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Abstract P2094: Atrial Fibrillation and Risk of Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Introduction: Atrial fibrillation (AF) and cognitive impairment are expected to double in prevalence over the next 20 years. While most literature on AF and risk of cognitive disorders is focused on dementia, there is little evidence on cognitive impairment or non-stroke populations. We addressed this question in the REGARDS cohort. Hypothesis: Baseline AF is associated with increased risk of incident cognitive impairment (ICI) in REGARDS participants with and without prevalent stroke. We tested for differences in this association by prevalent stroke, race (Black and White), and oral anticoagulant use, and for the attenuating effect of selected biomarkers on associations. Methods: REGARDS enrolled 30,239 persons > 45 years old in 2003-07. AF was defined by self-report or ECG. ICI was defined during follow-up by robust cognitive norms based on the Montreal Cognitive Assessment and Six-Item Screener. HRs of time to ICI with AF were calculated by Cox proportional hazards models (Table footnote), with censoring at death or last follow-up. Considered individually, interaction terms for prevalent stroke, race, and oral anticoagulant use with AF were assessed. Results: Among 23,638 participants with mean follow-up 12.8 years (mean age 64.3 years, 56.3% women, 37.6% Black), the association of AF with ICI was modest (HR 1.21; see Table). The adjusted HR was greater in those with prevalent stroke than without stroke (1.69 vs. 1.05). Among those with prevalent stroke, there was little impact of added adjustment for anticoagulant use; with added adjustment for each biomarker individually, there was small-modest attenuation by each biomarker. HRs did not differ by race or oral anticoagulant use (both p interactions >0.4). Conclusion: Independent of other factors including anticoagulant use, AF was associated with ICI in those with prevalent stroke, but not in those without prevalent stroke. Biomarkers had modest attenuating effects on the association among those with prevalent stroke. Results underscore the importance of considering cognitive impairment after stroke in those with AF and identifying underlying causes, which could involve inflammation.
Abstract P3158: Sex-specific association patterns of childhood maltreatment across TyG and TyG-BMI indices in young adults
Background: There is a high prevalence of childhood maltreatment (CM) among adults with cardiometabolic diseases. However, there is limited information available on the specific patterns of association between CM (cumulative CM, subtype, threat- and deprivation-based CM and co-occurrence) with cardiometabolic health indicators in young adults. Aims: To investigate the patterns of association between CM and cardiometabolic health indicators, including the triglyceride glucose (TyG) index and the TyG-body mass index (TyG-BMI), in a sex-specific manner among young adults. Methods: This cross-sectional study included 817 young adults from the University Student Cohort in Anhui Province, conducted in September 2022. Spearman correlations and linear regressions were used to test the association of cumulative CM, five subtypes of CM - physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional neglect - as well as the threat- and deprivation-based CM and co-occurrence (two or more subtypes of CM) with respect to the TyG index and the TyG-BMI index, in a sex-specific analysis. Results: Cumulative CM was associated with TyG index ( β = 0.06, 95% CI = 0.00 - 0.12). In contrast, none of the CM variables was associated with TyG-BMI index. We revealed profound sex-specific differences, with associations between cumulative CM and TyG index ( β = 0.10, 95% CI = 0.01 - 0.18), between emotional neglect and TyG index ( β = 0.10, 95% CI = 0.00 - 0.20), and between deprivation-based CM and TyG index ( β = 0.09, 95% CI = 0.00 - 0.18) in men only. Also, only men showed an association between deprivation-based CM and TyG-BMI index ( β = 3.06, 95% CI = 0.35 - 5.77). Conclusions: This study indicates that cumulative CM, emotional neglect and deprivation-based CM may be associated with poorer cardiometabolic health in young adults, with these associations being much stronger in men than in women.
A general framework for interpretable neural learning based on local information-theoretic goal functions
Despite the impressive performance of biological and artificial networks, an intuitive understanding of how their local learning dynamics contribute to network-level task solutions remains a challenge to this date. Efforts to bring learning to a more local scale indeed lead to valuable insights, however, a general constructive approach to describe local learning goals that is both interpretable and adaptable across diverse tasks is still missing. We have previously formulated a local information processing goal that is highly adaptable and interpretable for a model neuron with compartmental structure. Building on recent advances in Partial Information Decomposition (PID), we here derive a corresponding parametric local learning rule, which allows us to introduce “infomorphic” neural networks. We demonstrate the versatility of these networks to perform tasks from supervised, unsupervised, and memory learning. By leveraging the interpretable nature of the PID framework, infomorphic networks represent a valuable tool to advance our understanding of the intricate structure of local learning.
Abstract P2170: Mortality Rates Vary for Cardiovascular Disease Subtypes among Adults in Disaggregated Asian Groups—United States, 2018–2022
Background: Although Asian adults have the lowest cardiovascular disease (CVD) death rate in the US, prior research has shown important within-group variability for Asian subgroups through 2017. Recent data that examine death rates across CVD subtypes for Asian subgroups are needed to inform clinical and public health practice. Methods: We identified CVD deaths among US adults aged ≥18 years from the National Vital Statistics System using International Classification of Diseases, 10 th Revision codes and classified them into 7 non-mutually exclusive CVD subtypes listed as the underlying or contributing cause of death. Annual age-standardized mortality rates (ASMR) from 2018 to 2022 were calculated using U.S. Census 2000 standard population. Rate ratios (RRs) compared ASMR for adults in 6 non-Hispanic Asian subgroups to non-Hispanic Asian adults overall. Results: From 2018 to 2022, 123,566 CVD deaths occurred among Asian adults overall (79% heart disease, 29% stroke). Filipino adults had higher ASMR than Asian adults overall for all CVD subtypes (Figure), with RRs ranging from 1.09 for ischemic heart disease to 1.42 for valvular heart disease. Asian Indian adults had higher ASMR than Asian adults overall for all CVD subtypes except valvular heart disease and stroke, with RRs ranging from 1.08 for arrhythmia to 1.45 for heart failure. Japanese adults had ASMR that exceeded Asian adults overall for 2 CVD subtypes, with RRs of 1.06 for heart failure and 1.55 for valvular heart disease. Vietnamese adults had a stroke ASMR that was 1.24 times higher than Asian adults overall. Chinese adults and Korean adults had ASMRs that were similar to or lower than Asian adults overall for all CVD subtypes. Conclusions: CVD ASMRs for Asian adults in aggregate obscure important within-group variability across CVD subtypes, which have different implications for prevention and clinical management. Disaggregating CVD ASMR can identify subpopulations that might benefit from focused strategies to prevent, detect, and manage leading causes of death.
Abstract P3172: Type A Behavior Pattern and Incident Stroke: REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Introduction: Stroke is a leading cause of adult disability and the 5th leading cause of death in the United States. Both women and Black Americans have a higher lifetime risk of stroke. With stroke playing an important role in morbidity and mortality, there is a need for investigation of risk factors to aid in prevention. Type A behavior pattern (TABP) is characterized by certain behavioral tendencies and is categorized by time urgency/impatience (TUI) and achievement striving/competitiveness (ASC) components. Hypertension is a stroke risk factor and TABP is a risk factor for hypertension. Whether TABP is also a risk factor for stroke is unclear. Objective and Hypothesis: We sought to estimate the risk of incident stroke among adults without prior stroke by the level of TABP. We hypothesized that TABP will be associated with greater stroke risk. Methods: REGARDS enrolled 30,239 White and non-Hispanic Black participants aged ≥45 years in 2003-2007. Participants were contacted every 6 months through structured phone calls, medical records were obtained, and possible stroke events were adjudicated by experts. TUI and ASC (TABP components) were assessed with the Framingham Type A scale at baseline. Those with prior strokes or missing TABP were excluded. Cox proportional hazard models estimated the adjusted relative hazard of stroke by level of TUI and ASC scores separately. Because of significant TUI*race and TUI*sex interactions on incident stroke, TUI was stratified by race and sex. There were no significant ASC*race or ASC*race interactions on incident stroke, so ASC was not stratified. Results: There were 16,982 participants with TUI responses and 16,606 participants with ASC responses; baseline demographics, follow-up, and stroke incidence were similar in both TUI and ASC groups (mean [SD] 64 [10] years old, 65% women, 60% White race, median follow-up 11 years; 5.1 strokes/1000 person-years). As shown in Figure , higher levels of TUI for Black participants and men were associated with greater adjusted stroke risk. Higher ASC levels were associated with greater adjusted stroke risk overall. Conclusions: Higher scores in the TUI component of TABP in Black participants and men and the ASC component of TABP in all were associated with greater stroke risk. Screening and aggressive management of stroke risk factors like hypertension that are also associated with TABP might attenuate some of the excess burden of stroke among persons with greater TABP.
Giant quantum oscillations in thermal transport in low-density metals via electron absorption of phonons
Oscillations of conductance observed in strong magnetic fields are a striking manifestation of the quantum dynamics of charge carriers in solids. The large charge carrier density in typical metals sets the scale of oscillations in both electrical and thermal conductivity, which characterize the Fermi surface. In semimetals, thermal transport at low-charge carrier density is expected to be phonon dominated, yet several experiments observe giant quantum oscillations in thermal transport. This raises the question of whether there is an overarching mechanism leading to sizable oscillations that survives in phonon-dominated semimetals. In this work, we show that such a mechanism exists. It relies on the peculiar phase-space allowed for phonon scattering by electrons when only a few Landau levels are filled. Our measurements on the Dirac semimetal ZrTe 5 support this counterintuitive mechanism through observation of pronounced thermal quantum oscillations, since they occur in similar magnitude and phase in directions parallel and transverse to the magnetic field. Our phase-space argument applies to all low-density semimetals, topological or not, including graphene and bismuth. Our work illustrates that phonon absorption can be leveraged to reveal degrees of freedom through their imprint on longitudinal thermal transport.
Abstract P3047: Consumption of Ultra-processed Food and Risk of Major Complications in Adults with Type 2 Diabetes: The Atherosclerosis Risk in Communities Study
Background: The consumption of ultra-processed food may increase the risk of complications by adversely affecting cardiometabolic health. However, in persons with cardiometabolic disease such as type 2 diabetes, it is unclear whether ultra-processed food is associated with adverse outcomes. Methods: We conducted a prospective cohort analysis in middle-aged adults with type 2 diabetes in the Atherosclerosis Risk in Communities study, with follow-up from 1987-1989 until December 31, 2021. Diabetes was defined as fasting blood glucose ≥126 mg/dL, non-fasting blood glucose ≥200 mg/dL, self-reported physician diagnosed diabetes, or use of diabetes medication. Ultra-processed food was defined according to the NOVA classification from a 66-item food frequency questionnaire. We used Cox models to examine the association between residual-adjusted quartiles of ultra-processed food consumption and incident cardiovascular outcomes (coronary heart disease, stroke, or heart failure), incident chronic kidney disease, and all-cause mortality. Results: Among 1,624 participants (mean age of 56 years, 42% Black, 55% female), there were 1,398 deaths, 750 incident cardiovascular events, and 793 cases of incident chronic kidney disease over a median follow-up of 20 years. There were no significant differences in the risk of all-cause mortality, cardiovascular disease (overall and across subtypes), or chronic kidney disease across residual-adjusted quartiles of ultra-processed food consumption after adjusting for demographic, socioeconomic, and lifestyle characteristics (Table) . Conclusion: Among middle-aged adults with type 2 diabetes, higher levels of ultra-processed food consumption was not associated with higher risk of incident cardiovascular disease, chronic kidney disease, or mortality. In persons with cardiometabolic disease, consumption of ultra-processed food may not confer additional risk for major complications.
Abstract P2019: Alcohol Use and Cardiovascular Health: A Target Trial Emulation
Background: Observational studies on the cardiometabolic effects of alcohol are inconsistent. Long-term randomized trials on alcohol use are currently unavailable, and trials on increasing intake are unlikely. Methods: We emulated a target trial using data from the UK Biobank cohort (502,178 individuals aged 40–69). Eligible participants were all stable current drinkers, irrespective of intake level, who had no myocardial infarction, revascularization procedure, stroke, or liver disease in the past six months, no history of heart failure, cancer (breast, colon, or liver), dementia, or alcohol-related conditions, and were not on antithrombotic drugs or reporting poor health. Alcohol use was assessed at baseline (2006–2010) and again during follow-up (2012–2022). The primary endpoint was time to death or first cardiovascular disease (CVD) event (myocardial infarction, ischemic stroke, angina hospitalization, or coronary revascularization). Secondary endpoints were CVD, type 2 diabetes, and alcohol-related disease or death. We used clone-censor-weighting to estimate risks of endpoints, comparing participants who were moderate drinkers (>0–16g alcohol daily or almost daily) during follow-up with those who were social drinkers (>0–16g on 1–3 days/week or only monthly), adjusting for potential baseline confounders. We chose appendicitis and rheumatoid arthritis (RA) as negative control outcomes to assess unmeasured confounding. Results: Of the 65,594 eligible participants at baseline, 12,470 were moderate drinkers during follow-up and 53,124 were social drinkers, with 1,041 and 4,224 CVD events or deaths, respectively. Moderate drinkers had a 14% lower risk of CVD or death compared to social drinkers (adjusted risk ratio, 0.86; 95% confidence interval, 0.76–0.97). Negative control outcome results indicated similar relative risks for appendicitis (0.87; 0.70–1.08) and RA (0.80; 0.67–0.97) comparing moderate to social drinkers, indicating strong potential for unmeasured confounding. Relative risks for CVD, type 2 diabetes, and alcohol-related disease or death did not differ between the groups. Conclusions: Our analyses suggest that moderate alcohol use was associated with a lower risk of CVD or death compared to social drinking. However, even after comprehensively accounting for potential biases, unmeasured confounding may explain this lower risk, highlighting the need for trials to assess the health impacts of reducing intake. (ClinicalTrials.gov: NCT06583161).
Bioinspired ion-shuttling memristor with both neuromorphic functions and ion selectivity
The fluidic memristor has attracted growing attention as a promising candidate for neuromorphic computing and brain–computer interfaces. However, a fluidic memristor with ion selectivity as that of natural ion channels remains a key challenge. Herein, inspired by the structure of natural biomembranes, we developed an ion-shuttling memristor (ISM) by utilizing organic solvents and artificial carriers to emulate ion channels embedded in biomembranes, which exhibited both neuromorphic functions and ion selectivity. Pinched hysteresis I-V loop curve, scan rate dependency, and distinctive impedance spectra confirmed the memristive characteristics of the as-prepared device. Moreover, the memory mechanism was discussed theoretically and validated by finite-element modeling. The ISM features multiple neuromorphic functions, such as paired-pulse facilitation, paired-pulse depression, and learning–experience behavior. More importantly, the ion selectivity of the ISM was observed, which allowed further emulation of ion-selective neural functions like resting membrane potential. Benefiting from the structural similarity to membrane-embedded ion channels, the ISM opens the door for ion-based neuromorphic computing and sophisticated chemical regulation by manipulating multifarious ions with neuromorphic functions.
Abstract P3028: Dietary patterns, serum metabolites and risk of cardiovascular disease in the US Hispanic/Latino adults: the Hispanic Community Health Study/Study of Latinos
Objective: Healthy dietary patterns are recommended to prevent cardiovascular disease (CVD), yet the molecular mechanisms underlying the association between dietary patterns and CVD are not well-understood. We aimed to assess the associations of healthy dietary patterns and related serum metabolites with incident CVD in US Hispanics/Latinos. Methods: The study included 13,922 participants free of CVD at baseline aged 18-74 years from the Hispanic Community Health Study/Study of Latinos. Dietary pattern scores, including Healthy Eating Index (HEI)-2015, healthful Plant-based Diet Index (hPDI), and alternate Mediterranean diet (aMED), were constructed at baseline (2008-2011) using two 24-hour dietary recalls data. The primary outcome was incident CVD, encompassing myocardial infarction, heart failure, and stroke. Dietary-pattern-associated metabolite scores were calculated based on 40 serum metabolites measured in a subsample of baseline participants (n=5,154). Associations of dietary pattern scores, individual metabolites and metabolite scores with incident CVD were evaluated using multivariable Cox regression. Results: After adjusting for demographic, socioeconomic and behavioral factors, a 1-standard deviation (SD) increase in dietary pattern scores was associated with a lower risk of CVD with hazard ratios of 0.68 (95% confidential interval [CI], 0.47-0.98), 0.71 (0.58-0.88), and 0.69 (0.47-1.02) for HEI-2015, hPDI, and aMED, respectively. A negative metabolite score derived from 8 dietary-pattern-inverse metabolites showed a strong inverse association with three dietary scores, while a positive metabolite score based on 32 dietary-pattern-positive metabolites exhibited a robust positive association with three dietary scores (Figure 1A). The metabolite scores were significantly associated with risk of CVD, with hazard ratios of 1.44 (95% CI, 1.19, 1.75) and 0.79 (95% CI, 0.65, 0.97) for the negative and positive metabolite scores (per SD increase in metabolites scores), respectively (Figure 1B). Conclusion: Healthier diet patterns and related serum metabolite profiles were associated with lower risk of CVD in US Hispanic/Latino adults.
Abstract P2062: Differences in Social Determinants of Health among African American, African, and Caribbean participants in the Groceries for Black Residents of Boston to Stop Hypertension (GoFresh) Trials
Background: While it is known that adverse social determinants of health (SDOH) disproportionately affect Black persons in the United States (US), it is increasingly recognized that this group is heterogeneous. Nevertheless, there is limited research characterizing differences in SDOH across distinct Black heritage groups, specifically, those that report African American, African, and Afro Caribbean heritage. Greater understanding of these differences is critical for the development of effective interventions to address adverse SDOH. Objective: To characterize differences in SDOH across three Black ethnic groups using screening data from two community-based trials. Methods: The GoFresh Trials are two randomized controlled trials investigating the effects of the Dietary Approaches to Stop Hypertension (DASH) eating pattern on blood pressure after 12 weeks in adults with and without treated hypertension living in Boston. SDOH characteristics in GoFresh were assessed in the following categories: demographics characteristics (including car and home ownership, income, educational levels), social needs (via the AHC Health-Related Social Needs Scale), perceived stress levels (via the PSS-4 instrument), and discrimination (via the Krieger Discrimination Scale). We used age- and sex- adjusted models to compare SDOH across the three ethnic heritage groups. Results: Of 1,600 screened participants; 72% were female. The mean age (±SD) was 45 years (±16). Persons identifying as African American were 4.65 times more likely to report discrimination at school and 0.2 times less likely to face discrimination when receiving services compared to Africans. Africans were 0.39 (0.18, 0.78) and 0.57(0.35, 0.95) less likely to have a PCP compared to African Americans and Afro Caribbeans respectively. There were no differences in food security and income levels among the three groups. Conclusion: Persons identifying as African American are more likely to report experiences of discrimination at schools compared to African and Caribbean persons. Discrimination affects the different Black ethnic heritage groups to varying degrees. These differences in SDOH highlight the importance of awareness of these differences as they have implications to provision of care.
The neural bases of the reach–grasp movement in humans: Quantitative evidence from brain lesions
Visually guided grasping is a fundamental building block of animal behavior, the specific neural mechanisms of which remain poorly documented in the human brain. We have mapped the causal contribution of different brain parts to grasping behavior by studying the kinematic parameters of 33 patients with brain tumors, engaged in actions directed toward objects of different sizes. Using motion capture techniques, we analyzed the dynamics of grip aperture and wrist transport. Voxel-based lesion-symptom mapping analysis was applied to correlate lesion volumes with specific behavioral deficits. Results showed that lesions in the anterior and lateral bank of the intraparietal sulcus produced impaired finger scaling related to object size. Conversely, impaired velocity of finger aperture was associated with lesions in the dorsal premotor cortex (PMd). Grip aperture deficits following dominant hemisphere lesions were bilateral and were unilateral when following nondominant hemisphere lesions. Impaired wrist transport during reaching was associated with lesions in the first segment of the superior longitudinal fasciculus. Our work highlights an architecture of the grasping network in humans, with unique species-specific features. We hypothesize a model of human neural architecture in which object geometry for hand preshaping is first coded in the left anterior intraparietal cortex and then shared with the right hemisphere. Execution of the motor program of hand preshaping is then performed by the PMd on the corresponding side.
Abstract P3043: Circulating Omega-3 Polyunsaturated Fatty Acids and Early Type 2 Diabetes Risk Phenotypes: Longitudinal Analyses in the PROspective Metabolism and ISlet cell Evaluation (PROMISE) Cohort
Background: Literature on omega-3s and T2D risk has been heterogenous; however, most prior studies have used self-reported dietary intake or short-term supplementation regimens. Thus, further investigation is needed to assess longitudinal associations of circulating omega-3 with early T2D risk phenotypes. Objective: Assess longitudinal associations of circulating omega-3s with changes in insulin sensitivity (IS) and β-cell function (BCF) in the PROMISE cohort. Methods: Adults at-risk for T2D underwent four assessments over 9 years (n=472); blood samples were collected to determine insulin and glucose concentrations, and an OGTT was conducted. Baseline serum omega-3s (ALA, EPA, DPAn-3, DHA) were measured using gas chromatography-flame ionization detection. OGTT values were used to calculate validated IS (HOMA2-%S, ISI) and BCF (IGI/IR, ISSI-2) indices. Generalized estimating equations (GEE) analysis assessed the association between baseline omega-3s (mol%) with longitudinal change in IS and BCF indices after covariate adjustment. Results: Significant positive correlations were shown between EPA and DHA with IS measures (HOMA2-%S: EPA, r=0.18, DHA, r=0.23, all p<0.001; ISI: EPA, r=0.15, p<0.01, DHA, r=0.19, p<0.001) and between DHA and BCF indices (IGI/IR, r=0.14, p<0.01; ISSI-2, r=0.1, p<0.05). In adjusted GEE models, baseline EPA and DHA were positively associated with longitudinal change in IS (HOMA2-%S, p<0.001; ISI , p<0.01), and BCF (IGI/IR, p<0.05) ( Figure ) . Conclusions: Circulating omega-3s (specifically EPA and DHA) were positively associated with IS and BCF, which are important early T2D risk phenotypes. These findings add to growing evidence of the potential role omega-3s have in T2D primary prevention.
Abstract P1130: Patterns of Physical Activity from Midlife to Late Life: The Multi-Ethnic Study of Atherosclerosis (MESA)
Introduction: Physical activity (PA) is an important component of healthy aging, playing a key role in preserving mobility, preventing falls, and mitigating the risks of conditions like sarcopenia, osteoporosis, and cognitive impairment. Despite its importance, engagement in PA, particularly higher intensity exercise, tends to diminish as individuals age, yet there is limited understanding of the specific patterns and factors influencing this decline across diverse populations. The purpose of this study was to quantify patterns of PA change from midlife to older adulthood, by domain and intensity. Methods: Data are from 6,814 MESA participants (53% women, 39% White persons) who attended at least one exam. Participation in ten PA types or categories was measured by the MESA Typical Week PA Survey at each exam. To characterize the life-course, participant data from Exams 1-7 were grouped based on age categories (5-year age increments from <50 to ≥90 years). Participants reporting 0 min/week within the PA category determined non-participation in the respective category. Participation in PA categories was assessed for each intensity category (light, moderate, vigorous) for all activity categories, where appropriate. Findings are presented as heat maps. Results: Marked reductions in the endorsement of most PA types across increasing age groups was found, particularly in categories reflecting higher intensity sports and occupational activity categories (Figure). PA categories reflecting everyday lower intensity lifestyle activities, including television viewing, non-active commuting, and household chores, had a more stable endorsement over time. Walking, for both exercise and transportation, was common regardless of age. Conclusions: These findings present valuable insights into patterns of PA across an important life-course transition. Opportunities to further support the promotion of walking is needed to ensure adequate PA accumulation for health benefits in older adults.
Conformational free energy landscape of a glutamate transporter and microscopic details of its transport mechanism
Removing glutamate from the synaptic cleft is vital for proper function of the brain. Excitatory amino acid transporters mediate this process by uptaking the neurotransmitter from the synaptic cleft back to the cell after its release. The archaeal homolog, Glt Ph , an aspartate transporter from Pyrococcus horikoshii , presents the best structurally characterized model for this family of transporters. In order to transport, Glt Ph undergoes elevator-like conformational changes between inward-facing (IF) and outward-facing (OF) states. Here, we characterize, at an atomic level, the OF⇌IF transition of Glt Ph in different apo /bound states using a combination of ensemble-based enhanced sampling techniques, employing more than two thousand of coupled simulation replicas of membrane-embedded Glt Ph . The resulting free-energy profiles portray the transition of apo /bound states as a complex four-stage process, while sodium binding alone locks the structure in one of its states. Along the transition, the transport domain (TD) disengages from the scaffold domain (SD), allowing it to move as a piston sliding vertically with respect to the membrane during the elevator-like motion of TD. Lipid interactions with residues comprising the SD–TD interface directly influence the large-scale conformational changes and, consequently, the energetics of transport. Structural intermediates formed during the transition leak water molecules and may correlate to the uncoupled Cl − ion conductance observed experimentally in both prokaryotic and mammalian glutamate transporters. Mechanistic insights obtained from our study provide a structural framework for better development of therapeutic for neurological disorders.
Abstract P3173: Stroke Risk Associated with Atrial Fibrillation in the General Population: A Systematic Review and Bayesian Meta-Analysis
Objective: The contribution of atrial fibrillation (AF) to global stroke burden is not well described. This study synthesized available evidence using the Burden of Proof (BoP) methodology and a Meta-regression-Bayesian, Regularized, trimmed (MR-BRT) model, to provide a robust stroke risk estimate for the general population while accounting for multiple potential biases. Methods: We conducted a systematic review and Bayesian meta-analysis of population-based observational studies of AF and stroke, sourced from PubMed and EMBASE (1970-2024). To adequately capture potential global burden, all (paroxysmal, persistent/sustained, chronic and, unspecified) types of AF were considered as exposure and the study outcome was any types of incident (ischemic, hemorrhagic, or total) stroke. Relative risk (RR) assessments - hazard ratio, risk ratio, and odds ratio were extracted from published observational studies. Binary covariates were generated to identify potential systematic bias, including the representativeness, precision in exposure and outcome status determination, variations in definitions, and adjustment was made for confounders - age, sex, education, lifestyle factors, study design, and comorbidities. We used the MR-BRT model to estimate a conservative mean AF-stroke dichotomous risk function and the overall pooled mean RR, adjusting for study heterogeneity and publication bias. Results: Of 6,447 articles reviewed, 49 studies were included, with participants aged 18 to 99 and sample sizes ranging from 250 to 4.3 million. Individuals with AF had a 99% higher risk of stroke (RR 1.99, 95% uncertainty interval [UI]: 1.91, 2.08), with an increasing range of 92% to 108%, indicating a significant association despite study heterogeneity (γ). The most conservative estimate was 1.92 (95% UI: 1.90, 1.99). No publication bias was found based on the funnel plot analysis. Conclusion: This study quantifies the risk of all strokes in the general population due to any type of AF. Differences in age, comorbidities, and medication use (especially anticoagulants) across populations and the level of confounder adjustment may influence the observed risk. The BoP framework highlights the importance of synthesizing high-quality evidence to guide targeted interventions and health policy decisions aimed at reducing stroke globally. These findings support more aggressive AF management, particularly in lower-resource settings, as part of stroke prevention strategies to reduce stroke incidence.
Abstract P1022: Interatrial Septal Thickening as a Predictor of Atrial Fibrillation and Structural Heart Remodeling
Introduction: Lipomatous hypertrophy of the interatrial septum is characterized by adipose deposition in the interatrial septum (IAS). Although generally considered benign, its associations with arrhythmias and remodeling are not well understood and require further investigation. Understanding the role of IAS thickening in arrhythmogenesis and remodeling could improve detection and management. Hypothesis: We hypothesized that increased IAS thickness is associated with a higher prevalence of atrial fibrillation (AF), larger body surface area (BSA), interventricular septal thickness (IVS), coronary artery disease (CAD), and valvular disease. Methods: We conducted a retrospective analysis of 208 consecutive patients who underwent transesophageal echocardiography. IAS thickness was manually measured in the bicaval view by a trained physician at our academic center. IAS thickness was stratified into the groups <6 mm, 6-12 mm, and >12 mm. We analyzed variables including IVS thickness, valvular defects, electrocardiogram abnormalities, medications, and morbidities such as diabetes and hypertension. BMI and BSA were calculated. Chi-square and ANOVA were used to assess statistical significance (p < 0.05). Results: Among the 208 patients (mean age 60.5 years; 56% male), IAS thickening was significantly associated with increased BSA (p < 0.05), suggesting that body size and metabolic factors contribute to septal hypertrophy and structural heart changes. Patients with thicker IAS also had increased IVS thickness (p < 0.05), indicating that hypertrophic changes extend beyond the atrial septum to affect broader myocardial structures. IAS thickening was linked to CAD (p < 0.05) and mitral regurgitation (p < 0.05), suggesting that septal hypertrophy may serve as a marker for valvular pathology and atherosclerotic burden. AF was strongly correlated with increased IAS thickness (p < 0.05), reinforcing its link to electrical and structural heart remodeling. Conclusions: Increased IAS thickness may be associated with atrial arrhythmias, BSA, IVS thickness, CAD, and valvular dysfunction. Particularly in patients with cardiovascular risk factors, IAS thickening is linked to arrhythmias and structural heart changes. It may serve as a valuable marker for identifying at-risk patients and enabling earlier intervention to prevent adverse cardiac events. Larger studies are necessary to further explore these associations and deepen our understanding of IAS thickening’s clinical significance.
Fluidization and anomalous density fluctuations in 2D Voronoi cell tissues with pulsating activity
Cells not only can be motile by crawling but are also capable of nonmotility active motions like periodic contraction or pulsation. In this work, based on a Voronoi cell model, we show how this nonmotility activity affects the structure, dynamic, and density fluctuations of cellular monolayers. Our model shows that random cell pulsation fluidizes solid epithelial tissues into a hyperuniform fluid state, while pulsation synchronization inhibits the fluidity and causes a reverse solidification. Our results indicate this solidification is a Berezinskii–Kosterlitz–Thouless-type transition, characterized by strong density/dynamic heterogeneity arising from the annihilation of topological defects in the pulsating phase space. The magnitude and length scale of density heterogeneity diverge with the pulsating period, resulting in an opposite giant density fluctuation or anti-hyperuniformity. We propose a fluctuating hydrodynamic theory that can unify the two opposite anomalous fluctuation phenomena. Our findings can help to understand recent experimental observations in Madin-Darby canine kidney monolayers.
Abstract P2088: Impact Of Geographic Residence And Treatment Modality On Mortality Outcomes Among Adult Patients Diagnosed With Acute Myocardial Infarction
Background: In the United States, rural residents face unique challenges that affect their overall cardiovascular health and mortality including access to care for acute cardiovascular conditions. We assessed differences in mortality and mode of care among adult patients diagnosed with acute myocardial infarction (AMI) based on geographical residence. Methods: Using data from the Medicare Provider Analysis and Review files, we identified adult patients aged 45 and older who were diagnosed with AMI between 2015 and 2019. Cox-proportional hazards regression models were constructed to determine the association between patient’s geographic residence (rural vs. urban) on 30- and 90-day all-cause mortality. Results: A total of 868,955 adult patients diagnosed with AMI were included in this study. Twenty-six percent of the sample resided in rural areas. Among rural residents with AMI, 46% were managed invasively with either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery which was similar to 45% of urban residents. After controlling for age, race, sex, and comorbid conditions, rural residents had a higher risk of death compared to urban patients (aHR 1.04, p<0.001) at 30 and 90 days. In subgroup analyses, a similar pattern was observed among those who did not undergo invasive procedures (aHR 1.06, p<0.001), however, there was no differences in mortality at 30 days (aHR 0.99, p=0.30) and 90 days (aHR: 0.99, p=0.36) between rural and urban residents who were managed by PCI or CABG. Conclusion: Rural patients with AMI had a higher mortality risk than their urban counterparts, and this difference was driven by a higher death rate among those managed conservatively. Further investigation is needed to understand the underlying factors driving rural-urban disparities in mortality, particularly with non-invasive management of AMI.
Abstract P2006: Examining the Associations Between Resistance Exercise, Sleep, and Cardiometabolic Health in Young Black Women: Results from a 10-Week Randomized Controlled Trial
Introduction: Insufficient sleep, including short duration, poor efficiency, and high variability (night-to-night variation in sleep), is associated with increased cardiometabolic disease risk. Black adults are more likely to exhibit poor sleep in comparison to White adults, and Black women in particular are at high risk for poor cardiometabolic health. Effective strategies to attenuate these disparities are not well studied. Therefore, this study aimed to assess the impact of resistance exercise (RE) on sleep and cardiometabolic health in young Black women. Methods: 30 young Black women [25±4 yrs; body mass index (BMI)]: 30.3±9.5kg/m 2 ) completed a 10-week, twice weekly, supervised RE intervention. During pre and post-intervention visits we measured BMI, waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, triglycerides, and fasting blood glucose. We assessed objective sleep duration, efficiency, sleep timing standard deviation (SD), and midpoint using a Philips Actiwatch Spectrum PLUS watch. We measured self-reported sleep quality using the Pittsburgh Sleep Quality Index (PSQI). We assessed pre to post RE changes in variables of interest via t-tests (PSQI) or Wilcoxon Signed Rank tests (sleep duration, efficiency, timing SD, midpoint), and Spearman’s Rank Correlations to assess associations between baseline sleep metrics and cardiometabolic factors with α set to ≤ 0.05. Results: There were no differences in objective sleep measures from pre to post RE. In contrast, self-reported sleep quality improved after RE (PSQI global scores- pre: 5.5±2.1 vs. post: 4.6±1.6, p = 0.020). Regarding sleep and cardiometabolic health, higher sleep efficiency was associated with a lower BMI (r= -0.458, p = 0.013), WC (r= -0.445, p = 0.015), DBP (r= -0.489, p = 0.007), and glucose concentration (r= -0.433, p = 0.019). Higher sleep timing SD (i.e., bedtime) was correlated with higher fasting glucose concentration (r= 0.521, p = 0.013). Unexpectedly, increased sleep midpoint was associated with lower SBP (r= -0.615, p = 0.002) and DBP (r= -0.613, p = 0.002). Conclusion: Our data indicate that 10 weeks of RE improved self-reported, but not objective, sleep quality in young Black women. Pre-intervention sleep efficiency and variability were associated with select measures of cardiometabolic health. Future studies should promote strategies to increase consistent sleep habits to reduce the risks for cardiometabolic disease in Black women.