tbuckley/cabot-search huggingface dataset:
Abstract 4139230: Mapping the Molecular Progression of Human Coronary Atherosclerosis Confirms Key Role of Smooth Muscle Cell Phenotype and Highlights Novel Regulators of Phenotypic Fate
Authors: Sarah Parker, Chunhong Mao, Yizhi Wang, Austin Seals, Do-Kyun Kim, Yingzhou Lu, saurabh bhardwaj, Dongping Du, Genesio Karere, David Caudell, Richard Vanderheide, James Hixson, Jennifer Van Eyk, Yue Wang, David Herrington
Journal: Circulation (2024)

Background: clarity in the molecular mechanisms contributing to pre-clinical stages of coronary atherosclerosis is needed to develop novel early diagnostic tools and more effective preventive interventions. Methods: We completed untargeted proteomic and RNA expression analysis on proximal coronary arterial (CA) tissues from young adults who died of trauma with no antemortem suspicion of coronary disease (n=322, mean age (range): 34.1 yrs. (15-59); sex: M-239, F-83; race: W-218, B-88, other-16), including n=180 (56%) with morphologic evidence of pre-clinical atherosclerosis. Proteomic data (n=1900 proteins) were analyzed using manifold learning and unsupervised latent feature (LF) detection methods to define the pseudo-temporal progression of disease from normal to advanced atherosclerosis and to identify molecular drivers of disease initiation and progression. Correlation and network mapping of the mRNA data (n=16,707 transcripts, including n=1707 annotated transcription factors [TFs]) from the same arterial samples was used to define the transcriptional regulatory networks (TRNs) associated with the observed proteomic LF dynamics. Results: Four of seven identified LFs had a significant (FDR &lt;p.01) association with plaque progression. Among these, a standout LF clearly represented quiescent, contractile smooth muscle cells (SMC) with progressive and then poignantly reduced abundance in late-stage lesions. This LF was enriched with proteins related to cell adhesion and SMC contractility, including 14 previously implicated in the pathogenesis of atherosclerosis via GWAS analyses. Analysis of TRNs revealed 36 regulatory TFs with (1) a predicted binding site in the promotor of SMC LF marker proteins, (2) observed expression that was strongly associated with this SMC LF and (3) significant correlation between predicted activity and observed abundance, including the established SMC phenotype regulator SRF. Expression of regulatory TFs and SMC LF markers in public single-cell RNAseq data from normal and atherosclerotic human coronary tissues suggested both SMC intrinsic and cell-cell crosstalk TRNs. Conclusions: The pseudotemporal pattern of the SMC LF was consistent with SMC phenotype changes as early initiating events in atherosclerosis of the CA. Therapies to promote or inhibit activity of these identified TFs may prevent against early lesion formation and atherosclerosis progression by supporting SMC phenotype stability.
Abstract 4139180: Navigating Trust and Preferences in Research Data Sharing: Addressing Racial Disparities for Inclusive Research Practices
Authors: Stephanie Ninode Rivera, Sarah Eslami, Yihong Zhao, Ruth Masterson Creber
Journal: Circulation (2024)

Objective: Contemporary data sharing policies from the National Institutes of Health have expanded data sharing. Participants' perspectives are not well understood and could have an adverse impact on participation in cardiac research. We evaluated participants' preferences for health data, and strategies to enhance trust in data sharing practices. Methods: In March 2023, we conducted a nationally representative online survey with 610 US adults. We implemented a cross-sectional survey that assessed: (1) participant preferences about health data they are willing to share with external entities (e.g. health policy institutions, public health organizations, health technology companies, private foundations, etc), and (2) the impact on trust in research if participants could decide which external recipients (e.g, clinical symptom, biological, mental health, sexual health) receive the data. We used logistic regression models to assess sociodemographic variances in their willingness to share different types of data. Results: Among 610 participants, the mean age was 46 years (± 16; range 19-93) of which 50% were female, 77% identified as White and 7% identified as Hispanic/Latinx. Figure 1 shows the adjusted odds ratio (ORs) and 95% confidence intervals (95% CI) for willingness to share different data types with public health institutions and health technology companies by self-reported race. Black participants were significantly less likely to share most health data with public health organizations, including mental health (biological (OR: 0.562 [95% CI 0.342, 0.920]), clinical symptom (OR:0.455 [95% CI 0.275, 0.756]), and imaging data (OR:0.488 [95% CI 0.258, 0.714]) compared to White participants. Fewer racial differences were noted for sharing different types of data with health technology companies. Moreover, 63% of participants expressed that their trust in researchers would improve if given control over the data recipients (Figure 2). DISCUSSION: Participants exhibit reluctance to share specific types of personal research data, emphasizing strong preferences regarding external data access. This highlights the need for a critical reassessment of current data sharing policies to align with participant concerns. Conclusion: It is imperative for data sharing policies to integrate diverse patient viewpoints to mitigate the risk of distrust and a potential unintended consequence of lower participation among racial and ethnic minority participants in cardiac research.
Abstract 4138967: SLPI and Serpin E1 differentiate between and can be used as AKI biomarkers in obese and non-obese patients
Authors: Marcin Wozniak, Naomi Brown, Haiyan Pan, Barbara Horley, Lathishia Joel-David, Hardeep Aujla, Gavin Murphy, Bin BIN YANG
Journal: Circulation (2024)

Background: Acute kidney injury (AKI) is among the most common complications after cardiac surgery, with an 18% prevalence and is associated with an increased risk of death. Cardiopulmonary bypass surgery generates danger-associated molecular patterns that trigger a release of proinflammatory molecules that can lead to AKI. Obesity is also associated with chronic low-grade inflammation and an increased risk for AKI. We investigated the utility of inflammatory molecules in the diagnosis of AKI in obese and non-obese cardiac surgery patients. Methods: A panel of 13 circulating plasma molecules, including CXCL1, CXCL10, CXCL13, CCL22, IL-5,6,8,10,16, SLPI, TIM1, Properdin, Serpins E1 and A3, was measured using MAGPIX. The samples were collected from 95 MaRACAS patients (NCT02315183) before and 6-72 hours (h) after surgery. Obesity was defined as BMI&gt;=32, based on our previous study. Results: There was no significant difference in the incidence of AKI between obese (46%) and non-obese patients (58%). The levels of the selected molecules were compared between AKI and non-AKI groups in patients with and without obesity. In obese patients with AKI, the levels of serpin E1 were lower before surgery (22.16 vs 40.94ng/mL, q=0.03) and higher 6h post-surgery (49.26 vs 21.65ng/mL, q=0.02), while properdin was lower 72h post-surgery (11.12 vs 14.35ng/mL, q=0.01). In the non-obese group, CXCL10 was higher in the AKI group 6-48h post-surgery, peaking at 6h (218.5pg/mL vs 131.38pg/mL, q=0.02); CXCL13 was higher at 6h (435.78 vs 291.0pg/mL, q=0.04) and 24h (215.18 vs 157.49pg/mL, q=0.04); IL-16 was higher at 6h (256.01 vs 174.44, q=0.04) and 24h (344.94 vs 174.02, q=0.02); and SLPI was higher 6-72h post-surgery, peaking at 6h (50.44 vs 33.53 at 6h, q&lt;0.01). ROC AUC analyses showed that Serpin E1 had a diagnostic value for AKI in obese patients pre (75.6%, 58.3%-92.8%) and 6h post-surgery (80%, 64.6%-95.4%); while SLPI had a diagnostic value in non-obese patients 6h after surgery (75.0%, 62.2%-87.8%). Conclusions: AKI leads to different expression levels of proinflammatory molecules in obese and non-obese patients undergoing cardiac surgery. SLPI and Serpin E1 have diagnostic potential as biomarkers, but should be validated in larger cohorts.
Abstract 4138093: Impact of Pre-Existing Cardiovascular Diseases on Severe Maternal Morbidity and Mortality During Delivery in Pregnant Women with Atrial Fibrillation
Authors: Yong Hao Yeo, Boon Jian San, Tze Ern Ong, Min Choon Tan, Kamala Tamirisa, Nishaki Mehta
Journal: Circulation (2024)

Background: While the incidence of atrial fibrillation (AF) among pregnant women is increasing, the impact of pre-existing cardiovascular disease (CVD) on pregnant women with AF is not well-described in a large national database. Objective: This study aimed to compare pregnancy outcomes between those with AF alone and those with AF and pre-existing CVD categorized by the modified World Health Organization classification (mWHO). Methods: We used the Nationwide Readmissions Database and included all pregnant women with AF (2017-2020). We categorized the cohort into two groups depending on the presence of pre-existing CVD. We assessed the risk of severe maternal morbidity and mortality (SMM) outcomes, as defined by the CDC, between pregnant women with AF alone and those with AF and pre-existing CVD. Results: Out of the total 2,348 pregnant women with AF, 348 (14.8%) had pre-existing CVD. 69 (19.8%) had mWHO I- II CVD, 150 (43.1%) had mWHO II/III- IV CVD, and 129 (37.1%) had CVD not classified in mWHO. Overall, those with pre-existing CVD had higher rates of SMM/death (28.2% vs. 11.1%, P&lt;0.01), non-transfusion SMM/death (25.9% vs. 9.8%, P&lt;0.01), and cardiac SMM/death (21.6% vs. 5.5%, P&lt;0.01) than those with AF alone. After adjustment, those with pre-existing mWHO I- II CVD and AF were not associated with higher odds of SMM/death (aOR: 0.81, 95% CI: 0.34-1.92, P=0.64), non-transfusion SMM/death (aOR: 0.45, 95% CI: 0.14-1.46, P=0.18), and cardiac SMM/death (aOR: 0.55, 95% CI: 0.13-2.30, P=0.41) than those with AF alone. Patients with pre-existing mWHO II/III- IV CVD and AF had higher odds of SMM/death (aOR: 7.21, 95% CI: 4.94-10.53, P&lt;0.01), non-transfusion SMM/death (aOR: 7.38, 95% CI: 5.03-10.82, P&lt;0.01), and cardiac SMM/death (aOR: 12.02, 95% CI: 7.99-18.10, P&lt;0.01) than those with AF alone. Patients with pre-existing CVD not classified in mWHO and AF did not have higher odds of SMM/death (aOR: 1.64, 95% CI: 0.99-2.71, P=0.06) but had higher odds of non-transfusion SMM/death (aOR: 1.77, 95% CI: 1.06-2.97, P=0.03) and cardiac SMM/death (aOR: 1.96, 95% CI: 1.05-3.67, P=0.04). Conclusion: Compared to pregnant women with AF alone, those with pre-existing mWHO II/III- IV CVD and AF were associated with worse SMM/death, non-transfusion SMM/death, and cardiac SMM/death. However, similar findings were not noted in those with pre-existing mWHO I- II CVD and AF pregnant women.
Abstract 4138097: Single-Cell Analysis Reveals Critical Role of Macrophage Epsin in Regulating Origin of Foam Cell in Atherosclerosis
Authors: Kulandai Samy Arulsamy, Kui Cui, Kaifu Chen, Hong Chen
Journal: Circulation (2024)

Background: Excessive lipid aggregation in macrophages triggers foam cell formation, contributing to arterial plaque development. This underlies the chronic vascular condition of atherosclerosis like coronary heart disease and ischemic stroke. Epsins, endocytic adaptor proteins, are recognized as key accelerators of atherosclerosis progression, particularly in individuals adhering to a Western diet (WD). However, the intricate molecular mechanisms governing the role of epsins in foam cell formation, disease progression, and potential therapeutic interventions remain elusive. Here, we aim to probe the metabolic regulatory functions of epsins in atherosclerosis and design the potential treatment strategies. Methods: We established mouse models fed a WD (16 weeks), including ApoE-deficient (ApoE -/- ) mice and macrophage-specific deletion of epsin in ApoE-deficient backgrounds (LysM-DKO/ApoE -/- ). Foam cell formation is dramatically hindered in WD-fed LysM-DKO/ApoE -/- compared to ApoE -/- mice. Results: Single-cell transcriptomic profiling of aorta cells revealed 20 cell types, including seven VSMC subtypes, five macrophage subtypes, endothelial cells, and others. Pathway enrichment analysis showed that modulating VSMC1 is involved in inflammation and migration, while VSMC2 is associated with VSMC phenotype switching. We observed increased populations of modulating VSMC1, VSMC2, foamy-Trem2, and inflammatory macrophages in ApoE -/- mice, which decreased significantly in epsin-deficient mice. The RNA velocity analysis revealed that modulating VSMC2 transitioned towards macrophages with probabilities of 0.7 in ApoE -/- mice and 0.01 in LysM-DKO/ApoE -/- mice. Additionally, epsin deletion reversed endothelial cell dysfunction by preventing the endothelial-to-mesenchymal transition. Using MEBOCOST tool, we identified the cholesterol, glucose mediated cell-signals are downregulated in LysM-DKO/ApoE -/- . Moreover, enhanced inflammatory signals via ligands such as Il1b and C1qa in VSMCs are downregulated when epsin is depleted. Conclusion: Single-cell data analysis reveals that epsin deletion reduces foam cell formation and rewires VSMC cells function by inhibiting VSMC2 to macrophage transition. Cholesterol and glucose-mediated metabolic signals play a pivotal role in atherosclerotic lesion formation. Epsin deletion diminishes these metabolic, and inflammatory signals. Therefore, targeting epsin could offer a novel therapeutic strategy for treating atherosclerosis.
Abstract 4138067: Prognostic effect of echocardiography-assessed coronary flow reserve in heart failure with preserved ejection fraction
Authors: Xiaotong Cui, Yanyan Wang, Dan Liu, Yamei Xu, Yingjie Zhao, Yu Song, Xueting Han, Shuai Yuan, Shun Yao, Xueting Yu, Zhonglei Xie, zimu wang, Haiyan Chen, XIAN HONG SHU, kai hu, Jingmin Zhou, Junbo Ge
Journal: Circulation (2024)

Background: Coronary microvascular dysfunction (CMD) has been found common in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The simplest and most feasible method for evaluating CMD is to measure coronary flow reserve (CFR) using echocardiography. Hypothesis: Whether the echocardiography-assessed CFR could predict the outcome in HFpEF patients is still unknown. Aims: We designed a prospective cohort study to investigate the prognostic effect of echocardiography-assessed CFR in HFpEF. Methods: Between December 2021 and April 2024, confirmed hospitalized HF patients with left ventricular ejection fraction (LVEF) ≥40% in Zhongshan Hospital Fudan University (Shanghai, China) were prospectively and consecutively enrolled. During index hospitalization, patients underwent the adenosine-based transthoracic Doppler echocardiography to evaluate the CFR of the left anterior descending branch. Treatments were given according to guidelines. Follow-up after discharge was carried out at outpatient or by telephone call. The primary endpoint was all-cause mortality. Results: A total of 176 HFpEF patients (111 males, mean age 66.8 ± 11.8 years old) were included. Median follow-up time was 290 days. Totally 93 patients (52.8%) demonstrated CFR &lt;2.5, which is the classical CMD diagnostic threshold. However, CFR=2.5 had no significant discriminative ability in predicting mortality in this HFpEF cohort. Then the receiver operating characteristic curve combined with Youden's index were performed and indicated CFR=1.72 as the cut-off value to predict all-cause mortality. So patients were divided into two groups by CFR &lt;1.72 (n=28) and CFR ≥1.72 (n=148). Compared with patients with CFR ≥1.72, HFpEF patients with CFR &lt;1.72 were more likely to have atrial fibrillation, had higher level of high sensitive Troponin T, NT-proBNP, urinary albumin to creatinine ratio, and lower level of reactive hyperemia index measured by EndoPAT. During follow-up, 4 and 3 patients died in CFR &lt; or ≥ 1.72 group, respectively (14.3% vs. 2.0%, P=0.013). Kaplan-Meier curves showed that patients with CFR &lt;1.72 had poorer survival rate (Log-rank P=0.003). HFpEF patients had much higher risk in all-cause mortality if CFR &lt;1.72 (hazard ratio 7.873, 95% CI 1.683-36.840) after adjusted for age, sex, NYHA class and LVEF. Conclusions: Lower level of echocardiography-assessed CFR obtained in hospitalization was associated with higher risk of all-cause mortality after discharge in HFpEF patients.
Abstract 4138075: Trends in the Prevalence of Co-morbid Cardiovascular Disease and Cancer Survivorship: a National Health and Nutrition Examination Survey Analysis
Authors: Ryan Truitte, Joshua Jacobs, Alexander Zheutlin, Michael Ho, Caroline Himbert, Roberta Florido, Adam Bress
Journal: Circulation (2024)

Background: Cancer and cardiovascular disease (CVD) share risk factors including smoking, obesity, hypertension, and sedentary lifestyle. Advancements in cancer therapies have increased survivorship thereby increasing the likelihood of developing CVD among cancer survivors. Quantifying national trends in co-morbid cancer and CVD can help improve the integration of CVD prevention strategies along the cancer care continuum. Methods: We conducted serial, cross-sectional analyses of National Health and Nutrition Examination Survey (NHANES) participants from 2009-2020. We analyzed trends in cancer history, prevalent CVD, and prevalent predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk (categorized as &gt;20%, 7.5-&lt;20%, and 5-7.5%). Cancer and CVD history were defined by self-reported cancer diagnosis, and self-reported history of coronary artery disease, heart attack, angina, heart failure, or stroke, respectively. Predicted 10-year ASCVD risk was estimated using the pooled cohort equations. National estimates with 95% confidence intervals (95% CI) were calculated using NHANES survey weighting. Results: Of the 24,196 NHANES participants aged 18-75, 1,392 reported a history of cancer, representing a weighted prevalence of 13.5 million people. Among participants with a history of cancer, 2.3 million (17.0%; 95% CI, 14.2-19.9) had CVD. In those without CVD, 18.3% (95% CI, 15.4-21.1) had a ≥20% predicted risk, 33.8% (95% CI, 30.4-37.3) had a 7.5-&lt;20% risk, and 9.4% (95% CI, 7.4-11.4) had a 5-7.5% risk. Among the US population, the prevalence of co-morbid cancer and CVD, as well as a 10-year ASCVD risk ≥7.5%, increased from 0.93% (95% CI, 0.64-1.34) to 1.36% (95% CI, 0.99-1.87) and 2.02% (95% CI, 1.7-2.4) to 3.06% (95% CI, 2.4-3.8) respectively, between 2009 and 2020 (Figure). Conclusion: The rising prevalence of co-morbid CVD and cancer, coupled with the substantial proportion of cancer survivors at high risk for ASCVD, highlights the need to better integrate care strategies and preventive measures for CVD prevention and management among cancer survivors. Coordinated management and targeted interventions could significantly improve long-term health outcomes for this complex population.
Abstract 4138053: Chronic Kidney Disease Prevalence and Outcomes in Patients with Type 2 Diabetes or Prediabetes at High Cardiovascular Risk: Results from the CINEMA Program
Authors: Sanjana Datla, Zainab Albar, Elke Eaton, Jodie Porges, Matthew Nennstiel, Claire Sullivan, lloyd greene, Sadeer Al-Kindi, Aparna Padiyar, Mahboob Rahman, Sanjay Rajagopalan, Ian Neeland
Journal: Circulation (2024)

Introduction: Chronic kidney disease (CKD) is a global health concern, particularly among patients with type 2 diabetes mellitus (T2DM) and prediabetes, who are at high risk of cardiovascular disease (CVD). The Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) program at University Hospitals Cleveland Medical Center aims to address these challenges through a multidisciplinary, patient-centered intervention. This study evaluates CKD prevalence, outcomes, and guideline-directed treatments within the CINEMA program. Methods: Patients with T2DM or prediabetes at high-risk for cardiovascular events, including those with established atherosclerotic CVD, elevated coronary artery calcium score ≥100, chronic heart failure, ischemic stroke, peripheral arterial disease, CKD (defined as eGFR&lt;60mL/min/1.73m 2 and/or by the presence of albuminuria, UACR ≥30 mg/g) and obesity with metabolic syndrome were included. Results: From May 2020 to September 2022, 454 patients were enrolled in the CINEMA program with 45% having a diagnosis of CKD. Among those with CKD, the median age was 64 years, 48% were women, and 47% were Black. 93% had T2DM, 82% had HTN, 52% had established coronary artery disease, and 39% had heart failure. Median eGFR was 49 mL/min/1.73m 2 and median UACR was 42 mg/g. Over two-thirds of those with CKD were stage G3 or greater and 50% were stage A2 or greater. Persons with CKD were more likely to be older, Black, have diabetes and heart failure (p&lt;0.05 for all). UACR screening increased ~8-fold with the CINEMA program. The CINEMA intervention was associated with statistically significant improvements in cardiometabolic risk factors with reductions in body weight (-3.49 lbs), BMI (-0.54 kg/m2), systolic blood pressure (-2.65 mmHg), Hb A1c (-0.63%), total cholesterol (-9.01 mg/dL) and LDL cholesterol (-8.29 mg/dL) with p&lt;0.05 for all. No significant changes were seen in eGFR (p=0.58) or UACR (p=0.41). Notably, there was significant increase in prescription rates of SGLT2i (25% to 55%) and GLP-1RA (14% to 38%) in the CKD population from baseline to follow-up visit (p&lt;0.05). Conclusions: The CINEMA program demonstrates effectiveness in improving ASCVD risk factors and shows promise in addressing CKD outcomes among high-risk patients with T2DM or prediabetes. Enhanced screening for CKD, proper risk stratification, and aggressive implementation of guideline directed medical therapies in patients with CKD can lead to improved outcomes.