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Abstract TH852: Real-Time Mitral Valve Segmentation on 3-D Transesophageal Echocardiography with Quality Assurance for Intraoperative Decision Support

Circulation Dang Nguyen, Minh Le, Heath Rutledge-Jukes et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th852

Background: Intraoperative decision making for mitral valve repair relies on rapid, reliable assessment of leaflet anatomy from three-dimensional transesophageal echocardiography (3-D TEE). Current workflows depend on manual or semi-automated segmentation that is time-consuming, operator-dependent, and inconsistently exportable to meshes for sizing and simulation. Hypothesis: We hypothesize that an AI-powered 3-D TEE segmentation pipeline with single-pass, entropy-based quality assurance (QA) will deliver clinically actionable, real-time leaflet segmentations and clean mesh exports, supporting intraoperative repair planning and device sizing. Methods: We trained a transformer-based 3-D segmentation model (Swin-UNETR) on the MVSeg-2023 TEE dataset that consists of 150 end-diastolic TEE volumes. Volumes underwent intensity normalization, isotropic resampling to 0.6-mm voxels, and foreground cropping before inference. Temperature-scaled logits were converted to voxel-wise Shannon-entropy maps, a case-level quality score was thresholded using the validation set to gate low-confidence outputs. The primary endpoint was class-averaged Dice overlap for anterior and posterior leaflets. Secondary endpoints included boundary error (95th-percentile Hausdorff distance (HD95), average symmetric surface distance (ASSD)), mesh quality (non-manifold-edge rate), and end-to-end latency. Results: On the held-out test set, class-averaged Dice was high (0.832 ± 0.051). Boundary errors were low (HD95 = 4.2 ± 2.1 mm and ASSD = 0.39 ± 0.013 mm). Meshes were topologically clean (non-manifold edges = 0.21 ± 0.07%) and exported in real time (end-to-end time = 122 ± 35 ms with segmentation time = 104 ± 34 ms and peak GPU memory ≈4.0 GB). All test cases passed the entropy-based QA gate; within accepted cases, entropy and Dice were uncorrelated (Pearson correlation coefficient r = 0.016, p-value = 0.92). Across all test studies, the pipeline produced standardized leaflet masks and mesh exports automatically, enabling immediate downstream intraoperative support. Conclusions: Our transformer pipeline for TEE mitral-leaflet segmentation achieved high overlap accuracy, clean instant meshes, and real-time performance while providing a transparent QA signal, supporting its potential for intraoperative guidance and downstream computational modeling. Next steps include multi-vendor, multi-pathology external validation and extension to temporally consistent 4-D TEE.

Design, synthesis, molecular docking and cytotoxic evaluation of novel pyrimidine-based sulfonamide derivatives as potent anticancer agents: SAR insights and biological profiling

Scientific Reports Nesma M. Bayoumy, Ahmed A. Fadda, Hatem E. Gaffer et al. Mar 24, 2026 DOI: 10.1038/s41598-026-41711-z

Abstract The low selectivity and significant toxicity of current chemotherapeutic medicines make the research and development of novel anticancer agents an urgent necessity. This study used IR, NMR, MS, and elemental studies to rationally design, synthesize, and structurally characterize a novel class of pyrimidine-based sulfonamide derivatives. A wide variety of heterocyclic scaffolds, such as oxadiazoles, thiazolinones, chromenes, pyrazoles, pyrazolopyrimidines, triazolopyrimidines, imidazolidines, and triazines, were made possible by the synthetic approach. HepG2, MCF-7, WI-38, and VERO cell lines were used to test the synthetic compounds’ cytotoxic properties. With IC 50 values ranging from 7.4 to 10.2 µg/mL against HepG2 and 8.2 to 10.0 µg/mL against MCF-7, compounds 18 , 21 , 23 , and 24 showed extremely significant anticancer activity, nearly matching the potency of the reference medication 5-fluorouracil. Crucially, these substances showed a good therapeutic index with noticeably reduced toxicity toward normal WI-38 and VERO cells. The most active derivatives’ increased cytotoxicity and selectivity were shown to be largely due to electron-donating groups, balanced lipophilicity, and optimal heterocyclic substitution patterns, according to structure–activity relationship (SAR) research. The experimental results were corroborated by molecular docking experiments against thymidylate synthase (PDB: 2VF5), where compound 23 exhibited the highest binding affinity (S = − 5.5589 kcal/mol), creating strong H-bond interactions with Lys487 and Ala498 within the active region. Overall, compounds 18 , 21 , 23 , and 24 are identified as interesting lead candidates for additional development as effective and selective anticancer medicines based on the combined biology, SAR, and docking results. Future optimization, mechanistic research, and even in vivo assessment can all benefit from these discoveries.

Abstract 06: Comparative Effectiveness of Semaglutide and Tirzepatide on Cardiovascular Outcomes among Patients with Obesity and Established Cardiovascular Disease

Circulation Gwen Aubrac, Rafeya Raquib, Minh Le et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.06

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide have shown cardiovascular benefits in patients with diabetes. More recently, the indication for semaglutide was extended to cardiovascular risk management in patients without diabetes. However, direct comparative evidence on cardiovascular protection between semaglutide and tirzepatide in patients with obesity but without diabetes remains limited. Methods: We used an active comparator, new user design, and target trial emulation framework to compare the risk of 5-point MACE and 3-point MACE in new users of semaglutide and tirzepatide with obesity and established cardiovascular disease but without diabetes, identified from Komodo Health between November 8 th , 2023, and May 31 st , 2025. We used a per-protocol approach over 18 months of follow-up and censored patients who had a ≥90 day-gap in treatment supply or switched treatments. We created inverse probability of treatment weights (IPTW) to adjust for confounding and inverse probability of censoring weights (IPCW) to account for informative censoring. We estimated hazard ratios from weighted Cox proportional hazards models and incidence rate differences from weighted Kaplan-Meier survival curves, bootsrapped over 1,000 samples for robust confidence intervals. Results: We identified 6,903 new users of semaglutide and 6,937 new users of tirzepatide. Prior to weighting, semaglutide users tended to be older, have more comorbidities, and were more likely to have commercial insurance than Medicare or Medicaid, but balance was achieved after applying IPTW and IPCW weights. The risk of 5-point MACE was 18% higher in semaglutide users compared to tirzepatide users (HR=1.18, 95% CI: 1.09 to 1.31). The risk of 3-point MACE was not significantly different between treatment groups (HR=1.09, 95% CI: 0.94 to 1.27). Conclusions: The risk of cardiovascular events was lower for tirzepatide compared to semaglutide in initiators with obesity and a history of cardiovascular disease but without diabetes. Given the proven cardiovascular benefit of semaglutide compared to placebo from clinical trials in a similar population, these findings suggest that tirzepatide can be a promising alternative treatment option. Future research should confirm these results, which may have implications for expanding the indication of tirzepatide to include cardiovascular risk management.

Abstract TU159: Association Between Life’s Essential 8 and Hypertension Control: Evidence From NHANES 2021–2023

Circulation Darren Sackey, Kwabena Dankwa, Monica Gbuchie et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu159

Background: Hypertension remains a leading modifiable risk factor for cardiovascular disease, yet many U.S. adults fail to achieve adequate blood pressure (BP) control. The American Heart Association’s Life’s Essential 8 (LE8) provides a comprehensive measure of cardiovascular health: diet, physical activity, smoking, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. This study evaluates the association between LE8 and BP control among hypertensives in the newest NHANES cycle. To avoid circularity with the outcome, we excluded BP from the LE8 composite (LE8_noBP). Methods: We analyzed 6,317 U.S. adults aged ≥18 years with hypertension in NHANES 2021–2023. Hypertension was defined as mean systolic BP ≥130 mmHg, diastolic BP ≥80 mmHg, or self-reported diagnosis/medication use. Uncontrolled hypertension was defined categorically as systolic BP ≥130 or diastolic BP ≥80 mmHg despite diagnosis or treatment. LE8 scores (0–100) were calculated for all components. Analyses used the LE8_noBP composite, categorizing scores as Low (<50), Moderate (50–79), and High (≥80). Survey-weighted logistic regression estimated associations between LE8_noBP and uncontrolled hypertension, adjusting for age, sex, race/ethnicity, education, and income-to-poverty ratio. Results: Of 6,317 adults with hypertension, 1,714 had uncontrolled hypertension (unweighted prevalence: 27.1%). The weighted prevalence of uncontrolled hypertension was 24.7% (SE 0.8%). Mean LE8_noBP scores were lower among adults with uncontrolled vs controlled hypertension (59.2 vs 63.5). In adjusted models, each 10-point higher LE8_noBP score was associated with 15% lower odds of uncontrolled hypertension (OR 0.85, 95% CI 0.82–0.89). Compared with the Low group, Moderate (OR 0.62, 95% CI 0.52–0.74) and High (OR 0.35, 95% CI 0.23–0.54) categories had significantly lower odds of uncontrolled hypertension, demonstrating a dose-response relationship. Conclusion: Among U.S. adults with hypertension in NHANES 2021-2023, higher LE8_noBP scores were strongly associated with greater BP control. By excluding blood pressure from the composite, we ensured that associations reflect the contribution of lifestyle and non-blood pressure cardiovascular health metrics. These findings underscore the importance of promoting comprehensive cardiovascular health behaviors to improve hypertension control.

Abstract TH926: Association between Frailty and Peripheral Artery Disease among Older Adults: the Atherosclerosis Risk in Communities (ARIC) Study

Circulation Francis Ryan Avenido, Kunihiro Matsushita, Caitlin Hicks et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th926

Introduction: Peripheral artery disease (PAD) is a subtype of atherosclerotic cardiovascular disease (CVD) involving the occlusion of arteries in the lower extremities. Frailty has been associated with higher risk for several types of CVDs (i.e., stroke, myocardial infarction, heart failure), but its association with PAD is unclear. Objective: To estimate the association between frailty and risk of PAD hospitalization among older adults. Methods: Data were from 5390 ARIC study participants (mean age: 75.4 ± 5.1 years; 57.1% women; 21.3% Black persons) who attended visit 5 (2011-13). The Fried Frailty Index was used to classify participants as frail (≥3 components), pre-frail (1 to 2 components), or robust (0 components). We excluded prevalent PAD events at visit 5. Incident PAD hospitalizations were identified through ICD codes and participant follow-up for surveillance of events occurring after visit 5 until December 31, 2018. Cox regression was used to estimate the association between frailty status (frail or pre-frail vs. robust) and incident PAD hospitalization, adjusting for socio-demographic characteristics, smoking status (model 1), BMI (model 2), and C-reactive protein and multimorbidity status (model 3; fully adjusted). Results: 2887 participants (53.6%) were classified as either frail or pre-frail. There were 61 incident PAD hospitalization cases over a median follow-up time of 6.3 years. Of the 61 total PAD cases, 42 were from frail or pre-frail participants and 19 were from robust participants, respectively. Relative to robust participants, the PAD hazard ratio (HR) for frail or pre-frail participants was 2.10 (95% CI: 1.20-3.66) when adjusting for demographic factors and smoking; the HR was similar when additionally adjusting for BMI. In the fully adjusted model, the association was attenuated [HR: 1.78 (95% CI: 1.01-3.12)]. Conclusion: Among a sample of surviving older participants in ARIC, participants who were frail or pre-frail had a nearly two-fold higher risk of PAD hospitalization relative to robust participants. Currently, most emphasis is placed on secondary or tertiary prevention of PAD. Frailty becomes more common in later life and could be prevented or delayed through lifestyle (e.g., physical activity). If frailty is an independent risk factor for PAD, it could be targeted for risk stratification and targeted intervention.

TUBB2A related epilepsy: novel variants and genotype-phenotype correlation

Scientific Reports Wenwei Liu, Miaomiao Chen, Xiaowei Tang et al. Mar 24, 2026 DOI: 10.1038/s41598-026-44992-6

Abstract TU114: The Neighborhood Built Environment and Cardiometabolic Risk Factors in The Bogalusa Heart Study

Circulation Jenilee Cueto, Christopher Anderson, Hua He et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu114

Introduction: Rural residents are at a higher risk for early cardiovascular morbidity and mortality in midlife compared to urban populations. The neighborhood built environment (NBE), any human-made or modified feature of the physical environment, can be used to facilitate physical activity and improve health outcomes. However, the relationship between NBE features with cardiovascular (CV) risk factors in predominantly rural areas is unclear. Hypothesis: We evaluated whether NBE features conducive to physical activity are associated with healthier cardiometabolic risk factor measures in midlife. Methods: Data from Bogalusa Heart Study (2013-2016) participants were used to examine cross-sectional associations between NBE features and cardiometabolic risk factors including blood pressure, lipids, and glycemic markers. The Rural Active Living Assessment Street Segment audit tool and Google Street View were used to assess NBE features around participants’ residence. Scores were developed for path features, physical security, aesthetics, destinations, land use, and overall (high scores indicate feature promotes physical activity). Generalized estimating equations linear regression models accommodated for clustering within street segments and census tracts, and were adjusted for individual-level characteristics and neighborhood-level socioeconomic conditions. Results: A total of 1011 participants (mean age 48 years, 61% female, 33% Black) were analyzed. In fully adjusted models, a 1-point higher overall NBE score was associated with 0.5% higher high-density lipoprotein (p=0.035). A 1-point higher score for path features (p=0.006) and aesthetics (p=0.046) were also associated with 1% higher HDL. A 1-point higher destinations (p=0.040) score was associated with a 1.4% lower HDL. A 1-point higher aesthetics score was associated with a 0.7% lower hemoglobin A1c (p=0.038). A 1-point higher land use score was associated with 3.1% higher low-density lipoprotein (p=0.014). A 1-point higher physical security score was associated with a 0.7% lower systolic blood pressure when adjusted for individual-level covariates (p=0.047). Conclusion: Significant associations with cardiometabolic risk factors were identified for overall NBE, path features, aesthetics, destinations, and land use scores. Exploration into the mechanisms of these relationships may provide insight for informing rural communities to improve CV health outcomes.

Abstract WE555: Trends in Mortality Due to Use of Tobacco in Coronary Artery Disease Patients Among Younger and Older Adults from 1999-2023 in the USA

Circulation Laksh Kumar, Ayesha Ihsan, Muhammad Awais Bin Abdul Malik et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we555

Background: Tobacco use remains a major modifiable risk factor for coronary artery disease (CAD), amplifying cardiovascular risk when combined with other comorbidities. While cigarette smoking remains prevalent among older adults, the rise of e-cigarette use among younger populations complicates tobacco control efforts. Hypothesis: This study aims to evaluate national trends in CAD mortality attributable to tobacco use in U.S. adults aged 25 and older, with an emphasis on demographic and geographic disparities. Methods: We conducted a retrospective analysis using CDC WONDER data from 1999 to 2023. Age-adjusted mortality rates (AAMRs) attributable to CAD and tobacco use were calculated across sex, age groups, race/ethnicity, metropolitan status, and U.S. census regions. Joinpoint regression was used to assess changes in trends and estimate annual percent changes (APCs). Results: Between 1999 and 2023, there were 901,327 CAD deaths attributed to tobacco use in adults ≥25 years, with males (n=635,157) disproportionately affected. National AAMR increased from 2.6 (95% CI: 2.5–2.7) to 18.8 (95% CI: 18.6–19.0) per 100,000. Sex-stratified analysis showed a greater mortality burden among males, with trends plateauing after 2016. Age-stratified data revealed the highest AAMRs in older adults, peaking at 72.7 in 2021 before declining modestly. Racial disparities persisted, with non-Hispanic White and Black populations experiencing the highest burdens. Non-metropolitan regions consistently exhibited higher mortality rates compared to metropolitan counterparts. Regionally, the South and Midwest showed the steepest increases, while the Northeast and West demonstrated earlier plateauing. Conclusion: CAD mortality associated with tobacco use has significantly increased over the past two decades, particularly among males, older adults, and non-metropolitan populations. Racial and regional disparities underscore the urgent need for targeted public health interventions to reduce the cardiovascular burden of tobacco use and promote health equity.

Abstract TU276: Association Between Health Care Access and Cardiovascular Health Risk Among Reproductive-Aged Women in the SAFE HEART Study

Circulation Kwabena Dankwa, Faith Metlock, Kwabena Odei-Kumi et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu276

Background: Limited access to healthcare can influence cardiovascular health behaviors and outcomes. Few studies have examined this relationship, especially among women of reproductive age who often face unique barriers to care. We examined how indicators of access to care relate to overall CVH risk, defined by Life’s Essential 8 (LE8), among women in the SAFE HEART Study. Methods: We analyzed a cross-sectional sample of women aged 18–50 years. LE8 metrics (diet, physical activity, smoking, sleep health, body mass index, blood lipids, blood glucose, and blood pressure) were self-reported and scored as 0 vs 1 (optimal vs suboptimal levels as per AHA’s LE8 recommendations). Each participant received a composite CVH risk score (0-8), representing the number of suboptimal LE8 metrics. Access-to-care indicators included insurance status, PCP status, and self-reported transportation barriers (yes vs no for each indicator). Covariates included age, race, education, income, and employment status. Descriptive statistics and fully adjusted linear regression were used to assess associations between healthcare access and CVH risk. Results: Among N =178 women, the mean age was 32.4 years (SD = 8.0) and the mean CVH risk score was 2.26 + 0.88. Participants without insurance (n = 48) had a mean score of 2.29 + 0.80 versus 2.25 + 0.92 among those with insurance (n = 130; p = 0.79). Those without a PCP (n = 76) had a mean score of 2.25 + 0.84 versus 2.27 + 0.92 for those with a PCP (n = 102; p = 0.85). Participants reporting transportation barriers (n = 27) had a mean score of 2.22 + 0.93, compared with 2.27 + 0.88 among those without barriers (n = 151; p = 0.80). In fully adjusted linear regression, none of the healthcare access indicators were significantly associated with CVH risk: insurance (β = 0.22, p = 0.30), PCP (β = 0.09, p = 0.59), and transportation barrier (β = -0.03, p = 0.88). Conclusion: In this sample of reproductive-aged women, insurance, primary care provider, and transportation barriers were not independently associated with cardiovascular risk as measured by LE8 metrics. Beyond healthcare access, other social and behavioral determinants may play a larger role in cardiovascular health risk among reproductive-aged women.

Differential impact of various in-class physical exercise interventions on cognitive function and mathematics achievement in primary school children

Scientific Reports Christian Leukel, Benedikt Lauber, Juliane Leuders et al. Mar 24, 2026 DOI: 10.1038/s41598-026-45347-x

Abstract Physical activity is increasingly recognized for its dual role in enhancing both physical health and cognitive development. This study compared the effects of three types of in-class interventions—CARDIO (aerobic/anaerobic exercises), BALANCE (balance training), and MENTAL (cognitive training without physical activity)—on cognitive function and mathematics achievement among primary school students, including a subsample with lower concentration scores. A total of 157 students from the 2nd and 3rd grades were assigned to one of the intervention groups. The interventions were conducted daily for 15 min over a 5-week period. Cognitive function was assessed using the KoKi concentration test, and academic achievement in mathematics was evaluated with a curriculum-based assessment. Concentration levels were increased in all groups, but only the BALANCE and MENTAL groups showed significant improvements in both easy and complex math exercises. In students with lower concentration scores, greater gains in simpler math tasks were observed for BALANCE and MENTAL groups. Both physical (BALANCE) and non-physical (MENTAL) breaks were associated with improvements in concentration and mathematics performance. Considering widespread sedentary behavior, physically active breaks may provide added health-related benefits.

Abstract WE406: Unhealthy Alcohol Use and Sudden Death Among Working Age Adults

Circulation Shannon Parness, Jordan Besh, Ryan Sappington et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we406

Background: Unhealthy alcohol use may lead to arrythmias and cardiomyopathy, but its impact on sudden death is not well known. To investigate the association of unhealthy alcohol use with sudden death, we conducted a population-based case-control study in Wake County, a large (~1 million inhabitants), diverse county in North Carolina. Methods: We screened and adjudicated victims of sudden, unexpected, out-of-hospital deaths in adults aged 18-64 years reported by EMS between 2013 and 2015. We randomly selected sex- and age-matched control patients from a university health system. Characteristics of sudden death victims and controls were ascertained via standardized chart reviews. Unhealthy alcohol use was defined as any evidence of excessive alcohol use or alcohol-related diagnoses. We used logistic regression to estimate odds ratios (ORs) for the association of unhealthy alcohol use and sudden death, adjusting for age, sex, race, and other psychiatric diagnoses, including depression, anxiety, schizophrenia, bipolar disorder, and substance use disorders other than tobacco and alcohol. Smoking status was not available. We also calculated the E-value to estimate the impact of any unmeasured confounders. Results: We identified 399 sudden death victims of whom 374 (94%) had alcohol use data available. Among these 374 included victims, 256 (68%) were male and 239 (62%) were White with a median age at death of 55 years (IQR 48, 60). The demographic characteristics of the 1114 matched controls were similar to those of sudden death victims. Unhealthy alcohol use was present in 115 (31%) sudden death victims and 27 (2%) controls. In analyses adjusted for demographics only, unhealthy alcohol use was associated with higher incidence of sudden death, with an OR of 17.5 (95% CI 11.4, 27.8). When further adjusted for other psychiatric diagnoses, the OR was 11.2 (95% CI 7.1, 18.0). The calculated E-value was 21.8, meaning an unmeasured confounder would need to be associated with both unhealthy alcohol use and sudden death by 21.8-fold to explain away the observed OR. Conclusion: Unhealthy alcohol use was strongly associated with higher sudden death risk in working age adults. We could not adjust for smoking in this study; however, the E-value indicates it is unlikely that smoking alone would account for the observed association. Our findings suggest that interventions to reduce unhealthy alcohol use may be an effective strategy to prevent sudden death in working age adults.

Abstract WE497: The Geography of a Heartbeat: Mapping the Social Drivers of Cardiovascular Mortality

Circulation Kai Goldenstein Vonkiel, Jonathan Xiong, Lance Ridpath et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we497

Cardiovascular disease (CVD) is the number one cause of death in the US. Although most states have made significant headway in reducing their CVD death rates, some still lag behind. West Virginia has one of the highest rates of CVD in the country. To better understand risk levels in different communities, studies have found risk factors of CVD. Three of those factors are median household income (Income), primary care physician shortages (PCP shortage), and food desert status (FD). While each contributes to CVD mortality, no study focuses on the specific intersections between a combination of these factors and the CVD death rate. Aim: The study evaluates if multiple risk factors lead to a worse CVD prognosis compared to each factor individually. Method: Data collected were Income, PCP shortage, FD, and the death rate within WV from the Census Bureau, AMA, US Department of Agriculture, and the WV HHS, respectively. A multiple variable linear regression analysis was performed for each combination of factors towards the death rate. Results: Each factor (Income: F(1,537)=53.39, p<0.0001; PCP shortage: F(1,537)=21.49, p<0.0001; FD: F(1,537)=5.126, p=0.024) did show a significant correlation with CVD mortality, which is consistent with previous studies. When analyzing the intersections, two of the two-way combinations showed statistical significance (PCP need+Income: F(1,537)=22.03, p<0.001; FD+Income: F(1,537)=5.226, p=0.022), but the PCP+FD two-way combination and the three-way did not show any significance. Conclusion: The change in CVD mortality appears to be multifactorial, and focusing on a more holistic approach at the community level can lower the death rate.

Abstract WE551: A Population-Based Study of Modifiable Social and Behavioral Factors and Heart Aging

Circulation Erica Wood, Marwah Abdalla, Charles German et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we551

Introduction: The novel PREVENT risk age construct (age of a hypothetical person with the same absolute risk but optimal risk factors) may better communicate risk than absolute CVD risk. Social and behavioral factors shape CVD risk, and quantifying their associations with PREVENT risk age may better convey their impact when counseling patients. Hypothesis: Favorable behavioral and social metrics will be associated with lower PREVENT risk age and greater odds of having a risk age lower than chronological age. Methods: In adults from the 1999-2018 NHANES ( n =26,824, age: 30-79y, 50% female, 9% Black, 13% Hispanic), a new social advantage metric (SAM; 0-100), reflecting cumulative social determinants, was computed. Behavioral factors (sleep, diet, physical activity) were scored per Life’s Essential 8 and averaged to create a cumulative behavioral metric (BM). An aggregate social and behavioral metric (SBM) was also computed as the unweighted mean of SAM and BM; scores were categorized as high (80-100), moderate (50-79), or low (0-49). PREVENT risk age equations were used, and discordance between risk age and chronological age was estimated. Sex-stratified linear and logistic models examined associations of SBM and its components with age discordance. Results: Mean SBM was 60 in males and 62 in females. The mean PREVENT risk age was higher than chronological age for both sexes, but those with high vs. low SBM, SAM, and BM were more likely to have a risk age lower than their chronological age (Figure Panel A). Having high vs. low SBM, SAM, and BM was associated with lower age discordance (Figure Panel B). Similar associations were observed for all LE8 behavioral factors, with the strongest effect sizes being observed for diet. In logistic models, high vs. low SBM and its components were associated with up to 4- and 6-fold higher odds of having a risk age that is lower than their chronological age among males and females, respectively (Figure Panel C). In stratified analyses, associations persisted in all racial and ethnic groups but were strongest among White females ( p-interaction <0.01). Conclusion: Healthier lifestyle behaviors and greater social advantage are associated with lower PREVENT risk age vs. chronological age discordance and up to 6 times higher odds of having a lower risk age than their chronological age. Public health messaging and interventions addressing lifestyle changes and structural factors should incorporate the PREVENT risk age construct.

Association of anti SITH 1 antibody titer with mental stress and intracranial aneurysms

Scientific Reports Michiyasu Fuga, Hirokazu Koseki, Nobuyuki Kobayashi et al. Mar 24, 2026 DOI: 10.1038/s41598-026-42027-8

Abstract The role of mental stress in intracranial aneurysm rupture remains unclear. Serum anti–SITH-1 antibody titers have been proposed as a potential biomarker of chronic mental stress. This study investigated the association between serum anti–SITH-1 antibody titers and intracranial aneurysm rupture. Between June 2021 and September 2023, patients with ruptured intracranial aneurysms (RIAs), patients with unruptured intracranial aneurysms (UIAs), and healthy controls were prospectively enrolled from five institutions. Baseline characteristics, aneurysm morphology, and lifestyle factors were recorded. Serum anti–SITH-1 antibody titers were quantified using a fluorescent antibody technique. Blood samples were obtained once in each participant: within 1 month after enrollment in the UIA and Control groups, and within 24 h of subarachnoid hemorrhage onset in the RIA group. The primary outcome was the association between serum anti–SITH-1 antibody titer and aneurysm rupture. Eighty-five participants were registered; after exclusions, 24 patients with RIAs were included for analysis, along with 26 patients with UIAs and 23 controls. Baseline characteristics were generally comparable, except for higher statin use in the UIA group (p = 0.012). Larger aneurysm size (p < 0.001), the presence of aneurysmal blebs (p < 0.001), and distinct aneurysm locations (p = 0.001) were more frequent in the RIA group. Anti–SITH-1 antibody titers differed significantly among groups (p = 0.008), being highest in the UIA group, followed by the RIA and Control groups. In the UIA group, antibody titers showed a significant positive correlation with time from diagnosis to study enrollment (p = 0.028). Anti–SITH-1 antibody titers, used as a marker of mental stress, were significantly higher in patients with UIAs than in those with RIAs or in healthy controls. These findings suggest that chronic mental stress is unlikely to play a critical role in aneurysm rupture but may be more prominent in individuals diagnosed with UIAs.

The Future of Antithrombotic Therapy After Successful Catheter Ablation of Atrial Fibrillation

Circulation Atul Verma, David Birnie Mar 24, 2026 DOI: 10.1161/circulationaha.125.077744

Abstract MPTU06: Prediction of cardiovascular diseases using statistical and machine learning approaches: The Strong Heart Study

Circulation Mohammad Anwarul Islam, Steven Pan, Paul Rogers et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.mptu06

Background: Machine learning (ML) models are highly non-linear functions that are known to have good prediction ability in the classification paradigms, from binary to multi-class classification of a response variable. Predicting cardiovascular disease (CVD) outcomes based on demographic and clinical characteristics is important but also challenging. ML and deep learning (DL) models can also be sensitive to the population structure of the dataset. In recent years, though ML approaches have been used in CVD prediction and its associated risk factor analysis for various populations, this technology could benefit underserved and rural populations. Therefore, the aim of this study was to use ML and DL models to predict CVD outcomes of American Indians in the Strong Heart Study (SHS), a longitudinal study of CVD conducted in Arizona, Oklahoma, North Dakota, and South Dakota. Methods: A total of 3,248 SHS participants were initially examined between 1989 and 1991. They were followed through 2023. Multivariable logistic regression was used to identify important features that are associated with CVD outcomes, in addition to literature review. These selected features were then used to train and test the ML and DL models, which were applied to predict CVD, Coronary Heart Disease (CHD), and stroke events. Sensitivity, specificity, F1 scores, and ROC curves were examined to evaluate the prediction accuracy of these models. Results: Among ML models, the support vector machine (SVM) performed best with the highest accuracy of 64% and 67% in predicting CVD and CHD outcomes, respectively, which are similar to the accuracy of logistic regression models. Among DL models, artificial neural networks (ANN) achieved the highest accuracy of 63% in predicting CVD, while convolutional neural networks (CNN) performed best for CHD with 65% accuracy. Both ML and DL models performed similarly in predicting stroke, with an average accuracy of 89.41%. Conclusion: Our results showed that ML and DL prediction models performed better when the disease prevalence was low. ML and DL models provide additional tools for predicting rare disease outcomes.

Abstract TU127: Maternal gestational diabetes and childhood hypertension risk

Circulation Gang Hu, Wentao Cao, Ru Gao et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu127

Background: Several studies have investigated the association between maternal gestational diabetes mellitus (GDM) and the risk of elevated blood pressure in offspring, but findings have been inconsistent. Objective: This study aimed to examine the association between maternal GDM and offspring’s hypertension risk from 6 to 8 years of age. Methods: A total of 1,156 mother-child pairs (578 with GDM and 578 without GDM) were followed longitudinally at a mean of 5.9 ± 1.2 years postpartum. Of these, 912 pairs (486 GDM and 426 non-GDM) remained at a follow-up conducted at 8.3 ± 1.6 years postpartum. Childhood blood pressure was measured using standardized protocols. Results: At 5.9 years of age, children born to mothers with GDM had significantly higher mean value of systolic blood pressure Z scores compared to those born to mothers with normal glucose levels during pregnancy (0.05 vs. −0.21, P < 0.001). After adjusting for multiple variables, children of mothers with GDM had higher odds ratios of hypertension (OR 1.80, 95% confidence intervals [CI]: 1.73–1.86) and high blood pressure (OR 1.56, 95% CI: 1.06–2.31). At 8.3 years of age, the association between maternal GDM and childhood high blood pressure became stronger. Adjusted odds ratios were 2.89 (95% CI: 2.14–3.90) for hypertension and 2.16 (95% CI: 1.04–4.78) for high blood pressure. Conclusions: Maternal GDM was an independent risk factor for childhood hypertension at both 5.9 and 8.3 years of age. The strength of this association increased with the child’s age.

pH-responsive acetylated PAMAM dendrimer nanocarriers for enhanced intravesical delivery of Erdafitinib in urothelial carcinoma

Scientific Reports Gowdru Vishwanath Nahusha, Venkatesh Dinnekere Puttegowda, Mohamed Rahamathulla et al. Mar 24, 2026 DOI: 10.1038/s41598-026-42545-5

Letter by Zhang et al Regarding Article, “Evaluation of Lipoprotein(a) as a Prognostic Marker of Extracoronary Atherosclerotic Vascular Disease Progression”

Circulation Lingling Zhang, Zhican Liu, Mingyan Jiang Mar 24, 2026 DOI: 10.1161/circulationaha.125.077337

Abstract WE450: Association between Multiple Urinary Metals and Metal Mixtures and Ectopic Adiposity in Caribbean Men: The Tobago Health Study

Circulation Ruel Beresford, Natalie Price, Aaron Barchowsky et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we450

Background: Previous studies reported an association between several urinary metals/metalloids (e.g. arsenic, cadmium, lead) and obesity. However, the majority of studies assessed anthropometrics, only analyzed metals individually, and often had inconclusive results. Hence, there is a need for research on joint metal exposures and ectopic adiposity in the Caribbean, which has one of the fastest-growing rates of obesity and cardiometabolic disorders globally. Objective: This study investigated the associations between arsenic, barium, cadmium, copper, and lead, both individually and jointly, with ectopic adiposity in Afro-Caribbean men. Methodology: This cross-sectional study included 363 Afro-Caribbean men aged 40+, from the Tobago Health Study. Metals were measured from spot urine samples collected between 2014-2016 analyzed by inductively coupled plasma mass spectrometry. Ectopic adiposity was measured via CT scans of the abdomen (visceral and subcutaneous adiposity, psoas and paraspinal muscle density) , and calf. Skeletal muscle density (MD) proxies skeletal muscle adiposity (lower MD reflects more adiposity). Linear regression was used to model individual metal associations with adiposity outcomes, and weighted quantile sum regression was used to measure the mixture of metals with adiposity outcomes. These models were adjusted for age, height, requisite muscle size, total energy and fish intake, urinary creatinine, physical activity, and cardiometabolic disorders (diabetes and hypertension). Results: A higher urinary lead concentration was associated with lower calf(β=-1.23, p=0.0005), and paraspinal(β=-1.72, p=0.002) MD. Higher urinary copper was associated with lower calf MD(β=-1.11, p=0.03), while higher urinary cadmium was associated with lower BMI (β=-1.00, p=0.04), waist circumference (β=-2.72, p=0.04), and calf MD(β=-0.89, p=0.03). The mixture of As, Ba, Cd, Cu, and Pb was jointly associated with lower calf (β=-0.63; CI: -1.12, -0.02) and paraspinal MD (β=-0.80; CI: -1.46, -0.14). There was no association between urinary metals and psoas, visceral, nor subcutaneous adiposity. Discussion: Our findings suggest that individual lead exposure and joint exposure to a mixture of arsenic, barium, cadmium, copper, and lead may be significant risk factors for muscle adiposity and poor cardiometabolic health in African ancestral populations. Additional studies are needed to confirm these findings longitudinally and to identify underlying molecular mechanisms.