tbuckley/cabot-search huggingface dataset:
Abstract 12637: Sociodemographic Measures and Disparities in Obesity in US Rural vs Nonrural Counties, 2004-2019
Authors: Hanieh Sadat Tabatabaei Yeganeh, Brian D Lahr, Michelle M Mielke, Adrian Vella, Kent Bailey, Sagar Dugani
Journal: Circulation (2023)

Introduction: US rural, compared with nonrural, counties have a higher burden of CVD. Obesity is a major CVD risk factor with 40% prevalence in adults. However, the rural-nonrural disparities in obesity are incompletely described. We aimed to evaluate differences in prevalence of obesity by county-level rurality. Methods: We used CDC county-level data for adults aged ≥20 years, 2004–2019, available for 97.6% of US counties (n=3148/3226). CDC defined obesity (body mass index ≥30 kg/m 2 ) using self-reported weight and height. Rurality was based on six levels from large central metro (most urban) to noncore (most rural). We compared prevalence by rurality level using weighted least squares regression, adjusting for 13 county-level sociodemographic measures, and reported prevalence ratios (95% CI). Results: Counties with increasing rurality reflected older populations, as indicated by higher median age (from 35.6 years to 42.4 years). Also, increasing rurality was associated with differences in income and proportion uninsured. In age and sex ratio adjusted analysis (model 1), obesity prevalence was 1.05- to 1.06-fold higher in medium metro, small metro, and micropolitan counties compared with large central metro counties (global test, P &lt;.001). With further adjustment for sociodemographic measures (model 2; model 1 covariates plus race, state, income, proportion uninsured) these relative differences were preserved but attenuated (each 1.03-fold higher), while a greater difference was revealed for large fringe metro (1.06-fold higher) counties. In both models, differences in obesity prevalence between noncore and large central metro counties were minimal. (Table) Conclusion: Counties with intermediate rurality were associated with higher obesity prevalence. The association was partly accounted for by nonmodifiable and modifiable sociodemographic measures, which may be targeted to reduce rural-nonrural disparities in obesity.
Abstract 18742: Matrilysin (MMP7) as a Robust Predictor of Hypertension Incidence and Complications: Findings From a Proteomic Analysis in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Lena Mathews, Xiao Hu, Frances M Wang, Jingsha Chen, Bing Yu, Ron C Hoogeveen, Christie M Ballantyne, Elizabeth Selvin, Amil M Shah, Chiadi E Ndumele, Josef Coresh, Kuni Matsushita
Journal: Circulation (2023)

Introduction: Proteomic techniques can be applied for the discovery of common pathways underlying both incident hypertension and hypertension-related cardiovascular outcomes. Research Questions: To identify and validate proteins associated with incident hypertension and to examine the association of these validated proteins with hypertension-related cardiovascular events. Methods: We quantified the association of 4,955 plasma proteins (measured by SomaScan® Version 4 Assay) with incident hypertension (defined as systolic blood pressure (BP) ≥140, diastolic BP ≥ 90 mmHg, or hypertension medication use) in participants free of hypertension at ARIC visit 3 (1993-95) using Cox regression models adjusted for demographics, clinical characteristics and baseline BP. Significant associations were validated using proteomic measurements at ARIC visit 2 (1990-92). We then examined the association of validated proteins with incident coronary heart disease (CHD), stroke, and heart failure (HF) among participants with hypertension at visit 3 using Cox regression models additionally adjusted for hypertension duration and treatment. Results: There were 5,080 participants in the discovery cohort (mean age 59y, 13% Black, 54% women, median follow up 11 y) and 6,810 in the validation cohort (median follow up 3.1y). Four proteins were significantly associated with incident hypertension in the discovery cohort. One protein, Matrilysin (MMP7), remained significantly associated in the validation cohort (HR 1.22 [1.11-1.34]) (Figure1A). MMP7 was also significantly associated with all hypertension-related complications (Figure 1B-D). Conclusions: MMP7, a protein involved in extracellular matrix degradation, was robustly associated with incident hypertension and cardiovascular events. Future research examining the pathophysiologic mechanism of MMP7 could potentially yield drug targets for the prevention and treatment of hypertension.
Abstract 18125: Disparities in HFrEF Patients Excluded From Guideline Directed Medical Therapy at an NYC Safety Net Hospital
Authors: Adhya Mehta, Anna Huang, Yi-Yun Chen, Robert Faillace
Journal: Circulation (2023)

Introduction: Prescription of GDMT in heart failure with HFrEF patients is an important performance measure. However, little has been explored into the populations that are purposely excluded from the prescription of GDMT because of medical contraindications, patient refusal, cost, etc. We explored the disparities for the non-prescription of GDMT at an NYC hospital. This is essential to understand the gaps in the treatment of HFrEF patients. Hypothesis: No clinical or demographic disparities exist in the exclusion of patients from the prescription of GDMT. Methods: Data were collected retrospectively through the Get With The Guidelines™- Heart Failure registry for HFrEF (LVEF =&amp;lt;40%) patients admitted at NYC Health+Hospital/Jacobi Medical Center from 1/1/2017-5/31/2022. Only records without missing data for each medication class were included, resulting in 869 records for ACEI/ARB/ARNI, 373 for SGLT2i, 830 for beta-blocker, and 865 for MRA. Logistic regression including both demographic and clinical factors was used to analyze the exclusion outcome from each GDMT. Results were presented as adjusted odds ratios at 0.05 level of significance. Results: 50.29% had documented exclusion (e.g. contraindication, patient refusal, etc.) from the prescription of ACEI/ARB/ARNI, 46.65% from SGLT2i, 7.5% from beta-blockers, 42% from MRAs. Of these patients, 56.85%, 48.39%, 53.33% and 41.76% of patients had a “patient reason” for not being prescribed ACEI/ARB/ARNI, beta-blockers, SGLT2i, and MRAs at discharge, respectively. Results are summarized in the Table. Conclusions: Both clinical and demographic factors had significant associations with the nonprescription of GDMT. There is a sizable population of patients with non-medical reasons for nonprescription of GDMT. A more granular analysis of patient-related reasons (such as cost, patient education, etc.) should be explored to improve the prognosis of this vulnerable population with HFrEF.
Abstract 13305: Energetic Basis of Recovered Ejection Fraction in Human Heart Failure
Authors: Joseph R Goldenberg, Allison Hays, Refaat Gabr, Michael Schar, T. Jake Samuel, Gary Gerstenblith, Paul A Bottomley, Robert G Weiss
Journal: Circulation (2023)

Introduction: Left ventricular ejection fraction (LVEF) improvement in HFrEF patients is classified as heart failure with improved ejection fraction (HFimpEF) and is associated with better long-term outcomes than persistent HFrEF. HFimpEF is difficult to predict and underlying mechanisms remain poorly understood. Hypothesis: Better myocardial high-energy phosphate metabolism at baseline predicts future LVEF recovery and outcomes in a general HFrEF population Methods: We measured cardiac energetics, the ratio of the two main high-energy phosphates, phosphocreatine and ATP (PCr/ATP), and the rate of ATP synthesis through the primary cardiac energy reserve reaction creatine kinase (“CK flux”), in 37 nonischemic HFrEF patients (LVEF ≤40%) with 31 P cardiac magnetic resonance spectroscopy (MRS) at 3T. Baseline transthoracic echocardiogram (TTE) was obtained prior to 31 P MRS and follow-up consecutive TTEs with the two highest LVEFs meeting HFimpEF criteria (LVEF &gt;40% and ≥10% increase over baseline LVEF) over a median follow-up of 6.9 years were averaged and used to classify HFimpEF. Results: There were no significant differences in demographics, HF etiology, baseline TTE metrics, or medications between persistent HFrEF (n=22) and eventual HFimpEF (n=15). Cardiac CK flux was significantly higher at baseline in patients who later recovered to HFimpEF than in those who remained HFrEF (p=0.031). Better baseline cardiac CK flux was associated with increases in LVEF (p=0.025) and decreases in LV end-diastolic diameter (p=0.016) over time. By both dichotomous and continuous metrics, better preserved CK flux was associated with future HFimpEF. Fourteen subjects (38%), all persistent HFrEF, experienced cardiac death, transplant, or LVAD and had significantly lower baseline CK flux than outcome-free patients (p=0.017). Cardiac PCr/ATP was not associated with eventual HFimpEF, outcomes, or changes in TTE indices. Conclusion: Better preserved cardiac CK flux is associated with future LVEF recovery and LV reverse remodeling while lower CK flux is associated with worse cardiac outcomes in HFrEF patients. Interventions restoring CK flux, and possibly other energy-generating metabolic reactions, may elicit myocardial recovery in HFrEF patients.
Abstract 16797: The Role of Adiposity on Microvascular Dysfunction and Arterial Stiffness in Patients With New Onset Breast Cancer
Authors: Pratima Bajaj, Jacob Looney, Marsha Blackburn, Reva Crandall, jeffrey thomas, Tiffany Mukundi, Abigayle Simon, Avirup Guha, Neal L Weintraub, Priyanka Raval, Jordan Ciuro, Ryan A Harris
Journal: Circulation (2023)

INTRODUCTION: Increased adiposity is a risk factor for both cardiovascular disease (CVD) and cancer. Microvascular endothelial dysfunction and arterial stiffness are independent risk factors for CVD and can accelerate vascular aging. Whether or not adiposity plays a role in vascular aging over time in patients with new-onset breast cancer (BC) has yet to be elucidated. Hypothesis: Adiposity impacts microvascular dysfunction and arterial stiffness differently in women undergoing therapy for recent BC diagnoses. Methods: Two lean (L; BMI &lt; 25 kg/m 2 ) and four overweight and obese (Ow/Ob; BMI &gt; 25 kg/m 2 ) women diagnosed with BC within the last 3 months participated in the study. Using laser Doppler imaging, microvascular endothelial function was assessed with three protocols: 1) cutaneous post-occlusion reactive hyperemia (PORH), 2) local thermal heating (LTH), and 3) iontophoresis of acetylcholine. Arterial stiffness was assessed using pulse wave velocity (PWV) and pulse wave analysis (PWA). Assessments were made at baseline and at 3 and 6 months following enrollment. Data are reported as means ± SE. Results: No differences in age, height, blood pressure, or total cholesterol (all p &gt;0.05) were observed between L and Ow/Ob groups. Microvascular function and arterial stiffness were similar at baseline between groups. There was a greater decrease in LTH responses from baseline to 6 months post-baseline in Ow/Ob women (Δ-48±4 PU; p =0.001) compared to L women (Δ-16±13 PU; p =0.125). Similar responses in both groups were noted for PORH ( p =0.886) and iontophoresis ( p =0.784). PWV was similar from baseline to 6 months post-baseline in both groups; however, the PWA tended to increase over time in Ow/Ob women (Δ2.5±4.7) and decrease in L women (Δ-3.0±5.0). CONCLUSION: Ow/Ob women have a greater rate of decline in LTH responses compared with L women, whereas similar responses between L and OW/OB women were observed over time for PORH and iontophoresis. In addition, central aortic stiffness increased in Ow/Ob women and decreased in L women, while no change in PWV was observed. These findings suggest that adiposity may impact vascular beds differently over time following the initial diagnosis of breast cancer.
Abstract 15180: Inhibition of Tgfβ Signaling Enables Durable Ventricular Pacing by TBX18 Gene Transfer
Authors: Jinqi Fan, Nam Kyun Kim, Tae Yun Kim, David Wolfson, Rafael Ramirez, Hee Cheol C Cho
Journal: Circulation (2023)

Introduction: Somatic gene transfer of an embryonic transcription factor, TBX18, could directly reprogram ventricular myocytes to induced pacemaker myocytes. We and others have previously reported that direct myocardial gene delivery of TBX18 created ventricular pacing in heart block animals in vivo. However, the de novo biological pacing was short-lived, diminishing its translational value. Hypothesis: Our preliminary RNAseq and mass spec data indicate pronounced Tgfβ signaling in TBX18-transduced cardiomyocytes. Tgfβ signaling induces fibrosis in multiple organs including the heart. We hypothesized that TBX18 triggers Tgfβ signaling and results in fibrosis, leading to loss of durable ventricular pacing. Methods: Adenoviral vectors expressing TBX18 or GFP was delivered to neonatal rat ventricular myocytes (NRVMs) in vitro or to the left ventricular apex of adult rats with complete atrioventricular block (CAVB). Results: In vitro experiments showed increased population of vimentin+ fibroblasts and alpha smooth muscle actin+ myofibroblasts in TBX18-NRVMs compared to GFP-NRVMs at 2 weeks after gene transfer. Single cell transcriptome data indicated that TBX18 triggered substantial changes in extracellular matrix-related gene expression and Tgfβ signaling. Quantitative RT-PCR and ELISA validated scRNA-seq data, indicating fibroblast activation. TBX18-NRVMs showed faster automaticity than that control did, but their automaticity began wavering after day 7. Treatment of TBX18-NRVMs with a Tgfβ signaling inhibitor, A83-01, mitigated fibroblast activation by TBX18 and preserved their automaticity. Direct delivery of TBX18 into ventricular myocardium resulted in focal fibrosis as well as expansion of vimentin+ fibroblasts at day 7. TBX18 gene transfer initiated ventricular pacing in a rat model of CAVB, but ventricular pacing diminished after one week. In contrast, treating TBX18-injected animals with A83-01 enabled sustained biological pacing beyond three weeks of after gene delivery, accompanied by reduced fibrosis in situ. Conclusions: Inhibition of Tgfβ signaling is sufficient to achieve durable cardiac pacing by TBX18-induced biological pacemakers.
Abstract 17282: Ninety-Day Thrombotic Events in Patients With COVID-19, Association With Vaccination Status, and Changes Over Time: The Corona-VTE Network Study
Authors: Behnood Bikdeli, Darsiya Krishnathasan, Antoine Bejjani, Candrika D Khairani, Nicole D Porio, Julia Davies, Andre Armero, Anthony Tristani, Ali Assi, Victor Nauffal, Umberto Cambia, Zaid Almarzooq, Eric Wei, Aditya Achanta, Sirus Jesudasen, Bruce Tiu, Geno J Merli, John Fanikos, Alec Vishnevsky, Aditya Sharma, Mark Nehler, Judith A Hsia, James Welker, Brett Carroll, Marc P Bonaca, ZHou Lan, Samuel Goldhaber, Gregory Piazza
Journal: Circulation (2023)

Background: Venous thromboembolism (VTE) and arterial thrombosis are among serious complications of COVID-19 in the early post-infection period. Data are less consistent about subsequent risk during convalescence, the association between vaccination status and COVID-19-assocaited thrombosis, or how the event rates may have changed over time. Methods: In this multicenter study, adult patients who received inpatient or outpatient care for confirmed COVID-19 at Mass General-Brigham health system, Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System were included, with Brigham and Women’s Hospital serving as the coordinating center. Data were entered into a centralized database. Thrombotic events were adjudicated by independent physicians. Outcomes were assessed at 90-day follow-up. Findings were pre-specified to be assessed separately for hospitalized patients with COVID-19 vs outpatients. Results: The study included 9,932 patients (03/2020-06/2022, age: 54.8 ± 19.9 years; 55.7% female). In hospitalized patients, the 90-day cumulative incidence of VTE (n = 269) was 6.4% (95% CI: 5.6-7.2%). Respective 90-day event rates for arterial thrombosis (n = 98) were 2.3 % (95% CI: 1.8-2.9%). Event rates were lower for outpatients (Figure, Panel A). Ninety-day cumulative incidence of VTE and arterial thrombosis based on history of vaccination (restricted to cohort from 12/14/2020 onward) are presented in Panel B. The change in VTE and in arterial thrombotic events over time is represented in Figure, Panel C. Conclusions: In this multicenter study, 90-day adjudicated thrombotic events were important complications for hospitalized patients with COVID-19, while the event rates were very low among outpatients. Association between vaccination status and outcomes and trends over time require further investigation.
Abstract 14346: The Cardiovascular Disease Associations and Genetic Determinants of Pericardial Adipose Tissue
Authors: Joel Ramo, Shinwan Kany, Cody Hou, Samuel Friedman, Carolina Roselli, Victor Nauffal, Satoshi Koyama, Juha Karjalainen, Mahnaz Maddah, Aarno Palotie, Patrick T Ellinor, James Pirruccello
Journal: Circulation (2023)

Introduction: While previous studies have reported associations of pericardial adipose tissue (PAT) with cardiovascular diseases such as atrial fibrillation (AF) and coronary artery disease (CAD), they have been limited in sample size or drawn from selected populations. Additionally, the genetic determinants of PAT remain largely unknown. Hypothesis: PAT is associated with cardiovascular diseases and genetic loci influence variation in PAT. Methods: A deep learning model was trained to quantify PAT area from four-chamber CMR images in the UK Biobank using semantic segmentation. Cross-sectional and prospective cardiovascular disease associations were evaluated, controlling for sex and age. A genome-wide association study was performed, and a polygenic score (PGS) for PAT was examined in 453,733 independent FinnGen study participants. Results: A total of 44,725 UK Biobank participants (51.7% female, mean [SD] age 64.1 [7.7] years) were included. PAT was positively associated with male sex (β = +0.76 SD in PAT), age (r = 0.15), body mass index (BMI; r = 0.47) and waist-to-hip ratio (r = 0.55) (P &lt; 1x10 -230 for all). PAT was more elevated in prevalent heart failure (β = +0.46 SD units) and type 2 diabetes (T2D; β = +0.56) than in CAD (β = +0.22) or AF (β = +0.18). Baseline PAT was associated with incident heart failure (HR = 1.29 per +1 SD in PAT [95% CI 1.17-1.43]) and T2D (HR = 1.63 [1.51-1.76]) during mean (SD) 3.2 (1.5) years of follow-up; the associations remained significant when controlling for BMI. We replicated 2/2 known genetic loci and identified 5 novel loci, implicating transcriptional regulators of adipocyte morphology and brown adipogenesis ( EBF1 , EBF2 and CEBPA ) and regulators of visceral adiposity ( WARS2 and TRIB2 ). The PAT PGS was associated with T2D, HF, CAD and AF in FinnGen (ORs 1.03-1.06 per +1 SD in PGS, P &lt; 2x10 -10 for all). Conclusions: PAT shares genetic determinants with abdominal obesity and is an independent predictor of incident T2D and heart failure.
Abstract 18755: Engineered Nanoparticles for the Oral Delivery of Cardioprotective Small RNA Therapeutics
Authors: Shukuro Yamaguchi, Kazutaka Miyamoto, Xaviar M Jones, Alessandra Ciullo, Eduardo Marban, Ahmed G Ibrahim
Journal: Circulation (2023)

Background: RNA drugs have been applied to cardiovascular conditions including hypercholesterolemia and amyloidosis, but such drugs are deliverable only by parenteral routes. The ability to deliver RNA drugs orally would be highly desirable. Here we describe the development of a casein-chitosan-based formulation (dubbed C2) for the oral delivery of TY1, a 24-nucleotide chemically-modified Y RNA which we are exploring as a therapeutic candidate for cardiac fibrosis. Materials and Methods: We characterized the size distribution of C2-encapsulated TY1 (C2-TY1) micelles by nanoparticle tracking analysis. qPCR quantified the number of TY1 copies per micelle, as well as the presence of exogenous RNA in intestinal tissue from animals fed C2-conjugated RNA. Using a mucin precipitation assay, we assessed the ability of C2 micelles to adsorb onto mucin. We then tested the resistance of C2-TY1 micelles to degradation through incubation with proteinase K and RNase. To assess safety, healthy animals were fed C2-TY1 (0.15mg/kg, comparable to doses effective intravenously), or vehicle (H 2 O), twice weekly and evaluated at four weeks. Finally, we gauged the therapeutic potential of orally-administered C2-TY1 in a rat model of myocardial infarction. Results: C2 micelles are 100-500 nm in size and efficiently encapsulate TY1 (~10 4 TY1 copies per particle; n=3 technical replicates). After oral gavage, C2 efficiently delivered exogenous RNA to intestinal tissue within 60 minutes, as verified by qPCR (n=9). Chitosan played a significant role in the mucoadhesive property of C2 (n=6). C2 protected TY1 from enzymatic degradation compared with other formulations (p&lt;0.01; n=3 per group). In vivo , animals fed C2-TY1 had stable weight, exercise endurance, CBC and blood chemistry relative to controls, with no histologic abnormalities in vital organs (n=3-5 per group). When administered orally 20 minutes after reperfusion, C2-TY1 reduced infarct size (p&lt;0.01) and decreased circulating levels of troponin I (p&lt;0.05; n=3-6 per group). Preliminary findings show similar oral efficacy of two other, chemically-unrelated, small RNA drugs encapsulated in C2. Conclusion: The C2 formulation enables efficient and effective oral delivery of small RNA drugs for cardioprotection.
Abstract 14450: Effects of SGLT2 Inhibitors in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials
Authors: Fernando R Pessoa, Francisco Cezar A de Moraes, Maria Eduarda Cavalcanti Souza, Anna Rodrigues, Eric Pasqualotto, Isabela Fernandes, Antonio Maria Zacarias Araujo Monteiro, Dilma do Socorro Moraes de Souza
Journal: Circulation (2023)

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a class of drugs initially developed for the treatment of type 2 diabetes mellitus which demonstrated benefits in reducing cardiovascular complications. However, the benefits of using SGLT2i after acute myocardial infarction (AMI) still have limited evidence. Research Questions: Does the use of SGLT2i after percutaneous coronary intervention (PCI) due to AMI contribute to reducing mortality and hospitalization due heart failure (HF)? Aims: To assess the benefit of SGLT2i after AMI in patients undergoing PCI in reducing overall mortality, cardiovascular mortality and occurrence of HF. Methods: PubMed, Scopus, Cochrane Library and Web of science databases were searched for randomized controlled trials (RCTs) comparing SGLT2i with placebo after AMI in patients undergoing PCI. We computed risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). The heterogeneity was evaluated with I 2 statistics. R Software, version 4.2.1, was used for statistical analysis. The protocol was registered in PROSPERO (CRD42023424657). Results: A total of 4 RCTs with 1,311 patients, of whom 439 (33.48%) underwent SGLT2i therapy. The mean age was 60.2 (10.9) years in the SGLT2i group and 66.5 (13.8) years in the placebo group. Mean follow-up ranged from 23 to 96 weeks. In the pooled analysis, SGLT2i significantly reduced hospitalization due to HF (RR 0.39; 95% CI 0.20-0.75; p&amp;lt;0.01; I 2 =0%). There were no significant differences between SGLT2i and placebo regarding cardiovascular death (RR 0.52; 95% CI 0.23-1.18; p=0.12; I 2 =20%), non-cardiovascular death (RR 0.79; 95% CI 0.26-2.38; p=0.68; I 2 =0%) and all- cause death (RR 0.59; 95% CI 0.30-1.13; p=0.11; I 2 =12%). Conclusion(s): SGLT2i were associated with a reduction in hospitalization due to HF. However, no differences were found for cardiovascular, non-cardiovascular or all-cause deaths.