tbuckley/cabot-search huggingface dataset:
Abstract 043: Circulating Monocyte Gene Expression Profiles of Cardiac Remodeling and Incident Heart Failure: the Multi-Ethnic Study of Atherosclerosis
Authors: Tess Peterson, Yongmei Liu, Virginia Hahn, Jerome Rotter, Bharath Ambale-Venkatesh, Vinithra Varadarajan, Kurt Lohman, Jingzhong Ding, Margaret Doyle, Nels Olson, Peter Durda, Russell Tracy, Joao AC Lima, Katherine Wu, Wendy Post
Journal: Circulation (2025)

Introduction: The role of circulating monocytes in non-ischemic cardiac remodeling and heart failure (HF) is complex and unclear, due in part to monocyte heterogeneity and plasticity. We assessed the hypothesis that monocyte gene expression profiles reflecting activation and tissue inflammation are associated with cardiac structure and function and incident adjudicated HF in the Multi-Ethnic Study of Atherosclerosis. Methods: Monocytes were isolated from peripheral blood, and RNA was quantified using an Illumina BeadChip microarray. Cardiac magnetic resonance was performed concurrently. We used multivariable linear regression to estimate cross-sectional associations between gene expression levels and cardiac structure and function and Cox regression to estimate associations with time to incident HF. Results: We studied 12,369 transcripts mapping to 9,430 genes among 813 participants (mean age 69±9 years; 50% female; 22% Black; 29% Hispanic). Independent of traditional risk factors, expression levels of 55 transcripts were associated with left ventricular (LV) ejection fraction, 1136 with LV strain, 16 with LV geometry, 1020 with myocardial interstitial fibrosis, and 483 with left atrial size (FDR&lt;0.05). Enrichment analysis implicated T and B cell activation, cytokine production, phagocytosis, wound healing, oxidative stress, and cell migration. Expression levels of three genes—PCCB, MTCP1, and VIM—were associated with more than one cardiac metric as well as time to clinical HF ( n =45 events over a median follow-up of 7.7 years). Conclusion: These unique data support an association between monocyte-mediated immune processes and subclinical cardiac remodeling and incident HF in the absence of ischemic injury. Agnostically identified profiles were enriched for processes related to both pro-inflammatory and pro-resolving activated monocyte function and immunometabolism, as well as tissue migration and homeostasis. These insights may help generate hypotheses toward novel therapeutic targets for HF.
Abstract P1018: Incidence of Diagnosed Atrial Fibrillation in Community-Based Asian American, Native Hawaiian and other Pacific Islander Subpopulations: Findings from the PANACHE Study
Authors: Alan Go, Andrew Ambrosy, Rishi Parikh, Thida Tan, Connor Howick, Stacey Alexeeff, Joan Lo, Yihe Daida
Journal: Circulation (2025)

Introduction: Atrial fibrillation (AF) is a potent risk factor for stroke, cardiovascular disease (CVD), and death. Data suggest variation in AF across racial and ethnic groups, but little is known among Asian American, Native Hawaiian, and other Pacific Islanders (AANHPI). We evaluated the incidence of AF in disaggregated AANHPI subgroups vs. non-Hispanic Whites (NHW) in California and Hawaii. Methods: We identified adults between 2012-2022 aged ≥30 years in Kaiser Permanente Northern California and Hawaii integrated healthcare delivery systems with no prior CVD. AANHPI subgroups included Filipino (N=193,327), Chinese (N=182,776), South Asian (N=92,738), Native Hawaiian/other Pacific Islander (NH/PI, N=64,488), Vietnamese (N=50,141), Japanese (N=45,502), other Southeast Asian (N=26,602), and Korean (N=21,989), with 1,975,444 NHW. Incident AF was defined as a hospitalization, emergency department visit, or ≥2 outpatient visits with a diagnosis code for AF through December 2023. We calculated age- and sex-adjusted rates of AF by race and ethnicity, and then used Cox regression to assess the association of AANHPI subgroup with incident AF after adjustment for age, sex, and clinical CVD risk factors. Results: Among 2,653,007 eligible adults, mean±SD age was 49±15 years and 53% were women. Age- and sex-adjusted incidence (per 1000 person-years) of AF was 6.64 in NHW, and significantly varied in AANHPI subgroups: NH/PI (8.13), Filipino (5.32), other Southeast Asian (4.40), South Asian (3.79), Japanese (3.70), Korean (3.54), Chinese (3.45), and Vietnamese (3.28). Compared to NHW, in the fully-adjusted model, the adjusted hazard ratio (aHR, 95%CI) for AF was modestly higher for NH/PI (aHR 1.07, 1.02-1.13) but variably lower for Filipino (aHR 0.71, 0.69-0.73), other Southeast Asian (aHR 0.64, 0.57-0.71), Vietnamese (aHR 0.54, 0.50-0.59), Korean (aHR 0.54, 0.49-0.60), Chinese (aHR 0.53, 0.52-0.55), South Asian (aHR 0.51, 0.48-0.55) and Japanese (aHR 0.50, 0.48-0.53) ( Figure ). Conclusions: Notable variation exists in incident AF across disaggregated AANHPI subgroups living in California and Hawaii, with a higher adjusted rate in NH/PI and variably lower rates for other subgroups compared with NHW that was not explained by demographic and clinical CVD risk factors. Differentiating potential pathophysiological mechanisms vs. variable ascertainment of AF across AANHPI subgroups will help improve personalized care strategies for prevention and treatment of AF.
Abstract 011: Physician-Level Variation in Lipid Management for Secondary Prevention of Atherosclerotic Cardiovascular Disease: Opportunities for Practice Improvement
Authors: Danh Nguyen, Jimin Hwang, Eric Peterson, Anand Rohatgi, Parag Joshi, Amit Khera, Ann Marie Navar
Journal: Circulation (2025)

Introduction: While prior studies have documented suboptimal lipid therapeutic management and low rates of LDL-C goal achievement in patients with ASCVD, the degree of variability between cardiologists in lipid-lowering therapy (LLT) practice patterns is less well described. Hypothesis: Significant variability exists between cardiologists in their use of LLT and achievement of LDL-C goals in patients with ASCVD. Methods: We evaluated the use of LLTs and achievement of LDL-C &lt;70 mg/dL among adults with ASCVD (peripheral arterial disease, coronary artery disease, or ischemic cerebrovascular disease) followed by a cardiologist at a large academic medical center from 1/1/22-6/30/24. LLT utilization and LDL-C goal achievement were modeled using mixed-effects logistic regression with clustering at the cardiologist level, adjusting for patient age, insurance, ASCVD type, and diabetes. From this model, we quantified physician-level variability using the adjusted median odds ratios (aMOR). Results: Among 10,531 patients with ASCVD (mean age 68.5 years, 61.1% male, 69.8% White) seen across 55 cardiologists, 80.6% were on any statin, 51.5% were on a high-intensity statin, 14.9% were on ezetimibe, 5.6% were on bempedoic acid or a PCSK9 inhibitor, and 15.1% were not on any LLT. Of those with a lipid panel in the past year (n= 7,555), 45.9% achieved an LDL-C &lt; 70 mg/dL. Lipid management strategies varied substantially across cardiologists ( Figure ). In mixed-effects models adjusting for patient-level factors, significant physician-level variation was observed in high-intensity statin use (aMOR 1.33, 95% CI 1.25-1.45), ezetimibe use (aMOR 1.62, 95% CI 1.46-1.85), bempedoic acid or PCSK9 inhibitor use (aMOR 2.03, 95% CI 1.75-2.45), and attainment of LDL-C &lt; 70 mg/dL (aMOR 1.27, 95% CI 1.20-1.38). Conclusion: Even among cardiologists at the same academic medical center, practice patterns varied widely in the use of LLT and achievement of LDL-C goals for secondary prevention. Understanding the reasons for this variability and standardizing lipid management across the specialty may improve quality of care for patients with ASCVD.
Abstract P1024: Associations between DASH Diet Adherence and Cardiovascular-Kidney Metabolic (CKM) Syndrome Stages: 2011-2020 National Health and Nutrition Examination Survey
Authors: Chelsea Akubo, India Washington, Shanshan Song, Mojisola Olusola-Bello, Khadijat Adeleye, DJanee Kyeremeh, Samuel Gledhill, William Xiao, Samantha DeMarco, Valerie Sullivan, Yvonne Commodore-Mensah, Bunmi Ogungbe
Journal: Circulation (2025)

Background: Cardiovascular-kidney metabolic (CKM) syndrome substantially contributes to rising healthcare costs and reduced life expectancy, particularly in underserved communities. The relationship between dietary approaches such as Dietary Approaches to Stop Hypertension (DASH) in managing CKM syndrome is unclear. Objective: To assess the relationship between DASH adherence and CKM syndrome stages among US adults. Methods: Cross-sectional data from the 2011-2020 National Health and Nutrition Examination Survey (NHANES) were analyzed. DASH scores (range: 17-37) were divided into quintiles: Q1 (&lt;24.5, lowest), Q2 (&gt;24.5-27), Q3 (&gt;27-29), Q4 (&gt;29-32), and Q5 (&gt;32, highest). CKM syndrome stages were defined as stage 0: no CKM (reference); stage 1: excess adiposity, prediabetes; stage 2: metabolic risk factors, high-risk kidney disease; stage 3: very high-risk kidney disease; and stage 4: clinical CVD with CKM risk factors. Separate multivariable logistic regression models were fitted, modeling the odds of each CKD stage 1-4 vs. 0, adjusting for covariates. Results: Our sample included 22,746 adults, mean age: 49 ±17 years, 52% female, median DASH score of 26.5. Compared to Q5 (highest adherence), those in the lowest DASH adherence quintile (Q1) consistently showed higher odds of being in more advanced CKM syndrome stages ( Figure ). For CKM stage 1 vs. stage 0, participants in Q1 had 1.46 times the odds (95% CI: 1.08, 1.97) of being classified in stage 1. For CKM stage 2 vs. stage 0, individuals in Q1 were 1.87 times more likely (95% CI: 1.48, 2.37) to be in stage 2. The association was even stronger for advanced stages: for CKM stage 3 vs. stage 0, those in Q1 had 4.76 times the odds (95% CI: 1.92, 14.48) of being classified in stage 3. Similarly, for CKM stage 4 vs. stage 0, participants in Q1 were 3.46 times as likely (95% CI: 2.02, 6.11) to reach stage 4, compared to those demonstrating the highest level of DASH adherence. Conclusion: Our findings suggest that lower DASH adherence is associated with higher odds of advanced CKM syndrome stages, highlighting its potential role in CKM syndrome prevention beyond hypertension management.
Abstract P2108: Longitudinal Changes of Chemical Exposome on Blood Pressure after Bariatric Surgery among Adolescents
Authors: Shudi Pan, Zhenjiang Li, Qiran Jia, Jesse Goodrich, Brittney Baumert, Hongxu Wang, Sarah Rock, Todd Jenkins, Stephanie Sisley, Scott Bartell, Thomas Inge, Stavra Xanthakos, Catherine Mullins, Douglas Walker, Rob McConnell, Erika Garcia, Sandrah Eckel, David Conti, Justin Ryder, Lida Chatzi
Journal: Circulation (2025)

Background: The heterogeneous response in cardiometabolic outcomes following obesity treatment, such as bariatric surgery, is well documented, yet the underlying environmental contributors remain unclear. One potential factor is the chemical exposome which can have an obesogenic effect. To date, no prior studies have examined the longitudinal changes in chemical exposures after obesity treatment and their influence on cardiometabolic outcomes. This study aimed to assess the associations between chemical exposome trajectories and blood pressure after bariatric surgery among adolescents. Methods: We quantified the plasma chemical exposome in 5 classes (polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFAS), phthalates, pyrethroid pesticides and other pesticides) in plasma collected prior to surgery and post-surgery at 6-months, 1 year and 3 years using gas and liquid chromatography with high-resolution mass spectrometry. The cohort included 149 adolescents from the prospective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Outcomes were systolic and diastolic blood pressure measurements (SBP, DBP), mean arterial pressure (MAP) and pulse pressure at 3 years and 5 years following surgery. We used linear mixed models with random intercepts and slopes to estimate exposure trajectories, and model-based clustering based on each chemical exposure trajectories to generate aggregate exposure trajectory profiles. Linear regression was used to assess the associations of these profiles with blood pressure, adjusting for baseline age, race, sex, parents’ annual income, BMI and blood pressure medications. Results: Two distinct exposure trajectory profiles were generated based on longitudinal changes in individual chemicals. Profile 1 (100 participants) showed a decrease in pesticides and an increase in phthalates. Profile 2 (49 participants) showed the opposite trend. Compared with profile 1, profile 2 was statistically significantly lower for the association in MAP (b = -3.91 mmHg, 95%CI: -7.41, -0.41) and DBP (b = -3.41 mmHg, 95%CI: -6.68, -0.14) three years after bariatric surgery. The associations with blood pressure at five years were weaker. Conclusion: This study identified chemical exposome trajectory profiles after bariatric surgery and highlighted how longitudinal changes in these exposures may play an important role in explaining the heterogeneity in cardiometabolic outcomes after bariatric surgery.
Abstract 044: Urinary Metals and Incident Heart Failure: A Multi-Cohort Study and Meta-Analysis
Authors: Irene Martinez-Morata, Arce Domingo, Kathrin Schilling, Ronald Glabonjat, Katlyn McGraw, Joel Kaufman, Wendy Post, Daichi Shimbo, Amanda Fretts, Jason Umans, Shelley Cole, Maria Tellez-Plaza, Linda Valeri, R. Graham Barr, Steven Shea, Richard Devereux, Ana Navas-Acien
Journal: Circulation (2025)

Background: Environmental metals are recognized risk factors for cardiovascular disease, yet the role of urinary metals and metal mixtures on incident heart failure (HF) remains understudied. Objectives: To evaluate the prospective association of urinary metals on incident HF risk across three geographically and ethnically/racially diverse cohorts: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Strong Heart Study (SHS) in the United States, and the Hortega cohort in Spain. Methods: A total of 6,644, 2,917, and 1,334 adults 35-80 years old were included across MESA (39% non-Hispanic white, 27% non-Hispanic Black, 22% Hispanic/Latino, 12% Chinese-descent), SHS (100% American Indian), and Hortega (100% white), and followed up to 19 years. Urinary levels of inorganic arsenic, cadmium, molybdenum, selenium, and zinc were measured in all cohorts at baseline. The multi-adjusted (sociodemographic + clinical covariates) hazard ratios (HR) of HF per one interquartile range (IQR) difference in urinary metals were estimated for each metal using Cox proportional hazard models and a fixed-effects meta-analysis was run for each metal across cohorts. Flexible dose-response assessment was conducted using quadratic splines. We further estimated the HRs and 10-year-survival probability difference per IQR change in the mixture of five metals using Cox proportional hazard models with an Elastic Net penalty. Results: A total of 425 (MESA), 477 (SHS), and 103 (Hortega) participants developed HF over the study follow-up. Significant associations were identified for arsenic (Pooled HR (95%CI): 1.06 (1.00, 1.12), cadmium (HR: 1.15 (1.07, 1.24)), molybdenum (HR:1.14 (1.03, 1.26)), and zinc (HR: 1.23 (1.02, 1.49)) in the meta-analyses (Figure 1). A largely linear dose-response was identified for arsenic and cadmium (Figure 2). In fully adjusted models, the HRs (95% CI) and 10-year survival probability differences (95% CI) of incident HF per one IQR increase in the metal mixture were, respectively, 1.38 (1.00, 1.86) and -0.40 (-0.78, 0.00) in MESA, 1.55 (1.28. 1.97) and -1.24 (-2.20, -0.59) in SHS, and 1.08 (0.85, 1.63), and -0.03 (-0.21, 0.06) in Hortega. Conclusion: This multi-cohort study identified consistent associations between higher urinary metals and increased risk of heart failure across diverse populations, supporting the role of prevention strategies to reduce contaminant metal exposure to lower HF risk.
Abstract 045: Genome-wide Association Study for Metabolites in the Tryptophan Metabolism Pathway among African American Patients with Chronic Kidney Disease
Authors: Ruiyuan Zhang, Yixi Sun, Zhijie Huang, Yizhuo Liu, Morgan Grams, Tanika Kelly, Jing Chen, Jiang He, Changwei Li
Journal: Circulation (2025)

Introduction: Impaired tryptophan metabolism is a signature in chronic kidney disease (CKD), leading to adverse cardiovascular outcomes. Genome-wide association studies (GWAS) in CKD patients may uncover genes involved in tryptophan metabolism that are only detectable in individuals with CKD. Therefore, we conducted GWAS for tryptophan related metabolites among 1,322 African American participants of the Chronic Renal Insufficiency Cohort (CRIC), a minority patient group that genomic studies of tryptophan are lacking. Methods: Thirty-two tryptophan-related metabolites were profiled from baseline 24-hour urine samples. Genome-wide array data were imputed to the Trans-Omics for Precision Medicine reference panel. After stringent quality control, GWAS of each metabolite was conducted, adjusting for age, sex, and 10 genetic principal components. Variants with P &lt; 5×10 -8 were considered significant. Conditional association analysis using GCTA-cojo, followed by fine-mapping using SuSiE, was performed on the 1000 kb region around a significant variant to identify independent signals and causal variants. Results: Twenty-seven independent variants were identified for 17 tryptophan-related metabolites ( Table ). Seventeen, including 10 African specific, variants were novel. Of note, ACY3 intronic variant rs527362164 was associated with N-acetylkynurenine and was fine-mapped to two missense mutations, rs74533283 and rs76819752, in ACY3 . The three variants were African specific (minor allele frequency [MAF]&gt;1%) and missing in other populations (MAF&lt;0.1%). Interestingly, the two missense variants were also the causal variants of a previously reported African-specific intronic variant, rs115780269, associated with plasma N-acetyltryptophan . Similarly, AFMID missense variant rs61742958 was significantly associated with N-formylanthranilic acid and N-formylkynurenine . This variant was also African specific and fine-mapped as the causal variant of a previously identified intronic variant, rs114080902, for plasma N-formylanthranilic . We also replicated 12 associations for 10 independent variants in well-established genes involved in tryptophan metabolism. Conclusion: We identified 17 novel variants for tryptophan metabolism in African American CKD patients. Ten variants, including missense variants in AFMID and ACY3 genes, were African specific. Our findings underscore the importance of genetic studies in population subgroups to reveal novel mechanisms of tryptophan metabolism.
Abstract P1047: Pre- and Perinatal Determinants of Cardiovascular Health Trajectories Across Childhood and Adolescence
Authors: Izzuddin Aris, Sheryl Rifas-Shiman, Wei Perng, Marie-France Hivert, Sarah de Ferranti
Journal: Circulation (2025)

Introduction: The American Heart Association put forth the Life’s Essential 8 construct to assess cardiovascular health (CVH) status based on 8 health and behavioral factors. However, few studies have identified early-life determinants of CVH trajectories from childhood to adolescence, important life stages during which health behaviors and disease precursors are established. We sought to address this research gap in Project Viva, a prospective pre-birth cohort in Boston. Methods: We included 1,338 children with data on ≥3 CVH metrics in early childhood (median age 3.2y; range 2.8–6.2y) or ≥4 metrics in mid-childhood (7.7y; 6.6–10.9y), early adolescence (13.0y; 11.9–16.6y), or late adolescence (17.5y; 15.4–20.1y). We derived CVH score (range 0-100 points) at each life stage and used segmented mixed-effect models to estimate three CVH trajectory parameters: timing of inflection point when CVH score declines; slope before and after the inflection. Linear regression models evaluated associations of pre- and perinatal factors with each trajectory parameter, adjusting for maternal sociodemographic characteristics at enrollment. Results: The mean (SD) CVH score was 82.7 (8.4) in early childhood, 84.3 (8.2) in mid-childhood, 82.2 (9.7) in early adolescence, and 74.2 (11.4) in late adolescence. Estimated age of inflection when CVH score declined was 10.2y (0.7) for males and 10.0y (0.6) for females. Prepregnancy overweight or obesity (vs. healthy or under-weight), smoking during pregnancy (vs. never), and being weaned or formula-fed (vs. breastfeeding) in the first 6 months were each associated with persistently lower CVH from childhood to adolescence. Prepregnancy obesity (vs. healthy- or under-weight) was associated with later inflection (β 0.1y; 95% CI 0.0, 0.2) and slower subsequent CVH score decline (0.2 points/y; 0.1, 0.4). Gestational hypertension or preeclampsia (vs. normal blood pressure) was associated with faster CVH score gain before inflection (0.3 points/y; 0.1, 0.5), earlier timing of inflection (-0.1y; -0.2, 0.0), and faster CVH score decline (-0.3 points/y; -0.5, -0.1), while smoking during pregnancy (vs. never) was associated with later inflection (0.2y, 0.1, 0.3). Conclusions: This study provides insights into potentially modifiable pre- and perinatal factors of CVH trajectory across childhood and adolescence. Future work should examine whether early-life interventions addressing these factors would be effective in optimizing CVH in children.
Abstract 046: Associations of Long-Chain and Very-Long-Chain Saturated Fatty Acids with Outcomes of Sudden Cardiac Arrest
Authors: Jason Li, Jennifer Brody, Kerri Wiggins, Brenton Swenson, Paul Jensen, Lee Bockus, Rozenn Lemaitre, Nona Sootedehnia
Journal: Circulation (2025)

Background: Sudden cardiac arrest (SCA) due to ventricular fibrillation (VF) is a leading cause of mortality. Circulating fatty acids (FA) are influenced by diet and metabolism and have been linked to sudden cardiac arrest (SCA) risk. Certain long-chain saturated fatty acids (LSFA, defined as those with 14-18 carbons) and very long-chain saturated fatty acids (VLSFA, with 20+ carbons) have been associated with higher and lower risk of SCA, respectively. We hypothesized that higher LSFA and VLSFA levels would be associated with lower and higher likelihood of survival from SCA, respectively. Methods: We examined participants from the Cardiac Arrest Blood Study Repository, a study of SCA cases from Washington between 1988 and 2004. Patients were restricted to those with an initial rhythm of VF and who were greater than or equal to 18 years old. Six FA were studied: 3 LSFA (14:0, 16:0, and 18:0) and 3 VLSFA (20:0, 22:0, and 24:0). Poisson regression, adjusted for demographics and health services, was used to assess the association of SCA resuscitation outcomes with FA levels. A 2-sample Mendelian randomization (MR) using the 3 SNPs identified from the CHARGE consortium was conducted to assess causal association between 20:0 VLSFA levels and surviving SCA. Results: We examined 1351 SCA cases, of whom 700 died in the field, 332 died in the hospital, and 319 survived to hospital discharge. Our predominantly male (80%) cohort had an average age of 67±14 years. In multivariable analyses, higher 14:0 levels were associated with a lower likelihood (risk ratio 0.86, 95% CI: 0.77-0.96, P=0.008) of surviving to hospital discharge. Conversely, higher levels of 20:0, 22:0, and 24:0 were nominally associated with better survival (Figure), with 20:0 remaining significant after accounting for multiple testing (risk ratio 1.18; 95% CI: 1.08-1.29, P&lt;0.001). No FA was associated with likelihood of being admitted to the hospital following SCA. Using MR methodology, we found evidence for a causal association of 20:0. For each standard deviation increase in genetically predicted 20:0 levels there was an 84% (P=0.027) higher likelihood of survival. Conclusions: Lower levels of 14:0 LSFA and higher levels of 20:0 VLSFA are associated with higher SCA survival. MR analysis suggested that there was a causal relationship of higher 20:0 VLSFA levels with better survival following SCA. Future studies are needed to assess whether administration of 20:0 improve SCA survival.