Molecular Determinants of Thrombosis Recurrence Risk Across Venous Thromboembolism Subtypes.

Venous thromboembolism (VTE) is a frequent (annual incidence of 1-2 per 1,000) and potentially life-threatening (case-fatality rate up to 10%) disease. VTE is associated with serious short-term and long-term complications, including a recurrence rate approaching 20% within five years. Anticoagulant therapy, the mainstay of VTE treatment, drastically reduces the risk of early VTE recurrence, but it exposes patients to a substantial risk of bleeding.

Venous Thrombosis Associated with Different Types of SARS-CoV-2 Vaccines in the Netherlands-Results of the TERA Case-Control Study.

The magnitude of the risk of venous thromboembolism (VTE) after SARS-CoV-2 vaccines is debated.We included patients with a first VTE in 2021 and controls from a sample of Dutch citizens. Participants completed a questionnaire on VTE risk factors and vaccination, with data linked to Statistics Netherlands.

Plasma -Glycan Signatures Are Associated With a First Event of Venous Thromboembolism.

Background: Coagulation factors play important roles in the pathophysiology of venous thromboembolism (VTE), and most of them are glycoproteins, that is, proteins containing glycans attached. Although the connection between glycosylation and coagulation factors seems obvious, the association between glycosylation and VTE risk remains unexplored. We aimed to elucidate the association between -glycans in plasma and VTE risk in the MEGA study (Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis), a case-control study aiming to identify risk factors for VTE.

Metabotype identification via fasting and postprandial metabolomics and its association with type 2 diabetes incidence.

Background: Metabotypes represent distinct metabolic profiles that groups of individuals share, facilitating disease risk stratification. We aimed to apply metabolomics to identify metabotypes in different prandial states and examine its associations with type 2 diabetes mellitus (T2DM) risk.

Methods: Using fasting and postprandial metabolomic data from the Netherlands Epidemiology of Obesity (NEO) study (N = 5320), we applied -means clustering to identify individual’s metabotypes for three prandial states (fasting, postprandial [150 min after meal], and postprandial minus fasting, i.

A multiomics approach reveals novel regulators of plasma factor V levels, highlighting CLEC4M as a clearance receptor.

Coagulation factor V (FV) is a key protein in maintaining the hemostatic balance, with abnormal plasma levels associated with both thrombotic and hemorrhagic conditions. We propose a comprehensive bioinformatic analysis integrating large-scale proteogenomics and transcriptomic data from original and public data sets. We identify a biological fingerprint of 26 new proteins and loci involved in the regulation of plasma FV levels.

Risk of First Venous Thrombosis by Comparing Different Thrombin Generation Assay Conditions: Results from the MEGA Case-control Study.

Background: Hypercoagulability is a risk factor for venous thromboembolism (VTE). Thrombin generation (TG) is a global coagulation assay that measures an individual's clotting tendency. We hypothesise that slow-onset TG (achieved by using a low procoagulant stimulus or an inhibitor of coagulation) is the optimal responsive TG method for detecting hypercoagulability.

Excess mortality during the first 2 years of the COVID-19 pandemic (2020-2021) in the Netherlands: Overall and across demographic subgroups.

Objectives: The overall impact of the COVID-19 pandemic on mortality can be estimated by the assessment of excess deaths from all causes because the reported number of deaths due to COVID-19 do not accurately reflect the true death toll. We assessed excess mortality in 2020 and 2021 in the Netherlands.

Methods: All analyses were performed on data from comprehensive nationwide registers provided by Statistics Netherlands (Centraal Bureau voor de Statistiek), including demographic characteristics and mortality.

Robust Metabolomic Age Prediction Based on a Wide Selection of Metabolites.

Chronological age is a major risk factor for numerous diseases. However, chronological age does not capture the complex biological aging process. The difference between chronological age and biologically driven aging could be more informative in reflecting health status.

Genomic Landscape of Thrombosis Recurrence Risk Across Venous Thromboembolism Subtypes.

Venous thromboembolism (VT) is a frequent (annual incidence of 1 to 2 per 1,000) and potentially life-threatening (case-fatality rate up to 10%) disease. VT is associated with serious short-term and long-term complications including a recurrence rate of approximately 20% within five years. Anticoagulant therapy, the mainstay of VT treatment, drastically reduces the risk of early VT recurrence, but it exposes patients to a substantial risk of bleeding.

The effect of BCG vaccination in the elderly on infectious and non-infectious immune-mediated diseases.

Objectives: Previous research has suggested beneficial heterologous effects of the Bacillus Calmette-Guérin (BCG) vaccine on non-mycobacterial infections and other immune-mediated diseases. During the COVID-19 pandemic, randomized controlled trials BCG-PRIME (n = 5349) and BCG-CORONA-ELDERLY (n = 1907) investigated the impact of BCG on SARS-CoV-2 infections in older individuals. We extended the follow-up in these studies by one year (BCG-Long Term study), to assess the overall effects of BCG vaccination on infectious and immune-mediated diseases in individuals aged over 60.

Association Between Low Sex Hormone-Binding Globulin and Increased Risk of Type 2 Diabetes Is Mediated by Increased Visceral and Liver Fat: Results From Observational and Mendelian Randomization Analyses.

The aim of this study was to investigate the associations among sex hormone-binding globulin (SHBG), visceral adipose tissue (VAT), liver fat content, and risk of type 2 diabetes (T2D). In the Netherlands Epidemiology of Obesity study, 5,690 women (53%) and men (47%) without preexisting diabetes were included and followed for incident T2D. SHBG concentrations were measured in all participants, VAT was measured using MRI, and liver fat content was measured using proton magnetic resonance spectroscopy in a random subset of 1,822 participants.

Coagulation and inflammatory response after intramuscular or intradermal mRNA-1273 SARS-CoV-2 vaccine: secondary analysis of a randomized trial.

Background: Fractional-dosed intradermal (i.d.) vaccination produces antibody concentrations above the proposed proxy for protection against severe disease as compared with intramuscular (i.

Incidence rate of venous thrombosis in women switching combined oral contraceptives: a cohort study.

Background: The incidence rate of venous thrombosis (VT) in women switching combined oral contraceptives (COCs) is unknown.

Objectives: We hypothesize that women switching COCs may have a similar increased incidence rate of VT as women who start COCs. Switching means starting with a new COC, which may biologically approximate starting.

Hormonal contraceptive use after a first venous thrombotic event and the risk of recurrence in premenopausal women.

Background: Extensive evidence is available on hormonal contraceptive (HC) use and the risk of a first venous thromboembolism (VTE) event. Despite recommendations to discontinue combined HC (CHC) use, some women continue or start its use after a first VTE.

Objectives: We aimed to evaluate the VTE recurrence risk associated with HC use in premenopausal women.

Association between venous thromboembolism-associated genetic variants, coagulation factor levels, and thrombin generation potential.

Recently three large meta-analyses of genome-wide association studies for venous thromboembolism (VTE) identified over 130 genetic variants. However, mechanisms by which newly identified and therefore underexplored VTE-associated genetic variants influence VTE remain unclear. To elucidate the mechanism, we investigated the association between 61 newly identified VTE-associated genetic variants and the levels of coagulation factor (F) VIII, FIX, FXI, and fibrinogen as well as thrombin generation parameters (lag time, peak, endogenous thrombin potential, time-to-peak, and velocity), which are well-known biological traits associated with VTE.

Genomic science of risk prediction for venous thromboembolic disease: convenient clarification or compounding complexity.

Venous thromboembolism (VTE) refers to abnormal blood clots in veins occurring in 1 to 2 per 1000 individuals every year. While anticoagulant treatment can prevent VTE, it increases the risk of bleeding. This emphasizes the importance of identifying individuals with a high risk of VTE and providing prophylactic interventions to these individuals to reduce both VTE and bleeding risks.

Health-related quality of life after first venous thromboembolism in individuals aged 70 years and older.

Background: There is limited information on short- and long-term effects of venous thromboembolism (VTE) on health-related quality of life (HRQoL) in the elderly.

Objectives: To assess change in generic HRQoL and disease-specific HRQoL in patients 1 year after the VTE.

Methods: The Age and Thrombosis, Acquired and Genetic risk factors in the elderly (AT-AGE) study is a 2-center case-control study performed in Leiden, the Netherlands, and Vermont, United States, among individuals aged ≥70 years.

Plasma levels of coagulation factors VIII and IX and risk of venous thromboembolism: Systematic review and meta-analysis.

Introduction: The associations of plasma factor VIII (FVIII) and factor IX (FIX) levels with risk of venous thromboembolism (VTE) are not well defined. We performed a systematic review and meta-analysis of these associations.

Methods: Random effects inverse-variance weighted meta-analysis was used to estimate pooled odds ratios for comparisons across equal quartiles of the distributions and 90 % thresholds (higher versus lower), and for testing linear trends.

Sex-specific association between microvascular health and coagulation parameters: the Netherlands Epidemiology of Obesity study.

Background: Microvascular dysfunction is a growing determinant of sex differences in coronary heart disease (CHD). Dysregulation of the coagulation system is involved in CHD pathogenesis and can be induced by endothelial glycocalyx (EG) perturbation. However, little is known about the link between EG function and coagulation parameters in population-based studies on sex specificity.