tbuckley/cabot-search huggingface dataset:
Abstract 4132120: Down syndrome-trisomy-mediated gene, Dscr-1, protects against lifestyle-related vascular diseases
Authors: Takashi Minami
Journal: Circulation (2024)

Epidemiological studies indicate that individuals with Down syndrome (DS) have an increased risk of leukemia and neuronal diseases but a significantly reduced incidence of most solid tumors and advanced vascular dysfunction. This suggests that one or a combination of trisomy genes on human chromosome 21 (HSA21) or murine chromosome 16 ( Mmu16 ) may be responsible for protecting against vasculopathy. Our previous research has shown that the Down syndrome critical region (Dscr)-1 gene, located on HSA21 or Mmu16 , encodes a feedback modulator of calcineurin-NFAT signaling in endothelial cells (ECs). Null mutation or overexpression of Dscr-1 has been found to increase or prevent septic mortality, angiogenesis, liver steatosis, and susceptibility of tumor metastasizing to the lung, respectively, demonstrating its significant role in these processes. In a unique approach, we crossed DS model mice with ApoE -null mice and fed them a high-fat diet (HFD) for 12 weeks to survey the effects of DS-related genes on atherosclerosis. The results were striking, with HFD-mediated increased LDL and triglyceride levels in ApoE -null mice significantly reduced in the combined DS plus ApoE -null mice. This innovative method allowed us to observe a remarkable (~35%) reduction in ApoE-null mediated atheroma formation in the DS model. This finding was also replicated in EC-specific DSCR-1 transgenic (DSCR-1 ECTg ) mice. Furthermore, to test the effect of HSA21, we have collected DS patient-derived trisomy and disomy iPS cells and executed them for the chromatin conformation capture analysis and the in vitro ECs differentiation experiments. DS-derived trisomy iPS cells already changed the whole chromatin structure, typically within the X chromosome. Moreover, the trisomy iPS-derived ECs revealed less proliferation compared to the disomy. RNA-seqs indicated trisomy iPS derived ECs dramatically (21-fold) increased DSCR-1 , but some HSA21 genes, Alzheimer’s related App and Bace2 , e.g., were inversely reduced the expression. Our comprehensive studies not only shed new light on the mechanisms of atherosclerosis in vascular pathology but also offer potential therapeutic strategies. The discovery of the Dscr-1 gene on the DS chromosome, which could be a powerful tool in combating lifestyle-related vascular diseases, underscores the significance of our research.
Abstract 4131737: Atherosclerotic Cardiovascular Disease Risk Management in a Primary Care Residency Clinic
Authors: Kathryn Manalo, Xiarepati Tieliwaerdi, Megan Jackson, Alexis Arrigo, Mariah Mascara, Srijana Maharjan, Mrudula Gadani
Journal: Circulation (2024)

The 2018 AHA/ACC Multisociety Guideline on the Management of Blood Cholesterol recommends to target an LDL-C &lt;70mg/dL in very high risk ASCVD patients. If the patient is on maximally tolerated statin therapy and LDL-C remained &gt;70mg/dL, addition of ezetimibe was recommended. If LDL continued to be elevated, the addition of PCSK9 inhibitor was discussed. In 2019, the European Atherosclerosis Society recommended lowering the target LDL-C goal to &lt;55mg/dL in patients with very high ASCVD risk. This is based on prior studies demonstrating dose-dependent reduction in ASCVD with LDL-C reduction. The purpose of this study is to identify individuals at very high ASCVD risk and determine if they are on optimal medical therapy to achieve LDL &lt;55mg/dL with the intention to improve atheroscloertic cardiovascular risk management in primary care residency clinics. A review of electronic medical records from a primary care residency clinic was performed. Patients with hyperlipidemia and prior ASCVD event were identified. Additional data including lipid panel and current medical management were collected. Patients were stratified into very high risk and not very high risk groups according to AHA classification and analyzed. A total of 1,727 patients were found to have hyperlipidemia and a prior ASCVD event. The not very high risk group had an average age of 51 years with 54% (n=40) females and 45.9% (n=34) males. The very high risk group contained 95.7% (n=1,653) patients. The average age in the very high risk group was 68 years with 53.2% (n=879) of patients being female and 46.8% (n=774) being males. Of those patients, 73.6% (n=1,216) had an LDL ≥ 55 mg/dL. In these patients, 563 were on high intensity statin, 163 on moderate intensity statin and 15 on low intensity statin. There were 475 patients not on any statin. Of those on statin therapy, 66 were on ezetimibe alone and 10 were on both ezetimibe and PCSK9 inhibitors. Over 95% of patients with a prior ASCVD event were identified as being very high risk. Our data demonstrates that 3 in 4 patients were not on optimal medical therapy based on a stricter LDL goal. There was poor escalation of medical therapy as not all patients were on high intensity statin and only 10% of patients were on ezetimibe while even fewer patients were on additional PCSK9 inhibitor therapy. This study highlights the importance of risk stratification and vigilance in optimizing medical therapy.
Abstract 4132152: Cardiovascular Procedures for Hospitalized Patients with Hypertrophic Cardiomyopathy requiring Valvular Heart Repair/Replacement or Coronary Artery Revascularizations: A Risk-Stratified Analysis of a Large National Database
Authors: Saeed Shoar, Khaled Ali, Ahmed Abdelrazek, Elham Ahmad, Sadegh Asadi, Samin Sharma
Journal: Circulation (2024)

Background: Hypertrophic cardiomyopathy (HCM) is associated with increased mortality mainly due to sudden cardiac arrest. However, it is not clear how HCM affects in-hospital mortality among patients hospitalized due to other cardiovascular conditions requiring intervention. Methods: National Inpatient Sample (NIS) database was queried from 2016 to 2020 to identify hospitalized patients with a diagnosis of HCM. Patients with HCM were stratified based on their concomitant cardiovascular conditions necessitating interventions. Results: Data pertinent to 278,995 admission cases with HCM was analyzed. Of this, 15,035 cases had concomitant non-ST elevation MI (NSTEMI), and 1,230 cases had ST-elevation MI (STEMI). Additionally, 15,100 cases were diagnosed with aortic valve diseases (AVD), 33,580 had concomitant mitral valve diseases (MVD), 5,580 cases had tricuspid valve diseases (TVD), and 16,815 cases had pulmonary valve diseases (PVD). Cardiovascular procedures were more common among HCM patients with concomitant STEMI (43.5%) followed by HCM patients with AVD (17.1%) and HCM patients with NSTEMI (16.9%). Stratification of mortality rate based on cardiovascular procedures and the underlying indication revealed CABG to have the highest mortality rate for HCM patients with STEMI (25%), followed by PCI for HCM patients with STEMI and HFrEF (12.5%). HCM patients with NSTEMI undergoing revascularization had higher mortality when PCI was performed for HFrEF cases and when CABG was performed for HFpEF cases. For HCM patients with AVD requiring repair or replacement, TAVR was superior to SAVR if performed in patients with HFpEF but was inferior among HFrEF subgroup in terms of in-hospital mortality. For subgroup of HCM patients with MVD, transcatheter replacement was associated with a lower mortality than surgical repair regardless of concomitant heart failure. Data was insufficient for HCM patients with concomitant TVD or PVD undergoing repair or replacement procedures. Conclusions: Among hospitalized patients with HCM, concomitant HFrEF but not HFpEF is associated with a significantly higher mortality rate regardless of the underlying cardiovascular conditions requiring revascularization or heart valvular repair. A more comprehensive preoperative risk assessment could delineate the ideal procedures for HCM patients with certain comorbidities and specific need.
Abstract 4131951: The Safety Profile Of Inclisiran In Patients With Dyslipidemia And Intermediate To High Atherosclerotic Cardiovascular Disease Risk: A Systematic Review And Meta-Analysis
Authors: Maisha Maliha, Vikyath Satish, Kuan Yu Chi, Sriram Sunil Kumar, Amrin Kharawala, Gustavo Duarte, Shaunak Mangeshkar, Pawel Borkowski, Anita Osabutey, Eleonora GAshi, Supreeti Behuria
Journal: Circulation (2024)

Introduction: Inclisiran is a novel drug that employs ribonucleic acid (RNA) interference to lower levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, thereby improving the clearance of low-density lipoprotein (LDL) cholesterol from the bloodstream. It is given through subcutaneous injections at specified intervals and significantly reduces LDL cholesterol levels in patients with dyslipidemia and with intermediate to high risk of atherosclerotic cardiovascular disease (ASCVD). Goal: We aim to evaluate the safety of the use of inclisiran in patients with dyslipidemia and intermediate to high ASCVD risk. Methods: Three electronic databases of MEDLINE, Web of Science, and Embase were searched from inception to May 5th 2024 to identify relevant randomized controlled trials (RCTs) comparing safety profiles of inclisiran versus the control group . The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiovascular events (MACE), injection-site reaction and all treatment-emergent adverse events (TEAE). The effect estimates of outcomes were assessed using risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method given the inter-study variance was inevitable. The subgroup analysis was performed based on different dosing regimens. Results: We included 7 RCTs enrolling 4790 patients (63.8 ± 9.7 years, 66.8 % males) who received inclisiran. Compared to the control group, the use of inclisiran did not yield a significant effect on all-cause mortality (RR, 0.92; 95% CI, 0.54 to 1.54; I 2 = 0%), MACE (RR, 0.98; 95% CI, 0.82 to 1.17; I 2 = 0%), and TEAE (RR, 1.76; 95% CI, 0.74 to 4.15; I 2 = 74%). However, inclisiran use significantly increased injection-site reaction (RR, 7.08; 95% CI, 3.42 to 14.64; I 2 = 27%). Results are illustrated in the accompanying figure. Conclusions: Inclisiran use significantly increased injection-site reaction, with no increase in mortality and TEAE. Further trials are required to comprehensively assess the safety of inclisiran in the management of dyslipidemia in patients with ASCVD risk.
Abstract 4132288: Associations Between Health-Related Social Needs and Cardiovascular Health Among US Adults
Authors: Zefeng Zhang, Sandra Jackson, Angela Thompson-Paul, Xiaoping Yin, Robert Merritt, Fatima Coronado
Journal: Circulation (2024)

Background Unfavorable: health-related social needs (HRSNs) have the potential to worsen health and wellbeing and drive health disparities. Its associations with cardiovascular health (CVH), assessed by Life’s Essential 8 (LE8), have not been comprehensively examined among US adults. Research Questions/Hypothesis: Whether unfavorable HRSNs are associated with worse CVH. Goals/Aims: To determine associations between unfavorable HRSNs and CVH in a large, diverse, nationally representative sample of US adults. Methods: We used the National Health and Nutrition Examination Survey 2011–March 2020 data for adults aged ≥20 years. We grouped LE8 scores as low (0–49), moderate (50–79), and high (80–100) CVH. We identified 8 unfavorable HRSNs: unemployed, low family poverty-to-income ratio, food insecurity, less than high school education, no healthcare access, no health insurance, no homeownership, and living alone. We assigned a value of 1 for the unfavorable status of each. The number of unfavorable HRSNs was summed and ranged from 0 to 8, with higher numbers indicating more unfavorable HRSNs. We categorized unfavorable HRSNs as none, 1–2, 3–4, and ≥5. We used multivariable linear and multinomial logistic regression to examine the association between HRSNs and CVH. Results: We included 14 947 participants (n=7340 male [49.3%]; mean [SE] age, 46.4 [0.35] years). Of those, 29.1% were categorized as having HRSNs 0, 40.4%; HRSNs 1–2, 21.5% HRSNs 3–4, and 9.0% HRSNs ≥5. The prevalence of low, moderate, and high CVH was 14.7%, 63.5%, and 21.8%, respectively. Every one-unit increase in unfavorable HRSNs was associated with 1.59 points lower LE8 scores ( P &lt;.001). Comparing participants with HRSNs values of 1–2, 3–4, and ≥5 to those with none, the fully adjusted prevalence ratios for low CVH were 1.42 (1.17–1.73), 2.11 (1.69–2.63), and 2.42 (1.90–3.08), respectively. The corresponding prevalence ratios for high CVH were 0.77 (0.68–0.87), 0.58 (0.49–0.67), and 0.46 (0.38–0.55). The associations were consistent across subgroups and in sensitivity analyses. Conclusions: A graded association exists between unfavorable HRSNs and higher prevalence of low CVH or lower prevalence of high CVH. Public health interventions targeting unfavorable HRSNs might reduce health disparities and promote CVH.
Abstract 4131630: Comparative Outcomes of Left Atrial Appendage Occlusion Device Implantation in Atrial Fibrillation Patients with a Lower Stroke Risk
Authors: Amanda Nguyen, Muhammad Zia khan, Waleed Alruwaili, Siddharth Agarwal, sudarshan balla, Bilal Munir
Journal: Circulation (2024)

Introduction: Current guidelines recommend oral anticoagulation in atrial fibrillation (AF) patients with a CHA 2 DS 2 -VASc score ≥ 2 for stroke prevention. Left atrial appendage occlusion (LAAO) devices serve as alternatives to reduce stroke risk in select AF patients that are unable to tolerate long-term oral anticoagulation. However, Centers for Medicare&amp;Medicaid Services reimburses left atrial appendage occlusion (LAAO) for patients with CHA 2 DS 2 -VASc score ≥ 3. Objective: To evaluate differences in outcomes and complications of LAAO therapy in AF patients with a CHA 2 DS 2 -VASc score of ≥ 3 versus &lt; 3. Methods: National Inpatient Sample and International Classification of Diseases, 10th Revision codes were used to identify AF patients who underwent LAAO device implantation in the U.S. from 2016−2020. The study population was stratified by stroke risk into two groups, CHA 2 DS 2 -VASc ≥ 3 and &lt; 3. Study endpoints assessed included procedural complications, inpatient outcomes and resource utilization. A multivariable logistic regression model was used to assess the independent association of CHA 2 DS 2 -VASc score with study outcomes. Results: A total of 73,795 and 15,500 LAAO devices were implanted in patients with CHA 2 DS 2 -VASc ≥ 3 and &lt; 3, respectively. Compared to patients with CHA 2 DS 2 -VASc score of ≥ 3, patients with CHA 2 DS 2 -VASc &lt; 3 had lower overall (6.9% vs 9.9%, P&lt; 0.01) and major (4.5% vs 6.2%, P&lt; 0.01) complications in the crude analysis. After multivariable adjustment for potential confounders, CHA 2 DS 2 -VASc &lt; 3 was associated with lower overall complications (aOR 0.84, 95% CI 0.78 – 0.91), major complications (aOR 0.90, 95% CI 0.81-0.99) and cost of hospitalization (aOR 0.95, 95% CI 0.91-0.99). Conclusions: Patients with CHA 2 DS 2 -VASc &lt; 3 had lower complications and hospitalization costs after LAAO device implantation than patients with CHA 2 DS 2 -VASc ≥ 3 . These data, if redemonstrated in a large randomized trial can have important clinical implications for stroke prevention in AF patients.
Abstract 4131775: Effectiveness of Lipid-lowering therapy with Bempedoic Acid plus Ezetimibe in a Real-world Cohort
Authors: James Nelson, Leanne Bloedon, David Lewandowski, Machaon Bonafede, Evelyn Sarnes
Journal: Circulation (2024)

Introduction: Bempedoic acid and the combination with ezetimibe (BA+EZE) have demonstrated low-density lipoprotein cholesterol (LDL-C) lowering in clinical trials of adults with primary hyperlipidemia at high risk for or with cardiovascular disease. The impact of BA+EZE on LDL-C outcomes in a real-world cohort has not been studied. Aim: To evaluate the effectiveness of BA+EZE on LDL-C reduction and goal achievement using real-world data. Methods: This was a retrospective cohort study using deidentified electronic health records and linked claims data. Adult patients were included if they had a pharmacy claim for BA+EZE from March 1, 2020 to March 15, 2024 (date of first pharmacy claim = index date ), had ≥1 baseline LDL-C lab result on or within 6 months prior to the index date, and ≥2 LDL-C lab results post-index, including 1 lab result 12 months post-index (±60 days). Patients with documented use of ezetimibe on or within 6 weeks prior to index were excluded. For all patients with available valid lab results, LDL-C was determined at baseline (the value closest to but not after the index date), 3 months (±30 days), 6 months (±60 days) and 12 months (±60 days). Results: A total of 615 BA+EZE patients were identified (mean age 62±11 years, 52% women). At baseline, 64% had evidence of statin use in the prior 12 months and the mean LDL-C was 131±52 mg/dl. Figure 1 shows the change in the proportion of patients achieving LDL-C control at index, 3-, 6-, and 12-months post-index. The proportion of patients achieving LDL-C &lt;100 mg/dL more than doubled from index (30%) to 3 months (67%), and was sustained through 12 months (55%). At 12 months, there were fewer patients with LDL-C ≥130 mg/dL (24% vs 47% at index). The mean LDL-C reduction was 28% at 3 months (to 94±47 mg/dL), 27% at 6 months (96±44 mg/dL), and 22% at 12 months (102±47 mg/dL) (p&lt;0.0001 for all vs index). Conclusion: Patients who initiated BA+EZE showed early and sustained improvements in LDL-C. Future research should consider the impact of time on therapy and adherence on LDL-C control.
Abstract 4132212: Trends in Atrial Fibrillation or Flutter Related Mortality Among Adults in the United States: Insights from CDC WONDER Database from 1999-2020
Authors: Shurjeel Qazi, Eeman Ahmad, Danish Ali Ashraf, Fabeeha Shaheen, Tayyab Ahmad, Maham Afzal, Muhammad Hamza Anees, Bilal Ahmad, Amir Hassan, Neha Paryani
Journal: Circulation (2024)

Background: Atrial fibrillation or flutter (Afib/AFL) incidence rates continue to rise and are linked to significant mortality, particularly in older populations. Our analysis examines Afib/AFL mortality trends across different demographics and regions in the U.S. from 1999 to 2020, highlighting the importance of understanding these patterns. Aim: To guide preventive measures that alleviate the impact of Afib/AFL and identify high-risk populations and regions, we sought to quantify trends associated with Afib/AFL related mortality in the U.S. Methods: We conducted a comprehensive search of death certificates from 1999-2020 using Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database focusing on Afib/AFL mortality in adults with ICD-10 codes I48. Gender, race, geographical and urban-rural parameters were investigated by calculating annual percent change (APC) and age-adjusted mortality rates (AAMRs) per 100,000 persons using the Joinpoint Regression Program (Joinpoint V 4.9.0.0, National Cancer Institute). Results: A total of 2,581,488 deaths occurred in patients with Afib/AFL from 1999 to 2020. The AAMR displayed an abrupt rise from 2018 to 2020 (APC: 8.51; 95% CI: 4.84-10.47). Men consistently exhibited a higher AAMR (overall AAMR male: 79.4, 95% CI 79.3-79.6; female: 60.8, 95% CI 60.7-60.9). Non-metropolitan areas showed higher AAMRs than metropolitan areas (overall AAMR non-metropolitan areas: 74.9, 95% CI 74.7-75.1; metropolitan: 67.2, 95% CI 67.1-67.2). Disparities were also observed in AAMRs by region with the West region showing the highest mortality rate with a notable rise between 2010 and 2020 (APC: 3.70, 95% CI 3.30-5.37). Non-hispanic (NH) White population showed the highest mortality (overall AAMR: 74.2, 95% CI 74.1-74.3), followed by NH American Indian (AAMR: 50.3), NH Black (AAMR: 45.8), NH Asian (AAMR: 35.0) and Hispanic (AAMR: 37.9) populations. Conclusion: Mortality from Afib/AFL has risen from 1999 to 2020. Men, NH white populations, and residents in non-metropolitan areas and Western U.S. are at higher risk. Targeted interventions and strategic healthcare resource allocation are needed to address these disparities and improve outcomes.
Abstract 4131815: The Prevalence of Normal Coronary Arteries as Determined by a Coronary Artery Calcium Score of Zero Amongst Subjects with Diabetes Mellitus
Authors: Jonathan Phan, April Kinninger, Sion Roy, Srikanth Krishnan, Mrinal Bhandari, Logan Schwarzman, Matthew Budoff
Journal: Circulation (2024)

Background: The CDC reports that in 2021, 11.6% of the American population had diabetes mellitus (DM). Past literature has shown diabetes to be a significant risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). Research Question/Goal: Using data obtained through Computed Tomography Angiography (CTA), we aim to distinguish the risk factors associated with a coronary artery calcium (CAC) score of zero in subjects with DM and to identify the prevalence of non-calcified plaque in individuals with this score. Methods: We performed a retrospective study of patients with DM, who underwent CAC and CTA screenings from October 2004 to January 2024 at our center in Torrance, California to examine CTA outcomes in those with CAC Score of zero and greater than zero. Results: Among the cohort of 2,763 subjects with DM, the average age was 63.8±12.2 years, 62% male. Within this cohort, 465 (17%) subjects had a CAC Score of zero compared to 2,298 subjects with a CAC Score greater than zero with a median score of 428 (Interquartile range (IQR) 91-1267). DM subjects with CAC Score of zero were significantly younger (53.0±13.9 versus 66.0±10.6: p&lt;0.001), were more likely to be female and had significantly lower rates of hypertension (57% versus 76%: p&lt;0.001), and hyperlipidemia (63% versus 76%: p&lt;0.001). In DM subjects with CAC Score of zero, 133 (29%) had a total plaque severity score of 1 or greater (median 1, IQR 1-2) while 332 (71%) had normal coronaries on CTA. Conclusions: A significant percentage of subjects with DM were determined to have a CAC score of zero. Subjects with normal coronary arteries were more likely to be younger, female, and/or absent of other chronic diseases such as hypertension and hyperlipidemia. Although age and sex are nonmodifiable risk factors of ASCVD, limiting the comorbid conditions associated with DM may be beneficial in preventing ASCVD in individuals with diabetes.