tbuckley/cabot-search huggingface dataset:
Abstract 4139027: Glucagon-like Peptide-1 Receptor Agonist Use and Cardiac Outcomes in Patients with End Stage Kidney Disease
Authors: Benjamin Catanese, Cameron Miller, Myles Wolf, Daniel Edmonston
Journal: Circulation (2024)

Background: Despite the substantial cardiovascular (CV) risk experienced by people with end-stage kidney disease (ESKD), few medications improve CV outcomes in this population. Glucagon-like peptide-1 receptor agonists (GLP1RA) improve CV outcomes in CKD, and several are safe for use in ESKD, but no outcomes trial has studied GLP1RA in ESKD. We hypothesize that CV outcomes will be improved in people with ESKD and type 2 diabetes mellitus (T2D) who initiated GLP1RA as compared to dipeptidyl peptidase-4 inhibitors (DPP4i), an agent that comparably lowers glucose but has not been shown to improve CV outcomes. Methods: We analyzed electronic health records, claims, and Medicare Part D data from the United States Renal Data System between 2011 and 2021 to identify new users of GLP1RA or DPP4i after initiation of dialysis. We restricted the cohort to patients with T2D based on ICD codes and used 2:1 propensity score matching of DPP4i to GLP1RA users based on 22 covariates. The primary outcome was a modified major adverse cardiovascular events (MACE) composite of myocardial infarction (MI), stroke, and all-cause mortality. We applied cause-specific Cox proportional hazard models and Fine-Gray subdistribution hazard models to account for competing risks to analyze the primary outcome and its components. Results: The matched cohort included 10,196 DPP4i and 5976 GLP1RA initiators. The median age was 59 years, 49% were women, and 29% were of Black race. Compared to DPP4i initiators, GLP1RA initiators experienced a significantly lower risk of MACE (HR 0.92, 95% CI 0.89 – 0.96; Table). The risk of nonfatal MI or stroke was also significantly lower for GLP1RA initiators (HR 0.91, 95% CI 0.87-0.95). All-cause mortality did not differ based on cause-specific hazard modeling (HR 0.97, 95% CI 0.88-1.06), but was significant based on subdistribution hazard modeling (HR 0.86, 95% CI 0.79-0.94). Conclusion: Initiation of GLP1RA was associated with significantly lower risk of MACE in patients with T2D and ESKD compared to DPP4i.
Abstract 4139040: Prevalence and Clinical Characteristics of US Patients with Systemic Inflammation and Atherosclerotic Cardiovascular Disease With or Without Chronic Kidney Disease
Authors: Lei Lv, Meixia Liu, Matt Strum, Benjamin Chastek, Jonathan Johnson, Ty Gluckman
Journal: Circulation (2024)

Background: High-sensitivity C-reactive protein (hsCRP) is a well-established biomarker of inflammation. Systemic inflammation is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD); however, the prevalence of systemic inflammation (SI) and the associated patient characteristics remain unknown. Aim: To define the prevalence and clinical characteristics of patients with SI and ASCVD with or without chronic kidney disease (CKD). Methods: A retrospective cross-sectional analysis of US adults (aged ≥18 years) with any diagnoses of ASCVD evaluated with a hsCRP test using the Optum ® de-identified electronic health record dataset between 2017 and 2021. SI was defined as an hsCRP level of 2–10 mg/L. The prevalence of SI was evaluated by calendar year, stratified to three groups by presence of ASCVD, ASCVD with any stage of CKD, and ASCVD with stage 3 or 4 CKD. Concomitant comorbidities and medications used were assessed and stratified by CKD severity. Results: Across the study period, prevalence of hsCRP testing among patients with ASCVD remained relatively stable (0.87–0.98%). Among patients who underwent hsCRP testing, SI was present in 38.0%, 42.3% and 51.5% of patients with ASCVD, ASCVD with CKD, and ASCVD with stage 3 or 4 CKD averaged across the study period, respectively ( Figure 1 ). The prevalence of SI remained largely unchanged over the study period across the three groups ( Figure 1 ). Among those with SI, a higher Charlson Comorbidity Index was noted in those with CKD: 0.75–0.78 in those with ASCVD, 0.99–1.21 in those with ASCVD and CKD, and 1.71–1.89 in those with ASCVD and stage 3 or 4 CKD. The most common medications utilized in those with SI were lipid-lowering therapy (70.5% [ASCVD], 72.7% [ASCVD with any CKD] and 75.4% [ASCVD with stage 3 or 4 CKD]) and antihypertensive therapy (72.8% [ASCVD], 79.3% [ASCVD with any CKD] and 86.7% [ASCVD with stage 3 or 4 CKD]) averaged across the study period. Conclusion: Among patients with ASCVD undergoing hsCRP testing, SI was common, particularly among those with stage 3 or 4 CKD. This finding may help identify at-risk individuals who are likely to benefit from treatment of SI.
Abstract 4138146: Heart Failure and Cardiomyopathy Mortality Trends and Disparities among Obese Populations: A 20-Year U.S. Study
Authors: Yong Hao Yeo, Boon Jian San, Ela Ahmad, Min Choon Tan, Yuh Miin Sin, Milena Jani, Richard Bloomingdale
Journal: Circulation (2024)

Background: The prevalence of obesity has been increasing over the past decades. While heart failure (HF) and obesity management evolve, real-world data on their population-level mortality benefits is lacking. Objective: Our study aimed to assess the HF and cardiomyopathy-related mortality trends among patients with obesity in the United States (U.S.) and disparities across demographics. Methods: We queried the CDC WONDER database among adults aged ≥ 25 from 1999 to 2019. We included patients in whom HF and cardiomyopathy were listed as the main cause of death, with obesity as a contributing cause of death. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals. We determined trends over time by estimating the annual percent change (APC) using the Joinpoint regression program. We evaluated the social vulnerability of U.S. counties (2014-2018) using the CDC/ATSDR SVI database. Results: There were 29,334 deaths related to HF and cardiomyopathy among patients with comorbid obesity. The overall AAMR increased from 0.41 (95% CI, 0.38-0.44) in 1999 to 0.94 (95% CI, 0.90-0.98) in 2019, with an APC of 3.78 (95% CI, 3.41-4.14, P&lt;0.01). The percentage increase in the crude mortality rate of HF and cardiomyopathy among individuals with comorbid obesity was greater than that among those without comorbid obesity. Males had a higher AAMR than females (0.78 [95% CI, 0.77-0.79] vs 0.55 [95% CI, 0.54-0.56]). African Americans also had higher AAMR than Whites (1.35 [95% CI, 1.32-1.39] vs 0.62 [95% CI, 0.61-0.63]). The AAMR was higher in rural areas than in urban regions (0.76 [95% CI, 0.74-0.78] vs 0.66 [95% CI, 0.65-0.67]). The overall AAMR was higher in counties with social vulnerability index-Q4 (SVI-Q4) (most vulnerable) (1.08 [95% CI: 1.04-1.12]) compared to SVI-Q1 (least vulnerable) (0.63 [95% CI: 0.60-0.66]) with a risk ratio of 1.71 (95% CI: 1.61-1.83). Conclusion: Our study reveals the rising trend of HF and cardiomyopathy mortality in individuals with comorbid obesity. Males, African Americans, and individuals from rural regions had higher AAMR than their counterparts. This warrants the formulation of targeted healthcare policies for this vulnerable group.
Abstract 4138125: Interleukin-1 Antagonists in the Management of Recurrent Pericarditis due to Autoimmune Diseases: Beyond AIRTRIP and RHAPSODY
Authors: Jaideep Singh Bhalla, Ushasi Saraswati, Akiva Rosenzveig, Alveena Syed, Muhammad Majid, Allan Klein
Journal: Circulation (2024)

Background: Anakinra (AK) and Rilonacept (RL) are increasingly being used as steroid sparing agents in the management of recurrent pericarditis due to their antagonism of the IL-1 mediated innate immune activation. However, it is uncertain whether they would show a similar response in reducing recurrence of Autoimmune Pericarditis (AP), since this is mediated by the adaptive immune system and this cohort was excluded from the AIRTRIP/RHAPSODY trials. Hypothesis: IL-1 antagonists (IL-1#) maintain clinical remission in AP refractory to other disease modifying therapy (DMT). Aims: To evaluate the efficacy and safety of IL-1# in treating pericarditis associated with autoimmune diseases. Methods: We retrospectively analysed 31 adults at our Pericardial Center with AP that was refractory to treatment with standard DMT aimed at managing the underlying disorder and were started on AK/RL after shared decision making with the patient and their rheumatologist. Markers of disease activity (serologic/imaging) and adverse effects were obtained during the treatment period. Results: The cohort included 80% females with median age 51 y with ≥ 2 verified recurrences on standard DMT and treated with AK (68%)/RL (32%) for a median of 21 months. Majority of the patients had rheumatoid arthritis and inflammatory colitis. IL-1# therapy was associated with decreased number of flares, C-reactive protein levels, and late gadolinium enhancement on cardiac magnetic resonance imaging, the former 2 parameters reaching statistical significance. 6 cases of infection were noted; 2 required IL-1# cessation. No malignancies, major cardiovascular events or death was noted during follow-up. Conclusions: IL-1# (AK/RL) are associated with clinical improvement in patients with refractory AP, supporting the growing evidence from case reports in literature. This is the first study of this sample size analysing outcomes in patients with AP on IL-1#. This may suggest the presence of additional molecular immune pathways mediating recurrence in AP that need elucidation in future prospective studies.
Abstract 4139241: The Triple Medical Therapy Prevented Post-infarction Cardiac Rupture via Inhibiting MMPs Over-activation and Macrophage-induced Cardiac Fibroblasts Ferroptosis Through TRAF6/NF-κB/C/EBPβ Down-regulation mediated by different microRNAs.
Authors: Ruijie TANG, Lili ZHANG, Yuejin Yang
Journal: Circulation (2024)

Background: Percutaneous coronary intervention has significantly improved the prognosis of STEMI, though there is still the risk of fetal mechanical complications, particularly cardiac rupture(CR), which remains an international clinical problem unresolved. Hypothesis: We hypothesized that the combined triple medical therapy( ANT ) with A torvastatin, N icorandil and Chinese patent medicine T ongxinluo(TXL) could be effective in post-infarction CR precautions via significantly inhibiting macrophage activation and secondary ferroptosis of cardiac fibroblasts(CFs) through TRAF6/NF-κB/C/EBPβ pathway. Methods: The 14-day survival and CR rates of AMI mice treated with Atorvastatin, Nicorandil and Tongxinluo, singly or in dual and triple combination, were all compared via the Kaplan-Meier curves. Then the inflammation level and infarct region were measured via ELISA, immunoblot and histopathology. Sequentially immunoprecipitation, luciferase report gene and transcriptome sequencing were introduced to understand the role of the TRAF6/NF-κB/C/EBPβ pathway and its upstream micro-RNAs in CR prevention. Further, in-vitro experiments were performed to demonstrate the crosstalk between macrophages activation and CFs ferroptosis in CR prevention. Results: Among all therapies involved, the triple combined ANT therapy supremely reduced the incidence of post-infarction CR (from 26.7% to 10.0%) and the mortality of AMI (from 30.0% to 13.3%), during which macrophages reduced most nuclear NF-κB p65 and C/EPBβ by nearly 70% simultaneously through miR215-5p-, miR122-5p-, miR-299b-3p-mediated TRAF6 inhibition, with 50%+ MMP9 cut and more extracellular matrix remaining, especially collagens, Syndecan-1, Laminin and Agrin. And, with the ANT administration, only 20% macrophages remained in peri-infarct areas, accompanied by the lowest serum inflammatory level. Furthermore, CF ferroptosis alleviated most, evidenced by the 4-fold GPX4 and 3-fold FSP-1 up-regulation. Two independent anti-ferroptotic system, GPX4 and FSP-1, worked equally in the nicorandil effect on CF survival, however, with GPX4 or FSP-1 overwhelmingly underlying atorvastatin or Tongxinluo protection against CF ferroptosis respectively. Conclusions: Our results indicated the ANT combination upmost alleviated the excessive excitation of M1 macrophages and its induced CF ferroptosis via prohibiting TRAF6-mediated NF-κB and C/EBPβ translocation, and facilitated myocardial repair to prevent post-infarction cardiac rupture onset.
Abstract 4139035: Health Literacy in Men and in Women With Type 2 Diabetes Undergoing Coronary Angiography
Authors: Magdalena Neyer, Johannes Vogel, Pascal Elsner, Thomas Plattner, Alexander Vonbank, Arthur Mader, Barbara Larcher, Andreas Leiherer, Axel Muendlein, Matthias Frick, Heinz Drexel, Christoph H Saely
Journal: Circulation (2024)

Health literacy reflects the ability to make appropriate health decisions and affects health outcomes. It therefore is an important parameter in patient care and for health care providers. Health literacy in patients undergoing coronary angiography, the standard procedure for the definite evaluation of coronary artery disease (CAD) is unclear and is addressed in the present study. We recruited 515 consecutive patients (383 men and 132 women) undergoing coronary angiography for the evaluation of established or suspected stable CAD in a tertiary care setting in central Europe. Health literacy was measured using the validated HLS-EU-Q16 questionnaire. A response rate of 80.4% was achieved. Overall, 177 patients (i.e. 34.3% of the cohort) had type 2 diabetes (T2DM); the prevalence of T2DM was 36.8% in men and in 27.3% in women (p=0.047). Comparing T2DM patients to those who did not have diabetes, overall median health literacy scores (HLS) were 13 [IQR=11-15] vs. 13 [IQR=10-15] among men (p=0.424) and 12 [IQR=10-15] vs. 13 [IQR=10.25-15] among women (p=0.517). Prevalence rates of adequate (HLS 13-16), problematic (HLS 9-12) and inadequate (HLS 0-8) health literacy did not differ significantly between patients with T2DM vs. subjects without T2DM (53.0% vs. 55.4%, 34.8% vs. 29.9% and 12.2% vs. 14.7% among men and 37.5% vs. 55.6%, 45.8% vs. 31.9% and 16.7% vs. 12.5% among women, respectively. We conclude that among patients undergoing coronary angiography for the evaluation of established or suspected stable CAD, health literacy regardless of sex is suboptimal both in patients with T2DM and in non-diabetic subjects.
Abstract 4138942: Loss of the v-SNARE VAMP8 Protects Against Aortic Aneurysms: Implications of Impaired Platelet Cargo Release
Authors: Shayan Mohammadmoradi, Elizabeth Driehaus, Hammodah Alfar, Smita Joshi, Sidney Whiteheart
Journal: Circulation (2024)

Introduction and Objective: As vascular sentries, platelets, and their ability to release a host of bioactive molecules, are critical for vascular homeostasis as well as hemostasis. Despite data linking platelet activation to abdominal aortic aneurysms (AAA) and rupture, the underlying mechanisms remain poorly understood. This study addresses the hypothesis that VAMP8, the primary v-SNARE controlling platelet exocytosis, significantly contributes to AAA formation. Approach and Results: A retrospective, single-center, multiple comparisons study of adult aneurysmal patients admitted to UKHealthCare between 2004 and 2023 revealed a significantly lower platelet count in AAA patients than in healthy individuals. These results were also observed in experimental aneurysm models using an AngII-infused hypercholesterolemic mouse model, suggesting increased platelet consumption. Our results indicated a noticeable accumulation of platelets at elastin break sites and false lumen formation in the abdominal aortas of aneurysmal mice. The platelet accumulation showed significant colocalization with VAMP8, alongside a marked upregulation of VAMP8 in the thrombus segments of the aneurysmal tissue compared to the control. WT and VAMP8-/- mice were infused with AngII (1,000 ng/kg/min) or saline two weeks post PCSK9 AAV infection for 28 days using subcutaneously implanted Alzet mini-osmotic pumps. Our results revealed that VAMP8-/- mice are protected against AngII-driven aortic rupture. Both in vivo and ex vivo aortic diameter analysis indicated that VAMP8 deficiency profoundly attenuated AngII-induced AAA compared to controls. Bulk RNA-seq analysis on washed platelets isolated from VAMP8-/- compared to WT mice revealed distinct transcriptomic profiles with significant enrichment in pathways related to aortic remodeling and aneurysm pathogenesis. Further, RNA-seq analysis of suprarenal aortas (5-day AngII infusion) showed that VAMP8 deficiency significantly reduced extracellular matrix degradation and increased aortic wall stability, as observed by the downregulation of matrix metalloproteinases (MMPs) and the upregulation of collagen synthesis genes. Conclusion: VAMP8 deficiency results in the profound attenuation of aortic aneurysms, potentially via enhanced ECM stability, introducing a novel paradigm for understanding the impact of platelet cargo secretion in aortopathies.
Abstract 4138915: Exploring mediation through major bleeding between direct oral anticoagulants and cardiovascular (CV) events
Authors: Zhong Yuan, Martijn Schuemie, James Weaver, Elliot Barnathan
Journal: Circulation (2024)

Introduction: Although extracranial major bleeding (EMB) is often transient and manageable with supportive care, there is concern that EMB may have a subsequent detrimental effect on CV outcomes. However, a causal relationship is unclear, because the association is often confounded by underlying disease and comorbidities. Clinical trial data for more comprehensive analyses via advanced modeling are limited. Research Question: What is the effect of rivaroxaban vs. warfarin on CV outcomes mediated through EMB? Aim: To determine the extent of the effect of rivaroxaban vs. warfarin on CV outcomes that is mediated through their differential impact on EMB using a novel, advanced modeling approach (EUPAS1000000168). Methods: Using 5 US observational databases from routine clinical practice (01-11-2010 to 31-12-2022), adult patients with non-valvular atrial fibrillation (NVAF) were identified to establish the target and comparator cohorts, with 1 st exposure as index date. Treatment balance was achieved by matching on propensity scores derived from large-scale regularized regression. Cox proportional hazards models estimated the main effect on CV outcomes (myocardial infarction, ischemic stroke, and composite endpoint) for rivaroxaban vs warfarin, with target and comparator time-at-risk right-censored at therapy end or switch, event occurrence, or database observation end. The EMB mediation effect on outcomes was estimated by including EMB as time-varying covariate, while controlling mediator-outcome confounding by including a mediator risk score in the outcome model. Comparative analyses were conducted only when pre-specified diagnostics passed for covariate balance, equipoise, and systematic error estimated through negative controls. Results: In 5 databases, 378,384 rivaroxaban initiators were matched to 601,174 warfarin initiators with NVAF. Common comorbidities included hypertension, hyperlipidemia, coronary artery disease, and heart failure. Main effects and indirect effects (mediation effects) are in Table A. Conclusion: This analysis suggested that EMB had no impact on the effect of rivaroxaban vs. warfarin on CV outcomes. A limitation is that EMB occurrence and CV events after EMB were limited, which reduced mediation impact.
Abstract 4139087: An Interpretable Model for Predicting Preoperative Cardiorespiratory Fitness Using Wearable Data in Free-Living Conditions.
Authors: Iqram Hussain, Julianna Zeepvat, Cary Reid, Sara Czaja, Kane Pryor, Richard Boyer
Journal: Circulation (2024)

Introduction: Assessing preoperative cardiorespiratory fitness (CRF) is essential for determining surgical risk and outcomes. The advent of wrist-worn devices equipped with heart rate and activity monitoring presents new opportunities for CRF evaluation. Traditionally, CRF has been measured using submaximal exercise tests, such as the 6-minute walk test (6MWT). Monitoring CRF in everyday activities may offer valuable insights into patients' preoperative fitness levels. This study explores the potential of predicting 6MWT distances using a data-driven physiological CRF model derived from wearable devices in elderly patients in their free-living environments. Hypothesis: Machine-learning algorithms can accurately estimate CRF using data from fitness trackers. Methods: We examined heart rate and activity data from Fitbit devices worn by 65 older adult patients undergoing major noncardiac surgery. Data was collected over a week in free-living conditions. We aimed to utilize this wearable technology to forecast CRF in this group. A machine-learning ensemble regression model was employed to predict CRF, with 6MWT outcomes as the reference. The Shapley Feature Attribution method was applied to understand the contribution of specific features derived from wearable data to the model, aiding in personalized fitness predictions. Results: Higher CRF was associated with increased levels of moderate to vigorous physical activity (MVPA), maximal activity energy expenditure (aEEmax), 4-minute heart rate recovery (HRR), and non-linear heart rate variability (HRV) features. These measures positively correlated with improved 6MWT outcomes. Our regression models, including random forest and linear regression, showed strong predictive capabilities, with coefficients of determination (R^2) of 0.91 and 0.81, respectively. Shapley Feature Attribution analysis revealed that higher levels of MVPA, aEEmax, HRR240, and non-linear HRV dynamics are reliable indicators of better CRF test performance. Conclusions: Integrating wearable activity and heart rate data offers a robust framework for preoperative CRF assessment, enhancing surgical risk evaluation and patient outcomes in everyday conditions.