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Key natural influences on groundwater storage changes in Central and Southern Arizona

Abstract TH891: Association of Cardiovascular and Social Risk Factors with Cognitive Function in Low Income Hypertension Patients with Low Cognitive Reserve

Introduction: Increasing evidence has identified modifiable risk factors for Alzheimer’s disease and related dementias (ADRD). Yet most studies include individuals with few cardiovascular co-morbidities, high education/SES, and few racial/ethnic minorities. We analyzed relationships between modifiable risk factors and cognitive function in low-income, predominantly Black, hypertensive patients with a high burden of cardiovascular co-morbidities. Methods: This cross-sectional analysis included 1,308 low-income, racial minority hypertensive patients in 44 low resource clinics in Louisiana, Mississippi, and Texas. ADRD risk factors included: low education (<high school), obesity (BMI ≥ 30 kg/m 2 ), social contact (married or living with a partner), and self-reported prior diagnosis of diabetes, depression, and high cholesterol. Cognitive function was measured using the MoCA and a neuropsychological test battery assessing global cognitive function, executive function, and memory. Linear regression models assessed associations between each modifiable ADRD risk factor and MoCA score, standardized global cognitive, executive function, and memory scores. Models were adjusted for age, sex, race, and all other ADRD risk factors. Results: Participants had a mean age of 64.5 years, 62.5% were Black, 61.3% female, and the mean MoCA score was 19.8. About 60% were obese, 46% had diabetes, and 67% had high cholesterol. Social contact was associated with higher MoCA (β=0.47, p=0.03), higher global cognitive function (β=0.10, p=0.005), and higher memory (β=0.12, p=0.0009) but not with executive function after adjustment. Low education was associated with lower MoCA (β=-3.48, p<.0001), lower global cognitive function (β=-0.57, p<.0001), lower executive function (β=-0.45, p<.0001), and lower memory (β=-0.36, p<.0001). Diabetes was associated with lower standardized global cognitive score (β=-0.07, p=0.03) but not with MoCA, executive function, or memory. Obesity was associated with higher standardized global cognitive score (β=0.08, p=0.03) but not MoCA, executive function, or memory. Depression and high cholesterol were not significantly associated with cognitive outcomes after adjustment. Conclusions: Low education, diabetes, and less social contact were associated with lower cognitive function in understudied hypertensive patients. Targeting these factors could benefit cognition in low-income hypertensive patients with cardiovascular co-morbidities.

Abstract TH876: Twenty-four-month Changes in Lipid Optimization among Urban and Rural Veterans: VALOR-QI program

Background: Optimal lipid management is critical for reducing cardiovascular events among those with atherosclerotic cardiovascular disease (ASCVD). When implementing LDL-C lowering methods, rural populations may often be disproportionately affected due to unique challenges such as an increased average distance from the nearest VA site and pharmacy. Aims: This quality improvement program sought to determine whether a variety of lipid optimization strategies yielded similar benefits in veterans residing in rural versus urban areas in the US. Methods: VALOR-QI was conducted among veterans with prevalent ASCVD at 50 VA sites across the US between December 2022 to June 2025. Veterans were assigned either urban or rural designation based on the Geographic Information System (GIS). At each of the 50 VA sites, American Heart Association consultants conducted an assessment to identify barriers to lipid management and worked with sites to implement strategies tailored to the identified barriers. The primary outcome was the proportion of veterans with LDL-C treated to target (<70 mg/dL) between baseline and 24 months. Secondary outcomes included changed during the program in prevalence of LLT use, adherence to LLT, and absolute reduction in LDL-C. Results: A total of 11,827 veterans engaged in the program had repeated LDL-C data at 24 months. 8657 veterans were designated as urban and 3,170 were designated as rural. At 24 months, 34.5% of veterans in urban and 32.5% veterans in rural areas achieved LDL-C <70 mg/dL (p=003955). Mean LDL-C decreased by 16.1mg/dl for urban and by 15.9 mg/dl for rural veterans. Between baseline and 24 months, LLT use improved from 77.6% to 87.6% for urban and from 79% to 88% for rural. LLT adherence increased from 56.0% to 63.7% for urban and from 60.6% to 71.1% for rural veterans. Conclusion: This quality improvement program with a health coach demonstrated that addressing site-specific barriers to lipid management resulted in improvement in lipid optimization in both rural and urban veterans after 24 months.

Abstract TU256: Trends and Disparities in Mortality from Pulmonary Embolism by Place of Death in the United States, 1999–2023

Background: Pulmonary embolism (PE) is a life-threatening cardiovascular condition with significant mortality. Despite advances in care, limited data exist on place of death (POD) trends and associated disparities. Understanding POD offers insight into healthcare access and end-of-life equity. This study assessed national trends and sociodemographic differences in POD among U.S. adults who died from PE between 1999 and 2023. Methods: We conducted a retrospective analysis of CDC WONDER mortality data for adults aged ≥25 years with PE (ICD-10 I26) as the underlying cause of death from 1999–2023. POD was categorized as inpatient facility, outpatient/emergency department (ED), home, or hospice/nursing facility. Multivariable multinomial logistic regression was used to assess associations between demographic factors and POD. Results: A total of 790,088 PE-related deaths were identified. Most occurred in inpatient settings (54.7%), followed by home (17.9%), hospice/nursing facilities (13.8%), and outpatient/ED (13.5%). Adults aged 25–34 years had higher proportions of inpatient (44.6%) and outpatient/ED (36.2%) deaths. Those aged ≥85 years more frequently died in hospice/nursing facilities (29.9%). Black individuals had the highest outpatient/ED deaths (18.5%) and the lowest in hospice/nursing facilities (8.0%). Asian/Pacific Islander individuals had the highest inpatient mortality (64.9%). In multivariable models, Black individuals had significantly lower odds of hospice/nursing facility death compared to White individuals (adjusted odds ratio 0.28, 95% CI: 0.25–0.31). Hospice/nursing facility deaths were more common in medium/small metropolitan areas (15.7%) than in large metro (12.3%) or nonmetro areas (14.4%). Conclusions: Substantial sociodemographic disparities in POD among PE deaths persist in the U.S. Minority populations and urban residents were less likely to die in hospice or nursing facilities, suggesting inequities in access to end-of-life care. Findings underscore the need for targeted efforts to ensure equitable access to palliative and hospice services for patients with PE.

Exploring rainfall effects on the Xingfu Dayuan Landslide in Yecheng, Xinjiang, China using time-series InSAR technology and numerical simulation

Abstract WE570: Heat and cold waves are associated with increased stroke mortality in Brazil

Stroke is the second leading cause of death worldwide and a major public health concern in Brazil. Extreme heat is well recognized as a risk factor for ischemic stroke, but evidence on cold spells, event persistence, and their impact in tropical climates remains limited. We conducted a nationwide, municipality-level time-series analysis of stroke mortality in Brazil (2003–2023). Deaths from all-cause, ischemic, and hemorrhagic stroke were classified using ICD-10 codes. Temperature (adjusted for humidity) from ERA5-Land was the main exposure. Municipality-level days at or above the 90th/99th or below the 10th/1st percentiles defined Extreme Heat (EHE) and Cold Events (ECE), respectively. Additionally, indicators were created to identify if these extremes occurred on 2 or 3 consecutive days (e.g., EHE_x_3). Associations were estimated using stratified conditional quasi-Poisson regression with distributed lag nonlinear models (lag 0–7), adjusting for PM2.5, O3, NO2, SO2, and CO. Results were expressed as relative risks (RRs) with 95% confidence intervals (CIs) and attributable deaths per 1,000 nationally and by region. We analyzed 2,687,820 stroke deaths (827,930 ischemic; 1,698,904 hemorrhagic) from 3,610 municipalities. Extreme temperatures increased stroke mortality nationwide. For all-cause stroke, risk rose at the 90th percentile (RR 1.111, 95% CI 1.100–1.122) and 99th percentile (RR 1.227, 95% CI 1.199–1.256), and was amplified by persistence (EHE_99_3 RR 1.351, 95% CI 1.303–1.400). Cold extremes produced smaller but significant increases (ECE_10 RR 1.075, 95% CI 1.065–1.086; ECE_01 RR 1.129, 95% CI 1.105–1.153). Ischemic stroke was more heat-sensitive (EHE_99_3 RR 1.468, 95% CI 1.383–1.557), while hemorrhagic stroke was more cold-sensitive (ECE_01_3 RR 1.157, 95% CI 1.107–1.208). Attributable burdens reached up to 12 excess deaths per 1,000 person-days during persistent extreme heat. Regionally, risks were greatest in the South and Southeast, with ischemic stroke increasing under sustained heat (EHE_99_3 RR 1.664, 95% CI 1.433–1.933) and hemorrhagic stroke under cold (ECE_01_3 RR 1.747, 95% CI 1.426–2.139), while the North showed weak or null associations. Extreme temperatures increased stroke mortality in Brazil, with ischemic stroke more affected by heat and hemorrhagic by cold. Risks were further amplified by persistence, particularly for heat, underscoring the need for climate adaptation to reduce the cerebrovascular burden in vulnerable populations.

Abstract WE460: Impact of Socioeconomic Status on Outcomes of a Digital Cardiovascular Self-Management Program

Background: Digital health programs can expand access to preventive care and potentially reduce inequities driven by social determinants of health. However, individuals with fewer financial resources may be less likely to participate, risking wider gaps. This study examined whether SES influences enrollment, engagement, and healthcare utilization in a cardiovascular digital health program. Methods: We conducted a real world study of adults offered Hello Heart through their employer sponsored health benefits, comparing outcomes by SES proxied by area level median income. Lower income area residents (LARs) lived in tracts with median income below 138% of the federal poverty level (a Medicaid eligibility benchmark); others were classified as higher income area residents (HARs). We studied: (a) enrollment in the program, (b) engagement among enrolled users, measured as the number of blood pressure (BP) readings recorded within 6 months, and (c) healthcare utilization among participants with linked claims data, as compared to nonparticipants propensity matched on demographics and baseline health. Outcomes included primary care provider (PCP) visits and avoidable emergency department (ED) visits. Results: Enrollment: Among 118,700 eligible adults, enrollment was modestly higher among LARs versus HARs. Adjusted logistic regression controlling for age, gender, and plan relationship showed LARs were 11% more likely to enroll (aOR = 1.11, p < 0.001). Engagement: Among 16,538 enrollees, there was no difference in the number of blood pressures taken during the first six months of enrollment between LARs and HARs, t = −0.30, p = 0.77). Utilization: Difference in differences estimates showed increased PCP visits (LAR: +412 per 1,000; HAR: +331 per 1,000) and reduced avoidable ED visits (LAR: −46 per 1,000; HAR: −48 per 1,000) for participants relative to matched nonparticipants. Adjusted models confirmed significantly greater PCP use and lower avoidable ED utilization among participants ( ps < 0.05), with no significant interaction with area income ( ps > 0.05). Conclusions: In this large, real world evaluation, individuals from lower income communities enrolled in Hello Heart at slightly higher rates and engaged at levels comparable to those from higher income communities. Program participation was associated with increased PCP utilization and reduced avoidable ED use across income strata, suggesting potential to mitigate, rather than exacerbate, inequities linked to SES.

Abstract WE452: Association of Diabetes with Cardiac Structure and Function Among African Caribbeans in Tobago: A Population Based Cohort Study

Diabetes Mellitus (DM) is closely associated cardiovascular events and adversely effects the cardiac structure and function. Although persons from African ancestry are at high risk of diabetes-related cardiac abnormalities, little is known about diabetes associated echocardiographic abnormalities in Tobago at the population level. Therefore, the aim of this study was to investigate the association between DM and abnormal cardiac structure and function among African Caribbeans in Tobago. A total of 926 participants without history of heart failure underwent clinical examination and transthoracic echocardiography (TTE) from 2021 to 2024 in the Tobago Health Study (a community-based longitudinal cohort study of adults aged 40+ years). Echocardiographic images were captured using standard 2-D, M-mode doppler TTE conducted at a local cardiology clinic. Images were analyzed for left ventricular (LV) ejection fraction, left ventricular mass index (LVMI), left atrium mass index, diastolic dysfunction (DD), LV structural abnormalities (normal, concentric remodeling, and left ventricular hypertrophy [LVH]), E/e’ ratio, E/A ratio, and others by a centralized reading laboratory. Multivariable linear or logistic regressions were used, where age, sex, systolic blood pressure, body mass index (BMI), smoking status, and sedentary behavior which was assessed by TV watching were adjusted in each model. The mean age of this cohort was 60.8 with 61.2% female, 47.7% obesity (BMI >30 kg/m 2 ) and 20.2% self-reported DM. Most of the participants (77.2%) had LV structural abnormalities, predominantly concentric remodeling (69.5%). Additionally, the prevalence of DD was 13.4%, and LV ejection fraction <50% was 1.5%. The results of the multivariable regression analysis showed that self-reported DM is significantly associated with E/e’ ratio (p<0.001, Table) and LVMI (p=0.002, Table). In addition, in a subset of participants with fasting serum glucose (FSG, N=667), DM status was defined by FSG >125 mg/dL, oral diabetes medications, and/or use of insulin. DM based on FSG identified additional participants with undiagnosed DM but showed similar association with echocardiography metrics as those based on self-reported DM status. In conclusion, African Caribbean adults in Tobago with DM are at higher risk of abnormal LV structure and LV diastolic dysfunction. Thus, these results highlight the importance of DM awareness and control for optimal cardiac structure and function in Tobago.

Thermal, economic, and environmental assessment of optimal aerogel insulation thickness compared with conventional materials in syrian climates

Abstract The current study aims to optimize the use of insulation materials by determining the optimal thickness for exterior building walls across various Syrian climatic zones and different energy sources. The study focuses on a comparative analysis between nano-aerogel and conventional insulation materials, including Extruded Polystyrene (XPS), Polyurethane (PUR), and Glass Wool (GW), utilizing Heating and Cooling Degree-Days (HDD/CDD) methodology, to enhance energy efficiency in buildings. An integrated assessment was conducted through Life-Cycle Cost Analysis (LCC), encompassing thermal and environmental aspects, with a competitive advantage featuring the integration of space-saving requirements and the calculation of economic feasibility resulting from the rental of floor areas recovered through the use of low-thickness aerogel insulation. The results indicated that Glass Wool (GW) emerged as a highly feasible option prior to integrating space savings, with thicknesses ranging from 0.06 to 0.15 m. In contrast, aerogel achieved the highest efficiency when space savings were incorporated into the analysis, particularly in cities with high rental values such as Damascus, Aleppo (diesel fuel), and Latakia (diesel fuel), due to its remarkably low optimal thickness (0.001–0.011 m). Specifically, aerogel reached its peak efficiency in the city of Latakia (diesel fuel) at an exceptionally low optimal thickness of 0.001 m. At this level, the reduction in initial capital expenditure allowed space-saving revenues to dominate the economic balance, sharply decreasing the discounted payback period to just 1.2 years (the shortest value recorded in this study). This accelerated cost recovery pace enabled aerogel to outperform all studied conventional materials. The study concludes that there is a critical trade-off requiring a precise balance between the material’s embodied energy and the sustainable economic and spatial gains, making the selection of insulation material and its optimal thickness a decision that depends primarily on the economic and spatial context of the project. Environmentally, conventional materials achieved higher emission reduction rates compared to aerogel due to their larger adopted optimal thicknesses for all study scenarios presented.

Abstract TH841: Advancing Life’s Essential 8: Machine Learning Reveals Actionable Predictors of Cardiovascular Mortality in NHANES 1999–2018

Introduction: In 2022, the American Heart Association introduced the Life's Essential 8 (LE8) enhanced metric of cardiovascular health (CVH), a strong predictor of all-cause and cardiovascular disease (CVD) mortality in US adults, with evidence of a dose-response relationship. We aimed to identify the LE8 factors most strongly associated with lower all-cause and CVD mortality to inform prevention strategies. Methods: Data from 55,879 U.S. adults aged ≥20 years (mean age 47.5 years, 51.7% women) from NHANES 1999–2018 with mortality linkage through December 31, 2019 (mean follow-up 9.8 years) were used. LE8 lifestyle and biological factors and covariate data (age, sex, race/ethnicity, education, marital status, and poverty-income ratio) were imputed using multiple imputation (m=5 and m=10, predictive mean matching). Adaptive Least Absolute Shrinkage and Selection Operator (Lasso) variable selection was performed separately on each imputed dataset to identify the dominant LE8 predictors for all-cause and CVD mortality by removing less important variables. Factors selected in ≥60% of imputations were included in Cox proportional hazards adjusted models. Hazard ratios and 95% confidence intervals were pooled across imputations using Rubin's rules. Discrimination was assessed with Harrell's C-index. Results: During follow-up, 8,254 all-cause deaths (14.8%) and 2,112 CVD deaths (3.8%) occurred. Adaptive lasso consistently selected seven LE8 predictors of all-cause mortality (Table 1) and six predictors of CVD mortality (Table 2). Physical Activity was not selected (0%). Nicotine exposure was selected only in 40% of CVD models. Each 10-point increases in blood lipids were associated with small increments in all-cause and CVD mortality (HR for all-cause mortality 1.003, 95% CI 1.002-1.004, and for CVD mortality 1.002,1.0, 1.004). Each 10-point increases in nicotine exposure showed the largest reduction in all-cause mortality (HR 0.994, 95% CI 0.993–0.994). Meanwhile, each 10-point reduction in blood glucose yielded the greatest drop in CVD mortality (0.994, 0.993–0.996). The model C-index was 0.742 (95% CI 0.716–0.768) for all-cause mortality and 0.781 (0.751–0.811) for CVD mortality, both indicating good discrimination. Conclusion: Machine learning models identified six key CVH predictors most strongly associated with CVD mortality. Findings suggest that improving blood glucose and sleep health may offer the greatest mortality risk reduction.

Abstract MPTU12: Impact of the DASH4D Diet on Post-prandial Glucose Patterns assessed by Continuous Glucose Monitoring in Adults with Type 2 Diabetes

Introduction: In a recent randomized trial, we showed that a DASH-style diet optimized for adults with type 2 diabetes (DASH4D) reduced mean glucose assessed by continuous glucose monitoring (CGM). However, the impact of DASH4D on postprandial glycemic response (PPGR), or glucose dynamics following meal taking, is unclear. Objective: Quantify the effect of the DASH4D diet on the PPGR time series and evaluate the proportion of the overall glycemic benefit of the DASH4D diet attributable to PPGR. Methods: The DASH4D trial had a 4-period crossover design. Adults with type 2 diabetes were randomized to an order of four diets: DASH4D or a typical American dietary pattern (comparison), each with lower or higher sodium. Calories were adjusted to maintain a stable weight. As sodium was not expected to impact PPGR, we combined the lower and higher sodium arms within each diet. Feeding periods were 5 weeks, with ≥ 1 week break between periods. CGM devices were worn from the 3 rd to 5 th weeks, recording up to 14 days of data. In a subset of participants, staff recorded meal timing during CGM wear. We fit a functional model regressing the PPGR time series (CGM glucose 1 hour before to 4 hours after meal start time) on diet type, including participant-specific random effects and adjustment for age, sex, body mass index (BMI), and time of day. We also applied functional regression-based mediation analyses to estimate the proportion of the diet effect on mean glucose that was mediated by differences in PPGR. Results: We collected PPGR data from 768 meals across the 65 participants who consented to meal monitoring (median age 68 years, 66% female). The DASH4D diet reduced PPGR, ranging from a difference -4.5 mg/dL at meal onset to -14.7 mg/dL from 1-2 hours after the start of the meal ( Fig. 1a ). There was a significant difference in PPGR between the DASH4D and comparison diets over the entire observation period ( Fig. 1b ). Differences in PPGR mediated 88% of the overall effect of the DASH4D diet on CGM mean glucose ( Fig. 2 ). Conclusion: Among adults with type 2 diabetes, the DASH4D diet improved glycemic control primarily by reducing PPGR.

Epicardial Complement C3 Activation in Neonatal Cardiac Regeneration

A brain–edge co-evolution framework for zero-trust real-time hot patching in power equipment

Abstract WE458: Effects of a Food-is-Medicine Intervention on Blood Pressure Among Black and Hispanic Adults with Hypertension in Healthy Food Priority Areas: The THRIVE Pilot Trial

Background: Nearly half of all U.S. adults live with hypertension, the most significant modifiable contributor to cardiovascular morbidity and mortality. Food is Medicine (FIM) interventions are emerging strategies that improve access to both fresh produce and clinical nutrition support, yet implementation in underserved populations remains limited. Hypothesis: We tested whether a FIM intervention would lower systolic blood pressure (SBP) relative to produce bags alone, and whether adherence to DASH (Dietary Approaches to Stop Hypertension) would influence magnitude of treatment response. Methods: We conducted a 24-week pilot randomized controlled trial among 80 Black and Hispanic adults living with hypertension. Randomized participants were allocated to either THRIVE FIM intervention (produce prescriptions, personalized dietitian counseling, adaptive nutrition messaging) or enhanced usual care (EUC: produce bags alone). BP was measured at study entry, 12, 24 weeks. We calculated DASH scores as a mechanistic mediator. We used mixed-effects models to examine changes within and between groups, tested for treatment effect heterogeneity, stratified by DASH adherence (high ≥4.5 vs. low <4.5) and assessed threshold sensitivity. Results: Of 80 enrolled participants (mean age 54.5±11.4 years), 40 per group, 62% were Black and 34% were Hispanic. The mean BP was comparable in both groups at baseline (systolic: 136.3 vs. 137.4 mmHg, p=0.772; diastolic: 82.2 vs. 81.2 mmHg, p=0.658, Table 1 ). By week 24, THRIVE recipients had a SBP reduction of -6.8 mmHg (95% CI: -13.1, -0.5, p=0.035), compared to -0.3 mmHg (95% CI: -6.5, 6.0, p=0.935) in the EUC group. When stratified by DASH adherence ( Fig 1 ), participants with high DASH scores (≥4.5) in the THRIVE group had SBP reduction of -13.3 mmHg (95% CI: -23.3 to -3.2, p=0.010), compared to BP change of +2.0 mmHg (95% CI: -7.8 to 11.9, p=0.685) in the EUC group. Those with low DASH score had BP change of -2.4 mmHg in THRIVE group and -1.1 mmHg in EUC group. Threshold sensitivity testing showed BP-lowering effects across multiple DASH score cutpoints in THRIVE group: -7.4 mmHg at threshold ≥2.0 (p=0.038) to -13.3 mmHg at ≥4.5 (p=0.010), with progressive benefit magnitude at elevated thresholds ( Fig 2 ). Conclusion: This pilot trial shows that a FIM intervention integrating nutritious food access with individualized dietitian counseling and produce prescription lowers SBP, especially among those who achieve high dietary quality.

Abstract TU130: Food Insecurity and Pediatric Heart Health in US

Background: Food insecurity is a significant public health concern that may adversely affect children’s physical and emotional well-being, including cardiovascular health. Limited research has examined the relationship between food insecurity and reported heart conditions in U.S. children using nationally representative data. Methods: We analyzed data from the 2019 National Survey of Children’s Health (NSCH), including children aged 0–17 years with complete information on household food security (FOODSIT), parent-reported child heart condition (HEART), and relevant covariates. Weighted descriptive statistics and multivariable logistic regression models were used to examine associations between food insecurity and heart health outcomes, adjusting for sociodemographic and behavioral factors such as child age, sex, race/ethnicity, insurance status, parental education, family structure, physical activity, sleep, BMI category, and adverse childhood experiences (ACEs). Survey weights (FWC) were applied to ensure nationally representative estimates. Results: Among U.S. children, food insecurity was significantly associated with higher odds of having a reported heart condition (OR = 1.41, 95% CI: 1.12–1.77, p = 0.0038) after adjusting for confounders. Other significant predictors included lower parental education (OR = 1.17, 95% CI: 1.01–1.35, p = 0.036), inadequate sleep (OR = 1.32, 95% CI: 1.07–1.62, p = 0.011), and higher BMI class (OR = 1.16, 95% CI: 1.02–1.31, p = 0.024). Male sex was associated with lower odds of reported heart conditions (OR = 0.79, 95% CI: 0.64–0.98, p = 0.029). Conclusion: Findings suggest that food insecurity is independently associated with poorer cardiovascular health among children, even after accounting for demographic, behavioral, and family-level factors. Interventions to reduce food insecurity may contribute to improved child heart health outcomes and long-term cardiovascular prevention efforts.

Abstract WE422: Prognostic Value of Cardiovascular-Kidney-Metabolic Syndrome Stage 3 Components: Dallas Heart Study

Background: The Cardiovascular-Kidney Metabolic (CKM) Syndrome Stages are associated with heightened risk of cardiovascular diseases (CVD). However, the individual and additive impact of CKM Stage 3 (subclinical CVD) criteria on risk of incident clinical CVD is unclear. Methods: We included participants in the Dallas Heart Study, a population-sampled cohort from Dallas County, who attended study Visit 1 (2000-2002) and were categorized as Stage 2 or 3 CKM based on the presence of CVD risk factors or abnormal subclinical CVD biomarkers, respectively. CKM Stage 3 criteria included coronary artery calcium by cardiac CT (CAC) > 100 HU, abnormal left ventricular ejection fraction (< 50%) or mass (> 89 g/m 2 in women&> 112 g/m 2 in men) by cardiac MRI (CMR), elevated NT-proBNP (≥125 pg/mL), elevated high sensitive-troponin T or I (≥14 ng/L and ≥10 ng/L women; ≥22 ng/L and ≥12 ng/L in men, respectively) despite normal kidney function (eGFR> 90 mL/min/1.73 m 2 ), and high CVD risk based on very high risk by KDIGO HeatMap or PREVENT score > 20%. Participants were followed for incident coronary heart disease (CHD), heart failure (HF), stroke, or death through December 31, 2018. Multivariable Cox proportional hazard models adjusting for age, sex, and race/ethnicity were used to assess the association of Stage CKM 3 criteria with incident CVD using CKM Stage 2 as reference. Results: The study included 1,995 participants (1,568 CKM Stage 2, 427 CKM Stage 3) with a mean age of 45±10 years, 54% were female, and 50% reported Black race. Over a median follow-up of 17 years, 405 (20%) had incident CHD, HF, stroke, or died. Compared to Stage 2 participants, those who met two or three CKM Stage 3 criterion demonstrated higher risk of incident CVD compared to those who only met one Stage 3 criterion (Hazard Ratios 3.5 [95% CI 2.3-5.3] and 3.0 [95% CI 1.6-5.7] vs. 2.0 [95% CI 1.6-2.5], respectively; Figure 1A ). Among those with only 1 Stage 3 criterion (n=364), the most common was CAC (46%), followed by NT-proBNP (24%), troponin (15%), CMR (11%), and PREVENT score (5%). Those with elevated troponin alone were not at higher risk compared to Stage 2 (HR 1.3, 0.7-2.5, p=0.44), while the others were ( Figure 1B ). Conclusion: Within the CKM Syndrome framework, a greater number of Stage 3 criteria met is associated with greater risk of incident CVD compared to Stage 2. The prognostic value of isolated elevation of Tn to define Stage 3 requires further study.

A systematic review and meta-analysis of the impact of relaxation techniques to reduce burden of disease in patients with psychotic disorders

Abstract The role of psychosocial stress as a factor in both the development of psychosis and the exacerbation of acute psychotic episodes is increasingly well understood. Various approaches to stress reduction have been shown to be helpful for psychosis patients, but they are rarely included in guidelines and treatment algorithms. In this systematic review and meta-analysis, we examined the effectiveness and potential adverse effects of interventions that specifically aim to reduce stress in psychosis patients. To do so, we systematically searched five databases (PubMed, Scopus, Web of Science, PsycINFO, Cochrane-Library) for studies on relaxation interventions in psychosis treatment. Of the identified studies, 24 ( N  = 1292 patients) were eligible for inclusion. We performed a systematic review and general meta-analysis and a subgroup analysis for patient setting (inpatient, outpatient, rehabilitative, or mixed). The general analysis showed small to moderate effects of the interventions on general, positive, and negative symptoms but not for the reduction of stress. In the subgroup analysis, psychosis patients in outpatient and rehabilitative settings benefitted more from the interventions than those in an inpatient setting. No adverse effects were reported. These results help to consider the integration of relaxation techniques for stress reduction as an add-on therapy in psychosis treatment.

Abstract 24: Prospective Associations of PFAS with Cardiovascular Disease in Prediabetes: Diabetes Prevention Program

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants linked to cardiometabolic dysfunction, yet their prospective association with cardiovascular disease (CVD) in high-risk populations remains unclear. We evaluated whether baseline plasma PFAS concentrations predict incident CVD in adults with prediabetes in the Diabetes Prevention Program Outcomes Study (DPPOS). Methods: In 1,382 DPPOS participants, we measured baseline plasma concentrations of six PFAS (PFHxS, PFOS, PFOA, PFNA, MeFOSAA, EtFOSAA). Notably, MeFOSAA and EtFOSAA eventually metabolize to PFOS. We followed participants for a median of 21 years. Cox proportional hazards models estimated risks for CVD per interquartile range (IQR) increase in PFAS. We assessed PFAS mixture effects using a burden score and quantile g-computation and explored effect modification by age, sex/menopause, diet, and physical activity. Data provided by NIDDK CR, a program of the National Institute of Diabetes and Digestive and Kidney Diseases. Results: At baseline (1996-1999, mean [SD] age 52.1 [10.3] years), median PFAS concentrations were comparable to U.S. reference values (e.g., PFOS: 27.9 ng/mL; PFOA: 4.77 ng/mL). Incidence of major adverse cardiovascular events (MACE) was 9.6%; CVD death was 3.9%. Each IQR (1.1 ng/mL) increase in MeFOSAA was associated with a 16% higher risk of MACE (95% CI: 1.01–1.33) and 24% higher CVD death risk (95% CI: 1.02–1.52). PFHxS, PFOS, EtFOSAA, and PFOA were linked to elevated risks of non-fatal myocardial infarction, hospitalized congestive heart failure, and CVD death. Mixture and total PFAS burden analyses showed no significant associations. No consistent effect modification was observed by age, sex, diet, or physical activity. Sensitivity analyses accounting for additional covariates, including educational attainment, martial status, alcohol intake, physical activity, BMI, and fish intake, showed consistent results. Conclusion: Higher plasma concentrations of select PFAS, particularly MeFOSAA, were associated with increased CVD risk in adults with prediabetes, independent of lifestyle factors. These findings highlight PFAS as potential environmental contributors to CVD in metabolically vulnerable populations, warranting further investigation and clinical consideration.

Abstract WE481: Disrupted Circadian Rest-Activity Rhythms and Incident Heart Failure in the Aging Population: The Atherosclerosis Risk in Communities Study

Introduction: Circadian rhythm disruption is prevalent in older adults and has been linked to autonomic dysfunction, chronic inflammation, and metabolic dysregulation, which are key pathological processes implicated in the development of heart failure (HF). Despite these shared mechanistic pathways, the association between disrupted circadian rest-activity rhythms (RARs) and HF remains unknown. This longitudinal study investigated the association between circadian RARs and incident HF among older adults from the Atherosclerosis Risk in Communities (ARIC) study. Hypothesis: Disrupted circadian RARs are associated with increased risk of incident HF. Methods: We included participants free of HF at visit 6 (2016-17) when RARs were assessed using an accelerometer embedded in the Zio® XT ECG monitor. RARs were quantified using three nonparametric indices: relative amplitude (rhythm strength), interdaily stability (rhythm regularity), and intradaily variability (rhythm fragmentation). All three RAR measures were standardized to a mean of 0 and a standard deviation of 1 to enable direct comparison of effect sizes across metrics. Cox proportional hazards regression was used for analysis. Results: We analyzed data from 2,216 participants (median age, 78 years) with RAR evaluation over a median (IQR) of 13.8 (13.1-14.0) days of uninterrupted monitoring. During a median (IQR) follow-up of 6.6 (5.0-7.0) years, 294 (13.3%) participants developed incident HF. Lower relative amplitude, indicating reduced circadian rhythm strength, was significantly associated with elevated HF risk. After adjusting for baseline characteristics and prevalent cardiovascular disease, each one-standard-deviation decrease in relative amplitude was associated with a 36% (HR (95% CI), 1.36 (1.19-1.55)) higher risk of HF ( Table 1 ). Compared to those in the highest tertile, participants in the lowest tertile had a more than 2-fold higher risk of developing HF, while those in the middle tertile had a 64% higher risk. However, the risk of incident HF was not significantly different across tertiles of interdaily stability and intradaily variability. Conclusions: In this longitudinal study of community-dwelling older adults without prevalent HF, lower circadian rhythm strength (i.e., lower relative amplitude) was significantly associated with higher risk of developing HF. Circadian rhythm disruption may be a novel risk marker for early identification of individuals at elevated risk of HF.

Abstract WE514: Changes in epigenomics and metabolomics biomarkers after a lifestyle intervention with diet and physical activity for weight loss in high cardiovascular risk individuals

Background and aims: Obesity is recognized as an important cardiovascular risk factor. Consequently, weight loss is regarded as a protective factor. Nevertheless, the effects of weight loss on the epigenome and metabolome are not well understood. Our objective is to analyze changes in the epigenome (DNA methylation) and metabolome (serum/plasma) after 1-y of a lifestyle intervention in overweight/obese subjects at high cardiovascular risk. Methods: We conducted a randomized controlled trial for weight loss in high risk subjects (55-75 years; BMI: 27-40 kg/m2; and metabolic syndrome). Subjects were randomized 1:1 to the active intervention group (IG) consisting of an energy-restricted Mediterranean diet (MedDiet) and increased physical activity, or to the control group (CG) (minimal intervention with MedDiet). This is a 6-year intervention multicenter study, but we present here data from the Valencia-field center (n=465 at baseline). Details about the intervention have been registered and published. DNA methylation was measured in all participants at baseline with the EPICv1 array, as well as serum metabolites using the NMR-Nightingale platform. In a subsample (n=92) including responders and non-responders in order to maximize sample size we analyzed DNA methylation at baseline and 1-y (EPICv2) and metabolomics (in plasma) with the Global Discovery Panel of Metabolon. Normalization, feature selection and multivariable adjusted regression models were fitted to analyze changes. Results and conclusions: After 1y intervention we detected statistically significant differences (P<0.001) in weight loss between the IG (mean:-3.4+/-3.8% weight; range: -16.8 to 4.4 %) and the CG (mean:-0.42+/-3.1%; range:-14.7 to 6.3). At baseline, a methylation-wide signature was significantly associated (P<5x10-8) with weight loss in the IG, including cg22010309-intergenic, cg24800130-FAM108A1 (related to fat browning and lipid metabolism in adipocytes) and cg24978424-YTHDC1 (autophagy-related), among others. After 1-y intervention, we detected several statistically significant changes in epigenetic biomarkers (both in differentially methylated loci and composite biomarkers related to aging). Also, we found significant changes in some metabolites (stearoylsphingomyelin(d18:1/18:0), 5-oxoproline; cysteine, linoleate(18:2n6), stearate (18:0); 3-indoxyl sulfate; and 3-methyl-2-oxobutyrate, among others) showing an impact of weight loss on these markers, but more studies are needed.