tbuckley/cabot-search huggingface dataset:
Abstract 11703: Proteomic Analysis for the Formation of the Plexiform Lesions of a Rat Pulmonary Arterial Hypertension Model
Authors: Yoshihito Morimoto, Hidenori Yamamoto, Kiyotaka Go, Yoshie Fukasawa, Naoki Ohashi, Yoshiyuki Takahashi, Taichi Kato
Journal: Circulation (2023)

Introduction: Although plexiform lesions (PLs) are the hallmark of the severe pulmonary arterial hypertension, the mechanism of this lesion formation has not been fully elucidated. In this study, to explore the pathways associated PLs formation, we examined the proteome analysis using vascular tissue before and after the formation of PLs obtained by laser capture microdissection (LCM). Methods: 7 weeks old rats were injected Sugen 5416 subcutaneously, followed by exposed to hypoxia for 3 weeks. In addition, the rats were kept in room air for 5 weeks (8-week model) or 10 weeks (13-week model) thereafter. We obtained the tissue of vessels with medial hypertrophy from 8-week models (n=5) and PLs from 13-week models (n=5) by LCM. Those micro-dissected samples were then subject to a qualitative and then quantitative proteomics approach. Differentially expressed proteins (DEPs) were defined by abundance in mass spectrometry (MS) (P-value &lt; 0.05 and |log2 (fold change)| &gt; 0.5 or proteins deteced only in lesions extracted from one model). In addition, we investigated enhanced pathway by gene ontology (GO) analysis of the identified DEPs in each of the 8-week and 13-week models. Results: We identified 718 uniquely expressed proteins including 57 DEPs (31 in 8-week model versus 26 in 13-week model) by using LCM-MS. GO analysis revealed that the actin cytoskeleton organization, actin filament-based process, and actomyosin structure organization processes were enhanced in 8-week model. On the other hand, the innate immune system, G2/M check points, and cellular response to reactive oxygen species were enhanced in 13-week model. Conclusion: Pulmonary vascular lesions of 8-week and PLs of 13-week Sugen hypoxia model evaluated by proteomics using samples obtained by LCM methods showed differential protein expression. Analysis of these DEPs may contribute to elucidate the mechanisms of PLs formation.
Abstract 12134: The Utilization Rate of Intravenous Thrombolysis in Asian Countries: A Systematic Review and Meta-Analysis
Authors: Bikram Prasad Gajurel, Gaurav Nepal, Vikash Jaiswal, Song Peng Ang, Priyanshu Nain, Endurance O Evbayekha, Sujan Bohara, Nishat Shama, FNU Ruchika, Jillian Reeze Medina, Sanjeev Kharel, Dr. JAYANT KUMAR YADAV
Journal: Circulation (2023)

Introduction: Even though IV thrombolysis has been used for more than two decades, coverage remains inadequate. Asia, the region with the highest age-standardized incidence of ischemic stroke, has no regional data on IVT utilization at present. Objective: This study aimed to provide more accurate estimates of IVT usage for AIS in Asia. Methods: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 15th March 2023. Results: A total of 67 observational studies with a total of 778,046 patients with ischemic stroke were included in the final analysis. In terms of regional distribution of studies, East Asia was the most common (n=12), followed closely by Arab (n=18), Southeast Asia (n=15), South Asia (n=12) and lastly Central and North Asia (n=2). In terms of the income level stratified by GDP of these countries, 35.8 % of them were classified as high-income countries, 40.3% were of lower-middle income countries and the rest (23.9%) being upper-middle-income countries. Our pooled analysis of 67 Asian studies revealed an IV thrombolysis rate of 9.1%. We discovered substantial variation in the thrombolysis rate across Asia, with 11.3% receiving thrombolysis in HIC countries and only 8.1% in LMICs; far below the American Stroke Association's target rate of 50%. Conclusion: Patients with ischemic stroke in HIC countries, countries/hospitals with their own guidelines/protocols, living in urban areas, and receiving care in hospitals with a public-private partnership are more likely to receive thrombolysis, according to our findings. Improving thrombolysis rates throughout Asia would be greatly aided by reducing prehospital and hospital delays, enhancing local infrastructure and human resources, and educating the public about stroke.
Abstract 11631: Subclinical Atherosclerosis Risk of Isolated Diastolic Hypertension in Young Adults
Authors: Jindong Wan, Sen Liu, Yi Yang, Xinquan Wang, Peng Zhou, Peijian Wang
Journal: Circulation (2023)

Aim: Hypertension among young adults is common. Little is known regarding subclinical atherosclerosis development associated with isolated diastolic hypertension (IDH) among young adults. This study aimed to assess the relationship between IDH and some surrogate markers of subclinical atherosclerosis in young adults. Methods: From January 2018 to December 2022, we consecutively enrolled 576 IDH individuals (aged 18 to 39 years) without cardiovascular complications and 576 normotensive subjects matched for age, sex and body mass index (BMI). Each participant underwent anthropometric measurements, serum biochemistry evaluation, 24-h ambulatory blood pressure (BP) monitoring, echocardiography, and carotid ultrasonography. Surrogate markers of subclinical atherosclerosis included carotid intima-media thickness (cIMT), ankle-brachial index (ABI), coronary calcification, and biochemical parameters. IDH was defined as diastolic BP ≥ 90 mmHg and systolic BP &lt; 140 mmHg. Results: Individuals with IDH had higher cIMT, greater ABI, and a higher frequency of coronary calcification and albuminuria (all P &lt; 0.05). IDH was correlated with cIMT, ABI, coronary calcification, and albuminuria (Pearson’s correlation coefficients: 0.471, 0.365, 0.411, and 0.268, respectively; all P &lt; 0.05). Compared with normotensive individuals, IDH was related to odds ratios of 2.09 (95% confidence interval [CI], 1.21-3.16), 2.72 (95% CI, 1.52-4.56), 1.78 (95% CI,1.15-2.89), and 1.26 (95% CI, 0.48-2.05) for cIMT, ABI, coronary calcification, and albuminuria, respectively. Conclusion: Our findings emphasize the importance of assessing IDH in young adults to identify high-risk individuals for preventing subclinical atherosclerosis complications.
Abstract 11652: The Addition of Social Determinants of Health to Coronary Heart Disease Risk Prediction
Authors: Brittany S Murphy, Yunbi Nam, Robyn McClelland, Isaac Acquah, Miguel Cainzos Achirica, Khurram Nasir, Melinda Aldrich, Andrew P Defilippis
Journal: Circulation (2023)

Introduction: Coronary heart disease (CHD) remains a leading cause of death worldwide, with an unequal distribution of this burden placed on individuals of lower socioeconomic status. Individual social determinants of health (SDoH) have been shown to be associated with CHD; however, whether the addition of SDoH can improve current CHD risk prediction algorithms has not been delineated. Hypothesis: We hypothesize that the addition of SDoH to the Multi-Ethnic Study of Atherosclerosis (MESA) risk score improves the prediction of 10-year CHD events. Methods: In 6,286 individuals from the MESA cohort, we evaluated the additional predictive value of SDoH beyond the traditional factors included in the existing MESA Risk Score. SDoH considered were employment, family income, house tenure, financial strain, education, marital status, social support, chronic stress, discrimination, neighborhood characteristics, healthcare access, and health insurance, which were organized into five composite domains. A penalized Cox proportional hazards model was used to select SDoH variables with the potential to improve prediction, then an unpenalized Cox regression model was fitted with traditional risk factors plus the selected SDoH variables. Results: Statistically significant differences in the distribution of SDoH were observed between racial and ethnic groups. Notably, unfavorable SDoH were concentrated in Black and Hispanic/Latino persons. Economic stability, education, and community and social context were associated with CHD events. The area under the curve (AUC) for prediction of a 10-year CHD event was 0.816 without SDoH factors and 0.818 with the addition of SDoH. Conclusions: Racial and ethnic differences in social determinants of health were obsserved. Economic stability, education, and community and social context were significantly associated with cardiovascular events, however the addition of SDoH did not significantly improve CHD risk prediction.
Abstract 11917: Cardiometabolic Disease Staging and Major Adverse Cardiovascular Event Prediction in Two Prospective Cohorts
Authors: Carrie R Howell, Li Zhang, Tapan Mehta, Lua Wilkinson, April Carson, Emily B Levitan, Andrea Cherrington, Nengjun Yi, William T Garvey
Journal: Circulation (2023)

Background: Cardiometabolic risk prediction models that incorporate the presence and severity of metabolic syndrome traits to predict cardiovascular outcomes may help identify high-risk populations early in the progression of cardiometabolic disease. Objective: To examine whether a modified Cardiometabolic Disease Staging System (CMDS) - a validated diabetes prediction model - predicts major adverse cardiovascular events (MACE) in two prospective cohorts. Methods: We developed a predictive model using data accessible in clinical practice [fasting glucose, blood pressure, body mass index, cholesterol, triglycerides, smoking status, diabetes status, hypertension medication use] from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study using Bayesian logistic regression - with external validation in the Atherosclerosis Risk in Communities (ARIC) study - to predict MACE [cardiovascular death, nonfatal myocardial infarction, and/or nonfatal stroke]. Predictive performance was assessed using receiver operating characteristic (ROC) curves, mean squared errors, misclassification and area under the curve (AUC) statistics. Results: This analysis included 20,234 REGARDS participants who were enrolled at baseline (2003-2007) and had no history of stroke or myocardial infarction. Participants were a mean age of 64 years (SD 9.3), mostly female (58%), 41% were non-Hispanic Black, and 18% had diabetes. During a median 10-year follow-up, there were 2,695 incident MACE (13.3%). The CMDS development model in REGARDS for MACE had an AUC of 0.721; with an AUC of 0.737 in external validation (ARIC). Our CMDS model performed similarly to both the ACC/AHA 10-year risk estimate (AUC 0.721 vs 0.716) and the Framingham risk score (AUC 0.673). Conclusions: We found that the CMDS predicted the onset of major cardiovascular events with good predictive ability and performed similarly or better than two commonly known CVD prediction risk tools. These data underscore the importance of insulin resistance as a cardiovascular disease risk factor, and that CMDS can be used to identify individuals at high-risk for progression to CVD in order to enhance the efficacy and benefit/risk ratio for interventions for CMD prevention.
Abstract 12128: Catheter Ablation Outperforms Implantable Cardioverter Defibrillator Therapy in Improving Arrhythmic Outcomes of Brugada Syndrome
Authors: Le Li, Yan Yao, Likun Zhou, Ligang Ding, Lingmin Wu
Journal: Circulation (2023)

Background: Brugada syndrome (BrS) is characterized by ventricular arrhythmias that pose a significant risk to affected individuals. While ICD therapy is the primary treatment, it does not prevent VF episodes. Catheter ablation (CA) has shown promise in improving arrhythmic outcomes. This study aims to compare the efficacy of CA with ICD therapy in symptomatic BrS patients. Methods: A total of 49 symptomatic BrS patients were enrolled, with 21 patients undergoing CA and 28 patients receiving ICD therapy. Substrate modification techniques, including endocardial and epicardial approaches, were utilized along with VF-triggering PVC ablation strategies. The primary outcomes assessed were the occurrence of VF episodes and sudden cardiac death during the follow-up period. Results: The study population had a mean age of 44.3±10.4 years, with 44 patients (89.8%) being male. Among the participants, 40 (81.6%) exhibited the typical type 1 BrS electrocardiogram pattern, and 12 (24.5%) had a positive SCN5A mutation. VF-triggering PVCs were successfully ablated in 3 patients (14.3%), while VF substrates were eliminated in 18 patients (85.7%). Epicardial ablation was performed in 14 patients (66.7%). During a median follow-up of 46.2 (15.6-68.8) months, the primary outcomes occurred more frequently in the ICD group compared to the CA group (4.8% vs. 57.1%, Log-rank P = 0.006). Conclusion: Our findings suggest that CA is a more effective therapy for improving arrhythmic outcomes in symptomatic BrS patients compared to ICD implantation. These results highlight the potential of CA as a first-line therapeutic approach for managing symptomatic BrS.
Abstract 12140: Clinical Care for Life’s Essential 8 by Medical Specialty in the United States
Authors: Jeremy B Sussman, Madeline R Sterling, Michael E Johansen
Journal: Circulation (2023)

Background: The American Heart Association recognizes “Life’s Essential 8 (LE8)” as key to achieving cardiovascular health (CVH). Partnership between patients and clinicians will be vital to achieving LE8 and CVH, but one key question is which clinicians can influence their patients’ LE8. Here, we aimed to discover who provides clinical care for LE8 by clinician specialty. Method: We used all adult respondents from the nationally representative 2017-2019 Medical Expenditure Panel Survey. We classified visits to the specialties most relevant to LE8 care. Four LE8 measures represented what clinician type prescribed (1) statins, (2) diabetes mellitus medications, (3) anti-hypertensive medication, and (4) tobacco cessation medication (buproprion amongst tobacco users or varenicline). We assessed four other LE8 measures by which clinician saw a patient who reported: (1) low physical activity, defined as lack of moderate-vigorous physical activity 5 times per week, (2) obesity, (3) tobacco use, and (4) insomnia. We also evaluated report of a general check-up. We were unable to assess diet. We performed descriptive statistics with complex survey weights. The OhioHealth Institutional Review Board ruled the study exempt. Results: The study included 50,542 adults. Results, which are detailed in the table, found that for all measures, many people with gaps in LE8 saw neither a primary care doctor nor a cardiologist and between 2.5 and 5 times as many people with gaps in LE8 saw primary care without seeing a cardiologist than saw a cardiologist at all. Discussion: We found that primary care provides the large majority of medical care for all of LE8. Patients with gaps in LE8 who saw neither cardiology nor primary care were also common. Our findings emphasize how particular supporting primary care in their core functions of preventive care and chronic disease management will be key to achieving cardiovascular health.
Abstract 11802: IRF2BP2 Regulates Hormone Sensitive Lipase and Lipolysis in Human Adipocytes and in Mice
Authors: Yang Chen, Lin Liu, David Steger, Lan Cheng, Alexandre F STEWART, Patrick Seale
Journal: Circulation (2023)

Background: IRF2BP2, a transcriptional co-factor, has emerged as a potential regulator of circulating lipid levels based on several coronary artery disease (CAD) genome-wide association studies (GWAS) studies. However, the role of IRF2BP2 in adipocytes, which regulate fat storage, energy expenditure, and fatty acid release, remains unexplored. Our aim is to investigate the role of IRF2BP2 in adipocyte function regulation. Methods: Human adipocyte stem cells (hASC) were differentiated into adipocytes for in vitro studies. We used the CRISPR system and lentiviral expression constructs to knockout (KO) and overexpress (OE) IRF2BP2. Control, IRF2BP2 KO and IRF2BP2 OE adipocytes were assessed by several methods, including RNA-seq, western blot analysis, and functional assessment of lipolysis and glucose uptake. IRF2BP2 chromatin immunoprecipitation (ChIP)-seq was performed in vitro . Adiponectin-Cre mice were crossed with Irf2bp2 flox/flox mice to generate adipocyte-specific KO (AKO) animals. We evaluated the effect of IRF2BP2 KO on adipose morphology and gene profiles. Circulating fatty acids were assessed in control and AKO mice. Results: IRF2BP2 deletion or OE in hASC-differentiated adipocytes did not affect adipocyte differentiation or glucose uptake. However, triglyceride lipolysis was markedly increased in KO cells. Conversely, IRF2BP2 OE suppressed lipolysis. RNA-seq analysis of control vs. IRF2BP2 KO or OE cells identified the enrichment of lipid catabolic pathways. Notably, IRF2BP2 KO upregulated, whereas IRF2BP2 OE downregulated the mRNA and protein levels of LIPE (i.e. hormone sensitive lipase, or HSL). Further, ChIP-seq analysis demonstrates strong binding of IRF2BP2 to a LIPE enhancer, suggesting direct regulation. In mice, Irf2bp2 AKO increased circulating fatty acids, accompanied by a reduction of adipocyte size. LIPE mRNA and protein expression in adipose tissue was also elevated. Finally, Irf2bp2 AKO induces massive adipose tissue inflammation, evidenced by F4/80 staining and chemotaxis gene markers expression. Conclusions: We established IRF2BP2, as a novel transcriptional regulator of adipocyte lipolysis, through the key lipolytic gene LIPE, which may shed light on deciphering the role of IRF2BP2 in CAD.
Abstract 11632: Altered Autonomic Balance Linked to Arrhythmogenicity in Chronic Myocardial Infarction Ovine Model
Authors: Kanchan Kulkarni, Nestor Pallares-Lupon, Shivaram Poigai Arunachalam, Olivier Bernus, Richard Walton
Journal: Circulation (2023)

Background: Increased sympathetic drive resulting in decreased heart rate variability (HRV), has been linked to cardiovascular diseases such as heart failure and myocardial infarction (MI). Dynamic electrophysiological changes due to acute ischemia and chronic MI are known to be pro-arrhythmic. Objective: Evaluate the changes in autonomic tone resulting from substrate remodeling during the development of chronic MI in an in-vivo ovine model. Methods: ECG recordings were collected at baseline, post occlusion and 6 weeks post MI, in young adult sheep (n=16). Time domain, frequency domain and non-linear measures of HRV were evaluated from 10 minutes of ECG data at the 3 time points. RR interval, heart rate, SDRR (standard deviation of the RR intervals), RMSSD (root mean square of successive differences between normal heartbeats), QTc interval, pNN 50 , LF/HF ratio and SD1/SD2 ratio were calculated and compared between baseline, post acute coronary artery occlusion and after 6 weeks of chronic MI. 24-hour telemetry was also performed in an ambulatory animal for 6 weeks to monitor the progression of alterations in the T-wave morphology or duration, i.e. T-wave alternans, a known marker of ventricular tachyarrhythmias, with chronic MI. Results: Chronic MI led to significantly decreased RR interval (Fig.1A) and increased heart rate (Fig.1B), along with a significant prolongation of the QTc interval (Fig.1C). Significant rise was also observed in the SDRR (Fig1D) and LF/HF ratio (Fig1E) indicating a shift towards increased sympathetic tone and reduced parasympathetic drive. In addition to the autonomic changes, a significant rise in T-wave alternans burden (Fig1F) and localized action potential alternans inducibility was observed with progression of MI indicating increased arrhythmogenicity. Conclusion: Skewed autonomic balance is evident in chronic MI and may be closely linked to increased arrhythmogenicity.
Abstract 12054: Activated Clotting Time and Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the PROGRESS-CTO Registry
Authors: Bahadir Simsek, Athanasios Rempakos, Spyridon Kostantinis, Michaella Alexandrou, sevket gorgulu, Khaldoon Alaswad, Jarrod D Frizzell, Ufuk Yildirim, Paul Poommipanit, Nazif Aygul, Nidal Abi Rafeh, MD, FACC, Rodrigo Bagur, Rhian Davies, OMER GOKTEKIN, James W Choi, Niranjan Reddy, Elias Haddad, Jimmy Kerrigan, Deniz Mutlu, Olga Mastrodemos, Bavana V Rangan, Judit Karacsonyi, Salman S Allana, Kathleen E Kearney, Yader Sandoval, M Nicholas Burke, Emmanouil S Brilakis, Lorenzo Azzalini
Journal: Circulation (2023)

Introduction: The optimal range of activated clotting time (ACT) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. Methods: We examined the association between ACT and in-hospital ischemic and bleeding outcomes in patients who underwent CTO PCI in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO, NCT02061436). Results: ACT values were available for 4,377 patients who underwent CTO PCI between 2012 and 2023 at 29 centers. Mean ACT distribution was: &lt;250 seconds (19%), 250-349 seconds (50%), and ≥350 seconds (31%). The incidence of ischemic events was 0.8%, bleeding events 3.0%, and net adverse cardiovascular events (NACE, composite of in-hospital all-cause mortality, myocardial infarction, stroke, urgent repeat revascularization, pericardiocentesis, and bleeding) 3.8%. In multiple logistic regression analysis, increasing nadir ACT was associated with decreasing ischemic events: adjusted odds ratio (aOR) per 50-second increments: 0.69 (95% confidence interval [CI] 0.50-0.94, p=0.017); and increasing peak ACT was associated with increasing bleeding events: aOR per 50-second increments 1.17 (95% CI 1.01-1.36, p=0.032). A U-shaped association was seen between mean ACT and NACE, where restricted cubic spline analysis demonstrated that patients with low (&lt;200 seconds) or high (&gt;400 seconds) ACT had increasing NACE risk, compared with ACT 200-400 seconds (aOR 2.06, 95% CI 1.18-3.62, p=0.012) (Figure). Conclusions: Among patients who underwent CTO PCI, mean ACT had a U-shaped relationship with NACE, where patients with low (&lt;200 seconds) ACT (driven by ischemic events) or high (&gt;400 seconds) ACT (driven by bleeding) had higher NACE compared with ACT of 200-400 seconds.