Categorization of Patients with Pulmonary Embolism by Charlson Comorbidity Index.

BACKGROUND: Short-term outcomes of pulmonary embolism are closely related to right ventricular dysfunction and patient's hemodynamic status, but also to individual comorbidity profile. However, the impact of patients' comorbidities on survival during pulmonary embolism might be underrated. Although the Charlson Comorbidity Index (CCI) is the most extensively studied comorbidity index for detecting comorbidity burden, studies analysing the impact of CCI on pulmonary embolism patients' survival are limited. METHODS: We used the German nationwide inpatient sample to analyse all hospitalised patients with pulmonary embolism in Germany 2005-2020 and calculated CCI for each patient, compared the CCI classes (very-low: CCI=0points, mild: CCI=1-2 points, moderate: CCI=3-4, high severity: CCI>4 points) and impact of CCI class on outcomes. RESULTS: Overall, 1,373,145 hospitalizations of patients with acute pulmonary embolism (53.0% females, 55.9% aged ≥70years) were recorded in Germany between 2005 and 2020; the CCI class stratified them. Among these, 100,156 (7.3%) were categorized as very-low, 221,545; (16.1%) as mild, 394,965 (28.8%) as moderate, and 656,479 (47.8%) as patients with a high comorbidity burden according to CCI class. In-hospital case-fatality increased depending on the CCI class: 3.6% in very-low, 6.5% in mild, 12.1% in moderate and 22.1% in high CCI class (P<0.001). CCI class was associated with increased in-hospital case-fatality (OR 2.014 [95%CI 2.000-2.027], P<0.001). CONCLUSION: Our study results may help to better understand and measure the association between an aggravated comorbidity profile and increased in-hospital case-fatality in patients with pulmonary embolism.

Obesity-related inflammatory protein signature in cardiovascular clinical outcomes: results from the Gutenberg Health Study.

OBJECTIVE: The objective of this study was to investigate whether an obesity-related inflammatory protein signature (OIPS) is associated with adverse cardiovascular events. METHODS: The Olink Target 96 Inflammation panel was performed in 6662 participants from the population-based Gutenberg Health Study (GHS). The OIPS was selected by a logistic regression model, and its association with cardiovascular outcomes was evaluated by Cox regression analysis. The GHS-derived OIPS was externally validated in the MyoVasc study. RESULTS: The identified OIPS entailed 21 proteins involved in chemokine activity, tumor necrosis factor (TNF) receptor binding, and growth factor receptor binding. The signature revealed a novel positive association of axis inhibition protein 1 with obesity. The OIPS was associated with increased risk of all-cause and cardiac deaths, major adverse cardiovascular events, and incident coronary artery disease, independent of clinical covariates and established risk instruments. A BMI-stratified analysis confirmed the association of OIPS with increased death in those with obesity and overweight and with increased risk for coronary artery disease in those with obesity. The association of OIPS with increased risk of all-cause and cardiac deaths was validated in the MyoVasc cohort. CONCLUSIONS: The OIPS showed a significant association with adverse clinical outcomes, particularly in those with overweight and obesity, and represents a promising tool for identifying patients at higher risk for worse cardiovascular outcomes.

The Urban Environment and Cardiometabolic Health.

Urban environments contribute substantially to the rising burden of cardiometabolic diseases worldwide. Cities are complex adaptive systems that continually exchange resources, shaping exposures relevant to human health such as air pollution, noise, and chemical exposures. In addition, urban infrastructure and provisioning systems influence multiple domains of health risk, including behaviors, psychological stress, pollution, and nutrition through various pathways (eg, physical inactivity, air pollution, noise, heat stress, food systems, the availability of green space, and contaminant exposures). Beyond cardiometabolic health, city design may also affect climate change through energy and material consumption that share many of the same drivers with cardiometabolic diseases. Integrated spatial planning focusing on developing sustainable compact cities could simultaneously create heart-healthy and environmentally healthy city designs. This article reviews current evidence on the associations between the urban exposome (totality of exposures a person experiences, including environmental, occupational, lifestyle, social, and psychological factors) and cardiometabolic diseases within a systems science framework, and examines urban planning principles (eg, connectivity, density, diversity of land use, destination accessibility, and distance to transit). We highlight critical knowledge gaps regarding built-environment feature thresholds for optimizing cardiometabolic health outcomes. Last, we discuss emerging models and metrics to align urban development with the dual goals of mitigating cardiometabolic diseases while reducing climate change through cross-sector collaboration, governance, and community engagement. This review demonstrates that cities represent crucial settings for implementing policies and interventions to simultaneously tackle the global epidemics of cardiovascular disease and climate change.

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.

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.

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.

Transportation Noise Pollution and Cardiovascular Health.

Epidemiological studies have found that transportation noise increases the risk for cardiovascular morbidity and mortality, with solid evidence for ischemic heart disease, heart failure, and stroke. According to the World Health Organization, at least 1.6 million healthy life years are lost annually from traffic-related noise in Western Europe. Traffic noise at night causes fragmentation and shortening of sleep, elevation of stress hormone levels, and increased oxidative stress in the vasculature and the brain. These factors can promote vascular (endothelial) dysfunction, inflammation, and arterial hypertension, thus elevating cardiovascular risk. The present review focusses on the indirect, nonauditory cardiovascular health effects of noise. We provide an updated overview of epidemiological research on the effects of transportation noise on cardiovascular risk factors and disease, and mechanistic insights based on the latest clinical and experimental studies and propose new risk markers to address noise-induced cardiovascular effects in the general population. We will discuss the potential effects of noise on vascular dysfunction, oxidative stress, and inflammation in humans and animals. We will elaborately explain the underlying pathomechanisms by alterations of gene networks, epigenetic pathways, circadian rhythm, signal transduction along the neuronal-cardiovascular axis, and metabolism. We will describe current and future noise mitigation strategies. Finally, we will conduct an overall evaluation of the status of the current evidence of noise as a significant cardiovascular risk factor.

Impact of depersonalization on the course of depression: longitudinal observations from the gutenberg health study.

BACKGROUND: Symptoms of depersonalization (DP) and derealization (DR) are a risk factor for more severe impairment, non-response to various treatments, and a chronic course. In this study, we investigated the effects of DP/DR symptoms in patients with clinically significant depressive symptoms on clinical characteristics and various outcomes in a representative population-based sample with a 5-year follow-up. METHODS: The middle-aged sample comprised n = 10,422 persons at baseline, of whom n = 9,301 were free from depressive and DP/DR symptoms. N = 522 persons had clinically significant depression (PHQ-9 ≥ 10) and co-occurring DP/DR symptoms, and n = 599 persons had clinically significant depression (PHQ-9 ≥ 10) without DP/DR symptoms. RESULTS: There were substantial health disparities between persons with and without depression. These disparities concerned a wide range of life domains, including lower quality of the recalled early life experiences with the parents, current socioeconomic status, social integration (partnership, loneliness), current social and interpersonal stressors (family, work), functional bodily complaints (e.g., tinnitus, migraine, chest pain), unhealthy lifestyle, and the prevalence of already developed physical diseases. These disparities persisted to the 5-year follow-up and were exceptionally severe for depressed persons with co-occurring DP/DR symptoms. Among the depressed persons, the co-occurrence of DP/DR symptoms more than doubled the risk for recurrence or persistence of depression. Only 6.9% of depressed persons with DP/DR symptoms achieved remission at the 5-year follow-up (PHQ-9 < 5). Depression with and without co-occurring DP/DR worsened self-rated physical health significantly. The impact of depression with co-occurring DP/DR on the worsening of the self-rated physical health status was stronger than those of age and major medical diseases (e.g., heart failure). However, only depression without DP/DR was associated with mortality in a hazard regression analysis adjusted for age, sex, and lifestyle. CONCLUSIONS: The results demonstrated that DP/DR symptoms represent an important and easily assessable prognostic factor for the course of depression and health outcomes. Given the low remission rates for depression in general and depression with DP/DR in particular, efforts should be made to identify and better support this group, which is disadvantaged in many aspects of life.

Noise annoyance and cardiovascular disease risk: results from a 10-year follow-up study.

The relationship between noise annoyance and risk of cardiovascular disease (CVD) still needs to be fully elucidated. Thus, we examined the relationship between noise annoyance and CVD risk in a large population-based cohort study. Cross-sectional (N = 15,010, aged 35-74 years, baseline investigation period 2007-2012) and prospective data (5- and 10-year follow-up from 2012 to 2022) from the Gutenberg Health Study were used to examine the relationship between noise annoyance due to different sources and risk of prevalent and incident CVD comprising atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and venous thromboembolism. In cross-sectional analyses, noise annoyance was an independent risk factor for prevalent CVD, with the strongest associations seen for noise annoyance during sleep (e.g., neighborhood noise annoyance: odds ratio 1.20, 95% confidence interval 1.13-1.27, p < 0.0001). While in the 10-year follow-up, mostly positive associations (although not significant) between noise annoyance and incident CVD were observed, no indication of increased CVD risk was observed after 5 years of follow-up. Noise annoyance due to different sources was associated with prevalent CVD, whereas only weak associations with incident CVD were found. Further large-scale studies are needed to establish the relationship between noise annoyance and risk of CVD.

Outcomes of COMBO therapy for severe mitral regurgitation compared with transcatheter edge-to-edge repair.

Background: There are different types of transcatheter mitral valve repair (TMVr) currently in clinical use, including leaflet approximation, annular cinching, and restoration of the chordal apparatus of the mitral valve (MV). While the concomitant combination (COMBO) therapy of mitral transcatheter edge-to-edge repair (M-TEER) with another TMVr concept has been proven feasible, potentially offering patient-tailored treatment for severe mitral regurgitation (MR), a comparison with M-TEER alone has not been made. Aims: To evaluate the procedural and clinical outcome of COMBO therapies compared with M-TEER alone. Methods: We included consecutive patients undergoing COMBO and M-TEER between March 2015 and April 2018 at our Heart Valve Center, while excluding patients presenting a case of redo or with previous MV surgery. Procedural outcomes and all-cause mortality were compared between COMBO therapy vs. M-TEER alone. Results: A total of 357 patients (mean age 78.9 ± 7.0 years, 53.2% male, M-TEER n = 322, COMBO n = 35; COMBO: MitraClip and the Carillon mitral contour system n = 26, MitraClip and Cardioband n = 5, and MitraClip and NeoChord n = 4) were analyzed. Patients with COMBO therapy had larger left chamber sizes, a lower left ventricular systolic ejection fraction (LVEF; COMBO: 37.4 ± 13.8%, M-TEER: 47.9 ± 14.3%, p < 0.001), and a more severe MR grade (p < 0.001). There were no significant differences in the prevalence of residual MR ≧2+. However, the need for re-intervention, always employing M-TEER, was more common in the COMBO group. During a mean 3.6-year long-term follow-up, there was no significant difference of all-cause mortality between both groups (Log rank p = 0.921). Conclusions: COMBO therapy may still be a beneficial therapy option for patients with severe MR who already have a more dilated left ventricle (LV), a more severe MR, and a more pronounced LV systolic dysfunction. The higher need for re-intervention in the COMBO group may signal more complex anatomies and possibly underlines the necessity of treating significant MR earlier. Future research is required to establish the COMBO approach as a toolbox-like treatment option, thus offering a patient-tailored approach depending on the individual anatomy and pathology.

Crosstalk between Oxidative Stress and Inflammation Caused by Noise and Air Pollution-Implications for Neurodegenerative Diseases.

Neurodegenerative diseases are often referred to as diseases of old age, and with the aging population, they are gaining scientific and medical interest. Environmental stressors, most notably traffic noise and air pollution, have recently come to the forefront, and have emerged as disease risk factors. The evidence for a connection between environmental risk factors and neurodegenerative disease is growing. In this review, the most common neurodegenerative diseases and their epidemiological association with traffic noise and air pollution are presented. Also, the most important mechanisms involved in neurodegenerative disease development, oxidative stress, and neuroinflammation are highlighted. An overview of the in vivo findings will provide a mechanistic link between noise, air pollution, and neurodegenerative pathology. Finally, the importance of the direct and indirect pathways, by which noise and air pollution cause cerebral damage, is discussed. More high-quality data are still needed from both epidemiological and basic science studies in order to better understand the causal connection between neurodegenerative diseases and environmental risk factors.

Role of inflammatory signaling pathways involving the CD40-CD40L-TRAF cascade in diabetes and hypertension-insights from animal and human studies.

CD40L-CD40-TRAF signaling plays a role in atherosclerosis progression and affects the pathogenesis of coronary heart disease (CHD). We tested the hypothesis that CD40L-CD40-TRAF signaling is a potential therapeutic target in hyperlipidemia, diabetes, and hypertension. In mouse models of hyperlipidemia plus diabetes (db/db mice) or hypertension (1 mg/kg/d angiotensin-II for 7 days), TRAF6 inhibitor treatment (2.5 mg/kg/d for 7 or 14 days) normalized markers of oxidative stress and inflammation. As diabetes and hypertension are important comorbidities aggravating CHD, we explored whether the CD40L-CD40-TRAF signaling cascade and their associated inflammatory pathways are expressed in CHD patients suffering from comorbidities. Therefore, we analyzed vascular bypass material (aorta or internal mammary artery) and plasma from patients with CHD with diabetes and/or hypertension. Our Olink targeted plasma proteomic analysis using the IMMUNO-ONCOLOGY panel revealed a pattern of step-wise increase for 13/92 markers of low-grade inflammation with significant changes. CD40L or CD40 significantly correlated with 38 or 56 other inflammatory targets. In addition, specific gene clusters that correlate with the comorbidities were identified in isolated aortic mRNA of CHD patients through RNA-sequencing. These signaling clusters comprised CD40L-CD40-TRAF, immune system, hemostasis, muscle contraction, metabolism of lipids, developmental biology, and apoptosis. Finally, immunological analysis revealed key markers correlated with comorbidities in CHD patients, such as CD40L, NOX2, CD68, and 3-nitrotyrosine. These data indicate that comorbidities increase inflammatory pathways in CHD, and targeting these pathways will be beneficial in reducing cardiovascular events in CHD patients with comorbidities.

Bi-Gaussian analysis reveals distinct education-related alterations in spherical equivalent and axial length-results from the Gutenberg Health Study.

PURPOSE: The aim of this study is to investigate the distribution of spherical equivalent and axial length in the general population and to analyze the influence of education on spherical equivalent with a focus on ocular biometric parameters. METHODS: The Gutenberg Health Study is a population-based cohort study in Mainz, Germany. Participants underwent comprehensive ophthalmologic examinations as part of the 5-year follow-up examination in 2012-2017 including genotyping. The spherical equivalent and axial length distributions were modeled with gaussian mixture models. Regression analysis (on person-individual level) was performed to analyze associations between biometric parameters and educational factors. Mendelian randomization analysis explored the causal effect between spherical equivalent, axial length, and education. Additionally, effect mediation analysis examined the link between spherical equivalent and education. RESULTS: A total of 8532 study participants were included (median age: 57 years, 49% female). The distribution of spherical equivalent and axial length follows a bi-Gaussian function, partially explained by the length of education (i.e., < 11 years education vs. 11-20 years). Mendelian randomization indicated an effect of education on refractive error using a genetic risk score of education as an instrument variable (- 0.35 diopters per SD increase in the instrument, 95% CI, - 0.64-0.05, p = 0.02) and an effect of education on axial length (0.63 mm per SD increase in the instrument, 95% CI, 0.22-1.04, p = 0.003). Spherical equivalent, axial length and anterior chamber depth were associated with length of education in regression analyses. Mediation analysis revealed that the association between spherical equivalent and education is mainly driven (70%) by alteration in axial length. CONCLUSIONS: The distribution of axial length and spherical equivalent is represented by subgroups of the population (bi-Gaussian). This distribution can be partially explained by length of education. The impact of education on spherical equivalent is mainly driven by alteration in axial length.

Current and past depression as risk factors for incident type 2 diabetes mellitus and pre-diabetes in men and women: evidence from a longitudinal community cohort.

BACKGROUND: Depression is associated with an increased risk for type 2 diabetes mellitus. However, depression may take different courses, and it is not fully understood how these affect the development of diabetes. It is further to be determined whether sex modifies the association between depression and type 2 diabetes. METHODS: We analyzed data from the Gutenberg Health Study, a longitudinal and population-based cohort study (N = 15,010) in Germany. Depressive symptoms (measured by PHQ-9), history of depression, diabetes mellitus, and relevant covariates were assessed at baseline, and the outcomes of prediabetes and type 2 diabetes mellitus were evaluated 5 years later. Logistic regression was used to estimate odds ratios of incident prediabetes and type 2 diabetes mellitus, adjusting for potential confounders as identified in a Directed Acyclic Graph. RESULTS: In the confounder adjusted model, current depression (PHQ-9 ≥ 10 at baseline; OR = 1.79, 95% CI = 1.11 to 2.74, p = 0.011), and persistent depression had a statistically significant (OR = 2.44, 95% CI = 1.62 to 3.54, p = 0.005) effect on incident type 2 diabetes mellitus. A history of depression without current depression had no statistically significant effect on type 2 diabetes (OR = 1.00, 95% CI = 0.68 to 1.43, p = 0.999). The effect of depression on incident diabetes did not differ significantly between women (OR = 2.02; 95% CI = 1.32 to 3.09) and men (OR = 2.16; 95% CI = 1.41 to 3.31; p-value for interaction on the multiplicative scale p = 0.832 and on the additive scale p = 0.149). Depression did not have a significant effect on incident prediabetes. CONCLUSION: This study shows how the history and trajectory of depression shape the risk for diabetes. This raises interesting questions on the cumulative effects of depression trajectories on diabetes and body metabolism in general. Depression can negatively affect physical health, contributing to increased morbidity and mortality in people with mental disorders.

Endothelial Overexpression of TGF-ß-Induced Protein Impairs Venous Thrombus Resolution: Possible Role in CTEPH.

Endothelial cells play a critical role during venous thrombus remodeling, and unresolved, fibrotic thrombi with irregular vessels obstruct the pulmonary artery in patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study sought to identify endothelial mediators of impaired venous thrombus resolution and to determine their role in the pathogenesis of the vascular obstructions in patients with CTEPH. Endothelial cells outgrown from pulmonary endarterectomy specimens (PEA) were processed for mRNA profiling, and nCounter gene expression and immunohistochemistry analysis of PEA tissue microarrays and immunoassays of plasma were used to validate the expression in CTEPH. Lentiviral overexpression in human pulmonary artery endothelial cells (HPAECs) and exogenous administration of the recombinant protein into C57BL/6J mice after inferior Vena cava ligation were employed to assess their role for venous thrombus resolution. RT2 PCR profiler analysis demonstrated the significant overexpression of factors downstream of transforming growth factor beta (TGFß), that is TGFß-Induced Protein (TGFBI or BIGH3) and transgelin (TAGLN), or involved in TGFß signaling, that is follistatin-like 3 (FSTL3) and stanniocalcin-2 (STC2). Gene expression and immunohistochemistry analysis of tissue microarrays localized potential disease candidates to vessel-rich regions. Lentiviral overexpression of TGFBI in HPAECs increased fibrotic remodeling of human blood clots in vitro, and exogenous administration of recombinant TGFBI in mice delayed venous thrombus resolution. Significantly elevated plasma TGFBI levels were observed in patients with CTEPH and decreased after PEA. Our findings suggest that overexpression of TGFBI in endothelial promotes venous thrombus non-resolution and fibrosis and is causally involved in the pathophysiology of CTEPH.

Air pollution exposure and cardiometabolic risk.

The Global Burden of Disease assessment estimates that 20% of global type 2 diabetes cases are related to chronic exposure to particulate matter (PM) with a diameter of 2·5 µm or less (PM2·5). With 99% of the global population residing in areas where air pollution levels are above current WHO air quality guidelines, and increasing concern in regard to the common drivers of air pollution and climate change, there is a compelling need to understand the connection between air pollution and cardiometabolic disease, and pathways to address this preventable risk factor. This Review provides an up to date summary of the epidemiological evidence and mechanistic underpinnings linking air pollution with cardiometabolic risk. We also outline approaches to improve awareness, and discuss personal-level, community, governmental, and policy interventions to help mitigate the growing global public health risk of air pollution exposure.

Vascular dysfunction and arterial hypertension in experimental celiac disease are mediated by gut-derived inflammation and oxidative stress.

AIMS: We examined the cardiovascular effects of celiac disease (CeD) in a humanized mouse model, with a focus on vascular inflammation, endothelial dysfunction, and oxidative stress. METHODS AND RESULTS: NOD.DQ8 mice genetically predisposed to CeD were subjected to a diet regime and oral gavage to induce the disease (gluten group vs. control). We tested vascular function, confirmed disease indicators, and evaluated inflammation and oxidative stress in various tissues. Plasma proteome profiling was also performed. CeD markers were confirmed in the gluten group, indicating increased blood pressure and impaired vascular relaxation. Pro-inflammatory genes were upregulated in this group, with increased CD11b+ myeloid cell infiltration and oxidative stress parameters observed in aortic and heart tissue. However, heart function remained unaffected. Plasma proteomics suggested the cytokine interleukin-17A (IL-17A) as a link between gut and vascular inflammation. Cardiovascular complications were reversed by adopting a gluten-free diet. CONCLUSION: Our study sheds light in the heightened cardiovascular risk associated with active CeD, revealing a gut-to-cardiovascular inflammatory axis potentially mediated by immune cell infiltration and IL-17A. These findings augment our understanding of the link between CeD and cardiovascular disease providing clinically relevant insight into the underlying mechanism. Furthermore, our discovery that cardiovascular complications can be reversed by a gluten-free diet underscores a critical role for dietary interventions in mitigating cardiovascular risks associated with CeD.

Night shift work and cardiovascular diseases among employees in Germany: five-year follow-up of the Gutenberg Health Study.

OBJECTIVE: This study aimed to determine if there is an increased risk of incident cardiovascular diseases (CVD) resulting from cumulative night shift work in the German population-based Gutenberg Health Study (GHS). METHODS: We examined working participants of the GHS at baseline and after five years. Cumulative night shift work in the 10 years before baseline was assessed and categorized as low (1-220 nights ≙ up to 1 year), middle (221-660 nights ≙ 1-3 years), and high (>660 nights ≙ more than 3 years) night shift exposure. Hazard ratios (HR) were estimated for incident "quality-assured CVD events" using Cox proportional hazard models. RESULTS: At baseline, 1092 of 8167 working participants performed night shift work. During the follow-up, 202 incident cardiovascular events occurred. The crude incidence rates for CVD per 1000 person-years were 6.88 [95% confidence interval (CI) 4.80-9.55] for night shift workers and 5.19 (95% CI 4.44-6.04) for day workers. Cumulative incidence curves showed a higher cumulative incidence in workers exposed to night shift work compared to day workers after five years. The adjusted HR for incident CVD events were 1.26 (95% CI 0.68-2.33), 1.37 (95% CI 0.74-2.53) and 1.19 (95% CI 0.67-2.12) for employees in the low, middle and high night shift categories compared to employees without night shift work, respectively. CONCLUSIONS: The observed tendencies indicate that night shift work might be negatively associated with cardiovascular health. We expect the continued follow-up will clarify the long-term impact of night shift work.

Photon-Counting Detector CT Virtual Monoenergetic Images for Coronary Artery Stenosis Quantification: Phantom and In Vivo Evaluation.

BACKGROUND. Calcium blooming causes stenosis overestimation on coronary CTA. OBJECTIVE. The purpose of this article was to evaluate the impact of virtual monoenergetic imaging (VMI) reconstruction level on coronary artery stenosis quantification using photon-counting detector (PCD) CT. METHODS. A phantom containing two custom-made vessels (representing 25% and 50% stenosis) underwent PCD CT acquisitions without and with simulated cardiac motion. A retrospective analysis was performed of 33 patients (seven women, 26 men; mean age, 71.3 ± 9.0 [SD] years; 64 coronary artery stenoses) who underwent coronary CTA by PCD CT followed by invasive coronary angiography (ICA). Scans were reconstructed at nine VMI energy levels (40-140 keV). Percentage diameter stenosis (PDS) was measured, and bias was determined from the ground-truth stenosis percentage in the phantom and ICA-derived quantitative coronary angiography measurements in patients. Extent of blooming artifact was measured in the phantom and in calcified and mixed plaques in patients. RESULTS. In the phantom, PDS decreased for 25% stenosis from 59.9% (40 keV) to 13.4% (140 keV) and for 50% stenosis from 81.6% (40 keV) to 42.3% (140 keV). PDS showed lowest bias for 25% stenosis at 90 keV (bias, 1.4%) and for 50% stenosis at 100 keV (bias, -0.4%). Blooming artifacts decreased for 25% stenosis from 61.5% (40 keV) to 35.4% (140 keV) and for 50% stenosis from 82.7% (40 keV) to 52.1% (140 keV). In patients, PDS for calcified plaque decreased from 70.8% (40 keV) to 57.3% (140 keV), for mixed plaque decreased from 69.8% (40 keV) to 56.3% (140 keV), and for noncalcified plaque was 46.6% at 40 keV and 54.6% at 140 keV. PDS showed lowest bias for calcified plaque at 100 keV (bias, 17.2%), for mixed plaque at 140 keV (bias, 5.0%), and for noncalcified plaque at 40 keV (bias, -0.5%). Blooming artifacts decreased for calcified plaque from 78.4% (40 keV) to 48.6% (140 keV) and for mixed plaque from 73.1% (40 keV) to 44.7% (140 keV). CONCLUSION. For calcified and mixed plaque, stenosis severity measurements and blooming artifacts decreased at increasing VMI reconstruction levels. CLINICAL IMPACT. PCD CT with VMI reconstruction helps overcome current limitations in stenosis quantification on coronary CTA.