tbuckley/cabot-search huggingface dataset:
Abstract 4135025: Inflammation-related 5-hydroxymethylation signatures as markers for clinical presentations of coronary artery disease
Authors: Jing Xu, Hangyu Chen, Jian Lin, Yue-Jin Yang
Journal: Circulation (2024)

Background: Coronary angiography, an invasive method, remains the gold standard technique for coronary artery disease (CAD) diagnosis in clinical practice. However, due to its invasive nature, it cannot be used for mass population screening. There is an urgent need in the clinical to identify new liquid biopsy molecular markers for screening patients with CAD. Methods: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 724 CAD patients. To investigate the correlation between 5hmC modifications and CAD, we separated patients into training and validation cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict CAD patients in the validation cohort. Furthermore, we incorporated an external cohort comprising 167 samples to validate the reliability of our model. Results: We found that the differentially hydroxymethylated genes (DhMGs) in people with the normal coronary artery (NCA), nonfatal stable CAD (sCAD), non-ST-elevation myocardial infarction (NSTEMI), as well as ST-elevation myocardial infarction (STEMI) enriched in neutrophil-mediated inflammatory response pathways, and inflammation-related DhMGs can reflect the progression of atherosclerotic plaque. Furthermore, we used machine learning algorithms to develop a predictive model for predicting the occurrence of myocardial infarction (MI) based on 19 inflammatory markers, and the predictive model could effectively predict MI (NSTEMI and STEMI) (AUC = 0.913). Simultaneously, our model has demonstrated strong performance in external validation. Conclusions: We have identified a novel biomarker, the inflammation-associated 5hmC markers, which can reflect the clinical manifestations of CAD and can effectively predict the occurrence of MI.
Abstract 4132838: Coronary Collaterals Provide Cardioprotection in Hemorrhagic ST-elevation MI (STEMI)
Authors: Keyur Vora, Chirag Shah, Damien Sighaka Sighaka, Akrum Saleh, Nitya Panyala, Andreas Kumar, Ankur Kalra, Rohan Dharmakumar
Journal: Circulation (2024)

Introduction: Development of intramyocardial hemorrhage (IMH) in acute STEMI following reperfusion is estimated to affect 35-50% of patients. IMH is a lethal event as it contributes to larger MI size, compromised myocardial salvage, adverse left ventricular (LV) remodeling, lower LVEF, and consequential major adverse CV events post-MI. Whether coronary collateral circulation reduces the deleterious effects of IMH has not been investigated. Hypothesis: We hypothesized that coronary collaterals could reduce the extent of post-reperfusion IMH volume and offer cardioprotection to hemorrhagic MI patients. Methods: MIRON-CL (NCT05898425) recruited and studied STEMI patients (n=294) reperfused via PCI. Pre-PCI coronary angiography allowed for assessment of collateral vessels using the Rentrop grading system, from Grade 0 (no collaterals) to Grade III (complete collateral filling). Post-PCI cardiac MRI, performed 3 days later, was used to determine area affected (extent of myocardial edema) from T2 maps, extent of IMH from T2* maps and MI size from LGE as %LV. Statistical analyses were used to examine relationships between collateral grades, MI size, IMH, and area affected. Results: 124 patients were hemorrhagic and 170 were non-hemorrhagic. Patients with no collaterals (Grade 0; CL-) exhibited significantly higher IMH volumes (7.41 ± 5.33% LV) compared to those with collaterals (Grade I: 5.23 ± 3.21% LV, Grade II: 3.11 ± 2.78% LV, Grade III: 2.05 ± 1.89% LV; p&lt;0.001). Total area affected post-PCI was larger in CL- (37.62 ± 15.32% LV) compared to CL+ (21.48 ± 13.21% LV, p&lt;0.001). Presence of collateral circulation (Grade&gt;0 combined; CL+) was correlated with smaller MI sizes (CL-: 38.66 ± 14.63% LV vs. CL+: 19.84 ± 13.72% LV, p&lt;0.001) and reduced MVO volumes (CL-: 8.07 ± 6.60% LV vs. CL+: 2.17 ± 2.35% LV, p&lt;0.001). Patients with no collaterals had a significantly higher adj. risk of IMH (OR: 5.71, 95% CI: 3.16-10.33, p&lt;0.0001). Conclusion: Coronary collaterals reduce post-reperfusion IMH volume in STEMI patients and provide significant cardioprotection: reductions in area affected, MVO and MI size. Insight into collateral grade offers opportunities to improve risk stratification and management of revascularized STEMI patients.
Abstract 4137467: Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention: A systematic review, meta-analysis, and meta-regression of randomized controlled trials
Authors: Asad Rahman, Mushood Ahmed, Zain Nadeem, Hira Javaid, Hritvik Jain, Areeba Ahsan, Adeel Ahmad, Farhan Shahid, Raheel Ahmed
Journal: Circulation (2024)

Background: Intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) allows better visualization of atherosclerotic plaques than angiography alone. We conducted a systematic review and meta-analysis to comprehensively synthesize the available evidence regarding the efficacy of IVUS-guidance compared to angiography-guided PCI. Moreover, we conducted a sensitivity analysis to determine the applicability of IVUS guidance in complex PCI. Methods: We conducted a comprehensive literature search of major bibliographic databases from inception until May 2024 to identify randomized controlled trials (RCTs) comparing IVUS-guided versus angiography-guided PCI. Risk ratios (RR) with their corresponding 95% confidence intervals (CI) were pooled using the random-effects model, with a p-value &lt;0.05 considered statistically significant. We conducted meta-regression to determine the moderating of baseline covariates on pooled outcomes. Results: Sixteen RCTs were included with 10,993 patients undergoing PCI (IVUS-guided PCI: 5684 patients; angiography-guided PCI: 5157 patients). IVUS-guided PCI demonstrated a significantly lower risk of cardiac death [RR: 0.49; 95% CI: 0.35, 0.68], major adverse cardiovascular events [RR: 0.64; 95% CI: 0.51, 0.80], myocardial infarction [RR: 0.73; 95% CI: 0.59, 0.89], stent thrombosis [RR: 0.45; 95% CI: 0.27, 0.75], target lesion revascularization [RR: 0.60; 95% CI: 0.49, 0.74], and target vessel revascularization [RR: 0.56; 95% CI: 0.45, 0.70] than angiography-guided PCI. IVUS-guided PCI demonstrated a nonsignificant trend toward a reduced risk of all-cause mortality [RR: 0.79; 95% CI: 0.61, 1.04]. Meta-regression showed a nonsignificant moderating effect of the duration of follow-up, age of patients, baseline dyslipidemia, and hypertension status on pooled outcomes. A sensitivity analysis was conducted for patients undergoing complex PCI. The sensitivity analysis showed the superiority of IVUS-guided PCI compared to angiography-guided PCI by resulting in a significant improvement in the clinical outcomes. Conclusion: This meta-analysis concluded that IVUS-guided PCI resulted in a reduction in cardiac death, major adverse cardiovascular events, myocardial infarction, stent thrombosis, target lesion revascularization, and target vessel revascularization, compared to angiography-guided PCI. Moreover, we observed the superiority of IVUS guidance in complex PCI as well.
Abstract 4132351: Soluble Urokinase Plasminogen Activator Receptor Levels Predict Incident Cardio-Kidney-Metabolic Disease Risk
Authors: Adithya Yadalam, Chang Liu, Yan Sun, Arshed Quyyumi
Journal: Circulation (2024)

Introduction: Given the rising global incidence of cardio-kidney-metabolic (CKM) syndrome, there is an urgent need for novel risk prediction strategies for CKM disease. Hypothesis: As soluble urokinase plasminogen activator receptor (suPAR) levels have been associated with the development of cardio-kidney disease, we hypothesized that elevated suPAR levels would predict incident CKM disease risk. Methods: A total of 25,596 UK Biobank participants without CKM disease at enrollment were analyzed for the association of suPAR levels and incident CKM disease. CKM disease was defined as the first occurrence of CVD (heart failure, atrial fibrillation/flutter, coronary heart disease, stroke, and peripheral artery disease), chronic kidney disease (CKD), or metabolic disease (type 2 diabetes mellitus and obesity). Incident CVD, CKD, and metabolic disease were also analyzed separately as secondary outcomes. Kaplan-Meier analysis was performed to visualize the association between suPAR levels and the primary composite CKM outcome. Competing-risk regression, while accounting for competing non-CKM disease death, was performed to examine the association between suPAR levels and the primary composite CKM outcome. Models were adjusted for demographics, traditional risk factors, and CRP levels. Results: The mean age was 56.0 (SD 8.3) years, 44% were male, and 94% were White. suPAR levels were associated with a significantly higher rate of composite CKM events (P&lt;0.001) (Figure 1). During a median follow-up of 13.5 [IQR 1.7] years, 5,012 (20.0%) composite CKM events, 3,599 (8.3%) incident CVD events, 863 (3.4%) incident CKD events, and 1,397 (4.7%) incident metabolic disease events occurred. suPAR levels (per SD) significantly predicted the primary composite CKM outcome (sHR 1.23, 95% CI 1.19-1.27) after adjustment. suPAR levels (per SD) also significantly predicted incident CVD (sHR 1.24, 95% CI 1.19-1.29), incident CKD (sHR 1.41, 95% CI 1.30-1.53), and incident metabolic disease (sHR 1.17, 95% CI 1.10-1.24) after adjustment. Conclusion(s): In this large, longitudinal cohort study of UKB participants, plasma suPAR levels were a significant predictor of CKM disease risk, independent of demographics, traditional risk factors, and CRP levels.
Abstract 4137518: The implications of polygenic versus phenotypic characterization of obesity for cardiovascular-kidney-metabolic health
Authors: Ozan Dikilitas, Mohammadreza Naderian, Matt Kosel, Marwan Hamed, Daniel Schaid, Iftikhar Kullo
Journal: Circulation (2024)

Introduction: The overall amount and the distribution of body fat, proxied by body-mass index (BMI) and waist-to-hip ratio (WHR), are two important measures of obesity and have significant polygenic heritability. We aimed to investigate whether polygenic scores (PGS) for these traits have additional predictive utility, beyond phenotypic characterization of obesity, for cardiovascular-kidney-metabolic (CKM) health. Methods: We derived PGS for BMI (PGS BMI ) and WHR adjusted for BMI (PGS WHRadjBMI ) using PRS-CS-auto on summary statistics from ~700k individuals of European ancestry (EA) in the GIANT consortium and selecting ~1M common variants for each score. We conducted association analyses in the Atherosclerosis Risk in Communities study, a prospective cohort including 8,631 EA individuals with ascertainment of incident diabetes, hypertension, chronic kidney disease, atrial fibrillation, coronary heart disease, ischemic stroke, and heart failure. We used nested Cox models to measure the added predictive utility of PGS to BMI and WHR for incident CKM phenotypes. Results: The study cohort (age 54.4±5.7 years, 52.4% women, follow-up 24.5±7.6 years) had a baseline BMI of 26.4 kg/m 2 (median [IQR]; 21.6-29.6) and WHR of 0.94 (0.88-0.98). PGS BMI and PGS WHRadjBMI were associated with their phenotypes (partial R 2 ; BMI 0.11 and WHR 0.04, p &lt;0.001), although with a large phenotypic variability across the distribution of PGS (IQR for 1 st and 10 th deciles of PGS; BMI 19.6-28.3 and 22.6-35.9, WHR 0.79-1.03 and 0.87-1.05). Anthropometric measures of obesity were associated with a wider gradient of risk compared to PGS for obesity–most notable for diabetes and cardiovascular phenotypes (Table 1a). Addition of PGS BMI and PGS WHRadjBMI to BMI and WHR resulted in limited improvement in risk discrimination across incident CKM phenotypes (Table 1b). Conclusions: Observed anthropometric measures of obesity are sufficient, and for certain conditions far superior, to capture the risk of incident CKM phenotypes. These findings suggest PGS for adiposity traits likely have limited clinical utility to refine risk stratification for CKM syndrome among middle aged adults.
Abstract 4135229: Endothelial glycocalyx shedding during ST-elevation acute myocardial infarction
Authors: Carlos Miranda
Journal: Circulation (2024)

Background: Endothelial glycocalyx (eGC) is a layer of glycosaminoglycans adhered to proteoglycans that cover the inner surface of the vessels. The integrity of this structure sustains some vascular properties such as shear stress-induced nitric oxide release and the prevention of platelets and neutrophils adhesion on the vessel surface. eGC shedding could contribute to atherosclerotic plaque vulnerability and acute myocardial infarction (AMI) installation. This research investigated whether acute eGC damage and microvascular dysfunction occurred during AMI. Methods: Sublingual microcirculation was assessed through Capiscope HCVS Handheld Video Capillaroscopy System (KK Technology, Honiton, UK) during the first 72h of hospital admission because of ST-elevation AMI (before) and repeated around six months later (after). All images were automatically analyzed using the GlycoCheck (Alpine, UT, USA), which estimated the perfused vascular density (PVD), the red blood cell (RBC) filling of the vessels, the perfused boundary region (PBR) in µm, an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). This score ranges from 0-10; the lower its numerical value, the greater the microvascular impairment. Results: Twenty patients were included (61±10 years old, 85% males, 55% anterior AMI, 70% hypertension, 25% diabetes, 45% current smoker, all underwent primary PCI). The time between the two sublingual assessments was 188±31 days. The PBR [1.96±0.22µm vs. 1.84±0.19µm]; p=0.047 and flow-adjusted PBR [1.40±0.25µm vs. 1.24±0.16µm]; p=0.045 decreased statistically significant over time. The RBC filling [71.56±4.33% vs. 74.02±3.88%]; p=0.016 and the MVHS [4.28 (interquartile range (IRQ) 3.38-4.90) vs. 5.04 (IQR 4.37-6.00)]; p=0.044 increased statistically significant over time. The PVD [500±86 x10-2µm/mm vs. 522±84x10-2µm/mm]; p=0.255 did not modify over time. Conclusion: This finding was compatible with eGC shedding and microvascular dysfunction during AMI and later reconstitution of this structure after six months.
Abstract 4132409: Caspase-4/11 promotes a high-fat diet and chronic kidney disease-accelerated vascular inflammation via caspase-4/11-IL-1b two-tier trained immunity
Authors: Yifan Lu, Yu Sun, Fatma Saaoud, Ying Shao, keman xu, Xiao-feng Yang
Journal: Circulation (2024)

Introduction: Chronic kidney disease (CKD) is a common inflammatory disease affecting &gt;15% of the adult population and 50% of all patients with advanced/end stages (4 to 5) of CKD have cardiovascular disease. Research Questions: How multiple disease risk factors interplay to accelerate vascular inflammation in CKD. Aim: To determine whether hyperlipidemia and CKD have a synergy in accelerating vascular inflammation via trained immunity (TI). Methods: we performed aortic pathological analysis and RNA-sequencing in high-fat diet (HFD)-fed 5/6 nephrectomy CKD (HFD+CKD) mice. Results: 1) HFD+CKD increases aortic cytosolic lipopolysaccharide (LPS) levels, caspase-11 (casp11) activation, and 998 gene expressions of TI pathways in the aorta (first-tier TI mechanism); 2) Casp11 —/— decreases aortic neointima hyperplasia, aortic recruitment of macrophages, and casp11-gasdermin D-mediated cytokine secretion; 3) Casp11 —/— decreases N-terminal gasdermin D (N-GSDMD) membrane expression on aortic endothelial cells and aortic IL-1b levels; 4) LPS transfection into human aortic endothelial cells results in casp4 (human)/casp11 (mouse) activation and increases N-GSDMD membrane expression; 5) IL-1b serves as the second-tier mechanism underlying HFD+CKD-promoted TI. Conclusion: Hyperlipidemia and CKD accelerate vascular inflammation by promoting two-tier trained immunity
Abstract 4137587: Need for Testing Standardization and Improved Treatment of Elevated Lipoprotein(a) at a Large Urban Academic Medical Center
Authors: Willis Wong, CINDY HSIN-YI kao, Ruth schneider, Ann Marie Navar, Anand Rohatgi, Amit Khera, Parag Joshi
Journal: Circulation (2024)

Background: Lipoprotein(a) [Lp(a)] is causally linked to ASCVD events and aortic stenosis. Some guidelines now recommend screening of Lp(a) at least once in an adult’s lifetime. Currently, there is inconsistency in measurement modality (mg/dL vs. nmol/L), but most guidelines recommending testing in nmol/L due to less variability and improved standardization. We sought to determine the Lp(a) measurement practices, including testing modality and downstream interventions, at a large academic medical institution. Methods: We evaluated all patient encounter data at UT Southwestern Medical Center (UTSW) between January 1, 2017 to December 31, 2021 for any Lp(a) measurement. High Lp(a) was defined as &gt;50mg/dL or &gt;125 nmol/L. Aggregate data were used to summarize patient demographics, relevant ASCVD co-morbidities, and lipid lowering prescriptions. Chart-review was conducted on patients with high Lp(a) to assess referrals to specialty clinics. Results: From 2017 to 2021, there were 1,065 Lp(a) measurements among 938 patients, representing fewer than 0.1% of all patients with labs at UTSW. Most were ordered by cardiologists (71%). Lp(a) tests ordered by cardiologists increased 69% annually but remained stagnant for other specialties (figure 1, lines). Median Lp(a) levels across all tests were 17mg/dL and 43nmol/L. Lp(a) was high in 30% of all initial tests. A higher proportion of tests ordered in 2021 by cardiologists (84%) were in nmol/L, the recommended standard, compared with other specialties (55%) (figure 1, bars). Patients with high Lp(a) found by a non-cardiologist were infrequently referred to cardiology (16%), and 53% of patients with high Lp(a) were prescribed lipid lowering therapy within 3 months. Conclusion: Lp(a) testing at a major academic medical center was rare and only marginally increased during the 5-year study period. Measurement frequency and assay varied widely between specialties, and there were potential opportunities for downstream interventions. In addition to improving awareness of Lp(a), there is an opportunity to standardize practice patterns regarding its measurement and implications.
Abstract 4134825: Diabetic ketoacidosis and hyperglycemic hyperosmolar state outcomes in diabetes patients hospitalized with ST-elevation myocardial infarction
Authors: Turki Almutairi, Soha Dargham, Amin Jayyousi, Jassim Al Suwaidi, Charbel Abi Khalil
Journal: Circulation (2024)

Background: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are acute life-threatening hyperglycemia conditions. Aims: We aimed to assess their impact on type 2 diabetes patients admitted for ST-elevation myocardial infarction (STEMI). Methods: Data was extracted from the National Readmission Database (2016-2019). The primary endpoint was in-hospital mortality. Secondary endpoints included in-hospital arrhythmias, cardiogenic shock, and 30-day readmission and mortality. Results: A total of 112,829 patients hospitalized for STEMI with a concomitant diagnosis of type 2 diabetes were hospitalized between 2016 and 2019, of whom 112,799 were included in our analysis after the exclusion of patients with missing data ( Figure 1 ). Of those patients, 330 had a diagnosis of DKA, and 292 had a diagnosis of HHS. After 30 days from the initial hospitalization, 118 (35.7%) out of the initial DKA group, 102 (34.9%) out of the initial HHS group, and 26,523 (23.6%) of STEMI patients with diabetes were readmitted. The presence of DKA increased the odds of in-hospital mortality and cardiogenic shock by almost 2-fold (aOR = 2.30 [1.70-3.12], 2.055 [1.602-2.637], respectively) and renal failure by almost 5-fold (aOR = 5.175 [4.090-6.546]) ( Table 1 ). HHS was also associated with higher odds of mortality, acute renal failure, and cardiogenic shock. Within 30 days of initial admission, DKA and HHS increased the risk of readmission (aOR= 1.815 [1.449-2.75], 1.751 [1.376 - 2.228], respectively), but not mortality. Cardiovascular disease was the most common etiology of readmission in all patients ( Figure 2) . The prevalence of non-STEMI was the highest in DKA patients (22.9%), and the prevalence of STEMI was the highest in the HHS group (37.9%). Conclusion: The presence of diabetic ketoacidosis or hyperglycemic hyperosmolar states is associated with higher odds of mortality, renal failure, cardiogenic shock, and 30-day readmission in STEMI patients with type 2 diabetes.
Abstract 4137465: Estimating Arterial Stiffness Using a Smart Ring and the Impact of HIIT Exercise: A Pilot Study
Authors: Pauli Ohukainen, Aleksi Rantanen, Heikki Pentikainen, Julia Kosonen, Pirjo Komulainen, Kai Savonen, Heli Koskimaki
Journal: Circulation (2024)

Introduction: Arterial stiffness is an important marker of cardiovascular health, but measuring it requires specialized equipment and trained personnel. This study aimed to evaluate a novel method for estimating arterial stiffness using photoplethysmography (PPG) signals recorded by a commercially available device (Oura Ring) and to study the impact of a high-intensity interval training (HIIT) intervention on arterial stiffness. Research Questions: 1. Can a smart ring provide accurate estimates of arterial stiffness comparable to the reference device (Sphygmocor)? 2. Does a three-month supervised HIIT cycling protocol reduce arterial stiffness? Aims: 1. Evaluate a PPG-based arterial stiffness estimation method using a smart ring. 2. Assess the efficacy of HIIT in reducing arterial stiffness and improving VO2max. Methods: The study comprised two parts: 1. A cross-sectional study (N=300, age 18-78) for collecting arterial stiffness data using the Sphygmocor and the Smart Ring to evaluate the PPG-based algorithm. 2. A randomized exercise intervention pilot study (N=80, a subset of the cross-sectional study), assigned to either a three-month HIIT protocol or a control group. Arterial stiffness was measured pre- and post-intervention using both devices. Pearson’s correlation coefficients assessed the agreement between the novel method and reference device, and effects of the intervention were analyzed using ANCOVA. Results: The novel PPG-based method demonstrated good correlation with the Sphygmocor device (R = 0.77 and 0.80 in pre- and post-timepoints, respectively). However, despite improving the participants’ aerobic fitness (average increase in VO2max of 1.41 ml/min/kg; 95% CI: [0.15, 2.67], P = 0.029) the HIIT intervention did not significantly improve arterial stiffness, as measured by both methods. Conclusions: The developed smart ring method provides a reliable, non-invasive, and continuous estimation of arterial stiffness. This innovative approach could significantly impact how arterial stiffness is monitored in an everyday setting. The null results of the HIIT intervention suggest that HIIT may not be effective in reducing arterial stiffness, highlighting the need for further research into different exercise modalities for cardiovascular health improvement. This study underscores the potential of wearable technology in cardiovascular health monitoring and the importance of evaluating diverse exercise protocols for arterial health.