tbuckley/cabot-search huggingface dataset:
Abstract 4142669: Elevated remnant cholesterol, LDL cholesterol, and risk of peripheral artery disease: a Mendelian randomization study
Authors: Benjamin Nilsson Wadstrom, Carolina Borges, Anders Wulff, George Smith, Eleanor Sanderson, Borge Nordestgaard
Journal: Circulation (2024)

Background: Elevated remnant cholesterol and low-density lipoprotein (LDL) cholesterol both increase risk of coronary artery disease (CAD), but it is not known if the same is true for peripheral artery disease (PAD). Hypothesis: We tested the hypothesis that elevated remnant cholesterol and LDL cholesterol, each independent of the other, have causal effects on risk of PAD. Methods: We constructed genetic scores from variants near genes known to directly affect levels of remnant cholesterol and LDL cholesterol, identified through a genome-wide association study of individuals in the UK Biobank. We used univariable (remnant cholesterol and LDL cholesterol genetic scores separately) and multivariable (remnant cholesterol and LDL cholesterol genetic scores combined) Mendelian randomization to estimate the causal effects of higher remnant cholesterol and LDL cholesterol levels on odds ratios for PAD (N = 38,414 cases and 758,308 controls) and CAD (N = 221,445 cases and 770,615 controls). Results: Increments in remnant and LDL genetic scores corresponding to 1 mmol/L (39 mg/dL) higher remnant and LDL cholesterol, respectively, were associated with univariable odds ratios for PAD of 2.72 (95% confidence interval: 2.10-3.52) and 1.37 (1.25-1.51), respectively (Image 1); corresponding multivariable odds ratios were 2.16 (1.49-3.12) and 1.14 (1.00-1.30), respectively. For CAD, corresponding univariable odds ratios were 2.92 (2.34-3.64) and 1.67 (1.56-1.79), while multivariable odds ratios were 1.86 (1.39-2.47) and 1.44 (1.29-1.60), respectively. Conclusions: Elevated remnant cholesterol had a causal effect on risk of PAD even after accounting for elevated LDL cholesterol, whereas most of the causal effect from elevated LDL cholesterol on risk of PAD was dependent on simultaneously elevated remnant cholesterol. These results indicate that remnant cholesterol may be the major cholesterol fraction responsible for increased risk of PAD, which calls for clinical trials to test if remnant cholesterol-lowering therapy could prevent PAD.
Abstract 4142403: Temporal Trends And Procedural Safety of Mitral Valve Transcatheter Edge to Edge Repair (M-TEER) in Patients with Previous Coronary Artery Bypass Grafts (CABG). Insight From The National Inpatient Database
Authors: asmaa Ahmed, Mahmoud Eisa, Mohamed Mohamed, Andrew Takla, Muhammad Osama, Sahej Arora, Scott Feitell
Journal: Circulation (2024)

Introduction: M-TEER is a minimally invasive procedure for selected patients with symptomatic mitral regurgitation. Data about the safety of the procedure among post-CABG patients is limited. Methodology: We used the Nationwide Inpatient Sample data between January 2016 and December 2020 to identify M-TEER hospitalizations with history of CABG. Baseline characterestics including demographic data and comorbidities were identified. Primary outcomes were in-hospital all-cause mortality and net all cardiac periprocedural complications defined as a composite of acute myocardial infarction, pacemaker placement, cardiac tamponade, pericardiocentesis, pericardiotomy, pericarditis, and hemopericardium. Results: 48,835 cases of M-TEER were identified during the study period, of whom 9,655 (19.78%) had prior CABG. Patients with prior CABG undergoing M-TEER were older (76 vs. 75 years, p &lt;0.0001), more likely to be males (72% vs. 49%, p=0.0002), and with more comorbidities. During the study years, the number of M-TEER in post-CABG patients was increasing (2145 in 2016 vs. 2682 in 2020) with however downtrend in the percentage of periprocedural complications (11% in 2016 vs. 8% in 2020). On adjusted analysis, there was no significant difference in in-hospital mortality between the two cohorts [aOR 0.85, 95 % CI(0.85-1.32), p =0.47], however, post-CABG patients had lower odds of net all periprocedural cardiac complications [ aOR 0.72 ,95% CI (0.59-0.87), p=0.001] compared to the other group. Results remained the same on subgroup analysis for men and women, There was no significant difference in mortality between the two cohorts for both men and women [aOR 0.67, 95% CI (0.38- 1.2), p=0.18], [aOR 1.15,95% CI (0.59- 2.23), p=0.66] respecetively. Men and women with prior CABG had lower odds of net all periprocedural cardiac complications compared to the men [aOR 0.59,95% CI (0.47- 0.74), p&lt;0.001] and women [aOR 0.71,95% CI (0.52- 0.98), p=0.04] in the other cohort. Conclusions: Patients with prior CABG do not have amore dverse peri-procedural outcomes compared to other M-TEER patients. Despite the higher prevalence of comorbidities, our study suggests the overall safety of M-TEER in this subset of patients
Abstract 4142648: Cardiac Catheterization in Kidney Transplant Patients Presenting with Non-ST Segment Elevation Myocardial Infarction: A Five-year Nationwide Analysis
Authors: Mohannad Al Akeel, Daoud Eldawud, Mayank Jha, Arya Harikrishna, Hritvik Jain, Ammar Abdulfattah, Yazan Alamro, jeetendra patel
Journal: Circulation (2024)

Background: Cardiovascular disease is a significant cause of death among kidney transplant (KT) patients. The potential for contrast-induced nephropathy renders cardiac catheterization challenging for patients with non-ST segment elevation myocardial infarction (NSTEMI). Aims: To identify and evaluate the rates of all-cause mortality, intensive care unit (ICU) admission, cardiac catheterization, and length of stay between KT patients and non-KT patients who were admitted for NSTEMI. Methods: Our retrospective analysis utlized data from the Nationwide Inpatient Sample Database (NIS) from January 2016 to December 2020. A total of number of 31,51,154 non-KT were compared with 11,935 KT patients were admitted for NTSEMI. We identified patients who were admitted to the hospital in the US with discharge diagnosis of NSTEMI comapring their outcomes based on their renal transplant status. A multivariate logistic and linear regression analysis were conducted and adjusted for confounding variables such as age, gender, race, insurance, income, hospital region, and medical comorbidities to evaluate outcomes of interest. The adjusted odds ratio (aOR) and 95% confidence intervals (CI) were calculated. Results: Our analysis showed that patients with KT were less likely to undergo cardiac catheterization (aOR = 0.66, 95% CI: 0.60-0.73) compared to non-KT patients. There was no significant difference in the risk of cardiac arrest (aOR = 0.72, 95% CI: 0.43-1.22), ICU admissions (aOR = 1.09, 95% CI: 0.95-1.25), and the length of stay was found to be comparable in between the two groups. However, there was an increased risk of all-cause mortality (aOR = 1.28, 95% CI: 1.083-1.527) in KT patients when compared to non-KT patients. Conclusion: For NSTEMI, KT patients underwent cardiac catheterization significantly less frequently than their non-KT patients. patients Additionally, patients with KT had a higher risk of mortality than non-KT patients. Nonetheless, the risk of cardiac arrest, ICU admission, and duration of stay were comparable among the two groups, indicating that the potential side effects associated with left heart catheterization should not outweigh the benefits of performing left heart catheterization in KT patients.
Abstract 4142270: Epigenetics of Shared and Unique Pathways Associated with Atherogenic Lipoprotein Particle Content and Number Across the Early Adult Life Course
Authors: John Wilkins, Yishu Qu, Norrina Allen, Hongyan Ning, Lifang Hou, Donald Lloyd-Jones, Allan Sniderman, Brian Joyce, Yinan Zheng
Journal: Circulation (2024)

Intro: Exposure to atherogenic lipoproteins is a central determinant of atherosclerotic cardiovascular disease (ASCVD) events. Shared and unique biological pathways influence lipoprotein particle content (non-HDL-C, LDL-C) and number (apoB, LDL-P), but significant unexplained variance in blood lipoprotein levels remains. Understanding the associations between lipoprotein particle number, content, and repeated DNA methylation (DNAm) measures may provide novel insights into lipoprotein level determinants. Methods: We included 2962 participants from the Coronary Artery Risk Development in Young Adults study that had DNAm, LDL-C, non-HDL-C, apoB, and LDL-P measurements at exam years 15, 20, 25, and 30. Non-HDL-C and LDL-C were determined using standard laboratory technique. LDL particle number (LDL-P) and apoB were measured using NMR. DNAm was assessed using the Illumina Epic Array. We used separate mixed linear models adjusted for age, sex, race, and technical variables to quantify associations between DNAm sites and non-HDL-C, LDL-C, LDL-P, and apoB. We performed pathway analysis of DNAm located in gene promoter regions. We estimated % variance in lipid levels explained by associated DNAm sites using ANOVA. Results: There were 127, 182, 40, and 110 DNAm sites that were uniquely associated with LDL-C, non-HDL-C, LDL-P, and apoB, respectively. There were 114 DNAm sites associated with 3 or more of these atherogenic lipid measures. Of note, 6 DNAm sites were in the promoter of LDLR. Shared pathways included cholesterol and fatty acid metabolism, steroid and alcohol biosynthesis, as well as cellular protein transport (Table).Unique pathways generally included cholesterol synthesis for LDL-C, and energy metabolism, inflammation, and calcium transport for apoB and LDL-P. In total, identified CpGs in circulating blood leukocytes explained 14%, 24%, 16%, and 17% variance in LDL-C, non-HDL-C, LDL-P, and apoB, respectively. Conclusions: Assessment of longitudinal epigenetic patterns in peripheral leukocytes suggest unique and shared pathways mediate a large % variance in atherogenic lipids. Further exploration of the function of these DNAm sites may enhance mechanistic insight into the determinants of atherogenic lipid exposure.
Abstract 4142676: Advancing towards the development of an AI application for angina diagnosis through medical interviews
Authors: Kosuke Fujita, Yudai Shoda, Honoka KANNO, Hisashi Handa, Gaku Nakazawa
Journal: Circulation (2024)

Background: Interview techniques for angina pectoris in patients with chest pain have demonstrated a low positive probability of 35.7% (PROMISE study) when using the Diamond-Forrester approach, which evaluates pre-test probability (PTP) based on classic chest symptoms, age, and gender. Therefore, it is beneficial to use artificial intelligence (AI) to create a more precise medical interview system by combining patient clinical data. Our objective is to create such a system. Methods: A medical interview is taken from patients presenting with chest pain as a chief complaint. Then, coronary artery examinations (CAG, contrast-enhanced CT, stress tests) will be conducted to definitively diagnose angina. The results of these definitive diagnoses will be combined with the patients' baseline data to develop an AI algorithm. The input attributes used for the interview are listed in Table 1. A multilayer perceptron (MLP) was applied to predict patients diagnosed with angina pectoris, and these models were validated using 10-fold cross-validation. Results: There were a total of 315 patients, of whom 135 were diagnosed with angina pectoris. Additionally, patient information including atherosclerosis risk factors such as diabetes (102 cases), dyslipidemia (216 cases), hypertension (225 cases), and smoking status (never: 141 cases, past: 124 cases, current: 23 cases) were added as attributes and analyzed. Using only medical interviews and setting the threshold at 80% (where the AI determined the probability of angina to be 80% or higher), the prediction accuracy was 62.6%, with a sensitivity of 30.8% and a specificity of 87.7%. The precision was 66.6%. Additionally, when the four atherosclerosis risk factors were included, the prediction accuracy increased to 69.9%. Notably, the precision reached 79.9%. (Figure1) Conclusion: Our AI system based on interview data demonstrated high accuracy for diagnosis of angina while it was improved by adding the attribute of the four atherosclerosis risk factors. Further investigation is needed to complete a highly accurate AI-based application by increasing the number of samples.
Abstract 4142415: Higher t-PA Doses are Associated with Reduced In-Hospital Mortality in Pulmonary Embolism Patients Undergoing Catheter-Directed Thrombolysis
Authors: Colin Hinkamp, Jason Liu, Matthew Nardi, Alexander Postalian, Ajith Nair, Matthew Segar
Journal: Circulation (2024)

Background: Pulmonary embolism (PE) is a leading cause of cardiovascular death and preventable hospital mortality in the US. High-risk acute PE has a 30% mortality rate, despite new treatments like catheter-directed thrombolytics (CDT). CDT has shown to improve right ventricle/left ventricle (RV/LV) diameter ratio compared to anticoagulation alone, but the optimal t-PA dose is uncertain. Traditional dosing is 10-24 mg over 12-24 hours, but clinical trials have showed similar RV/LV diameter ratio reductions with lower doses and shorter infusions. No prospective data has shown a mortality benefit. Hypothesis: Higher t-PA doses will improve in-hospital mortality, length of stay (LOS), pulmonary artery (PA) pressure reduction, and cardiac biomarker reduction in patients receiving CDT for acute PE. Methods: We retrospectively analyzed patients who presented with PE and underwent CDT at a single center, tertiary hospital. Patients were stratified by t-PA dose (&lt;24mg vs ≥24mg). Outcomes were compared using adjusted linear or logistic regression models. Results: Among 133 patients, 105 (80%) received t-PA ≥24mg. Patients who received higher doses of t-PA were younger (61 vs. 71 years, p=0.02), more likely to have bilateral PE (93% vs 77%; p=0.03) and had higher BMI (35 vs 30.5; p=0.04) and PA pressure (51 vs 40.5 mmHg; p=0.003) at baseline. In unadjusted analysis, no significant difference in in-hospital mortality was observed with t-PA ≥24mg (3.8% vs. 16.4%, p=0.08). However, in the adjusted analysis, a significantly lower risk in-hospital mortality rate was observed with t-PA ≥ 24mg (OR 0.15, 95%CI 0.02-0.97, p=0.046) (Table). No significant differences were observed in BNP reduction, PA pressure change, or LOS (Table). Conclusion: In acute PE patients undergoing CDT, t-PA dosing ≥24mg was associated with reduced in-hospital mortality. Prospective randomized controlled trials are needed to further define optimal dosing protocols.
Abstract 4142693: Deletion of Prekallikrein enhances atherosclerotic plaque stability and prevents plaque rupture by modulating macrophages and smooth muscle cells
Authors: Fu Yu, Hong Jiang, Lilei Yu
Journal: Circulation (2024)

Background: Atherosclerosis plaque rupture is the pathological basis and chief culprit of most acute cardiovascular events and death. Emerging evidence suggests that prekallikrein plays an important role in the pathogenesis of atherosclerosis including control of coagulation, complement, and inflammation processes, and regulation of cholesterol levels. However, little is known about the modulation mechanisms of prekallikrein in atherosclerotic plaque stability. Method: We divided 120 ACS patients into those with and without plaque rupture (PR and non-PR, respectively) based on optical coherence tomography image analysis, and quantified the patients' serum prekallikrein levels. Next, we engineered KLKB1 deficient mice (Klkb1 -/- Apoe -/- ) and a murine atherosclerosis model with vulnerable plaques was induced with high-cholesterol diet and perivascular carotid collar placement surgeries in Apoe -/- mice. Pathological staining was used to detect necrotic plaque cores, ratios of neutral lipids and cholesterol crystal, as well as collagen fiber contents in these mice to characterize plaque stability. Finally, we further investigated the role and mechanism of prekallikrein in smooth muscle cells and macrophages phenotype switching, proliferation and migration by in vitro experiments. Result: The serum prekallikrein levels of PR patients is significantly higher than that of non-PR patients, and significantly correlated with the thickness of the fibrous cap of the plaque and the length and arc of the lipids. which may be an effective predictor of PR. On a high-fat diet, Klkb1 -/- Apoe -/- mice exhibit reduced necrotic plaque cores, as well as neutral lipid and cholesterol crystal ratios, with increased collagen fiber content. Additionally, macrophage apoptosis and phenotypic changes of smooth muscle cells are inhibited in the plaques of Klkb1 -/- Apoe -/- mice. In vitro, Klkb1 deficiency inhibits ox-LDL-induced macrophage autophagy and the smooth muscle cells phenotype switching, proliferation and migration. Conclusion: In the present work, we uncover a crucial role for prekallikrein in atherosclerosis as an important regulator of macrophage apoptosis and macrophages phenotype switching and subsequently atherosclerotic plaque destabilization. Cumulatively, these results suggest that targeting prekallikrein may represent a new treatment strategy for the prevention and treatment of acute cardiovascular deaths caused by PR.
Abstract 4142747: Role of Cardiomyocyte Mechanotransduction in Triggering Atrial Arrhythmias in Pulmonary Hypertension
Authors: Peter Bronk, Peng Zhang, Eric Wang, Yichun Lu, Debolina Banerjee, Madigan Stanley, frank sellke, Glenn Radice, Gaurav Choudhary, Cao Tran, Bum-rak Choi
Journal: Circulation (2024)

Introduction: Pulmonary arterial hypertension (PAH) is a chronic disease associated with atrial fibrillation (AF). Chronic pressure overload in right atria (RA) may disrupt cardiomyocyte mechanotransduction resulting in remodeling that triggers arrhythmias. The mechanosensitive adaptor protein, vinculin, interacts with Nav1.5 as well as indirectly stabilizing connexin-43 gap junctions. Goal: To show that the influence of chronic overload in RA under conditions of PAH disrupts mechanotransduction signaling and increases susceptibility to arrhythmias. Methods: We used the Sugen/Hypoxia (Su/Hx) rat model of PAH for optical mapping of action potentials in isolated right atria as well as immunohistochemistry of atrial tissue. Results: PAH rats have enlarged RA (82.2 ± 22.3 mg PAH vs. 38.5 ± 4.7 mg control, p=0.02, t-test). In comparison to controls, isolated RA of PAH rats show slower conduction velocity (CV) (0.4 ± 0.07 mm/ms PAH vs. 0.5 ± 0.06 mm/ms control, p=0.02, t-test) together with increased local heterogeneity, an increase in APD (Fig. 1A) and APD dispersion (11.2 ± 3.7 ms PAH vs. 5.6 ± 1.3 ms control, p=0.006, t-test). Traditionally, AF is usually associated with shorter APD, so the prolonged APD we recorded in PAH RA represents a unique electrophysiological change. This electrical remodeling in PAH rats promotes conduction block in the posteromedial RA and reentry formation (Fig. 1B). Immunohistochemistry shows that vinculin is reduced at N-cadherin cell-cell contacts and redistributed to the lateral membrane in PAH RA (Fig. 2) with a 2D FFT radial sum intensity major to minor peak ratio: 1.02 ± 0.002 vs 1.008 +/- 0.001 control, p=0.02, t-test. Conclusion: RA of PAH rats show high arrhythmia risks compared to controls. The unique electrophysiological changes could be a critical feature of AF in PAH. Vinculin redistribution may create a substrate for RA arrhythmias and may play an important role in regulating the electrical remodeling of RA in PAH.
Abstract 4142487: ST-Elevated Myocardial Infarction in the Postpartum Period: Incidence and Predictors
Authors: Elizabeth Davis, Danielle El Haddad, Yong Shan, Diann Gaalema, Hani Jneid
Journal: Circulation (2024)

Introduction: The US maternal mortality rate is rising, with cardiovascular disease being the main cause of death. Acute myocardial infarction in particular (most commonly ST-elevation myocardial infarction (STEMI)) is associated with excess mortality. There have been no recent large, population-based studies estimating the current incidence of postpartum STEMI or identifying its risk factors. Research Question: Given the increasing risk of postpartum STEMI and the consequences of such a diagnosis we sought to identify recent incidence of postpartum STEMI and understand its predictors. Goal: The purpose of this study was to describe the incidence and risk factors of acute postpartum STEMI in the USA. Methods: This study was performed using MarketScan Commercial Claims and Encounters Data. Patient selection was from all deliveries resulting in a live birth between 2017 and 2020 with claims data available for 12 months prior and 6 months following delivery data. For all births, STEMI within 6 months was noted and the following risk factors were collected: age, hypertension (HTN), thrombophilia, anemia, diabetes mellitus (DM), and smoking. We then performed multivariate logistic regression models to estimate odds ratio (95% confidence interval) for STEMI adjusted for the aforementioned risk factors. Results: 327,570 delivery cases were identified, of which 3330 (1%) had a STEMI in the time from hospital admission to 6 months postpartum. Most STEMIs occurred close to the time of delivery: 2823 (84.8%) cases within 24 hours of delivery and an additional 132 within 1 week, 80 within 2 weeks, and 52 within 4 weeks (cumulative totals of 89.4%, 91.8%, and 93.3% respectively). The following factors had a significant, independent, positive correlation with STEMI: age ≥40 (OR 1.6 [95% CI 1.4-1.9]), DM (OR 1.6 [95% CI 1.5-1.7]), HTN (OR 1.6 [95% CI 1.5-1.7]), and smoking (OR 1.5 [95% CI 1.3-1.8]). These are shown in Figure 1. Conclusion: Although rare, postpartum STEMI is associated with high morbidity and mortality and is occurring at an increasing rate. While maternal age is not modifiable, HTN, smoking and DM are, and more should be done to address these risk factors in those who are, or plan to become, pregnant.