The Higher Prevalence of Venous Thromboembolism in the Hungarian Roma Population Could Be Due to Elevated Genetic Risk and Stronger Gene-Environmental Interactions
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ABSTRACT:
SUBMITTER: Natae S
PROVIDER: S-EPMC8576195 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:GxE interaction and VTE risk in the Hungarian population
| PRJEB47437 | ENA
Project description:Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. We use multiplex proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, to identify Complement Factor H Related Protein 5 (CFHR5), a regulator of the alternative pathway of complement activation, as a novel VTE associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
2023-03-25 | PXD040913 | Pride
Project description:Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism, and a combination of environmental and genetic risk factors contributes to VTE risk. Within environmental risk factors, some are provoking (e.g., cancer, surgery, trauma or fracture, immobilization, pregnancy and the postpartum period, long-distance travel, hospitalization, catheterization, and acute infection) and others are nonprovoking (e.g., age, sex, race/ethnicity, body mass index and obesity, oral contraceptive or hormone therapy use, corticosteroid use, statin use, diet, physical activity, sedentary time, and air pollution). Additionally, VTE has a strong genetic basis, with approximately 50 to 60% of the variance in VTE incidence attributed to genetic effects. Some genetic susceptibility variants that contribute to risk have been identified in candidate genes, mostly related to the clotting system and responsible for inherited hypercoagulable states (e.g., factor V Leiden, prothrombin, fibrinogen gamma, or blood group non-O). Other susceptibility single-nucleotide polymorphisms have been identified from genome-wide association studies, such as the two new loci in TSPAN15 (rs78707713) and SCL44A2 (rs2288904) genes. Risk factors are not always associated with VTE in isolation; however, and an understanding of how environmental and genetic factors interact may provide insight into the pathophysiology of VTE, possibly identifying opportunities for targeted prevention and treatment.
| S-EPMC5146955 | biostudies-literature
Project description:Approximately 10% of the general population has elevated blood concentrations of hepatic enzymes, which are linked to increased coagulation markers. We tested whether elevated hepatic enzymes are associated with increased risk of venous thromboembolism (VTE).We followed 12,604 adults with measurements of alanine transaminase, aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) prospectively for VTE occurrence.AST and GGT above the laboratory normal values were associated over two decades of follow-up with increased risk of total (n = 532) and provoked VTE (n = 332), but with not unprovoked VTE (n = 200). In a model adjusted for age, race, sex, hormone replacement, alcohol intake, diabetes, body mass index, estimated glomerular filtration rate, and C-reactive protein, the hazard ratios (HR) (95% confidence interval) for high versus normal AST were 1.46 (1.00-2.11) for total VTE and 1.83 (1.21-2.79) for provoked VTE. For high GGT, the HR were 1.34 (1.06-1.69) for total VTE and 1.43 (1.07-1.91) for provoked VTE. When follow-up was limited to the first 10 years, associations were even stronger (HR ? 1.7 for total VTE).Elevated concentrations of two hepatic enzymes (AST and GGT) in this general middle-aged population are associated with a modestly increased risk of VTE.
| S-EPMC4254154 | biostudies-literature
Project description:A recent study found that approximately 1 in every 6 patients hospitalized for the 1st episode of syncope had an underlying pulmonary embolism (PE). As current guidelines do not strongly emphasize evaluation for PE in the workup of syncope, we hypothesize that there might be a higher rate of 30-day readmission due to untreated venous thromboembolism (VTE). The objective of this study is to measure the 30-day readmission rate due to VTE and identify predictors of 30-day readmission with VTE among syncope patients. We identified patients admitted with syncope with ICD9 diagnoses code 780.2 in the Nationwide Readmission Database (NRD-2013), Healthcare Cost and Utilization Project (HCUP). The 30-day readmission rate was calculated using methods described by HCUP. Logistic-regression was used to identify predictors of 30-day readmission with VTE. Discharge weights provided by HCUP were used to generate national estimates. In 2013, NRD included 207,339 eligible patients admitted with syncope. The prevalence rates of PE and DVT were 1.1% and 1.4%, respectively. At least one syncope associated condition was present in 60.9% of the patients. Among the patients who were not diagnosed with VTE during index admission for syncope (N = 188,015), 30-day readmission rate with VTE was 0.5% (0.2% with PE and 0.4% with DVT). In conclusion, low prevalence of VTE in patients with syncope and extremely low 30-day readmission rate with VTE argues against missed diagnoses of VTE in index admission for syncope. These results warrant further studies to determine clinical impact of work up for PE in syncope patients without risk factors.
| S-EPMC7153877 | biostudies-literature
Project description:AimCholesteryl ester transfer protein (CETP) is an important lipid transfer factor in plasma that enhances prothrombinase activity in purified systems. This study was conducted to test the association of plasma CETP activity with venous thrombosis (VTE) and to address the procoagulant mechanism of CETP activity in prothrombinase assays.MethodsWe measured CETP lipid transfer activity in plasmas of 49 male VTE patients and in plasmas of matched controls. CETP procoagulant activity was tested in purified prothrombinase systems.ResultsCETP lipid transfer activity levels were significantly higher in VTE patients than in controls (p=0.0008). A subset of patients carrying the CETP mutations Ala373Pro and Arg451Gln, which were also linked to the VTE risk, showed significantly higher plasma CETP activity than the noncarriers. The plasma CETP activity negatively correlated with APTT, suggesting that the CETP activity is associated with plasma coagulability. Recombinant (r) CETP bound to both factor Xa (Kd=15 nM) and Gla-domainless factor Xa (Kd=59 nM), whereas rCETP enhanced prothrombin activation by factor Xa, but not by Gla-domainless factor Xa. rCETP also required factor Va for enhancement of prothrombinase activity. When we addressed the effects of mutations in CETP on prothrombinase activity, Gln451-rCETP was found to have five-fold higher thrombin generation activity than wt-rCETP or Pro373-rCETP.ConclusionsElevated CETP lipid transfer activity in plasma was associated with the risk of VTE. Gln451-CETP, which is linked to VTE, has much higher procoagulant activity than wt-CETP. CETP might act as a physiologic procoagulant by mechanisms that involve its direct binding to factor Xa.
| S-EPMC5064881 | biostudies-literature
Project description:Traumatic brain injury (TBI) patients are known to have a high rate of venous thromboembolism (VTE), and additional neuromuscular blockade or barbiturate coma therapy has the theoretical risk of exacerbating baseline hemostasis and elevating the incidence of thromboembolic events. We conducted a single-institution retrospective review of patients surviving severe TBI, as determined by need for intracranial pressure (ICP) monitoring, who further required paralytics or barbiturate therapy to maintain ICP control. Patients were administered VTE prophylaxis as clinically appropriate. Predictors for VTE were subsequently determined with univariate and logistic multivariate regression analyses. The main cohort includes 144 patients, 34 of whom received pharmaceutical immobilization for ICP control. Mean ISS and GCS at intake were 31.9 and 5.2, respectively. Among those receiving vs not-receiving paralytics and/or barbiturate therapy, there was a statistical difference of 12/34 (35.3%) vs 18/110 (16.4%, p = 0.0280) in VTE events, at a mean time greater than two weeks from the time of trauma. Multivariate logistics regression indicated 3.2 times increased odds of developing a VTE (log odds = 1.17, p = 0.023). No pediatric patients were positive for an event (0/12 vs 7/22, p = 0.0356), and infections were only documented among those with VTE (0/22 vs 4/12, p = 0.0107). Overall, paralytics and barbiturate therapy were correlated with a higher incidence of VTE among TBI patients. Although the need for ICP control will outweigh an increase in thromboembolic risk, there is value for increased surveillance and screening during the prolonged inpatient stay of these patients.
| S-EPMC8253589 | biostudies-literature
Project description:Nutritional epidemiology studies on Roma people are scarce and, to date, their nutrient-based dietary patterns with regards to both healthy and sustainable dietary considerations have never been reported. We report, for the first time, adherence to healthy and sustainable dietary patterns using scoring and regression models, based on recommendations defined by the World Health Organization, in the Dietary Approaches to Stop Hypertension (DASH) study and the EAT-Lancet report, as well as dietary quality based on Dietary Inflammatory Index (DII) among the Hungarian Roma (HR) population living in North East Hungary, with Hungarian general (HG) adults as reference. Data were obtained from a complex, comparative health survey involving dietary assessment, structured questionnaire-based interview, physical and laboratory examinations on 359 HG and 344 HR subjects in Northeast Hungary. Poisson regressions were fit to models that included DASH, EAT, DII and Healthy Diet Indicator as dependent variables to assess the influence of ethnicity on healthy and sustainable nutrient-based patterns. Adjusted models controlled for all relevant covariates using the residual method indicated poor dietary quality with regards to the selected dietary patterns. These associations were not ethnicity-sensitive, except for DII, where Roma ethnicity was linked to a decrease of DII score (β = -0.455, 95%CI: -0.720; -0.191, p < 0.05). Currently, HR dietary patterns appear to be relatively unhealthy and unsustainable, rendering them vulnerable to elevated risk of ill-health. Nevertheless, their dietary patterns did not strongly differ from HG, which may contribute to Hungarians being one of the most obese and malnourished nations in Europe. Further prospective research on the potential public and environmental health effects of these findings is warranted.
| S-EPMC7996132 | biostudies-literature
Project description:ObjectivePatients with cirrhosis are at increased risk for venous thromboembolism (VTE) and portal vein thrombosis (PVT). Cirrhosis due to non-alcoholic steatohepatitis (NASH) appears to be particularly prothrombotic. We investigated hospitalized patients with NASH cirrhosis to determine if they are at increased risk for VTE.MethodsData on adult hospitalized patients with cirrhosis and VTE (deep vein thrombosis and/or pulmonary embolism) between November 1, 2010 and December 31, 2015 were obtained. Cases with VTE were matched by age, gender, and model for end stage liver disease (MELD) score to corresponding controls without VTE.ResultsTwo hundred and ninety subjects (145 matched pairs) with mean age of 58.4?±?11.8 years and MELD score of 16.0?±?7.2 were included. Baseline characteristics were similar between cases and controls. Independent adjusted risk factors for VTE included NASH (OR: 2.46, 95% CI: 1.07-5.65, p?=?0.034), prior VTE (OR: 7.12, 95% CI: 1.99-25.5, p?=?0.003), and presence of PVT (OR: 2.18, 95% CI: 1.03-4.58, p?=?0.041). Thrombocytopenia was associated with decreased risk (OR: 0.49, 95% CI: 0.26-0.95, p?=?0.035).ConclusionsNASH is an independent risk factor for VTE among cirrhosis patients and provides further evidence that NASH is a hypercoagulable state. While all hospitalized patients with cirrhosis at risk for VTE should be considered for medical thromboprophylaxis, those with NASH cirrhosis are at particularly increased risk and therefore a high index of suspicion for VTE should be maintained even in the presence of thromboprophylaxis.
| S-EPMC5862151 | biostudies-literature
Project description:Metabolic syndrome (MetS) is a cluster of clinical conditions that poses a major health burden worldwide. In the present study, we investigate the changes in the prevalence of MetS and its components among the Roma in two disadvantaged counties in Northeastern Hungary focusing on a seven-year-long period. The database of the present study is based on cross-sectional surveys of the Hungarian Roma population (aged 20-64 years) conducted in 2011 (n = 458) and 2018 (n = 374). The increase in the prevalence of MetS itself in the whole Roma population was not found to be significant in the period examined (although it increased from 40.0% up to 46.0%, p = 0.080); however, regarding its components, there was a significant increase in the prevalence of central obesity (from 62.7% to 73.3%, p = 0.001) and raised blood pressure (BP) or treated hypertension (from 45.2% to 54.5%, p = 0.007). These changes were mainly observed in the younger age groups, so the risk for MetS increased significantly in the 20-34 (OR = 1.10, p = 0.038) and 35-49 (OR = 1.07, p = 0.048) year age groups in the 2018 study population compared the 2011 one. The increasing prevalence of hidden hypertension and, consequently, untreated individuals with raised BP (from 29.6% to 43.5%, p = 0.014) among females is quite alarming; therefore, a targeted public health strategy and targeted interventions are desperately needed to prevent further worsening of the current situation.
| S-EPMC8304367 | biostudies-literature