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Abstract TH803: Depression and Cancer History Interact to Exacerbate Clinical Cardiovascular Disease Burden Within the Cardiometabolic–Kidney Framework Among US Women, 2017–2024 Behavioral Risk Factor Surveillance System

Circulation Julianne Mercer, Benjamin Encino, Laurajo Ryan et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th803

Introduction: Women show a stronger depression-cardiovascular disease (CVD) link yet receive 20% less guideline-directed cardiopreventive care. Using nationally representative data, we estimate how depression modifies the cancer-CVD association in women on synergistic scales within the cardiometabolic-kidney (CKM) disease framework. We hypothesized that comorbid cancer and depression yield excess absolute risk of clinical CVD-in-CKM beyond the sum of their independent effects. Methods: We analyzed pooled 2017–2024 Behavioral Risk Factor Surveillance System data for adult women with cancer (excluding skin). Clinical CVD-in-CKM was defined per the 2023 AHA CKM framework as self-reported myocardial infarction, stroke, or coronary heart disease among those with prediabetes/diabetes, kidney disease, or overweight/obesity. Age- and year-adjusted prevalence estimates and multivariable logistic regression models assessed cancer-CVD associations. Additive interaction quantified the joint effects of cancer and depression overall and by age, income, and race using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S). Analyses accounted for the complex survey design. Results: Among 84.4 million women (n=1,242,574), 8.6% (95% CI 8.5–8.7) reported cancer history. Depression was more common in women with cancer than without (30.5% vs 25.8%; p<.001). Adjusted prevalence of clinical CVD-in-CKM was higher in women with cancer than without (9.5% vs 5.6%; p<.001). Among survivors, overweight/obesity (66.4%), diabetes (18.5%), and kidney disease (8.6%) were the most common CKM components. Cancer history was linked to 42% higher odds of clinical CVD-in-CKM (aOR 1.42; 95% CI 1.35–1.49; p<.001). The cancer×depression interaction term showed excess joint risk (RERI=0.92; AP=0.22; S=1.4) (Figure 1). About 22% of the CVD-in-CKM burden among women with both exposures was attributable to their interaction. The combined impact of both exposures was strongest among younger, higher-income, Hispanic, and other race/multiracial women, with smaller but positive combined effects in older and lower-income groups. Conclusion: Depression and cancer synergistically increased CVD-in-CKM burden, producing greater-than-expected risk among U.S. women. These findings emphasize the need for integrated cardiometabolic and psychosocial risk management in female cancer survivors.

Abstract WE405: Atrial Fibrillation and Late Onset Epilepsy: Evidence of Bidirectionality in the Atherosclerosis Risk in Communities Study

Circulation Faye Norby, Peter Husnik, Alvaro Alonso et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we405

Introduction: Atrial fibrillation (AF) and late onset epilepsy (LOE) are common conditions, particularly among older adults. These conditions have several shared risk factors, and there is mechanistic evidence that epilepsy can lead to cardiac dysfunction and vice versa. We conducted a population-based study to investigate this potential bidirectional association between AF and LOE. Methods: A total of 15,792 ARIC participants were followed from baseline (1987-1989) to 2022. At baseline, we excluded those with conduction disorders, those on anti-arrhythmic medications, those with prevalent AF and LOE events, and those with events within 2 years of baseline. AF and LOE were identified through active surveillance, primarily using ICD codes. AF and LOE were modeled as time-dependent exposures, and covariates were measured at baseline or updated throughout follow-up when modeled as incident mediators. We used Cox proportional hazards models to assess the association with each incident outcome, adjusting for demographics and cardiovascular disease (CVD) risk factors. Results: After exclusions, our analysis included 15,138 participants (26% black race, 55% female, mean age 54). In demographic and CVD risk-factor adjusted models (Table, Model 3), AF was associated with a 2.09 times higher risk of LOE (95% CI: 1.72-2.53). After additional adjustment for incident CVD, the risk was attenuated but remained significant [HR (95% CI): 1.38 (1.12-1.70]. In Model 3, LOE was associated with a 1.71 times higher risk of AF (95% CI: 1.40-2.09). After adjustment for incident CVD, the risk was attenuated but remained significant [HR (95% CI): 1.24 (1.01-1.52)]. Conclusion: In this population-based cohort, there was a bidirectional association between AF and LOE, even after adjustment for incident CVD, supporting a shared mechanistic pathway hypothesis.

Abstract TH937: Utilizing Life's Essential 8 for Hypertension Management Among Black Patients at a Federally Qualified Health Center (FQHC)

Circulation Nishka Dalal, Caroline Metz, Bowen Kim et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th937

Introduction: Hypertension (HTN), a leading cause of preventable mortality, disproportionately affects marginalized communities due to persistent healthcare disparities and socioeconomic barriers. Less than half of patients with HTN achieve blood pressure (BP) control, with Black Americans experiencing lower rates of control (34.9%) than non-Hispanic White Americans (45.0%). This pilot study evaluates the effectiveness of a telephone-based outreach intervention designed to improve BP control through self-management in a historically underserved population. Methods: A pre-post, single cohort telephone-based quality improvement study was conducted from August 2024 to January 2025 at a Federally Qualified Health Center (FQHC). Patients with uncontrolled hypertension were contacted by trained student ambassadors (SAs) who delivered Life's Essential 8 hypertension education, lifestyle goal-setting guidance, BP self-monitoring support, and facilitated referrals to address health-related social needs (HRSN) during a series of three calls. During in-person “Hypertension Heroes” classes, patients who requested them received BP monitors and education on self-monitoring BP and lifestyle modification. Results: Of the 333 Black patients with uncontrolled hypertension (mean age = 58 years; 52.3% female, 47.7% male), 570 call attempts were made. Of these, 117 patients completed Call 1, 40 completed Call 2, and 13 completed Call 3. At baseline, 61 participants reported owning a BP cuff, while 36 expressed interest in obtaining one. The cohort’s mean systolic and diastolic blood pressures were 162.51 mmHg (SD = 13.00) and 90.75 mmHg (SD = 14.01), respectively. Among patients with complete post-intervention data (n=50, 43%), the mean systolic BP decreased from 161.62 mmHg to 146.14 mmHg (Δ = -15.48 mmHg, 95% CI -22.40 to -8.56) and diastolic BP decreased from 86.18 mmHg to 83.46 mmHg (Δ = -2.72 mmHg, 95% CI -7.63 to 2.19), suggesting meaningful systolic improvements. In addition, 60 referrals were placed to address HRSN, and 170 patients participated in one or more in-person hypertension-related events. Conclusions: Results show that integrating telephone outreach, clinician-led classes, and resource navigation can meaningfully reduce BP among Black patients. Participants reported improvements in self-managing BP, achieving lifestyle goals, and obtaining resources for HRSN. Future research should assess long-term sustainability, engagement strategies, and cost-effectiveness.

Role of FePt grain size on writing performance for next-generation magnetic recording technology

Scientific Reports Khanitta Yuanmae, Mara Strungaru, Wasan Pantasri et al. Mar 24, 2026 DOI: 10.1038/s41598-026-45522-0

Task-evoked functional connectivity exhibits novel and strengthened relationships with executive function relative to the resting state

Proceedings of the National Academy of Sciences Mackenzie E. Mitchell, Eric Feczko, Damien A. Fair et al. Mar 24, 2026 DOI: 10.1073/pnas.2516929123

Executive functioning in children has been linked to intrinsic brain network organization assessed during the resting state, as well as to brain network organization during the performance of cognitive tasks. Prior work has established that task-based brain networks are stronger predictors of behavior than resting state networks, yet it is unclear if tasks only strengthen relationships that exist weakly at rest or if tasks also evoke unique relationships. A lack of discernment regarding how tasks and the resting state commonly and uniquely support executive functions precludes a holistic understanding of the neurobiological basis of executive functions. This project investigated differences in brain network organization and relationships with executive function ability between the resting state and two executive function tasks, a stop signal task and an emotional n-back task, using the Adolescent Brain and Cognitive Development Study dataset. Both executive function tasks evoked a more integrated network organization than the resting state, and executive function ability was related to different aspects of brain network organization during the resting state and during the tasks. Further, task-related shifts in brain network organization evoked several new relationships with executive function that were not detectable during the resting state and strengthened a relationship with executive function that existed weakly during the resting state. Overall, this study establishes a distinction between common and unique features of intrinsic and task-evoked brain function that facilitate executive function in children.

Abstract TH971: Life’s Essential 8-Based Models Predict Subclinical Cardiovascular Disease And Are Not Strengthened by the Inclusion of Social Determinants of Health

Circulation Jordan Sill, Elaine Urbina, Jessica Woo Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th971

Introduction: Life’s Essential 8 (LE8) is validated method of quantifying cardiovascular health (CVH). Although SDoH impact CVH, LE8 lacks direct SDoH measures. Hypothesis: We hypothesized that adding SDoH metrics would enhance subclinical CV disease (SCVD) prediction beyond LE8 alone in a cohort of Black and White women in mid-life. Methods: We analyzed 219 women (mean age 46±1 years; 54% Black) from the NHLBI Growth and Health Study. Anthropometrics and laboratory evaluation were performed. Participants completed validated questionnaires related to SDoH (education, income, Early Trauma Inventory (ETI), Everyday Discrimination Index (EDI), Relationship Satisfaction Survey, Perceived Stress Scale (PSS) and PROMIS Psychosocial Scales). Current addresses were geocoded for place-based measures of SDoH (Deprivation Index (DI), median neighborhood rent, Enhanced Vegetation Index for green spaces and environmental particulate matter). SCVD was assessed via carotid IMT, pulse wave velocity (PWV) and left ventricular mass indexed by height 2.7 (LVMI). Variables were log transformed if indicated. Correlations (Pearson or Spearman) and regression models with backward selection were used to identify predictors of SCVD from LE8 and SDoH variables. Results: LE8 (mean overall LE8 score 60.3±17.8) was inversely correlated with adverse SDoH including logDI, neighborhood rent, logETI, PSS, and PROMIS scores - anxiety, depression, global pain, social isolation, and fatigue (p<0.01 for all). Positive correlations were observed with education, income, friendship quality, and social roles (p<0.01 for all). LE8 was inversely correlated with SCVD: logIMT, logPWV, LVMI (p<0.01 for all). SCVD measures also correlated with SDoH. Greater logIMT was correlated with lesser education, greater logDI and PROMIS sleep disturbance score (p<0.05 for all). Greater logPWV was correlated with greater logETI, EDI, PSS, and PROMIS scores for anxiety, depression, and friendship quality (p<0.05 for all). LVMI was correlated with lower PROMIS global pain (p<0.01). In regression analyses, lower LE8 was a significant predictor of all measures of SCVD. No SDoH remained significant in final models. Conclusions: LE8 was significantly associated with both SDoH and SCVD. While multiple SDoH measures correlated with SCVD, none improved the explanatory power of LE8-based models. Future work should explore alternative SDoH constructs or modeling approaches to better capture their contribution to CVH.

Abstract 48: Echocardiogram Video Vision Foundation Model (Echo-Vision-FM): A Pre-training and Fine-tuning Framework for Automated Echocardiogram Analysis

Circulation Jiancheng Ye, Ziyang Zhang, Qinxin Wu et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.48

Introduction: Echocardiography is essential for cardiac assessment, yet interpretation requires substantial expertise and suffers from inter-observer variability. Current AI approaches often rely on limited labeled data or process individual frames rather than full videos. Objective: To develop Echo-Vision-FM (Echocardiogram Video Vision Foundation Model), a self-supervised video foundation model designed to enhance automated echocardiographic analysis across diverse clinical tasks. Methods: We pre-trained a video encoder using masked auto-encoding on 525,328 unlabeled echocardiogram videos from the MIMIC-IV-ECHO dataset. A novel Spatial-Temporal Fusion Network (STF-Net) was developed to integrate spatial and temporal correlations from learned representations. The model was evaluated on three downstream tasks: (1) cardiac morphological value estimation (LVEF, LVESV, LVEDV), (2) heart function diagnosis (LVEF classification), and (3) aortic stenosis severity assessment. Performance was validated on external datasets including EchoNet-Dynamic (n=10,030), CAMUS (n=500), and TMED-2 (n=599). Results: Echo-Vision-FM achieved superior performance across all tasks. For LVEF estimation, the model attained MAE of 3.87% and R-squared=0.825 on EchoNet-Dynamic, and MAE of 4.42% with R-squared=0.658 on CAMUS, outperforming state-of-the-art segmentation-based and supervised methods. For heart function diagnosis using LVEF threshold of 50%, the model achieved accuracy=0.905, AUC=0.931, and F1=0.941 on EchoNet-Dynamic. For aortic stenosis classification, AUC reached 0.849. The addition of STF-Net consistently improved performance across all tasks compared to the encoder alone (all p<0.05). Linear probing experiments demonstrated strong transferability of learned representations even with limited labeled data. Conclusions: Echo-Vision-FM represents the first echocardiogram video foundation model trained exclusively on publicly available data, demonstrating robust performance across multiple institutions and clinical scenarios. This self-supervised approach addresses the annotation bottleneck in medical AI while providing a scalable, end-to-end solution for comprehensive cardiac assessment with significant potential for clinical implementation.

Abstract TH810: PILI Aina: A Multilevel, Culturally Grounded Intervention to Improve Diet and Cardiometabolic Health in Native Hawaiian Homestead Communities

Circulation Claire Ing, Adrienne Dillard, Chantal Keliihoomalu et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th810

Background: Native Hawaiians (NHs), especially those living on homesteads, face disproportionate burdens of obesity, type 2 diabetes, hypertension, and dyslipidemia. Structural inequities and reduced access to healthy foods contribute to these disparities. Partners for Improving Lifestyle Intervention (PILI) Aina (land) is a multilevel intervention designed to improve diet and cardiometabolic health by integrating individual, household, and community strategies rooted in NH culture. Methods: At the individual and household level, we are conducting a group-randomized trial with 180 NH adults who have overweight or obesity and at least one cardiometabolic condition. At the individual level, all participants complete a 3-month, culturally adapted Diabetes Prevention Program–Lifestyle Intervention. Individuals are then randomized. They and their household receive either standard follow-up or PILI Aina, which includes raised-bed gardening, family goal setting, and monthly cooking and cultural lessons. The PILI Aina primary outcome is changes in overall diet quality (e.g., Healthy Eating Index score). Secondary outcomes include changes in weight, BMI, blood pressure, HbA1c, lipid profiles, physical activity, household food patterns, and social cohesion. Homestead communities also implement Ai Pono (healthy eating), community-wide, quarterly cooking demonstrations of healthy diets with cultural teachings. The Ai Pono outcomes are social cohesion and household food patterns. Data are collected at baseline, 3, 9, and 12 months (PILI Aina) and annually across communities (Ai Pono). Results: Enrollment and implementation are ongoing. Pilot data support feasibility and suggest improvements in diet, weight, blood pressure, and activity. Early Ai Pono events have been widely attended and enthusiastically received. Conclusions: This multilevel intervention combines household and community strategies to reconnect NH on homestead lands with cultural ideas related to eating and food, boost fruit and vegetable intake, and enhance cardiometabolic health. PILI Aina is among the first NH-specific trials to blend an evidence-based lifestyle curriculum with a home gardening and cooking program focused on food sovereignty. By embedding the intervention within NH homestead communities and aligning with cultural principles of ohana (family) and malama aina (caring for the land), we expect strong community engagement and sustainability.

A vision transformer model for the detection of glaucoma from optic disc photographs

Scientific Reports Ella Bouris, Brayden K. Leyva, Ojo Perpetua Odugbo et al. Mar 24, 2026 DOI: 10.1038/s41598-026-44662-7

Abstract This study uses a deep learning algorithm to analyze optic disc photographs (ODPs) and classify eyes as glaucomatous or healthy based on optic nerve appearance. ODPs from three databases were independently graded by two glaucoma specialists. Images were preprocessed using the open-source language R and RimNet, a deep learning model for optic disc segmentation, to prepare inputs for training. The model was developed with Python based on Google’s Vision Transformer (ViT). After assessing the ODPs, the model provided an output between 0 and 1 to predict glaucoma likelihood (≥ 0.5 signified glaucoma). Model performance was evaluated using the area under the receiver operating curve (AUC), where 1 indicates perfect classification. A total of 1,432 glaucomatous eyes with a mean MD of − 2.09 dB were analyzed using the model. The model achieved AUCs of 1.00, 0.98, and 1.00 in the training, validation, and test phases respectively. Overall accuracy in test images was 0.987, sensitivity was 0.994, and specificity was 0.969 with grader labels as the ground truth. A later assessment using 956 advanced glaucomatous eyes (MD < − 6 dB) with a mean MD of − 11.71 reached 99.9% accuracy. The model demonstrated high accuracy in detecting glaucomatous optic nerve damage from ODPs. The model’s strong potential for early disease detection suggests that deep learning can be a valuable, cost-effective tool in glaucoma screening, especially in resource-limited regions. Our study demonstrates the potential of deep learning in providing accessible, early-stage glaucoma detection, supporting global efforts to prevent vision loss.

Insights into cephalochordate genome and gene evolution from the early-diverging amphioxus <i>Asymmetron lucayanum</i>

Proceedings of the National Academy of Sciences Yifan Ren, Zepu Miao, Che-Yi Lin et al. Mar 24, 2026 DOI: 10.1073/pnas.2521280123

Cephalochordates (amphioxus or lancelet) are considered as living proxies for ancestral chordates due to their key phylogenetic position and slow evolutionary rate. The genomes of living amphioxus thus can help to reveal the genetic basis shaping the evolutionary transition from nonvertebrate animals to vertebrates. To gain a comprehensive understanding of the genome architecture in amphioxus, we generated a chromosome-anchored genome assembly for Asymmetron lucayanum , representing the earliest diverging cephalochordate genus. We show that Asymmetron has an enlarged genome compared to those of the other four cephalochordate genomes decoded so far (all in the genus Branchiostoma ), caused by pervasive expansions of intergenic transposable elements (TEs). Nevertheless, both macrosynteny and microsynteny remain highly conserved between Asymmetron and Branchiostoma , enabling reconstruction of the ancestral genomic architecture of the cephalochordate lineage for tracing genome evolutionary processes during deuterostome and chordate diversification. Integration of developmental transcriptomic data further reveals that selective constraints on cotranscriptional regulation underline the maintenance of the conserved microsynteny blocks among cephalochordate species. We also examine the evolutionary history of the Hox cluster in cephalochordates and vertebrates, and identify species-specific inversions and TE invasions at this locus in both Asymmetron and Branchiostoma . Finally, we survey key molecular building blocks underlying both innate and adaptive immunity (e.g., TLR , NLR , MHC, and RAG ) and uncover their evolutionary dynamics and plausible ancestry in chordates. Taken together, our findings illuminate the genome and gene evolution of cephalochordates and provide valuable resources for understanding the early evolution of chordates and the origin of vertebrates.

Abstract TH850: Explainable Digital Twins for Noninvasive Echocardiographic Reconstruction of Left Ventricular Pressure-Volume Loops

Circulation Dang Nghiem, Tram Le, Dang Nguyen et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th850

Introduction: Pressure-volume (PV) loops are central to characterizing ventricular function but typically require invasive catheterization. Apical four-chamber (4CH) echocardiography is noninvasive and widely available, yet routine metrics such as ejection fraction (EF) omit pressure information and limit mechanistic insight. Hypothesis: Building on the existing physics-informed self-supervised learning framework (Med-Real2Sim) for medical digital twins, we hypothesize that our targeted explainable improvements in synthetic data generation with physiologic filtering, pretext/interpolator modeling, and the PSSL framework optimization would reduce EF error while yielding physiologically consistent and clinically interpretable parameter attributions. Methods: We conducted a retrospective model development using the public CAMUS dataset with reference end-diastolic volume (EDV), end-systolic volume (ESV), and EF. First, a “pretext” stage generated 1,450 synthetic cardiovascular parameter sets that were retained; a differentiable interpolator was then trained to map these parameters to EDV/ESV. Next, a deep video network ingested each 4-CH cine and predicted seven patient-specific parameters—cycle duration, starting ventricular volume, maximum and minimum elastance, mitral and aortic valve resistances, and the zero-pressure volume. The primary endpoint was mean absolute error (MAE) in EF compared with the echocardiographic reference. Model interpretability was assessed with Shapley additive explanations (SHAP) at both the interpolator and full pipeline levels to quantify the contribution of each parameter to EDV, ESV, and EF. Results: In the synthetic pretext set, the interpolator achieved an EF MAE of 1.34% (as compared to 2.30% reported in the previous work). In end-to-end testing on CAMUS, we achieved a test EF-MAE of 6.37%, which was modestly better than the supervised 3D-CNN baseline (6.58%). Explainability analyses were clinically coherent: maximum elastance and cycle duration were the principal drivers of EF, zero-pressure volume ranked next, and valve resistances contributed modestly. These patterns align with cardiovascular physiology. Conclusions: our proposed explainable digital-twin pipeline built on 4-CH echocardiography reconstructed PV loops and estimated EF fraction with competitive accuracy. These findings support the feasibility of bedside hemodynamic phenotyping from echocardiography in settings where invasive data are unavailable.

Abstract TU176: Differential Impacts of Wild Blueberry Consumption on Cardiometabolic Health in Middle-Aged/Older Adults with Above-Normal Blood Pressure

Circulation Nancy Ghanem, Sylvia Lee, Emily Woolf et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu176

Background: Evidence suggests polyphenol-rich wild blueberry (WBB) consumption can improve cardiovascular health, but research in middle-aged and older adults with above-normal blood pressure (BP) is needed. Objective: Our study investigated the impact of 12 weeks of daily WBB consumption on vascular function (i.e., endothelial function, arterial stiffness), BP, blood biomarkers, and gut microbiota composition in adults with above-normal BP. Methods: In a randomized, double-blind, placebo-controlled, parallel-arm trial, postmenopausal women and men aged 40–75 y with elevated BP or stage-1 hypertension (HTN) (i.e., systolic BP 120–139 and/or diastolic BP (DBP) 80–89 mmHg) were randomized to consume either 22 g/d freeze-dried WBB powder or isocaloric placebo for 12 weeks. Endothelial function (primary outcome) was assessed using reactive hyperemia index (RHI) and Framingham RHI (fRHI). Secondary outcomes included arterial stiffness (carotid–femoral pulse wave velocity, augmentation index), brachial and aortic hemodynamics, cardiometabolic biomarkers, and gut microbiota composition. Outcomes were assessed at baseline and 12 weeks using linear mixed-effects models including treatment, time, and their interaction, with covariates retained via backward elimination. Alpha- and β-diversity, and differential abundance analyses assessed community structure and taxa associations. Results: Of 52 participants randomized, 44 completed the study (WBB = 24; placebo = 20; ~96% compliance/group). Participants were 57 ± 1.41 y, 34% female, and 64% with HTN. There were no main or interaction effects on RHI or fRHI. Aortic pulse pressure increased after 12 weeks of WBB consumption compared to placebo (+2.97 mmHg; 95% CI 0.29, 5.67). Within-group, placebo participants had increases in brachial DBP (+2.32 mmHg; 95% CI 0.16, 4.48), aortic DBP (+2.87 mmHg; 95% CI 0.39, 5.36), mean arterial pressure (MAP) (+2.61 mmHg; 95% CI 0.07, 5.15), AIx (+3.27%; 95% CI 0.15, 6.40), and AIx@75 (+4.68%; 95% CI 1.66, 7.70), but not in WBB group. AIx@75 at Week 12 was higher in placebo group compared to WBB (+4.99%; 95% CI 0.29, 9.69). β-diversity analyses showed main effect of treatment on overall community composition (PERMANOVA R 2 = 0.03, p = 0.048). Conclusions: Daily WBB consumption for 12 weeks did not improve vascular function, though data suggest it attenuated increases in DBP, MAP, and AIx indices, suggesting potential cardiovascular-protective effects and warranting further investigation.

Abstract TH966: Allostatic load and subclinical atherosclerosis in young adults

Circulation Fangqi Guo, Xinci Chen, Lora Whitfield et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th966

Introduction: Allostatic load (AL) is a composite measure of multisystem physiological dysregulation. Elevated AL has been identified as a precursor to cardiovascular and metabolic diseases in older adults, but its role in young adults remains unclear. Methods: In this cross-sectional study, we examined the association between AL and three markers of subclinical atherosclerosis among 304 young adults (mean age=25.1 years) participating in the MetaAir2 study from 2018 to 2025. AL score was generated from 14 biomarkers representing four physiological domains: 1) HPA axis and sympathetic nervous system: cortisol, epinephrine, norepinephrine; 2) Inflammatory system: C-reactive protein, interleukin-6; 3) Metabolic system: BMI, total cholesterol, HDL, HbA1c, glucose, insulin; and 4) Cardiovascular system: systolic and diastolic blood pressure, heart rate. Each biomarker was dichotomized as 1 (high risk; exceeding clinical cut points) or 0 (low risk). System-specific scores were calculated as the mean of dichotomized biomarkers within each system. The four system-specific scores were then summed to generate a total AL score (range: 0–4), with higher values indicating greater physiological dysregulation. Subclinical atherosclerosis was assessed using 3 measures obtained from carotid artery ultrasonography: intima-media thickness (IMT), arterial stiffness (distensibility), and gray-scale median of the intima-media complex (IM-GSM). Associations between AL and subclinical atherosclerosis were evaluated using multivariable linear regression, adjusting for age, sex, race, ethnicity, physical activity, and parental education. Results: Higher overall allostatic load (AL) scores were significantly associated with greater IMT (β=25.5, 95% CI: 8.7, 39.6), lower arterial distensibility (β=-3.9, 95% CI: -5.7, -2.1), and lower IM-GSM (β=-3.8, 95% CI: -7.4, -0.3), indicating that increased physiological wear and tear is linked to thicker arterial walls, reduced elasticity, and greater lipid deposition—characteristics of early atherosclerosis. Further, system-specific analysis indicated that the inflammatory system score was significantly associated with IMT and IM-GSM, the metabolic system was associated with all three markers, and the cardiovascular system was associated with arterial distensibility only. Conclusion: Higher AL scores across multiple physiological systems are associated with greater risk of specific components of subclinical atherosclerosis in young adults.

Utilizing of KNO3, KCl, and NaCl as phase change materials within the refrigerator for energy saving

Scientific Reports Sami Samir, Mahmoud Salem, A. S. A. Mohamed et al. Mar 24, 2026 DOI: 10.1038/s41598-026-41662-5

Abstract Practical experiments were conducted on a home refrigerator with a capacity of 289 L, under hot weather conditions, to improve energy consumption and coefficient of Performance (COP) using several phase change materials (PCMs). A comparison was made between different materials (KNO 3 , KCl, and NaCl) at a mixture ratio of 10% with 90% H 2 O, and using H 2 O. A stainless-steel container with volumes of 1 L and 1.5 L was placed under the evaporator, without sacrificing any space for freezing or cooling. PCM materials have demonstrated their effectiveness in minimizing temperature variations within a refrigeration environment. The results indicate that using a 1 L KNO 3 mixture achieved the most significant improvement, increasing COP by 12.1% and reducing electricity consumption by 8.6%. The KCl mixture came in second place, followed by NaCl, while the least effective was H 2 O. All results showed that PCM contributes to reducing compressor operating periods by up to 7.1%.

Abstract TH983: Endometriosis and Subsequeent Risk of Hyperlipidemia

Circulation Emily Wickens, Bin Yan, Leslie Farland et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th983

Background: Endometriosis affects 11% of reproductive-aged women in the US. Endometriosis has been associated with increased risk of hypercholesterolemia (&gt;240 mg/dL total cholesterol) in the Nurses’ Health Study II (NHS II). Limited research has investigated this finding in a US population-based sample, and expanded beyond total cholesterol to include elevated triglycerides. Methods: We leveraged the Utah Population Database to perform a 25-year retrospective study (1996–2021) of 2,939,380 among reproductive-aged women. Endometriosis cases were identified using electronic health records (ICD 9: 617* and ICD 10: N80*). Using Cox proportional hazard models and generalized linear models, we estimated adjusted hazard ratios (aHRs), risk ratios (aRR), risk differences (aRD) and 95% confidence intervals (CIs) for hyperlipidemia (ICD 9: 272.4* and ICD 10: E78*), comparing women with versus without endometriosis. Results: Among our study cohort, 99,978 (3.4%) were diagnosed with endometriosis; 2,839,402 (96.6%) were without an endometriosis diagnosis over the study period. Hyperlipidemia was more than twice as common in women with endometriosis than those without (12.8% vs 5.1%). Women with endometriosis had a 50% higher aHR (95% CI: 51%, 57%) and a 28% higher aRR (95% CI: 1.26, 1.30) of hyperlipidemia after adjusting for birth year, race/ethnicity, and baseline parity and body mass index. In absolute terms, endometriosis was associated with an additional 3.6 cases (95% CI: 3.4, 3.9) of hyperlipidemia per 100 women after adjustment for important confounding factors. Conclusion: We found a 28% increased risk of hyperlipidemia among women with, versus without, endometriosis. Our results are in line with the NHS II, which found a 22% higher aRR (95% CI: 1.15, 1.31) of hypercholesteremia. Direct comparison of the results is difficult given the use of self-report of hypercholesterolemia in the NHS II versus our use of ICD-codes of hyperlipidemia; and the ability of the NHS II to adjust for additional lifestyle factors, which we were limited in assessing. Given prior evidence that chronic disease risk varies by endometriosis typology (e.g., superficial, deep infiltrating, ovarian endometriomas, and adenomyosis), future research should investigate associations between endometriosis subtypes and hyperlipidemia, in addition to assessing differing risks for the spectrum of lipid abnormalities and considering other important confounding and mediating factors.

Abstract 31: Association of Multiple Dimensions of Sleep with Lifespan Trajectories of Blood Pressure from Childhood through Early Adulthood

Circulation Julio Fernandez-Mendoza, Kaylee Rice, Anthony Rahawi et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.31

Objective: To investigate whether inadequate sleep confers long-term risk on the lifespan trajectories of blood pressure (BP) levels from childhood through adolescence into young adulthood. Methods: A total of 698 participants from the Penn State Child Cohort underwent in-lab polysomnography (PSG) and seated BP measurements at three visits. At visit 1, subjects were children aged 5-12. At the second visit, 5.8 to 13.0 years later (Md=7.4), 421 of them were adolescents aged 12-19 (90%) or young adults aged 20-23 (10%). At the third visit, 12.3 to 23.8 years later (Md=16.2), 307 of them were young adults aged 20-24 (50%) or early adults aged 25-33 (50%). We used growth mixture models to classify each participant’s systolic (SBP) and diastolic (DBP) age-related trajectory into latent classes; non-linear polynomials were included when testing three- and four-class solutions. We tested the longitudinal association of insomnia symptoms (IS), apnea/hypopnea index (AHI), and total sleep time (TST) with each SBP and DBP trajectory. We adjusted these models for sex, age, race/ethnicity, body mass index, anti-hypertensive medication, periodic limb movements, sleep apnea treatment, and time-to-follow-up. Results: SBP latent classes 1 (57.7%) and 2 (39.4%) followed linear trajectories, while class 3 (2.9%) a quadratic trajectory. DBP latent classes 1 (64.6%) and 4 (2.3%) followed quadratic trajectories, while classes 2 (30.9%) and 3 (2.2%) linear trajectories. IS were associated with 7.1 (3.3) mmHg higher SBP levels in class 3 (p=0.03). AHI was associated with 8.5 (4.0) mmHg higher SBP levels in class 3 (p=0.03) and with 3.0 (1.2) and 5.1 (2.6) mmHg higher DBP in classes 2 (p=0.01) and 4 (p=0.04). TST was associated with 2.0 (0.9) mmHg higher SBP levels in class 1 (p=0.03) and with 9.6 (3.5) mmHg higher DBP levels in class 4 (p=0.01). Conclusion: While inadequate sleep is known to acutely elevate BP levels, this study shows that specific sleep dimensions differentially impact the lifespan trajectories of BP levels as children grow into early adulthood. Early screening and interventions on sleep are warranted in order to prevent adverse cardiovascular outcomes later in life.

Abstract 39: Risk Factor Contributions Toward Incident Cardiovascular Disease Among Younger Adults With Short- and Long-Term Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) Risk: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort

Circulation Mohan Satish, joanna Ringel, Ghislaine Jumonville et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.39

Background: The American Heart Association’s PREVENT risk equations estimate both 10-year and 30-year risks for cardiovascular disease (CVD) in younger adults aged 30–59 years. Recent analyses show that many younger adults have low short-term (10-year) risk but high long-term (30-year) predicted CVD risk. However, it is unclear which risk factors can be prioritized for the largest population benefit to mitigate long-term CVD risk within this PREVENT risk strata. Objective: We quantified the contribution of risk factors for incident CVD in younger adults classified as having low short-term risk but high long-term risk by PREVENT within the national REGARDS prospective cohort. Methodology: We included participants 45-59 years of age in the REGARDS cohort without prevalent atherosclerotic CVD (ASCVD) or heart failure (HF) recruited in 2003-07 from the continental United States. We estimated the sex-specific prevalence, age and race adjusted hazard ratios accounting for competing risk of non-CVD death, and the population attributable risk percent (PAR%) for incident CVD associated with hypertension, dyslipidemia, obesity, diabetes, current smoking, chronic kidney disease [CKD], high-sensitivity C-reactive protein (hs-CRP) ≥ 3 mg/dL, and a family history of ASCVD. The prevalence and PAR% were calculated for the low 10-year (&lt; 12.5%)/high 30-year (≥30%) risk group of interest by PREVENT, and stratified by sex. A low 10-year total CVD risk threshold (&lt;12.5%) was defined by a risk percentile method consistent with a low 10-year ASCVD risk (&lt;7.5%). Results: Among 6,761 participants, 1,421 (21.0%) had low 10-year/high 30-year PREVENT risk (703 women and 718 men). Overall, there were 566 incident CVD events over a median follow-up of 14.4 years, of which there 194 incident CVD events occurred in the low 10-year/high 30-year PREVENT risk group. Within the low 10-year/high 30-year PREVENT risk group, the highest PAR% for incident CVD were for hypertension (65%), diabetes (45%), and obesity (35%) in women, in comparison to hypertension (40%), hs-CRP ≥ 3 mg/dL (26%), and dyslipidemia (25%) in men (Table 1). Conclusion: Hypertension is the largest contributor to incident CVD among younger adults with low short-term but high-long term predicted CVD risk, and supports the role of early primary prevention strategies focusing on treating hypertension in this population.

Synthetic lethality between RB-loss and E2F3 inhibition in small cell cancers targeted by pyrimidine synthesis blockade

Proceedings of the National Academy of Sciences Evan R. Abt, Liang Wang, Grigor Varuzhanyan et al. Mar 24, 2026 DOI: 10.1073/pnas.2532814123

Small cell carcinoma is a highly lethal cancer variant often found with neuroendocrine (NE) features, as exemplified by small cell lung cancer and small cell NE prostate cancer (SCPC). A genome-wide CRISPR dependency screen using SCPC models generated through human prostate cell transformation identifies a requirement for the transcription factor E2F3. E2F3 dependency is linked to RB inactivation, a near universal occurrence across small cell cancers. The requirement for E2F3 is shared by RB-deficient cells originating from the prostate, lung, and adnexa. In RB-deficient cancer cells, E2F3 inhibition restrains cell cycle progression, proliferation, and tumor growth in vivo. Inhibition of de novo pyrimidine synthesis limits E2F3 expression and suppresses small cell carcinoma proliferation in culture. Directly or indirectly targeting E2F3 to leverage a pan-cancer synthetic lethality resulting from RB inactivation represents a potential treatment strategy.

Abstract TU277: Ironing Out Risk Using the Women’s Health Initiative Study: Low Ferritin Levels are Linked to Elevated Cardiovascular Risk in Postmenopausal Women

Circulation Shabitri Dasgupta, Elizabeth Helzner, Rose Calixte et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu277

Background: Postmenopausal women face an elevated risk of cardiovascular disease (CVD), the leading cause of death among women. Improving the prediction of adverse cardiovascular events (ACE) in this population requires identifying biomarkers that extend beyond traditional risk factors, while being clinically useful and cost-effective. Ferritin, commonly used to assess iron status, is an acute-phase protein implicated in CVD risk. Its role in postmenopausal women remains understudied. Objective: To investigate the association between serum ferritin and ACE in postmenopausal women from the Women’s Health Initiative (WHI) study. Methods: A nested case-control study was conducted within the WHI, including 1,382 postmenopausal women (313 adjudicated ACE cases and 1,069 controls). Ferritin concentrations were categorized into quartiles based on the control distribution (≤49, 50-85, 86-146, ≥147 ng/mL). To estimate the association between ferritin and ACE, doubly robust logistic regression was used, adjusting for traditional CVD risk factors and pertinent demographic, clinical, lifestyle, and menopausal variables. Results: Ferritin levels did not differ significantly between ACE cases and controls (median: 85 ng/mL; p ≥ 0.05). However, cases were older, had greater waist circumference, higher prevalence of diabetes, hypertension, and hyperlipidemia (p &lt; 0.05), but similar AHEI scores. Bilateral oophorectomy was more common among cases, whereas hormone therapy use was more prevalent among controls. Inflammatory markers such as hs-CRP were higher among cases, although IL-6 levels were similar. Compared with women in the lowest ferritin quartile (≤49 ng/mL), women in the second, third, and fourth quartiles had 47% (OR: 0.53; 95% CI: 0.36-0.79), 47% (OR: 0.53; 95% CI: 0.35-0.79), and 40% (OR: 0.60; 95% CI: 0.41-0.88) lower odds of ACE, respectively. The association plateaued across quartiles 2-4 and remained significant in sensitivity analyses, including anemia and sarcopenia. Conclusions: Low serum ferritin (≤49 ng/mL) was associated with higher odds of ACE in postmenopausal women, while higher levels appeared protective. These results suggest an inverse association with a threshold effect, consistent with prior studies of older women. Our findings provide preliminary support for ferritin as a potential CVD risk marker in postmenopausal women and warrant further study.

Abstract TU282: Postpartum Proteomic Networks Are Predictive of Future Cardiovascular Disease Risk in Women

Circulation Jie Hu, Xiumei Hong, Guoying Wang et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu282

Introduction: Cardiovascular disease (CVD) is the leading cause of death for US women. However, female-specific risk factors, especially pregnancy-related factors, are not included in CVD risk assessment for women. Whether alterations in biological pathways after delivery are associated with future CVD is unknown. In this study, we aim to identify postpartum proteomic networks associated with incident CVD. Methods: This case-control study is nested in the Boston Birth Cohort, a predominantly urban, low-income, and multiethnic birth cohort in the US. We included 31 women with incident CVD and 42 controls (up to 21 yrs of follow-up; 74% Black). Maternal postpartum (24-72 hrs after delivery) plasma proteomic profiling was performed using the mass spectrometry-based Seer Proteograph platform; 5,333 proteins were available after quality controls. CVD cases were identified based on International Classification of Diseases codes derived from longitudinal electronic health records, including congestive heart failure (CHF), ischemic heart disease (IHD), and stroke. We defined CVD as a composite of CHF, IHD and stroke. Proteomic networks were identified using WGCNA (Weighted Gene Co-expression Network Analysis), and their associations with incident CVD were examined using Cox proportional-hazards models. Results: Women developed CVD had higher pre-pregnancy body mass index and higher prevalence of preterm delivery and hypertensive disorders of pregnancy (HDP). WGCNA identified 22 proteomic network modules; 6 modules were associated with at least one CVD outcomes (p&lt;0.05) in the fully adjusted model, and these modules consist of proteins involved in estrogen signaling, brain aging, lipid metabolism, coagulation, inflammation, and immune function. The observed associations slightly attenuated after additionally adjusting for adverse pregnancy outcomes for 3 modules, but not for others. Notably, for one module consisting of 10 proteins (mostly keratins that are highly expressed in skin, arteries, and female reproductive organs), the association with CVD remained after Bonferroni correction for 22 modules (p&lt;0.0023), and 8 constituting proteins (6 are keratins) were associated with CVD. This module mediates 20% of the association between HDP and incident CVD. Conclusions: Network-based analysis identified postpartum plasma proteomic modules associated with incident CVD in women and suggested a mechanistic link between HDP and future CVD risk. Our findings need to be validated.