tbuckley/cabot-search huggingface dataset:
Abstract 4124065: Clonal Hematopoiesis of Indeterminate Potential (CHIP) in Chronic Coronary Artery Disease: A Report from the ISCHEMIA Trials Biorepository
Authors: Matthew Muller, Richard Liu, Jiyuan Hu, Claes Held, Iftikhar Kullo, Bruce McManus, L. Kristin Newby, Mandeep Sidhu, Sripal Bangalore, Harmony Reynolds, Judith Hochman, David Maron, Kelly Ruggles, Jeffrey Berger, Jonathan Newman
Journal: Circulation (2024)

Introduction: CHIP is associated with CAD and mortality. The prognostic relevance of CHIP for high-risk patients with confirmed CAD is unknown. Hypothesis: CHIP variants are associated with cardiovascular (CV) events and mortality in high-risk patients with known CAD in the ISCHEMIA Trials Biorepository. Methods: 895 ISCHEMIA and ISCHEMIA-CKD (hereafter, ISCHEMIA Trials) participants with moderate-severe ischemia and next-generation sequencing performed for CHIP variant allele fractions of ≥2% (CHIP) and ≥10% (large CHIP) were included. Unadjusted and multivariable adjusted (age, sex, diabetes, eGFR not on HD, HD, and LVEF) associations of CHIP and large CHIP with a) ISCHEMIA Trials initial phase primary endpoint (CV death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, RCA) and b) ISCHEMIA Trials combined initial and extended follow-up phase (hereafter, Cumulative) endpoint of all-cause death . Results: Median (IQR) age of sequenced participants was 67 (56 – 79) years, 19% were female, 83% white, and 6% Hispanic. Hypertension (84%), diabetes (45%) and obesity (47%) were common, 26% had an eGFR &lt;60 ml/min/1.73m 2 . The prevalence of CHIP and large CHIP was 23% and 7%, and both increased with age ( Figure 1a ). CHIP mutations in DNMT3A were detected in 106 (12%), TET2 CHIP in 44 (5%), and ASXL1 CHIP in 21 (2%) participants ( Figure 1b ). DNMT3A, TET2, and CREBBP mutations collectively comprised 199 (52%) of overall CHIP mutations, including individuals with multiple mutations in the same gene (N overall = 385); 67 participants (7%) had mutations in &gt;1 gene. Over 3.1 years of RCT follow-up there were 135 (20%), 32 (16%) and 15 (18%) primary endpoints for no CHIP, CHIP and large CHIP, respectively. Over 6.8 years of EXTEND follow-up, there were 126 (18%), 47 (23%) and 24 (29%) deaths in the no CHIP, CHIP and large CHIP groups, respectively. After multivariable adjustment there was no association between CHIP or large CHIP and CV events or mortality ( Figure 1c ). Conclusion: Neither CHIP nor large CHIP was associated with adverse outcomes in 895 high-risk individuals with confirmed CAD, despite a high prevalence of these mutations.
Abstract 4123864: Fractional flow reserve-guided complete revascularization versus culprit-only revascularization in patients with myocardial infarction and multivessel disease: A GRADE assessed meta-analysis of randomized controlled trials
Authors: Asad Rahman, Mushood Ahmed, Hira Javaid, Areeba Ahsan, Priyansha Singh, Hritvik Jain, Adeel Ahmad, Sohail Khan, Kamleshun Ramphul, Farhan Shahid, mahboob alam, Raheel Ahmed
Journal: Circulation (2024)

Background: Fractional flow reserve (FFR) guided complete revascularization (CR) is an approach that can be used to improve clinical outcomes in patients with acute myocardial infarction (MI) and multivessel disease (MVD). The objective of the present meta-analysis was to investigate whether FFR-guided CR leads to better cardiovascular outcomes as compared to culprit-only revascularization (COR) in acute MI and MVD by pooling recently published data. Methods: A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception until April 2024 to retrieve eligible randomized controlled trials (RCTs). Clinical outcomes were assessed using the random-effects model by pooling risk ratios (RRs) along with 95% confidence intervals (CIs). We assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Results: Four RCTs were pooled with 3,175 patients. FFR-guided CR significantly reduced the risk of repeat revascularization as compared to COR (RR = 0.52; 95% CI: 0.33-0.81, p = 0.004) [absolute risk difference 83 fewer per 1,000 patients (95% confidence interval: 116 to 33 fewer) moderate certainty]. Though there was a reduction in the risk of MACE with FFR-guided CR (RR = 0.68, 95% CI: 0.44-1.04, p = 0.08; moderate certainty), it didn't attain statistical significance. Clinical outcomes such as all-cause death (RR = 1.10, 95% CI: 0.84-1.45, p = 0.48; moderate certainty), cardiac death (RR = 0.79, 95% CI: 0.53-1.17, p = 0.24; high certainty), risk of MI (RR = 0.94, 95% CI: 0.54-1.66, p = 0.84; moderate certainty) and major bleeding (RR = 0.95, 95% CI: 0.54-1.67, p = 0.87; moderate certainty) were comparable between the two groups. Conclusion: FFR-guided CR in patients with MI and MVD can lead to a decreased risk of repeat revascularizations while not affecting all-cause and cardiac deaths.
Abstract 4123509: The Intersection of Race and Ethnicity, Social Determinants of Health, and Hypertension Prevalence: A Community-Level Analysis
Authors: Mia Cajita, Susan Dunn, Rosalba Hernandez, Ardith Doorenbos
Journal: Circulation (2024)

Background: Despite being one of the most diverse cities in the United States, Chicago is also notably segregated. The distinct separation among its 77 communities provides an opportunity to examine racial and ethnic segregation and the impact of social determinants of health (SDOH) on health outcomes. Research Question: How do race/ethnicity and SDOH influence hypertension (HTN) prevalence? Aim: To examine the relationships between race/ethnicity, SDOH, and HTN prevalence at the community level. Methods: This cross-sectional study used data from the Chicago Health Atlas collected between 2021 and 2022. The sample included data from all 77 Chicago communities and 2,738,956 of its residents. Two-step latent profile analyses were performed to classify each of the community according to the predominant race/ethnicity of its residents (Asian, Black, Hispanic, or White) and SDOH level (low, moderate, high), which was defined as how favorable the physical and social conditions are within the community and determined using 14 indicators (Table 1). Kruskal-Wallis tests were used to compare the prevalence of HTN among the communities by predominant race/ethnicity and SDOH level. Results: Among the 77 communities, 28 were predominantly Black, 27 were predominantly White, 21 were predominantly Hispanic, and 1 was predominantly Asian. HTN prevalence was highest in predominantly Black communities (39.9%), then the Asian community (35.8%), Hispanic communities (28.8%), and White communities (25.2%), p &lt;.001. Based on the 14 SDOH indicators, 26 of the communities were classified as low SDOH (unfavorable conditions), 25 as moderate SDOH (moderately favorable), and 26 as high SDOH (favorable). HTN prevalence was highest in low SDOH communities (36.3%), followed by moderate SDOH communities (31.4%), and lowest in high SDOH communities (27.2%), p =.003. Conclusions: The findings highlight significant disparities in HTN prevalence across Chicago's communities, with higher rates observed in predominantly Black and low SDOH areas. These results underscore the need for targeted public health interventions to address the intersection of racial/ethnic segregation and SDOH.
Abstract 4124039: Aging-Associated Protein Medin Induces Human Coronary Artery Endothelial Proinflammatory and Prothrombotic Activation
Authors: Nina Karamanova, Kaleb Morrow, Alana Maerivoet, Jillian Madine, Ming Li, Raymond Migrino
Journal: Circulation (2024)

Background: Age is the most important risk factor for coronary artery disease (CAD), independent of traditional risk factors such as hypertension, diabetes (DM), hyperlipidemia and smoking, through poorly understood mechanisms. Medin, a cleavage product of MFGE8 protein that forms the most common human amyloid, accumulates in the vasculature with age, including the coronary arteries. Although medin amyloid has been implicated in various diseases such as Alzheimer’s disease, vascular dementia and aortic aneurysms, its role in CAD remains unknown. Medin was shown to induce changes characteristic of vascular aging, such as endothelial and smooth muscle dysfunction in human donor cerebral arteries. Medin also induced proinflammatory activation of human brain microvascular endothelial cells through NFκB activation . Aims: To determine the effects of medin on pro-inflammatory and prothrombotic activation of human coronary artery endothelial cells (HCAECs). Methods: Primary HCAECs (passages 6-8) were exposed for 20 hours to physiologic doses of recombinant medin (0.5, 1 and 5 µM) and gene expression of pro-inflammatory proteins (IL-6, IL-8, IL-1b and intercellular adhesion molecule (ICAM)-1), prothrombotic protein (plasminogen activator inhibitor (PAI)-1) and anticoagulant membrane protein thrombomodulin were quantified using rtPCR and compared. Separately, HCAECs were exposed to medin (0.5, 1 and 5 µM) with or without small molecule specific inhibitor of NFκB (RO106-9920, 10 uM) for 20 hours and protein expression of IL-6 in conditioned media was measured using ELISA. Results: Medin caused dose-dependent increases in gene expressions of pro-inflammatory cytokines IL-6, IL-8, IL-1b, ICAM-1 (Figure 1 A-D). Medin caused a dose-dependent increase in PAI-1 and a dose-dependent decrease in thrombomodulin (Fig. 1 E-F). Co-treatment with RO106-9920 prevented medin-induced increase in IL-6 protein expression (Fig. 1G). Conclusions: Medin induces pro-inflammatory and prothrombotic activation of human coronary artery endothelial cells. The proinflammatory activation is likely NFκB-dependent. Medin is a promising potential novel mediator of CAD and vascular aging.
Abstract 4122694: The <i>ICAM1</i> p.K56M Variant and Risk of Heart Failure Among Individuals with Chronic Kidney Disease
Authors: Kasen Culler, Leila Zelnick, Rupal Mehta, Giselle Rodriguez de Sosa, Mayank Kansal, Panduranga Rao, Zeenat Bhat, Jonathan Taliercio, Edward Horwitz, Jing Chen, Jiang He, Sanjiv Shah, Tamara Isakova, Ravi Patel
Journal: Circulation (2024)

Background: Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein that facilitates inflammation through leukocyte adhesion. Approximately 35% of African American individuals carry at least one copy of an ICAM1 missense variant (rs5491; p.K56M), which has been associated with increased risk of heart failure with preserved ejection fraction (HFpEF). Individuals with chronic kidney disease (CKD) are at high risk for HF, but whether the risk of HFpEF conferred by rs5491 extends to individuals with prevalent CKD is unknown. Hypothesis: We hypothesized that in a CKD population, rs5491 is specifically associated with HFpEF, but not HF with reduced ejection fraction (HFrEF). Methods: In the Chronic Renal Insufficiency Cohort (CRIC), participants were enrolled based upon an estimated glomerular filtration rate (eGFR) of 20 to 70 mL/min/1.73m 2 . We estimated associations of rs5491 with incident HF and HF subtypes among African American individuals who were free from HF at baseline in CRIC. Models were adjusted for age, sex, systolic blood pressure, eGFR, body mass index, smoking, diabetes, C-reactive protein, the first 10 principal components of ancestry, and study site. Results: Among 1267 African American participants without HF at baseline (mean age 57±11 years, 51% female, mean eGFR 45±15 mL/min/1.73m 2 ), 464 (37%) had at least one copy of rs5491. During a median follow-up of 10.3 years (IQR: 4.7 – 15.0 years), there were 309 incident overall HF hospitalizations (160 HFpEF, 111 HFrEF, and 38 HF with unknown EF). Each additional rs5491 allele was significantly associated with incident HFpEF (HR 1.35 [95% CI: 1.03-1.76], P=0.029; Figure). The rs5491 variant was not associated with incident overall HF (HR 1.14, 95% CI: 0.93-1.39, P = 0.20) or incident HFrEF (HR 0.76, 95% CI: 0.53-1.10, P=0.15). Conclusion: The ICAM1 p.K56M variant specifically confers increased risk of incident HFpEF among individuals with CKD.
Abstract 4123501: Coronary Artery Calcium in Asymptomatic Arabs: Prevalence and Distribution
Authors: Abdulhamied Alfaddagh, Ahmed El Mugharbil, Altayyeb Yousef
Journal: Circulation (2024)

Background: Coronary artery calcification (CAC) is an established marker of subclinical atherosclerosis and predictor of cardiovascular events. Despite extensive research on CAC in various populations, data focusing on Arab populations, particularly asymptomatic individuals, is limited. Methods: We analyzed data from 2,739 asymptomatic self-referred Arabs included in the Kuwait Hospital Awareness Campaign for Early Detection of Atherosclerotic Coronary Artery Disease study. Traditional CVD risk factors were assessed, and ECG-gated cardiac CT imaging was used to measure using the Agatston method. Results: The mean±SD age of the sample was 48.4±9.8 and 41.8% were females. Kuwaitis comprised 61.6% of the sample, Egyptians 20.5%, and Levantines 16.4%. CAC was &gt;0 in 32.3%, ≥100 in 11.5%, and ≥400 in 4% of the sample. CAC prevalence increased with age and was higher in Arab males with a 12 year earlier onset in males than females. The 50 th , 75 th , 90 th and 95 th percentiles of CAC for Arab females were, 0, 0, 39, and 167 and for males were 0, 25, 191, and 470, respectively. The presence of CAC was associated with traditional risk factors including diabetes, smoking, hypertension and LDL-C. Levantines and Kuwaitis had the highest prevalence of CAC and CVD risk factors; these groups were independently associated with higher CAC levels. In all age and sex subgroups except older males, the 75 th percentiles of CAC were below 100. Therefore, a larger number of subjects were identified as high risk using the 75 th age- and sex-specific CAC percentile than with CAC≥100 (19.3% vs 11.5%). Conclusion: This study provides comprehensive insights into subclinical atherosclerosis in asymptomatic Arabs, emphasizing the importance of early risk stratification for primary CVD prevention using CAC scoring. Our findings highlight that Arabs are not a homogeneous group with regards to prevalence of CVD risk factors and CAC. This study underscores the need to consider both absolute and age- and sex-specific CAC percentile values to inform primary prevention strategies in this predominantly young population.
Abstract 4124267: Comparison of Right Ventricular Failure Prediction Models to Predict Right Ventricular Assist Device (RVAD) After HeartMate3 Implantation
Authors: Zhiyu Liu, Dae Hyun Lee, Chase Lewellen, Jason Lee, Robby Wu, Ricardo Restrepo-Jaramillo, Guilherme Oliveira, Debbie Rinde-Hoffman, Jason Feliberti, Benjamin Mackie, Ioana Dumitru
Journal: Circulation (2024)

Introduction: The requirement for right ventricular-assisted device (RVAD) implantation portends poor outcomes after left ventricular-assisted device (LVAD) implantation. We investigate RVF prediction models to help prediction of RV failure requiring RVAD implantation after centrifugal-flow LVAD HeartMate3 (HM3) placement. Methods: A total of 124 patients who underwent HM3 implantation at our institution from 2015-2023 were included in our analysis. We collected clinical variables used in EUROMACS RVF Risk Score (Circulation 2018), Utah Model (Am J Cardiology 2010), Michigan RVF Risk Score (JACC 2008), and CRITT (ATS 2013). Baseline scoring systems were compared with our cohort of patients with and without RVAD implantation after HM3 placement with ROC Area Under the Curve (AUC) statistical analysis. In addition, we investigated the pulmonary artery pulsatility index (PAPi) as a predictor for RV failure requiring RVAD. Results: There were 17 patients (13.7%) who underwent RVAD implantation after HM3 placement. Patients who required RVAD implant had worse survival (p = 0.037). The EUROMACS score differentiated those patients who required RVAD from those who did not (AUC: 0.66; 95% C.I: 0.51-0.81). In contrast, CRITT (AUC: 0.64; 95% C.I: 0.49-0.78), Michigan score (AUC: 0.37; 95% C.I: 0.25-0.51), and Utah (AUC: 0.53; 95% C.I: 0.40-0.68) scores did not differentiate those who required RVAD. PAPi was significantly lower in patients requiring RVAD (2.5±1.2 vs 3.9±3.0, p=0.001). Also, even as a single parameter, PAPi had an AUC of 0.63 (95% C.I: 0.50-0.76). Conclusion: RVAD implantation is associated with high early mortality. Existing RVF prediction models were not able to predict future RVAD requirements with high AUC, with the EUROMACS system having the only statistical significance. There is a lack of a strong predictive model for RV failure in HM3. Future efforts are needed to establish predictors for RV failure requiring RVAD implants in the HM3 population, especially utilizing novel hemodynamic markers such as PAPi.
Abstract 4123899: Stroke Risk in Patients with an Isolated Interventricular Membranous Septal Aneurysm
Authors: Joseph Elias, Swiri Konje, Edgar Argulian
Journal: Circulation (2024)

Aim: This study investigates the prevalence of isolated interventricular membranous septal (IVMS) aneurysms detected via echocardiography and assesses the associated stroke risk without other classical risk factors. Methods: We searched the echocardiography database at Mount Sinai Morningside from January 2017 to September 2023. Identified echocardiograms were reviewed to confirm IVMS aneurysms and exclude sinus of Valsalva aneurysms. Patients with concurrent structural heart anomalies were excluded. Medical records were examined for baseline characteristics, risk factors, and cortical brain infarcts. Results: From 51,732 subjects, 18 were identified with IVMS aneurysms, yielding a prevalence of 0.04%. Four patients with significant structural heart disease were excluded, resulting in a final sample size of 14. Of these, 9 (64%) were female with a mean age of 59.6, and 5 (36%) were male with a mean age of 55.4. The mean BMI was 27.9 kg/m 2 , with 4 classified as obese. All patients were nonsmokers; 2 had a family history of stroke. One patient had diabetes, 8 had hyperlipidemia, and 9 had hypertension. Only one patient had paroxysmal atrial fibrillation, with a CHA2DS2-VASc score of 0. Echocardiography revealed structurally normal hearts with a mean left ventricular ejection fraction of 61% and a mean left atrial volume index of 24.8 mL/m 2 . The mean neck diameter of the aneurysm was 8.7 mm, and the mean diameter was 11.9 mm. Two patients had inter-atrial septal aneurysms, and one had a patent foramen ovale. Out of the 14 patients, 5 had a history of ischemic stroke (4) or transient ischemic attacks (1), all of whom were 64 years or younger with a mean RoPE Score of 6 and a mean CHA2DS2-VASc score of 1.6 at the time of their first neurologic event. All patients were treated with aspirin and statin therapy. Two patients had recurrent strokes, one of whom had four recurrent strokes, all cortical infarcts. These patients were switched to clopidogrel after 3 months of dual antiplatelet therapy. No anticoagulation was used. Conclusion: This retrospective study highlights a notable association between isolated IVMS aneurysms and an increased risk of ischemic stroke (36%) and recurrent ischemic stroke (14%). Despite their rarity, these anomalies should be considered in unexplained strokes. Optimal management strategies remain ambiguous, but anticoagulation may be favored based on presumed stroke mechanisms. Large-scale multicenter studies are needed for validation.
Abstract 4123540: Cardiovascular Health and Cancer Incidence and Mortality: NHANES-III and -Continuous study
Authors: Omar Elsayed, Harikrishnan Hyma Kunhiraman, Tochi Okwuosa, Daniel Addison, Jorge Cortes, Susan Dent, Sarju Ganatra, Malcolm Bevel, Sadeer Al-Kindi, Catherine Hedrick, Ryan Harris, Khurram Nasir, Neal Weintraub, Xiaoling Wang, Avirup Guha
Journal: Circulation (2024)

Background: Cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Limited evidence is available regarding the relationship between CVD, cardiovascular risk factors (CVRF), and cancer mortality; and how CVRF further modify that relationship. Methods: The first part included 438 and 2100 CVD patients aged 65+ from NHANES-III and Continuous (1999-2016) datasets, respectively. Competing risk models with subdistribution hazards ratio (aHR) were used to identify risk factors for cancer incidence. The second part included 44,591 adult individuals from NHANES-Continuous merged with Medicare and National Death Index mortality data until the end of 2018. We included individuals with no history of cancer at baseline. We used competing risk modeling to test the relationship between CVD at baseline and cancer mortality. We also conducted a comprehensive risk factor analysis. Results: In the first part (Figure), females in NHANES-III had lower cancer risk (aHR 0.39, P=0.001) compared to males. Poor physical activity was associated with increased cancer risk in both datasets (aHR 2.59 in NHANES-III, aHR 1.59 in Continuous). In NHANES-Continuous, age (aHR 1.07, P&lt;0.001) and current smoking (aHR 2.55, P=0.001) showed a significant association with developing cancer. No other factors investigated showed significant associations. In the second analysis (Table), the included sample size represented 1,738,423,317 individuals (52% females, 67% non-Hispanic Whites, and 9% Hispanics). Competing risk modeling showed a significantly higher risk of cancer mortality in individuals with CVD (aHR 1.37, 95% CI 1.07-1.76, P=0.01) after adjusting for age, sex, and race/ethnicity. Notably, cancer mortality increased with aging (aHR 1.08, 95%CI 1.05-1.11, P&lt;0.0001), current smoking status (aHR 6.78, 95%CI 3.43-13.42, P&lt;0.0001), and obesity (aHR 2.32, 95%CI 1.13-4.79, P=0.02). Finally, a significant interaction (P=0.034) was found where those with CVD and obesity showed higher cancer mortality than those with normal BMI (aHR, 95%CI 1.03-2.91, P=0.04). Conclusions: Our study highlights the close relationship between cardiovascular health and cancer, including among CVD patients. Our findings suggest that physical activity and obesity may play a significant role in cancer incidence and mortality among the general population and CVD patients. These findings emphasize the need for more proactive approach in the management of shared risk factors for CVD and cancer.