Prevalence of current suicidal thoughts and lifetime suicide attempts in individuals with cancer and other chronic diseases in Germany: Evidence for differential associations from a representative community cohort.

BACKGROUND: Research indicates an elevated risk for suicidal thoughts and behaviors (STBs)1 among individuals with cancer, but community-based studies on the prevalence of STBs in comparison to the general population and other chronic diseases are lacking. METHODS: Data was drawn from the representative population-based, prospective Gutenberg Health Study (GHS).2 Participants (N = 12,382; age: M = 59.5, SD = 10.8; 48.9 % women) completed highly standardized medical assessments and validated questionnaires such as the PHQ-9. In addition to prevalence estimates (stratified by STBs and gender), logistic regression models were calculated (controlling for confounders). RESULTS: The sample included 1910 individuals with cancer, 8.2 % of whom reported current suicidal thoughts and 2.0 % reported lifetime suicide attempts. There was neither a significant association between a cancer diagnosis and suicidal thoughts (p = .077) nor suicide attempts (p = .17) in models adjusting for age, gender, and income. Other chronic diseases were linked to suicidal thoughts and attempts only in men. LIMITATIONS: Although the investigation of the two kinds of STB are a strength of the study, the items' different time frames complicate comparisons. In addition, the cross-sectional design limits the ability to understand observed relationships and to identify periods of risk. CONCLUSION: This study expands the evidence base regarding the vulnerability to STBs in individuals with cancer, including long-term survivors. It highlights their heterogeneity, differential risk factors underlying suicidal thoughts and attempts, and the relevance of other (contextual) factors shaping an individual's susceptibility to suicidal crises.

Change of self-rated physical health predicts mortality in aging individuals: results of a population-based cohort study.

BACKGROUND: Self-rated physical health (SRPH) is known as an important predictor of mortality. Previous studies mostly used baseline values of self-rated health to predict long-term mortality. The effect of change in self-rated physical health on mortality during the course of aging has rarely been researched. The present study aimed to determine SRPH over time in women and men of an aging population, assess whether and how change in SRPH affects mortality while adjusting for known determinants of mortality, and test effect modification by sex on the relation between course of SRPH and mortality. METHODS: Data of N = 12,423 respondents of the 5-year follow-up of the Gutenberg Health Study (GHS) with participation at the baseline assessment were analysed. All-cause mortality from 5-year follow-up onwards was defined as the primary outcome. SRPH was assessed by a single item. Cox proportional hazards models with adjustment for age, sex, socio-economic status and physical diseases were fitted to assess the predictive power of baseline score and course of SRPH. Additionally, effect modification by sex was assessed. RESULTS: During a median follow-up period of 7.3 years (quartiles 6.0-8.5 years), 618 (5%) participants died. Overall, 70.9% of the participants indicated good or very good SRPH at baseline (T1) and follow-up (T2), 6.9% rated their SRPH as not so good at T1 and T2, and 0.6% reported bad SRPH at T1 and T2. An improvement of SRPH was indicated by 9.6% and 12.0% indicated deterioration of their SRPH. Change in SRPH added substantial predictive information to the Cox proportional hazards models, when adjusting for relevant covariates. In men, deterioration and constantly bad SRPH were associated with the strongest increase in risk of mortality by 87%, resp. 228%. While improvements increased mortality risk in men (67%), women with an improved SRPH had a lower risk (57%). CONCLUSION: A sizeable subgroup of aging participants reported deterioration of SRPH over five years. The association between change of SRPH and mortality is modified by sex. Deterioration of SRPH predicts mortality over baseline-assessment even when adjusted for relevant covariates. SRPH should be assessed regularly as part of an older individual's health evaluation. Deterioration, constantly bad and improved SRPH should be taken seriously as unfavorable prognostic indicators, the latter only in men.

Sarcopenia influences usage of reperfusion treatment in patients with pulmonary embolism aged 75 years and older.

Background: Although pulmonary embolism (PE) and sarcopenia are common diseases, only a few studies have assessed the impact of sarcopenia in PE on usage of reperfusion treatments in PE. Methods: All hospitalizations of PE patients aged ≥75 years 2005-2020 in Germany were included in this study and stratified for sarcopenia. Impact of sarcopenia on treatment procedures and adverse in-hospital events were investigated. Results: Overall, 576,364 hospitalizations of PE patients aged ≥75 years (median age 81.0 [78.0-85.0] years; 63.3 % females) were diagnosed in Germany during the observational period 2005-2020. Among these, 2357 (0.4 %) were coded with sarcopenia. PE patients with sarcopenia were in median 2 years older (83.0 [79.0-87.0] vs. 81.0 [78.0-85.0] years, P<0.001) and showed an aggravated comorbidity-profile (Charlson Comorbidity Index 7.00 [5.00-9.00] vs. 6.00 [4.00-7.00], P<0.001). Although signs of hemodynamic compromise such as shock (5.2 % vs. 4.1 %, P=0.005) and tachycardia (4.1 % vs. 2.8 %, P<0.001) were more prevalent in sarcopenic PE patients, systemic thrombolysis (1.9 % vs. 3.5 %, P<0.001) was less often used in these patients. Sarcopenia was independently related to an underuse of systemic thrombolysis (OR 0.537 [95 %CI 0.398-0.725], P<0.001). This underuse might driven by higher rates of bleeding events (gastro-intestinal bleeding: 3.1 % vs. 1.9 %, P<0.001, necessity of transfusion of blood constituents: 18.9 % vs. 11.3 %, P<0.001), but also stroke (5.6 % vs. 3.3 %, P<0.001). Conclusions: Sarcopenia represents a widely overlooked condition in PE patients. Although sarcopenic PE patients were more often afflicted by hemodynamic compromise, systemic thrombolysis was less often administered. This underuse might be caused by contraindications like bleeding events and stroke.

Effects of Short-Term Gluten-Free Diet on Cardiovascular Biomarkers and Quality of Life in Healthy Individuals: A Prospective Interventional Study.

INTRODUCTION: The exposome concept includes nutrition as it significantly influences human health, impacting the onset and progression of diseases. Gluten-containing wheat products are an essential source of energy for the world's population. However, a rising number of non-celiac healthy individuals tend to reduce or completely avoid gluten-containing cereals for health reasons. AIM AND METHODS: This prospective interventional human study aimed to investigate whether short-term gluten avoidance improves cardiovascular endpoints and quality of life (QoL) in healthy volunteers. A cohort of 27 participants followed a strict gluten-free diet (GFD) for four weeks. Endothelial function measured by flow-mediated vasodilation (FMD), blood testing, plasma proteomics (Olink®) and QoL as measured by the World Health Organisation Quality-of-Life (WHOQOL) survey were investigated. RESULTS: GFD resulted in decreased leucocyte count and C-reactive protein levels along with a trend of reduced inflammation biomarkers determined by plasma proteomics. A positive trend indicated improvement in FMD, whereas other cardiovascular endpoints remained unchanged. In addition, no improvement in QoL was observed. CONCLUSION: In healthy individuals, a short-term GFD demonstrated anti-inflammatory effects but did not result in overall cardiovascular improvement or enhanced quality of life.

Incidence and impact of venous thromboembolism in hospitalized patients with acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) and venous thromboembolism (VTE) remain common and potentially lethal disease entities. AP might be an important trigger of systemic inflammtion and may activate the coagulation system with increased VTE risk. METHODS: The German nationwide inpatient sample was screened for patients admitted due to AP (ICD-code K85) 2005-2019. AP hospitalizations were stratified for VTE as well as risk-factors and the impact of VTE on in-hospital case-fatality rate were investigated. RESULTS: Overall, 797,364 hospitalizations of patients due to AP (aged in median 56.0 [IQR 44.0-71.0] years), 39.2 % females) were detected in Germany 2005-2019. Incidence of VTE in hospitalized AP patients was 1764.8 per 100,000 hospitalizations (1.8 %) with highest VTE rate between 5th and 6th decade. Cancer (OR 1.656 [95 %CI 1.513-1.812], P < 0.001), any surgery (OR 4.063 [95 %CI 3.854-4.284], P < 0.001), and heart failure (OR 1.723 [95 %CI 1.619-1.833], P < 0.001) were independently associated with VTE occurrence. Case-fatality (8.8 % vs. 2.7 %, P < 0.001) was more than 3-fold higher in AP patients with than without VTE. VTE was associated with increased case-fatality in AP patients (OR 3.925 [95 %CI 3.684-4.181], P < 0.001). CONCLUSIONS: VTE is a life-threatening event in hospitalized AP patients associated with an almost 4-fold increased case-fatality rate. Cancer, any surgery, thrombophilia and heart failure were important risk factors for occurrence of VTE in AP.

Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation.

Aims: The cytokine interleukin-6 (IL-6) plays a central role in the inflammation cascade as well as cardiovascular disease progression. Since myeloid cells are a primary source of IL-6 formation, we aimed to generate a mouse model to study the role of myeloid cell-derived IL-6 in vascular disease. Methods and results: Interleukin-6-overexpressing (IL-6OE) mice were generated and crossed with LysM-Cre mice, to generate mice (LysM-IL-6OE mice) overexpressing the cytokine in myeloid cells. Eight- to 12-week-old LysM-IL-6OE mice spontaneously developed inflammatory colitis and significantly impaired endothelium-dependent aortic relaxation, increased aortic reactive oxygen species (ROS) formation, and vascular dysfunction in resistance vessels. The latter phenotype was associated with decreased survival. Vascular dysfunction was accompanied by a significant accumulation of neutrophils, monocytes, and macrophages in the aorta, increased myeloid cell reactivity (elevated ROS production), and vascular fibrosis associated with phenotypic changes in vascular smooth muscle cells. In addition to elevated Mcp1 and Cxcl1 mRNA levels, aortae from LysM-IL-6OE mice expressed higher levels of inducible NO synthase and endothelin-1, thus partially accounting for vascular dysfunction, whereas systemic blood pressure alterations were not observed. Bone marrow (BM) transplantation experiments revealed that vascular dysfunction and ROS formation were driven by BM cell-derived IL-6 in a dose-dependent manner. Conclusion: Mice with conditional overexpression of IL-6 in myeloid cells show systemic and vascular inflammation as well as endothelial dysfunction. A decrease in circulating IL-6 levels by replacing IL-6-producing myeloid cells in the BM improved vascular dysfunction in this model, underpinning the relevant role of IL-6 in vascular disease.

Quantitative flow ratio or angiography for the assessment of non-culprit lesions in acute coronary syndromes, a randomized trial.

BACKGROUND: Patients undergoing percutaneous coronary intervention for acute coronary syndromes often have multivessel disease (MVD). Quantitative flow ratio (QFR) is an angiography-based technology that may help quantify the functional significance of non-culprit lesions, with the advantage that measurements are possible also once the patient is discharged from the catheterization laboratory. AIM: Our two-center, randomized superiority trial aimed to test whether QFR, as compared to angiography, modifies the rate of non-culprit lesion interventions (primary functional endpoint) and improves the outcomes of patients with acute coronary syndromes and MVD (primary clinical endpoint). METHODS: In total, 202 consecutive patients (64 [56-71] years of age, 160 men) with STEMI (n = 69 (34%)), NSTEMI (n = 94 (47%)), or unstable angina (n = 39 (19%)) and MVD who had undergone successful treatment of all culprit lesions were randomized 1:1 to angiography- vs. QFR-guided delayed revascularization of 246 non-culprit stenoses (1.2/patient). RESULTS: The proportion of patients assigned to percutaneous intervention was not different between groups (angiography group: 45 (45%) vs. QFR: 56 (55%), P = 0.125; relative risk = 0.80 (0.60-1.06)). At 12 months, a primary clinical endpoint event (composite of death, nonfatal myocardial infarction, revascularization, and significant angina) occurred in 24 patients (angiography-guided) and 23 patients (QFR-guided; P = 0.637, HR = 1.16 [0.63-2.15]). None of its components was different between groups. DISCUSSION: QFR guidance based on analysis of images from the primary intervention was not associated with a difference in the rate of non-culprit lesion staged revascularization nor in the 12-month incidence of clinical events in patients with acute coronary syndromes and multivessel disease. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04808310).

Hypertensive Retinopathy is Not Associated with Low or High Birth Weight - Results from the Population-Based German Gutenberg Health Study.

This study investigates the association between self-reported birth weight (BW) and the prevalence of hypertensive retinopathy (HR) in a large population-based cohort in Germany, as part of the Gutenberg Health Study (GHS). The study involved analyzing fundus photographs of 6855 participants, aged 35 to 74, to assess signs of HR, classified according to the Mitchell-Wong Classification. The research aimed to explore the correlation between fetal growth restriction indicated by BW and the frequency of HR. The results showed that the frequency of HR did not significantly differ among groups with different BW ranges. In the univariable analysis, HR was initially associated with high BW, but this association disappeared after adjusting for age, sex, and cardiovascular risk factors. No association was found between low BW and HR. The study reveals novel insights as there are no prior population-based studies specifically exploring this association.

Environmentally Not So Friendly: Global Warming, Air Pollution, and Wildfires: JACC Focus Seminar, Part 1.

Environmental stresses are increasingly recognized as significant risk factors for adverse health outcomes. In particular, various forms of pollution and climate change are playing a growing role in promoting noncommunicable diseases, especially cardiovascular disease. Given recent trends, global warming and air pollution are now associated with substantial cardiovascular morbidity and mortality. As a vicious cycle, global warming increases the occurrence, size, and severity of wildfires, which are significant sources of airborne particulate matter. Exposure to wildfire smoke is associated with cardiovascular disease, and these effects are underpinned by mechanisms that include oxidative stress, inflammation, impaired cardiac function, and proatherosclerotic effects in the circulation. In the first part of a 2-part series on pollution and cardiovascular disease, this review provides an overview of the impact of global warming and air pollution, and because of recent events and emerging trends specific attention is paid to air pollution caused by wildfires.

Association between socioeconomic and psychosocial factors with use of interventional and surgical treatments and outcomes in patients with myocardial infarction - Inpatient data of the largest European health care system.

BACKGROUND: Myocardial infarction (MI) is an important driver of both morbidity and mortality on a global scale. Elucidating social inequalities may help to identify vulnerable groups as well as treatment imbalances and guide efforts to improve care for MI. METHODS: All hospitalized patient-cases with confirmed MI 2005-2020 in Germany were included in the study and stratified for socioeconomic or psychosocial factors (SPF) and the impact of SPF on treatment usage and adverse in-hospital events was analyzed. RESULTS: Overall, 4,409,597 hospitalizations of MI patients were included; of these, 17,297 (0.4 %) were coded with SPF. These patients were more often of female sex (49.4 % vs. 36.9 %, P<0.001), older (median 77.0 [IQR: 65.0-84.0] vs. 73.0 [62.0-81.0] years, P<0.001) and revealed an aggravated cardiovascular profile. Although SPF were independently associated with increased usage of cardiac catheterization (OR 1.174 [95 %CI 1.136-1.212]) and percutaneous coronary intervention (OR 1.167 [95 %CI 1.130-1.205]), they were accompanied by higher risk for a prolonged length of in-hospital stay >7 days (OR 1.236 [95 %CI 1.198-1.276]) and >10 days (OR 1.296 [95 %CI 1.254-1.339]). While SPF were associated with increased risk for deep venous thrombosis and/or thrombophlebitis (OR 1.634 [95 %CI 1.427-1.870]), pulmonary embolism (OR 1.337 [95 %CI 1.149-1.555]), and acute renal failure (OR 1.170 [95 %CI 1.105-1.240), these SPF were inversely associated with in-hospital case-fatality (OR 0.461 [95 %CI 0.433-0.490]). CONCLUSIONS: This study demonstrates that SPF in hospitalized MI patients have significant impacts on treatments and outcomes. Fortunately, our data did not revealed an underuse of interventional treatments in MI patients with SPF.

Water, Soil, Noise, and Light Pollution: JACC Focus Seminar, Part 2.

Various forms of pollution carry a substantial burden with respect to increasing the risk of causing and exacerbating noncommunicable diseases, especially cardiovascular disease. The first part of this 2-part series on pollution and cardiovascular disease provided an overview of the impact of global warming and air pollution. This second paper provides an overview of the impact of water, soil, noise, and light pollution on the cardiovascular system. This review discusses the biological mechanisms underlying these effects and potential environmental biometrics of exposure. What is clear from both these pollution papers is that significant efforts and redoubled urgency are needed to reduce the sources of pollution in our environment, to incorporate environmental risk factors into medical education, to provide resources for research, and, ultimately, to protect those who are particularly vulnerable and susceptible.

Guideline-endorsed follow-up after percutaneous valve therapies-non-attendance of TAVI and MitraClip patients.

BACKGROUND: Percutaneous valve therapies (PVT) are performed on a large number of patients. With increasing procedural volume, the need for follow-up has also increased. Follow-up in the heart valve clinic is endorsed by recent guidelines but utilization is unknown, making resource allocation in the clinic difficult. Central follow-up in valve centers may not be feasible for all patients in the future. METHODS: In our center, follow-up for PVT patients is scheduled at 1 month and 12 months after the index procedure. Patients are reminded of their appointment by invitation letters or phone calls. We analyzed 150 consecutive patients who underwent transcutaneous aortic valve implantation (TAVI) and MitraClip implantation (n = 300) at our center. RESULTS: At 1 month, 72.7% of patients attended their follow-up, while at 12 months the rate dropped to 58%. Patients who underwent TAVI were older than the MitraClip patients (82.7 vs. 76.1 years) but had lower mean logEuroSCORE (22.6% vs. 25.9%). There was no significant difference in 1­year mortality between TAVI and MitraClip patients (20% vs. 17.3%). By contrast, the rate of missed follow-up visits was higher for TAVI compared to MitraClip patients (52% vs. 33.3%; p = 0.002). Female patients less frequently attended follow-up (p = 0.005), whereas age, EuroSCORE, NYHA class, ejection fraction, and health status (EQ-5DVAS) were not predictors of attendance in multivariable analysis. Although the result of the EQ-5D assessment was not associated with mortality or attendance, completing the questionnaire was associated with overall survival (p < 0.001). CONCLUSION: In our heart valve clinic, we observed a high percentage of missed follow-up appointments (42% at 12 months) despite a structured follow-up plan. Factors significantly associated with non-attendance in multivariable analysis were female gender and having a TAVI rather than MitraClip. Future follow-up concepts should take such findings into account, and decentralized approaches need to be explored.

Quantifying Hemodynamic Cardiac Stress and Cardiomyocyte Injury in Normotensive and Hypertensive Acute Heart Failure.

BACKGROUND: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. METHODS: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90-140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). RESULTS: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611-1956) versus 827 (448-1419) pg/mL, and 5890 (2959-12,162) versus 4068 (1986-8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24-71) versus 33 (19-59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31-2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. CONCLUSION: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

Noise annoyance due to different sources is associated with tinnitus presence and distress in the general population.

BACKGROUND: The pathophysiology of tinnitus is not yet fully understood. Although there is a large amount of evidence associating traffic noise exposure with non-auditory health outcomes, there is no evidence regarding the impact of noise annoyance on auditory disorders such as tinnitus. OBJECTIVE: Thus, we aimed to investigate the association between noise annoyance due to different sources and tinnitus presence and distress in the general population. METHODS: Data of 6813 participants from a large German population-based cohort were used (Gutenberg Health Study). Participants were asked about the presence of tinnitus and how much they were bothered by it. In addition, information on annoyance from road traffic, aircraft, railways, industrial, and neighborhood noise during the day and sleep was collected through validated questionnaires. RESULTS: The prevalence of tinnitus was 27.3%, and the predominant sources of noise annoyance in these subjects were aircraft, neighborhood, and road traffic noise. Overall, logistic regression results demonstrated consistent positive associations between annoyance due to different noise sources and prevalent risk of tinnitus with increases in odds ratios ranging from 4 to 11% after adjustment for sex, age, and socioeconomic status. Likewise, consistent increases in odds ratios were observed for tinnitus distress in subjects with prevalent tinnitus. For instance, neighborhood noise annoyance during the sleep was associated with a 26% increase in tinnitus distress (OR 1.26, 95% CI 1.13; 1.39). IMPACT: This is the first study investigating the association between noise annoyance and tinnitus presence and distress in a large cohort of the general population. Our results indicate consistent and positive associations between various sources of noise annoyance and tinnitus. These unprecedented findings are highly relevant as noise annoyance and tinnitus are widespread. The precise etiology and locus of tinnitus remain unknown, but excessive noise exposure is thought to be among the major causes. This study suggests that transportation and neighborhood noise levels thought merely to contribute to annoyance and non-auditory health effects may be sufficient to cause or exacerbate tinnitus.

Drivers and recent trends of hospitalisation costs related to acute pulmonary embolism.

BACKGROUND AND AIMS: The socio-economic burden imposed by acute pulmonary embolism (PE) on European healthcare systems is largely unknown. We sought to determine temporal trends and identify cost drivers of hospitalisation for PE in Germany. METHODS AND RESULTS: We analysed the totality of reimbursed hospitalisation costs in Germany (G-DRG system) in the years 2016-2020. Overall, 484 884 PE hospitalisations were coded in this period. Direct hospital costs amounted to a median of 3572 (IQR, 2804 to 5869) euros, resulting in average total reimbursements of 710 million euros annually. Age, PE severity, comorbidities and in-hospital (particularly bleeding) complications were identified by multivariable logistic regression as significant cost drivers. Use of catheter-directed therapy (CDT) constantly increased (annual change in the absolute proportion of hospitalisations with CDT + 0.40% [95% CI + 0.32% to + 0.47%]; P < 0.001), and it more than doubled in the group of patients with severe PE (28% of the entire population) over time. Although CDT use was overall associated with increased hospitalisation costs, this association was no longer present (adjusted OR 1.02 [0.80-1.31]) in patients with severe PE and shock; this was related, at least in part, to a reduction in the median length of hospital stay (for 14.0 to 8.0 days). CONCLUSIONS: We identified current and emerging cost drivers of hospitalisation for PE, focusing on severe disease and intermediate/high risk of an adverse early outcome. The present study may inform reimbursement decisions by policymakers and help to guide future health economic analysis of advanced treatment options for patients with PE.

Endothelial PTP1B Deletion Promotes VWF Exocytosis and Venous Thromboinflammation.

BACKGROUND: Endothelial activation promotes the release of procoagulant extracellular vesicles and inflammatory mediators from specialized storage granules. Endothelial membrane exocytosis is controlled by phosphorylation. We hypothesized that the absence of PTP1B (protein tyrosine phosphatase 1B) in endothelial cells promotes venous thromboinflammation by triggering endothelial membrane fusion and exocytosis. METHODS: Mice with inducible endothelial deletion of PTP1B (End.PTP1B-KO) underwent inferior vena cava ligation to induce stenosis and venous thrombosis. Primary endothelial cells from transgenic mice and human umbilical vein endothelial cells were used for mechanistic studies. RESULTS: Vascular ultrasound and histology showed significantly larger venous thrombi containing higher numbers of Ly6G (lymphocyte antigen 6 family member G)-positive neutrophils in mice with endothelial PTP1B deletion, and intravital microscopy confirmed the more pronounced neutrophil recruitment following inferior vena cava ligation. RT2 PCR profiler array and immunocytochemistry analysis revealed increased endothelial activation and adhesion molecule expression in primary End.PTP1B-KO endothelial cells, including CD62P (P-selectin) and VWF (von Willebrand factor). Pretreatment with the NF-κB (nuclear factor kappa B) kinase inhibitor BAY11-7082, antibodies neutralizing CD162 (P-selectin glycoprotein ligand-1) or VWF, or arginylglycylaspartic acid integrin-blocking peptides abolished the neutrophil adhesion to End.PTP1B-KO endothelial cells in vitro. Circulating levels of annexin V+ procoagulant endothelial CD62E+ (E-selectin) and neutrophil (Ly6G+) extracellular vesicles were also elevated in End.PTP1B-KO mice after inferior vena cava ligation. Higher plasma MPO (myeloperoxidase) and Cit-H3 (citrullinated histone-3) levels and neutrophil elastase activity indicated neutrophil activation and extracellular trap formation. Infusion of End.PTP1B-KO extracellular vesicles into C57BL/6J wild-type mice most prominently enhanced the recruitment of endogenous neutrophils, and this response was blunted in VWF-deficient mice or by VWF-blocking antibodies. Reduced PTP1B binding and tyrosine dephosphorylation of SNAP23 (synaptosome-associated protein 23) resulting in increased VWF exocytosis and neutrophil adhesion were identified as mechanisms, all of which could be restored by NF-κB kinase inhibition using BAY11-7082. CONCLUSIONS: Our findings show that endothelial PTP1B deletion promotes venous thromboinflammation by enhancing SNAP23 phosphorylation, endothelial VWF exocytosis, and neutrophil recruitment.