Abstract 4116285: Safety and Efficacy of Early Direct Oral Anticoagulants Versus Low Molecular Weight Heparin in Patients with Ischemic Stroke and Immobility: A Multi-National Database Study

Circulation, Volume 150, Issue Suppl_1, Page A4116285-A4116285, November 12, 2024. Background:Low molecular weight heparin (LMWH) is the preferred anticoagulant for venous thromboembolism (VTE) prophylaxis in patients with ischemic stroke and reduced mobility. However, some patients may have indications for early direct oral anticoagulants (DOACs) and are continued on this therapy rather than transitioning to LMWH. Whether outcomes differ between these groups is unknown. We compared the safety and efficacy of early DOACs versus LMWH from a large retrospective database.Methods:Patients within the TriNetX Research Network receiving either DOACs or LMWH within 72 hours of ischemic stroke and a Modified Rankin Scale of 4-5 were included. A 1:1 propensity score matching analysis was performed using 27 covariables including demographic information, comorbidities, and medications. Chi-square and independentt-tests were used in bivariable analyses. Outcomes were all-cause mortality, VTE, intracranial and extracranial hemorrhage at 30 and 90 days.Results:Of 5,492 propensity-matched patients, mean age was 73±13, and 43% were male. Mortality in the DOAC group was significantly lower than in the LMWH group at 30 days (RR=0.59, 95% CI: 0.51-0.69) and 90 days (RR=0.63, 95% CI: 0.56-0.71). Risk of VTE was not significantly different at 30 days (RR=0.80, 95% CI: 0.43-1.50) or 90 days (RR=0.74, 95% CI: 0.45-1.22). Risk of intracranial hemorrhage was not significantly different at 30 days (RR=0.81, 95% CI: 0.36-1.80) or 90 days (RR=0.62, 95% CI: 0.34-1.15).Conclusions:In patients with acute ischemic stroke and reduced mobility, early use of DOACs was associated with lower mortality compared to early use of LMWH.

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Novembre 2024

Abstract 4132212: Trends in Atrial Fibrillation or Flutter Related Mortality Among Adults in the United States: Insights from CDC WONDER Database from 1999-2020

Circulation, Volume 150, Issue Suppl_1, Page A4132212-A4132212, November 12, 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.

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Novembre 2024

Abstract 4146081: Hospital Outcomes in Hispanic Children with Long QT Syndrome: A Large National Database Study

Circulation, Volume 150, Issue Suppl_1, Page A4146081-A4146081, November 12, 2024. Background:Long QT Syndrome (LQTS) is an inherited arrhythmia syndrome that predisposes patients to sudden death. Prior studies on racial disparities in LQTS have shown similar number of cardiac events, but longer QTc in Black patients compared to non-Hispanic Whites (NHW). There is limited data on cardiac events in Hispanic children with LQTS. We hypothesized that Hispanic children with LQTS have worse outcomes compared to NHW children.Methods:This retrospective cohort study of the Pediatric Health Information System (PHIS) database included children ages 0 – 17 years hospitalized from 2013-2024 with an International Classification of Disease 9thor 10thedition code for LQTS listed in the first five admission diagnoses. Patients with congenital heart disease and chromosomal abnormalities were excluded. The primary predictor variable was race/ethnicity, with covariables including age, sex, and insurance type. Our primary outcome variable was a documented lethal arrhythmia, and secondary outcomes included pacemaker and/or implantable cardioverter defibrillator (ICD) placement. Chi-square was used to assess patient characteristics. Univariable mixed-effect log-binomial regression was used to assess risk of outcomes by characteristics using hospital as a random effect with multivariable models generated via backward elimination.Results:We identified 6,476 children (24% Hispanic, 76% NHW). Compared to NHW children, Hispanic children were more often male and presented earlier (median age 11y vs 13y, 25-75 IQR 6-15; p

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Novembre 2024

Abstract 4134912: Geographic, Gender,&Racial Trends in Mortality Due to Coronary Artery Disease in Diabetes among Adults Aged 25 and Older in the United States, 1999-2020: A CDC WONDER Database Analysis

Circulation, Volume 150, Issue Suppl_1, Page A4134912-A4134912, November 12, 2024. Background:Coronary artery disease (CAD) is a significant contributor to mortality among adults with diabetes mellitus (DM) in the United States. This study examines the patterns of CAD-related mortality in individuals aged 25 and above with DM, with a particular focus on geographic, gender, and racial/ethnic discrepancies from 1999 to 2020.Methods:The study analyzed death certificate information from the CDC WONDER database from 1999 to 2020. Age-adjusted mortality rates (AAMRs), annual percent change (APC), and average annual percentage change (AAPC) were computed per 100,000 individuals, categorized by year, gender, race/ethnicity, and geographic areas.Results:Between 1999 and 2020, CAD in individuals with DM resulted in 1,462,279 deaths among adults aged 25 and above in the United States. The majority of these deaths occurred in medical facilities (44.2%) and at home (29.3%). The overall age-AAMR for CAD in DM-related deaths decreased from 36.3 in 1999 to 31.7 in 2020, with an AAPC of -0.96 (95% CI: -1.29 to -0.77 p < 0.000001). Men had higher AAMRs (41.6) compared to women (22.6), with a more significant decrease in women (AAPC: -2.10, p < 0.000001) than in men (AAPC: -0.34, p = 0.001200). Racial/ethnic disparities showed the highest AAMRs in American Indians/Alaska Natives (43.6), followed by Blacks (37.8), Hispanics (33.8), Whites (29.7), and Asians/Pacific Islanders (22.5). The most significant decrease was in Hispanics (AAPC: -1.64, p < 0.000001). Geographically, AAMRs ranged from 13.7 in Nevada to 51.3 in West Virginia, with the highest mortality observed in the Midwest (AAMR: 34.5). Nonmetropolitan areas exhibited higher AAMRs (35.2) than metropolitan areas (29.7), with a more pronounced decrease in urban areas (AAPC: -1.22, p < 0.000001) compared to nonmetropolitan areas (AAPC: -0.03, p = 0.854629).Conclusion:The decrease in AAMRs for CAD among individuals with DM from 1999 to 2020 indicates improvements in healthcare management. However, the ongoing disparities based on race, gender, and geography call for targeted public health interventions to guarantee fair access to cardiovascular care. Additional endeavors are necessary to comprehend and alleviate the root causes of these inequalities.

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Novembre 2024

Abstract 4141933: Supraventricular Tachycardia (SVT) Related Mortality Rates Among Adults (25 Years and Above) in The United States from 1999 to 2020; A CDC WONDER Database Study.

Circulation, Volume 150, Issue Suppl_1, Page A4141933-A4141933, November 12, 2024. Introduction:Supraventricular tachycardia (SVT) is known to affect children and teenagers predominantly but can also occur in adults. However, due to a presumed good disease outcome, fatality rates of SVT in adults (above 25 years) are yet to be explored.Aim:This study aims to shed light on the mortality trends of SVT in the adult population across the United States from 1999 to 2020.Methodology:The CDC WONDER database was used to identify SVT-related deaths using ICD-10 code I47.2 in adults (above 25 years) from 1999 to 2020. The reported data was in the form of crude rate and age-adjusted mortality rate (AAMR) per 100,000 individuals and was stratified by year, ten-year age groups, gender, races, census region, census division, states, and rural-urban division. The Joinpoint regression was then used to determine the changes in trends and annual percentage change (APC).Results:From1999 to 2020, 31,036 (AAMR=0.6) SVT-related deaths were reported. AAMR showed an initial steep decline from 0.9 in 1999 to 0.5 in 2011 (APC -5.11 [95% CI -6.08 to -4.14]), followed by a gradual increase till 2020 (0.8) (APC 5.14 [95% CI 3.41 to 6.90]). The crude death rates increased with age and were reported to be highest in ages greater than or equal to 85 (9.1); the trend showed a steep decrease from 1999 (12.4) to 2008 (7.9) (APC -4.35 [95% CI -5.36 to -3.33]), followed by a gradual decline till 2017 (7.8) (APC -0.66 [95% CI -2.04 to 0.73]), and ultimately rising sharply till 2020 (10.6) (APC 9.23 {95% CI 3.32 to 15.47]). Among races, Blacks and Whites displayed the highest mortality (0.7). Blacks showed an initial decrement from 1999 (1.0) to 2017 (0.6) (APC -2.71), followed by a rise back to 1.0(2020) (APC 19.58), while whites showed an initial fall (0.9 (1999) to 0.6 (2008), APC -4.91), followed by no change till 2017 (APC 0.18), and ultimately rise to 0.9 in 2020 (APC 13.66). Although no significant gender or geographical variations were observed, more deaths were seen in rural areas (1.0) than in Urban (0.6).Conclusion:Following an initial decline, the incidence of SVT-related mortality has been increasing over the years, pre-dominantly among the 85+ age group, Blacks, and rural populations. However, due to a limited understanding of the epidemiology of SVT in adult populations, more extensive research is needed to formulate better preventive and management strategies.

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Novembre 2024

Abstract 4146039: Temporal Trends in Hypertension and Malignant neoplasm-related mortality in the United States: Cross-sectional Analysis of a National Database from 1999 to 2020

Circulation, Volume 150, Issue Suppl_1, Page A4146039-A4146039, November 12, 2024. Background:While hypertension (HTN) is a major risk factor causing morbidity and mortality following anticancer treatment, the current trends regarding its impact remain unclear.This study utilizes CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) to examine HTN and malignancy-related deaths in the US.Methods:CDC WONDER accessed mortality data for adults aged ≥25 from 1999 to 2020, citing HTN and malignant neoplasms as contributing causes of death. Results, presented as age-adjusted mortality rates (AAMRs) per 100,000, underwent Joinpoint regression for trend analysis and annual percentage change (APC)Results:From 1999 to 2020, 1,067,143 deaths occurred in patients with neoplasms and HTN (AAMR = 22.3, 95% CI: 22.3 – 22.4). Males had higher mortality (AAMR = 27.9) than females (AAMR = 18.4). AAMRs varied across racial groups: highest in non-Hispanic blacks (NHB) (35.9), followed by non-Hispanic Whites (NHW) (21.2), Hispanics (17.9), non-Hispanic American Indian/Alaska Native (NH-AIAN) (16.4), and lowest in non-Hispanic Asian/Pacific Islander (NH-API) (15.3). Region-wise analysis showed that mortality rates were highest in the Midwest region (23.2, 95% CI: 23.1 – 23.3) followed closely by the South region at (23.0, 95% CI: 22.9 – 23.0), and then the West region rates of (22.3, 95% CI: 22.2 -22.4) while the Northeast reported the lowest mortality rate (19.8, 95% CI: 19.7 – 19.9). Mortality rates in rural areas were consistently greater throughout the study period compared to urban areas (Rural: 26.0, 95% CI: 25.8 – 26.1; Urban = 22.2, 95% CI: 22.1 – 22.3). Overall AAMR increased sharply from 12.0 in 1999 to 18.1 in 2001, followed by a gradual increase till 2018 (24.4) and then 29.9 in 2020 (APC: 3.9 [95% CI=3.4,4.4]). AAMR rose in men (APC:4.3), and women (APC: 3.4) throughout the study (FigureA). Across races, NH-AIAN showed the largest increase (APC: 5.5), followed by NHW (APC: 4.4), Hispanic (APC: 4.8), NHB (APC: 2.1), and NH-API (APC: 2.0) (FigureB)Conclusion:Despite recent improvements, HTN-malignancy-related mortality is rising. AAMR increased among men, all racial groups, and those in rural areas. Associated risk factors and examining social determinants of health are crucial for better care

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Novembre 2024

Abstract 4142236: Safety and Efficacy of Early Aspirin Versus Aspirin Plus Low Molecular Weight Heparin in Patients with Ischemic Stroke and Immobility: A Multi-National Database Study

Circulation, Volume 150, Issue Suppl_1, Page A4142236-A4142236, November 12, 2024. Background:Early aspirin is standard of care after acute ischemic stroke (AIS). There is increased incidence of venous thromboembolism (VTE) in patients with AIS and reduced mobility, but thromboprophylaxis with low molecular weight heparin (LMWH) must be weighed against the risk of bleeding. We compared safety and efficacy of early aspirin with or without LMWH in AIS and reduced mobility.Methods:Patients with AIS and Modified Rankin Scale of 4-5 were identified in the TriNetX Research Database. Patients were categorized as either aspirin alone or aspirin plus LMWH within 72 hours of AIS. We excluded patients receiving any other anticoagulant, thrombolytic agents, or with history of long-term anticoagulation or atrial fibrillation. Bivariable analysis was performed with chi-square and independentt-tests. Cohorts were then 1:1 propensity score-matched by 26 relevant covariables including demographics, comorbidities, and medications. Outcomes were all-cause mortality, VTE, intracranial hemorrhage, and extracranial hemorrhage at 30 and 90 days.Results:We included 2,572 patients in each cohort. Mean age and SD was 71±13, and 48% were male. There was no significant difference in all-cause mortality in patients treated with aspirin alone versus aspirin plus LMWH at 30 days (RR=1.1, 95% CI: 0.91-1.3) or 90 days (RR=1.2, 95% CI: 0.98-1.3). Similarly, the risks of VTE and intracranial or extracranial hemorrhage were not significantly different at either timepoint.Conclusions:In patients with AIS and reduced mobility, the early addition of LMWH to aspirin may have similar risks of bleeding, all-cause mortality, and VTE.

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Novembre 2024

Abstract 4147456: Serum and Glucocorticoid Regulated Kinase 1 (SGK1) Inhibition Induces Anti-Fibrotic and Anti-Inflammatory Responses: Relevance to Cardiac Fibrosis

Circulation, Volume 150, Issue Suppl_1, Page A4147456-A4147456, November 12, 2024. Background:Cardiac fibrosis is a condition characterized by deposition of extracellular matrix proteins and myofibroblasts, leading to scar formation, cardiac dysfunction and arrhythmogenesis. Various cardiometabolic stressors can promote fibrosis and scarring, including MI, hypertension, diabetes and obesity. Targeted therapy to prevent cardiac fibrosis is therefore an important unmet medical need. In a mouse model of obesity-related atrial fibrillation (AF), inhibition of SGK1 reduced markers of inflammation and fibrosis, suggesting SGK1 as a novel target. Several SGK1 inhibitors are being evaluated in clinical studies for the treatment of long QT syndrome, paroxysmal AF, and heart failure.Hypothesis:SGK1 activation is a significant driver of inflammation and fibrosis, and its inhibition may offer a new therapeutic strategy for treating fibrotic diseases, including those of the cardiovascular system.Methods:Primary hepatic stellate cells, lung fibroblasts, and proximal tubule cells were treated with TGFβ for 24-48 hours to induce fibrosis and measure the effects of SGK1 inhibition on markers of fibrosis (alpha SMA and collagen 1). Three, selective and potent, SGK1 inhibitors (SGK1-I 1,2,3) were tested in a BioMAP fibrosis panel at concentrations ranging from 0.3 to 10 µM. The fibrosis panel includes three systems that model TGFβ and TNFα driven myofibroblast differentiation during chronic inflammation and wound healing. Markers of fibrosis, tissue remodeling, myofibroblast activation, and inflammation were measured quantitatively. IC50s were determined using GraphPad Prism.Results:In primary human stellate cells, SGK1-I,1,2,3 inhibited αSMA and collagen 1 mRNAs with IC50s ranging from 0.1- 0.8 µM and 1.0-3.0 µM, respectively. In primary lung fibroblasts, treatment with SGK1-I reduced the mRNA and protein expression of αSMA. Treatment of cells from different tissues with TGFβ resulted in a 1.5-to-3.0-fold increase in SGK1 mRNA and protein and this was blocked by the TGFβ receptor inhibitor SB525334. SGK1 inhibitors displayed anti-inflammatory and anti-fibrotic properties in the BioMAP panel, with inhibition of IL-6, IL-8, MCP-1, and αSMA, collagen 1, and TIMP1 respectively.Conclusion:SGK1 is an important effector of TGFβ signaling. The development of SGK1 inhibitors may represent a new therapeutic strategy for treating fibrotic diseases. Additional studies are warranted to further evaluate novel SGK1 inhibitors in cardiac fibrosis

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Novembre 2024

Cohort profile: the Nanjing Diabetes Cohort database – a population-based surveillance cohort

Purpose
To study epidemiology, complications, risk factors, clinical course and treatment patterns of diabetes, the Nanjing Diabetes Cohort (NDC) was established using anonymised electronic health records from 650 hospitals and primary care since 2020. This cohort provides valuable data for researchers and policy-makers focused on diabetes management and public health strategies.

Participants
Diabetes was defined as having inpatient or outpatient encounters with a diagnosis of diabetes International Classification of Diseases-9/10 codes, any use of insulin or oral hypoglycaemic drugs, or one encounter with haemoglobin A1C >4.8 mmol/mol or 6.5%. Patients with diabetes have been continuously enrolled on hospitals and primary care in Nanjing since 2020. Demographic, medications and comorbidities data were extracted from clinical notes, diagnostic codes, labs, prescriptions and vital signs among different types of diabetes.

Findings to date
The NDC consisted of 1 033 904 patients from 1 January 2020 to 31 December 2022, the majority were male (50.62%) and from the Gulou district (30.79%). The clinical characteristics and medication usage of patients with type 1 diabetes, type 2 diabetes, gestational diabetes and other diabetes were assessed. The prevalences of hypertension, ischemic heart disease, and cerebrovascular disease were 49.72%, 17.85% and 24.90%, respectively.

Future plans
NDC will annually enrol eligible patients and include socioeconomic data in future updates. The data of NDC are maintained by the Department of Medical Informatics at Nanjing Medical University.

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Novembre 2024

Avoiding anti-inflammatories: a randomised controlled trial testing the effect of an eHealth information package on primary healthcare patient medication knowledge and behaviour in Aotearoa New Zealand

Background
Patient medication knowledge and health literacy affect patient safety. Taking angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin II receptor blockers (ARBs), with diuretics and non-steroidal anti-inflammatory medications (NSAIDs) is nephrotoxic. Patients may not know of this risk. An eHealth information package was developed to inform patients at risk of taking this combination of medication.

Objective
To assess the impact of the eHealth information package on patient knowledge and behaviour.

Design
This was a two-arm, parallel, randomised control trial. A knowledge quiz and NSAID use survey were undertaken at baseline, and repeated after two weeks. The intervention group accessed the information package after completing the baseline assessment. The control group received normal care.

Setting and participants
Primary healthcare patients prescribed an ACE-i or ARB plus a diuretic in Aotearoa New Zealand.

Intervention
A novel eHealth information package was made available to participants in the intervention group consisting of a downloadable PDF and online education activity. This took approximately 15 min for participants to complete.

Primary outcome measures
Change in knowledge scores and in NSAID use between pre-intervention and post-intervention assessment.

Secondary outcome measures
Self-reported patient intentions regarding future NSAID use

Results
The 201 participants who completed the study had high baseline NSAID medication knowledge, which did not substantially change at follow-up. The intervention group had a 0.35 (95% CI: -0.18, 0.88) higher knowledge score than the control group. NSAID use decreased over the study; the intervention group had 62% lower odds of NSAID use at follow-up assessment compared with the control group (OR=0.37, 95% CI: 0.14, 1.03). There was no substantial difference between study groups at follow-up for self-reported action. The information package was considered acceptable and useful.

Conclusion
This tailored eHealth information package may reduce NSAID use in patients at increased risk from NSAID-related harm.

Trial registration number
Australian New Zealand Clinical Trial Registry (ACTRN:12622001132730).

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Novembre 2024

Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke

Stroke, Ahead of Print. BACKGROUND:Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), aStachybotrys microsporatriprenyl phenol family member, may extend this therapeutic window.METHODS:In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a study, JX10 or placebo was administered as a single intravenous infusion to Japanese patients with acute ischemic stroke who were unable to receive tissue-plasminogen activator or thrombectomy within 12 hours of last known normal. Primary end point was incidence of symptomatic intracranial hemorrhage with a worsening National Institutes of Health Stroke Scale score of ≥4 points within 24 hours of drug administration (symptomatic intracranial hemorrhage incidence).RESULTS:Ninety patients received either placebo (n=38; female 26.3%) or JX10 at 1, 3, or 6 mg/kg (n=6, 18, 28; female 0%, 33.3%, and 42.9%, respectively). Median age (range) and baseline median (range) National Institutes of Health Stroke Scale scores were respectively 76.5 (42–87) and 8 (6–21) for the combined JX10 cohort (JX10 Cohorts) and 75.0 (34–85) and 8 (6–22) for placebo. Median (range) dosing time since last known normal was 9.5 (5.0–12.1) and 10.0 (3.7–12.0) hours for JX10 Cohorts and placebo, respectively. Symptomatic intracranial hemorrhage incidence was 0% (0/52 [95% CI, 0.0–5.6]) for JX10 Cohorts versus 2.6% (1/38 [95% CI, 0.1–13.8]) for placebo (P=0.42). Vessel patency at 24 hours (secondary end point) in patients with baseline arterial occlusive lesion score

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Novembre 2024