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Tim-3-targeted vaccines overcome tumor immunosuppression and reduce cDC1 dependence to elicit potent anti-tumor immunity

Conventional type 1 dendritic cells (cDC1s) are specialized for cross-presenting tumor antigens and determining the efficacy of immunotherapies, including immune checkpoint blockade and adoptive cell therapy. However, their rarity and tumor-induced dysfunction severely limit CD8 T cell priming and represent a central bottleneck to therapeutic efficacy. While strategies such as anti–DEC-205-mediated antigen delivery and Flt3L-driven DC expansion can enhance host DC function, their reliance on functional cDC1s remains a significant constraint. We developed Tim-3-targeted vaccines by conjugating tumor antigens or neoantigens to anti–Tim-3 antibodies. These vaccines delivered antigens to both cDC1s and cDC2s, and elicited robust, durable CD8 T cell responses. Remarkably, Tim-3-targeted vaccines endowed cDC2s with efficient cross-presentation capacity that matched that of cDC1s. In tumor-bearing mice or in CD11c-β-catenin active mice, which model β-catenin-driven DC dysfunction, Tim-3-targeted vaccination restored cross-priming and counteracted tumor- and DC-mediated immunosuppression. In Batf3 −/− mice lacking cDC1s, anti-Tim-3-based vaccines still elicited significant CD8 T cell cross-priming and tumor control—albeit both were reduced compared to wild-type mice— demonstrating that cDC1s contribute to but are not essential for Tim-3-targeted vaccine–induced CD8 T cell priming and anti-tumor efficacy. Strikingly, a single dose of anti-Tim-3–neoantigen vaccination eradicated large established MC38 tumors in a CD8 T cell–dependent manner. Together, these data identify Tim-3-targeted vaccines as a next-generation cancer vaccine platform that broadens DC engagement, reduces reliance on cDC1s, and overcomes tumor- and DC-mediated immunosuppression, addressing key limitations of current DC-based cancer vaccines.

Abstract MPTU19: Gut Microbiota, Plasma Hippuric Acid, Fiber Intake, and Cardiometabolic Health in U.S. Populations.

Introduction: Hippuric acid is a gut microbiota-derived metabolite of polyphenols. Few population studies have characterized human gut microbial features related to this metabolite. Hypothesis: To identify gut microbial species associated with plasma hippuric acid levels, investigate the relationships between diet, gut microbiota composition, and hippuric acid, and explore the prospective associations of circulating hippuric acid with the risks of type 2 diabetes (T2D), cardiovascular disease (CVD), and weight gain (WG) through a systematic, integrated approach. Methods: We included 287 men from Men's Lifestyle Validation Study (MLVS) with plasma metabolomics, fecal metagenomic data, and 7-day diet records. Findings were replicated in 207 women from Mind Body Study (MBS), 1833 women from Microbiome Among Nurses (MICRO-N), and 3,035 men and women from the Hispanic Community Health Study/Study of Latinos Gut Origins of Latino Diabetes (GOLD). Prospective associations between hippuric acid concentrations and risks of T2D, CVD, and WG were examined in 5,472 participants from the Nurses' Health Study (NHS), NHSII, and HPFS. Results: We identified 26 microbial species significantly associated with plasma hippuric acid, mainly from Lachnospiraceae and Oscillospiraceae families. A gut microbiome (GMB) species score developed in MLVS was strongly correlated with hippuric acid (Pearson r =0.73), replicating in MBS ( r =0.29) and GOLD ( r =0.14). Dietary fiber correlated with hippuric acid ( r =0.35) and 68% of this relationship was mediated by hippuric acid–associated bacteria, primarily fiber-fermenting Firmicutes . The GMB score was inversely associated with prevalent T2D (per SD: OR = 0.97, 0.95–0.99) in GOLD, and incident T2D (0.80, 0.66–1.00) and WG (-0.17 kg/2 years) in MICRO-N. In NHS and HPFS, higher plasma hippuric acid was associated with lower incident T2D risk (Q5 vs. Q1: HR = 0.77, 0.64–0.94) and slower BMI gain (β=-0.01 per SD). No association with CVD was observed. Conclusions: Our findings confirm gut microbiota's essential role in hippuric acid production in humans, and highlight its potential role in mediating the relationship between dietary fiber and plasma hippuric acid. Overall these data elucidate novel pathways partially underlying the health benefits of fiber intake on improving cardiometabolic health. Further studies are needed to clarify how fiber facilitates the hippuric acid production via interactions with polyphenol intake and the gut microbiome.

Abstract TU246: A Meta-Analytic Review of Blood Pressure Responses to Transcendental Meditation

Background: Hypertension is a public health burden, the most prevalent risk factor for cardiovascular disease. Transcendental meditation (TM) is a promising treatment to reduce blood pressure and improve hypertension outcomes. The objective of this review was to systematically evaluate the effects of TM on systolic (SBP) and diastolic blood pressure (DBP). Methods: A systematic review and meta-analysis was conducted to evaluate the effects of TM on systolic (SBP) and diastolic blood pressure (DBP). Four databases were searched: PubMed, APA PsycInfo, CINAHL, and Scopus. Citations in past reviews, meta analyses, and other relevant articles were searched. Two team members extracted and coded articles and all authors discussed disagreements. Coded were study characteristics, sample demographics, and outcomes; we assessed methodological study quality (risk of bias) by coding concealed allocation, group assignment (random vs. nonrandom), blinded data collector, a priori power calculation, type of comparison group, intention-to-treat analysis, comparison of participants’ characteristics at baseline, intervention fidelity, and attrition rate. Outcomes were analyzed both (1) on a repeated-measures (post vs. pre) for both controlled and uncontrolled trials and (2) a between-groups basis for controlled trials. Results: Thirty-five TM interventions were included: 24 randomized controlled trials (RCTs), 3 quasi-experimental, and 8 uncontrolled studies; five were unpublished reports. Quality was mixed, with trials overall satisfying about 50% of the items; RCTs had higher quality than non-RCTs (mainly because they were not RCTs). In total, 2,010 participants were included, predominantly overweight, middle-aged, racial and ethnic minority adults with stage 1 hypertension. TM was associated with statistically and clinically significant reductions in SBP and DBP (means = −4.72 mmHg and −3.52 mmHg, respectively) compared to baseline levels. Reductions were greatest among participants with higher baseline BP, those with cardiovascular conditions, in uncontrolled studies, and in earlier studies. Conclusions: TM was associated with modest but clinically meaningful reductions in BP and appears to be a beneficial nonpharmacologic intervention for hypertension management. Unexplained heterogeneity warrants further investigation to clarify other factors associated with trial success.

Abstract TH965: Equol-Producing Status and Carotid Plaque and Carotid Intima-Media Thickness in Older Adults

Background: Carotid plaque and carotid intima-media thickness (CIMT) are established subclinical markers of atherosclerosis and predictors of cardiovascular events. Equol, a metabolite of the soy isoflavone daidzein produced by the gut microbiome, binds to estrogen receptor β (ERβ) in vascular endothelial and smooth muscle cells. ERβ activation promotes vasodilatory, anti-inflammatory, and anti-proliferative effects that may slow arterial aging. While 50-70% of East Asian adults produce equol after consumption of soy isoflavones, only 20-30% of Western adults do, and its vascular significance remains unclear. Objective: To examine whether equol producers have less carotid plaque presence and burden and lower CIMT, a marker of vascular aging, compared with non-producers at baseline. Methods: The Arterial Stiffness, Equol, and Cognition (ACE) trial, a multicenter, double-blind, placebo-controlled clinical trial, included 325 older adults aged 65-85 years (mean age 72.0 ± 4.9, 51% female, 15% African American) from the University of Pittsburgh and Wake Forest sites. Participants consuming soy products or soy isoflavones ≥2 times per week were excluded. Equol-producing status was defined after a 3-day soy challenge as urinary log10(Equol/Diadzein) ≥ -1.75. Carotid plaque and CIMT were compared by equol status using t-tests and chi-square tests. Associations were examined using multivariable linear and logistic regression, adjusting for demographics, lipids, blood pressure, diabetes, smoking, BMI, and physical activity. Results: Equol-producing status was not associated with carotid plaque presence (OR 0.71, p = 0.26) or plaque burden (all p > 0.30) at baseline. Age remained the only independent predictor of plaque burden. Equol-producing status was not associated with mean CIMT (β = 0.01, p = 0.54) or maximum CIMT (β = 0.02, p = 0.60) after adjustment. Age, sex, HDL cholesterol, and triglycerides were independently associated with CIMT (p < 0.05). Conclusions: In this cross-sectional cohort of older adults at baseline, equol-producing status was not associated with carotid plaque measures or CIMT. Although experimental studies suggest vascular benefits of equol, these findings indicate that producer status alone may not strongly influence vascular structure later in life. Further studies examining circulating equol levels, exposure duration, and dietary soy intake are warranted.

Regulation of the immune CD155–CD226–TIGIT axis by cyclin D-CDK4/6

Cyclin D-CDK4/6 is a component of mammalian cell-cycle machinery that drives cell proliferation. Small-molecule inhibitors of CDK4/6 have been approved for treatment of breast cancer patients. In addition to halting cell-cycle progression, inhibition of CDK4/6 can affect other tumor cell-intrinsic and -extrinsic functions. Here, we examined the impact of CDK4/6 inhibition on the CD155–CD226–TIGIT pathway that operates at the interface of tumor cells and the immune environment. We demonstrate that inhibition of CDK4/6 upregulates the expression of surface CD155 protein in cancer cells and downregulates an immuno-inhibitory receptor TIGIT in tumor-infiltrating lymphocytes. We observed these effects in human breast cancer cell lines, in mouse mammary carcinoma allograft models, in freshly resected human breast tumors and in paired pre-/on-treatment biopsies of breast cancers from patients undergoing monotherapy with a CDK4/6 inhibitor. We propose that inhibition of CDK4/6, through its tumor cell-intrinsic and -extrinsic effects, may shift the balance from the immunoinhibitory CD155–TIGIT to the immunostimulatory CD155–CD226 interaction, and through this mechanism may augment the antitumor immunity. Our results suggest that coadministration of CDK4/6 inhibitors and anti-TIGIT antibodies may further promote CD155–CD226-signaling and may have a strong synergistic antitumor effect.

Abstract WE544: Rural Patient Populations Overestimate the Effect of Diet on Common Disease Development

Background: Without proper informational couseling, past studies suggest that patients underestimate the effect of diet in chronic disease progression, specifically in gastrointestinal diseases and type 2 diabetes (T2D). It is unclear, however, the perception of the same patient population on the relative impact that proper diet can play on multiple different diseases. Understanding the complexity of these views and opinions, especially in a rural population, can help identify educational gaps and improve dietary counseling in rural areas. Hypothesis: We hypothesize that a rural patient population will inaccurately estimate the effect of diet on the development of several common diseases, with considerable variation in perceived dietary impact across conditions. Methods: This quantitative, cross-sectional, observational analysis utilized an online survey distributed via a HIPPA compliant platform to adults in rural Georgia. Patient responses were analyzed with descriptive statistics while single-sample t-tests assessed mean perception relative to evidence-based data by condition. Results: Across all 7 chronic diseases studied, patients demonstrated a high perceived impact of diet, with the average patient responses higher than the literature-based value in all instances (Table 2). The highest mean perceived diet based risk was for T2D (74.6%) and Major Cardiovascular Disease (CVD) (70.6%). Compared to evidence-based literature values, the magnitude of overestimation was most pronounced for cardiovascular conditions, with the perceived reduction of about 71% for Major CVD being over three times the literature value of 21% (Figure 1). Conclusions: We attribute both targeted public health messaging and intuitive patient knowledge of diease pathology to the high reported responses for diabetes and major CVD. It is important to note the high prevalence of these conditions in the rural population surveyed, possibly increasing baseline knowledge and awareness. Similarly, the largest perception-evidence gaps for these same diseases may occur because while this cause-and-effect linkage messaging is effective for raising awareness, it often lacks quantitative context on the actual risk reduction. This leads to an oversimplified belief in diet as a near-complete preventive solution, overshadowing the multifactorial nature of these diseases which also require pharmacological and alternative lifestyle interventions.

Abstract 03: Impact of SGLT 2 inhibitors and GLP-1 receptor agonists dual therapy on Cardiovascular Outcomes in patients with Heart Failure with Reduced Ejection Fraction and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Propensity-Matched Cohort

Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) affects 20–30% of patients with heart failure (HF). Conversely, patients with MASLD have a 1.5-fold higher risk of developing HF of which about 24% is HFrEF. SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RAs) have shown to offer benefits in patients with HFrEF. Moreover, GLP-1 RAs have also shown to be beneficial in MASLD. However, the impact of combined SGLT2i + GLP-1 RA therapy on patients with HFrEF coexisting with MASLD is not studied. Objective: To compare major adverse cardiovascular events (MACE), cardiac arrest, and all-cause mortality in HFrEF patients with MASLD treated with SGLT2i + GLP-1 RA vs. SGLT2i only. Methods: We conducted a propensity score-matched (PSM) retrospective cohort study using the TriNetX Global Network (160 organizations, 2005-2025). Using ICD-10 codes, we identified adults with systolic heart failure and MASLD (Defined as fatty liver plus ≥1 metabolic condition: hypertension, diabetes, obesity or dyslipidemia) and excluded those with diastolic HF and alcoholic liver disease. Patients were divided into two groups: combination therapy (SGLT2i + GLP-1 RA) and SGLT2i only. Outcomes included three-point MACE, cardiac arrest and all-cause mortality. PSM was based on demographics, comorbidities, HF risk factors, liver conditions, and HF background therapy. Results: We identified 2,554 patients on combination therapy and 13,455 on monotherapy that were reduced to 2,544 per group after PSM. The mean age for both cohorts was ~ 59 years, with about 61% males, a mean BMI of 36.5, and mean follow-up of ~ 2 years. A significant reduction was found with combination therapy for three-point MACE (RR 0.732; 95% CI (0.571, 0.937); HR 0.762, 95% CI (0.588, 0.986) p 0.038), all-cause mortality (RR: 0.619, 95% CI (0.505, 0.759) HR 0.650, 95% CI (0.526, 0.802) p <0.001), and cardiac arrest (RR 0.570 , 95% CI (0.363, 0.896); HR 0.596 , 95% CI (0.378, 0.941) , p 0.025) despite the statistically insignificant difference in HbA1c reduction [0.142, 95% CI (-0.034, 0.318) , p = 0.11]. Conclusion: In HFrEF patients with MASLD, SGLT2i + GLP-1 RA combined therapy had significantly better cardiovascular outcomes vs. those on SGLT2i alone that was not attributable to HbA1c reduction supporting the benefit of combination therapy and perhaps also exploring benefits of adding GLP-1 RA to GDMT in this high-risk population warranting further prospective studies.

Abstract TH913: Serum Metabolomics and the Association between Social Determinants of Health and Heart Failure: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Adverse social determinants of health (SDOH) are associated with greater heart failure (HF) risk, but data regarding underlying biologic mechanisms are limited. Methods: Among 3,321 HF-free Atherosclerosis Risk in Communities (ARIC) study participants at baseline (1987-1989), we used exploratory factor analysis to derive a SDOH-based latent factor comprised of income, education level, and area deprivation index (ADI), and assessed its association with incident HF using Cox proportional hazards regression. Due to differential distributions of SDOH between race groups, we stratified this analysis by self-reported race. Linear regression was used to relate 334 metabolites to the SDOH factor in race strata adjusting for demographics (age, sex) and batch at false discovery rate (FDR) p<0.05. We then assessed the association between SDOH-associated metabolites with incident HF at FDR p<0.05 using Cox regression adjusting for demographics, comorbidities (BMI, smoking, hypertension, diabetes, chronic kidney disease (CKD), and coronary artery disease (CAD)), and batch. We performed causal mediation analysis for SDOH and HF-associated metabolites in both race strata using FDR p<0.05 to define significant mediation effects. Results: Mean age was 54±6 years, 59% were female, and 60% identified as Black race. Over 20 [IQR 16-20] years, 201 White and 308 Black participants developed HF. The SDOH latent factor was associated with incident HF in Black (HR 1.47 [95% CI 1.26-1.72] and White (HR 1.49 [95% CI 1.27-1.76]) participants. In Black participants, the SDOH latent factor was cross-sectionally associated with 92 metabolites, 28 also associated with incident HF. In White participants, 87 metabolites associated with the SDOH factor, 8 of which associated with incident HF. We identified four metabolites including pseudouridine, a marker of RNA degradation, two γ-glutamyl amino acids, and 1-lineoleoylglycerophosphocholine (18:2n6), a marker of phospholipid remodeling, which mediated the association between the SDOH factor and HF in both strata. Proportion of the observed association that was mediated by these metabolites ranged from 2-10%. Conclusions: Large-scale metabolomic profiling identified metabolites linking adverse SDOH and HF risk reproducibly across race groups, suggesting perturbations in phospholipid remodeling and RNA turnover processes. These findings strengthen our understanding of the biologic pathways connecting SDOH to CV risk.

Correction for Allcott et al., The effects of Facebook and Instagram on the 2020 election: A deactivation experiment

Abstract 44: Symptoms Associated with Early Adverse Echocardiographic Changes in Community-based Cohort in Tobago

Introduction: Transthoracic echocardiography (TTE) is often part of the cardiac evaluation of patient-reported symptoms. Guidelines for obtaining TTE assume its ready availability, which may not be the case in resource-limited settings. Identifying symptoms associated with abnormalities of cardiac structure and function may help future selection of patients for TTE, particularly in low resource settings. Hypothesis: Individuals with symptoms associated with heart disease will be more likely to have echocardiographic evidence of cardiac dysfunction. Methods: The Tobago Health Study (THS) is a longitudinal community-based cohort study in adults on the Caribbean island of Tobago. Starting in 2021, an ancillary study conducted standard 2-D, M-mode, Doppler TTE at a local cardiology office in 905 THS participants without a history of heart failure, COPD, or coronary heart disease. Participants also completed clinical exams and health history questionnaires, including the Rose Angina Questionnaire. Associations between self-reported cardiac-related symptoms with TTE-determined cardiac structure and function were examined in regression models adjusted for age, sex, BMI, hypertension, smoking, and asthma. Sensitivity and specificity of symptoms for features of cardiac structure and function were calculated. Results: Participants were aged 41-88 (mean 63 years) and 38% female. Mean BMI was 30 kg/m2, 59% were hypertensive, 11% were current or former smokers, and 5.9% had asthma. In total, 60% of participants reported at least one symptom on the Rose Questionnaire, lower extremity edema and chest pain being the most common (Table 1). Echocardiography-defined clinical outcomes present in the THS included reduced (<50%) left ventricular ejection fraction (LVEF) in 2.3% (mean LVEF 64%), diastolic dysfunction in 12.8%, aortic stenosis (aortic valve peak velocity >2m/s) in 2.1% and left ventricular hypertrophy (LVH) in 7.6%. Table 2 displays multivariable-adjusted associations between symptoms and these features on TTE. Overall, symptoms provided low sensitivity, but higher specificity for reduced LVEF or aortic stenosis (Table 3). Sleeping with 2 or more pillows to help breathing yielded >93% specificity for reduced LVEF or aortic stenosis. Conclusions: In persons without a history of cardiovascular disease in resource limited settings, the presence of symptoms, particularly severe chest pain or orthopnea, is associated with presence of reduced LVEF and/or aortic stenosis.

Abstract WE576: Acute Myocardial Infarction Risk Following COVID-19 Infection and Vaccination in the United States

Introduction: The relationship between COVID-19 infection, COVID-19 vaccination, and myocardial infarction (MI) remains unclear. Characterizing these associations would benefit both clinical practice and public health intervention strategies. Hypothesis: We assessed the hypothesis that both COVID-19 infection and vaccination are associated with MI risk. Methods: Using 2020-2022 All of Us data, a case-control study compared COVID-19 infection during an exposure period of 90 days and a washout period of 2 days between matched on the timing of event MI cases and non-diseased controls. A similar structured study assessed MI following COVID-19 vaccination. Exclusion criteria included prior history of heart disease and missing data for sex or birth date. COVID-19 infection and MI were defined through electronic health records. COVID-19 vaccination status was defined based on the number of doses received. Other covariates included demographics, comorbidities, and cardiovascular medication. Crude and adjusted logistic regression models were used to test the association between COVID-19 infection/vaccination and MI. Results: In the first study, out of 70,282 included participants, around 1% had COVID-19 infection within the 90-day exposure period, and 0.5% suffered MI. In the second study, 37,800 participants were included, of whom 0.34% had MI and 21%, 21%, and 20% received the first, second, and additional (booster or third) doses, respectively. A total of 30.66% participants received any COVID-19 vaccine dose within the exposure period. In both studies, most MI cases were White (65.24% vs 68.99% accordingly) and taking cardiovascular medication (94.51% vs 92.25%), had existing comorbidities (85.06% vs 87.60%), and a mean age older than 64 years. In the 90-day exposure period, COVID-19 infection was associated with a higher odds of an MI when compared to COVID-19 vaccination and the odds of an MI [COVID-19 infection–MI adjusted OR 4.81 (95% CI 2.90-7.98), COVID-19 first dose-MI 1.52 (0.97-2.38), second dose-MI 1.51 (0.96-2.37), additional dose-MI 1.60 (1.05-2.42), and any COVID-19 vaccine-MI 1.11 (0.73-1.67)]. Conclusions: In conclusion, our findings indicated COVID-19 infection was associated with increased odds of MI. In contrast, COVID-19 vaccination was not associated with MI, except for a small increase observed with additional vaccine doses. This contrast may indicate that by reducing serious infection, vaccines may also benefit cardiovascular health.

Abstract TH906: Design of the HerStory First Study: A Step Toward Understanding Stress, Resilience, and Diet Quality for Culturally Restorative CVD Prevention in Young African American Women

Purpose: High stress contributes to poor diet quality, a key driver of cardiovascular disease (CVD) risk among young African American women (YAAW). Few studies examine psychological resilience—defined as one’s self-reported ability to bounce back from stress—as a predictor of dietary behaviors. Formative mixed-methods research offers an opportunity to understand how stress, resilience, and related resources influence diet quality. The current study describes the design of HerStory First , a community-engaged formative study conducted as Phase I of a planned resilience training pilot behavioral trial for YAAW. Methods: HerStory First employed an explanatory-sequential, mixed-methods design framed by Staudinger’s resilience and aging framework and a participatory approach. Three iterative phases were conducted: (0) early community engagement and integration of resilience theory to build trust, define shared resilience experiences, and review prior evidence; (1) co-design of a mixed-methods study (survey, n=233; four mini–focus groups, n=34) identifying stressors and resilience resources related to diet; and (2) translation of formative findings into a pilot resilience intervention (in progress). Community stakeholders guided study design, measure selection, recruitment strategies, and pilot development. Quantitative and qualitative strands were linked through joint displays and sequence-based integration, with survey data used to identify high- and low-resilience pools for focus group recruitment. Data analysis is ongoing. Results/Discussion: HerStory First demonstrates the potential importance of theory-driven, community-engaged formative research in informing preventive behavioral interventions for YAAW. Integrating mixed-methods approaches with community insight may support the identification of cultural resources as intervention targets for building resilience and fostering sustainable partnerships for the co-design of a behavioral clinical trial. By centering participants’ lived experiences, HerStory First moves away from deficit models and may establish a foundation for a culturally restorative, resilience-based behavioral trial aimed at preventing CVD among YAAW. Findings are forthcoming.

Deep critical zone controls on shallow landslides

The deep critical zone (CZ) has long been recognized for its importance in influencing shallow landslides but was not considered feasible to include in slope stability models at the watershed scale. Here, we demonstrate that simple approximations of the CZ in a fully coupled hydrologic and soil slope stability model can effectively capture the location, timing, and likely size of shallow landslides. To achieve this, we use coupled, process-based models that incorporate the effects of 1) deep CZ structures, 2) three-dimensional transient hydrology, and 3) multidimensional slope stability, calibrated with data from an intensively monitored field site. Our results show that the hydrologically active deep CZ guides groundwater flow, influencing where it drains from or exfiltrates to the soil mantle and producing distinct patterns of soil saturation and seepage forces at the soil–bedrock boundary. A deep conductive, weathered bedrock drains the soil mantle, reducing the likelihood of destabilizing pore pressures, while the downslope thinning of the CZ forces groundwater to the surface. This pattern creates localized instability and a tendency for similar-sized landslides across the landscape. In contrast, the absence of conductive weathered bedrock results in more widespread destabilizing pore pressures, leading to larger landslides and the likelihood of landslides earlier in a storm than in landscapes underlain by a deep CZ. Our findings suggest that first-order variations of deep CZs can provide physical explanations for variations observed in the susceptibility, magnitude, and timing of shallow landslides, and that CZ structure may be inferred from patterns and timing of landsliding.

Abstract TU249: Associations Between Healthy Eating Efficacy, Stress Eating and BMI Among Puerto Ricans in Puerto Rico and New York

Background: Obesity remains a public health problem for Puerto Ricans in the mainland US and on the island, influenced by suboptimal diet quality and high stress exposure. The Theory of Planned Behavior (TPB) helps explain how healthy eating self-efficacy influences obesogenic behaviors, like stress eating. Yet, this relationship and its variation by sociocultural context remain understudied. This study examines associations between healthy eating self-efficacy, stress eating, and BMI among young Puerto Rican adults in the Bronx-NY, and San Juan-PR. Methods: This cross-sectional analysis used data from the Boricua Youth Study-Health Assessment, a sample of Puerto Rican adults in San Juan, PR (n=410) and the South Bronx, NY (n=356; mean age=23y). Healthy eating self-efficacy was assessed with a 7-item scale on perceived control, attitudes, and confidence toward healthy eating (higher scores=greater efficacy). Stress eating was measured with two items on overeating or consuming sweets/fatty foods to cope (‘most of the time’, ‘some of the time’, ‘rarely’, ‘never’). BMI was derived from measured height and weight. Site-stratified multivariable models examined associations between (1) self-efficacy and stress eating and (2) stress eating and BMI. Results: Mean (SE) healthy eating efficacy scores were 40.0(0.4) in NY and 38.6(0.3) in PR. The proportion of those reporting ‘never’ overeating was 48.3% in NY and 26.8% in PR; ‘ never’ eating sweets/fatty foods was 39.2% in NY and 35.1% in PR. In adjusted models, in PR, each unit increase in healthy eating efficacy was linked to 8% (0.86-0.99) lower odds of overeating and 11% (0.85-0.94) lower odds of eating sweets/fatty foods most of the time (vs. never). This was not observed for those in NY. In NY, those reporting overeating ‘ most of the time’ or ‘ some of the time’ (vs. never) had BMIs that were 4 units higher on average (B=3.9; 95%CI=0.1-7.7; and B=3.8, 95%CI=1.6-6.1, respectively), while no associations were found for eating sweets/fatty foods. In PR, stress eating behaviors were not associated with BMI. Conclusion: Healthy eating self-efficacy appeared protective against stress eating in PR but not NY, suggesting environmental or sociocultural influences. Stress eating was linked to higher BMI in NY only, indicating geographic variation. Findings underscore the need for context-specific, TPB-based interventions to promote healthy eating and reduce stress-related obesity among Puerto Ricans across contexts.

Abstract TH873: Plasma Proteins Underlying Changes In Triglyceride Metabolism With Exercise Training

Introduction: Angiopoietin like proteins (ANGPTL) 3, 4, and 8 and their complexes (ANGPTL 3/8 and 4/8) are established inhibitors of lipoprotein lipase (LPL), all of which regulate triglyceride (TG) metabolism. Regular exercise is known to decrease plasma TG levels and increase LPL activity, and we recently showed that exercise training decreases ANGPTL3/8 levels. However, the molecular underpinnings of exercise-induced changes in regulators of TG metabolism have not been fully elucidated. The purpose of this study was to identify proteins associated with TG, LPL activity, C-terminal domain-containing (CD)-ANGPTL4, ANGPTL3/8, and ANGPTL4/8 responses to exercise training. Methods: Data on cardiometabolic phenotypes and plasma proteins (Olink 5K) measured before and after 20 weeks of endurance training were available in 617 adults (55% Female, 37% Black, 17-65 yrs) of the HERITAGE Family Study. Linear mixed models were used to test the associations of change in individual proteins with changes in TG-related traits, adjusting for age, sex, race, and baseline trait and baseline protein levels. Significant (FDR<0.05) proteins were entered in LASSO regression models with 10-fold cross-validation to identify proteomic signatures of exercise-induced changes in TG-related traits. Results: At baseline, mean age was 35 yrs, BMI 26 kg/m 2 , and lipid profile values were within the normal range. Changes in the abundance of 141 unique proteins were associated with the exercise training changes of at least one of the four traits (none associated with ΔLPL; Table 1 ), with little overlap of associated proteins across traits ( Figure 1 ). The associated proteins were overrepresented in pathways related to peptide hormone metabolism, lipoprotein assembly, remodeling and clearance, assembly of LPL and LIPC complexes, G protein-coupled receptor signaling, and clotting cascade ( Table 1 ). Proteomic signatures consisting of 24, 28, 22, and 13 proteins explained 20%, 22%, 21%, and 28% of the variance in training-induced changes in TG, ANGPTL3/8, ANGPTL4/8, and CD-ANGPTL4, respectively. Top contributing proteins for each signature are shown in Figure 2 . Conclusions: We identified several plasma proteins whose changes in response to regular exercise were associated with concomitant changes in TG and ANGPTL complex and protein traits. Our findings indicate several shared but also unique biological pathways underlying the exercise responsiveness of key regulators of TG metabolism.

Abstract TU280: Endometriosis subtypes and risk of type 2 diabetes: advancing research in cardiovascular health and endometriosis study (ARCHES) retrospective cohort study

Endometriosis is a chronic inflammatory condition that affects ~11% of reproductive-aged women and is characterized by growth of endometrial-like tissue outside the uterus. Chronic inflammation contributes to the development of type 2 diabetes (T2D) by impairing insulin sensitivity and glucose uptake. Despite overlapping inflammatory pathways, prior studies have reported inconsistent associations between endometriosis and T2D. We conducted a population-based retrospective cohort study using the Utah Population Database (UPDB), a statewide, multigenerational resource that links electronic health records, vital records, and administrative data. The cohort included women born in or after 1935 with documented Utah residency between 1996 and 2021 (N = 2,939,380). Endometriosis diagnoses (n = 99,978) were ascertained from International Classification of Diseases (ICD-9/10) codes and categorized as superficial peritoneal (SE), ovarian (OE), deep infiltrating (DE), adenomyosis, or other site (OS; including scar, bladder, umbilicus, and lung). T2D diagnoses were identified using ICD-9 codes 250.x0 and 250.x2 and ICD-10 codes E11. We fit Cox proportional hazards models with time-varying endometriosis exposure and calendar time as the time scale to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident T2D, adjusting for birth year, birth state, race/ethnicity, age, and body mass index (BMI) at cohort entry. Women with endometriosis had a 46% higher risk of developing T2D compared with women without endometriosis (aHR = 1.46; 95% CI: 1.43, 1.50). Elevated hazards were observed across all subtypes: SE (aHR = 1.67; 95% CI: 1.61, 1.74), OE (aHR = 1.61; 95% CI: 1.53, 1.68), and DE (aHR = 1.45; 95% CI: 1.24, 1.69). The strongest association was for OS endometriosis (aHR = 2.00; 95% CI: 1.90, 2.10); adenomyosis was also associated with increased risk (aHR = 1.34; 95% CI: 1.20, 1.38). These findings underscore the importance of understanding the metabolic consequences of chronic inflammatory conditions such as endometriosis.

Boosting crops’ natural capabilities could help feed a warming world

Abstract WE567: Population Attributable Fractions of Prognostic Factors Associated with Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: Systematic Review and Meta-Analysis

Introduction: Patients who have had a transient ischemic attack (TIA) or minor stroke have an increased of risk of stroke for at least the next 10 years. Identifying key prognostic factors and understanding their contribution to long-term stroke risk is essential for enabling more targeted and effective secondary prevention strategies. We therefore aimed to estimate the population attributable fraction (PAF) of prognostic factors associated with long-term risk of stroke in patients with TIA or minor stroke. Methods: We searched MEDLINE, Embase, and the Web of Science (from inception up to August 2025) for observational studies including patients with TIA or minor stroke that evaluated prognostic factors for subsequent stroke over a follow-up period of at least one year. We used random-effects meta-analysis to determine, for each factor, the pooled prevalence and hazard ratio for long-term stroke risk, adjusted for relevant confounders. We then estimated the pooled PAF for each factor using Levin's formula: p(aHR-1)/[1+p(aHR-1)], where p is the pooled prevalence of the factor and aHR is the pooled adjusted hazard ratio. Results: Of the 14732 records identified, we included 23 studies comprising 83,597 patients (mean age 65-71 years; 52-60% male patients). The figure shows the pooled prevalence, adjusted hazard ratio, and the corresponding PAF of each factor. Of the non-modifiable factors, an initial minor stroke (vs. TIA) accounted for the largest PAF (28.0% [95% CI], 10.1-47.6]), followed by paresis (22.0% [3.8-43.4]), any infarct on neuroimaging (19.0% [5.0-38.9]), aphasia or dysarthria (14.0% [7.0-25.0]), male sex (13.0% [7.8-18.7]), and history of stroke or TIA before the index event (12.0% [5.2-21.4]). Of the modifiable factors, hypertension accounted for the highest PAF (19.3% [95% CI, 8.4-31.6]), followed by etiologic stroke subtypes such as small vessel disease (16.8% [5.0-34.3]), cardioembolism (14.6% [3.1-33.5]), and large artery atherosclerosis (13.2% [5.1-25.5]); smoking (11.1% [1.0-30.7]), ischemic heart disease (10.7% [2.8-22.9]), diabetes mellitus (7.7% [3.1-14.1]), and atrial fibrillation (3.8% [0.3-9.9]). Conclusion: We have quantified the impact of several key factors on the long-term risk of stroke, taking into account their prevalence and relative magnitude of association. This information can aid in developing and implementing targeted interventions to better prevent future strokes in patients who have had a TIA or minor stroke.

Abstract WE401: Sex Disparities in Accuracy of Physician-Reported Versus Computed CHA ₂ DS ₂ -VASc Scores in the Get With The Guidelines–AFIB Registry

Introduction: The CHA 2 DS 2 -VASc score is a widely used tool for stroke risk stratification in atrial fibrillation/ flutter (AF/AFL). Inaccurate scores can lead to inappropriate treatment. Data are limited on whether reporting accuracy differs by patient sex. Hypothesis: We hypothesized that inaccurate physician-reported CHA 2 DS 2 -VASc scores disproportionally affect younger females with AF/AFL, in whom underreporting may result in missed opportunities for stroke prevention. Methods: We included reproductive-age patients (≤50 years) with AF/AFL from the Get With The Guidelines–AFIB registry from May 2013 to March 2024. Physician-reported CHA 2 DS 2 -VASc scores were compared with registry-computed scores and categorized as accurate, underreported, or overreported. Misreporting consequences (no change, undertreatment, or overtreatment) were based on guideline-recommended anticoagulation thresholds. Associations between sex and reporting accuracy were assessed using chi-square tests and multivariable logistic regression to estimate odds ratios (ORs), which were adjusted for age, race/ethnicity, and insurance. Results: This analysis included 8,092 patients with 27.1% female and mean ages 42.5 ± 7.0 (females) and 42.0 ± 7.4 years (males). Physician-reported CHA 2 DS 2 -VASc scores were 1.35 ± 0.61 for females and 1.27 ± 0.52 for males. Compared to registry scores, females were significantly more likely to have underreported physician scores (60.9% vs 31.8%), whereas males were more often overreported (30.0% vs 7.6%; p<0.001, Table 1). Unadjusted regression analyses confirmed that females had over twice the odds of underreporting (OR 2.32, 95% CI 2.08–2.59) and 69% lower odds of overreporting (OR 0.31, 95% CI 0.26–0.37) versus males (Table 2). These findings persisted after adjustment for age, race/ethnicity, and insurance. Potential consequences of misreporting also differed by sex. Females were more likely to be undertreated (34.3% vs 26.0%, p<0.001), while males were more likely to be overtreated with anticoagulation based on physician-reported scores (14.0% vs 0.0%, p<0.001). Conclusion: Among reproductive-age patients with AF/AFL, physician-reported CHA 2 DS 2 -VASc scores were less accurate for females than males, primarily due to underreporting. These sex-based discrepancies may contribute to undertreatment and missed opportunities for stroke prevention in younger women. Efforts to improve accuracy in scoring are needed to ensure equitable preventative care in AF/AFL.

Abstract 02: Systemic Inflammation and Traditional Cardiovascular-Kidney-Metabolic Risk Mediate the Association Between Social Determinants of Health and Incident Heart Failure: Insights from A Multi-Ethnic Cohort

Background: Adverse social determinants of health (SDOH) are strongly associated with incident heart failure (HF), yet the associated biological mechanisms remain poorly defined. We examined whether systemic inflammation (hs-CRP) and traditional cardiovascular-kidney-metabolic (CKM) risk (AHA PREVENT HF risk score) mediate the relationship between SDOH and incident HF. Methods: A validated 14-component composite SDOH index (scaled 0-100; 5 domains as per the WHO framework) was estimated among MESA cohort participants without HF at baseline. Sequential Cox regression and causal mediation analyses (using bootstrap confidence intervals) quantified the extent to which hs-CRP, AHA PREVENT HF risk score, CAC score, and hs-cTnT explained the association of SDOH index with adjudicated incident HF events over 15.3±5.7 years of follow-up (HR adj per 10-points: 1.08, 95% CI: 1.02-1.15; Fig 1 ). Indirect effects were estimated using non-parametric bootstrap resampling (5,000 replicates) with percentile-based 95% confidence intervals. Models controlled for race/ethnicity, subclinical atherosclerosis (CAC score), and myocardial injury (hs-cTnT). Results: Among participants (mean age 62±10 years; 52.8% women; 61.5% non-White), 462 developed HF. In fully adjusted models, systemic inflammation (hs-CRP) mediated 15.6% of the SDOH-HF association (indirect HR: 1.011, 95% CI: 1.006-1.018), demonstrating a robust inflammatory pathway linking social adversity to HF risk (unadjusted mediation: 19.2%). Traditional CKM risk (PREVENT score) mediated an additional 18.1% (indirect HR: 1.017, 95% CI: 1.012-1.024). Notably, CKM-mediated effects attenuated substantially from 35.1% in unadjusted models to 18.1% after adjusting for race and subclinical disease markers, suggesting confounding ( Fig 2 ). Together, inflammation and traditional CKM risk explained approximately one-third of the SDOH-HF association, with substantial residual effects not yet examined (~66%), potentially attributable to genomic and exposomic pathways. Conclusions: Adverse SDOH increase HF risk through both systemic inflammation and traditional CKM pathways, independent of subclinical atherosclerosis and myocardial injury. However, additional mediating pathways require further evaluation. These findings support inflammation as a key molecular interface through which SDOH shapes HF risk and emphasize targeting social–biological intersections to prevent HF in vulnerable populations.