical measurements were collected. RESULTS: Heavy alcohol consumption was associated with an increase in PAI-1act in the total population after adjustment for triglycerides and waist circumference. In participants with increased triglyceride concentrations (>/= 1.7 mmol/l) and in abdominally obese and obese (BMI >/= 30 kg/m2) participants who drank heavily, PAI-1act was significantly higher than in non-drinkers. This alcohol-related increase in PAI-1act was not observed, however, in individuals with normal waist circumference measurements or in individuals with normal triglyceride concentrations. In the total population, moderate alcohol consumption was associated with a decrease in fibrinogen concentration, compared with non-drinkers, and reached a plateau with heavy alcohol consumption. This association was also seen in participants with normal waist circumference and BMI, as well as in overweight participants. However, in abdominally obese participants and those with a BMI of more than 30 kg/m2, the consumption of moderate amounts of alcohol was not associated with a decrease in fibrinogen concentrations. Neither gender, the 4G/5G polymorphism (PAI-1 only) nor urbanisation significantly influenced the associations between alcohol consumption and fibrinogen or PAI-1act. CONCLUSION: Despite the finding that fibrinogen concentration is generally higher, and PAI-1act lower, in black South Africans than in Caucasians, the association between these two haemostatic risk factors and alcohol consumption seems to follow the same pattern as in Caucasian populations. Heavy alcohol consumption was associated with an increase in PAI-1act. while moderate alcohol consumption was associated with a decrease in fibrinogen concentration, which was not further decreased in the heavy alcohol consumers. Normal triglyceride concentrations and waist circumference, however, seem to protect against the alcohol-related PAI-1act increase in this black African population.Master