Browse Articles

Abstract TU110: Latent Classes of Health-Related Social Needs and Associated Cardiovascular Risk in US Older Adults: Findings from the National Health and Aging Trends Study (NHATS)

Introduction: Health related social needs (HRSN) are associated with adverse cardiovascular (CV) outcomes in the growing US older adult population. Identifying subgroups with distinct HRSN profiles and their associated CV and geriatric risks would support the design and targeting of novel preventive interventions. Hypothesis: Older adults form distinct HRSN-defined subgroups, with higher HRSN subgroups having higher burden of CV risk and geriatric conditions and likelihood of hospitalization. Methods: Using 2015 NHATS data, we performed latent class analysis to identify HRSN subgroups among 8,334 US adults age ≥65, representing 42.5 million Medicare beneficiaries, using the following indicator variables: homebound status, social isolation, transportation disadvantage, digital isolation, food insecurity, and financial insecurity. Optimal number of classes was determined using model fit statistics (Table 1). We assigned participants based on their posterior class membership probabilities. We compared self-reported demographics, CV conditions, and geriatric conditions across classes using χ 2 tests, and compared marginal predicted probabilities of one-year hospital admission using logistic regression. Survey weights were applied to account for complex sampling design. Results: Latent class analysis identified 3 distinct classes according to HRSN (Table 2). Class 1 (72% prevalence) had the lowest rates of all HRSNs. Classes 2 (23%) and 3 (5%) shared high prevalence of homebound status (56% and 63% vs. 6% in Class 1). Class 2 had the highest prevalence of digital isolation and social isolation, while Class 3 had the highest prevalence of food insecurity, financial strain, and transportation disadvantage. Both Classes 2 and 3 had higher burdens of CV risk factors and geriatric conditions, with Class 2 being older with more dementia, and Class 3 having the greatest burden of metabolic risk factors (Table 3). Classes 2 and 3 had higher prevalence of CVD than Class 1. The probability of subsequent one-year hospital admission was higher for individuals in Classes 2 (33%; 95% CI 30-36) and 3 (30%; CI 23-36) versus Class 1 (18%; CI 17-20). Conclusions: There are distinct older subpopulations with greater HRSN burdens, higher CV risk, and greater likelihood of hospitalization. Interventions addressing HRSNs, tailored to subgroups with higher digital and social isolation, or with more food insecurity and financial strain, may improve CV outcomes in the aging US population.

Breaking the rate limiting barrier in lithium||sulfur batteries via spin state engineering

Comparative efficacy and safety of Chinese botanical drug injection in patients with sepsis: A systematic review and Bayesian network meta-analysis of randomized clinical trials

Background Sepsis represents a significant global health challenge, contributing to considerable morbidity, mortality, and healthcare costs. Integrating Chinese botanical drug injections (CBDIs) with Western Medical Treatments (WMT) has been increasingly recognized for its enhanced therapeutic effects in sepsis management. This Bayesian network meta-analysis aims to identify the optimal combination regimen of CBDIs and WMT for sepsis therapy. Methods A comprehensive literature search was conducted across eight electronic databases to identify Randomized Controlled Trials (RCTs) relevant to our study criteria, spanning from their inception until January 1, 2024. The quality of included studies was rigorously assessed using the Cochrane Collaboration's Risk of Bias 2 (ROB 2) tool. Data synthesis and analysis were performed utilizing R 4.1.2 and Stata 17.0 software. Additionally, publication bias was assessed through the construction of funnel plots. Results This network meta-analysis assessed 72 RCTs involving 6,351 participants to evaluate the effectiveness of seven CBDIs in conjunction with WMT. It found Huangqi injection to be the most effective in improving APACHE II scores. Tanreqing injections significantly reduced procalcitonin (PCT) levels, with particularly superior. Shenmai injection was most effective in decreasing C-reactive protein (CRP) levels. In terms of reducing tumor necrosis factor-alpha (TNF-α), Shenmai injection with WMT showed the best results. Xuebijing injection stood out in lowering white blood cell counts (WBC). Huangqi injection was noted for its best effectiveness in the 28-day mortality rates. Conclusion The therapeutic efficacy of CBDIs in treating sepsis is underscored by our research findings, wherein certain botanical drugs exhibit heightened efficacy and safety attributes. The incorporation of these alternative modalities into contemporary sepsis management paradigms is advocated by the outcomes of our investigation. Nonetheless, rigorous, large-scale trials are imperative to substantiate and enhance these preliminary discoveries.

Abstract WE471: Entrenched Geography of the United States Ischemic Heart Disease Mortality: Geotemporal Persistence and Social Determinants Through 2016-2023.

Background: Ischemic heart disease (IHD) remains the leading cause of death in the United States, with longstanding geographic disparities. The COVID-19 pandemic disrupted care delivery and exposed systemic vulnerabilities, raising questions about whether cardiovascular mortality patterns changed post- pandemic. This study examined pandemic-era IHD mortality hotspots and evaluated their persistence in relation to social determinants of health (SDoH). Methods: County-level geospatial analysis of IHD mortality (ICD-10: I20–I25) using CDC WONDER data, comparing pre-pandemic (2016–2019) and pandemic-era (2020–2023) epochs was conducted using crude mortality rates (CMR). Poverty, insurance, and primary care physician density was analyzed as SDoH. Univariate Getis-Ord Gi* (p<0.05) identified hotspots and coldspots, while bivariate Local Moran’s I assessed spatial overlap of high-CMR clusters with adverse SDoH and with median age to evaluate age-related confounding. Results: County-level comparison revealed remarkable persistence in the geography of the IHD mortality. Hotspots and coldspots decreased slightly from 379 to 373 and 423 to 408, respectively. Reflecting spatial stability with modest consolidation. High-burden clusters remained concentrated across the Mississippi Delta, central and southern Appalachia, and the rural Southeast, with smaller persistent pockets in the Midwest and Southwest. Coldspots persisted in the Mountain West, Pacific Northwest, and New England. Mean hotspot CMRs were nearly unchanged (207.25 vs. 206.90 per 100,000), while coldspot means rose marginally (95.34 vs. 95.73), indicating ongoing concentration within entrenched regions. Bivariate mapping showed overlap between older populations and IHD hotspots; however, median age increased more in coldspots (38.71 to 39.38) than hotspots (43.16 to 43.21), suggesting age alone does not explain disparities. Poverty exhibited the strongest, most stable spatial concordance with mortality hotspots, especially across the Southeast and Appalachia. Limited primary care access showed a similar but narrower alignment, while uninsuredness showed weaker, region-specific overlap in the South-Central region. Conclusion: The pandemic reinforced rather than restructured the geography of IHD mortality. Persistent hotspot belts, aligned with entrenched poverty and constrained healthcare access, underscore the structural durability of regional inequities in cardiovascular outcomes despite nationwide systemic shock.

Abstract WE563: Loneliness, Social Support and Cardiovascular Risk Among Midlife Adults: A Population-Based Study Using the 2023 Behavioral Risk Factor Surveillance System.

Introduction: Loneliness and low social support are potential risk factors for cardiovascular disease (CVD). Both are linked to stress-related neuroendocrine and inflammatory changes, but population-level evidence linking these exposures to CVD remains limited. This study investigates how loneliness and social support interact to contribute to cardiovascular risk among U.S. adults aged 45–64, a critical window for CVD prevention. Methods: We used 2023 Behavioral Risk Factor Surveillance System data from adults aged 45-64 to assess how the joint exposure of loneliness and social support were associated with CVD risk. Both variables were dichotomized and combined into four exposure groups. Elevated CVD risk was defined as ≥ 3 of six of AHA Life’s Essential 8 factors: smoking, physical activity, obesity, hypertension, hypercholesterolemia, and diabetes. Multiple imputation was used to address missing data, and survey weights were applied. Weighted prevalence ratios were quantified using adjusted Poisson regression models with a robust variance estimator and 95% confidence intervals were used to compare outcomes across exposure groups. Adjusted models controlled for age, sex, race and education. Results: Overall, 67,541,291 individuals were included; 26% of whom reported loneliness and 17% reported low social support. Approximately, 10% of individuals reported high loneliness and low support. CVD risk factors were disproportionately prevalent among lonely and low social support groups. For example, diabetes prevalence was 16% among lonely + low support adults vs. 7% among those not lonely + high support. In adjusted models, the prevalence of elevated CVD risk among adults who were lonely and had low social support was 1.36 times (95% CI 1.15–1.61) the prevalence among those with high support who weren’t lonely. Individuals who were lonely but had high support also had a higher prevalence of elevated CVD risk (PR 1.23, 95% CI 0.98–1.54), while those who were not lonely but had low support exhibited modestly higher prevalence of heightened CVD risk (PR 1.14, 95% CI 0.96–1.32). Conclusion: Our findings add nationally representative evidence that loneliness and low social support, particularly in combination, are associated with elevated CVD risk in midlife. Addressing loneliness and strengthening social support through public health interventions that promote peer support and social cohesion are needed to mitigate suboptimal CVD outcomes and promote cardiovascular equity.

Antigen-specific immunotherapy with a CD4+ T cell neoepitope restrains CD8+ T cell differentiation in murine pancreatic islet grafts

Abstract TH975: Limited English Proficiency and its Association with Hypertension Cascade among a Nationally Representative Sample of Reproductive-aged Women

Background: Hypertension is a major risk factor for cardiovascular disease among reproductive-aged women. Language barriers may contribute to disparities in hypertension awareness, diagnosis, and treatment. This study examines the association between limited English proficiency (LEP) and hypertension outcomes using nationally representative data. Hypothesis: Women of reproductive age with limited English proficiency have lower odds of hypertension awareness, prevalence, and treatment compared to English-proficient women. Methods: We analyzed a cross-sectional sample of women of reproductive age (18-50 years) using data from the National Health and Nutrition Examination Survey (2005-2023). LEP was defined as completing any portion of the interview in a language other than English or requiring an interpreter. Hypertension was defined as average systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg, or self-reported diagnosis. Outcomes included awareness (diagnosed; yes/no), prevalence (measured BP), and treatment (medication use; yes/no). Survey-weighted multivariable logistic regression models estimated the odds of hypertension outcomes and LEP adjusting for age, education, race/ethnicity, marital status, insurance, employment, and income. Results: Among 29,772,084 women of reproductive age, 3.9% had LEP. Hypertension was less prevalent among LEP vs. English-proficient women (10.1% vs. 15.9%), though not significant after adjustment (adjusted odds ratio [aOR] 0.55, 95% CI 0.26–1.17). Hypertension awareness (8.6% vs. 14.3%; aOR 0.41, 95% CI 0.14–1.18) and treatment (61.6% vs. 68.7%; aOR 0.27, 95% CI 0.02–4.55; p = 0.35) were also lower among LEP women vs. English-proficient women, respectively. Conclusion: Women of reproductive age with LEP exhibit lower hypertension prevalence despite lower awareness and treatment rates. This pattern suggests the presence of protective pathways such as cultural health practices or differing health behaviors, that warrant further investigation. Advancing linguistically inclusive public health strategies and examining these potential protective factors are essential to improve cardiovascular equity.

Abstract TU215: Associations Between Rurality and Early Pregnancy Cardiovascular Health Behaviors in a Central Appalachian Cohort

Introduction: Ideal cardiovascular health behaviors are associated with lower rates of cardiovascular and other pregnancy complications. Since such complications are more prominent in rural areas compared to urban areas, this study aimed to evaluate whether rurality is associated with first trimester Life’s Essential 8 (LE8) CVH behaviors, including physical activity, sleep, diet, and avoidance of nicotine. Hypothesis: Those living in rural areas would have worse CVH behaviors in early pregnancy than their urban counterparts. Methods: This study presents a secondary analysis of the Mountain Mama and Baby Study cohort (n=417) from the first trimester of pregnancy. Participant’s physical addresses were translated into the United States Department of Agriculture’s 2020 Primary Rural-Urban Commuting Area (RUCA) Codes and classified into three categories: 1) Urban-Metropolitan (1-3), 2) Rural-Micropolitan (4-6), and 3) Rural-Small Town (7-10). CVH behavior scores were assessed using the LE8 framework, calculated from self-report instruments for physical activity (Pregnancy Physical Activity Questionnaire), sleep duration (Pittsburgh Sleep Quality Index), diet (Mediterranean Eating Pattern for Americans), and past/current nicotine exposure. Each CVH behavior was scored from 0 (least healthy) to 100 (most healthy) and an overall mean score was calculated by adding the scores for each measure and dividing by 4. The overall score and each component were classified into two CVH categories: 1) high (≥80) and 2) low-to-moderate (≤79). Adjusted logistic regression models evaluated the associations between rurality and overall CVH behaviors and each component, adjusting for age, race/ethnicity, and education. Results: In the adjusted analysis, living in rural-micropolitan areas and rural-small towns in central Appalachia were associated with significantly higher odds of low-to-moderate CVH behavior in early pregnancy compared to living in urban-metropolitan areas (rural-micropolitan: OR = 1.8, 95% CI: 1.0, 3.1; rural-small towns: OR = 2.3, 95% CI: 1.2, 4.6). However, no statistically significant associations were found between rurality and having low-to-moderate individual CVH behaviors, including physical activity, sleep, diet, or nicotine exposure (See Table 1). Conclusion: Poorer CVH behaviors in pregnancy may contribute to disparities but also provide an intervention strategy to reduce pregnancy-related morbidity and mortality among rural populations.

Hipk transduces nutrient signals to control intestinal stem cell proliferation and fate in Drosophila

Regulation of physical activity and energy expenditure through Phf6 in the medial preoptic area

Abstract WE466: Al Ritmo del Corazón: Regional Differences in Physical Activity and Hypertension Across Puerto Rico, Hawaii, and the Mainland United States

Introduction: Hypertension (HT) remains a leading driver of cardiovascular disease in the US, but its burden is unevenly distributed across regions. The prevalence of HT varies significantly across US regions, including Puerto Rico (PR) and Hawaii (HI), despite shared geography and governance. However, limited research has examined how geographic context interacts with physical activity (PA) levels to influence HT risk. The aim of the study is to examine the association between HT and the intersection of geographic location (PR, HI, and mainland US) and PA levels. Hypothesis: There will be a significant interaction effect between geographic location and PA levels on HT. Methods: A total of 265,930 adults from the 2023 Behavioral Risk Factor Surveillance System were included. Participants self-reported whether they had ever been diagnosed with HT, which served as the dependent variable. Geographic location was categorized as PR, HI, or the mainland US. Two PA variables were analyzed: meeting aerobic PA guidelines (≥150 min/week) and weekly PA levels (0, 1–299, or ≥300 min/week). Multiple logistic regressions were conducted for each PA variable, with HT regressed on geographic location, PA, and their interaction, adjusting for demographic covariates. Results: Among the participants (49.7% female; 97.1% mainland, 2.0% HI, 0.9% PR), 41.3% reported HT. Prevalence differed by region (χ2=122.58, p <.05): 41.3% in the mainland U.S., 35.9% in HI, and 48.9% in PR. Participants meeting aerobic PA guidelines had lower HT prevalence (37.98%) than those who did not (χ2=1854.20, p <.05). In logistic regression, living in HI was associated with lower odds of HT (OR=0.82, 95% CI [0.74, 0.92]), while living in PR was associated with higher odds (OR=1.58, 95% CI [1.42, 1.76]). Meeting PA guidelines was associated with lower odds of HT (OR=0.84, 95% CI [0.82, 0.85]), and the interaction between region and PA was not significant ( p >.05). Similar results were found with the regression of weekly PA, PA remained independently associated with lower odds of HT (OR=0.79-0.85, p <.05), and PR remained at higher risk (OR=1.55, 95% CI [1.39, 1.73]) with no interaction effect observed. Conclusions: Despite the benefits of PA, regional differences in HT, especially the higher prevalence in PR, indicate that the contextual and structural factors play a significant role. Tailored interventions addressing both lifestyle and social determinants may be needed to mitigate these disparities.

Abstract WE484: Mortality From Coexisting Metabolic Syndrome and Cardiac Arrhythmias Increased in the United States From 1999 to 2023

Introduction: Metabolic syndrome (MS), represented by a constellation of metabolic abnormalities is a prothrombotic and proinflammatory state, known to interrupt the electrical configuration of the SA node, resulting in cardiac arrhythmia (CA) . In this study we analyze the mortality trends and uncover disparities over the past 25 years (1999-2023), for patients where both MS and CA co-occur. Methods: We analyzed CDC WONDER death-certificate data (1999–2023) for U.S. adults aged ≥25 years. Outcomes used ICD-10 codes for metabolic-syndrome components (E10–E14, E66, E78, E88, I10) and cardiac arrhythmias (I44–I49). Age-adjusted mortality rates were calculated per 100,000. Joinpoint regression estimated APC and AAPC; significance was defined as 95% CIs excluding zero (p<0.05). Forecasts used ARIMA models to project future trends. Results: A total of 1,844,767 deaths occurred from MS and CA. AAMR started from 17.24 and rose to 24.48 in 2001 [APC: 16.85 (95% CI: 6.52 – 28.17)]. After 2001 it slowly increased to 35.96 in 2018 [APC: 1.96]. Post 2018, AAMR rose to 51.87 in 2021 [APC: 13.94] before dropping to 47.54 in 2023. Overall, there was a positive mortality trend [AAPC: 4.08 (95% CI, 3.03 – 5.14)]. Males had 48.44% deaths, with its AAMR starting from 20.09 and following the overall population’s trend before ending at 58.32 [AAPC: 4.36]. Females AAMR started from 15.02 and ended at 38.99 [AAPC: 3.79], following similar patterns. Non-Hispanic (NH) Whites with 83.01% deaths had an AAMR average of 33.46 and saw the greatest overall increase in their AAMR, starting from 16.99 and ending at 52.00 [AAPC: 4.51]. Individuals aged 65+ had the highest overall AAMR rise [AAPC: 4.37], deaths (88.28%) and AAMR average (145.44). Midwestern region had the highest AAMR average (34.68), but the region of South had the most deaths (35.51%) and the greatest overall increase [AAPC: 4.69]. Urbanization and states data, limited till 2020, revealed nonmetropolitan areas having a higher AAMR (34.64) than metropolitan ones (29.49), with the state of Vermont being affected the most with a total AAMR of 49.86, followed by Ohio (44.06) and Oregon (40.80). Conclusions: Despite improvement in medical care, mortality remains substantial and has been steadily increasing for patients in which MS and CA co-occur, with a sharp rise occurring from 2018 till 2021. Males, NH Whites and 65+ adults and the residents of Midwest and the state of Vermont, Ohio and Oregon are disproportionately affected.

Predictive modeling of influenza strain drugs using temperature-based topological indices and regression analysis via multi-criteria decision making techniques

Ancient DNA reveals 4000 years of grapevine diversity, viticulture and clonal propagation in France

Abstract WE463: Circulating Metabolites Mediate the Association Between Polygenic Risk Score and Incident Hypertension

Objective: Genetic susceptibility quantified by a polygenic risk score (PRS) is associated with incident hypertension, yet the metabolic pathways linking genetic risk to disease remain unclear. We investigated which circulating metabolites are associated with incident hypertension and whether they mediate the PRS–hypertension association. Methods: We analyzed 8,458 community-dwelling Japanese adults aged ≥20 years (mean [SD] 57.9 [11.8]; 71.0% women) free of hypertension at baseline. Nuclear magnetic resonance spectroscopy quantified 43 plasma metabolites (amino acids, ketone bodies, glycolytic intermediates, etc.). A PRS for systolic blood pressure was derived from a prior genome-wide association study meta-analysis. Incident hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or self-reported antihypertensive treatment. Modified Poisson regression estimated risk ratios (RRs) for PRS–hypertension; multiple linear regression assessed associations between the PRS and each metabolite; mediation analysis quantified metabolite-specific indirect effects. Results: Over a median of 4.3 years of follow-up, 1,333 cases occurred. A higher PRS was associated with incident hypertension (RR 1.44, 95% CI 1.34–1.55). 2-Hydroxybutyric acid, creatinine, glycerol, and caffeine were associated with a higher risk, whereas methionine and acetic acid were associated with a lower risk. Five metabolites, including 2-hydroxybutyric acid, were positively correlated with the PRS, and seven were negatively correlated. 2-Hydroxybutyric acid modestly mediated the PRS–hypertension association (proportion mediated ≈1.0% [95% CI 0.2–3.0%]). Conclusion: 2-Hydroxybutyric acid slightly mediates the association between genetic susceptibility and incident hypertension, suggesting metabolic pathways that could inform prevention or therapeutic strategies.

Cardiac Magnetic Resonance Before Ventricular Tachycardia Ablation and During Follow-Up

Ambrisentan attenuates cisplatin-related mitochondrial dysfunction in the heart via regulation of p53 and NF-κB signaling

Abstract Ambrisentan, an endothelin receptor A (ET A ) antagonist, confers beneficial effects in cardiovascular diseases, but its role in mitigating chemotherapy-induced cardiotoxicity remains unexplored. This study investigates the protective effects of ambrisentan against cisplatin-induced cardiotoxicity in H9c2 cardiomyoblasts, focusing on its regulatory role via the p53 and NF-κB signaling pathways. Ambrisentan reduced cisplatin-induced apoptosis by downregulating caspase-3/7 activity and BAX expression while upregulating Bcl-2. Cisplatin-induced inflammation was also attenuated by ambrisentan through the reduction of TNFα and IL6 levels. Furthermore, ambrisentan protected cells against cisplatin-induced mitochondrial damage by lowering ROS levels, promoting mitochondrial fusion (OPA1, MFN1), inhibiting fission (DNM1, FIS1), and enhancing mitochondrial biogenesis (ATP5A, NRF1, PGC1α). Structured illumination microscopy revealed that ambrisentan preserved tubular mitochondrial morphology and reversed cisplatin-induced fragmentation. In addition, ambrisentan restored mitochondrial respiration and glycolysis, evidenced by improved oxygen consumption rate and extracellular acidification rate, along with increased pro-survival molecules (p-Akt and p-Erk1/2), under cisplatin-mediated stress. Mechanistically, pharmacological inhibition of p53 and NF-κB enhanced the protective effects of ambrisentan, whereas their activation exacerbated cisplatin-induced cardiac injury. Therefore, ambrisentan may serve as a potential agent for suppressing apoptosis, inflammation, and mitochondrial impairments, offering protection against cisplatin-associated cardiotoxicity through modulation of the p53 and NF-κB pathways.

Nanoscale exchange-bias magnetic tunnel junctions enabled memristive synapse and leaky-integrate-fire neuron for neuromorphic computing

Abstract Neuromorphic computing implemented by spintronic memories offers computational advantages, including in-memory computing capability, high energy efficiency, and near-unlimited endurance. However, their basic units, magnetic tunnel junctions (MTJs), face inherent challenges in emulating analog synapses and spiking neurons due to their bistable resistance states and lack of bio-realistic switching dynamics. Here, we experimentally demonstrate on-chip co-integrated memristive synapse and leaky-integrate-fire (LIF) neuron designed with nanoscale exchange-bias MTJs (EB-MTJs). By exploiting the spatial distribution of antiferromagnets and its current-dependent modulation, we achieve stable continuous multi-state synaptic behavior with spike-timing-dependent-plasticity (STDP) characteristics in compact (~100 nm) EB-MTJs. Furthermore, time-resolved measurements reveal that EB-MTJs can be progressively programmed by 0.4 ns pulses, emulating LIF neuronal dynamics with high operational bandwidth in the gigahertz range. Finally, we construct a convolutional spiking neural network based on EB-MTJs and achieve 96% accuracy in gesture recognition via a hybrid backpropagation-STDP algorithm, highlighting their potential in neuromorphic computing.

Abstract 52: Long-term Diabetes Incidence Among Young Adults By Glycemic Status And Risk Scores: 35-Year Follow-Up in the Coronary Artery Risk Development In Young Adults (CARDIA) Study

Introduction: Young adulthood is increasingly recognized as an important window for diabetes prevention. While lifestyle interventions and pharmacotherapy are available to young adults, early identification of those at risk of diabetes progression is essential to targeted prevention. Diabetes risk progression has been extensively studied in other age groups, but it is unknown whether younger adults with prediabetes have similar risk of progression. Long-term studies of diabetes outcomes from young adulthood can fill this gap. Objective: To characterize 35-year diabetes incidence among young adults in a diverse population-based cohort by baseline glycemic status and risk scores. Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) study followed a cohort of individuals aged 18-30 at enrollment, with balanced subgroups of race (Black and White), gender, and education level, in 4 US cities. Individuals had 8 glycemic examinations from 1985-1986 through 2020-2022. We determined diabetes incidence density, cumulative incidence, and Kaplan-Meier survival, by baseline glycemic status (normoglycemia or impaired fasting glucose [IFG]) and ADA-CDC Prediabetes Risk Test scores (“high-risk” defined >=4; score components gender, BMI, family history, physical inactivity, hypertension). Results: We followed 4985 participants for a median 30.1 years (Table 1). Overall diabetes incidence density was 21.2 cases per 3500 person-years (21.2 cases/100 individuals in 35 years; cumulative incidence 16%), and 58.8 cases for baseline IFG (n=101; cumulative incidence 38%). Individuals with both IFG and high-risk score had highest incidence (123.8 cases; cumulative incidence 73%), followed by baseline normoglycemia and high-risk score (67.5 cases; cumulative incidence 43%) then IFG and low-risk score (48.5 cases; cumulative incidence 31%). (Table 2; Fig 1) Conclusions: 35-year diabetes incidence among young adults with IFG was lower than prior long-term studies in middle-aged cohorts. Those with IFG with high-risk scores had highest incidence, and baseline normoglycemia with high-risk scores had higher incidence than IFG overall or IFG with low-risk scores. These findings support increased use of risk-assessment tools in young adults, lowering the threshold for ADA-CDC Prediabetes Risk Test from 5 to 4 for young adults (for Diabetes Prevention Program eligibility), and highlight a need for validated, young adult-specific diabetes risk screening approaches.

Abstract 69: Healthy Dietary Pattern, Blood Transcriptomic Profile, and Risk of Cardiovascular Disease: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Background: A healthy diet is crucial for preventing cardiovascular disease (CVD) by modulating gene expression, but the gene pathways remain poorly studied. Hypothesis: Healthy dietary intake is associated with a favorable blood transcriptomic profile, which in turn is associated with a lower CVD risk. Methods: Among HCHS/SOL participants with dietary and transcriptome data ( n = 6796), we performed cross-sectional analyses to identify whole-blood RNA sequencing (RNA-seq) signatures of a healthy dietary pattern assessed by Alternative Healthy Eating Index (AHEI), where higher scores indicate a healthier diet. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to characterize diet-related gene modules and examined their associations with incident CVD. Results: Out of 18989 RNA-seq features, we identified 375 RNA-seq signatures associated with AHEI (FDR- q <0.10; Fig. A ). These identified RNA-seq signatures were clustered into four co-expressed gene modules ( Fig. B ), including an adaptive immunity module and an innate immunity&oxidative stress module involving IL-17 and NF-κB signaling ( Fig. C ). The adaptive immunity module was positively associated with AHEI and with blood immune traits reflecting adaptive immune activation (e.g., higher proportions of activated CD4+ and CD8+ T lymphocytes). By contrast, the innate immunity&oxidative stress module was negatively associated with AHEI and positively with traits indicative of innate immune activation (e.g., higher neutrophil proportions; Fig. D ). Furthermore, higher levels of adaptive immunity module were associated with a lower CVD risk (HR [95% CI]: 0.84 [0.72–0.98]), whereas higher levels of innate immunity&oxidative stress module were associated with a higher CVD risk (1.19 [1.02–1.39]; Fig. E ). Conclusions: Adherence to a healthy dietary pattern is associated with a favorable blood transcriptomic profile related to adaptive and innate immune pathways, which may help explain the protective association between healthy diet and CVD.