tbuckley/cabot-search huggingface dataset:
Abstract 14381: Patient-specific Fluid Structure Interaction Simulations of Anomalous Origins of Right Coronary Arteries in Adults Correlate With Measured Instantaneous Wave-free Ratio
Authors: Michael X Jiang, Muhammad O Khan, Joanna Ghobrial, Ian S Rogers, Eugene H Blackstone, Alison L Marsden
Journal: Circulation (2020)

Introduction: Anomalous coronaries are associated with ischemia and sudden death, but the recommendation to undergo surgery is often uncertain, especially for asymptomatic individuals with an anomalous aortic origin of the right coronary artery (AAORCA). For risk stratification, dobutamine-stress instantaneous wave-free ratio (iFR) is increasingly used. Meanwhile, advances in fluid-structure interaction (FSI) modeling have enabled the simultaneous simulation of blood flow and tissue deformation that may elucidate the mechanism of ischemia in AAORCA. Hypothesis: We hypothesized that the iFR simulated by patient-specific FSI models of AAORCA correlates with the measured iFR at rest and dobutamine-stress, and the hemodynamic mechanism is mainly due to the intramural geometry. Methods: Using the Simvascular software package, we constructed 6 FSI models of the AAORCA which encompassed the aortic root, the intramural course (if present), and coronary outlets coupled to lumped parameter networks that included the dynamic microvascular compression. Each model was customized to the patients’ computed tomography angiography, vitals, and cardiac output. Results: All 6 AAORCAs had an interarterial course, and all but one had an intramural course. Measured iFRs ranged from 0.98 to 0.95 at rest, and from 0.95 to 0.80 with dobutamine-stress. The FSI model yielded realistic pressures and flows waveforms (Fig. 1). After we tuned the resistances to achieve flow rates at stress to be triple those at rest, the FSI simulations adequately matched the measured iFR (r = 0.85, RMSE = 0.04). Conclusions: Patient-specific FSI modeling is a promising non-invasive tool to assess the hemodynamic effects of AAORCA including the intramural course. However, the iFR’s sensitivity to the flow rate suggests a future role for quantitative stress-perfusion imaging to augment the iFR measurements for AAOCA risk stratification.
Abstract 17467: Early Vascular Aging Predicts the Incidence of Diabetes in Hypertensives
Authors: Dimitrios Terentes-Printzios, Georgia Christopoulou, Lampros Korogiannis, Nikolaos Ioakeimidis, Konstantinos Aznaouridis, Dima Ioanna, Vasiliki Gardikioti, Konstantia P Gkini, Eirini Solomou, Panagiotis Xydis, Dimitrios Tousoulis, Charalambos Vlachopoulos
Journal: Circulation (2020)

Introduction: Diabetes is associated with vascular aging. Arterial stiffness, a marker of vascular aging, is an independent predictor of cardiovascular events and mortality. However, the role of arterial stiffness in the incidence of diabetes has not been investigated. Hypothesis: We sought to investigate the role of carotid-femoral pulse wave velocity (PWV) in the prediction of incident diabetes in hypertensives and hypertensives under treatment with statins. Methods: 376 never-treated hypertensives (mean age 53±13 years, 175 females) without a known history of diabetes or cardiovascular disease at baseline, were included in the study. Markers of target organ damage [carotid-femoral PWV, aortic augmentation index corrected for heart rate (AIx@75) and estimated glomerular filtration rate (eGFR)] were evaluated at baseline in all patients. eGFR was estimated using the Cockcroft-Gault formula. Hemoglobin A1c (HbA1c) and blood glucose were measured in venous blood samples. Patients were followed-up prospectively for the incidence of diabetes as defined by the American Diabetes Association criteria. 139 patients received statins during follow-up. Results: During a median of 13.6 years follow-up, 55 patients (13.4%) patients were diagnosed with diabetes. In multivariable logistic regression analysis, higher PWV (Odds Ratio [OR] = 1.29, 95% Confidence intervals [CI]: 1.02-1.63, P = 0.034) was associated with a higher risk of incident diabetes, which was independent of relevant confounders. In further analysis, receiver operating characteristic (ROC) curves were generated to evaluate the ability of PWV to discriminate subjects with diabetes. The area under the curve (AUC) and 95% CIs of the ROC curve was AUC=0.67 (95% CI: 0.59-0.74, P&lt;0.001) for PWV. In the subgroup of patients under treatment with statins, higher PWV (OR = 1.69, 95% CI: 1.19-2.40, P = 0.004) was also independently associated with a higher risk of incident diabetes. AIx@75 was not associated with the incidence of diabetes. Conclusions: Higher arterial stiffness, a marker of early vascular aging, is associated with the incidence of diabetes and also can identify subjects under treatment with statins that are more likely to present with diabetes in the future.
GPs' participation in decisions about non-urgent tertiary referral is appropriate
Authors: D. A Viniker
Journal: BMJ (1996)

EDITOR,—S Bridger and S R Cairns's study of general practitioners' views of consultants' non-urgent referral of outpatients to other consultants highlights one of the multitude of changes in clinical, managerial, and educational aspirations and requirements currently facing hospital doctors.1 It …
Abstract 13787: Efficacy of Lowering Low-density Lipoprotein Cholesterol in Elderly Subjects: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Baris Gencer, Nicholas A Marston, KyungAh Im, Peter S Sever, Anthony C Keech, Robert Giugliano, Marc S Sabatine
Journal: Circulation (2020)

Introduction: The clinical benefit from LDL-C lowering therapy in the elderly remains debated. Aim: To synthesize the efficacy of lowering LDL-C in patients aged ≥75 years in the light of most recently published data. Methods: Medline database was searched for the most recent evidence (2015-2020). The key inclusion criterion was a randomized controlled cardiovascular outcome trial testing an LDL-C lowering therapy with data available in patients aged ≥75 years at randomization. For efficacy, we meta-analyzed the risk ratio (RR) of major vascular events (a composite of cardiovascular (CV) death, myocardial infarction, stroke or coronary revascularization) per 1-mmol/L reduction in LDL-C. Results: Among 244,090 patients from 29 trials, 21,492 (8.8%) were elderly; 11,750 from statin trials, 6209 from ezetimibe trials, and 3533 from PCSK9 inhibitor trials. Median follow-up ranged from 2.2-6.0 years. LDL-C lowering therapy significantly reduced major vascular events (n=3519) in the elderly by 26% per 1-mmol/L LDL-C reduction (RR 0.74 [0.61-0.89], P=0.002), which was at least as good as the magnitude of effect seen in the non-elderly patients (RR 0.85 [0.78-0.92]; P interaction =0.24). Amongst the elderly, the RR was similar for statin (0.81 [0.70-0.94]) and non-statin therapy (0.67 [0.47-0.95]; P interaction =0.60). The benefit of LDL-C lowering in the elderly was observed for each component of the composite, including CV death (RR 0.85 [0.73-0.996], P=0.045), myocardial infraction (RR 0.80 [0.70-0.92], P=0.001), stroke (RR 0.71 [0.58-0.87], P=0.001) and coronary revascularization (RR 0.78 [0.63-0.96], P=0.017). Conclusion: In patients 75 years and older, lipid-lowering therapy is as effective in reducing CV events as it is in younger adults. These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin therapy, in the elderly.
Circular RNA hsa_circ_0004872 inhibits gastric cancer progression via the miR-224/Smad4/ADAR1 successive regulatory circuit
Authors: Cunying Ma, Xiaoying Wang, Fenghua Yang, Yichen Zang, Jiansong Liu, Xinyi Wang, Xia Xu, Wenjuan Li, Jihui Jia, Zhifang Liu
Journal: Molecular Cancer (2020)

Abstract Background Emerging evidence has shown that circular RNAs (circRNAs) play a crucial regulatory role in the occurrence and development of cancer. Exploring the roles and mechanisms of circRNAs in tumorigenesis and progression may help to identify new diagnostic markers and therapeutic targets. In the present study, we investigated the role and regulatory mechanism of hsa_circ_0004872 in gastric cancer (GC). Methods qRT-PCR was used to determine the expression of hsa_circ_0004872 in GC tissues and cells. EdU, CCK-8, transwell and scratch wound healing assays were used to assess the role of hsa_circ_0004872 in GC cell proliferation, invasion and migration, respectively. Subcutaneous and tail vein tumor injections in nude mice were used to assess the role of hsa_circ_0004872 in vivo. RIP assay, biotin-coupled probe pull-down assay, FISH and luciferase reporter assay were performed to confirm the relationship between hsa_circ_0004872 and the identified miRNA. ChIP assay, luciferase reporter assay and western blot were used to determine the direct binding of Smad4 to the promoter of the ADAR1 gene. Results In this study, we found that hsa_circ_0004872 was dramatically downregulated in GC tissues compared with adjacent noncancerous tissues. The expression level of hsa_circ_0004872 was associated with tumor size and local lymph node metastasis. Enforced expression of hsa_circ_0004872 inhibited the proliferation, invasion and migration of GC cells, whereas knockdown of hsa_circ_0004872 had the opposite effects. Nude mice experiments showed that ectopic expression of hsa_circ_0004872 dramatically inhibited tumor growth and metastasis in vivo. Moreover, we demonstrated that hsa_circ_0004872 acted as a “molecular sponge” for miR-224 to upregulate the expression of the miR-224 downstream targets p21 and Smad4. Importantly, we found that the RNA-editing enzyme ADAR1 inhibited hsa_circ_0004872 expression and further led to the upregulation of miR-224. Smad4, the downstream target of miR-224, could further affect hsa_circ_0004872 levels by directly binding to the promoter region of ADAR1 to inhibit ADAR1 expression. Conclusions Our findings showed that hsa_circ_0004872 acted as a tumor suppressor in GC by forming a negative regulatory loop consisting of hsa_circ_0004872/miR-224/Smad4/ADAR1. Thus, hsa_circ_0004872 may serve as a potential biomarker and therapeutic target for GC.
Prognostic Biomarkers in ST-Segment Elevation Myocardial Infarction: A Step Toward Personalized Medicine or a Tool in Search of an Application?**Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Luigi M. Biasucci, Roberta Della Bona
Journal: Journal of the American College of Cardiology (2011)
Abstract 12891: Psychosocial Factors at Middle Age and Zero Coronary or Extra-coronary Calcium at Older Age: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Yasuyuki Honda, Yejin Mok, Frances Wang, Miguel Cainzos Achirica, Shoshana Ballew, Gail Daumit, Anna Kucharska-newton, Candace Howard, Kenneth R Butler, Lynne E Wagenknecht, Aaron R Folsom, Matthew J Budoff, Michael J Blaha, Kunihiro Matsushita
Journal: Circulation (2020)

Background: Psychosocial factors are associated with atherosclerotic disease. However, their link to “healthy cardiovascular aging” is unknown. Aim: We aimed to comprehensively investigate the association of psychosocial factors at middle age with zero coronary artery calcium (CAC) or extra-coronary calcium (ECC) at age ≥75 years in the ARIC study. Methods: We studied 1,935 participants free of coronary heart disease history, who completed a psychosocial evaluation in 1990-1992 (mean age 53 [SD 4] years) and a cardiac computed tomography scan in 2018-2019. We assessed trait anger by the Spielberger Trait Anger Scale, depressive symptoms by the Maastricht Questionnaire, social support by the Interpersonal Support Evaluation List, and social network by the Lubben Social Network Scale. CAC/ECC was quantified by the Agatston score, and ECC included aortic valve ring, aortic valve, mitral valve, and ascending and descending aorta calcium. Results: The proportion of participants with zero calcium was 10 % for coronary artery, 15 % for aortic valve ring, 54 % for aortic valve, 52 % for mitral valve, 74 % for ascending aorta, and 11 % for descending aorta. Less trait anger was independently associated with zero CAC and aortic valve calcium (odds ratios [ORs] for one SD decrement of the score, 1.21 [95%CI, 1.02-1.45] and 1.16 [95%CI, 1.05-1.28], respectively) ( Figure A ). Less depressive symptoms, more social support, and larger social network were not positively associated with zero CAC or ECC ( Figure B-D ). The associations of less trait anger with zero CAC and aortic valve calcium remained significant when we applied inverse probability weighting to account for attrition. Conclusions: Among the psychosocial factors at middle age, only less trait anger was independently associated with zero CAC and aortic valve calcium at older age. Our findings suggest that the identification of less trait anger at middle age may be important for healthy cardiovascular aging.
Abstract 12787: Meta-analysis of Dual Antiplatelet Theraphyversus Single Antiplatelet Theraphyafter Transcatheter Aortic Valve Implatation: A Popular Forecast
Authors: GonÃ§alo Costa, Lino Gonçalves, rogerio P teixeira
Journal: Circulation (2020)

Background: Despite improving experience and techniques, ischemic and bleeding complications after transcatheter aortic valve implantation (TAVI) remain prevalent and affect survival. Recent guidelines recommend dual antiplatelet therapy (DAPT) in the initial period after TAVI. Explorative studies have suggested DAPT is associated with higher rate of major bleeding without a decrease in thromboembolic complications. Purpose: To compare DAPT (aspirin plus clopidogrel) versus single antiplatelet therapy (SAPT) (as aspirin) alone as antithrombotic treatment following TAVI for the prevention of cerebrovascular events, bleeding events and all-cause death. Methods: We systematically searched PubMed, Embase and Cochrane databases, in April 2020, for both interventional or observational studies comparing DAPT with (SAPT) following TAVI. Random-effects and meta-analysis for DAPT and SAPT were performed. Results: Nine studies were included (six registry-based or unrandomized studies and three randomized clinical trials) providing a total of 19389 patients, and 631 pooled stroke or transient ischemic attack. There was no statistically difference between DAPT and SAPT for the prevention of cerebrovascular events after TAVI (pooled OR 1.04 [0.85, 1.26], P=0.04, I 2 = 0%). Similarly, there was a similar rate of all-cause mortality (pooled OR 1.07 [0.81, 1.42], P=0.33, I 2 = 50%). Furthermore, the rate of major bleeding or life-threatening events was significantly higher for the DAPT compared with SAPT group (pooled OR 1.46 [1.19, 1.78], P&lt;0.01, I 2 = 79%), although with a considerable amount of heterogeneity between studies in the magnitude of effect. Conclusions: Our pooled data suggests that after TAVI, the clinical benefit of DAPT compared to SAPT is questionable. The POPular-TAVI trial Cohort A is expected to clarify this research question during 2020.
Abstract 14430: Effect Modification of Statin Therapy on the Relationship of Low-density Lipoprotein Cholesterol With Incident CKD in Us Veterans
Authors: Jui-Ting Hsiung, Maria Marroquin, Kamyar Kalantar-Zadeh
Journal: Circulation (2020)

Background: Studies suggests that in the general population, hyperlipidemia may confer higher risk of developing chronic kidney disease (CKD). But, there is conflicting data as to whether statins can protect renal function or slow renal degradation. We sought to examine the impact of statins on the association of low-density lipoprotein cholesterol (LDL) and risk of incident CKD. Methods: Our cohort included 1,439,756 US veterans without chronic kidney disease (CKD), but with LDL measured between 2004-2006, who were followed until 2014. Incident CKD was defined as over 3 estimated glomerular filtration rate (eGFR) measurements &lt;60 mL/min/1.73m 2 at least 90 days apart. Patients with a statin prescription at the time of LDL measurement were identified. Cox models were used to estimate the associations between LDL with incident CKD. Model adjustments include demographics, comorbidities, smoking status, prescription of fibrate or niacin, body mass index, albumin, high-density lipoprotein cholesterol, and triglycerides. Results: The cohort included 5% females, 16% African Americans, 26% diabetics, and 30% statin-users, with a mean age of 60±13 years. The median [IQR] of LDL and eGFR were 109 [88,133] mg/dL and 83 [72,94] mL/min/1.73m 2 , respectively. A J-shaped association between LDL and incident CKD were observed in both those on statin and not on a statin after adjustment. Low LDL (&lt;70 mg/dL) was associated with a higher risk of incident CKD compared to the reference (LDL 70-&lt;100 mg/dL) regardless of statin use. High LDL ≥160 mg/dL was associated with the highest of risks of incident CKD (HR: 1.08, 95% CI: 1.04, 1.13, and HR: 1.10, 95% CI: 1.07, 1.12, for statin use and no statin use, respectively). Conclusion: Both high and low LDL were associated with higher incident CKD risk independent of statin use in this US veteran cohort. Further studies are needed to understand how to manage cardiovascular disease risk by lowering LDL while simultaneously reducing risk of CKD.
Abstract 15830: Uncontrolled and Undertreated Cholesterol in Patients With Severe Hypercholesterolemia at a Large Healthcare System
Authors: Catherine P Benziger, Nicole Groth
Journal: Circulation (2020)

Introduction: Patients with phenotypic severe hypercholesterolemia (SH) (low-density lipoprotein-cholesterol (LDL-c) ≥ 190 mg/dL), should have at least 50% LDL-c lowering by treatment with a maximally tolerated statin to goal LDL-c&lt;100 mg/dL for primary prevention. Despite even more aggressive goals in Europe, these targets are not widely implemented. Methods: Cross-sectional study using an electronic medical record-based SH registry defined by ever having an LDL-c ≥ 190 mg/dL from 01/01/2000-01/16/2020 (n=17,925) at Essentia Health (MN, WI, and ND). Patients excluded if they had no visit at EH within the past 5 years (n=274), were &lt;20 or &gt;75 years old (n=3,171) or deceased (n=34). Results: We included 14,661 SH patients (81.1%) (mean age 59.8 ± 10.3 years; 58.9% female). A total of 40.7% were untreated for SH, 23.2% on a high-intensity statin, and 0.4% on proprotein convertase subtilisin/kexin type 9 inhibitor. Statins were prescribed in 31.8%, 47.9%, 56.1% and 65.4% of patients aged 20-39, 40-49, and 50-59, 60-75 years, respectively. There were 1,111 with a highest ever LDL-c &gt; 250 mg/dL (32.8% not currently on lipid medication (n=365) and 14.5% of this group had LDL-c&lt;100 mg/dL. Overall, 25.0% achieved at least 50% LDL-lowering (Table 1) and 19.8%, a most recent LDL-c&lt;100 mg/dL; 64.1% of men and 69.5% of women treated with any lipid medication still had an elevated LDL-c. In the no medication group, only 17.2% (n=1,025) had a statin allergy/intolerance. Females were less likely to be on a statin than males (p&lt;0.001). High-intensity statin was the strongest predictor of an LDL-c at goal, then highest ideal cardiovascular health score (adjusted RR 13.2; 95% CI: 11.1-15.6). Conclusions: Majority of patients at very high risk of CVD with SH remain untreated or undertreated with recent LDL-c levels above target. It is necessary to obtain better control of lipid levels in patients already being treated, increase the detection of SH and improve adherence to the current guidelines.
Reduction-active Fe3O4-loaded micelles with aggregation- enhanced MRI contrast for differential diagnosis of Neroglioma
Authors: Bo Wu, Kai Deng, Shu-Ting Lu, Cai-Ju Zhang, Ya-Wen Ao, Huan Wang, Hao Mei, Cai-Xia Wang, Haibo Xu, Bin Hu, Shi-Wen Huang
Journal: Biomaterials (2020)
Abstract 17106: Prediction of Recurrent Atherosclerotic Cardiovascular Disease Risk Using Machine Learning and Electronic Health Record Data
Authors: Ashish Sarraju, Andrew Ward, Sukyung Chung, Jiang Li, David Scheinker, Fatima Rodriguez
Journal: Circulation (2020)

Introduction: Patients with atherosclerotic cardiovascular disease (ASCVD) have high risk for recurrent ASCVD events despite statin use. Pooled cohort equations (PCE) are used for ASCVD risk prediction in primary prevention but there are no validated models for recurrent risk prediction in secondary prevention. Machine learning (ML) demonstrates promise in developing novel risk prediction models using electronic health record (EHR) data. Methods: We included adults with prior ASCVD from EHR data from an outpatient Northern California system between January 1, 2009 and December 31, 2018 with at least 2 visits at least 1 year apart and 5 years of follow up. The outcome was a recurrent ASCVD event defined as the first myocardial infarction, stroke, or fatal coronary artery disease in the 5 year follow-up period. We trained ML models to predict recurrent ASCVD risk: random forests (RF), gradient boosted machines (GBM), extreme gradient boosted models (XGBoost), and logistic regression with a standard L 2 penalty (LR) and an L 1 penalty (Lasso). We evaluated performance of ML models and the PCE on a 20% held-out test cohort using the areas under the receiver operating characteristic curves (AUCs). Results: Our cohort consisted of 32,192 patients with ASCVD (Mean age 70 years, 46% women, 12% Asian and 6% Hispanic). Less than half (49%) were on guideline directed statins. XGBoost and GBM were the best performing models for recurrent ASCVD risk prediction, while the PCE performed poorly (Figure). The top 20 predictive variables for recurrent ASCVD risk included prior events (ischemic stroke, myocardial infarction), traditional risk factors (age, blood pressure, lipid levels) and socioeconomic factors (income, education). Conclusions: EHR-trained machine learning models facilitated recurrent ASCVD risk prediction in real-world secondary prevention patients. Machine learning models developed from large datasets may help bridge contemporary gaps in ASCVD risk prediction.
Associations of Late Adolescent or Young Adult Cardiovascular Health With Premature Cardiovascular Disease and Mortality
Authors: Amanda M. Perak, Hongyan Ning, Sadiya S. Khan, Joshua D. Bundy, Norrina B. Allen, Cora E. Lewis, David R. Jacobs, Linda V. Van Horn, Donald M. Lloyd-Jones
Journal: Journal of the American College of Cardiology (2020)