tbuckley/cabot-search huggingface dataset:
Abstract 4136873: The Role of Socioeconomic Status in the Association Between Cardiovascular Polygenic Risk Score and Cardiovascular Events
Authors: Saigeetha Bhaskar, James Pirruccello, Thomas Hoffmann, Alexis Beatty
Journal: Circulation (2024)

Introduction: Polygenic risk scores (PRS) provide a summation of small-effect genetic variants that predict cardiovascular (CV) disease risk. Socioeconomic status (SES) can also impact CV risk, but it is unknown whether SES modifies the effects of PRS on CV events. Hypothesis: The association between CV PRS and CV events is modified by SES. Methods: Participants without CV disease at baseline from the UK Biobank prospective cohort study were followed from recruitment (2006-2010) through 2023. We included participants with genetic data (for CV PRS) and CV risk factors assessed at baseline (hemoglobin A1c, total cholesterol, blood pressure, body mass index, physical activity, tobacco use, and sleep). The CV PRS was centered at zero and standardized to one unit variance within each ancestry group. SES was defined by tertiles of index of multiple deprivation (from housing, crime, income, education, employment, health deprivation and disability, and neighborhood environment). The primary outcome was CV events (myocardial infarction, heart failure hospitalization, stroke, or death). Using Cox proportional hazard models, we estimated the total effect of PRS on CV events, tested for interaction of SES in the association between PRS and CV events, and estimated the direct effect of PRS on CV events by adjusting for age, sex, CV risk factors, and SES. Results: There were 201,374 participants (mean age 55.9 (± 8.1), 53.4% female). CV events occurred in 21,916 (10.9%) participants: 5,754 (2.9 %) myocardial infarctions, 4,061 (2.0%) strokes, 4,312 (2.1%) heart failure hospitalizations, and 12,782 (6.4%) deaths. Each unit of PRS was associated with 1.17 times the risk of CV events (HR 1.17, 95%CI 1.15 to 1.18, p-value &lt; .001, adjusted for age and sex). People with the lowest SES had 1.22 times the risk of CV events (HR 1.22; 95%CI 1.18 to 1.26; p-value &lt;.001) and the middle SES had 1.07 times the risk of CV events (HR 1.07; 95%CI 1.03 to 1.10; p-value &lt;.001) compared to the highest SES, adjusted for age, sex, and CV risk factors. PRS remained associated with CV events (HR 1.15, 95%CI 1.13 to 1.16, p-value&lt;.001) after adjusting for age, sex, CV risk factors, and SES. There was no significant multiplicative interaction between SES and PRS for CV events (interaction p-value = 0.45). Conclusions: SES is associated with CV events but does not modify the effect of PRS on CV events. Genetic risk remains independently important in CV event risk beyond traditional CV risk factors and SES.
Abstract 4136741: Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Lipid Reduction: A Network Meta-Analysis
Authors: Hua Shen, Meng Chai, Yujie Zhou
Journal: Circulation (2024)

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors offer additional lipid reduction beyond that achieved with statins. However, the optimal PCSK9 therapy for lowering lipid levels in patients with hypercholesterolemia and/or hyperlipidemia on background statin therapy remains unclear. Methods: PubMed and EMBASE databases were searched for RCTs assessing tafolecimab, evolocumab or alirocumab vs. placebo (administrated Q2W or Q4W, 12-week treatment) in patients with hypercholesterolemia and/or hyperlipidemia on medium-intensity statin up to March 28, 2024. The outcomes of interest were the percentage change in low-density lipoprotein cholesterol (LDL-C) or lipoprotein(a) from baseline to the 12th week. A frequentist random-effect network meta-analysis was applied to calculate MD and 95% CI using Stata 16.0 software. Results: A total of 4960 patients [PCSK9 inhibitors (n=3230), placebo (n=1730)] across 13 RCTs were included. At week 12, tafolecimab, evolocumab and alirocumab (either Q2W or Q4W) all induced significant reductions in LDL-C levels compared to placebo ( Figure ). The efficacy of evolocumab Q2W was significantly higher compared with alirocumab Q2W (MD=-18.67%, 95% Cl [-29.59%, -7.74%]), while similar LDL-C reduction was observed in tafolecimab Q2W vs. alirocumab Q2W and evolocumab Q2W vs. tafolecimab Q2W. Furthermore, tafolecimab Q4W and evolocumab Q4W were more effective in lowering LDL-C levels compared to alirocumab Q4W (tafolecimab vs. alirocumab: MD=-23.66%, 95% Cl [-32.58%, -14.74%]; evolocumab vs. alirocumab: MD=-25.84%, 95% Cl [-34.21%, -17.46%]), while there was no difference between evolocumab Q4W and tafolecimab Q4W. Lastly, the ranking of the effects for reducing lipoprotein(a) levels was as follows: tafolecimab &gt; evolocumab&gt; alirocumab (either Q2W or Q4W). Conclusions: In patients with hypercholesterolemia and/or hyperlipidemia treated with medium-intensity statins, tafolecimab and evolocumab (either Q2W or Q4W) might be preferred choices for lowering LDL-C. Additionally, tafolecimab (either Q2W or Q4W) appears to be the most effective agent for reducing lipoprotein(a) levels.
Abstract 4135835: Prevalence of Diabetes Mellitus in Calcutta Schoolteachers and its Relationship with Cardiovascular Risk as Assessed by the ASCVD Model
Authors: Madhab Ray, Dr. Santanu Guha, Bipasha Ray, Varun Saxena, Rohan Menon, Virang Desai, Meghna Ray, Vivaan Desai, Trisha Sagar Dey, Neev Goel, Lisa John, Julie Soohoo, Maria John, Arja Sarkar, Khushal Gogada, Anushri Pal, Ahana Ghosh, Sonali Sikder, Badri Viswanathan, Srijan Mandal, Avik Karak, Basabendra Chowdhury, Sudipta Chaudhuri, Prakash Hazra, Robert Goldberg, Deepak Bhatt, Harry Selker
Journal: Circulation (2024)

Introduction: Cardiovascular disease (CVD) is rising in prevalence in India with economic development and the adoption of a Western lifestyle. Hypothesis: The increase in incidence and prevalence of CVD is possibly due to a rise in the incidence of risk factors like diabetes mellitus (DM), hypertension, hyperlipidemia, lack of physical activity and obesity, among various other causes. Aims: 1. To estimate the prevalence of DM in the community of Calcutta schoolteachers 2. To examine the relationship between the prevalence of DM and CVD risk as assessed by the different traditional CVD risk factors (age, sex, hypertension, current smoking, DM, and hyperlipidemia). Methods: We recruited 4,150 schoolteachers from 400 schools in Calcutta, India between June, and August 2019 with approval of the Tufts IRB and the local Ethics Committee. Participants were asked questions about their different risk factors to ascertain their cardiovascular risk by the ASCVD risk calculator. Baseline values (total cholesterol 170 mg/dL, HDL-C 50 mg/dL, no DM) were used when a participant’s glycemic status or lipid profile was not available. Based on the risk score, participants were stratified as mild (&lt;5%), moderate (5-10%), or high (&gt;10%) risk for developing ASCVD. A total of 240 participants were randomly selected from a stratified sample of the participants for evaluation for diabetes using HbA1c. DM was diagnosed when the Hb A1 C was 6.5% or more. Results: The mean age of the participants was 44 years, and 41% were male. Out of a total of 4,150 participants, 85.7% (3,558) were in the low-risk for CVD category, 9.0% (374) were moderate-risk, and 5.3% (218) were high-risk. Among the 240 screened for DM, 17.1% (41) were found to have the condition, and 41.3% (99) were pre-diabetic. There was no significant difference in prevalence of DM between men and women in the overall study population and in the mild risk group. However, more women in the medium risk group and more men in the high-risk group were found to be diabetic (p value &lt;0.001 in both). Some participants were reclassified based on their new diagnosis of DM. Conclusions: The prevalence of DM was high among Calcutta schoolteachers, which contributes to being at increased risk for ASCVD. Most participants were unaware of their DM or cardiovascular risk, highlighting the need for increased testing and awareness. The estimates from this study may be used to understand the community burden of DM and cardiovascular risk.
Abstract 4136636: Analysis of Racial Disparities in the Training Path to Cardiology: Trends from 2012 to 2022
Authors: Jay Gopal, Maryam Rahafrooz, Nathan Chan, Devraj Gopal, Joshua Kepler, Junling Ren, Indulekha Gopal, Jacob Joseph
Journal: Circulation (2024)

Introduction: Substantial evidence indicates that racial and ethnic diversity among the physician workforce bridges cultural gaps and improves patient care. Trends in racial diversity across the full training pipeline from undergraduate to practicing cardiologist are not yet well-characterized. Aims: We analyze racial disparities at each stage of training towards becoming a practicing cardiologist, and identify changes in these disparities between 2012 and 2022. Methods: We conducted a retrospective analysis of data specifying the racial composition of medical trainees acquired from the Association of American Medical Colleges, Accreditation Council for Graduate Medical Education, and Electronic Residency Application Service. Population data was acquired from the US Census Bureau. We computed the representation quotient (RQ) for each racial group at each stage to compare representation among the trainees or physicians to age-matched segments of the US population. Results: RQ decreases from undergraduate to active cardiologist for African Americans (0.719 to 0.314), Hispanics (0.660 to 0.359), American Indians (0.551 to 0.221), and Native Hawaiians (1.121 to 0.512). The lowest RQs of 0.133 and 0.137 were observed for American Indian active internal medicine residents and cardiology fellows, respectively. Racial disparities in medical education declined between 2012 and 2022, with RQs increasing from 0.541 to 0.735 for African American medical school matriculants and from 0.444 to 0.578 for Hispanic medical school matriculants. Similar increases were seen in the active cardiologist population for African Americans (2013 RQ: 0.227, 2022 RQ: 0.342) and Hispanics (2013 RQ: 0.283, 2022 RQ: 0.375). Conclusion: While racial diversity in the cardiology training pipeline has increased over the last decade, significant disparities persist for under-represented minorities. Addressing these barriers will help achieve a cardiology workforce reflective of the diverse population it serves.
Abstract 4137019: Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Mohammad Tanashat, Mahmoud Shaaban Abdelgalil, Mohamed Abuelazm, AlMothana Manasrah, Mohamed Abouzid, Mohanned Abu El Haija, Suhaib El Khatib, Mutaz Abu-Laila, Mohammed Ayyad
Journal: Circulation (2024)

Background: Despite the effectiveness of drug-eluting stents (DES) in preventing restenosis, many patients still experience DES restenosis. Neointimal hyperplasia and neoatherosclerosis can develop within these stents, leading to recurrent coronary syndromes. Hypothesis: Repeated stenting with DES is limited by additional metal layers, the need for prolonged dual antiplatelet therapy, and heightened risks of stent thrombosis. Locally acting drugs with sustained efficacy may prevent this progression. Paclitaxel delivery via contrast medium or drug-coated balloon catheters could exert antiproliferative effects, reducing neointimal proliferation. Aims: To synthesize existing evidence on the efficacy and safety of Paclitaxel-Coated Balloons versus Uncoated Balloons in coronary in-stent restenosis. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched five electronic databases (PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science) to identify eligible studies reported up to March 23, 2024. Using R version 4.4.0, we reported outcomes as risk ratios (RRs) or mean differences (MD) and confidence intervals (CIs). This review has been registered and published in PROSPERO (CRD42024527412). Results: The meta-analysis included a total of six trials with 1,541 patients. PCB significantly reduced the incidence of myocardial infarction (RR 0.65, 95% CI [0.42, 1.00], p = 0.052), stent thrombosis (RR 0.26, 95% CI 0.08, to 0.83], p = 0.023), major adverse cardiac events (RR 0.32, 95% CI 0.25, to 0.42], P &lt; 0.001), target lesion revascularization (RR 0.34, 95% CI [0.14, 0.84], p &lt; 0.001). No significant differences were observed between PCB and UCB regarding cardiac-related mortality, target vessel revascularization, percutaneous coronary intervention, all-cause death, Q wave and non-Q wave myocardial infarction, coronary artery bypass grafting, and target vessel failure. Conclusion: PCB for ISR significantly reduced the incidence of myocardial infarction, MACE, and stent thrombosis compared to UCB.
Abstract 4135273: Frailty increases the risk of in-hospital mortality and post-procedural complications in patients undergoing Cardiac Implantable Electronic Devices placement
Authors: Andres Quevedo Ramirez, Sharan Malkani, Badri Aryal, Vivek Jha
Journal: Circulation (2024)

Background: Heart failure with reduced ejection fraction (HFrEF) often necessitates the use of cardiac implantable electronic devices (CIED) such as cardiac resynchronization therapy defibrillators (CRT-D) or implantable cardioverter-defibrillators (ICD). These devices are proven to reduce mortality, prevent hospitalizations, and improve symptoms and quality of life. Frailty, characterized by an age-associated decline in physiological reserve, significantly impacts outcomes in these patients. This study uses the Hospital Frailty Risk Score (HFRS) to assess the effect of frailty on mortality and post-procedural complications in HFrEF patients undergoing CIED implantation. Hypothesis: Frail patients with HFrEF have worse in-hospital outcomes after CIED placement Methods: We conducted a retrospective cohort study using the 2020 National Inpatient Sample database from the Healthcare Utilization Project. Our population included patients aged 18 years or older with HFrEF who underwent CRT-D or ICD placement, identified using ICD-10 procedure codes. The primary risk factor was frailty, classified by an HFRS score of ≥5 (frail) or &lt;5 (not frail). The primary outcome was in-hospital mortality, and the secondary outcome was the composite of post-procedural complications. Multivariate regression analysis was used to estimate the odds ratio. Results: Out of 24,809 patients who underwent ICD or CRT-D placement, 48.8% were frail. Non-Frail patients had lower mean age compared to Frail patients (66.2 vs 67.3 years old, p=0.003). In-hospital mortality was 1.1%, and 7% experienced post-procedural complications. In-hospital mortality was higher in frail patients compared to non-frail patients (2% vs 0.3%, p&lt;0.001). In the multivariate analysis, frail patients had higher odds of in-hospital mortality compared to the non-frail group subset (OR=5.97; 95% CI: 2.77-12.88, p&lt;0.001). Additionally, frailty was associated with higher odds of post-procedural complications (OR=1.28; 95% CI: 1.01-1.63, p&lt;0.001), increased length of stay (5 vs 11.6 days, p&lt;0.001), and total hospital charges (215,668 vs 324,474 , p&lt;0.001). Conclusion: Frailty significantly increases the risk of in-hospital mortality and post-procedural complications in HFrEF patients. This highlights the importance of considering frailty as part of a pre-procedural risk stratification assessment and tailoring management strategies to improve outcomes for these high-risk patients.
Abstract 4135852: Safety and Post-operative Complications of Endovascular Versus Surgical Versus Follow-up and Medical Treatment for Patients with Vertebrobasilar Artery Stenosis: Propensity Score Weighting and a Machine Learning Driven Analysis
Authors: Ahmed Shaheen, Ram Saha, Nour Shaheen
Journal: Circulation (2024)

Background: Vertebrobasilar artery stenosis (VBAS) can cause posterior circulation strokes (PCS). Optimal management is controversial, with options including medical therapy (MT), endovascular stenting (ES), and surgical revascularization (SR). This study compares outcomes of these treatments and evaluates the correlation between clinical features and medical history with 30-day outcome. Methods: Patients with VBAS were identified from the 2017-2018 National Inpatient Sample (NIS). Propensity scores adjusted for baseline differences. Outcomes included mortality, neurological complications (NC), discharge destination (DD), length of stay (LOS), total charges (TC), and procedural complications (PC). Predictive ability of clinical variables was assessed using logistic regression (LR) and machine learning techniques (MLT). Results: Of 1,343 patients, 1,061 (79.0%) received NI, 234 (17.4%) underwent ES, and 24 (1.8%) had SR. Mean age was 69.45 years, with 64.1% male. Demographics: 69.8% White, 14.9% Black, 10.0% Hispanic, and 5.3% other races. Hypertension (HTN, 85.4%) and diabetes (DM, 18.9%) were prevalent. After propensity weighting, ES was associated with higher odds of mortality, surgical/medical complications (SMC), and device/graft complications (DGC) compared to NI. SR showed a non-significant trend toward higher non-home discharges (NHD). ES and SR groups had higher resource utilization with longer LOS and greater TC. Clinical variables alone were weak predictors, with AUC values ranging from 0.454 to 0.71 across different outcomes and models. Conclusion: ES of VBAS was associated with higher mortality and complication rates compared to MT alone, with inconsistent benefits for NC. SR also carried elevated risks without clear advantages over MT. These results support that current clinical independent variables from the NIS are weak predictors. This highlights the limitation of the database in relying solely on clinical and medical history, and suggests that future use of radiological and anatomical features can improve predictions of outcomes and determination of subgroups that can benefit from certain treatment. More studies should be conducted, including post hoc analyses based on radiological and anatomical features, to better inform treatment decisions and determine subgroups that can benefit from intervention or surgery. These findings suggest a need for judicious patient selection and reinforce the role of optimal MT.
Abstract 4135700: Effects of Mitochondrial Dysfunction on Extracellular Vesicle Release and Subsequent Disruption of the Lung Vascular Endothelial Barrier
Authors: Eleftheria Letsiou, Mohammed Yaman AL Matni, Lucille Meliton, Rachel Lawrence-Foster, Aras Kadioglu, Steven Dudek
Journal: Circulation (2024)

Background: Lung endothelial cell (EC) barrier disruption is a hallmark of acute lung injury (ALI), which is commonly caused by bacterial pneumonia. Alveolar epithelial cells (AEC) are the first line of defence against invading respiratory pathogens in the lungs and can mediate inflammatory signaling to the adjacent EC contributing to barrier disruption. We have previously demonstrated that pneumolysin (PLY), a major Streptococcus pneumoniae virulence factor, induces both mitochondrial dysfunction in lung AEC and release of large extracellular vesicles (EVs). These EVs, which are enriched with mitochondrial cargo, contribute to increased permeability of the lung EC barrier. Here, we investigate strategies to inhibit mitochondrial dysfunction in AEC and examine how these interventions impact EC barrier function. Methods: Human alveolar epithelial cells (A549) or immortalized AEC (Cell Biologics) were pre-treated with mitoTEMPO (mtROS scavenger), P110 (excessive fission inhibitor), or ensifentrine [dual phosphodiesterase (PDE) 3/4 inhibitor] prior to PLY treatment (100-300 ng/ml, 4 hrs). Mitochondrial function was assessed by the JC-1 assay. EVs were isolated from cell media and analyzed for their mitochondrial content (Tom20 and Tim23 expression). To assess their functional role, EVs were added to TNF-α treated human lung microvascular EC, and barrier function was then determined using the ECIS assay to measure transendothelial electrical resistance (TER). Results: PLY-induced mitochondrial dysfunction was reduced in the presence of mitoTempo or P110. EVs from PLY-treated AEC (EV PLY ; enriched mitochondrial content) exacerbated TNF-α-induced EC barrier permeability as indicated by the significant decrease in TER. EV PLY derived from MitoTEMPO or P110-pretreated AEC contained less mitochondrial cargo and resulted in less EC permeability after TNF-α. Compared to mitoTEMPO and P110, ensifentrine exhibited superior protection against mitochondrial dysfunction after PLY exposure. In addition, in the presence of ensifentrine, the quantity of EV release and their extracelllular mitochondrial content were both dramatically reduced. In contrast to control EV PLY , EV PLY from ensifentrine-pretreated AEC demonstrated no barrier disruptive properties. Conclusions: Mitochondrial dysfunction in AEC contributes to vascular endothelial injury in ALI through mechanisms involving the release of barrier-disruptive EVs, which can be effectively targeted by inhibiting PDE3/4.
Abstract 4136040: Wearable Device-Measured Physical Activity and Incident Cardiovascular Diseases In Cancer Survivors
Authors: chengqing Jiang, ziang Li, Haiyan Xu, Yongjian Wu
Journal: Circulation (2024)

Background: Cardiovascular diseases (CVD) is the leading cause of non-cancer mortality among cancer survivors. Despite the known benefits of physical activity on cardiovascular health in the general population, evidence regarding post-diagnosis physical activity and CVD risk among cancer survivors is limited. Objectives: To explore the associations of wearable device-measured moderate-to-vigorous intensity physical activity (MVPA) with CVD risk in long-term cancer survivors. Methods: The retrospective analysis involved a prospective cohort of 6109 cancer survivors without CVD from the UK Biobank accelerometry subsample. Cancer diagnoses were obtained from national cancer registries (International Classification of Diseases-10 [ICD-10], C00-C97, except for non-melanoma skin cancer, in situ, and non-well-defined cancers), and participants were followed up through December 31, 2022. A machine-learning algorithm was utilized to categorize MVPA into four groups based on guideline-recommend MVPA duration (0-75 min/week, 75-150 min/week, 150-300 min/week, ≥300 min/week). Results: Over a median follow-up of 7.88 years, there were 539 incident CVD events, including 361 incident CAD events, 155 incident HF events, and 109 incident stroke events. A clear inverse linear dose-response relationship between MVPA volume and the incidence of CVD was observed (P for nonlinear=0.49), with no maximal threshold for the benefits. Adjusted CVD incidence rates (95% confidence intervals [CIs]) across MVPA groups (0-75 min/week, 75-150 min/week, 150-300 min/week, ≥300 min/week) were 15.30 (12.90, 18.10), 13.50 (11.00, 16.40), 12.00 (10.20, 14.10), and 9.86 (8.35, 11.60) per 1000 person-years, respectively. Adjusted hazard ratios (95% CI) for CVD, CAD, HF, and stroke in the highest MVPA group (≥300 min/week) compared with those with the lowest MVPA group (0-75 min/week) were 0.63 (0.49, 0.80), 0.68 (0.51, 0.91), 0.66 (0.42,1.06), 0.72 (0.42, 1.23), respectively. Conclusions: Findings from the UK Biobank study suggest that longer durations of MVPA are associated with reduced incident CVD risk in cancer survivors, particularly in CAD risk reduction, underscoring the potential for physical activity to serve as a key component in cardio-oncology care.