tbuckley/cabot-search huggingface dataset:
Abstract MP68: Mosaic Chromosomal Alterations, Frailty and Cardiovascular Disease Mortality: A Population-based Cohort Study Among Chinese Adults
Authors: Mingyu Song, Yuxuan Zhao, Yuting Han, Jun Lv, Canqing YU, pei pei, Ling Yang, Iona Millwood, Robin Walters, Yiping Chen, Huaidong Du, Xiaoming Yang, Junshi Chen, Zhengming Chen, Giulio Genovese, Chikashi Terao, Liming Li, Dianjianyi Sun
Journal: Circulation (2025)

Background: Mosaic chromosomal alterations (mCAs), representing a group of large-scale structural alterations detected in a fraction of peripheral leukocytes, serve as an indicator of genomic aging. We aim to investigate the association between expanded mCAs (cell fraction ≥10%) and cardiovascular disease (CVD) mortality, and examine whether combining mCAs with frailty index (FI), an indicator of phenotipic aging, contribute to the prediction of CVD mortality. Methods: A total of 100,297 genotyped participants aged 30-79 years from China Kadoorie Biobank were included, whose baseline information were collected from 2004-2008 and followed till Dec 31, 2023. MoChA pipeline was used to detect expanded mCAs events, including mCAs on autosomes, and the loss of X and Y chromosomes. FI was calculated using a previously validated equation using 28 health-related variables, which categorized participants into three groups: robust (FI≤0.1), prefrail (0.1&lt;FI≤0.25), and frail (FI≥0.25). We used Cox proportional hazards models to estimate the associations of the expanded mCAs, FI, as well as joint categories of expanded mCAs and FI with CVD mortality. Results: After a median follow-up of 17.2 years (IQR: 15.7-18.2), 13,655 deaths from CVD diseases were recorded. Expanded mCAs were associated with an increased risk of CVD mortality independent of FI (hazard ratio [HR] and 95% confidence interval [CI]=1.24 [1.13, 1.36]), including deaths from ischaemic heart diseases (IHD, 1.24 [1.08, 1.42]), from strokes (1.20 [1.03, 1.39]) and from pulmonary heart diseases (PHD, 2.20 [1.03, 4.68]). Compared with robust participants without expanded mCAs, frail participants with expanded mCAs had around three-times increased risks of CVD mortality (2.98 [2.17, 4.07]), deaths from IHD (3.18 [2.03, 4.96]), and death from strokes (2.79 [1.64, 4.74]), and had sixteen-times increased risks of PHD mortality (16.51 [3.63, 75.01]). Conclusion: Combining expanded mCAs, a novel pre-symptomatic marker, with frailty index might increase the prediction of death from multiple CVD diseases.
Abstract P1013: Ideal cardiovascular health is associated with reduced epigenetic aging: cross-sectional findings from the INSPIRE-T cohort
Authors: Mathilde Strumia, Vanina Bongard, Samuel Thuriot, Philippe Cestac, SALLERIN brigitte, Lemaitre Jean Marc, Sophie Guyonnet, Bruno Vellas, Sandrine Andrieu, Laure Rouch
Journal: Circulation (2025)

Introduction: Chronological age is the main non-modifiable risk factor for morbidity, but it cannot be the only factor responsible for these age-related changes. Several teams have taken an interest in the biological mechanisms underlying ageing and have developed biological clocks, in particular epigenetic clocks such as DNAm GrimAge. These clocks could help to identify factors protecting against accelerated ageing and associated diseases. In this context, our aim was to assess the association between ideal cardiovascular health and reduced epigenetic ageing. Method Our cross-sectional analysis included participants from the INSPIRE-T human translational cohort. Cardiovascular health (CVH) was assessed using the Life’s Essential 8 composite score (0 to 100 points, higher means better) and calculated as the average of 8 component metric scores (healthy diet, physical activity, avoidance of nicotine, healthy sleep, healthy weight, and healthy levels of blood lipids, glucose and blood pressure). Overall CVH scores of 80-100 points were considered high CVH, 50-79, moderate CVH; 0 to 49, low CVH. Epigenetic aging was derived from the residuals of a linear regression of epigenetic age calculated using the GrimAge epigenetic clock and chronological age. Linear regression models were used in the analyses. Results We included 937 subjects (age range 20-100, mean age 60 years, 67% men). On average, the subjects had an LE8 score of 68 points (± 9.7) and 11.7% had a high CVH. After adjustment for chronological age and sex, compared to those with low to moderate CVH, subjects with high CVH had reduced epigenetic aging (β = -1.1 ± 0.4, p =0.002). Among LE8 components and per 1-unit increase in scoring (0 to 100) physical activity (β = -0.9 ± 0.4, p =0.02), BMI (β = -1.3 ± 0.2, p &lt;0.001), diabetic status (β = -0.4 ± 0.1, p =0.001), smoking status (β = -3.6 ± 0.3, p &lt;0.001) and blood pressure level (β = -0.9 ± 0.3, p =0.004) were significantly associated with a reduction in epigenetic ageing. This association was not found for dietary score, lipid levels or sleep. Discussion Our study reported an association between ideal global CVH and optimal levels of multiple health behaviors and health factors with reduced epigenetic aging after adjustment for chronological age and sex. This suggests that epigenetic aging is potentially modifiable by healthy lifestyle and control of cardiovascular risk factors although a potential underlying causal relationship remains to be established.
Abstract MP31: Association of Eicosanoid Metabolites with Insulin Resistance
Authors: Juhi Parekh, Mandana Chitsazan, Athar Roshandelpoor, Mona Alotaibi, Mohit Jain, Susan Cheng, Jennifer Ho
Journal: Circulation (2025)

Introduction: Eicosanoids are bioactive lipids that govern upstream initiation of inflammation. Their role in the development of cardiometabolic disease including insulin resistance remains unclear. Objective: We sought to investigate the association of specific pro- and anti-inflammatory eicosanoid metabolites with insulin resistance in the community. Methods: We ascertained eicosanoid metabolites among Framingham Heart Study (FHS) offspring cohort participants using a directed, non-targeted mass spectrometry-based platform, and examined associations with insulin resistance (HOMA-IR) using multivariable linear regression after excluding individuals with diabetes. Statistical significance was determined at a false discovery rate (FDR) q-value &lt;0.01. Results: We studied 2055 individuals (65 ± 9 years; 58% women, HOMA-IR 3.3 ± 1.9 mg*μU/dL*mL). Of 650 eicosanoids analyzed, 76 showed significant associations with HOMA-IR (Figure for putative metabolite identities). Top hits associated with higher HOMA-IR included prostaglandins (15-epi-PGA1, β = 0.18, SE = 0.02), arachidonic acid derivatives (5S-HpETE, β = 0.14, SE = 0.02), and epoxides (12,13 EpOME, β = 0.12, SE = 0.02) with known pro-inflammatory actions. By contrast, top hits associated with lower HOMA-IR included docosahexaenoic derivatives (resolvins) and oxylipins (10,11-DiHDPA, β = -0.11, SE = 0.02), known to have anti-inflammatory actions. Conclusions: We identified 76 eicosanoid metabolites associated with HOMA-IR. Of these, 51 were linked with higher HOMA-IR including epoxides and arachidonic acid derivatives known to be pro-inflammatory, while 25 eicosanoids were associated with lower HOMA-IR including resolvins and oxylipids with known anti-inflammatory properties. These findings highlight bioactive lipids that may underlie adverse cardiometabolic consequences of insulin resistance.
Abstract P3108: Pilot Evaluation of the Healthy Kids, Inc. Central Kitchen Food Project: Insights from a Childcare Center-Based Nutrition Program In West Virginia.
Authors: Claire Ugo-Ike, Jennifer Herbert, Mary Hastings, Brice Haines, Mandy Curry, Sally Honeycutt
Journal: Circulation (2025)

Introduction: Childhood obesity is a public health crisis that increases the risk of lifelong obesity and associated conditions like hypertension, sleep apnea, Type II diabetes, depression, and social stigma. Diet-related diseases are worsened by high intake of ultra-processed foods and insufficient whole foods rich in fiber. Addressing food insecurity and promoting a healthy diet in early childcare settings is critical, especially in West Virginia, where food insecurity and childhood obesity rates are among the nation's highest. In 2023, the American Heart Association’s (AHA) Social Impact Fund supported Healthy Kids, Inc. (HKI) to implement a Child Nutrition Program in childcare centers in Morgantown, West Virginia. The program provided children with healthy meals to improve dietary behavior and health outcomes. Hypothesis: Implementing HKI’s Program would increase children's fruit and vegetable (F&amp;V) consumption. Methods: The AHA Evaluation team conducted a mixed-methods evaluation from February to July 2024. Retrospective surveys were completed by parents/guardians of children in participating childcare centers, with 54 eligible responses. Semi-structured interviews were conducted with five childcare center staff to assess the program's impact. Survey data were analyzed using descriptive statistics, and interviews were coded for themes related to outcomes and challenges. Results: Findings showed that over 90% of respondents (n=54) rated their child’s health as excellent or very good. Additionally, 60% of parents/guardians reported an increase in their child’s F&amp;V consumption. The frequency of families eating healthy meals with their children increased, with 65% reporting they ate together more than five times a week after the program, compared to 44% before. Interviews with childcare center staff revealed positive experiences with the HKI Program, highlighting improved access to fresh, healthy meals, improved meal quality, and increased children’s willingness to try new foods. Conclusions: Findings from the pilot evaluation suggest that the HKI Program increased children’s F&amp;V consumption and willingness to try new healthy foods. These findings indicate that community-driven nutrition programs can address children's and households' nutritional needs, highlighting the need for nutrition educational opportunities for families. Further research is needed to explore long-term effects and identify strategies for sustaining and scaling these outcomes.
Abstract 040: Statin Initiation Is Not Associated With Gut Microbiome Changes: Findings from the Baltimore Longitudinal Study of Aging
Authors: Curtis Tilves, Toshiko Tanaka, Bruno Bohn, Chee Chia, Noel Mueller
Journal: Circulation (2025)

Introduction: Gut microbiome (GMB) has been implicated in the cholesterol-lowering effects of statins. Observational studies and animal models suggest statins increase GMB diversity and alter GMB composition. However, secondary analyses of a rosuvastatin trial (N=20/arm) did not support these findings. This trial was limited in demographics (Norwegian women) and GMB measurement (16s rRNA sequencing, which lacks data on species and function). We sought to emulate a randomized trial of statins on GMB in a longitudinal cohort with greater demographic inclusion and higher-resolution GMB sequencing. Hypothesis: Statins increase GMB diversity and alter GMB composition and function. Methods: We selected statin initiator and non-initiator-matched participants from the Baltimore Longitudinal Study of Aging. Eligible participants had to have 2+ GMB samples (collected between 2013 and 2019), be statin naïve at start of collection, have non-missing matching covariate data, and be statin eligible at their baseline visit (using 2013 ACC/AHA Guidelines). We used a 1:1 matching algorithm on the baseline propensity score, with nearest-neighbor matching on age, BMI, education, LDL-c, and ASCVD lifetime risk category (Yes/No/Prior ASCVD event); and exact matching on sex, diabetes status, smoking, and race. We measured GMB features (diversity, composition, and functional genes) using shotgun sequencing. We tested associations of statin initiation with post-treatment GMB alpha diversity and with changes in GMB beta diversity using ANCOVA g-computation, and with differential abundance of microbial species and functional genes using ANCOM-BC2. We adjusted models for the baseline matching covariates; alpha diversity models were further adjusted for baseline alpha diversity. Results: We identified N=30 matched pairs (N=60 total; 40% female, 30% Black). Matching covariates were well-balanced (all absolute standardized mean differences &lt;0.1). Samples were also balanced on baseline GMB features. Among treated participants, statins lowered LDL-c (B: -40.7, 95%CI: -53.8 to -27.6), but did not affect other lipids. Statins were not associated with GMB diversity. Statins decreased Bifidobacterium pseudocatenulatum and altered 10 functional genes (mostly increased fatty acid biosynthesis) (all p &lt;0.05); however, these associations were not significant at FDR &lt;0.20. Conclusions: Using an emulated randomized trial, statins did not alter GMB diversity, but may induce changes in GMB function.
Abstract P1080: Barriers and Facilitators to Treatment Adherence: An Exploration of the Lived Experience of Patients with Heart Failure
Authors: William Burrows, Carolyn Lauckner, Anna Kucharska-Newton, Mary Leigh, Erin Abner, Daniela Moga, Meredith Duncan
Journal: Circulation (2025)

Background: Research suggests that only ~50% of patients with HF meet recommended medication adherence; rates of overall treatment adherence, which additionally includes lifestyle changes and cardiac rehabilitation attendance, are even lower. Drivers of treatment nonadherence in this population remain poorly understood. This qualitative study aims to identify barriers and facilitators of treatment adherence among patients with HF. Methods: We recruited 19 adult patients with a diagnosis of HF from 2 clinics in Kentucky to participate in interviews. All patients had access to a phone to facilitate the interview and were free of genetic heart conditions. Treatment adherence was defined as a patient’s ability to follow the recommended treatment prescribed by their healthcare provider. A semi-structured interview guide was used to ask patients about experiences, habits, barriers, and facilitators to engaging in their HF treatment. Six patients participated in follow-up interviews to assess the study team’s interpretation of their prior responses and to ask clarifying questions to ensure saliency of the findings. Results: Over half of the participants identified physician communication as crucial to their experience, specifically: open dialog, honest explanations of treatment side effects, and willingness to listen. Many patients identified goal setting as critical to their treatment adherence, especially after initial diagnosis. By setting small, obtainable goals with their medical team, patients described feelings of increased self-confidence and reported making positive lifestyle changes. Rising cost of medication, food, and other therapies were identified as adherence barriers. Finally, 42% of patients discussed having significant fear regarding their HF diagnosis which began after a precipitating traumatic event, such as a hospitalization or heart attack, and persisted years later. However, some patients found this fear to be a motivation to make and maintain lifestyle changes. Several patients also expressed feelings of depression or isolation resulting from reduced autonomy. Conclusion: These qualitative findings suggest that patients are more likely to engage with their treatment plan when they have effective communication with their physician, set obtainable goals, and are able to afford both food and medication. Interventions to improve outcomes for patients with HF should focus on the patient-doctor relationship and connection to available financial resources.
Abstract P3101: Predictive Modeling of Glycemic Variability and its Association with Metabolic Health: A Precision Nutrition Approach Using Korean National Data
Authors: Dahyun Park, Min-Jeong Shin
Journal: Circulation (2025)

The global burden of metabolic diseases, particularly diabetes and hyperglycemia, presents ongoing challenges for effective treatment and management. Conventional glycemic control strategies may not be suitable for healthy individuals and those with prediabetes. To enhance the personalized characterization of glycemic variability (GV), which reflects long-term glycemic trends rather than short-term responses to individual meals, this study developed a predictive model for Time in Range (TIR). This model enables monitoring of metabolic effects associated with lifestyle choices without the need for a continuous glucose monitoring system (CGMS). To estimate TIR, we applied a backward elimination linear regression model to optimize predictions based on lifestyle factors such as physical activity, sleep, stress, and dietary intake from 48 CGMS clinical study participants. The model showed a strong correlation between predicted TIR and actual metrics (R = 0.743, p &lt; 0.001). Using data from 24,564 adults from the Korean National Health and Nutrition Examination Survey, we confirmed the association between predicted TIR values and metabolic health indicators. The results demonstrated a significant association between predicted TIR and reduced risk of metabolic diseases, particularly hypertension (Q1 vs. Q5: OR = 0.87; 95% CI = 0.79–0.95) and hypercholesterolemia (Q1 vs. Q5: OR = 0.82; 95% CI = 0.73–0.92). These findings may contribute to the development of precision nutrition-based healthcare for personalized prevention and management of metabolic diseases.
Abstract MP66: Sex Differences in the Association of Baseline and Longitudinal Changes in Cardiac Biomarkers with Risk of Heart Failure subtypes – a post-hoc analysis of the Look AHEAD trial
Authors: Zainali Chunawala, Lajjaben Patel, Neil Keshvani, Matthew Segar, Mark Espeland, Christie Ballantyne, James Januzzi, Carolyn Lam, Alain Bertoni, Katelyn Garcia, Thomas Wang, Antoni Bayes-Genis, Ambarish Pandey
Journal: Circulation (2025)

Background: Elevated levels of biomarkers of neurohormonal stress (NT-proBNP) and myocardial injury (hs-TnT) are associated with an increased risk of heart failure (HF) in diabetes. While sex differences in these biomarker profiles and the HF epidemiology are well-established, it is unclear if the prognostic association of biomarkers with the risk of HF differs by sex. Methods: The study included participants of the LookAHEAD trial with overweight/obesity and T2DM. NT-proBNP and hs-TnT were measured at baseline, 1- and 4-year follow-up. HFpEF (LV EF&gt; 50%) and HFrEF (LV EF &lt;50) incidence were adjudicated based on HF hospitalization reports using a well-established protocol. Separate adjusted Cox models were constructed to assess the associations of baseline and longitudinal biomarker changes with the risk of HF subtypes, including sex*biomarker interaction terms. Results: The study included 3959 participants (age: 59 years, 59.3% women, BMI=36 kg/m 2 ) with 108 HFpEF (men vs women: 3.3% vs 2.3%) and 84 HFrEF (men vs women: 2.9% vs 1.6%) events over 12.4 years of follow-up. At baseline, higher NT-proBNP levels were more strongly associated with the risk of HFpEF in females than males (P-int=0.02). In contrast, the association between NT-proBNP and the HFrEF risk was significant and comparable for both sexes ( Table ). The association of elevated hs-TnT levels with the risk of HFpEF did not differ by sex. In contrast, the risk of HFrEF associated with hs-TnT was significantly modified by sex, with a greater risk noted among males (vs. females, Table ). Among those with biomarker assessment on follow-up, an increase in NT-proBNP levels over time was more strongly associated with risk of HFpEF in females than males (P-int=0.01). In contrast, the association between an increase in NT-proBNP levels over time and HFrEF risk did not differ by sex. Repeated measures of hs-TnT over time were not associated with the risk of either HF subtype, with no significant interaction by sex. Conclusion: Among individuals with T2DM with overweight/obesity, the prognostic relevance of cardiac biomarkers for HF outcomes varies by sex. Elevated baseline levels and increase in NT-proBNP over time are more strongly associated with HFpEF risk in females than males. In contrast, elevated hs-TnT is more strongly associated with the risk of HFrEF in males. Further research is needed to determine if sex-specific biomarker screening strategies can inform HF prevention in high-risk individuals.
Abstract 048: Effects of Replacing Solid Fats and Added Sugars with Avocado in Adults with Elevated Cardiometabolic Risk: A Randomized Controlled Trial
Authors: Nana Gletsu-Miller, Meredith Wilcox, Lisa Spence, Amy Wright, Liana Guarneiri, Muhammad Nadeem, Mark Hutter, Karen Sprague, Andrew Brown, Allon Friedman, Kevin Maki
Journal: Circulation (2025)

Background: Limited high-quality evidence exists from randomized controlled trials on the impact of an avocado-containing diet on cardiometabolic risk factors. Objective: The purpose of this randomized, double-blind, outpatient, controlled feeding, crossover study (NCT04990817) in adults with increased cardiometabolic risk was to assess the effects of replacing energy from solid fats and added sugars with energy from one avocado on blood lipids and other indicators of cardiometabolic health. Methods: For two 3-week periods separated by a 2-week washout, 42 healthy adults with elevated triglycerides (TG, 135-499 mg/dL) consumed a typical American diet that included either one avocado (~180 g/day, ~300 kcal/day) or approximately 300 kcal/day from saturated fats and added sugars. The same study products (muffins, granola bites, dressing, salsa, marinade, pesto) delivered the avocado or control ingredients, and green food dye was added to the control study products to facilitate the double-blinding of the conditions. Non-high-density lipoprotein cholesterol (non-HDL-C, the primary outcome), other blood lipids, fasting and postprandial glucose, insulin and blood pressure were measured at baseline and at the end of each diet condition. Linear mixed models were used to generate estimates for the percent change in outcomes. Results: Of the 42 participants, 37 completed the avocado condition and 39 completed the control condition. An intention-to-treat analysis showed significantly greater percent changes from baseline during the avocado vs. control conditions for non-HDL-C: -4.6%, 95% CI -9.0, -0.1%, P=0.047; TG: -17.4%, 95% CI -25.0, -9.0%, P&lt;0.001; and total cholesterol:HDL-C ratio: -6.6%, -95% CI -12.0, -0.8%, P=0.028. Total cholesterol change from baseline during the avocado vs. control condition was: -3.1%, 95% CI -6.3, 0.1%, P=0.060. Other blood lipids, fasting and postprandial glucose, insulin and blood pressure did not significantly differ (P&gt;0.1). Conclusions: Replacing solid fats and added sugars in the typical American diet with avocado improves the lipoprotein lipid profile in adults with elevated triglycerides.