tbuckley/cabot-search huggingface dataset:
Abstract P2021: Association between Alcohol Consumption and the Risk of Cardiovascular Events by Renal Function Status in Japanese Community Dwellers
Authors: Aya Hirata, Sei Harada, Miho Iida, Naoko Miyagawa, Minako Matsumoto, Takuma Shibuki, Ryota Toki, Shun Edagawa, Kazuyo Kuwabara, Daisuke Sugiyama, Tomonori Okamura, Toru Takebayashi
Journal: Circulation (2025)

Introduction: The association between alcohol consumption and cardiovascular events differs according to the presence or absence of cardiovascular risk factors such as hypertension or dyslipidemia. However, the effect of renal function on that association is unclear in general populations. Hypothesis: Renal function status modifies the association between alcohol consumption and cardiovascular disease (CVD) risk. Methods: We followed 10,515 Japanese community dwellers (4,824 men and 5,691 women) without a history of CVD, who participated in the baseline survey of a population-based cohort study conducted between 2012 and 2015, until June 2023. Participants were classified into five groups based on alcohol consumption status: G1 (non-drinkers), G2 (former drinkers), G3 (&gt;0 to &lt;20g/day), G4 (≥20 to &lt;40g/day), and G5 (≥40g/day). Renal dysfunction was defined as estimated glomerular filtration rate (eGFR) &lt;60mL/min/1.73m 2 or non-negative of semi-quantitative screening tests for urine protein. Hazard ratios (HRs) of alcohol consumption status for CVD, atherosclerotic cardiovascular disease (ASCVD), and intracerebral hemorrhage events were estimated using a Cox proportional hazard model adjusted for confounders. A stratified analysis was performed by renal function status. Results: During a 9.4-year follow-up, 321 CVD, 206 ASCVD, and 52 intracerebral hemorrhage events were identified. Compared to non-drinkers, alcohol consumption reduced the risk of both CVD and ASCVD. However, in participants with non-negative urine protein, alcohol consumption increased CVD and ASCVD risk, while in those with negative urine protein, it reduced the risk [HR (95% CI) for CVD: G2: 1.00 (0.61-1.66), G3: 0.67 (0.46-0.98), G4: 0.73 (0.48-1.10), G5: 0.66 (0.44-0.99) in negative urine protein; G2: 2.79 (1.04-7.44), G3: 1.19 (0.46-3.08), G4: 3.13 (1.29-7.59), G5: 2.29 (0.95-5.47) in non-negative urine protein]. Reduced eGFR did not affect the association between alcohol consumption and the risk of these events. For intracerebral hemorrhage, alcohol consumption increased risk regardless of renal function. Conclusions: Alcohol consumption was associated with lower CVD and ASCVD risk in Japanese community dwellers. However, it increased the risk in those with urinary protein and not in those without urinary protein. Reduced eGFR had no effect. These findings suggest that CVD risk from alcohol consumption should be evaluated considering renal dysfunction and the type of pathophysiology.
Abstract P1153: Hypoxia Response Markers are Associated with Early Metabolic Imbalance: The U.S. National Health and Nutrition Examination Survey
Authors: David Cistola, Luis Mendiola, Alok Dwivedi
Journal: Circulation (2025)

Introduction: The metabolism spectrum considers cardiometabolic health&amp;disease as a series of four distinct categories, with progressing onset and severity of the underlying pathophysiology (Fig. 1). While prediabetes and metabolic syndrome are widely recognized categories, early metabolic imbalance (EMI) has largely been overlooked. Prevalent in teens and young adults, EMI is characterized by compensated insulin resistance, where fasting glucose, triglycerides, HDL cholesterol (HDL), and hemoglobin A1c are all within normal limits. Thus, EMI does not meet the criteria for prediabetes or metabolic syndrome and eludes risk screening for type 2 diabetes and ASCVD. In EMI, high circulating insulin overproduces nitric oxide, possibly leading to oxidized hemoglobin and a subclinical impairment of oxygen delivery to cells and tissues. Here, we investigated the association of hypoxia response markers with EMI in the U.S. population. Hypothesis: Individuals with EMI show a compensatory response suggestive of subclinical hypoxia. Methods: The fasting subsample from the 2015-2018 U.S. National Health&amp;Nutrition Examination Survey was analyzed: 6,227 observations representing 270.2 million people in the U.S. ages 12 and up. Population-weighted multinomial logistic regression was performed using Stata v18.5. The outcome variable was cardiometabolic health, categorized into 1 of 4 groups: healthy balanced metabolism, EMI, prediabetes/dyslipidemia (PD), or type 2 diabetes/ASCVD (Fig. 1). EMI was defined using prognostic insulin cutpoints derived from timeROC analysis of the CARDIA cohort. The 1° exposure was blood hemoglobin concentration. Resting pulse rate, serum globulin/albumin ratio (chronic inflammation), and serum GGT (cell damage) were 2° exposures. The adjusted covariates are listed in Table 1. To quantify association, the effect size was relative risk ratio with 95% confidence interval and p-value. Results: After adjusting for covariates, markers of the hypoxia response (hemoglobin, resting pulse rate, globulin/albumin ratio, GGT) were elevated in EMI compared with healthy balanced metabolism (Table 1, bottom panel). These increases were not apparent from a simple inspection of the unadjusted median values (top panel). Conclusion: EMI includes an insidious compensatory response to hypoxia. This observation is consistent with prior observations that dysfunctional hemoglobin is coupled to poor metabolic health. Further investigation is warranted.
Abstract 038: Association of Circulating Metabolites with Incident Heart Failure and its Subtypes in Multi-ethnic Populations
Authors: Eun Hye Moon, Taryn Alkis, Kai Luo, Megan Grove, Eric Boerwinkle, Clary Clish, Robert Gerszten, Michael and Jo Alice Hall, Lifang Hou, Scott Hutton, Robert Kaplan, Donald Lloyd-Jones, Bruce Psaty, Laura Raffield, Carlos Rodriguez, Jerome Rotter, Amil Shah, Sanjiv Shah, Kent Taylor, Kari Wong, Vanessa Xanthakis, Vasan Ramachandran, Bing Yu
Journal: Circulation (2025)

Introduction: Metabolic dysregulation is recognized in heart failure (HF). A comprehensive assessment of circulating metabolites, specifically on HF subtypes, in multi-ethnic populations is limited. Hypothesis: We hypothesize that circulating metabolites are significantly associated with the risk of HF and have differential effects on HF subtypes. Methods: Circulating metabolites from seven studies in the Trans-Omics for Precision Medicine Program were analyzed among 21,398 HF-free participants (58% non-Whites, 58% women), from which 1,160 incident HF, 373 HF with reduced (HFrEF), and 439 HF with preserved ejection fraction (HFpEF) events were ascertained with an average of 11.5 years of follow up. Cox proportional hazard regressions were applied by the study, followed by random-effect meta-analyses, to produce metabolite HF associations. Over-representation analyses were performed to identify relevant metabolite pathways. Results: Out of 1,015 metabolites analyzed, 54 were significantly associated with incident HF (Bonferroni corrected p&lt;0.05) after accounting for clinical risk factors. Eleven metabolic pathways were mapped; pentose and glucuronate interconversions and pyrimidine metabolism demonstrated over-representation (FDR&lt;0.05). Most identified metabolites (93%) were positively associated with HF, and the strength of the associations persisted with further adjustment of kidney function. Thirteen metabolites showed consistent effects from all participating studies, and subtype analyses indicated that most metabolites were more strongly associated with HFpEF than HFrEF ( Figure ). For example, N-acetylputrescine, a precursor of γ-aminobutyric acid (GABA), and 4-acetamidobutanoate, a derivative of GABA, were associated with an increased risk of HFpEF but not HFrEF. Conclusions: We identified circulating metabolites associated with the risk of HF in multi-ethnic populations, highlighting the need to better understand the differential metabolic etiology of HFpEF compared to HFrEF.
Abstract P1111: Metabolomic Architecture of Different Composition of Fat, Carbohydrates, and Proteins in Randomized Weight-Loss Diet Intervention Trial
Authors: Yoriko Heianza, Difei Liu, Jennifer Rood, Frank Hu, George Bray, Frank Sacks, Lu Qi
Journal: Circulation (2025)

Background and Aims: Low-calorie weight loss diets with different macronutrient compositions have shown to result in clinically meaningful long-term weight loss. We aimed to identify plasma metabolites that significantly changed over two years in an intervention trial of low-calorie weight-loss diets with varying amounts of fats, carbohydrates, and proteins, and to investigate which changes in plasma metabolites are linked to better long-term weight loss. Materials and methods: The present study included participants who were randomly assigned to one of 4 diets in the POUNDS Lost trial. Untargeted plasma metabolomics was performed; changes in 856 metabolites across various metabolic pathways from baseline to the end of the two-year intervention were calculated in 533 participants. Results: We observed 571 metabolites (67%) showing statistically significant changes ( P- FDR &lt; 0.05) following the two-year diet intervention (Figure panel a). We also identified core metabolites that significantly changed across all diet groups as well as specific metabolites that changed only in each of the 4 diet groups (panel b). Of the significantly modified metabolites by diets, 239 were significantly associated with 2-year weight changes, while others were not linked to weight loss (panel c). When stratifying by diet group, we identified 230 metabolites related to weight loss in response to one of the 4 diet interventions, including 22 metabolites within the lactoyl amino acid pathways, which showed the strongest sub-pathway associations with weight changes over two years in all diet groups. Conclusion: Our study identified core and specific metabolic pathways associated with changes in all or each of three macronutrients that contribute to better long-term weight loss.
Abstract P1004: Epigenetic Age Acceleration Predicts All-cause and CVD-specific Mortality over 20-years in a national-representative population
Authors: Junming Gong, Lina Mu, Zhongzheng Niu
Journal: Circulation (2025)

Background: Epigenetic age acceleration (EAA), the difference between DNA methylation-calculated age (DNAmAge) and chronological age, reflects biological aging. However, few studies have examined the prospective association of EAA with mortality in a national-representative sample. This study aims to investigate whether EAA is predictive of all-cause and cardiovascular disease (CVD) specific mortality over 20-year follow-up in the National Health and Nutrition Examination Survey (NHANES, cycle 1999–2002). Methods: We included 2,353 participants aged over 50 who had DNA methylation data at baseline and have been linked to the National Death Index in 2019. EAA was calculated by regressing DNAmAge on age and cell composition, using six estimators (Horvath, Hannum, SkinBlood, PhenoAge, GrimAgeMort, GrimAge2Mort). CVD deaths were identified by specific ICD-10 codes. Survival month was defined as the interval between baseline and the time of death or censorship. Cox proportional hazards models, adjusted for demographics, socioeconomic status, smoking, BMI, and chronic diseases, were used. Analyses were stratified by pre-existing CVD and BMI. Results: Over a median follow-up of 207 months, 1,210 deaths (385 CVD-specific) occurred. All EAA measures were significantly associated with increased all-cause mortality (except for SkinBlood-EAA) and CVD-specific mortality (except for Horvath-EAA). For instance, per 5-year increment of Hannum-EAA was associated with a 13% higher risk of all-cause mortality (HR: 1.13, 95% CI: 1.07 – 1.21), and 25% higher risk of CVD-specific mortality (HR: 1.25, 95% CI: 1.12 – 1.40). In those with pre-existing CVD, all EAA measures (excluding Horvath-EAA) were significantly associated with CVD mortality (e.g., PhenoAge-EAA HR: 1.13, 95% CI: 1.02–1.24), while no significant associations were found for participants without pre-existing CVD (e.g., Hannum-EAA HR: 1.08, 95% CI: 0.88–1.32). Stratified by BMI, obese individuals showed the highest hazard ratios. For instance, Hannum-EAA in obese participants was associated with an HR of 1.17 (95% CI: 1.04–1.32), compared to normal-weight (HR: 1.12, 95% CI: 1.00–1.25) and overweight participants (HR: 1.06, 95% CI: 0.95–1.18). Conclusion: Accelerated biological aging, as indicated by epigenetic clocks, was associated with increased all-cause and CVD-specific mortality risk in a US representative sample over 20 years. Associations were stronger among those with pre-existing CVD or obesity.
Abstract P1074: Assessing Health Literacy and the Role of Race and Social Determinants in Cardiac Patients.
Authors: Celestine Odigwe, Hanna Mayfield, rajasekhar mulyala, Mariam Riad, Hajira Malik, Brent Ruiz, Madhuri Mulekar, Christopher Malozzi, Bassam Omar, Nasser Lakkis
Journal: Circulation (2025)

Background: Health literacy is a crucial factor influencing the care outcomes of patients with cardiovascular disease (CVD). This study aimed to explore how socioeconomic factors, particularly income, education, and digital health literacy, contribute to patients’ understanding of their diagnosis and treatment following acute cardiac events. Methods: Over 3 months, we surveyed 50 patients at their first clinical visit post-hospitalization. The information was analyzed, social determinants were evaluated using Fisher's t-test, and logistic regression was used to study the predictive power of various factors. Results: The median age was 55 years, with 52% male and 50% identifying as African American. Education and income were key factors: 66.7% of participants had a high school or lower education level, and 71% had an annual income below $50,000. Notably, 50% of patients accessed their healthcare records via a digital patient portal, while 20% reported conducting personal research to better understand their condition. While 60% of participants expressed a good understanding of their diagnosis, 36% understood their treatment plans, and just 8% comprehended all aspects of their care, including expected clinical outcomes. Digital health literacy, specifically accessing healthcare records through the portal, was strongly associated with a better understanding of treatment plans. Income and educational attainment also played significant roles, with lower levels linked to greater challenges in understanding care instructions. Conclusion: Contrary to expectations, race and gender were not significant predictors of health literacy in this study. These findings suggest the need for targeted interventions focused on improving digital health literacy and supporting patients with lower education and income levels to enhance their understanding of cardiac care.
Abstract P1126: Cognitive Decline is Associated with Fewer Daily Steps and More Sedentary Behaviors Among Older Adults in Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Erin Dooley, Bjoern Hornikel, Alexandra Munson, Timothy Hughes, Jose Luchsinger, Susan Heckbert, Benjamin Boudreaux, Keith Diaz, Priya Palta, Kelley Gabriel
Journal: Circulation (2025)

Introduction: Despite known benefits of physical activity (PA) on cognition, little is known about how cognitive decline may relate to PA patterns. Hypothesis: We hypothesized that cognitive decline is associated with lower levels of PA and higher sedentary behaviors (SED) and differing patterns of accumulation across the week. Methods: Data are from 700 MESA participants (ages 70.1 ± 6.7 years; 55% women) with a cognitive battery at Exam 6 (2016-18) and Exam 7 (2022-24) and a hip accelerometer (valid wear: ≥4 of 7 days with ≥10 hrs) at Exam 7. The cognitive battery included the Cognitive Abilities Screening Instrument (CASI), a global measure of cognitive function (range 0-100). We calculated change in CASI test scores (△ = Exam 7 – Exam 6). Evenson vector magnitude (VM) cutpoints for older adults were used to estimate minutes by intensity category. We used linear mixed models to examine daily patterns of steps and minutes of SED, low light intensity PA, high light intensity PA, and moderate/vigorous intensity PA (MVPA) by cognitive change. Models were adjusted for age, sex, race/ethnicity, center, education, income, employment status, obesity, hypertension, diabetes, smoking status, and Exam 6 CASI score. Results: On average (± SD), participants spent 9.1 ± 3.2 hours in SED, 4.4 ± 1.3 hours in low light intensity PA, 2.0 ± 0.8 hours in high light intensity PA, and 45.2 ± 35.1 minutes in MVPA per day. Sunday was the least active/most sedentary day across the week (Figure). Average change (± SD) in CASI score was -1.2 ± 4.8 items. For every 1 item reduction in CASI score, there was 4.6 minutes (95% CI: 1.2, 8.0) higher SED and 95 fewer steps (95% CI: 24, 165) per day. No statistically significant interactions between cognitive change and gender or race/ethnicity with PA patterns were observed. Conclusions: In an ethnically diverse cohort of older adults, decline in 6-year cognitive performance was associated with more sedentary time and less steps. Consequences of cognitive decline on movement suggests need to support sit less, move more strategies.
Abstract P3114: Measured Obesity and Overweight in the Adult Population: the Italian Health Examination Survey 2023-2024 - CUORE Project
Authors: BENEDETTA MARCOZZI, Cinzia Lo Noce, Serena Vannucchi, Anna Di Lonardo, cecilia damiano, Alessandra Cardinale, DANIELA GALEONE, Paolo Bellisario, Luigi Palmieri, Chiara Donfrancesco
Journal: Circulation (2025)

Introduction: Obesity is associated with an increased risk of non-communicable diseases, such as diabetes, coronary heart disease, stroke, cancers, and other conditions, including obstructive sleep apnea and osteoarthritis. Obesity is largely preventable, and the WHO recommends to Member States to halt the rise of obesity by 2025, considering 2010 as baseline. Hypothesis: This analysis aims to assess if Italy can meet the WHO target in the general adult population using data measured in the periodic health examination surveys (HESs) conducted within the CUORE Project. Methods: In the HES started in 2023, mean level of BMI and prevalence of obesity (BMI&gt;=30 kg/m 2 ) and overweight (25&lt;=BMI&lt;30 kg/m 2 ) were assessed in representative random samples of resident population, aged 35-74 years, stratified by age and sex (1,216 men and 1,235 women), from 12 (of 20) Italian Regions, in Northern, Central and Southern Italy. Weight and height were measured using standardized methods. Insufficient physical activity was defined as less than 150 minutes of moderate-intensity activity per week or less than 75 minutes of vigorous-intensity activity per week. The survey is implemented with the technical and financial support of the Ministry of Health - National Centre for Disease Prevention and Control. Results: Prevalence of obesity was 23% (95% Confidence Interval -95% CI: 18-28%) in men and 24% (95% CI: 19-28%) in women; prevalence of overweight was 47% (95% CI: 41-52%) in men and 30% (95% CI : 25-35%) in women. Mean level of BMI was 27.6 kg/m 2 (95% CI : 27.3-27.9 kg/m 2 ) in men and 27.3 kg/m 2 (95% CI : 26.5-28.1 kg/m 2 ) in women. Obesity had a tendency to be higher in persons with insufficient physical activity (28% - 20-36% in men; 27% - 20-33% in women) than among those with sufficient physical activity (19% - 13-24% in men; 20% - 14-27% in women), and in persons with primary or secondary school education (30% - 21-40% in men; 32% - 22-42% in women) than in those with higher educational level (20% - 14-25% in men; 20% - 15-25% in women). Conclusions: Going in the direction of WHO target, preliminary data collected within 2023 showed a prevalence of obesity not statistically different compared to HES data of 15 and 5 years ago, both in men and women. However, 70% of men and 55% of women are in the overweight/obesity condition. Preventive actions at national and community level should be still massively implemented.
Abstract P2146: Multiple Pathways of CD34 <sup>+</sup> Cell Differentiation during Embryogenesis
Authors: Ting Wang, Hui Gong, Guoguo Ye, Qingbo Xu
Journal: Circulation (2025)

Introduction: CD34 + progenitor cells are widely used for stem cell therapy for cardiovascular diseases, but the effectiveness of the treatment is variable. To understand the fundamental mechanism of CD34 + cell development, we aimed to investigate cell fates of CD34 + progenitors during the embryogenesis of mice and humans. Methods: Human embryos from PCW 6 to 12 were obtained from patients who had undergone induced or spontaneous abortions and samples were subjected to mass spectrometry. For the animal model, embryos were obtained among C57BL/6J, Cd34 -DreER T2 ; IR, CD34 -CreER T2 ; R26-tdTomato, Cdh5 -dre; IR; Cd34 -creER, Cd34 -CreER T2 ; R26-tdTomato; Kdr flox , Cd34 -CreER T2 ; R26-tdTomato; Pdgfra flox mice. Single-cell RNA sequence (scRNA-seq) was performed using the databases generated from our group and publicly data from NCBI Gene Expression (GEO) Omnibus (E6.5 to E18.5 cells). Additionally, whole-mount staining and three-dimensional reconstruction were used to depict different types of CD34 + progenitor distribution within transparent embryos. Results: The proteomics unveiled an assumed intricate orchestration in developing human embryos from patients who experienced induced or spontaneous abortions. Our study demonstrated that the high level of CD34-expressing cells uncovered the potential naïve pluripotency to differentiate during embryonic development. Moreover, deletion of Kdr in CD34-derived cells resulted in stalled vessel development in stages spanning E6.5 to E8.5, which is crucial to endothelium development. Also, the activation of the cell cycle machinery was identified as a driver of endothelial-to-hematopoietic transition (EHT) in Cd34 + Runx1 + Cd44 + cells from E9.5 to E11.5. Until late embryogenesis, CD34 + progenitors gave rise to fibroblasts. Finally, CD34 + cells contribute to the quiescent stem cell pool in the adult stage and enter the cell cycle when the body suffers damage. Conclusions: Our results conducted a comprehensive study on the spatial and temporal induction of CD34 + cells and their intricate functions in embryonic development. These findings enlightened us on paving the way to innovatively tackle the complex hurdles present in stem cell and regenerative medicine, particularly in stem cell therapy.