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Abstract TU172: Sodium and Potassium in 24-h Urine among Adults: Italian Health Examination Survey 2023-2025 - CUORE Project

Introduction: One of the most cost-effective ways to reduce the burden of NCDs is the reduction of sodium intake. WHO recommends a 30% relative reduction in mean population intake of sodium within 2025 (baseline 2010) and an adequate potassium intake. In Italy, the Ministry of Health has strengthened prevention/health promotion and financed national health examination surveys (HESs) conducted within the CUORE Project to monitor the habitual salt and potassium intake in the general adult population. A new survey started in 2023 and is still ongoing, promoted and financed by the Ministry of Health – CCM and the European Commission through JACARDI. Hypothesis: This analysis aims to assess if Italy can meet the WHO target on salt intake and to monitor the levels of potassium intake in the general adult population. Methods: In the period 2023-2025, a 24h urine sodium and potassium excretion assessment within a new HES was implemented. Up to now, data from random samples of residents in 17 Regions (of 20 regions) distributed in North, Centre and South of Italy are available (1616 men, 1609 women, aged 35-74 years). Urinary excretion is assayed by a central lab. Persons with urinary volume < 500 ml and/or a urinary creatinine content referred to body weight outside the range of population mean ± 2 standard deviations are excluded. Statistics were standardized by Italian 2024 age-sex distribution. Results: An adequate salt intake level (lower than 5g/day - WHO recommended target) was detected in 10.6% (95% confidence interval: 7.6-13.6%) of men and 23.6% (19.5-27.8%) of women and an adequate potassium intake level (higher than 3510 mg/day - WHO recommended target) was detected in 25.8% (21.5-30.0%) of men and 12.7% (9.4-15.9%) of women. Mean level of salt per day was 9.3 g (8.9-9.6 g) and 7.1 g (6.9-7.4 g), and mean level of potassium per day was 3.0 g (2.9-3.1 g) and 2.5 g (2.4-2.6 g) for men and women respectively. Conclusions: In Italian adults, compared to 2008, the habitual salt intake decreased of about 12% in 2018 and remained stable in 2023/2025; the habitual potassium intake remained stable in 2008, 2018 and 2023/2025; the salt and potassium intake mean levels are still not adequate. These results justify and encourage the ongoing preventive initiatives of Ministry of Health, facilitating the meeting of WHO targets.

Abstract WE495: Deprivation Index and Cardiovascular Diseases Risk Factors in the Italian Adult Population: Results from CUORE Project

Introduction: Cardiovascular diseases (CVDs) are shaped by multiple factors, including socio-economic status. Deprivation Indexes (DIs) are increasingly used to improve the stratification of CVD risk and targeting interventions. Hypothesis: This study assess whether contextual deprivation, measured by DI, is associated with CVD risk factors and estimated 10-year risk of CVDs. Methods: Two national health examination surveys (1998–2002 and 2008–2012) were conducted in Italy within the CUORE Project. Random samples of residents aged 35–74 years were examined (4,702 men, 4,597 women – and – 3,660 men, 3,699 women). The DI, as composed score of low level of education, unemployment, non-home ownership, one-parent family and overcrowding calculated in each municipality and census block using 2001 and 2011 Censuses of Population data, was assigned geolocating each participant residence. The 10-year risk of first fatal and non-fatal CVDs was estimated using the CUORE Project risk score. Statistics were standardized by the 2013 European age-sex distribution and reported by DI quintiles (Q1 and Q5). Results: In 1998–2002, CVD risk resulted slightly higher in the most deprived (Q5) (men: 8.5 in Q1 vs 8.8% in Q5; women: 3.0 vs 3.6%). A significant association was observed between DI quintiles and obesity (m: 14.7 vs 19.5%; w: 16.6 vs 29.4%), BMI mean (m: 26.5 vs 27.1 kg/m 2 ; w: 25.6 vs 27.6 kg/m 2 ), sedentary lifestyle during leisure time (m: 31 vs 40%; w: 38 vs 64%), smoking habits (m: 28 vs 41%; w: 23 vs 24%), diabetes (m: 11vs 13%; w: 6 vs 10%), and hypertension (m: 55 vs 52%; w: 41 vs 50%). In 2008–2012, CVD risk remained slightly higher in Q5 (m: 12.5 vs 13.1%; w: 4.8 vs 4.9%) and again a significant association was observed between DI quintiles and obesity (m: 22 vs 31%; w: 20 vs 33%), BMI mean (m: 27 vs 28kg/m 2 ; w: 26 vs 28kg/m 2 ), sedentary lifestyle (m: 29 vs 35%; w: 40 vs 49%), diabetes (m: 10 vs 15%; w: 6 vs 12%), and for women hypertension (m: 53% in both Q1 and Q5; w: 35 vs 43%). No significant association was found for mean of SBP, diastolic blood pressure, glycemia, triglycerides, total and HDL cholesterol, and hypercholesterolemia prevalence in both periods, and smoking habits prevalence for the latter period. Conclusions: The study confirms also in Italy the association between deprivation and CVD risk factors, with DI emerging as a robust index of social and material disadvantage, supporting targeted health promotion strategies in deprived urban areas.

Abstract TU170: Evidence and Gap Map Summarizing the Relationship between Supplemental Potassium and CVD-related Indicators and CVD Morbidity and Mortality

Background: Potassium supplementation has emerged as a promising strategy to reduce blood pressure and cardiovascular disease (CVD) risk. However, uncertainties remain regarding optimal dosing, forms of potassium, and strength and consistency of the effect of potassium supplementation on hard CVD outcomes such as CVD death. Objective: To systematically map the existing evidence on potassium supplementation—with and without sodium reduction—on CVD outcomes in adults, identifying gaps to inform future clinical guidelines and research priorities. Methods: We systematically reviewed recent evidence on potassium supplementation and cardiovascular outcomes, including morbidity and mortality, searching Medline and Cochrane Central for articles published between January 2018 to June 2025. Eligible exposures included potassium supplementation (e.g., chloride, bicarbonate, citrate, gluconate, lactate, nitrate, phosphate, magnesium citrate, and enriched foods) with or without sodium reduction. Outcomes of interest included intermediary endpoints (i.e., blood pressure, arterial stiffness, coronary artery calcification) and hard endpoints (e.g., incident hypertension, cardiovascular morbidity and mortality). Minimum follow-up was ≥4 weeks for intermediary and ≥12 months for hard endpoints. Full text screening and data extraction is ongoing and performed by independent reviewers. Data will be synthesized into an interactive map using EPPI-Mapper. Results: We reviewed 6,392 unique citations with 22 meeting inclusion criteria. Twelve studies examined the effect of salt substitutes on cardiovascular health. Studies of supplemental potassium chloride and potassium nitrate were also identified with one study examining potassium-enriched foods. The evidence suggested an association between potassium supplementation and reduced CVD risk with most citations ( n =18) utilizing a randomized design. There were few studies on the effect of potassium on arterial stiffness and coronary artery calcification and few among healthy populations and those with chronic kidney disease. Conclusion: This evidence and gap map provides an overview of the current evidence for potassium supplementation and CVD outcomes. Findings will inform the need for a full systematic review and potential updates to chronic disease risk reduction recommendations. The results are expected to have significant implications for clinical practice, public health guidance, and future research agendas.

Abstract 68: Metabolomic Profiles of Cardiac Structure and Function and Their Associations with Incident Heart Failure in Multi-Ethnic Populations

Introduction: Metabolic dysregulation is associated with heart failure (HF). However, comprehensive evaluation of the effect of circulating metabolites on cardiac function, a critical measure for predicting HF risk and prognosis, in multi-ethnic populations remains limited. Objectives: We aim to identify circulating metabolites associated with cardiac function and HF risk in multi-ethnic populations. Methods: We evaluated 21,638 HF-free participants (57% non-White, 57% women) from seven studies, who had contemporaneous circulating metabolite and echocardiography (echo) measures. We used linear regressions (within study) to evaluate the cross-sectional associations between metabolites and cardiac structure/function traits, adjusting for clinical risk factors. Random-effect meta-analyses were performed to produce overall estimates. Cox proportional hazard regression was used to examine the association of echo-related metabolites with incident HF, and its subsets, HF with reduced and preserved ejection fraction (HFrEF, HFpEF). Results: Of 1,027 analyzed metabolites in relation to 42 echo measures, 604 were significantly associated with 28 echo measures (FDR <0.05), including cardiac structure and left and right ventricular function traits. In the prospective analyses, 156, 59, and 73 metabolites showed a significant association with incident HF, HFrEF, and HFpEF, with an average hazard change of 21%, 13%, and 32% per SD difference in metabolite level. Many identified metabolites showed consistent effects across echo measures and HF risk (Figure). High levels of acisoga, an end-product of polyamine metabolism and a potential biomarker for HF, were associated with greater left atrial size and HFpEF risk; high levels of homoarginine, an amino acid with anti-inflammatory properties, were associated with low left ventricular mass and a lower risk for HFrEF and HFpEF. Some metabolites demonstrated divergent effects-high levels of glycerol, a precursor for the synthesis of triacylglycerols and phospholipids, were associated with low left ventricular mass yet a high risk of HFrEF. Conclusions: Metabolomic profiling revealed distinct and mostly consistent associations between circulating metabolites, cardiac structure/function, and incident HF in multi-ethnic populations. Our findings provide insights into the metabolic pathways underlying cardiac remodeling and HF pathogenesis, and raise the possibility that novel metabolites may inform HF risk stratification.

Correction for Ghimenti et al., Clever algorithms for glasses work by time reparameterization

Abstract TH968: Piloting Feasibility of Conducting Arterial Stiffness Measurements in the Emergency Department

Introduction: Chest pain remains one of the most common and complex presentations in the emergency department (ED), requiring rapid and accurate identification of acute coronary syndrome (ACS). Arterial stiffness (AS), a novel noninvasive biomarker, could refine risk stratification for ACS in ED patients with chest pain. We conducted a feasibility study measuring AS in ED patients with chest pain. Hypothesis: We hypothesized that one AS device would demonstrate superior feasibility. Methods: This ongoing observational pilot study included adults (≥ 18 years) with chest pain and a negative initial troponin at the UNC Medical Center ED. Key exclusions were non-English speakers, critically ill patients, non-cardiac or trauma-related chest pain, and contraindications to AS testing. Eligible participants were identified through electronic health record (EHR) screening and confirmed in-person. After the first 11 participants were assessed under a three-device protocol, all subsequent participants completed the BP+ and were randomized to either the VaSera VS-2000 or SphygmoCor XCEL to reduce participant burden. Each participant completed two AS assessments: BP+ (one measurement repeated three times) and VaSera or SphygmoCor (two measurement sites per device, each repeated three times). Feasibility outcomes included assessment time, completion rates, and reasons for incompletion. Results: Of 21 enrolled participants, 11 were assessed under the original three-device protocol, 5 were assigned VaSera and BP+, and 5 to SphygmoCor and BP+. Average assessment times were 32 minutes for VaSera, 30 for SphygmoCor, and 10 for BP+. Completion rates were 87%, 71%, and 95%, respectively. Incompletion most often resulted from subject discomfort (VaSera, BP+), clinical interruption (BP+), and technician error or device malfunction (SphygmoCor). Conclusions: This pilot study is one of the first to implement AS measurements for chest pain in the ED. BP+ was the most time-efficient device, while VaSera had the highest completion rate. SphygmoCor presented the greatest challenges due to technician errors and device malfunctions. These findings highlight practical barriers to AS measurement and demonstrate that AS assessment is feasible in the ED. Future studies will evaluate its potential to inform ED decision making.

Abstract TH963: Performance of PREVENT-HF Risk Equations across HFpEF vs HFrEF

Background: The recent PREVENT-HF risk equations were developed to estimate 10-year risk of overall HF. While HF with preserved vs reduced ejection fraction (HFpEF; HFrEF) have common risk factors, distinct differences in risk conferred by older age, obesity, and coronary artery disease are known. In this context, we sought to evaluate the performance of PREVENT-HF equations relative to HFpEF vs HFrEF. Methods: We examined participants from 4 pooled community-based cohort studies: the Multi-Ethnic Study of Atherosclerosis (MESA), Framingham Heart Study (FHS) offspring exam 6, Cardiovascular Heart Study (CHS), and Prevention of Renal and Vascular End-stage Disease (PREVEND) study. We excluded those with ages <30 and >79 years, prevalent HF, prevalent CVD, and missing key clinical information. We compared the performance of the PREVENT-HF equation in predicting incident HFpEF vs HFrEF at 10 years using Uno’s C-statistics and area under receiver operating characteristic (AUROC). Results: Among 22,061 participants (age 59 ± 14 years, 54% women, BMI 27 ± 5 kg/m 2 ), 322 developed HFpEF and 464 HFrEF during a median follow-up of 10 years. The PREVENT-HF risk equation performed well for both HFpEF (c-statistic 0.81, 95% CI 0.80-0.83) and HFrEF (c-statistic 0.78 (95% CI 0.76-0.80), with similar improvement compared with age and sex alone (HFpEF: c-statistic 0.78, 95% CI 0.76-0.80; HFrEF: c-statistic 0.75, 95% CI 0.73-0.76, P<0.001 for delta for both). The AUROC remained stable across 1-10 years demonstrating consistently strong discrimination for both HFpEF and HFrEF. Time-dependent AUCs were generally higher for HFpEF compared with HFrEF, indicating slightly better discrimination for HFpEF across all time horizons ( Figure ). Conclusions: Our findings demonstrate overall similar performance of the PREVENT-HF risk model with respect to HFpEF and HFrEF. Future studies on subtype-specific risk models may improve upon current risk prediction tools for overall HF.

Abstract WE522: Association of Body Roundness Index (BRI) with Left Ventricular Systolic Function: The Framingham Heart Study

Introduction: Obesity, as assessed by body mass index (BMI), is associated with excess burden of cardiovascular disease, including heart failure, but BMI does not account for body shape or composition and may not be the optimal metric for obesity. In contrast to BMI, the novel body roundness index (BRI = 364.2 – 365.5*SQRT(1-(WC/(π*HT)) 2 ) incorporates both girth (waist circumference, WC) and height (HT). We sought to determine whether BRI is associated with differences in two measures of left ventricular (LV) systolic function: ejection fraction (EF), and myocardial contraction fraction (MCF), the dimensionless ratio of LV stroke volume to myocardial volume. MCF assesses the volume of blood ejected per unit volume of myocardium (LV mass) and is a metric complementary to EF. Methods: Participants from the Framingham Offspring cohort who underwent cardiac magnetic resonance (CMR) imaging were included in the study. Participants were divided into sex-specific tertiles of BRI, after which a referent group (REF) of Offspring free of prevalent cardiovascular disease (CVD), wall motion abnormalities on CMR, significant valve disease, or any history of hypertension was identified. We used sex-specific linear regression analysis to test for trends across BRI tertiles for LVEF and MCF. Finally, we considered the ratio of LV mass to end-diastolic volume as a measure of concentricity (CONC). Results: Of the total 1764 participants (Age: 69±9yrs; 53% Women), 775 (57% women) met REF criteria. Within each tertile mean LVEF and mean MCF were greater among women versus men (Table). MCF decreased with greater BRI for each sex. In contrast to MCF, LVEF increased significantly with greater BRI tertile among both men and women. CONC also increased across tertiles of BRI. Conclusion: LVEF increased, while MCF decreased, with greater tertile of BRI. The decrease in MCF was concomitant with increasing concentricity. These results raise the possibility that the increase in LVEF with greater BRI is associated with geometric remodeling of the ventricle rather than intrinsically greater contractility. Whether this association between BRI-characterized obesity and LV systolic function is related to incident adverse CVD events, particularly heart failure with preserved EF, remains to be investigated.

Spatially structured inflammatory response in the presence of a uniform stimulus

Inflammatory responses occur within the complex spatial context of tissues and organs, and many questions remain about how tissue structure and cellular communication shape their spatiotemporal dynamics. Here, we use a multiplexed RNA in situ hybridization approach, together with analytical tools, to study inflammatory gene expression in the larval zebrafish tailfin in response to a bath of lipopolysaccharide. We use this model system to address whether spatial structure emerges in the tissue response even absent the spatial variation introduced by a pathogen. We find that epithelial cells in the tailfin express several proinflammatory genes, and that across these genes, the uniform stimulus triggers a spatially nonuniform response. We use a graph-based spectral decomposition method to analyze its structure, and find that it is consistent with a diffusion-consumption model of secondary signaling. Overall, long-wavelength modes dominate the signal, creating zones of activation which account for a majority of the variation in gene expression. Our results show that epithelial cells are important producers of proinflammatory effector molecules in this system, and that tissue induces spatial correlations even absent a structured input.

Abstract TU179: Leveraging Pleiotropy to Improve Polygenic Risk Scores for Dyslipidemia Prediction

Background: Current genomic risk prediction models explain only a small fraction of lipid variability and often underperform in non-European populations. Because many lipid-associated variants exert shared effects across multiple lipid traits, integrating pleiotropic genetic information provides an opportunity to enhance prediction accuracy and clinical utility of polygenic risk scores (PRS) in diverse populations. Methods: Genome-wide association summary statistics for HDL, LDL, triglycerides, and total cholesterol were meta-analyzed from three African-ancestry cohorts, ACCME (~8,800), AWI-Gen (~11,700), and GRC-Uganda (~6,400), using METAL. Trait-specific PRS were constructed with PRSice2 and combined using PRSmixPlus to generate a multi-trait PRS that leverages pleiotropic effects across lipid traits. Dyslipidemia was defined by NCEP ATP III criteria. Model performance was evaluated in the UK Biobank African-ancestry cohort (~6,000; 75 % training, 25 % test) using logistic regression adjusted for age, sex, and ancestry principal components, with discrimination assessed by R squared and AUC. Results: In the UK Biobank African-ancestry cohort, the multi-lipid PRS that integrated pleiotropic effects across HDL, LDL, triglycerides, and total cholesterol outperformed all single-trait PRS models for predicting dyslipidemia. The multi-lipid PRS explained 7.6 percent of phenotypic variance (R-squared = 0.076, 95 percent CI 0.047 to 0.104, p = 2 x 10^-7), representing a 23 percent improvement over the best-performing single-trait PRS based on total cholesterol (R-squared = 0.061, 95 percent CI 0.035 to 0.087, p = 4 x 10^-6). Single-trait PRS for LDL and triglycerides showed smaller predictive power (R-squared = 0.049 and 0.014, respectively), while the HDL PRS did not contribute significantly. Conclusions: Integrating pleiotropic genetic effects across lipid traits modestly improves genomic prediction of dyslipidemia in African-ancestry populations. This approach could enhance early identification of individuals at elevated cardiovascular risk and inform precision prevention strategies tailored to diverse populations.

Abstract TU205: The Effect of Physical Activity on the Gut Microbiome in Prediabetes: Results from a Randomized Controlled Trial

Objective: To test the effect of physical activity on the gut microbiome and circulating short chain fatty acids among sedentary overweight/obese adults with prediabetes. We hypothesized that randomization to increased physical activity would result in gut microbiome changes. Methods: \We randomized 77 adults with prediabetes and a sedentary lifestyle into one of two groups: 1) Intervention Group: Invited to engage in home-based moderate intensity walking 3x/week for 30 minutes/session in weeks 1-4 and for 45 minutes/session during weeks 5-8 of the 8-week intervention; or 2) Control Group: Maintained habitual physical activity levels. We performed metagenomic sequencing from stool collected at baseline, week 4, and week 8, with short-chain fatty acids (SCFA) measured from serum collected at baseline and week 8. Taxonomic and functional profiling were performed on the metagenomic reads; alpha diversity metrics were subsequently derived. Linear regression assessed the difference in change between the intervention and control groups for alpha-diversity and SCFA levels. Results: We screened 1,533 participants for eligibility and consented 132. Of these, 87 entered the run-in phase and 77 were randomized. Participants were 51.4±8.9 years old, 87.7% female, and 74% non-Hispanic White. Mean fasting glucose was 103.3±13.2 while mean BMI was 34.4±5.7. In comparison to the control group, the intervention group experienced decreased alpha diversity as characterized by Shannon, Richness, and Faith’s diversity indices by week 8 of the intervention (P<0.05). SCFA levels trended towards improvement in the intervention group, but the results were not statistically significant. Functional analysis of KEGG ontologies revealed themes consistent with a microbiome with enhanced metabolic activity and host-relevant metabolic signaling (Figure). Conclusions: Randomization to a walking intervention resulted in modest gut microbiome changes among adults with overweight/obesity and prediabetes.

Abstract TU193: Plasma proteomics of fatigue and risk of incident heart failure in the Atherosclerosis Risk in Communities (ARIC) Study

Background: Among individuals at risk for heart failure (HF), general and exertional fatigue are common symptoms and are associated with HF development. The biological mechanisms underlying the associations of fatigue measures with incident HF are poorly understood and may be further clarified using proteomic profiling. Methods: We evaluated 4,558 individuals without clinical HF at ARIC Visit 5 (2011-2013), who had ~ 5000 plasma proteins quantified from stored Visit 5 samples using an aptamer-based platform (SomaScan). Moderate/severe fatigue was defined as a score of ≥ 52.5 on the Patient Reported Outcomes Information System (PROMIS) fatigue scale (general fatigue) and/or a score of >2 on the MRC Breathlessness Scale (exertional fatigue). In cross-sectional analysis, we used multivariate logistic regression to identify proteins associated with any fatigue and with individual fatigue types, using the false discovery rate (FDR) to account for multiple comparisons. Among individuals with fatigue, we used Cox regression to identify proteins associated (at FDR significance) with incident HF after Visit 5 through 12/31/23. We assessed for overlap between proteins associated with fatigue and those with future HF in the setting of fatigue. Results: Within the study population (mean age 75, 59% female, 19% black), 24% had moderate/severe fatigue. In cross-sectional analysis, 7 proteins were associated with any fatigue (vs no fatigue) after multivariable adjustment. Among these, 4 proteins were associated with exertional fatigue only, and none with general fatigue only. In those with moderate/severe fatigue, 301 proteins were associated with incident HF. Among these, 5 proteins were associated with both moderate/severe fatigue cross-sectionally and risk of incident HF prospectively (Figure). These included epidermal growth factor receptor (EGFR), CUB domain containing protein 1 (CDCP1), growth differentiation factor-15 (GDF15), Hepatitis A virus cellular receptor 2 (HAVCR2), and golgi membrane protein 1 (GOLM1) (Figure). These proteins are implicated in inflammation, cytokine production, and myocardial fibroblast activity. Conclusions: In older adults without prevalent HF, we identified several proteins associated both with moderate/severe fatigue and with the risk of HF in the setting of fatigue. These results provide new insights into potential mechanisms underlying the associations of fatigue with HF development.

Quantifying the fidelity of in vitro human cell culture systems using a biomedical foundation model

Primary cell culture is fast becoming a dominant method for discovery work regarding human disease. Currently, there are no methods to quantitatively benchmark these systems. Here, we apply a uniform in vitro culture system of human intestinal epithelial cells (IECs) to achieve this goal. We previously established methods for long-term two-dimensional (2D) cultivation of mouse IECs using an air–liquid interface (ALI) technique. Here, we further refined these methods for long-term 2D cultivation of human IECs, with histological and molecular features of differentiated intestinal epithelia. Leveraging the power and scalability of a biomedical foundation model (BMFM) trained on single-cell RNA sequencing data (BMFM-RNA), we performed classification tasks to identify cell types across sample sources and to quantitatively benchmark our in vitro differentiated cells against cells collected from patient biopsies. We observed a striking concordance between our in vitro differentiated cells and the corresponding cell types in vivo for multiple differentiated secretory cell types. This approach using BMFM-RNA holds promise to expand our understanding of the regulatory mechanisms, including gene–gene regulation underlying homeostasis and regeneration, as well as the functions of rare and poorly understood lineages within the human intestinal epithelia. Moreover, these methods may be applicable to other organs, model systems, and experimental modalities. We propose that the framework used here can be deployed as a standard benchmarking methodology, ultimately improving the fidelity of primary human culture systems.

Abstract WE506: The Association of Dairy-Related Metabolites with High Blood Pressure: The Coronary Artery Risk Development in Young Adults Study

Introduction: Hypertension is a major risk factor for cardiovascular disease. Dairy products provide nutrients that may affect blood pressure, but evidence on associations of dairy-related metabolites with high blood pressure is limited. We aimed to identify metabolites related to dairy intake and assess their association with incident high blood pressure. Hypothesis: We hypothesized that higher dairy intake and its related metabolites would be associated with a lower risk of high blood pressure. Methods: We analyzed 2,171 adults (mean age 32 years, 45% female, 58% White) who attended the year 7 Coronary Artery Risk Development in Young Adults (CARDIA) exam (1992-93) and with metabolomics data. High blood pressure was defined as systolic pressure ≥ 130 mmHg and diastolic ≥ 80 mmHg or hypertension medicines use. Cox proportional hazard models assessed the associations of incident high blood pressure by year 15 across quartiles of dairy intake, adjusting for demographics, lifestyle, and diet quality. Multivariable linear regression models were used to identify dairy-related metabolites. A dairy-related metabolites score was derived by principal component analysis (PCA). The first principal component was included as covariate in a Cox model to evaluate their association with incident high blood pressure. Results: Over a median follow-up of 7.5 years (575 incident high blood pressure cases), participants in quartile 4 of dairy intake had significantly lower risk of high blood pressure compared to those in quartile 1 (hazard ratio [HR]: 0.70; 95% CI 0.53, 0.93; P trend = 0.03). Twenty-three serum metabolites were associated with dairy intake (See Heatmap below). The first principal component representing dairy-related metabolites patterns was significantly associated with incident high blood pressure ( Δ -2LL x 2 , df = 4.74, p = 0.03). Participants in quartile 4 of the principal component 1 score had a lower risk of high blood pressure compared with those in quartile 1 (HR = 0.78, 95% CI: 0.62, 0.98, P trend = 0.03). Exploratory enrichment analysis indicated activation of transport pathways for vitamins, nucleosides, bile salts, organic acids, and metal ions (False Discovery Rate < 0.15). Conclusion: We found higher dairy intake was linked to lower high blood pressure risk. Dairy-related metabolites and their patterns were also associated with lower incident high blood pressure. This suggests metabolomics as a tool to clarify diet-blood pressure mechanisms.

Abstract TU202: Pilot Data: Respiratory Exchange Ratio Predicts Perceived Exertion During Graded Maximal Exercise Testing

Introduction: Perceived exertion (RPE) and physiological indices measured during cardiopulmonary testing gauge exercise intensity. Since oxygen consumption (VO2) absent from a known VO2 max does not provide a relative intensity, we evaluated whether respiratory exchange ratio (RER) alone can estimate RPE across submaximal to maximal effort. Hypothesis: RER can predict RPE across submaximal to maximal exercise. Methods: Seven adults (5 males: 21.6±0.55 years, 77.83±6.7 kg, 181.74±6.3 cm, BMI 24.0±6.2 kg/m 2 ; 2 females: 21±0 years, 63.55±8.3 kg, 167.55±5.6 cm, BMI: 22.6±1.5) completed a maximal effort graded exercise treadmill test. Metabolic data was collected continuously (Vyntus CPX). The discontinuous protocol consisted of six 3-minute exercise stages (2 walking and 4 running) each separated by 1 minute of slow walking. Following the last 3-minute running stage, grade was increased 1% each minute until volitional fatigue. RER and RPE (Borg scale) were recorded during the final 15 seconds of each exercise stage. Linear mixed-effects regression analyzed the association of RPE to RER. RER was centered at 1.0 and scaled per 0.10 to report ΔRPE per +0.10 RER. A piecewise ‘above-threshold’ analysis tested for a different slope at RER≥1.0. Given non-standardized stage increments, the primary model omitted stage. Additionally, a sensitivity model with an ordinal stage covariate was also examined. Significance was set at α=0.05. Results: RER was strongly associated with RPE as each +0.10 higher RER corresponded to +3.05±0.29 RPE units (p<0.001). Expressed directly in RER units, RPE≈−16.46+30.5×RER (slope 95% CI 24.70–36.31). The additional slope above RER=1.0 was not significant (p=0.38), supporting a single linear relation across the RER range of ~0.80–1.20. In a sensitivity model adjusting for an ordinal stage index, the RER slope was unchanged as primary vs stage-adjusted slopes produced a similar RER effect: +3.05 vs +3.0 RPE per +0.10 RER (both p<0.001). Conclusion: In this pilot dataset, RER quantitatively tracked RPE during graded maximal exercise, independent of stage. This model provides a practical mapping of metabolic response to perceived effort which is also useful for verifying whether reported exertion matches physiological strain across submaximal to maximal efforts in real time. These findings warrant confirmation in larger, diverse samples and across standardized exercise protocols to refine precision and clinical utility.

Abstract MPTH75: Linking Pulmonary Function Decline and Cardiovascular Disease Risk via Plasma Proteomics

Background: Pulmonary function decline is associated with an increased risk of cardiovascular disease (CVD), yet the underlying molecular mechanisms remain unclear. We aimed to identify plasma proteins associated with forced expiratory volume in one second (FEV1) decline and subsequent CVD risk and to uncover their shared molecular mechanisms. Methods: Spirometric measurements of FEV1 were collected at visits 2 (1990–92) and 5 (2011–13) in the Atherosclerosis Risk in Communities (ARIC) Study for discovery, and at years 6 (1993–94) and 18 (2005–06) in the Cardiovascular Health Study (CHS) for replication ( Figure 1 ). Plasma proteomics (5K SomaScan) were assayed at baseline for each cohort. Annualized FEV1 decline was assessed using linear regression, adjusting for age, sex, race, smoking, BMI, kidney function, and baseline FEV1. Proteins associated with FEV1 decline were examined for incident coronary heart disease (CHD), heart failure (HF), and all-cause mortality, adjusting for clinical risk factors. Colocalization analyses were performed to assess shared genetic architecture between replicated proteins, FEV1, and clinical outcomes. Results: Among 4,766 proteins, 24 were associated with FEV1 decline (FDR<0.05) in ARIC (N = 3,435; baseline mean age: 54 years; 18% Black; 58% female). Of these, eleven were associated with incident CHD, 20 with HF, and 21 with mortality (FDR<0.05) ( Figure 2A ). Of the 24 proteins from ARIC, 20 (83%) displayed consistent directional effects with FEV1 decline in CHS (N = 663; baseline mean age: 85 years; 16% Black; 64% female) ( Figure 2B ). Five proteins showed robust replication associations across all outcomes (FDR < 0.05): CA2D3 and OMGP demonstrated risk-decreasing effects, whereas GBRL1, Apo F, and lectin, mannose-binding 2 indicated risk-increasing effects ( Figure 2C ). Colocalization analyses showed that Apo F and FEV1, and Apo F and CHD shared the same underlying causal variants (posterior probabilities>0.7). Conclusion: We identified and replicated plasma proteins, notably Apo F, linking pulmonary function decline to cardiovascular outcomes, offering insight into shared molecular mechanisms of cardiopulmonary disorders and providing potential intervention targets.

Autogenic spinal excitatory circuit ensures skilled hand movements in primates

Skillful hand movements are a hallmark of primates, including humans, requiring sophisticated motor planning and execution. Building on the well-established cortical basis of dexterous control, our findings show that spinal excitatory reflex circuits form a critical complementary pathway that contributes substantially to the planning and execution of skillful hand movements. Using a combination of experimental approaches with behaving nonhuman primates and predictive simulation, we identified a group of excitatory spinal interneurons that orchestrate a closed-loop, positive feedback mechanism during voluntary wrist movements. This mechanism is characterized by a bidirectional interaction between interneuronal spiking and muscle activity, mediated by motoneuronal efferent signals and proprioceptive afferent signals from the same agonistic muscles. Furthermore, we demonstrate that the temporal profile of muscle activity during movement execution, including amplitude and duration, is predetermined during motor planning at the spinal interneurons, functioning as a force-feedback gain within the excitatory circuit. These findings suggest that autogenic, Ib spinal excitatory circuits play a predominant role in shaping overall muscle activation during motor execution, provided the proper reflex gain is preset by higher neural systems during motor planning. Together, our findings provide cellular-level evidence that spinal reflex loops operate in parallel with cortical mechanisms to support skilled voluntary movements in primates.

Abstract WE423: Intersection between Cardiovascular-Kidney-Metabolic (CKM) Syndrome and Inflammation in Incident Cardiovascular Disease (CVD) and All-cause Mortality: MESA and CARDIA

Background: Limited data exists on the longitudinal joint associations of CKM syndrome and systemic inflammation with incident CVD events. Hypothesis: Systemic inflammation modifies the association between preclinical CKM syndrome stages and incident CVD events. Methods: The AHA classifies CKM syndrome into five stages, spanning optimal cardiovascular health to clinical CVD. We included 9,069 CVD-free participants (median age 54) from the MESA (exam 1, 2000–2002) and CARDIA (exam 7, 2005–2006) studies. We reclassified preclinical CKM syndrome by combining Stages 0 and 1, and subdividing Stage 2 at the median number of Stage 2 components. Baseline interleukin-6 (IL-6), a marker of systemic inflammation, was analyzed both categorically and continuously. Multivariable-adjusted Cox regression models were used to assess the specific associations of preclinical CKM syndrome and IL-6, with risks of incident CVD and all-cause mortality. Models were adjusted for age, sex, race/ethnicity, smoking status, and physical activity. Effect modification was evaluated, and specific estimates were made. Results: Over a median follow-up of 18.2 years, 1,439 atherosclerotic CVD events, 475 heart failure (HF), and 2,115 deaths were recorded. Incidence rates for both atherosclerotic CVD and HF increased with advancing CKM stages, regardless of IL-6 elevation. Notably, the incidence rate of all-cause mortality was higher among participants at CKM Stage 2a with elevated IL-6 levels compared to those at Stage 2b with low IL-6 (178 v.s. 158 per 10,000 py). Elevated IL-6 was independently associated with increased risk of atherosclerotic CVD [HR 95% CI: 1.33 (1.19, 1.49)], HF [1.37 (1.13, 1.66)], and all-cause mortality [1.42 (1.29, 1.56)]. Furthermore, within each CKM stage, the strength of association between IL-6 and CVD outcomes was consistent between individuals with high and low IL-6 levels ( Table ). Effect modification by IL-6 was tested and found to be non-significant. Additionally, individuals at Stage 2b with elevated IL-6 exhibited the highest risk across all outcomes compared to those at Stage 0,1 with low IL-6: atherosclerotic CVD [3.57 (2.83, 4.50)], HF [3.84 (2.52, 5.85)], and all-cause mortality [1.98 (1.66, 2.37)]. Conclusions: IL-6 does not act as an effect modifier. Rather, it is independently associated with CVD events, with a consistent magnitude of association observed across CKM stages. Higher IL-6 coupled with CKM stage 2b is a powerful predictor of future events.

Abstract TH801: Survival predictors vary according to amyloidosis type: a pilot study comparing AL and ATTTR

Introduction: Cardiac amyloidosis (CA) is characterized by a wide spectrum of clinical manifestations, with prognosis primarily determined by the specific amyloidosis subtype and the degree of cardiac involvement. Although novel therapeutic approaches have altered the natural history of the condition, parameters for effectively monitoring prognostic changes remain to be established, especially when considering subtypes’ differences. Objective: This study sought to explore factors associated with survival in patients with CA and examine potential effects of Amyloidosis type (AL versus ATTR). Method: This pilot study included 29 patients diagnosed with either AL (n=14) or ATTR (n=15) cardiac amyloidosis. Data were collected between January 2020 and May 2025. Predictors were assessed at baseline: Nutritional status (Subjective Global Assessment), 6MWT, SF-36, KCCQ, NT-proBNP, global longitudinal strain (GLS), and stroke volume index (SVi). Outcomes were coded as low if in the lowest tertiles (binary transformation). Survival status was assessed after 1567±224 days. Kaplan-Meier analysis and the Log-Rank (Mantel-Cox) test were used to compare groups according to predictors. Results: At follow-up, 13 deaths were recorded (6 AL, 7 ATTR). When both AL and ATTR groups were combined, malnutrition (p=0.005), Energy/Fatigue Score (SF-36; p=0.045), Pain Score (SF-36; p=0.003), and 6MWT distance (p=0.034) were significant predictors of death. Upon separate analysis, survival among AL patients was significantly associated with malnutrition status (p=0.010), low physical limitation (KCCQ; p=0.002), low physical component score (SF-36; p=0.003), low energy/fatigue score (SF-36; p=0.017), low pain score (SF-36; p<0.001), and reduced 6MWT distance (p=0.035). For ATTR patients, no significant predictors of survival were identified. Conclusions: Traditional markers such as NT-pro-BNP, GLS, and SVi were not predictive of survival in our patient cohort. Notably, malnutrition, quality of life (QoL), and 6MWT distance demonstrated a strong prognostic value in patients with AL amyloidosis. These results underscore the importance of routinely adopting individualized evaluations and standardized multidisciplinary assessments in disease progression monitoring. Further large-scale studies are recommended to validate these findings and to investigate the influence of nutritional status on patient outcomes.

Abstract TU245: Relationships of Motivation, Self-Efficacy, and Social Support with Healthy Eating Behaviors Among Adolescents

Introduction: This study investigated the relationships of adolescents’ autonomous motivation, self-efficacy, and social support with the healthy eating index (HEI) total (primary outcome), whole fruit, total fruit, vegetable, sodium, added sugar, and caloric intake (secondary outcomes). Hypothesis: It was hypothesized that higher levels of autonomous motivation, self-efficacy, and social support would be positively associated with higher HEI scores and increased intake of fruits and vegetables, and negatively associated with intake of sodium, added sugar, and total calories. Methods: A secondary analysis of baseline data from a randomized controlled trial was conducted. A total of 935 5 th - 8 th graders, aged 10 to 14 years, were included. Generalized linear models and structural equation models examined relationships of motivation, social support, and self-efficacy for healthy eating behaviors. Results: Results show that family social support showed positive associations with HEI total score, HEI fruit, HEI whole fruit, and HEI added sugars. Additionally, age was positively associated with HEI added sugars. In generalized linear models, family social support was significantly associated with HEI fruit and caloric intake. Higher social support for healthy eating significantly increased motivation and self-efficacy, which in turn was associated with higher HEI total scores and lower added sugar and sodium intake. Conclusion: In conclusion, these findings add to the growing body of research on adolescent nutrition by emphasizing the complex interplay of psychosocial factors in shaping specific dietary behaviors.