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Abstract 065: Lower Acute Healthcare Utilization Associated with Virtual Cardiometabolic Health Programs

Background: Type 2 diabetes and hypertension are common and costly conditions that increase risk for hospitalization. Lifestyle-focused virtual health programs may offer an effective and accessible self-management solution for these conditions and reduce future high-cost acute care encounters. The purpose of this study was to evaluate the differences in inpatient and emergency room (ER) healthcare utilization between patients enrolled in a virtual health program (VH) for cardiometabolic lifestyle management vs. usual care (UC) controls at 6 and 12 months. Methods: We conducted a real-world, retrospective secondary analysis of healthcare claims incurred between July 2019 and May 2023 from multiple payers. Inclusion criteria included continuous coverage for ≥6 months pre- and post-index, an age range of 18-64 years, and having commercial insurance. Index date was defined as the program enrollment date for VH patients or an outpatient claim with a type 2 diabetes and/or hypertension diagnosis code for UC patients. VH patients were enrolled in Omada for Diabetes (DM; n=317), Hypertension (HTN; n=1,102), or Diabetes&Hypertension (DM+HTN; n=315) program and 1:3 propensity score matched (demographics, clinical characteristics and pre-index costs) to UC controls (n=951, n=3,306, and n=945, respectively). Mean differences in post-index inpatient, ER, and acute (inpatient+ER) encounter counts were compared at 6 and 12 months using t-tests. Results: After matching, the VH and UC groups had no statistically significant differences in pre-index characteristics. VH patients across all programs had fewer inpatient, ER, and acute encounters at 6 and 12 months vs. UC (absolute mean difference range -0.01 to -0.33, relative difference range: -5% to -63%). Specifically, DM VH patients had 63% lower inpatient utilization at 12 months, 46% lower ER utilization at 6 months, and 54% and 52% lower acute utilization at both 6 and 12 months vs. UC (all p<.05). HTN VH patients experienced significant reductions at both 6 and 12 months for ER and acute utilization vs. UC (ER: -56%, -43%; Acute: -51%, -40%; all p<.05). Finally, DM+HTN patients had 43% lower ER utilization at 6 months vs. UC (p=.04). Conclusions: Using a lifestyle-focused virtual health program to support cardiometabolic disease management may lead to meaningful reductions in high-cost acute care encounters, indicating the value of using virtual solutions as an effective and accessible approach to between-visit care.

Abstract P2111: Analysis of C-reactive protein omics-measures associates methylation risk score with obstructive sleep apnea-related measures

Introduction: DNA methylation (DNAm) predictors of high sensitivity C-reactive protein (CRP) offer a stable and accurate means of assessing chronic inflammation, bypassing the CRP protein fluctuations secondary to acute illness. Poor sleep health is associated with elevated inflammation and blood CRP levels which may explain associations of sleep insufficiency with metabolic, cardiovascular and neurological diseases. Our study aims to characterize the relationships obstructive sleep apnea (OSA)-associated phenotypes and CRP markers —blood, genetic, and epigenetic indicators—within the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: Multiple polygenetic risk score (PRS)-CRP scores were evaluated for their association with circulating CRP in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort to select the best-performing PRS-CRP for association analysis in HCHS/SOL. Methylation risk scores (MRS)-CRP and PRS-CRP were constructed separately in HCHS/SOL for each individual as weighted sums of methylation beta values or allele counts, respectively. OSA-related phenotypes were measured using self-reported questionnaires and objective measurements. Survey-weighted linear and logistic regressions estimated the associations between OSA-related phenotypes (apnea-hypopnea index (AHI), minimum oxyhemoglobin saturation during sleep (min SpO2), and excessive daytime sleepiness (EDS)), diabetes and hypertension with CRP markers while adjusting for age, sex, BMI, study center, and the first five principal components of genetic ancestry. Results: We included 2221 HCHS/SOL participants (age range 37-76 yrs, 65.7% female) in the analysis. Both the MRS-CRP (95% confidence interval (CI): 0.32-0.42, p = 3.3 x 10 -38 ) and the PRS-CRP (95% CI: 0.15-0.25, p = 1 x 10 -14 ) were associated with blood CRP level. MRS-CRP was associated with AHI, min SpO2, diabetes and hypertension, while PRS-CRP markers was not. EDS was associated only with circulating CRP levels, while diabetes was associated with both circulating and MRS-CRP. Associations between OSA traits and metabolic comorbidities weakened after adjusting for MRS-CRP, with a strong impact of diabetes. Conclusions: MRS-CRP is a promising estimate for systemic and chronic inflammation, which either mediates or serves as a common cause of the association between OSA-related phenotypes and related comorbidities, especially diabetes.

DeltaC and DeltaD ligands play different roles in the segmentation clock dynamics

Abstract 043: Circulating Monocyte Gene Expression Profiles of Cardiac Remodeling and Incident Heart Failure: the Multi-Ethnic Study of Atherosclerosis

Introduction: The role of circulating monocytes in non-ischemic cardiac remodeling and heart failure (HF) is complex and unclear, due in part to monocyte heterogeneity and plasticity. We assessed the hypothesis that monocyte gene expression profiles reflecting activation and tissue inflammation are associated with cardiac structure and function and incident adjudicated HF in the Multi-Ethnic Study of Atherosclerosis. Methods: Monocytes were isolated from peripheral blood, and RNA was quantified using an Illumina BeadChip microarray. Cardiac magnetic resonance was performed concurrently. We used multivariable linear regression to estimate cross-sectional associations between gene expression levels and cardiac structure and function and Cox regression to estimate associations with time to incident HF. Results: We studied 12,369 transcripts mapping to 9,430 genes among 813 participants (mean age 69±9 years; 50% female; 22% Black; 29% Hispanic). Independent of traditional risk factors, expression levels of 55 transcripts were associated with left ventricular (LV) ejection fraction, 1136 with LV strain, 16 with LV geometry, 1020 with myocardial interstitial fibrosis, and 483 with left atrial size (FDR<0.05). Enrichment analysis implicated T and B cell activation, cytokine production, phagocytosis, wound healing, oxidative stress, and cell migration. Expression levels of three genes—PCCB, MTCP1, and VIM—were associated with more than one cardiac metric as well as time to clinical HF ( n =45 events over a median follow-up of 7.7 years). Conclusion: These unique data support an association between monocyte-mediated immune processes and subclinical cardiac remodeling and incident HF in the absence of ischemic injury. Agnostically identified profiles were enriched for processes related to both pro-inflammatory and pro-resolving activated monocyte function and immunometabolism, as well as tissue migration and homeostasis. These insights may help generate hypotheses toward novel therapeutic targets for HF.

Abstract P1004: Epigenetic Age Acceleration Predicts All-cause and CVD-specific Mortality over 20-years in a national-representative population

Background: Epigenetic age acceleration (EAA), the difference between DNA methylation-calculated age (DNAmAge) and chronological age, reflects biological aging. However, few studies have examined the prospective association of EAA with mortality in a national-representative sample. This study aims to investigate whether EAA is predictive of all-cause and cardiovascular disease (CVD) specific mortality over 20-year follow-up in the National Health and Nutrition Examination Survey (NHANES, cycle 1999–2002). Methods: We included 2,353 participants aged over 50 who had DNA methylation data at baseline and have been linked to the National Death Index in 2019. EAA was calculated by regressing DNAmAge on age and cell composition, using six estimators (Horvath, Hannum, SkinBlood, PhenoAge, GrimAgeMort, GrimAge2Mort). CVD deaths were identified by specific ICD-10 codes. Survival month was defined as the interval between baseline and the time of death or censorship. Cox proportional hazards models, adjusted for demographics, socioeconomic status, smoking, BMI, and chronic diseases, were used. Analyses were stratified by pre-existing CVD and BMI. Results: Over a median follow-up of 207 months, 1,210 deaths (385 CVD-specific) occurred. All EAA measures were significantly associated with increased all-cause mortality (except for SkinBlood-EAA) and CVD-specific mortality (except for Horvath-EAA). For instance, per 5-year increment of Hannum-EAA was associated with a 13% higher risk of all-cause mortality (HR: 1.13, 95% CI: 1.07 – 1.21), and 25% higher risk of CVD-specific mortality (HR: 1.25, 95% CI: 1.12 – 1.40). In those with pre-existing CVD, all EAA measures (excluding Horvath-EAA) were significantly associated with CVD mortality (e.g., PhenoAge-EAA HR: 1.13, 95% CI: 1.02–1.24), while no significant associations were found for participants without pre-existing CVD (e.g., Hannum-EAA HR: 1.08, 95% CI: 0.88–1.32). Stratified by BMI, obese individuals showed the highest hazard ratios. For instance, Hannum-EAA in obese participants was associated with an HR of 1.17 (95% CI: 1.04–1.32), compared to normal-weight (HR: 1.12, 95% CI: 1.00–1.25) and overweight participants (HR: 1.06, 95% CI: 0.95–1.18). Conclusion: Accelerated biological aging, as indicated by epigenetic clocks, was associated with increased all-cause and CVD-specific mortality risk in a US representative sample over 20 years. Associations were stronger among those with pre-existing CVD or obesity.

Abstract P2134: Fatigue category, quality of life, and risk of incident clinical heart failure in those with stage B heart failure in the Atherosclerosis Risk in Communities (ARIC) Study.

Background: General and exertional fatigue are common in clinical heart failure (HF) and associated with worse quality of life (QOL) and increased risk of HF re-admission and mortality. However, little is known about general and exertional fatigue in those with pre-HF. Methods: We included 2,972 individuals at Visit 5 (2011-13) of the ARIC study without clinical HF but meeting criteria for pre-HF (stage B HF per ACC/AHA guidelines) by echocardiography or elevated cardiac biomarkers, and with complete fatigue data. Using previously defined PROMIS fatigue (general fatigue) and MRC Breathlessness (exertional fatigue) scale score thresholds, individuals were cross categorized into 4 groups: low/no fatigue, high general fatigue, high exertional fatigue, and the co-occurrence of high general and high exertional fatigue. Adjusting for sociodemographic and clinical characteristics, we determined the cross-sectional association of fatigue category with physical and mental QOL (SF-12 scale) using linear regression, and prospective associations with incident clinical HF using Cox regression. To reduce the contribution of indolent HF to results, we conducted a sensitivity analysis excluding individuals with an outpatient diagnosis of clinical HF from Centers for Medicare and Medicaid Services claims data. Results: Participants were 60% female, 18% Black, and had a mean age of 76 years. Compared to the low/no fatigue category, all individuals in higher fatigue categories had lower physical QOL scores. The co-occurrence of high general and exertional fatigue was associated with the lowest QOL [β (95% CI) = -11 (-13, -10)] (Table). More modest, but significant, associations were seen for fatigue categories with mental QOL. Compared to the low/no fatigue category, those with high exertional fatigue, and those with the co-occurrence of high general and high exertional fatigue, had higher risk of incident clinical HF [HRs (95% CI) = 1.9 (1.4, 2.5) and 2.2 (1.5, 3.2), respectively]. Associations were similar after excluding individuals with an outpatient clinical HF diagnosis. Conclusions: In those with pre-HF, worse fatigue category was associated with worse QOL and increased risk of incident clinical HF, independent of traditional risk factors. Assessment of general and exertional fatigue may provide prognostic information in individuals with pre-HF.

Correction for Liu et al., Cytoskeleton remodeling mediated by circRNA-YBX1 phase separation suppresses the metastasis of liver cancer

Designing polymersomes with surface-integrated nanoparticles through hierarchical phase separation

Abstract P2042: Descriptive Analysis of Geographic and Sociodemographic Patterns in Poor Cardiovascular Health Across U.S. Census Tracts

Introduction: Examining geographic and sociodemographic differences in Poor Cardiovascular Health (PCVH) across U.S. neighborhoods can help identify where the most significant disparities in cardiovascular disease exist. We sought to map and examine the distribution of PCVH across U.S. census tracts by levels of social vulnerability and rurality from 2017 to 2021. Hypothesis: We hypothesize that PCVH will be more prevalent in regions with greater social vulnerability and in rural areas. Methods: We examined area-level PCVH score based on the Life’s Essential 8 (LE8) framework across 60,632 U.S. census tracts (~85% of Continental U.S. census tracts). Prevalence data for seven LE8 components (high blood pressure, poor sleep, physical inactivity, diabetes, smoking, obesity, and high cholesterol), as well as the Social Vulnerability Index (SVI) were from the Centers for Disease Control and Prevention. Rural-Urban Commuting Area (RUCA) codes and limited access to healthy food, used as a proxy for poor diet, were obtained from the U.S. Department of Agriculture. Percentile estimates from the eight components were averaged to generate a composite PCVH score for each tract (range 0-100), then classified as quartiles based on percentile ranking (Q4=poorest PCVH). We then mapped PCVH quartiles across census tracts (Figure 1). Differences in PCVH score were analyzed across SVI quartiles, urbanicity status (metro vs. rural), U.S. census regions, and racial/ethnic groups. Results: The median PCVH score was 62.5, with an interquartile range of 46.8 to 78.1. The mean PCVH score was higher in rural (61.2, SD = 16.6) compared to metropolitan (47.2, SD = 22.7) tracts. Tracts with the lowest SVI (less vulnerable) had a mean PCVH of 30.9 (SD = 15.2), while those in the highest quartile had 69.4 (SD = 17.4) (data not shown). Additionally, tracts in the South [60.7 (SD = 22.1)] and Midwest [52.9 (SD = 21.4)] states had a higher PCVH score compared to West and Northeast [35.3 (SD = 18.1] and 44.5 (SD = 19.5), respectively]. Tracts with larger Black or African American populations were overrepresented in the upper PCVH quartiles [30.1% (SD = 31.79) in PCVH Q4 vs 4.6% (SD = 7.1) in Q1]. Conclusion: These findings highlight geographic and sociodemographic disparities in PCVH across U.S. census tracts, with a higher burden found in the South and Midwest, as well as in rural and more socially vulnerable census tracts.

Abstract MP37: Proteomics Of Prediabetes Progression And Remission: The Atherosclerosis Risk In Communities (ARIC) Study

Introduction: Proteomics could improve our understanding of the mechanisms underlying short-term prediabetes progression and remission, i.e., reverting to normoglycemia. Objective: To identify proteomic predictors of 3-year progression from prediabetes to diabetes and remission. Method: We used data from the Atherosclerosis Risk in Communities (ARIC) Study visit 2 (1990-2) and visit 3 (1993-5). We examined associations of 4,955 plasma proteins (SOMAScan v4.0) in participants with baseline prediabetes (fasting glucose [FG] 100-125 mg/dL without diabetes). We used multivariable logistic regressions to examine protein associations with 3-year progression from prediabetes to diabetes (physician diagnosis, medication, or FG ≥126 mg/dL) or remission (FG <100 mg/dL). Analyses were adjusted for demographics, cardiometabolic risk factors, and baseline glucose. Statistical significance was based on p<10 -5 . We explored biologic pathways enriched among top proteins and calculated the delta-AUC for models with (and without) the associated proteins. Results: The 3,788 participants with prediabetes were mean aged 57 years (SD:6), 52% were women, 18% self-identified as Black. The 3-year cumulative incidence of diabetes was 6% and was 40% for prediabetes remission. We identified 6 proteins associated with 3-year progression to diabetes (e.g., lower adiponectin [ADIPOQ]) and 8 proteins (e.g., higher insulin growth factor binding protein 2 [IGFBP2], lower complement C3 [C3]) associated with prediabetes remission. Adipogenesis and Jak/STAT signaling were among the pathways enriched in diabetes-associated proteins. Regulation of IGF transport and uptake by IGFBPs and C3/C5 activation were pathways for remission-associated proteins. The 6 proteins collectively improved diabetes progression prediction (covariate only AUC=0.798; delta-AUC=0.03 p<0.001). The 8 proteins collectively improved remission prediction (covariate only AUC=0.722; delta-AUC=0.03 p<0.001). Conclusions: In persons with prediabetes, we identified known and novel proteins that were associated with 3-year progression to diabetes and remission. Proteins associated with remission relate to reduced inflammation and improved insulin sensitivity.

Abstract P2132: Impact of Midlife Physical Activity on Multimorbidity in a Rural Setting: Insights from the Bogalusa Heart Study

Introduction: The prevalence of multiple chronic conditions (CCs), especially cardiovascular-related, is increasing, leading to higher disability and mortality. Midlife is a critical period for the development of CCs, necessitating interventions to prevent progression to multimorbidity. Physical activity (PA) is a key intervention to reduce the risk of developing multimorbidity. However, the impact of midlife PA on CCs in rural communities remains under-explored. This study examined the relationship between PA and multimorbidity (defined as >2 CCs) in a rural middle-aged population. Hypothesis: Participants in midlife with higher levels of PA would be less likely to present multimorbidity compared to those with low PA. Methods. We examined 1,289 participants (mean age 48 ± 5.24 years; 34.6% Black, 65.4% White) from the Bogalusa Heart Study, a long-term longitudinal rural study. Logistic regression models assessed the association between PA scores low (minimal or no PA), moderate (>=600 MET-Minutes/week), and high (>=3,000 MET-Minutes/week) using the International Physical Activity Questionnaire (IPAQ) long form and multimorbidity defined as >2 CCs. Eight CCs (hypertension, dyslipidemia, diabetes, chronic kidney disease, cardiovascular disease, cancer, depression, and chronic obstructive pulmonary disease) were selected based on Centers for Medicare&Medicaid Services guidance using self-reported medical history. Models were adjusted for age, race, and sex. Results: Moderate PA was associated with lower odds of multimorbidity compared to low PA (Unadjusted OR=0.724, 95% CI=0.534–0.983, p =0.038), though this was not statistically significant after adjustment (OR=0.782, 95% CI= 0.57–1.06, p =0.114). Individuals with high PA scores also showed lower odds of multimorbidity in the unadjusted model (OR=0.88, 95% CI=0.62–1.24, p =0.482) but was not statistically significant after adjustment (OR=0.91, 95% CI=0.64-1.30, p =0.627). Conclusion: The data suggest a possible link between PA and multimorbidity, though no direct association was established. The reduced odds of multimorbidity with higher PA diminished after adjusting for sociodemographic factors, highlighting the need to consider these influences when evaluating PA's benefits in rural settings. Future studies should aim to better understand sociodemographic factors to develop effective and tailored PA interventions that can promote health and reduce CCs in rural populations.

Emergent quantum Majorana metal from a chiral spin liquid

Abstract P2120: Assessing the Accuracy of OpenStreetMap Sidewalk Data: A Comparative Study with Google Street View

Purpose: OpenStreetMap (OSM) serves as an open-and-crowd-sourced geospatial database widely utilized as a data-source in walkability studies, yet its sidewalk data accuracy remains unverified. Methods: An OSM base-map of Maryland was generated, excluding roads inaccessible to pedestrians, then clipped to 141 randomly selected census tracts (~10% of total census tracts), stratified by population density tertiles. Fifty points within each census tract were randomly distributed across qualifying roads. The OSM base-map and Google Street View (GSV) at each point were reviewed visually by trained researchers to determine sidewalk presence (one or both sides of the street) or absence. Points with unavailable GSV were excluded, and unclear points were re-reviewed for consensus. Percent agreement in sidewalk data between GSV and OSM was calculated for all tracts and for a subset excluding tracts with 0 sidewalks in GSV. ANOVA and post-hoc pairwise tests compared mean accuracy scores by population density tertiles. Results: Of the 7,050 points reviewed, across 141 census tracts, 6103 points were available in GSV, with 3674 points having sidewalks in GSV. When points without sidewalks were excluded from analysis, 11 census tracts were removed, showing that they had no points with sidewalks; all were from the low-density tertile. Agreement at all points and points with sidewalks in GSV are presented in Table 1. ANOVA analysis conducted at all points showed significant differences based on population density tertiles. Pairwise comparison found the low-density tertile had significantly (p>0.001) higher agreeance from mid and high-density tertiles. ANOVA and pairwise comparison for points with sidewalks in GSV showed no difference (p>0.05) between population density tertiles. Conclusions: OSM sidewalk data exhibits limited accuracy, with results showing underreporting of sidewalk presence in OSM. In 72% of points with sidewalks in GSV, OSM did not report sidewalks. The higher agreement at all points shows a lack of walkability, especially in lower density census tracts, combined with the default reporting setting of OSM, which is no sidewalks. These findings highlight the need to evaluate sidewalk presence when updating OSM content. Variations between census tracts may be caused by demographic factors, however, additional research is necessary. Potential limitations include availability and date of GSV images, and issues with generalizability outside study location.

Abstract P2144: The Duration of Expectant Management During Hypertensive Disorders of Pregnancy and Blood Pressure 2-7 Years After Delivery

Expectant management of preterm pregnancies with hypertensive disorders (HDP), such as preeclampsia (PE), is standard practice for neonatal benefit, although the effects on the maternal cardiovascular (CV) system from longer exposure to endothelial inflammation is uncertain. Latency of expectant management is the time from HDP diagnosis to delivery. Studies from administrative databases suggest a higher rate of adverse CV outcomes several years post-pregnancy with latency >7 days. Using the nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Heart Health Study) cohort, we evaluated the relation between latency in nulliparas expectantly managed with HDP and mean systolic and diastolic blood pressure (BP) 2-7 years post-pregnancy. In the primary study (nuMoM2b), pregnancy diagnoses and outcomes were prospectively ascertained and biospecimens were obtained. We included those with HDP (PE with or without severe features, and gestational HTN) diagnosed <37 weeks. Latency was defined as short (2-7 days) or long (>7 days). We excluded those with chronic hypertension (HTN) or pregestational diabetes at index pregnancy, if exposure or outcome data were missing from the index pregnancy or HHS visit, or if latencies were implausible based on timing of diagnosis and delivery. We used linear regression models to examine the association between latency with BP and markers of CV risk (high-sensitivity CRP (hs-CRP), lipids, HgbA1C, NTproBNP, and ACC/AHA CV risk score) obtained 2-7 years post-pregnancy. We planned a sensitivity analysis of those with early-onset HDP (diagnosis <34 weeks). 150 participants, 32 with short and 118 with long latency, met inclusion criteria (Table 1). BP at HHS follow-up was not different by latency duration (Table 1, Fig 1). hs-CRP was significantly higher in those with long latency, including after adjustment for confounders (age, race, BMI, baseline CV markers, gestational diabetes, small for gestational age infant, and smoking [Fig 2]). The other markers of CV risk were not statistically different between groups [Table 1]. In sensitivity analysis, BP was not different between groups; however, hs-CRP was significantly higher in the longer latency group. In this cohort of prospectively adjudicated pregnancy outcomes, longer latency in those with expectantly managed preterm HDP was not associated with overall differences in CV risk, including BP 2-7 years after a first delivery. The finding of elevated hs-CRP warrants follow-up in a larger cohort.

Abstract P2146: Multiple Pathways of CD34 ⁺ Cell Differentiation during Embryogenesis

Introduction: CD34 + progenitor cells are widely used for stem cell therapy for cardiovascular diseases, but the effectiveness of the treatment is variable. To understand the fundamental mechanism of CD34 + cell development, we aimed to investigate cell fates of CD34 + progenitors during the embryogenesis of mice and humans. Methods: Human embryos from PCW 6 to 12 were obtained from patients who had undergone induced or spontaneous abortions and samples were subjected to mass spectrometry. For the animal model, embryos were obtained among C57BL/6J, Cd34 -DreER T2 ; IR, CD34 -CreER T2 ; R26-tdTomato, Cdh5 -dre; IR; Cd34 -creER, Cd34 -CreER T2 ; R26-tdTomato; Kdr flox , Cd34 -CreER T2 ; R26-tdTomato; Pdgfra flox mice. Single-cell RNA sequence (scRNA-seq) was performed using the databases generated from our group and publicly data from NCBI Gene Expression (GEO) Omnibus (E6.5 to E18.5 cells). Additionally, whole-mount staining and three-dimensional reconstruction were used to depict different types of CD34 + progenitor distribution within transparent embryos. Results: The proteomics unveiled an assumed intricate orchestration in developing human embryos from patients who experienced induced or spontaneous abortions. Our study demonstrated that the high level of CD34-expressing cells uncovered the potential naïve pluripotency to differentiate during embryonic development. Moreover, deletion of Kdr in CD34-derived cells resulted in stalled vessel development in stages spanning E6.5 to E8.5, which is crucial to endothelium development. Also, the activation of the cell cycle machinery was identified as a driver of endothelial-to-hematopoietic transition (EHT) in Cd34 + Runx1 + Cd44 + cells from E9.5 to E11.5. Until late embryogenesis, CD34 + progenitors gave rise to fibroblasts. Finally, CD34 + cells contribute to the quiescent stem cell pool in the adult stage and enter the cell cycle when the body suffers damage. Conclusions: Our results conducted a comprehensive study on the spatial and temporal induction of CD34 + cells and their intricate functions in embryonic development. These findings enlightened us on paving the way to innovatively tackle the complex hurdles present in stem cell and regenerative medicine, particularly in stem cell therapy.

Full-color tuning in multi-layer core-shell nanoparticles from single-wavelength excitation

Abstract P2126: Physical Activity, Inflammation, and Cardiometabolic Risk in Diabetic Kidney Disease: A Population-Based Study

Introduction: Diabetic kidney disease (DKD) increases morbidity and mortality in individuals with diabetes. This study aimed to examine the relationships between cardiometabolic factors, high-sensitivity C-reactive protein (hs-CRP), physical activity (PA) measured as total METs, and the risk of DKD in adults. Additionally, it explored moderators of the association between total PA METs-DKD. Hypothesis: We hypothesized that lower levels of cardiometabolic factors and hs-CRP, along with higher levels of total PA METs are associated with reduced DKD risk in adults. We also posited that age and race/ethnicity moderate the relationship between total PA METs and DKD. Methods: The study analyzed 5,856 adults aged ≥18 years (mean age = 49.89) from the 2017-2018 National Health and Nutrition Examination Survey. DKD was defined by diabetes with an estimated glomerular filtration rate of <60 mL/min/1.73m2 or an albumin to creatinine ratio was ≥30 mg/g. The International Physical Activity Questionnaire was used to subjectively measure PA in the survey. Multiple imputations were conducted to address the missing data. Hierarchical logistic regression was used to assess the odds of DKD and identify moderators. Results: DKD was present in 13.32% of participants. Age strongly predicted DKD, with those aged 70-80 having an 18.13 times higher risk than those aged 20-29. Non-Hispanic Black participants had 1.51 times higher DKD risk than non-Hispanic Whites. Among metabolic and inflammatory markers, high systolic blood pressure, elevated fasting glucose level, and hs-CRP were associated with increased odds of DKD. Conversely, total cholesterol levels of 5.2-6.2 mmol/L and total PA METs ≥1,110 METs-minutes/week were linked to a 24% and 25% reduction in DKD odds, respectively. Age and race/ethnicity did not moderate the relationship between total PA METs and DKD. Conclusions: Most cardiometabolic markers and hs-CRP were associated with increased DKD risk, while total cholesterol and total PA METs were associated with reduced DKD risk. Contrary to our hypothesis, age and race/ethnicity did not moderate the relationship between total PA METs and DKD risk.

Abstract P2143: Adverse Pregnancy Outcomes – Planning for Fourth Trimester Interventions to Promote Equitable Long-Term Cardiovascular Health

Introduction: Adverse pregnancy outcomes (APOs) are significantly associated with future cardiovascular disease and cardiovascular mortality and disproportionately affect women from minority racial and ethnic groups. Maternal and perinatal morbidity in the Southeast US is among the highest in the country, and cardiovascular disease (CVD) is the #1 cause of death in pregnant and nonpregnant patients. Therefore, we sought to define the contemporary epidemiology of APOs among pregnant and postpartum individuals at a major tertiary center in the Southeast US to plan a fourth-trimester cardiovascular disease intervention. We assessed the hypothesis that there is racial and ethnic variation in the epidemiology of APOs. Methods: We performed a retrospective study including pregnant/postpartum patients from a tertiary center between 2013 and 2018. The primary outcome was APO prevalence, defined as ≥1 of the following diagnoses during pregnancy or <6 weeks postpartum: hypertensive disorders of pregnancy (HDP), preterm birth (PTB), diabetes, placental abruption, intrauterine fetal demise (IUFD), and small for gestational age (SGA) neonate. Secondary outcomes included trends in APO prevalence, and prevalence of and adjusted relative risks (aRR) of APOs by self-reported race/ethnicity. Results: Of 24,637 patients included in this study, all baseline characteristics significantly differed between groups. APOs occurred in 11,507 (47%) of pregnancies. Overall trends of HDP increased dramatically across the study period from 17% to 22% (p<0.001). APO prevalence in Non-Hispanic Black, Non-Hispanic White, and Hispanic individuals were significantly different at 53%, 32%, and 12% (p<0.001) (Figure). In adjusted analysis with Non-Hispanic White as a reference, Non-Hispanic Black individuals had an increased risk of APO aRR 1.03 (95% confidence interval (CI) 1.01-1.04), while Hispanic individuals had a reduced risk of APOs aRR 0.91 (95% CI 0.88-0.94). Hispanic individuals had an increased risk of diabetes aRR 1.73 (95% CI 1.51-1.94) while Non-Hispanic Black patients had an increased risk for IUFD aRR 1.33 (95% CI 1.05-1.60) and SGA aRR 1.32 (1.25-1.39). Conclusion: Nearly half of the patients in the study period experienced an APO with marked racial/ethnic disparities. As APOs are associated with future CVD - the #1 cause of death - these findings underscore an urgent need for timely fourth-trimester interventions to promote equitable cardiovascular health.

Abstract P2166: Neighborhood-level socioeconomic deprivation associates with monocyte phenotypes involved in atherogenesis: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Chronic neighborhood stressors contribute to disparate CVD outcomes, with neighborhood socioeconomic deprivation (NSD) linked to inflammation. Separately, relationships have been seen with CVD and specific monocyte phenotypes. However, the connection between neighborhood exposures and monocyte subsets is less clear. Thus, we examined NSD with monocyte phenotypes, hypothesizing that chronic NSD cross-sectionally associates with monocyte subsets. Methods: This study utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based prospective cohort of adults aged 45-84 years (N=6814). NSD was scored from principal factor analyses using U.S. Census data (2000), with higher values indicating higher deprivation. Monocyte phenotypes were measured from cryopreserved peripheral blood mononuclear cells by flow cytometry at MESA Exam 1 (2000-02). Subsets were characterized as classical monocytes (CMs, CD14++CD16-), intermediate monocytes (IMs, CD14+CD16+), and non-classical monocytes (NCMs, CD14+CD16++). Linear regression models were used to examine associations between NSD and monocyte phenotypes, adjusting for individual-level covariates. Results: Of the MESA cohort, participants with monocyte phenotypes (n=1527) were included in analyses (age 62.9±10.5 years, 50.5% male, 37.4% White, 28.6% Black, 20.6% Hispanic). Higher NSD was associated with lower CMs but higher IMs and NCMs (Table). When gender-stratified, relationships remained significant for CMs but not for IMs. In men, higher NSD was associated with higher NCMs but not when adjusted for covariates. Conclusion: Neighborhood deprivation as a marker of chronic stress was associated with shifts in monocyte subsets in a partially sex-dependent manner, with differential relationships with CMs, IMs, and NCMs. With IMs and NCMs associated with accelerated CVD, these findings may help illuminate the role of monocytes in how neighborhood exposures lead to CVD. Future analyses will examine interactions with race/ethnicity and inflammatory biomarkers.

Binary peptide coacervates as an active model for biomolecular condensates

Abstract Biomolecular condensates formed by proteins and nucleic acids are critical for cellular processes. Macromolecule-based coacervate droplets formed by liquid-liquid phase separation serve as synthetic analogues, but are limited by complex compositions and high molecular weights. Recently, short peptides have emerged as an alternative component of coacervates, but tend to form metastable microdroplets that evolve into rigid nanostructures. Here we present programmable coacervates using binary mixtures of diphenylalanine-based short peptides. We show that the presence of different short peptides stabilizes the coacervate phase and prevents the formation of rigid structures, allowing peptide coacervates to be used as stable adaptive compartments. This approach allows fine control of droplet formation and dynamic morphological changes in response to physiological triggers. As compartments, short peptide coacervates sequester hydrophobic molecules and enhance bio-orthogonal catalysis. In addition, the incorporation of coacervates into model synthetic cells enables the design of Boolean logic gates. Our findings highlight the potential of short peptide coacervates for creating adaptive biomimetic systems and provide insight into the principles of phase separation in biomolecular condensates.