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Abstract 16: Cardiorespiratory Fitness, Coronary Artery Calcium, and Later-Life Dementia: The Cooper Center Longitudinal Study
Introduction: Cardiorespiratory fitness (CRF) and coronary artery calcium (CAC) score, both established cardiovascular risk markers, may be interrelated; however, their individual and joint associations with dementia risk remain unclear. We examined midlife CRF and CAC in relation to later-life dementia in a large prospective cohort. Methods: Individual participant data from the Cooper Center Longitudinal Study (CCLS; 1998–2018) were linked to Medicare claims records (1999–2019). CAC was measured by cardiac computed tomography and dichotomized as <100 or ≥100 Agatston units (AU). CRF was estimated using a maximal treadmill exercise test following a modified Balke protocol. Participants were categorized into low, moderate, or high CRF based on age- and sex-specific cutoffs. Incident all-cause dementia was identified via Medicare surveillance using the Chronic Condition Warehouse. Pertinent participant characteristics were assessed at the baseline clinic visit, and stroke or transient ischemic attack (TIA) during follow-up was recorded as an interim event. Illness-death models with semi-competing risks were used to estimate hazard ratios for dementia associated with CAC and CRF categories, adjusting for demographic and clinical covariates. Results: Participants free of cardiovascular disease and dementia with complete exposure and outcome data were analyzed [n=11,259; mean (SD) baseline age, 56.8 (7.0) years; 3,400 (30.2%) women]. The prevalence of clinically-meaningful CAC (≥100 AU) decreased across CRF categories, from 34.4% in the low CRF group to 29.6% in the moderate group and 26.8% in the high CRF group. The mean (SD) time between the clinic visit and the start of Medicare surveillance was 8.6 (5.6) years. During a mean (SD) Medicare follow-up of 6.7 (5.0) years, 923 cases of dementia were identified. Higher CRF was associated with a lower risk of dementia, whereas higher CAC was associated with a higher risk. These associations persisted across models with hierarchical adjustment for demographics, cardiovascular risk factors, interim stroke/TIA, and the other primary exposure (CAC or CRF; see Table). Conclusions: In this cohort of generally healthy adults, higher CRF and lower CAC in midlife were associated with a reduced risk of later-life dementia. These associations were independent of traditional cardiovascular risk factors and interim cerebrovascular events, highlighting the potential importance of fitness and vascular health in dementia prevention.
Abstract WE403: Development and Implementation of an Artificial Intelligence-Based Predictive Model for Sudden Cardiac Death by Integrating Personal Health Records and Clinical Data
Background: In Japan, approximately 90,000 individuals die annually from sudden cardiac death (SCD). Predicting SCD using electronic health records (EHRs) from hospitals remains difficult. The growing use of wearable devices enables the continuous collection of personal health records (PHRs) and offers an opportunity to develop robust databases by integrating PHRs with EHRs. Applying artificial intelligence (AI) to these combined datasets may enable the early detection of SCD precursors. Objective: To develop an AI-based predictive model for SCD and related cardiovascular events by integrating PHRs with EHRs. Methods: We are prospectively enrolling high-risk patients—those with prior heart failure (HF), acute coronary syndrome (ACS), or out-of-hospital cardiac arrest—from seven Japanese centers. Participants use wearable devices (e.g., Fitbit, Apple Watch, or VINSTA ring) and home monitors to collect body weight and blood pressure. These data is integrated with EHRs, including clinical outcomes, laboratory tests, electrocardiograms, and echocardiograms. The primary endpoint is SCD, and the secondary endpoints include ACS, lethal arrhythmias, and hospitalization for HF. AI-based analysis was utilized to identify physiological changes preceding cardiovascular events. Results: From April 2024 to October 2025, 212 patients (mean age 58 ± 13 years; 77% male) were enrolled, yielding 167 person-years of follow-up. There were 12 cardiovascular events (3 HF, 3 ACS, 6 lethal arrhythmias) and no SCD. Temporary analysis revealed: 1. In HF, pulse rate increased from baseline 14 days prior, followed by weight gain seven days prior, and increased subjective symptoms three days before hospitalization. (Fig. 1) 2. In ACS, ST-segment depression detected by VINSTA ring appeared two days before the onset and resolved after treatment. (Fig. 2) 3. Event-positive participants showed higher mean pulse rate (81 ± 11 bpm vs. 70 ± 11 bpm; n = 4 vs. 66), greater orthostatic systolic drop (-2.3 ± 14.1 mmHg vs. -0.5 ± 7.2 mmHg; n = 2 vs. 19), and more frequent reports of subjective symptoms (1.9 ± 1.4 items vs. 0.7 ± 1.4 items; n = 4 vs. 57) seven days prior to the events. (Fig.3) Discussion: Integrating PHRs with EHRs enables continuous, personalized monitoring and early detection of cardiovascular deterioration. AI-driven analysis of these multimodal data may substantially enhance SCD risk prediction and support timely interventions to prevent adverse events.
Abstract TU100: Assessment of the Sarcopenia Index for Detecting Sarcopenia in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Introduction: Sarcopenia is the age-related loss of muscle mass, strength, and function, and is a risk factor for cardiovascular disease, all-cause mortality, and reduced quality of life. The Sarcopenia Index (serum creatinine/cystatin C × 100) is a proposed biomarker for diagnosis and severity assessment, with lower values indicating a greater likelihood of sarcopenia. However, most studies on the Sarcopenia Index investigated hospitalized patients, with limited data from the general population. Research Question: What is the performance of the Sarcopenia Index for identifying sarcopenia among adults aged ≥50 in the general population? Methods: We analyzed Black and white REGARDS study participants aged ≥50 years without stroke, leg amputation, and not on dialysis. Sarcopenia was defined according to the 2016 Sarcopenia Definition on Outcome Consortium recommendation: low muscle strength (5-repetition chair stand test <15 sec) and low physical function (4-meter gait speed <0.8 m/s). We estimated the Sarcopenia Index’s c-index, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at three cut-points: optimal (Youden’s Index), lowest sensitivity >0.70, and lowest specificity >0.70. Results: Among 11,000 participants (mean age 78±8), 34% were Black and 55% were women. Sarcopenia prevalence was 24% overall, increasing with age (50–65: 16%, 66–79: 23%, ≥80: 36%), and was 33% in Black women, 27% in Black men, 23% in White women, and 18% in White men. The median (25th–75th percentile) Sarcopenia Index was 89 (76 –104). A spline analysis showed that sarcopenia’s prevalence was flat above Sarcopenia Index values of 100 but increased as values declined below this threshold ( Figure 1 ). The c-index for identifying sarcopenia was 0.58 (95% CI: 0.57–0.59). Table 1 shows performance metrics at the three cut-points. In race-gender subgroups, the c-index ranged from 0.57 (Black men) to 0.61 (White women). In a sensitivity analysis of participants aged ≥65 years with Medicare and no claims for osteoarthrosis (n=2,201), the c-index was 0.58 (95% CI: 0.55–0.61). Limitation: Muscle mass measurements are unavailable in REGARDS. Conclusion: The Sarcopenia Index showed modest ability to distinguish between individuals with and without sarcopenia, defined by muscle strength and physical function. While limited for clinical use, it may be useful in epidemiologic studies where direct measures are unavailable.
Abstract WE536: Causal Effects of Physical Activity and Sedentary Behavior on Stroke Risk: A Systematic Review and Meta-analysis of Mendelian Randomization Studies
Background: Stroke is a major health burden and the second leading cause of death globally, only after ischemic heart disease. While observational studies have elaborated on the effect of physical activity (PA) and sedentary behavior (SB) on stroke risk, their findings remain inconsistent and are often influenced by confounding factors and reverse causation. Mendelian randomization (MR) can help overcome these shortcomings and assess potential causal relationships using genetic variants as proxies for exposures. Methods: We conducted a systematic review and meta-analysis of MR studies investigating the effects of PA and SB on stroke risk. Following PRISMA guidelines, we searched PubMed and Google Scholar through May 2025. Eligible studies used two-sample MR designs to estimate the impact of moderate-to-vigorous physical activity (MVPA) and sedentary leisure behavior (SLB) on stroke outcomes. MVPA exposures included self-reported activity and accelerometer-derived measures (e.g., leisure time MVPA ≥425 mg), while SLB included television, screen time, sitting, etc. Key outcomes of interest were any stroke and ischemic stroke events. Random-effects models were used for meta-analysis and heterogeneity was assessed with the I2 statistic. Leave-one-out sensitivity analyses were performed to ensure robustness of the results. Results: Six studies met inclusion criteria. Genetically predicted MVPA was associated with a lower risk of stroke (pooled OR = 0.73; 95% CI: 0.53–1.01; p = 0.06), though the result was not statistically significant (I2= 79.5%). In contrast, SLB showed a significant association with increased stroke risk (pooled OR = 1.15; 95% CI: 1.01–1.31; p = 0.03; I2 = 89.9%). Sensitivity analyses confirmed that findings were not influenced by any single study. Conclusion: These findings support a causal association between SLB and increased stroke risk, with suggestive but non-significant evidence for MVPA’s protective role. Despite significant association, high heterogeneity warrants conscious interpretation of findings. Further MR studies using standardized exposure definitions and updated genetic data are needed to strengthen the results.
Abstract WE424: Cardiovascular-Kidney-Metabolic Syndrome Across a Decade: Trajectories in Relation to Social Determinants of Health among Middle-Aged and Older Adults in the United States
Background: Cardiovascular-Kidney-Metabolic (CKM) syndrome, a cluster of conditions, including cardiovascular disease, chronic kidney disease, and type 2 diabetes, is classified by the American Heart Association (AHA) into five stages of severity (0-4). Since 2023, CKM has been widely recognized as a major health concern in the United States (U.S.); however, evidence of social determinants of health (SDOH) influencing its trajectory under current medical care remains limited. Objective: This study investigated 5- and 10-year patterns of CKM trajectories and their association with SDOH among U.S. adults. Methods: Data were pooled from two U.S. cohort studies: the Multi-Ethnic Study of Atherosclerosis and the Coronary Artery Risk Development in Young Adults. CKM stages were defined according to AHA criteria, and their trajectories were classified as regressed, stable, and progressed, based on 5-year (2000-2005) and 10-year (2000-2010) stage changes, which were assessed as a binary outcome (progressed vs. regressed/stable). SDOH were evaluated across four major domains: economic stability, education, community and social context, and health care. Multivariable logistic regression was applied to examine associations between SDOH and CKM trajectories. Results: A total of 6543 adults with CKM were included (mean age 53.3 years (SEM 0.16); 54.1% female; 46.3% White), and most had stable CKM status (Y5: 67.1%; Y10: 55.6%). Over a 5-year follow-up, being unmarried was associated with higher odds of progression after adjusting for demographic and lifestyle factors (OR 1.15, 95% CI 1.01-1.31). Over 10 years of follow-up, being unemployed (OR 1.38, 95% CI 1.03-1.84) and unmarried (OR 1.14, 95% CI 1.00-1.29) were associated with higher odds of progression. Individuals with ≥ 3 adverse SDOH factors were more likely to experience progression over 5- (OR 1.11, 95% CI 1.02-1.20) and 10-year follow-up (OR 1.09, 95% CI 1.01-1.17) consistently. Conclusion: This study demonstrates that individuals with adverse SDOH profiles are more likely to experience CKM progression over 5- and 10-year follow-up. These findings highlight the need for tailored strategies for CKM syndrome management that specifically address the impact of unfavorable SDOH.
Atomic-level architecture and assembly mechanism of high-order structures of RIPK1 fibril revealed by integrated structural biology
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) regulates cell death pathways through RHIM domain–mediated amyloid fibril formation. While amyloid fibrils typically exist as single filaments, we identified a higher-order architecture—the mouse RIPK1 (mRIPK1) fibril network—formed by the self-assembly of mRIPK1 fibrils into quadrilateral/hexagonal lattices under slightly acidic conditions. Using an integrative approach combining solid-state NMR, transmission electron microscopy, atomic force microscopy, X-ray diffraction, Cryo–electron tomography, and molecular dynamics simulations, we elucidated the atomic structure and assembly mechanism of this network. In this study, solid-state NMR analysis demonstrates that the mRIPK1 fibril core adopts an N-shaped parallel β-sheet conformation, with dynamic regions flanking the fibril core that likely participate in network formation. We propose that the electrostatic interactions between fibril core edge residues D516-K519 or D537-K519 are essential for the network formation, with proper positioning and exposure for interaction determined by the fibril structure and the length of the dynamic flexible domain, particularly the periodic twist of the fibril. Site-directed mutagenesis confirms the critical role of these edge residues in maintaining network integrity. This study presents an atomic model of a higher-order assembly formed by naturally occurring amyloid fibrils, offers fundamental insights into hierarchical fibril assembly, and establishes a framework for designing engineered amyloid-based materials.
Abstract WE524: Metabolomic Analysis in Three US Cohorts With 40 Years of Follow-Up Identifies Metabolomic Profiles Reflecting Metabolic States Associated with Long-Term Obesity Trajectory and Its Related Chronic Disease Risk.
Background: Obesity, a leading risk factor for coronary artery disease (CHD) and other chronic diseases, is a multifactorial condition with heterogenous etiologies and comorbidity profiles. Hypothesis: Circulating metabolome can capture metabolic states associated with obesity trajectory and inter-person variation in obesity-related disease risk. Methods: We analyzed up to 40-yr of longitudinal data of 10754 participants from the Nurses’ Health Studies and Health Professionals Follow-Up Study. Baseline plasma levels of 288 metabolites were profiled using LC-MS. Body mass index (BMI) was collected biennially, and its trajectory was estimated using function principal component (FPC) analysis. We categorize participants as having early- (<60y) or late-onset (>70y) obesity-related diseases based on age of first onset of 14 chronic diseases (Fig A). Linear regression was used to examine metabolites-BMI trajectory associations; elastic net regression to derive metabolomic signatures for BMI trajectory; Cox model to examine association with disease risk; and Mendelian randomization (MR) analysis to infer potential causal relationships. Results: The FPC1 of BMI trajectory accounted 81% of variation. We identified extensive associations between baseline metabolites with BMI-FPC1 (240 at FDR<0.05; Fig B). Further stratified analysis identified 63 metabolites, including glycine, alanine and C52:2 TAG, showing stronger associations with BMI-FPC1 among participants with early-onset vs late-onset of obesity-related diseases (Fig C). In MR analysis, genetically predicted levels of 26 metabolites were associated with at least one of these diseases (e.g., C4-OH carnitine with CHD; Fig D). We identified a metabolomic signature for BMI-FPC1, which was associated with risk of any chronic disease in multivariable-adjusted analysis (HR=1.99, p=4e-47). A second metabolomic signature, derived from the 63 metabolites differentially associated with BMI-FPC1 between two disease groups, was associated with disease risk after adjusting for the BMI-FPC1 signature (HR=1.2, p=5e-10). The two signatures showed an additive effect (p-interaction=6e-4), with participants in the highest vs. lowest quartiles of both signatures having a 11.3-fold higher disease risk (p=3e-50; Fig E). Conclusions: We identified metabolomic profiles reflecting metabolic states related to long-term BMI trajectory and inter-individual variation in obesity-related disease risk, which may facilitate personalized intervention.
Abstract WE464: Blood Pressure Lowering To Prevent Clinical Dementia: Systematic Review And Meta-Analysis
Background: High blood pressure (BP) is associated with higher dementia or cognitive impairment risk in observational studies. Prior clinical trial meta-analyses suggested BP-lowering reduces dementia or cognitive impairment risk but evidence for prevention of clinically-ascertained dementia was not definitive. Methods: PubMed was searched for randomized controlled BP-lowering trials reporting a clinical dementia outcome published from database inception through May 9, 2025. Search terms replicated those of a 2020 meta-analysis but added pragmatic trials comparing more intensive BP-lowering with usual care. Two investigators independently screened articles; trials enrolling >1000 hypertensive participants without baseline cognitive impairment and comparing greater BP-lowering using antihypertensive agents with “control” (placebo, active control, or usual care) were extracted. Primary outcome was new dementia diagnosis independently ascertained by study clinicians. Trials only reporting change in cognitive score without clinical dementia diagnostic assessment were excluded. Publication bias was assessed via funnel plot. Results: Systematic literature search identified 2742 BP-lowering studies; 13 defined clinically-ascertained dementia as an outcome. Of these, three were excluded for only reporting a composite dementia or cognitive impairment outcome and ten were included in the meta-analysis. Among 91,659 unique participants and over a median 3.95 years follow-up , 1713 dementia events occurred in 46,319 individuals in treatment arms and 1860 events in 45,340 individuals in comparator arms. Greater BP-lowering treatment in intervention arms led to a relative risk of dementia of 0.90 compared with control (95% CI 0.83-0.97; Figure). There did not appear to be publication bias. Conclusion: Greater BP-lowering in hypertensive patients reduces clinically-ascertained dementia risk. These findings reinforce 2025 ACC/AHA guidelines recommending hypertension treatment to reduce risk of cognitive decline and dementia in addition to the known cardiovascular disease risk reduction benefits.
Abstract 28: Relationship between endometriosis and cardiovascular disease: Insights from mediation analyses within the UK Biobank
Background: Endometriosis has been linked to a higher risk of cardiovascular disease, although the mechanisms are not fully understood. It has been suggested that undergoing a hysterectomy, with or without removal of the ovaries (oophorectomy), may partly explain the relationship between endometriosis and cardiovascular disease. Methods: We used data from the UK Biobank to examine the association between endometriosis and composite cardiovascular disease, defined as a combination of fatal and non-fatal coronary heart disease and stroke, as well as cardiovascular mortality and overall mortality. Cox regression models were applied, adjusting for conventional and emerging cardiovascular risk factors, lifestyle and demographic risk factors, and female-specific risk factors. In addition, we conducted counterfactual mediation analyses to explore whether hysterectomy with or without oophorectomy contributes to the link between endometriosis and cardiovascular disease. Results: Our study included 261,581 females with a median age of 57 years, of whom 8,101 had endometriosis. Over a total of 3,440,869 person-years of follow-up, 22,066 females developed cardiovascular disease. Endometriosis was associated with an 18% higher risk of cardiovascular disease (HR 1.18 [95% CI 1.09-1.28, P<0.001]), primarily driven by angina (HR 1.43 [1.23-1.66, P<0.001]). In contrast, endometriosis was linked to a 12% lower risk of all-cause mortality (HR 0.88 [0.79-0.98, P=0.019]). No significant association was found with cardiovascular mortality. Mediation analysis indicated that hysterectomy accounted for 61% (95% CI 27-94%) of the excess cardiovascular risk (indirect HR 1.11 [1.09-1.12, P<0.001]). Conclusion: Women with endometriosis have an increased risk of cardiovascular disease, particularly angina. The results suggest that hysterectomy, with or without oophorectomy, may partially explain this association. These findings underscore the importance of monitoring cardiovascular risk in women with endometriosis and evaluating the long-term effects of treatment options.
Gut microbe–derived <i>N</i> -acyl serinol lipids shape host postprandial metabolic homeostasis
Although strong evidence links the gut microbiome to metabolic disease, the mechanisms linking microbiota to hormonal and metabolic responses to food are not well understood. After a meal, gut bacteria produce a wide array of small molecule, protein, and lipid metabolites originating from bacterial sources. Attributing physiological function to select gut microbe–derived metabolites is critical to understanding diet–microbe–host interactions, and to developing microbiome-inspired therapies to improve human health. Here, we have investigated the role of a poorly annotated class of gut microbiome-derived lipids called N -acyl amides in postprandial metabolic physiology. Here, we show that both bacterial production and provision of exogenous N -acyl amides reorganize host hormone-driven metabolic transition after a meal. Moreover, N -acyl amides exert broad effects on the meal- and circadian-related reorganization of gene expression, metabolic hormones, and gut microbiome composition. Collectively, these results demonstrate that microbiota-derived N -acyl amides play a physiologic role in postprandial metabolic homeostasis in the host.
Abstract MPWE25: Clinical Predictors of Future Cardiovascular Disease at the Initiation of Prenatal Care
Introduction: Identifying cardiovascular disease (CVD) risk in adults under age 50 remains an unmet need. Pregnancy offers a unique opportunity to identify CVD risk given high health care engagement and frequent medical follow-up. We aimed to develop a prediction model for long-term CVD risk using clinical factors that can be ascertained at prenatal care initiation. Methods: We conducted a retrospective study in an electronic health record-based pregnancy cohort from a single institution. We included singleton pregnancies from individuals aged ≥18 years who delivered between 1998 and 2016, had ≥3 months of postpartum follow-up data, and were free of CVD before pregnancy. We split the cohort into training (60%) and validation (40%) sets. We used Cox regression to model time from delivery to diagnosis of CVD, with censoring at the last non-obstetric encounter, the next delivery, or 12/31/2024. We identified CVD using diagnostic codes for atherosclerotic CVD and heart failure. Predictors were adapted from the PREVENT equations and included universally available factors at initiation of prenatal care: age (years), pre-pregnancy diabetes, pre-pregnancy hypertension (HTN), pre-pregnancy smoking, 1 st trimester body mass index (kg/m 2 ) and systolic blood pressure (mmHg), and the social deprivation index. We used time-varying predictors to account for multiple pregnancies per individual. We assessed model performance using the C-statistic, smoothed calibration curves and the integrated calibration index (an index = 0 indicates perfect calibration) at 10 years. Results: We included 46,392 pregnancies from 32,600 individuals (Table 1). Participants had a mean (SD) age at delivery of 31.6 (5.6) years. Over a median (IQR) of 7.3 (2.4, 13.6) years, 2.1% of individuals overall (n=561 [training], n=400 [validation]) experienced CVD. Hazard ratios for CVD for each of the predictors are given in Table 2. In the validation dataset, the model had a C-statistic of 0.668, indicating moderate discrimination. The model demonstrated excellent calibration, with an integrated calibration index of 0.00197 (Figure 1). Conclusions: A prediction model based on clinical factors routinely available at the initiation of prenatal care demonstrated moderate discrimination and excellent calibration in predicting 10-year CVD risk.
Abstract TH931: Investigating the Association Between α <sub>1</sub> -antagonist Use and Symptomatic Lower Extremity Venous Disease
In this study, we tested the hypothesis that α 1 -antagonist use is associated with the onset of lower-extremity (LE) venous disease. Methods: We conducted a retrospective cohort study to examine the effect of α 1 -blocker exposure on venous disease incidence. At the initial visit, all participants were verified to be free of venous disease by venous duplex ultrasonography. Participants were followed longitudinally, and a follow-up ultrasound was performed to assess for incident venous disease. Follow-up duration ranged from 9 to 13 years. To further evaluate whether α 1 -antagonist use was associated with symptomatic manifestations of venous disease, we conducted a cross-sectional study on a separate sample. All participants completed a survey assessing major symptoms of LE venous disease (heavy legs, aching legs, swelling, night cramps, restless legs, throbbing, itching, and/or tingling). Logistic regression was used to test for associations between α 1 -antagonist use and venous disease symptoms, adjusting for age, sex, diabetes (DM) and smoking. Results: Our cohort study included 821 participants, of whom 14 were taking an α 1 -blocker. The mean age at enrollment was 58 years; 65% of the cohort were female, 5% had DM, and 55% were never-smokers. A total of 330 subjects developed incident venous disease during follow-up. α 1 -blocker use was associated with a 43% higher risk of venous disease (RR = 1.43, AR% = 30%, NNH = 5.8); however, this association was not statistically significant (Fisher’s test, p = 0.27; 95% CI 0.6–7.1). To assess whether α 1 -antagonist use was associated with self-reported venous symptoms, we performed a cross-sectional analysis of 1,056 individuals, of whom 25 were taking an α 1 -blocker and 534 had venous disease. The mean age was 70 years; 67% were female, 10% had DM, and 67% were never-smokers. We did not find a significant association between α 1 -blocker use and reports of any venous disease symptoms (p = 0.34), although the trend was positive (OR = 1.52). However, we found that α 1 -antagonist use was associated with higher odds of restless legs (OR = 3.3; p = 0.073; 95% CI: 0.73–10.94). Suggestive but non-significant positive associations were also found for leg swelling (OR = 1.87; p = 0.29) and burning (OR = 2.67; p = 0.38). Conclusion: Our findings suggest that α 1 -antagonist use may be a risk factor for the development of symptomatic LE venous disease. Further analyses with greater statistical power are warranted to validate this association.
Abstract TH967: Exploring the association between coronary artery calcium score and behavioral and social determinants of subclinical atherosclerosis in an Appalachian population
Background: Coronary artery calcium (CAC) scoring, a noninvasive method for measuring subclinical atherosclerosis, is an early indicator of future cardiovascular events. Although biological/clinical risk factors for CAC are known, the role of behavioral and social determinants of health (SDOH) remains understudied in high-risk population such as those in Central Appalachian. Understanding how these determinants interact with CAC in Central Appalachia will uncover pathways that contribute to premature disease and widening health inequities. This study aims to examine the association between behavioral/SDOH and CAC among asymptomatic adults in the Appalachian region. Methods: Electronic Health Records of patients screened for CAC using CT between 2019 and 2024 were acquired from a health system with 29 facilities across Central Appalachia. The CAC score was the outcome of the study and was assessed as follows: 0 = no CAC, 1-99 = mild CAC, 100-400 = moderate CAC, and >400 = severe CAC. In addition to clinical risk factors for CAC and medication use, data on health behaviors and SDOH were collected. Descriptive statistics and ordinal logistic regression analyses were conducted. We report results of summary statistics along with adjusted odds ratios (aORs), 95% confidence Intervals (CIs), and p-values with a significance ≤0.05 . Results: A total of 8,300 asymptomatic patients with CAC scores were included in the analysis. Of these patients, 51.3% had a CAC score ≥1. For these individuals, mean CAC score was 128.12±128.85. Ordinal logistic regression results show that only health condition significantly associated with increased CAC score was BMI>30 [aOR=1.13, CI: 1.03-1.24]. Among health behaviors examined, smoking was significantly associated with CAC score [Current: aOR = 1.73, CI: 1.51-1.99; Former: aOR=1.40, CI: 1.26-1.55]. Although illicit drug use was positively associated with CAC score, it did not show any difference. Among the SDOH, while being a female significantly reduced the likelihood of a high CAC score by 56% compared to males [aOR=0.44; CI: 0.40-0.49]. Additionally, increasing age was associated with higher CAC score compared to patients aged <30 years. Conclusion: Behavioral/SDOH such as smoking, obesity, and age remain strong drivers of CAC burden, highlighting an urgent need for regionally tailored equity-driven interventions that integrate SDOH screening, behavioral modification, and community-based prevention into cardiovascular care.
A CHKA–PML autophagy checkpoint enables tumors to evade glutamine starvation
Glutamine metabolism is essential for tumor cell proliferation and biosynthesis. However, solid tumors often face chronic glutamine deprivation, and the underlying adaptive mechanisms remain incompletely understood. Here, we show that glutamine scarcity upregulates choline kinase alpha (CHKA), whose monomerization enhances its noncanonical protein kinase activity. CHKA phosphorylates promyelocytic leukemia (PML) at tyrosine 339, promoting its cytoplasmic localization. Notably, this reflects a compartment-specific switch in PML activity: while nuclear PML facilitates protein degradation through Small Ubiquitin-like Modifier (SUMO)-ubiquitin cascades, cytoplasmic PML acts oppositely to block degradation. Specifically, cytoplasmic PML then induces SUMOylation of WD Repeat Domain Phosphoinositide-Interacting Protein 2 (WIPI2) at lysines 281 and 283, thereby blocking HUWE1-mediated ubiquitination and proteasomal degradation. Stabilized WIPI2 increases autophagic flux, supporting tumor cell survival under metabolic stress. This study identifies a critical CHKA–PML–WIPI2 axis mediating adaptation to glutamine deprivation, providing insight into metabolic plasticity and a potential therapeutic target for glutamine-dependent cancers.
Abstract MPTU11: Prediabetes Progression In Young American Adults: A Pooling Project
Introduction: There is growing clinical concern about increases in prediabetes and type 2 diabetes in young adults. Novel weight-loss medications, e.g., glucagon-like peptide-1-receptor agonist (GLP1-RA), can prevent progression from prediabetes to diabetes. Characterizing risk and risk factors for progression to diabetes could help identify high-risk subgroups to prioritize for intensive lifestyle interventions and novel medications in the growing population of young adults with prediabetes. Objective: To characterize 5-year risk and risk factors for progression from prediabetes to diabetes in adults <40 years. Methods: We pooled and harmonized data from participants aged 18 to 40 years with prediabetes (fasting glucose [FG] 100-125 mg/dL) from three cohorts (HCHS/SOL, CARDIA, FHS-Gen3). We used Poisson regression to estimate 5-year risk and age- and cohort-adjusted rate ratios (95%CI) for incident diabetes (FG ≥126 mg/dL or medication use), overall and according to demographics, FG categories (FG 100-109 mg/dL,110-125 mg/dL), and GLP1-RA eligibility criteria for weight loss (body mass index ≥30 kg/m 2 or body mass index ≥27 kg/m 2 with dyslipidemia or hypertension) during a median follow-up of 6.2 years. Results: The 610 young adults with prediabetes had a mean age of 32 (SD, 6) years, 32% were women, and 38% self-identified as Hispanic/Latino. The 5-year risk of progression from prediabetes to diabetes was 8.7% (95%CI: 6.6, 10.8) ( Table ). The 5-year risk of diabetes for young adults with prediabetes who met GLP-1RA eligibility criteria for weight loss was 14.0% (95% CI: 9.9, 18.1), and for those with FG between 110 to 125 mg/dL was 21.5% (95% CI: 14.1, 29.0). The 5-year risk of diabetes was highest for young adults who met GLP1-RA eligibility criteria and FG between 110 to 125 mg/dL (36.1%), which was ~5-times (95% CI: 2.8, 8.6) the risk for those meeting neither criteria. Conclusion: In young adults with prediabetes, we identified subgroups with elevated risk of progression, with a 5-year diabetes risk of 33% in the highest risk group. This highlights opportunities for targeted approaches for intensive lifestyle and pharmacologic interventions for diabetes prevention.
Abstract TU99: Changes in DNA methylation-based biological aging predict structural and vascular brain damage in older adults: Age, Gene/Environment Susceptibility - Reykjavik Study
Background: DNA methylation (DNAm)-based biological aging (BA) is linked to poor structural and functional brain integrity, but prior studies often had small samples, cross-sectional designs, or focused narrowly on specific brain health indicators. We examined whether changes in BA are associated with multiple domains of brain health. Methods: Data were drawn from the Age, Gene/Environment Susceptibility–Reykjavik Study (AGES-RS), including participants with DNAm, MRI, and cognitive data (baseline mean age = 75.5 ± 4.8 years; 57.6% women). DNAm was assayed using the Illumina Infinium MethylEPIC array. Brain volumes and infarcts were measured by MRI, and cognition by standard tests. BA pace was estimated with DunedinPACE (DDPACE; >1 = faster aging). Baseline data (2002–2006) included 2,602 individuals, with 2,081 re-examined after ~5 years. Associations between baseline DDPACE and brain volume, infarcts, and cognition at follow-up were analyzed, adjusting for age, sex, education, batch, and blood cell composition. DDPACE and continuous outcomes were standardized. Additionally, mediation analyses tested whether baseline DDPACE mediated associations between midlife lifestyle (e.g., smoking) and health factors (e.g., total cholesterol), their composite score (Life’s Simple 7), and late-life brain outcomes (mean age = 81 ± 4.8 years). Results: Higher baseline DDPACE was inversely associated with white matter (WM, β=-0.14, 95% CI -0.19 – -0.09), gray matter (GM, β=-0.09, -0.14 – -0.05), and total brain volume (TBV, β=-0.12, -0.17– -0.08), and positively with WM lesions (WML, β=0.06, 0.01–0.11) at follow-up, all P<0.05. Associations remained significant after adjusting for baseline brain volumes, except WML. Higher baseline DDPACE also predicted poorer cognition (e.g., processing speed β=-0.10, -0.14 – -0.05, P<0.001) and greater brain infarct risk (OR=1.22, 1.07–1.39, P<0.01). Participants who shifted to faster aging (>1 SD above mean at follow-up) had higher WML (β=0.05, 0.01–0.09, P<0.01). Mediation analyses indicated that DDPACE accounted for 18.9–30.7% of the association between midlife smoking and late-life WM, GM, TBV, and WML, and 15–18% of the LS7 effect on these outcomes (all P < 2.2×10 -16 ). Conclusion: A DNAm-based biomarker of aging predicts brain damage and mediates the association of midlife cardiovascular health-related risk factors with late-life brain health.
Abstract 50: Extending the Observational Medical Outcomes Partnership Common Data Model to Harmonize Dietary Exposure Survey Questions Across Studies
Introduction: Numerous dietary assessments and scores in survey format have been used in cardiovascular disease (CVD) research jointly with study participants’ EHR data. While harmonization of EHR data across institutions has been facilitated through established Common Data Models (CDMs), equivalent methods for harmonizing dietary exposure survey questions remain underdeveloped. Currently, investigators must undertake labor-intensive, study-specific remapping efforts. Moreover, treating each food item as a distinct question generates hundreds of variables, a number that increases exponentially when qualifiers such as portion size, food frequency, or preparation method are included. Methods: We compiled four dietary survey instruments used in CVD studies (Mediterranean Diet Score, AHEI, DASH, and FFQ) and applied fuzzy matching, sentence embeddings, and large language model (LLM)-assisted inference to map survey questions to the NIH Common Data Elements (CDEs). To address low direct mapping rates against NIH CDEs, we developed a new dietary exposure table within the Observational Medical Outcomes Partnership (OMOP) CDM, a widely adopted community standard for observational health data. The proposed relational database table includes fields such as dietary concept, dietary exposure duration, exposure unit, frequency, frequency per day, quantity concept, quantity per day, dietary preparation method, and family relation. Mapped dietary questions were then represented as rows in this table. Results: Direct mapping of dietary survey questions to NIH CDEs achieved less than 10% coverage. Incorporation of the new dietary exposure table increased mapping coverage to over 80%. All introduced columns were standardized using SNOMED vocabulary concepts via embedding and LLM-based mapping. Approximately 99% of item fields conformed to a frequency–quantity composite schema, enabling normalization into a single occurrence table and reducing more than 1,500 raw survey variables into a concise, query-ready dataset. The total runtime of mapping was 4 hours with GPUs. Conclusion: We developed a dietary exposure table within OMOP CDM format to represent, store, and harmonize dietary exposure survey questions and responses using embeddings, LLM, and SNOMED. This extension enables both syntactic and semantic interoperability of dietary data, substantially simplifying cross-study integration and facilitating large-scale, comparative nutrition research across diverse data sources.
Abstract TH808: Culturally Tailored Positive Psychological Intervention in a Cluster-Randomized Trial of Blood Pressure Reduction in Spanish-Speaking Hispanics/Latinos with Uncontrolled Hypertension
Introduction: Positive psychological interventions (PPIs) have demonstrated benefits for mental health and health behaviors, but their effects on physiologic cardiovascular outcomes remain underexamined. We tested whether ¡Alégrate! , a culturally adapted, church-based PPI, lowers blood pressure (BP) and promotes medication adherence in Spanish-speaking Hispanic/Latino adults with uncontrolled hypertension. Hypothesis: We hypothesized that ¡Alégrate! participants would show greater BP reductions and better adherence than controls, with stronger effects among those attending more sessions. Methods: In a cluster-randomized controlled design (six urban-area churches), 96 adults (51 intervention, 45 control) with uncontrolled hypertension (2017–2019) were enrolled. Medication adherence was assessed using the 8-item Morisky Medication Adherence Scale, and seated blood pressure (mm Hg) was measured objectively following a standardized protocol. The 8-week, group-based curriculum was delivered in Spanish and embedded cultural values (familism, religiosity). Core modules included mindfulness, gratitude, positive reappraisal, and goal setting to promote psychological well-being. Assessments occurred at baseline, 8 weeks, and 12 weeks. We used linear mixed models with random intercepts to estimate fixed effects of group, time, and their interaction, and conducted exploratory dose–response analyses by attendance. Results: Group × time interactions for systolic and diastolic BP did not reach statistical significance ( p = 0.09 and 0.07), though both trended toward improvement in the intervention arm. At 8 weeks, mean systolic BP decreased by –5.8 mm Hg ( p = 0.045) and diastolic BP by –4.0 mm Hg ( p = 0.065) versus control; effects attenuated by 12 weeks. In exploratory analyses, participants attending ≥ 6 sessions maintained more stable BP trajectories. No between-group differences were observed in medication adherence. Conclusions: In this pilot community-based trial, a culturally tailored PPI produced short-term systolic BP reductions in Spanish-speaking Hispanic/Latino adults with uncontrolled hypertension. These findings support the potential of positive psychological approaches to reduce hypertension disparities. Larger, longer trials are needed to confirm and extend these effects.
Abstract TU125: Lessons Learned from Assessing Body Composition in 24-Month-Old Children Using Air Displacement Plethysmography
Background: The pediatric option of BOD POD Body Composition System (COSMED USA) utilizes air displacement plethysmography to provide a fast, non-invasive assessment of body composition; however, its feasibility and operational challenges in young children are poorly documented. Understanding rates of and factors influencing successful measurement are essential for planning future studies. Objective: To describe the feasibility of body composition assessment using the Bod Pod in 24-month-old children, comparing completers with non-completers, and summarizing lessons learned. Methods: This descriptive study included 47 children (23–24 months; 42.6% girls). Parents consented to BOD POD assessment of their children, including a maximum of three trials assessing body volume. Assessment outcome was categorized as refusal, attempted test without a result (e.g., error message), or completed test with a computed result by the device. The technician recorded movement and crying/vocalization in each trial. Group comparisons used permutation t-tests and chi-squared tests. The coefficient of variation across repeated body volume measurements assessed device precision. Results: Of the 47 children, 33 (70.2%) entered the chamber for at least one attempt, while 14 (29.8%) refused. Only 23 (48.9%) obtained a computed result; ten had invalid data due to insufficient trials (n=9) or error message (n=1). Completers had higher BMI-for-age z-score (difference, 0.45; 95% CI, 0.02–0.89) than non-completers. No other differences were observed between groups (Table). Most children remained quiet without crying/vocalization events (78.3–91.3% across trials), but movement was frequent, with only 13–26% remaining still in each trial (Figure). Despite this, device precision was high, with a low coefficient of variation across the body volume measurements (mean 0.3 ± 0.2%, range 0.1–0.7%). Conclusion: Feasibility of BOD POD measurements in 24-month-olds was low, with only half completing tests with computed results. Refusal to enter and insufficient trials were the main barriers. Although most children did not cry/vocalize, movement was typical. For those who completed all trials, the method proved precise despite motion, though accuracy could not be assessed. Future studies could include familiarization strategies to enhance feasibility and should plan for larger sample sizes to account for non-participation.
Abstract TU167: A Culturally Competent Journey in Nutrition Education
Introduction: Nutrition education is a key strategy in combating obesity and heart disease. The purpose of this exploratory study was to implement A Taste of African Heritage (ATOAH), a culturally relevant nutrition and cooking intervention designed to increase knowledge and promote healthier eating behaviors among aging African American women. The following research questions were examined: (1) How does a 6-week culturally relevant program influence the intake and adoption of fruits and vegetables, and whole grains? (2) How does a 6-week culturally relevant program impact meal planning and cooking confidence? Methods: 16 African American women (M age 76.7 years) across two assisted living communities were recruited via flyers and brochures for this six-week study. Women between the ages of 60 and 75 who expressed an interest in cooking. An adapted version of the ATOAH intervention was conducted over a six-week period with weekly two-hour sessions. Each session included a nutrition lesson, recipe demonstration, group discussion, and hands-on tasting. The USDA Food Frequency questionnaire was administered pre and post intervention to evaluate changes in fruit, vegetable and whole grain intake (Willett et al., 1985). Data Analysis/Results: A subsample (n=8) completed both pre and post intervention survey measures. Descriptive statistics were used to calculate pre- and post-intervention percentages to assess changes in participants’ dietary behaviors. At baseline, 25% of participants reported consuming fruit at least once per day, which increased to 62.5% at posttest, a 37.5 percentage point improvement. Vegetable intake also increased, with 12.5% consuming green salad more than once per week at baseline, which increased to 50% post-intervention. Whole grain consumption also showed positive change, increasing from 12.5% to 37.5% of participants reporting intake more than once per week, a 25-percentage point increase. Cooking confidence also improved, with 12.5% of participants initially reporting they were “somewhat confident” in using healthy ingredients from the program in a meal, increasing to 20% post-intervention. Conclusion: Improvements in fruit and vegetable intake among aging African American women, suggest that the additional considerations for a culturally tailored nutrition education may show greater promise in promoting dietary behavior change than traditional intervention approaches.