The Plasma Proteome and Risk of Future Venous Thromboembolism-Results from the HUNT Study.

Background:  This study aimed to identify novel plasma proteins associated with first-lifetime venous thromboembolism (VTE) and molecular pathways involved in VTE pathogenesis.

Methods:  A case-cohort comprising incident VTE cases ( = 294) and a randomly sampled age- and sex-weighted subcohort ( = 1,066) was derived from the Trøndelag Health Study (HUNT3, n = 50,800). Blood samples were collected and stored at cohort inclusion (2006-2008), and participants were followed up to 5 years.

High microRNA-145 plasma levels are associated with decreased risk of future incident venous thromboembolism: the HUNT study.

MicroRNA-145 (miR-145) has been reported to downregulate the expression of tissue factor and factor XI in vitro and decrease venous thrombus formation in animal models. However, the association between miR-145 and risk of future venous thromboembolism (VTE) in the general population remains unknown. We investigated the association between plasma levels of miR-145 and risk of future VTE in a case-cohort study.

High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism.

Background: C1-inhibitor (C1INH) is a broad-acting serine protease inhibitor with anticoagulant activity. The impact of C1INH plasma levels within the normal physiological range on risk of venous thromboembolism (VTE) is unknown. We assessed the association of plasma C1INH levels and VTE risk and evaluated the impact of C1INH on thrombin and plasmin generation in ex vivo assays.

Complement factors B, D, C3bBbP and risk of future venous thromboembolism.

The complement system appears to be involved in the pathogenesis of venous thromboembolism (VTE). We investigated the association of complement factors (CF) B, D, and the alternative pathway convertase, C3bBbP, measured at inclusion, with the risk of future VTE in a nested case-control study; 380 VTE patients and 804 age- and sex-matched controls derived from the Tromsø study. Odds ratios (ORs) with 95% confidence intervals (95% CI) for VTE across tertiles of CF concentrations were estimated using logistic regression.

Cross-Ancestry Investigation of Venous Thromboembolism Genomic Predictors.

Background: Venous thromboembolism (VTE) is a life-threatening vascular event with environmental and genetic determinants. Recent VTE genome-wide association studies (GWAS) meta-analyses involved nearly 30 000 VTE cases and identified up to 40 genetic loci associated with VTE risk, including loci not previously suspected to play a role in hemostasis. The aim of our research was to expand discovery of new genetic loci associated with VTE by using cross-ancestry genomic resources.

High Levels of Complement Activating Enzyme MASP-2 Are Associated With the Risk of Future Incident Venous Thromboembolism.

Background: Experimental studies have shown that the complement activating enzyme MASP-2 (mannose-binding lectin associated serine protease 2) exhibits a thrombin-like activity and that inhibition of MASP-2 protects against thrombosis. In this study, we investigated whether plasma MASP-2 levels were associated with risk of future venous thromboembolism (VTE) and whether genetic variants linked to MASP-2 levels were associated with VTE risk.

Methods: We conducted a population-based nested case-control study involving 410 VTE patients and 842 age- and sex-matched controls derived from the Norwegian Tromsø Study.

Plasma lipopolysaccharide-binding protein is a biomarker for future venous thromboembolism: Results from discovery and validation studies.

Background: Effect-size underestimation impedes biomarker identification. Long follow-up time in prospective studies attenuates effect-size estimates for transient biomarkers, while disease category-specific biomarkers are affected by merging of categories. Venous thromboembolism (VTE) encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE).

Elevated plasma levels of plasminogen activator inhibitor-1 are associated with risk of future incident venous thromboembolism.

Background: Plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of fibrinolysis, is frequently elevated in obesity and could potentially mediate the risk of venous thromboembolism (VTE) in obese subjects. However, whether PAI-1 is associated with VTE remains uncertain.

Objective: To investigate the association between plasma PAI-1 levels and risk of future incident VTE and whether PAI-1 could mediate the VTE risk in obesity.

Plasma levels of platelet-derived microvesicles are associated with risk of future venous thromboembolism.

Background: Microvesicles (MVs) are small double-membrane encapsulated particles shed from cells. Case-control studies have reported elevated plasma levels of platelet-derived MVs (PDMVs) in patients with venous thromboembolism (VTE). However, it is not known whether high PDMV levels is a risk factor or a consequence of the acute VTE event.

Plasma procoagulant phospholipid clotting time and venous thromboembolism risk.

Background: Negatively charged procoagulant phospholipids, phosphatidylserine (PS) in particular, are vital to coagulation and expressed on the surface membrane of extracellular vesicles. No previous study has investigated the association between plasma procoagulant phospholipid clotting time (PPL) and future risk of venous thromboembolism (VTE).

Objectives: To investigate the association between plasma PPL and the risk of incident VTE in a nested case-control study.

Rosuvastatin treatment decreases plasma procoagulant phospholipid activity after a VTE: A randomized controlled trial.

Background: Venous thromboembolism (VTE) is a frequent cardiovascular disease with severe complications, including recurrence and death. There is a great need for alternative prophylactic treatment options as anticoagulation is accompanied by increased bleeding risk. Statins are reported to reduce the risk of incident and recurrent VTE, but the mechanisms are elusive.

Elevated plasma D-dimer levels are associated with risk of future incident venous thromboembolism.

Background: D-dimer, a global biomarker for activation of the coagulation and fibrinolysis systems, is useful in assessing individual risk of venous thromboembolism (VTE) recurrence. However, there is limited information on the association between D-dimer and risk of a first lifetime VTE event.

Objectives: To investigate the association between plasma D-dimer levels and risk of future incident VTE.

Impact of a Vancomycin-Induced Shift of the Gut Microbiome in a Gram-Negative Direction on Plasma Factor VIII:C Levels: Results from a Randomized Controlled Trial.

Background:  Inflammation is present in several conditions associated with risk of venous thromboembolism. The gut microbiome might be a source of systemic inflammation and activation of coagulation, by translocation of lipopolysaccharides from gram-negative bacteria to the systemic circulation.

Objective:  To investigate whether a vancomycin-induced shift of the gut microbiome in a gram-negative direction influences systemic inflammation and plasma factor (F) VIII procoagulant activity (FVIII:C).

Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism.

The role of complement in the pathogenesis of venous thromboembolism (VTE) is unclear. We wanted to investigate (1) whether plasma complement component C5 (C5) levels are influenced by genetic variants or chronic inflammation and (2) the association between plasma C5 and risk of future VTE in a nested case-control study of 415 patients with VTE and 848 age- and sex-matched controls derived from the Tromsø Study. Plasma C5 levels were measured at inclusion.

Plasma Levels of Leptin and Risk of Future Incident Venous Thromboembolism.

Background:  Circulating levels of leptin, an adipocyte-derived hormone, are frequently elevated in obesity. Leptin has been reported to upregulate prothrombotic hemostatic factors in vitro and could potentially mediate venous thromboembolism (VTE) risk in obesity. However, whether leptin is associated with VTE remains uncertain.

Prothrombotic genotypes and risk of venous thromboembolism in occult cancer.

Background: Studies have reported that the combination of some prothrombotic genotypes and overt cancer yields a synergistic effect on VTE risk. Whether individual prothrombotic genotypes or number of risk alleles in a genetic risk score (GRS) affect VTE risk in occult cancer have not been addressed. The aim of this study was to investigate the joint effect of five prothrombotic genotypes and occult cancer on VTE risk.

Combined effects of plasma von Willebrand factor and platelet measures on the risk of incident venous thromboembolism.

Plasma von Willebrand factor (VWF) and platelet reactivity are risk factors for venous thromboembolism (VTE), and VWF can promote hemostasis by interaction with platelets. In this study, we explored the combined effects of plasma VWF and platelet measures on the risk of incident VTE. A population-based nested case-control study with 403 cases and 816 controls was derived from the Tromsø Study.

Rewarming From Hypothermic Cardiac Arrest Applying Extracorporeal Life Support: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims at comparing outcomes of rewarming after accidental hypothermic cardiac arrest (HCA) with cardiopulmonary bypass (CPB) or/and extracorporeal membrane oxygenation (ECMO). Literature searches were limited to references with an abstract in English, French or German. Additionally, we searched reference lists of included papers.

Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism.

Background: The impact of the combination of obesity and multiple prothrombotic genotypes on venous thromboembolism (VTE) risk remains unclear.

Objective: To investigate the joint effect of obesity and a genetic risk score (GRS) composed of established prothrombotic single nucleotide polymorphisms (SNPs) on VTE risk using a population-based case-cohort.

Methods: Cases with incident VTE ( = 1,470) and a subcohort ( = 12,826) were derived from the Tromsø Study (1994-2012) and the Trøndelag Health Study (HUNT) (1995-2008).

Plasma levels of von Willebrand factor and future risk of incident venous thromboembolism.

Several case-control studies have reported elevated plasma von Willebrand factor (VWF) levels in patients with venous thromboembolism (VTE) compared with controls. However, because few studies have investigated the association in a prospective design, it is unclear whether elevated plasma VWF is a risk factor or a consequence of the VTE event. Therefore, we aimed to investigate the prospective association between plasma VWF levels and risk of VTE, as well as to perform subgroup analyses of deep vein thrombosis (DVT) and pulmonary embolism.

Combined effects of five prothrombotic genotypes and cancer on the risk of a first venous thromboembolic event.

Background: The role of combined prothrombotic genotypes in cancer-related venous thromboembolism (VTE) is scarcely studied. We aimed to investigate the impact of a 5-single nucleotide polymorphism (SNP) score on the risk of VTE in patients with and without cancer using a population-based case-cohort.

Methods: Cases with a first VTE (n = 1493) and a subcohort (n = 13 072) were derived from the Tromsø Study (1994-2012) and the Nord-Trøndelag Health Study (1995-2008).

Prothrombotic genotypes and risk of major bleeding in patients with incident venous thromboembolism.

Background: Genotypes associated with venous thromboembolism (VTE) may protect against bleeding due to a hypercoagulable state. Whether the risk of major bleeding is reduced in parallel with an increasing number of prothrombotic genotypes during anticoagulant treatment in VTE remains unknown.

Objectives: To investigate the association between multiple prothrombotic genotypes and risk of major bleeding in patients with VTE.

D-Dimer Measured at Diagnosis of Venous Thromboembolism is Associated with Risk of Major Bleeding.

Identification of patients at risk of major bleeding is pivotal for optimal management of anticoagulant therapy in venous thromboembolism (VTE). Studies have suggested that D-dimer may predict major bleeding during anticoagulation; however, this is scarcely investigated in VTE patients. We aimed to investigate the role of D-dimer, measured at VTE diagnosis, as a predictive biomarker of major bleeding.