Venous thromboembolism (VTE) is a life-threatening disease with risk of recurrence. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) is effective to prevent thromboembolic recurrence. We aimed to investigate the quality of OAC of VTE patients in regular medical care (RMC) compared to a telemedicine-based coagulation service (CS). The thrombEVAL study (NCT01809015) is a prospective, multi-center study to investigate OAC treatment (recruitment: January 2011–March 2013). Patients were evaluated using clinical visits, computer-assisted personal interviews, self-reported data and laboratory measurements according to standard operating procedures. Overall, 360 patients with VTE from RMC and 254 from CS were included. Time in therapeutic range (TTR) was higher in CS compared to RMC (76.9% (interquartile range [IQR] 63.2–87.1%) vs. 69.5% (52.3–85.6%), p < 0.001). Crude rate of thromboembolic events (rate ratio [RR] 11.33 (95% confidence interval [CI] 1.85–465.26), p = 0.0015), clinically relevant bleeding (RR 6.80 (2.52–25.76), p < 0.001), hospitalizations (RR 2.54 (1.94–3.39), p < 0.001) and mortality under OAC (RR 5.89 (2.40–18.75), p < 0.001) were consistently higher in RMC compared with CS. Patients in RMC had higher risk for primary outcome (clinically relevant bleedings, thromboembolic events and mortality, hazard ratio [HR] 5.39 (95%CI 2.81–10.33), p < 0.0001), mortality (HR 5.54 (2.22–13.84), p = 0.00025), thromboembolic events (HR 6.41 (1.51–27.24), p = 0.012), clinically relevant bleeding (HR 5.31 (1.89–14.89), p = 0.0015) and hospitalization (HR 1.84 (1.34–2.55), p = 0.0002). Benefits of CS care were still observed after adjusting for comorbidities and TTR. In conclusion, anticoagulation quality and outcome of VTE patients undergoing VKA treatment was significantly better in CS than in RMC. Patients treated in CS had lower rates of adverse events, hospitalizations and lower mortality. CS was prognostically relevant, beyond providing advantages of improved international ratio (INR) monitoring.

Lipids are important modifiers of protein function, particularly as parts of lipoproteins, which transport lipophilic substances and mediate cellular uptake of circulating lipids. As such, lipids are of particular interest as blood biological markers for cardiovascular disease (CVD) as well as for conditions linked to CVD such as atherosclerosis, diabetes mellitus, obesity and dietary states. Notably, lipid research is particularly well developed in the context of CVD because of the relevance and multiple causes and risk factors of CVD. The advent of methods for high-throughput screening of biological molecules has recently resulted in the generation of lipidomic profiles that allow monitoring of lipid compositions in biological samples in an untargeted manner. These and other earlier advances in biomedical research have shaped the knowledge we have about lipids in CVD. To evaluate the knowledge acquired on the multiple biological functions of lipids in CVD and the trends in their research, we collected a dataset of references from the PubMed database of biomedical literature focused on plasma lipids and CVD in human and mouse. Using annotations from these records, we were able to categorize significant associations between lipids and particular types of research approaches, distinguish non-biological lipids used as markers, identify differential research between human and mouse models, and detect the increasingly mechanistic nature of the results in this field. Using known associations between lipids and proteins that metabolize or transport them, we constructed a comprehensive lipid–protein network, which we used to highlight proteins strongly connected to lipids found in the CVD-lipid literature. Our approach points to a series of proteins for which lipid-focused research would bring insights into CVD, including Prostaglandin G/H synthase 2 (PTGS2, a.k.a. COX2) and Acylglycerol kinase (AGK). In this review, we summarize our findings, putting them in a historical perspective of the evolution of lipid research in CVD.

The integration of multi-omics data offers transformative potential for elucidating complex molecular mechanisms underlying biological processes and diseases. In this study, we developed a lipid–metabolite–protein network that combines a protein–protein interaction network and enzymatic and genetic interactions of proteins with metabolites and lipids to provide a unified framework for multi-omics integration. Using hyperbolic embedding, the network visualizes connections across omics layers, accessible through a user-friendly Shiny R (version 1.10.0) software package. This framework ranks molecules across omics layers based on functional proximity, enabling intuitive exploration. Application in a cardiovascular disease (CVD) case study identified lipids and metabolites associated with CVD-related proteins. The analysis confirmed known associations, like cholesterol esters and sphingomyelin, and highlighted potential novel biomarkers, such as 4-imidazoleacetate and indoleacetaldehyde. Furthermore, we used the network to analyze empagliflozin’s temporal effects on lipid metabolism. Functional enrichment analysis of proteins associated with lipid signatures revealed dynamic shifts in biological processes, with early effects impacting phospholipid metabolism and long-term effects affecting sphingolipid biosynthesis. Our framework offers a versatile tool for hypothesis generation, functional analysis, and biomarker discovery. By bridging molecular layers, this approach advances our understanding of disease mechanisms and therapeutic effects, with broad applications in computational biology and precision medicine.

Background. Anticoagulant therapy, the cornerstone treatment in acute venous thromboembolism (VTE), strongly impacts thrombin generation (TG). Until now, the appearance of the TG curve in platelet rich plasma (PRP) from patients with acute VTE has not been investigated. Methods. We analyzed the shape of TG curves measured in PARP of 180 acute VTE patients. Results. Normal shape of TG curves was observed in 110 patients, 50 patients showed no TG and 20 patients showed biphasic TG curve. The linear regression analysis, adjusted for age, sex, VTE clinical phenotypes and therapy showed that the appearance of biphasic curves is significantly associated with female sex, presence of cancer and therapy with Factor Xa inhibitors. Conclusions. This study demonstrated that despite taking anticoagulants, TG in presence of platelets is still present in the majority of acute VTE patients. Appearance of unusual TG curves is strongly related to the intake of anti-Factor Xa inhibitors. The clinical relevance of biphasic TG curve appearance requires further investigation.

Oral anticoagulation (OAC) is effective at preventing and treating thromboses and thromboembolism in patients with normal renal function. We aimed to research the impact of severe renal failure (RF) on patient outcome and to determine the potential benefit of caring for these patients in a specialized coagulation service (CS). A total of 1516 usual medical care patients and 756 CS-managed patients of the thrombEVAL multicenter (21 centers), prospective, cohort study (NCT01809015) were analyzed in a 3-year follow-up. Patients with RF (serum creatinine >3 mg/dL, no renal replacement therapy) were compared to patients without RF in usual care and a CS. The fluctuations in the international normalized ratios were significantly lower in CS-managed patients, and regardless of treatment in usual care or a CS, the time in therapeutic range was significantly lower in RF patients. Cox regression-adjusted hazard ratios for long-term outcome (1.5, 95% CI: 1.22–1.83, p < 0.001), death (1.62, CI: 1.27–2.08, p < 0.001), and hospitalization (1.21, CI: 1.02–1.44, p = 0.032) were significantly higher in RF patients in usual care. Furthermore, there was a trend of more bleeding events in RF patients. CS-treated patients had significantly lower adjusted hazard ratios for death (0.24, CI: 0.14–0.39, p < 0.001), hospitalizations (0.41, CI: 0.34–0.5, p < 0.001), clinically relevant bleeding (0.29, CI: 0.18–0.47, p < 0.001), and major bleeding (0.33, CI: 0.18–0.59, p < 0.001). Thus, patients who required oral anticoagulation therapy benefitted significantly from being managed in a specialized coagulation service, regardless of their renal function.