tbuckley/cabot-search huggingface dataset:
Abstract 4146404: The Strain of Pregnancy: Markers of Cardiac Strain and Inflammation in Pregnancies with and without Hypertension – a Case Control Study
Authors: Lara Kovell, Mawulorm Denu, Sravya Shankara, Ekaterina Skaritanov, Julia Berkowitz, Leslie Panella, Ben Maxner, Stephen Juraschek
Journal: Circulation (2024)

Background: Pregnancy poses physiologic changes that can precipitate severe or fatal cardiovascular events among women with hypertension (HTN). Understanding mechanisms by which delivery might contribute to these events in women with HTN is critical for prevention. Aims: To examine trends in markers of cardiac wall strain or inflammation measured via N-terminal pro b-type natriuretic peptide (NTproBNP) and high-sensitivity C-reactive protein (hs-CRP) in pregnancies with and without HTN. Methods: In a prospective, 1:1 case-control design, we enrolled pregnant women with and without HTN between 24-32 weeks gestation (2019-2022). HTN was defined by a clinician diagnosis of chronic or gestational HTN or a baseline blood pressure (BP) ≥140/90 mm Hg. The control group (no HTN) had a systolic BP &lt;120 mm Hg and no diagnosis of HTN. Serum was collected at baseline, pre-delivery (at the delivery admission), and postpartum day 1. We used mixed effects tobit models to compare log-transformed NTproBNP and hs-CRP, across HTN groups and over time, adjusted for age and BMI. Results: The mean age of the HTN group (N=38) was 33.6 (SD 5.4) vs. 30.3 (5.8) years for the no HTN group (N=38). Mean (SD) baseline BP was 131.1 (14.7)/88.2 (13.5) for the HTN group and 110.1 (7.2)/70.9 (8.2) mm Hg for no HTN. At baseline, NTproBNP was 29.6 (4.2) in the HTN group and 29.5 (4.4) pg/mL in the no HTN group ( Figure ). Compared to baseline, there was a non-significant change in NTproBNP pre-delivery and an increase at postpartum for both groups (114% [49-208%] for HTN, 120% [51-219%] for no HTN). Baseline hs-CRP was 6.9 (1.1) in the HTN group and 5.1 (0.8) mg/L in the no HTN group. Compared to baseline, there was a non-significant change in hs-CRP pre-delivery and an increase at postpartum for both groups (550% [337-867%] for HTN, 662% [407-1050%] for no HTN). Across all time points, there were no significant differences in NTproBNP and hs-CRP between the two groups. Conclusion: While HTN was not associated with greater cardiac wall strain or inflammation compared to no HTN, delivery alone led to an approximately 2-fold increase in cardiac wall strain and 7–fold increase in inflammation from mid-pregnancy to immediate postpartum.
Abstract 4145608: Calibration and Discrimination of Cardiovascular Risk Scores in Women with Breast Cancer in the Women’s Health Initiative
Authors: Elena Wadden, Joseph Larson, Su Yon Jung, Matthew Nudy, Yangbo Sun, JoAnn Manson, Wayne Levy, Marcia Stefanick, Kerryn Reding, Ana Barac, Michael Simon, Alexi Vasbinder, Richard Cheng
Journal: Circulation (2024)

Introduction: Women with breast cancer (BC) are at increased risk for cardiovascular disease (CVD). Currently, there is no standardized approach to assess CVD risk in women with BC, despite recommendations for risk assessment. We estimated and compared the performance of established ASCVD risk scores (Framingham Risk Score [FRS], Atherosclerotic Cardiovascular Disease [ASCVD] Risk Estimator, and Life’s Essential 8 [LE8]) in a cohort of postmenopausal women with BC. Methods: Women who were diagnosed with BC (stage I-III) and free of CVD from the Women‘s Health Initiative were included in this study. The primary outcome was 10-year risk of ASCVD, defined as a composite of adjudicated coronary heart disease, myocardial infarction, or stroke. For each risk score, we examined calibration and discrimination. Calibration was assessed by calculating bias, slope, standard error of the estimate (SEE), and root mean square deviation (RMSD). Discordance was defined as the percent difference between expected and observed events. Discrimination was evaluated using the c-statistic. We reassessed calibration and discrimination after recalibrating the FRS and ASCVD scores. Results: In 6,946 participants (mean age BC diagnosis: 70 years; 89.7% White), the 10-year incidence of ASCVD was 8.6%. FRS underestimated ASCVD risk by 31.1%, whereas ASCVD and LE8 scores overestimated the risk by 53.7% and 9.3%, respectively (Hosmer-Lemeshow P&lt;0.001 for all scores) (Figure). Discordance was consistent throughout the risk continuum for FRS and ASCVD. However, for LE8, discordance was minimal for those at moderate- to high- risk and overestimated in those at low-risk. The ASCVD risk score had the highest c-statistic of 0.76, compared to 0.62 and 0.71 for the FRS and LE8, respectively (Figure). After recalibration, the discordance for FRS and ASCVD was reduced where the FRS overestimated the risk by 3.7% and the ASCVD overestimated the risk by 37.3%. There were no changes in c-statistics. Conclusions: In this analysis, LE8 had the best calibration, whereas ASCVD had the best discrimination. The ASCVD risk score had a c-statistic of 0.76, suggesting it may be a practical tool to aid in 10-year CVD risk stratification in women with BC.
Abstract 4146392: Prognostic Models for Mortality in an Obese Cohort of Heart Failure with Preserved Ejection Fraction
Authors: Vivek Jani, Eli Fisher, Masih Tajdini, Radu Tanacli, Virginia Hahn, David Kass, Kavita Sharma
Journal: Circulation (2024)

Introduction: Prognostic metrics like NT-proBNP are often low or even normal in patients in Heart Failure with Preserved Ejection Fraction (HFpEF), particularly in HFpEF patients with severe obesity. Here, we use machine learning survival prediction models to investigate predictors of outcomes in HFpEF. Methods: Patients enrolled in the Johns Hopkins Hospital HFpEF registry from July 2014 to May 2024 were included. HFpEF was defined based on clinical signs and symptoms, echocardiographic and laboratory findings, or by right heart catheterization. Starting with 44 features, a two-stage model, in which variables associated with at least a 15% change in hazard ratio by univariate Cox regression were included for subsequent machine learning. Models tested include a random survival forest with and without gradient boosting. Model accuracy was assessed on the test set with a C-statistic. Results: A total of 356 HFpEF patients were included, with 284 (80%) assigned to a train set and 72 (20%) to the test set. A gradient boosted random survival forest was found to be the best model with hyperparameter tuning, with a C-statistic of &gt;0.99 and 0.87 in the train and test set, respectively. The most important prognostic features include N-terminal brain natriuretic peptide, systolic blood pressure, age, and the ratio of cystatin C to albumin. Individually, each of these features associate with survival with a C-statistic &lt; 0.70, which is worse compared to collective model performance ( Fig 1A ). Other relevant features are shown in Fig 1B . For more effective clinical translation, models including the top 15, top 10, and top 5 features were subsequently trained and were found to have similar performance to the model with all features. Conclusion: Here we report a prognostic model for mortality prediction in a cohort of obese HFpEF patients. Efforts to benchmark this model against other HFpEF prognostic models and test in an external HFpEF patient cohort are underway.
Abstract 4146481: Association of Atrial Fibrillation with Lamotrigine in Bipolar I Disorder: An Observational Cohort Study
Authors: Sodam Kim, Landon Welch, Bertha De Los Santos, Przemyslaw Radwanski, KIBUM KIM, Mark Munger
Journal: Circulation (2024)

Objective: Atrial fibrillation (AF) is the most common arrhythmia with the incidence and prevalence increasing worldwide. Lamotrigine (L) is a widely prescribed medication for Bipolar I disorder (BPI). L reduces intracellular sodium through inhibition of the voltage-gated sodium channels which slows cardiac conduction velocity. The mechanism can lead to an onset of AF. The aim of this study was to examine the incidence of AF in L patients without a history of cardiac arrhythmias or structural heart disease (SHD) vs controls prescribed common medications for BPI. Methods: We identified adult patients with BPI who received L or control agents (C) including lithium, quetiapine, valproate, and risperidone from Merative MarketScan ® Commercial Claims and Medicare Supplemental Database. Patients were naive from AF at least six months prior to receiving L or C. Onset of AF was determined using ICD 9 and 10 codes. Patients were censored for generating the Kaplan-Meier cumulative incidence if switched between L and C, discontinued L or C during follow-up, end of continuous enrollment or end of one-year follow up. Onset of AF on L versus C was compared using hazard ratio (HR) calculated from a multivariable Cox-proportional hazard regression model. As a sensitivity analysis, we performed an analysis using a propensity score matched cohort. Results: The BPI cohort consisted of 150,470 L vs. 204,704 C patients with 145,467 pairs for PSM. The 1-year cumulative incidence of AF from L and C was 0.764% and 0.642%, respectively, calculating a HR of 1.257 [95% CI: 1.0878-1.4534], p =0.0019. (Figure 1). The number of patients needed for one AF incidence/year is 820. Results from the sensitivity analysis were very similar. Conclusions: In adult naïve AF patients, L compared to C taking commonly prescribed BPI medications was associated with a higher risk of AF.
Abstract 4145649: Proteomics Characteristics of Patients with Acute Coronary Syndrome
Authors: Yiying Liu, Rong Huang
Journal: Circulation (2024)

Background: Acute coronary syndrome (ACS) remains a significant cause of morbidity and mortality worldwide, with its molecular characteristics at the protein level still poorly understood. This study aims to elucidate the proteomic signatures of ACS patients using a comprehensive proteomic approach. Methods: 182 ACS patients and 62 age and gender-matched healthy controls (HC) were randomly selected from our longitudinal multi-omic ACS cohort. Circulating proteins levels were measured with the Olink-Explore 3072 panel. Spearman correlation was used to examine the associations between proteins and clinical variables. Differential expression of proteins was analyzed using Benjamini-Hochberg-corrected T-tests. Results: Firstly, we screened proteins associated with clinical characteristics such as age, BMI and lipid profiles. As shown in figure 1, we identified several protein biomarkers associated with aging such as Elastin (ELN), Prokineticin 1 (PROK1), or exhibited gender-specific variations such as Kunitz Type 3 (SPINT3), and Insulin Like 3 (INSL3) in both healthy subjects and ACS patients. Proteins such as SSCD4 were significantly associated with BMI and lipids, suggesting a potential role in regulating lipid homeostasis. Then we analyzed the differential proteomic characteristics in ACS patients compared to HC patients and identified 1361 proteins with differential expression (false discovery rate, q&lt;0.05 for all). We subsequently conducted a pathway enrichment analysis on the differential proteins. We found pathways involved in regulation of cardiac muscle function, interleukin signaling, and regulation of the neuro-inflammatory response were upregulated while pathways related to the regulation of vascular-associated smooth muscle cell proliferation and platelet activation were downregulated. Conclusion: Our study demonstrates the efficacy of plasma proteomics in discerning demographic variations and elucidating the proteomic landscape of ACS patients. The significant differential protein expression observed underlines the value of a comprehensive proteomic approach in advancing our understanding of ACS pathophysiology and potentially facilitating the discovery of novel biomarkers.
Abstract 4146374: Geographic polygenic heterogeneity of obesity across the United States
Authors: Buu Truong, Tetsushi Nakao, Satoshi Koyama, Romit Bhattacharya, Michael Honigberg, Whitney Hornsby, Pradeep Natarajan
Journal: Circulation (2024)

Introduction: The rising prevalence of obesity represents a public health crisis. Genetic analyses have established the strong heritable basis of body-mass index (BMI), which can be estimated by polygenic risk scores (PRS). However, the geographic distribution of the genetic risk of obesity is unknown. Hypothesis: BMI and BMI PRS vary across US regions and social indices interplay with BMI PRS. Methods: We use the nationwide All of Us Research Program to quantify BMI and BMI PRS heterogeneity in the European ancestry across US regions. Social indices include median income, vacant housing, deprivation index, having health insurance and poverty. PRS was computed using LDpred2 with 681275 individuals from GIANT consortium and UK Biobank. We compared heterogeneity within/between ZIP codes and states using linear mixed models. BMI and BMI PRS were adjusted with the first 100 principal components (PC) of ancestry. Our analyses were adjusted for age, sex and the first 10 PCs. Results: Across 93825 individuals, the mean (standard deviation,SD) age was 58.5(16.9) years, 56369(60%) were female, and the mean (SD) BMI was 29.2(7.2) kg/m 2 . BMI PRS explained 11.8%(95%CI 11.4-12.1%,P&lt;2x10 -16 ) of BMI variance. Pennsylvania had the highest significant variance explained (R 2 ) by PRS with 13.2%(N=14288,P&lt;2x10 -16 ). BMI and BMI PRS were both spatially clustered (Moran’s I spatial autocorrelation=0.83 and 0.77, P&lt;10 -16 ,respectively). Urban areas had 0.12 SD-lower BMI compared to rural areas(P=4x10 -9 ). Within each state, BMI and BMI PRS varied significantly, e.g. east Pennsylvania has a significantly lower BMI than the west. BMI variance explained by ZIP code was higher than by state (R 2 =2%,P=2x10 -37 vs R 2 =0.6%,P=7x10 -14 ,respectively). High vacant housing and low median income were the strongest social indices associated with high BMI(P&lt;2x10 -16 ). Per 1-SD higher PRS,1-SD higher vacant housing and lower median income additionally increased BMI by 0.01 and 0.02 SD(interaction P&lt;2x10 -16 ),respectively. High poverty,no health insurance and low deprivation index are independently associated with low BMI. Conclusion: Understanding BMI differential distributions by genetic effects and social indices may uncover drivers of obesity across the US.
Abstract 4146364: A refined definition for low-risk pulmonary arterial hypertension patients including mortality and morbidity
Authors: Charles Fauvel, Yongqi Liu, Priscilla Correa-Jaque, Allen Everett, Manreet Kanwar, Rebecca Vanderpool, Sandeep Sahay, Shili Lin, Raymond Benza
Journal: Circulation (2024)

Background: According to the European Guidelines, “low-risk” pulmonary arterial hypertension (PAH) patients is defined as a risk of death &lt; 5% within a year and represents a treatment-goal. However, the impact of morbidity (e.g. hospitalization and clinical worsening), were not included in this definition. Research Questions: Can REVEAL 2.0 risk score further identify low-risk PAH patients for both morbidity and mortality? Aims: Using the REVEAL 2.0 risk score, to propose a modified definition of “low-risk” to include the risk of both morbidity and mortality at 1- and 3-years, respectively. Methods: A harmonized dataset from 8 PAH randomized controlled trials from the FDA was used for this analysis and REVEAL 2.0 risk score was calculated for each patient. Modified low-risk was a priori defined by “risk of death ≤ 5% at 3-years and risk of clinical worsening ≤10% at 1-year”. Clinical worsening was defined as any of the following: lung transplantation or hospitalization due to PAH worsening, initiation of prostanoids/chronic oxygen, 15% decrease in 6-MWD from baseline, a worsening of NYHA, addition of a new PAH medication. Results: A total of 4,122 PAH patients were included: median age 49 (36, 62) yo, mPAP 50 (40, 60) mmHg, PVR 10 (7, 14) WU, 6MWD 375 (306, 423) m, NTproBNP 884 (230, 3010) pg/mL. Patients with a REVEAL 2.0 risk score ≤ 4 had a 1-year clinical worsening free-survival and 3-year survival rate of 92% and 95% ( Figure 1 ). The 3-years survival was significantly better in patients with a REVEAL 2.0 ≤ 4 compared to 5-6: HR=0.47, 95%CI[0.27-0.84], p=0.01. Compared to patients with REVEAL 2.0 risk score of 5-6 (“classical” low-risk), those with a REVEAL 2.0 risk score ≤ 4 (“refined low-risk”) had a better clinical, biological, hemodynamic presentation, and outcomes ( Table 1 ). Conclusion: This study is the first embedding both morbidity and mortality within the definition of low risk for PAH patients and suggests that PAH patients with REVEAL 2.0 risk score ≤ 4 meet this definition. This definition may be a promising new treatment-goal strategy in future randomized controlled trials but also for daily clinical practice.
Abstract 4146453: Efficacy of Bilateral Cardiac Sympathetic Denervation in Treating Different Etiologies of Nonischemic Cardiomyopathy: A Subset Analysis
Authors: Rachad Ghazal, Nikhila Chelikam, Aashish Katapadi, Adnan Ahmed, Danish Bawa, Douglas Darden, Rakesh Gopinathannair, Naga Venkata Pothineni, Rajesh Kabra, ahmed romeya, Donita Atkins, Dhanunjaya Lakkireddy
Journal: Circulation (2024)

Background: Bilateral cardiac sympathetic denervation (BCSD) has shown promise in treating patients with nonischemic cardiomyopathy (NICM) suffering from refractory multifocal premature ventricular contractions (PVCs) and ventricular tachycardia (VT). Despite its growing use, the effectiveness of BCSD across different NICM etiologies has not been extensively studied. Research Question: How effective is BCSD across a variety of NICM etiologies? Goals: To evaluate the effectiveness of BCSD on left ventricular ejection fraction (LVEF) and PVC burden in patients with NICM. Methods: We conducted a subset analysis on a previous retrospective, observational study of NICM patients who underwent BCSD. Eight NICM etiologies were assessed. Results: 43 NICM patients underwent BCSD (mean age 52.3±14.7 years; 30% females). Overall, LVEF significantly improved (38.7±7.9% to 46.2±9.6%, p &lt;0.001), and PVC burden (PVCb) significantly decreased (23.7±9.9% to 1.3±1%, p &lt;0.001). A similar phenomenon was seen in idiopathic/dilated cardiomyopathy (CM) (LVEF: +8.7%, p &lt;0.001; PVCb: -20.6%, p &lt;0.001), post-viral CM (LVEF: +4.8%, p =0.2; PVCb: -24.2%, p &lt;0.001), familial CM (LVEF: +10%; PVCb: +23.3%), giant cell CM (LVEF: +10%; PVCb: + 30.5%), and arrhythmogenic right ventricular CM (LVEF: +12.5%, p=0.09; PVCb -30.6%, p =0.001). Catecholaminergic polymorphic VT had a non-significant increase in LVEF (+5%, p=0.5) but a significant decrease in PVCb (-21.8%, p=0.02), whereas sarcoidosis had the opposite effect with significant increase in LVEF (LVEF: +13.4%, p=0.3) but non-significant decrease in PVCb (-16.1%, p=0.02). Lastly, hypertrophic CM remained unchanged in LVEF (30%) but PVCb decreased (-8%). Conclusion: BCSD demonstrates efficacy in improving LVEF and reducing PVCb across almost all NICM with refractory VT. However, a case-by-case evaluation is still needed for its use.
Abstract 4146044: Evaluating Myeloperoxidase(MPO) as a Predictor of new-onset and recurrent Atrial Fibrillation (AF): A meta-analysis
Authors: Mehak Preet Singh Marwah, Sai Prasanna Lekkala, Srivatsa Surya Vasudevan, Aayushi Rajani, Ritika Parekh, Ishita Gupta, Mipasha Patel, Hajra Mehdi, Rupak Desai
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) pathogenesis is strongly linked to inflammation, but the role of inflammatory biomarkers like myeloperoxidase (MPO) levels is inconclusive. This meta-analysis is conducted to evaluate the association of myeloperoxidase (MPO) with atrial fibrillation (AF) onset or recurrence. Methods: We conducted a literature search in Pubmed, Scopus, and Google Scholar for studies relevant to predictors of AF onset specifically with MPO. A fixed-effects meta-analysis was performed to pool unadjusted and adjusted odds ratio effects across studies. Sensitivity analysis was performed to analyze the consistency of the overall results. Meta-regression was used to evaluate the confounders associated with the outcomes. p&lt;0.05 was considered statistically significant. Results: We included eight studies with a total of 451,884 patients in this meta analysis. Our meta-analysis of the unadjusted model showed statistically significant odds (OR: 1.01, 95% CI: 1.00-1.02, p = 0.003) of AF onset for MPO levels. In the adjusted analysis, the overall OR was 1.00 (95% CI: 0.99-1.01), suggesting no significant association (Z = -0.59, P = 0.55) (Figure 1a). However, on sensitivity analysis of the adjusted model, we found there was a statistically significant association of MLO with AF onset (OR = 1.02, 95% CI: 1.00 - 1.03, p = 0.01) (Figure 1b). Meta-regression analysis with age (Figure 1c), sex, and follow-up shows there was no significant association of these variables with the overall outcomes. Conclusion: MPO levels had a significant association with predicting the onset and recurrence of AF. We recommend clinicians use MPO as a potential biomarker and add it to their diagnostic modalities to detect AF onset or recurrence.
Abstract 4146494: Multi-Omic Profiling of Adiposity Distribution Patterns
Authors: Michael Pan, Jacqueline Dron, Art Schuermans, Saaket Agrawal, Lindsay Fourman, Satoshi Koyama, Whitney Hornsby, Gina Peloso, Pradeep Natarajan
Journal: Circulation (2024)

Background: Distribution patterns for visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue are strongly associated with cardiovascular disease. Circulating metabolites and proteins are dynamic indicators of biological processes and reflect metabolic health. It is not yet clear how these analytes are associated with adiposity distribution patterns. Aims: To determine the multi-omic profiles of adiposity distribution and their associated metabolomic and proteomic measurements. Methods: MRI-derived volumes of VAT, ASAT, and GFAT adjusted for BMI were available for 40,032 UK Biobank participants. Circulating metabolites and proteins were measured using the Nightingale Health NMR biomarker platform and Olink platform, respectively. We used linear regression models to assess the association between each analyte and VAT, ASAT, and GFAT. Models were adjusted for sex, age at MRI, MRI batch, and time between enrollment and MRI. Functional protein pathway enrichment was performed using the DAVID annotation tool. Results: Among 40,032 UK Biobank participants with adiposity volumes, 22,630 (56.5%) and 5023 (12.5%) had 168 metabolomic and 2910 proteomic measurements, respectively. In the metabolomic subset, the mean (SD) age was 55.7 (7.5) years, 10,992 (48.6%) were male, and all self-reported as white. In the proteomic subset, the mean (SD) age was 54.9 (7.8) years, 2417 (48.1%) were male, and all self-reported as white. Multi-variable linear regression revealed 39, 139, and 146 significant metabolite associations (P &lt;1.7e-5) and 65, 207, and 708 significant protein associations (P &lt;1.7e-5) for ASAT, GFAT, and VAT, respectively. We observed opposite directions of effect for 126 (99.2%) metabolites significantly associated with VAT and GFAT, except for pyruvate. Additionally, while proteins involved in cell adhesion were associated with all fat depots, inflammatory response proteins were only associated with VAT. Conclusion: Among the fat depots, VAT had the most associations with circulating proteins and metabolites, while ASAT had the least. Assessment of associations with coronary artery disease may further delineate connections between fat deposition and cardiometabolic health.