Microplastics and Nanoplastics in Atheromas and Cardiovascular Events.

BACKGROUND: Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking. METHODS: We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease. The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis, and electron microscopy. Inflammatory biomarkers were assessed with enzyme-linked immunosorbent assay and immunohistochemical assay. The primary end point was a composite of myocardial infarction, stroke, or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs. RESULTS: A total of 304 patients were enrolled in the study, and 257 completed a mean (±SD) follow-up of 33.7±6.9 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 µg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 µg per milligram of plaque. Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris. Radiographic examination showed that some of these particles included chlorine. Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end-point event than those in whom these substances were not detected (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001). CONCLUSIONS: In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected. (Funded by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale and others; ClinicalTrials.gov number, NCT05900947.).

Understanding the Cardiovascular and Metabolic Health Effects of Air Pollution in the Context of Cumulative Exposomic Impacts.

Poor air quality accounts for more than 9 million deaths a year globally according to recent estimates. A large portion of these deaths are attributable to cardiovascular causes, with evidence indicating that air pollution may also play an important role in the genesis of key cardiometabolic risk factors. Air pollution is not experienced in isolation but is part of a complex system, influenced by a host of other external environmental exposures, and interacting with intrinsic biologic factors and susceptibility to ultimately determine cardiovascular and metabolic outcomes. Given that the same fossil fuel emission sources that cause climate change also result in air pollution, there is a need for robust approaches that can not only limit climate change but also eliminate air pollution health effects, with an emphasis of protecting the most susceptible but also targeting interventions at the most vulnerable populations. In this review, we summarize the current state of epidemiologic and mechanistic evidence underpinning the association of air pollution with cardiometabolic disease and how complex interactions with other exposures and individual characteristics may modify these associations. We identify gaps in the current literature and suggest emerging approaches for policy makers to holistically approach cardiometabolic health risk and impact assessment.

Environmental Exposome and Atrial Fibrillation: Emerging Evidence and Future Directions.

There has been increased awareness of the linkage between environmental exposures and cardiovascular health and disease. Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting millions of people worldwide and contributing to substantial morbidity and mortality. Although numerous studies have explored the role of genetic and lifestyle factors in the development and progression of atrial fibrillation, the potential impact of environmental determinants on this prevalent condition has received comparatively less attention. This review aims to provide a comprehensive overview of the current evidence on environmental determinants of atrial fibrillation, encompassing factors such as air pollution, temperature, humidity, and other meteorologic conditions, noise pollution, greenspace, and the social environment. We discuss the existing evidence from epidemiological and mechanistic studies, critically evaluating the strengths and limitations of these investigations and the potential underlying biological mechanisms through which environmental exposures may affect atrial fibrillation risk. Furthermore, we address the potential implications of these findings for public health and clinical practice and identify knowledge gaps and future research directions in this emerging field.

Toward Heart-Healthy and Sustainable Cities: A Policy Statement From the American Heart Association.

Nearly 56% of the global population lives in cities, with this number expected to increase to 6.6 billion or >70% of the world's population by 2050. Given that cardiometabolic diseases are the leading causes of morbidity and mortality in people living in urban areas, transforming cities and urban provisioning systems (or urban systems) toward health, equity, and economic productivity can enable the dual attainment of climate and health goals. Seven urban provisioning systems that provide food, energy, mobility-connectivity, housing, green infrastructure, water management, and waste management lie at the core of human health, well-being, and sustainability. These provisioning systems transcend city boundaries (eg, demand for food, water, or energy is met by transboundary supply); thus, transforming the entire system is a larger construct than local urban environments. Poorly designed urban provisioning systems are starkly evident worldwide, resulting in unprecedented exposures to adverse cardiometabolic risk factors, including limited physical activity, lack of access to heart-healthy diets, and reduced access to greenery and beneficial social interactions. Transforming urban systems with a cardiometabolic health-first approach could be accomplished through integrated spatial planning, along with addressing current gaps in key urban provisioning systems. Such an approach will help mitigate undesirable environmental exposures and improve cardiovascular and metabolic health while improving planetary health. The purposes of this American Heart Association policy statement are to present a conceptual framework, summarize the evidence base, and outline policy principles for transforming key urban provisioning systems to heart-health and sustainability 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.

Air Pollution, Built Environment, and Early Cardiovascular Disease.

As the world's population becomes increasingly urbanized, there is growing concern about the impact of urban environments on cardiovascular health. Urban residents are exposed to a variety of adverse environmental exposures throughout their lives, including air pollution, built environment, and lack of green space, which may contribute to the development of early cardiovascular disease and related risk factors. While epidemiological studies have examined the role of a few environmental factors with early cardiovascular disease, the relationship with the broader environment remains poorly defined. In this article, we provide a brief overview of studies that have examined the impact of the environment including the built physical environment, discuss current challenges in the field, and suggest potential directions for future research. Additionally, we highlight the clinical implications of these findings and propose multilevel interventions to promote cardiovascular health among children and young adults.

Unraveling the Role of Sex in Endothelial Cell Dysfunction: Evidence From Lineage Tracing Mice and Cultured Cells.

BACKGROUND: Biological sex differences play a vital role in cardiovascular diseases, including atherosclerosis. The endothelium is a critical contributor to cardiovascular pathologies since endothelial cells (ECs) regulate vascular tone, redox balance, and inflammatory reactions. Although EC activation and dysfunction play an essential role in the early and late stages of atherosclerosis development, little is known about sex-dependent differences in EC. METHODS: We used human and mouse aortic EC as well as EC-lineage tracing (Cdh5-CreERT2 Rosa-YFP [yellow fluorescence protein]) atherosclerotic Apoe-/- mice to investigate the biological sexual dimorphism of the EC functions in vitro and in vivo. Bioinformatics analyses were performed on male and female mouse aortic EC and human lung and aortic EC. RESULTS: In vitro, female human and mouse aortic ECs showed more apoptosis and higher cellular reactive oxygen species levels than male EC. In addition, female mouse aortic EC had lower mitochondrial membrane potential (ΔΨm), lower TFAM (mitochondrial transcription factor A) levels, and decreased angiogenic potential (tube formation, cell viability, and proliferation) compared with male mouse aortic EC. In vivo, female mice had significantly higher lipid accumulation within the aortas, impaired glucose tolerance, and lower endothelial-mediated vasorelaxation than males. Using the EC-lineage tracing approach, we found that female lesions had significantly lower rates of intraplaque neovascularization and endothelial-to-mesenchymal transition within advanced atherosclerotic lesions but higher incidents of missing EC lumen coverage and higher levels of oxidative products and apoptosis. RNA-seq analyses revealed that both mouse and human female EC had higher expression of genes associated with inflammation and apoptosis and lower expression of genes related to angiogenesis and oxidative phosphorylation than male EC. CONCLUSIONS: Our study delineates critical sex-specific differences in EC relevant to proinflammatory, pro-oxidant, and angiogenic characteristics, which are entirely consistent with a vulnerable phenotype in females. Our results provide a biological basis for sex-specific proatherosclerotic mechanisms.

Artificial intelligence-based assessment of built environment from Google Street View and coronary artery disease prevalence.

BACKGROUND AND AIMS: Built environment plays an important role in the development of cardiovascular disease. Tools to evaluate the built environment using machine vision and informatic approaches have been limited. This study aimed to investigate the association between machine vision-based built environment and prevalence of cardiometabolic disease in US cities. METHODS: This cross-sectional study used features extracted from Google Street View (GSV) images to measure the built environment and link them with prevalence of coronary heart disease (CHD). Convolutional neural networks, linear mixed-effects models, and activation maps were utilized to predict health outcomes and identify feature associations with CHD at the census tract level. The study obtained 0.53 million GSV images covering 789 census tracts in seven US cities (Cleveland, OH; Fremont, CA; Kansas City, MO; Detroit, MI; Bellevue, WA; Brownsville, TX; and Denver, CO). RESULTS: Built environment features extracted from GSV using deep learning predicted 63% of the census tract variation in CHD prevalence. The addition of GSV features improved a model that only included census tract-level age, sex, race, income, and education or composite indices of social determinant of health. Activation maps from the features revealed a set of neighbourhood features represented by buildings and roads associated with CHD prevalence. CONCLUSIONS: In this cross-sectional study, the prevalence of CHD was associated with built environment factors derived from GSV through deep learning analysis, independent of census tract demographics. Machine vision-enabled assessment of the built environment could potentially offer a more precise approach to identify at-risk neighbourhoods, thereby providing an efficient avenue to address and reduce cardiovascular health disparities in urban environments.

Exposome in ischaemic heart disease: beyond traditional risk factors.

Ischaemic heart disease represents the leading cause of morbidity and mortality, typically induced by the detrimental effects of risk factors on the cardiovascular system. Although preventive interventions tackling conventional risk factors have helped to reduce the incidence of ischaemic heart disease, it remains a major cause of death worldwide. Thus, attention is now shifting to non-traditional risk factors in the built, natural, and social environments that collectively contribute substantially to the disease burden and perpetuate residual risk. Of importance, these complex factors interact non-linearly and in unpredictable ways to often enhance the detrimental effects attributable to a single or collection of these factors. For this reason, a new paradigm called the 'exposome' has recently been introduced by epidemiologists in order to define the totality of exposure to these new risk factors. The purpose of this review is to outline how these emerging risk factors may interact and contribute to the occurrence of ischaemic heart disease, with a particular attention on the impact of long-term exposure to different environmental pollutants, socioeconomic and psychological factors, along with infectious diseases such as influenza and COVID-19. Moreover, potential mitigation strategies for both individuals and communities will be discussed.

Deep image prior cine MR fingerprinting with B1 + spin history correction.

PURPOSE: To develop a deep image prior (DIP) reconstruction for B1 + -corrected 2D cine MR fingerprinting (MRF). METHODS: The proposed method combines low-rank (LR) modeling with a DIP to generate cardiac phase-resolved parameter maps without motion correction, employing self-supervised training to enforce consistency with undersampled spiral k-space data. Two implementations were tested: one approach (DIP) for cine T1 , T2 , and M0 mapping, and a second approach (DIP with effective B1 + estimation [DIP-B1]) that also generated an effective B1 + map to correct for errors due to RF transmit inhomogeneities, through-plane motion, and blood flow. Cine MRF data were acquired in 14 healthy subjects and four reconstructions were compared: LR, low-rank motion-corrected (LRMC), DIP, and DIP-B1. Results were compared to diastolic ECG-triggered MRF, MOLLI, and T2 -prep bSSFP. Additionally, bright-blood and dark-blood images calculated from cine MRF maps were used to quantify ventricular function and compared to reference cine measurements. RESULTS: DIP and DIP-B1 outperformed other cine MRF reconstructions with improved noise suppression and delineation of high-resolution details. Within-segment variability in the myocardium (reported as the coefficient of variation for T1 /T2 ) was lowest for DIP-B1 (2.3/8.3%) followed by DIP (2.7/8.7%), LRMC (3.5/10.5%), and LR (15.3/39.6%). Spatial homogeneity improved with DIP-B1 having the lowest intersegment variability (2.6/4.1%). The mean bias in ejection fraction was -1.1% compared to reference cine scans. CONCLUSION: A DIP reconstruction for 2D cine MRF enabled cardiac phase-resolved mapping of T1 , T2 , M0 , and the effective B1 + with improved noise suppression and precision compared to LR and LRMC.

Synthetic multi-contrast late gadolinium enhancement imaging using post-contrast magnetic resonance fingerprinting.

Late gadolinium enhancement (LGE) MRI is the non-invasive reference standard for identifying myocardial scar and fibrosis but has limitations, including difficulty delineating subendocardial scar and operator dependence on image quality. The purpose of this work is to assess the feasibility of generating multi-contrast synthetic LGE images from post-contrast T1 and T2 maps acquired using magnetic resonance fingerprinting (MRF). Fifteen consecutive patients with a history of prior ischemic cardiomyopathy (12 men; mean age 63  ±  13 years) were prospectively scanned at 1.5 T between Oct 2020 and May 2021 using conventional LGE and MRF after injection of gadolinium contrast. Three classes of synthetic LGE images were derived from MRF post-contrast T1 and T2 maps: bright-blood phase-sensitive inversion recovery (PSIR), black- and gray-blood T2 -prepared PSIR (T2 -PSIR), and a novel "tissue-optimized" image to enhance differentiation among scar, viable myocardium, and blood. Image quality was assessed on a 1-5 Likert scale by two cardiologists, and contrast was quantified as the mean absolute difference (MAD) in pixel intensities between two tissues, with different methods compared using Kruskal-Wallis with Bonferroni post hoc tests. Per-patient and per-segment scar detection rates were evaluated using conventional LGE images as reference. Image quality scores were highest for synthetic PSIR (4.0) and reference images (3.8), followed by synthetic tissue-optimized (3.3), gray-blood T2 -PSIR (3.0), and black-blood T2 -PSIR (2.6). Among synthetic images, PSIR yielded the highest myocardium/scar contrast (MAD = 0.42) but the lowest blood/scar contrast (MAD = 0.05), and vice versa for T2 -PSIR, while tissue-optimized images achieved a balance among all tissues (myocardium/scar MAD = 0.16, blood/scar MAD = 0.26, myocardium/blood MAD = 0.10). Based on reference mid-ventricular LGE scans, 13/15 patients had myocardial scar. The per-patient sensitivity/accuracy for synthetic images were the following: PSIR, 85/87%; black-blood T2 -PSIR, 62/53%; gray-blood T2 -PSIR, 100/93%; tissue optimized, 100/93%. Synthetic multi-contrast LGE images can be generated from post-contrast MRF data without additional scan time, with initial feasibility shown in ischemic cardiomyopathy patients.

Midterm follow-up after computed tomography angiography planned left atrial appendage closure.

BACKGROUND: While studies have shown the advantages of computed tomography angiography (CTA) over transesophageal echocardiography (TEE) in left atrial appendage closure (LAAC) preprocedural planning for WATCHMAN™ legacy and FLX devices, there has been no reported long-term data for this approach. OBJECTIVES: We sought to evaluate long-term outcomes using CTA-based preprocedural planning for LAAC using the WATCHMAN™ device. METHODS: A prospective analysis of 231 consecutive patients who underwent LAAC in a single, large academic hospital in the United States was conducted over a 5-year period. CTA-guided preprocedural planning was performed in all. Procedural success, adverse events, length of procedure, number of devices used, and length of stay were evaluated. Rates of death, cerebral embolism, systemic embolism, and major and minor bleeding were recorded. Adjusted predicted stroke and major bleeding rates were derived from CHA2DS2-Vasc and HAS-BLED scores, respectively. RESULTS: From January 26, 2017, to November 23, 2021, 231 patients underwent LAAC with CTA preprocedural planning by two operating physicians. The mean age of patients was 76.5 ± 8.4. 59.7% of patients were male. Mean CHA2DS2VASc and HAS-BLED scores were 4.5 ± 1.4 and 3.9 ± 0.9, respectively. All procedures were performed with intracardiac echo (100%). The procedural success rate was 99.1%. The CTA sizing strategy accurately predicted the implant size in 93.5% of patients. Mean number of devices used was 1.10 ± 0.3. Peri-procedural complication rate was 2.2%. 6 patients were lost to follow-up. Mean follow-up was 608.94 days with a total of 377.04 patient years. Median follow-up period of 368 days (interquartile range: 209-1067 days). There were 51 deaths from all causes (13.52 per 100 patient-years), 10 cases of cerebral embolism (2.65 per 100 patient-years), 2 cases of systemic embolism (0.53 per 100 patient-years), 17 cases of major bleeding (4.50 per 100 patient-years), and 31 cases of minor bleeding (8.2 per 100 patient-years). All-cause mortality at 1, 2, and 3 years was 12.7%, 20.9%, and 29.2%, respectively. CV event rates at 1, 2, and 3 years were 2.1%, 6.6%, and 10.5%, respectively. CONCLUSIONS: CTA-based preprocedural planning is accurate in predicting device size for LAAC and associated with excellent clinical outcomes at 5 years.

Incidence, progression, and predictors of left atrial appendage sealing after Watchman FLX device implantation with computed tomographic assessment.

BACKGROUND: Limited data exists regarding incidence, progression, and predictors of left atrial appendage (LAA) sealing after transcatheter LAA closure. We aimed to evaluate the incidence, progression, and predictive factors associated with LAA sealing after LAA closure. METHODS: This study includes patients who underwent successful LAA closure with Watchman FLX device and had both pre- and postprocedural computed tomography (CT). Postprocedural CT was performed 45 days after LAA closure and used to evaluate residual LAA patency. Patient who had residual LAA patency at 45 days underwent 1-year follow-up CT. RESULTS: A total of 105 patients (mean age: 75.2 ± 9.6 years; 53.3% female) who underwent successful LAA closure with Watchman FLX device and had pre- and postprocedural CT at 45 days were included. Residual patency was observed in 35 (33.3%) patients: 21 (20.0%) patients showed complete contrast opacification in LAA (complete LAA patency) while 14 (13.3%) patients showed contrast opacification only in the distal LAA (distal LAA patency). Among patients with residual LAA patency at 45 days, the rate of LAA sealing at 1 year was significantly higher in the distal LAA patency group than in the complete LAA patency group (75.0% vs. 16.7%; p = 0.019). Increased depth oversizing was associated with both distal LAA patency and complete LAA patency. CONCLUSION: Postprocedural CT at 45 days detected patent LAA in one-third of patients after LAA closure. LAA sealing was more frequently observed at 1 year among the distal LAA patency group than the complete LAA patency group.

Elevated myocardial extracellular volume fraction is associated with the development of conduction pathway defects following transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an established method of aortic stenosis treatment but suffers from the risk of heart block and pacemaker requirement. Risk stratification for patients who may develop heart block remains imperfect. Simultaneously, myocardial fibrosis as measured by cardiac magnetic resonance imaging (CMR) has been demonstrated as a prognostic indicator of ventricular recovery and mortality following TAVR. However, the association of CMR-based measures of myocardial fibrosis with post-TAVR conduction disturbances has not yet been explored. AIMS: We evaluated whether myocardial fibrosis, as measured by late gadolinium enhancement and extracellular volume (ECV) from CMR would be associated with new conduction abnormalities following TAVR. METHODS: One hundred seventy patients who underwent CMR within 2 months before TAVR were retrospectively reviewed. Septal late gadolinium enhancement (LGE) and ECV measurements were made as surrogates for replacement and interstitial fibrosis respectively. New conduction abnormalities were defined by the presence of transient or permanent atrioventricular block, new bundle branch blocks, and need for permanent pacemaker. Association of myocardial fibrosis and new conduction derangements were tested using receiver operator curve (ROC) and regression analysis in patients with and without pre-existing conduction issues. RESULTS: Forty-six (27.1%) patients developed post-TAVR conduction deficits. ECV was significantly higher among patients who experienced new conduction defects (26.2 ± 3.45% vs. 24.7% ± 4.15%, p value: 0.020). A greater fraction of patients that had new conduction defects had an elevated ECV of ≥26% (54.3% vs. 36.3%, p value: 0.026). ECV ≥ 26% was independently associated with the development of new conduction defects (odds ratio [OR]: 2.364, p value: 0.030). ROC analysis revealed a significant association of ECV with new conduction defects with an area under the receiver operating characteristic curve (AUC) of 0.632 (95% confidence interval: 0.555-0.705, p value: 0.005). The combination of prior right bundle branch block (RBBB) and ECV revealed a greater AUC of 0.779 (0.709-0.839, p value: <0.001) than RBBB alone (Delong p value: 0.049). No association of LGE/ECV with new conduction defects was observed among patients with pre-existing conduction disease. Among patients without baseline conduction disease, ECV was independently associated with the development of new conduction deficits (OR: 3.685, p value: 0.008). CONCLUSION: The present study explored the association of myocardial fibrosis, as measured by LGE and ECV with conduction deficits post-TAVR. Our results demonstrate an association of ECV, and thereby interstitial myocardial fibrosis, with new conduction derangement post-TAVR and introduce ECV as a potentially new risk stratification tool to identify patients at higher risk for needing post-TAVR surveillance and/or permanent pacemaker.

County-level socio-environmental factors and obesity prevalence in the United States.

AIMS: To investigate high-risk sociodemographic and environmental determinants of health (SEDH) potentially associated with adult obesity in counties in the United States using machine-learning techniques. MATERIALS AND METHODS: We performed a cross-sectional analysis of county-level adult obesity prevalence (body mass index ≥30 kg/m2) in the United States using data from the Diabetes Surveillance System 2017. We harvested 49 county-level SEDH factors that were used in a classification and regression trees (CART) model to identify county-level clusters. The CART model was validated using a 'hold-out' set of counties and variable importance was evaluated using Random Forest. RESULTS: Overall, we analysed 2752 counties in the United States, identifying a national median (interquartile range) obesity prevalence of 34.1% (30.2%, 37.7%). The CART method identified 11 clusters with a 60.8% relative increase in prevalence across the spectrum. Additionally, seven key SEDH variables were identified by CART to guide the categorization of clusters, including Physically Inactive (%), Diabetes (%), Severe Housing Problems (%), Food Insecurity (%), Uninsured (%), Population over 65 years (%) and Non-Hispanic Black (%). CONCLUSION: There is significant county-level geographical variation in obesity prevalence in the United States, which can in part be explained by complex SEDH factors. The use of machine-learning techniques to analyse these factors can provide valuable insights into the importance of these upstream determinants of obesity and, therefore, aid in the development of geo-specific strategic interventions and optimize resource allocation to help battle the obesity pandemic.

Continuous glucose monitoring for glycaemic control and cardiovascular risk reduction in patients with type 2 diabetes not on insulin therapy: A clinical trial.

AIM: To evaluate the impact of the Dexcom G6 continuous glucose monitoring (CGM) device on glycaemic control and cardiometabolic risk in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk who are not on insulin therapy. MATERIALS AND METHODS: Adults with T2DM with glycated haemoglobin (HbA1c) >7% and body mass index (BMI) ≥30 kg/m2 not using insulin were enrolled in a two-phase cross-over study. In phase 1, CGM data were blinded, and participants performed standard glucose self-monitoring. In phase 2, the CGM data were unblinded, and CGM, demographic and cardiovascular risk factor data were collected through 90 days of follow-up and compared using paired tests. RESULTS: Forty-seven participants were included (44% women; 34% Black; mean age 63 years; BMI 37 kg/m2; HbA1c 8.4%; 10-year predicted atherosclerotic cardiovascular disease risk 24.0%). CGM use was associated with a reduction in average glucose (184.0 to 147.2 mg/dl, p < .001), an increase in time in range (57.8 to 82.8%, p < .001) and a trend towards lower glucose variability (26.2 to 23.8%). There were significant reductions in HbA1c, BMI, triglycerides, blood pressure, total cholesterol, diabetes distress and 10-year predicted risk for atherosclerotic cardiovascular disease (p < .05 for all) and an increase in prescriptions for sodium-glucose cotransporter 2 inhibitors (36.2 to 83.0%) and glucagon-like peptide-1 receptor agonists (42.5 to 87.2%, p < .001 for both). CONCLUSIONS: Dexcom G6 CGM was associated with improved glycaemic control and cardiometabolic risk in patients with T2DM who were not on insulin. CGM can be a safe and effective tool to improve diabetes management in patients at high risk for adverse cardiovascular outcomes.

PM2.5-induced cellular senescence drives brown adipose tissue impairment in middle-aged mice.

Airborne fine particulate matter (PM2.5) exposure is closely associated with metabolic disturbance, in which brown adipose tissue (BAT) is one of the main contributing organs. However, knowledge of the phenotype and mechanism of PM2.5 exposure-impaired BAT is quite limited. In the study, male C57BL/6 mice at three different life phases (young, adult, and middle-aged) were simultaneously exposed to concentrated ambient PM2.5 or filtered air for 8 weeks using a whole-body inhalational exposure system. H&E staining and high-resolution respirometry were used to assess the size of adipocytes and mitochondrial function. Transcriptomics was performed to determine the differentially expressed genes in BAT. Quantitative RT-PCR, immunohistochemistry staining, and immunoblots were performed to verify the transcriptomics and explore the mechanism for BAT mitochondrial dysfunction. Firstly, PM2.5 exposure caused altered BAT morphology and mitochondrial dysfunction in middle-aged but not young or adult mice. Furthermore, PM2.5 exposure increased cellular senescence in BAT of middle-aged mice, accompanied by cell cycle arrest, impaired DNA replication, and inhibited AKT signaling pathway. Moreover, PM2.5 exposure disrupted apoptosis and autophagy homeostasis in BAT of middle-aged mice. Therefore, BAT in middle-aged mice was more vulnerable to PM2.5 exposure, and the cellular senescence-initiated apoptosis, autophagy, and mitochondrial dysfunction may be the mechanism of PM2.5 exposure-induced BAT impairment.

Trends in tracheal, bronchial and lung cancer attributed to smoking in South America: Global Burden of Disease analysis 1990-2019.

Objective: To investigate the burden of tracheal, bronchus, and lung (TBL) cancer due to tobacco exposure in the last 30 years in 12 South American countries. Methods: We used the Global Burden of Disease (GBD) 2019 exposure-response function to analyze the total tobacco, smoking, and secondhand smoke exposure-related TBL cancer deaths and disability-adjusted life years (DALYs), for 12 South American countries, between 1990 and 2019. Metrics were described as absolute numbers or rates per 100 000 individuals. The relative change in burden was assessed by comparing the 1990-1994 to 2015-2019 periods. Results: In 2019, the all-ages number of TBL cancer deaths and DALYs associated with tobacco exposure in South America was 29 348 and 658 204 in males and 14 106 and 318 277 in females, respectively. Age-adjusted death and DALYs rates for the region in 2019 were 182.8 and 4035 in males and 50.8 and 1162 in females, respectively. In males, 10/12 countries observed relative declines in TBL death rates attributed to tobacco exposure while only 4 countries reduced their mortality in females. Conclusion: While significant efforts on tobacco control are under place in South America, substantial burden of TBL cancer persists in the region with significant sex-specific disparities. Increased country-specific primary data on TBL cancer and tobacco exposure is needed to optimize healthcare strategies and improve comprehension of regional trends.

Coronary artery calcium scoring for cardiovascular risk assessment in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with higher incidence of atherosclerotic cardiovascular disease (ASCVD). Data investigating the role of coronary artery calcium (CAC) scoring in identifying subclinical atherosclerotic disease in IBD patients is scarce. METHODS: Using data obtained from the CLARIFY registry, a prospective study of no-charge coronary artery calcium (CAC) testing at University Hospitals, we reviewed patients with ulcerative colitis (UC) or Crohn's disease (CD) who underwent CAC scoring from 2014 to 2020. We investigated the concordance between CAC risk and 10-year estimated ASCVD risk by AHA/ACC pooled cohort equation using pre-established thresholds for statin prescription (CAC≥100, 10-year ASCVD risk ≥7.5%). We additionally investigated the association between CAC, preventive therapy initiation and Major Adverse Cardiovascular Events (MACE). RESULTS: A total of 369 patients with IBD were included (174 UC, 195 CD), with median age of 60 years. The median CAC score was 14.9 with no significant difference between UC and CD (P = .76). Overall, 151 (41%) had CAC of 0, 108 (29%) had CAC 1-99, 61 (17%) had CAC 100 to 399, and 49 (13%) had CAC ≥400 with no difference in CAC distribution between CD and UC (P = .17). There was no difference in median CAC between IBD or age/sex-matched controls (P = .34). Approximately half of the patients (52%) with IBD had 10-year estimated ASCVD risk of 7.5% or higher. Among patients with ASCVD risk <7.5% (n = 163), 29 (18%) had CAC≥100 and among patients with ASCVD risk ≥7.5% (n = 178), 102 (57%) had CAC <100. There was no difference between CAC<100 vs CAC≥100 with respect to CRP, use of immunosuppressive or amino-salicylate therapy, IBD severity or complications. CAC score (AUROC 0.67 [0.56-0.78]), but not PCE ASCVD risk (AUROC 0.60 [0.48-0.73]), was predictive of MACE. The best cut-off for CAC score was 76 (sensitivity = 60%, specificity = 69%), and was associated with 4-fold increase in MACE (Hazard Ratio 4.0 [2.0-8.1], P < .001). CONCLUSION: Subclinical atherosclerosis, as evaluated by CAC scoring, is prevalent in patients with IBD, and is associated with cardiovascular events. Further studies are needed to understand underlying biological processes of increased atherosclerotic disease risk among adults with IBD.

Neighbourhood-level social deprivation and the risk of recurrent heart failure hospitalizations in type 2 diabetes.

BACKGROUND: The importance of type 2 diabetes mellitus (T2D) in heart failure hospitalizations (HFH) is acknowledged. As information on the prevalence and influence of social deprivation on HFH is limited, we studied this issue in a racially diverse cohort. METHODS: Linking data from US Veterans with stable T2D (without prevalent HF) with a zip-code derived population-level social deprivation index (SDI), we grouped them according to increasing SDI as follows: SDI: group I: ≤20; II: 21-40; III: 41-60; IV: 61-80; and V (most deprived) 81-100. Over a 10-year follow-up period, we identified the total (first and recurrent) number of HFH episodes for each patient and calculated the age-adjusted HFH rate [per 1000 patient-years (PY)]. We analysed the incident rate ratio between SDI groups and HFH using adjusted analyses. RESULTS: In 1 012 351 patients with T2D (mean age 67.5 years, 75.7% White), the cumulative incidence of first HFH was 9.4% and 14.2% in SDI groups I and V respectively. The 10-year total HFH rate was 54.8 (95% CI: 54.5, 55.2)/1000 PY. Total HFH increased incrementally from SDI group I [43.3 (95% CI: 42.4, 44.2)/1000 PY] to group V [68.6 (95% CI: 67.8, 69.9)/1000 PY]. Compared with group I, group V patients had a 53% higher relative risk of HFH. The negative association between SDI and HFH was stronger in Black patients (SDI × Race pinteraction < .001). CONCLUSIONS: Social deprivation is associated with increased HFH in T2D with a disproportionate influence in Black patients. Strategies to reduce social disparity and equalize racial differences may help to bridge this gap.