Browse Articles
Discover research articles across all indexed journals
Evolution of the <i>JULGI–SMXL4/5</i> module for phloem development in angiosperms
Bifacial cambium, which produces xylem and phloem, and monopodial architecture, characterized by apical dominance and lateral branching from axillary buds, are key developmental features of seed plants, consisting of angiosperms and gymnosperms. These allow seed plants to adapt to diverse environments by optimizing resource allocation and structural integrity. In seed plants, SUPPRESSOR OF MAX2-LIKE ( SMXL ) family members function in phloem development and strigolactone-induced inhibition of axillary bud outgrowth. Although strigolactone signaling regulates most SMXL family members, the only known regulator of SMXL4 and SMXL5 is the RNA-binding protein JULGI. We demonstrate that in angiosperms, by directly regulating SMXL4/5 expression, JULGI uncouples SMXL4/5 activity from strigolactone signaling. JULGI and ancestral SMXL s from seedless vascular plants or SMXL4/5 from seed plants are coexpressed in the phloem tissues of vascular plants, from lycophytes to angiosperms. Core angiosperm SMXL4/5 mRNAs contain a G-rich element in the 5′ untranslated region (UTR) that serves as a target sequence for JULGI to negatively regulate SMXL4/5 expression. Heterologous expression of JULGI s from various angiosperms rescued the Arabidopsis jul1 jul2 mutant. Expressing SMXL4/5 s from seed plants and ancestral SMXL s rescued Arabidopsis smxl4 smxl5 . Angiosperm SMXL4/5s lack an RGKT motif for proteasomal degradation. Indeed, treatment with the synthetic strigolactone analog rac -GR24 induced proteasomal degradation of SMXL from ferns and SMXL5a from gymnosperms, but not SMXL4/5 from angiosperms. These findings suggest that in ancestral angiosperms, the 5′ UTR of SMXL4/5 gained G-rich elements, creating a regulatory module with JULGI that allows the phloem development pathway to act independently of strigolactone signaling.
Abstract P2141: Developing a Targeted Educational Intervention Addressing Barriers to Home Blood Pressure Monitoring for Pregnant People with Hypertensive Disorders of Pregnancy
Introduction: Hypertension (HTN) is a leading cause of maternal morbidity and mortality. Home blood pressure monitoring (HBPM) is essential in pregnancy due to blood pressure variability, limited medication options, and high rates of Whitecoat HTN. However, there is no standard for counseling, and utilization is inconsistent. Hypothesis: To identify patient- and provider-reported barriers to HBPM in pregnancies complicated by hypertensive disorders (HDP) to guide the development of a targeted educational intervention. Methods: From April to August 2023, pregnant participants (n = 21, mean age 31.6 years, SD 5.3) with HDP and perinatal healthcare providers (n = 4) were recruited from an academic tertiary care center. In-person interviews explored experiences with HBPM, identified barriers, and gathered recommendations for change. Qualitative analysis was used to generate and reconcile themes and subthemes. Discrepancies were resolved by consensus. Root cause analysis was conducted using the "5 Why Technique," and a Plan-Do-Study-Act (PDSA) cycle informed the design of our intervention. Results: Of the 21 participants, 71.4% utilized HBPM, but only 13.3% received guidance from providers. The average confidence level in HBPM was 6.67 (SD 3.4) on a 0-10 Likert scale. The major root causes leading to decreased confidence in utilizing HBPM included: 1) no standardized guidance or resources for providers and patients regarding HBPM and alert values during pregnancy; 2) no streamlined process recommended or taught to patients; and 3) no consolidated resources on available validated cuffs for this patient population. To address these issues, we developed a patient-centered educational intervention, including physical pamphlets, a video guide, and online links to a template log and validated cuffs currently accessible for this patient population. Conclusion: In conclusion, we identified critical barriers to HBPM in pregnancies with HDP, including insufficient guidance, inadequate access to resources, and absence of standardized processes. A new targeted educational intervention, including patient-focused materials and provider resources, was developed to address these barriers. Ongoing post-intervention data collection aims to refine and optimize the intervention for broader reach and improved confidence in HBPM practices. Targeted solutions like this may ultimately improve maternal outcomes and reduce risks associated with hypertensive disorders in pregnancy.
Abstract 004: Longitudinal Change in Cardiovascular Health by Repeated Measures of Self-Reported Sexual Orientation Discrimination in the CARDIA Study Cohort
Introduction: Few studies have investigated the association of self-reported discrimination based on sexual orientation with cardiovascular health. Objective: We assessed if repeated self-reported sexual orientation discrimination was associated with longitudinal cardiovascular health among males and females in the CARDIA study. Methods: CARDIA participants completed cardiovascular health assessments and sexual orientation discrimination measures in 1992-1993 (Year 7 Exam), 2015-2016 (Year 30 Exam), and 2020-2022 (Year 35 Exam). For each exam, participants reported if they experienced discrimination attributable to sexual orientation in 6 different contexts (at school, getting a job, at work, at home, getting medical care, and in public settings). The number of reported discrimination contexts was summed at each time point and assigned to one of four levels (0, 1, 2, or 3 or more experiences). Multiple imputation by chained equations was used to estimate missing exposure and outcome variables. Linear mixed models stratified by sex were used to estimate the associations between age, sexual orientation discrimination, and Life’s Simple 7 (LS7). The interaction of age and discrimination was used to estimate differences in change in LS7 over time (i.e., age) by levels of discrimination. Results: Median participant age was 54 years (SD 12.7 years), 55.3% of participants were female, and 49.7% were Black. Combining participant reports of females across all 3 exams, 83.5% reported 0, 4.8% reported 1, 2.6% reported 2, and 4.2% reported 3 or more contexts of sexual orientation discrimination. Among males, these percentages were 84.7%, 4.6%, 2.4%, 4.2%, respectively. The mean LS7 score across all visits for all participants was 7.68 (SD 1.78). Females who reported 3 or more sexual orientation discrimination contexts had significantly lower cardiovascular health than those who reported no sexual orientation discrimination (b = -0.60, p=0.008), but no significant difference in their rate of LS7 change from Year 7 to Year 35 Exam (b=0.02, p=0.15). There was no significant association between sexual orientation discrimination and cardiovascular health in males. Conclusions: Among females, sexual orientation discrimination was inversely associated with cardiovascular health. No significant differences were detected in males. Future studies will investigate if these findings vary by sexual identity and race.
Abstract P3012: Increased Circulating Concentrations of Soluble Cell Adhesion Molecules and Fibrin-D-Dimer in Adults with Periodontal Disease
Periodontal disease, specifically periodontitis, is a progressive multidimensional inflammatory disease of the oral cavity. In addition to adverse oral health consequences, periodontitis is associated with increased risk of atherothrombotic cardiovascular disease and events. Importantly, periodontitis affects >40% of adults in the United States over the age of 30 years. Despite improved management of many of the oral health consequences associated with periodontitis, factors that initiate and promote increased atherothrombotic risk and events are poorly understood. Elevated levels of circulating soluble cell adhesion molecules and fibrin D-dimer are markers of a proatherogenic vascular environment and strong prognostic indicators of atherothrombotic events. We tested the hypothesis that circulating levels of soluble cell adhesion molecules and fibrin D-dimer are elevated in adults with periodontitis, which, in turn, may contribute to the heightened risk of vascular disease and events in this population. Peripheral blood was collected from 26 middle-aged adults: 13 without periodontitis (9 M/4F; age: 49 + 3 yr; BMI: 28.5 + 0.9 kg/m 2 ) and 13 clinically diagnosed with periodontitis (7 M/6 F; 54 + 4 yr; 26.0 + 1.6 kg/m 2 ). All subjects were free of overt cardiovascular and metabolic disease. Plasma concentrations of extracellular soluble adhesion molecules (intracellular adhesion molecule-1 [sICAM-1], vascular adhesion molecule-1 [sVCAM-1], platelet endothelial cell adhesion molecule-1 [sPECAM-1] and E-selectin) and fibrin D-dimer were determined by immunoassay. sICAM-1 (265±14 vs 218±11 ng/mL), E-selectin (48±4 vs 36±3 ng/mL) and fibrin D-dimer (408±47 vs 278±31 ng/mL) were significantly higher (~25-50%) in adults with periodontitis. There were no significant group differences in either sVCAM-1 (595±38 vs 596±53 ng/mL) or sPECAM-1 (10±1 vs 9±1 ng/mL). Elevated circulating levels of sICAM and sE-selectin are sensitive biomarkers of vascular endothelial cell activation and adhesion and have been linked with increased risk of atherogenesis; in addition, elevated fibrin D-dimer is a direct indicator of thrombotic activity. Thus, the increased risk and prevalence of atherothrombotic events in adults with periodontitis may be mediated, in part, by increased expression of cell adhesion molecules and a prothrombotic environment as indicated by elevated soluble cell adhesion molecules and fibrin D-dimer levels.
State-dependent motion of a genetically encoded fluorescent biosensor
Genetically encoded biosensors can measure biochemical properties such as small-molecule concentrations with single-cell resolution, even in vivo. Despite their utility, these sensors are “black boxes”: Very little is known about the structures of their low- and high-fluorescence states or what features are required to transition between them. We used LiLac, a lactate biosensor with a quantitative fluorescence-lifetime readout, as a model system to address these questions. X-ray crystal structures and engineered high-affinity metal bridges demonstrate that LiLac exhibits a large interdomain twist motion that pulls the fluorescent protein away from a “sealed,” high-lifetime state in the absence of lactate to a “cracked,” low-lifetime state in its presence. Understanding the structures and dynamics of LiLac will help to think about and engineer other fluorescent biosensors.
Abstract P2151: Good Sleep Health Is Associated With Better Cardiometabolic Health In Adolescents: A Multidimensional-Multimethod, Factor-Analytic Approach
Background: Life’s Essential 8 highlights the importance of adequate sleep duration in for cardiovascular health. Current evidence demonstrates that health is also influenced by the quality, consistency, and timing of sleep within the 24-hour day. However, no studies have explored which sleep variables contribute to adolescent cardiometabolic health. Hypothesis: The quality, consistency, and timing of sleep will contribute differently to metabolic syndrome (MetS) and each of its components in adolescents. Methods: 307 adolescents (16 yr; 47% female; 23% racial/ethnic minority) from the Penn State Child Cohort had at least 3-nights of actigraphy (ACT), in-lab 9h polysomnography (PSG), self-reported (SR) insomnia symptoms, daytime sleepiness, sleep schedules, completed a physical exam, and a fasting blood draw. A continuous MetS (cMetS) score was calculated as the sum of sex-and age adjusted z-scores of waist circumference (WC), mean arterial pressure (MAP), HDL, triglycerides, and HOMA-IR. Common factor analysis was performed to understand the factor and correlation structure of 58 standardized sleep variables. LASSO Regression selected sleep variables and assessed their importance to cMetS and its components, independently. Results: Factor analysis identified five sleep domains: 1. Timing and Irregularity: means and standard deviations of SR bedtime and waketime, ACT sleep midpoint, and PSG sleep midpoint; 2. Efficiency: means of ACT sleep efficiency (SE), wake after sleep onset (WASO), sleep onset latency (SOL), and number of awakenings; 3. Duration: mean ACT total sleep time (TST), time in bed (TIB), and SR habitual bedtime; 4. Catch-up and Social Jetlag: differences in weekday and weekend SR waketime and TIB and ACT TST and sleep midpoint; 5. Physiologic Sleep Disturbance: PSG TST, SE, SOL, WASO, apnea-hypopnea index (AHI). Results from LASSO indicate that lower PSG AHI contributed to lower cMetS, WC, MAP, triglycerides, and higher HDL, while longer PSG TST contributed to higher HDL and lower MAP. Earlier sleep midpoint contributed to higher WC, HDL and higher sleep regularity contributed to lower HDL. Longer catch-up sleep contributed to lower MAP, and lower social jetlag contributed to lower MAP. Conclusions: Objective measures of sleep contribute most to cardiometabolic health in adolescents, while subjective sleep measures do not contribute to the same extent. These findings highlight the multidimensional association of sleep and cardiometabolic health.
Abstract 037: Proteo-Transcriptional Characterization of Aortic Stenosis Prioritizes Novel Targets Relevant to Heart Failure
Background: Aortic stenosis (AS) initiates a series of molecular alterations that predate cardiac remodeling and development of heart failure (HF). We hypothesized that integrating circulating mediators (proteome) from large-scale epidemiological cohorts with their cell-specific gene expression in the heart (transcriptome) may prioritize novel targets in human AS. Methods: Among individuals with severe AS, we measured the circulating proteome (Olink) and examined associations with myocardial structure/function (N=519), cardiac MRI-based tissue fibrosis (N=145), and clinical outcomes (N=802). We constructed proteomic signatures of cardiac remodeling and tested their association with mortality and HF in the UK Biobank (UKBB; N=36,668). We then examined a "remodeling proteome” prioritized by proteome-phenotype relations at the transcriptional level via single nuclear RNA-sequencing in 20 human hearts (11 with AS at the time of SAVR and 9 donor hearts unused for transplant). Results: We identified three principal components (PCs) of cardiac remodeling (across 12 echocardiographic measures in 503 patients with severe AS) loaded on cardiac morphology, systolic, and diastolic function traits. Proteins associated with these PCs specified both known and novel mediators of fibrosis, LVH, and oxidative stress. Proteomic signatures were strongly linked to mortality (AS cohort, UKBB) and incident HF (UKBB). At a myocardial level, we observed cell-specific differential gene expression, particularly prominent in fibroblasts, cardiomyocytes, and endothelial cells, featuring convergent fibrosis pathways ( WNT9A , ITGA6 , AGRN , CRIM1 , SEMA4C , LAYN, PTX3 , HMOX1 ) and metabolic-inflammatory signaling ( ENPP2/ATX, TNF), among others. Conclusions: Proteo-transcriptional prioritization in human AS identifies both known and novel targets that are mechanistically relevant to HF pathogenesis. Future integrative studies that link longitudinal circulating biomarkers in large-scale cohorts directly to myocardial tissue are warranted to inform pathways of HF progression.
Abstract P3062: Active Screening in Black, Hispanic/LatinX, Asian/Pacific Islander, and Native American Individuals Reduces Racial Disparities in Abdominal Aortic Aneurysm Diagnosis
Introduction: Abdominal aortic aneurysm (AAA) screening and diagnosis in Black, Hispanic/LatinX, Asian/Pacific Islander and Native American people is challenging given the asymptomatic clinical presentation necessitating access to and utilization of the healthcare system. While previous studies report higher AAA risk in patients who identify as White, institutionalized racism and mistrust of the healthcare system limits representation of non-White individuals biasing AAA risk assessments. Large scale analysis of diverse patient cohorts is essential to understand the true incidence of AAA. Objective: To evaluate the impact of race on diagnosis rates for AAA in a diverse patient population. Methods: Patients over the age of 65 seen at the Mount Sinai Healthcare System were retrospectively reviewed from 2002 to 2024 to assess diagnosis rates in patients eligible for screening by U.S. Preventative Services Task Force (USPSTF) guidelines and those with aortic ultrasound screening. Multivariate logistic regression with interaction factors between patient reported race/ethnicity, screening eligibility, and aortic ultrasound (US) screening were included to assess the impact of US screening and race on AAA diagnosis. Results: A total of 1,070,367 patients were evaluated during the study period of which 54.6% self-identified as female, 11.4% Black, 42.9% White, 10.4% Hispanic/LatinX, 4.6% Asian, 0.08% Native American, 0.54 Pacific Islander, and 9.5% as Other Race. The diagnosis rate in men over 65 who smoked was slightly higher than the diagnosis rate for individuals who did not meet USPSTF guidelines (OR=3.087, 97.5% CI = 0.8-10.36, p=.075). Overall, after adjusting for race/ethnicity, eligibility, and US screening, diagnosis was significantly impacted by race (p<.05), screening (p=0.001), and the interaction effect between race and US screening (p=.008). Contrary to the results of previously studies, the significance of race and screening on diagnosis was driven by ~20% higher odds of a positive AAA diagnosis from screening Black or Hispanic/LatinX patients compared to White patients. Conclusion: AAA incidence in people who identify as Black, Hispanic/LatinX, Asian/Pacific Islanders, and Native Americans is likely much higher than previously reported. With the historic barriers to healthcare access and under representation, active AAA screening programs in these communities could drastically increase diagnosis rates leading to decreased mortality due to ruptured AAA.
Abstract P3053: Disparities in the Association Between Diabetes Mellitus and All-Cause Mortality Among Asian American Subgroups: Findings From the National Health Interview Survey (NHIS) (1997–2018)
Introduction: The prevalence of diabetes mellitus (DM), a well-established mortality risk factor, is higher among Asian Americans collectively than non-Hispanic White (NHW) populations. Despite known racial/ethnic differences in diabetes-related outcomes, Asian Americans are often studied as a homogeneous group. This study investigates the disparities in the association between DM and all-cause mortality rates among different Asian American subgroups relative to NHWs. Hypothesis: We assessed the hypothesis that the associations between diabetes mellitus and all-cause mortality rates differ among Asian American subgroups compared to NHWs. Methods: Data from the National Health Interview Survey (NHIS) (1997–2018) was linked with the 2019 National Death Index (NDI). A total of n = 418,681 individuals were analyzed, with diabetes prevalence and all-cause mortality rates compared among Asian Indian (n = 5,478), Chinese (n = 5,848), Filipino (n = 6,419), and NHW (n = 400,936) groups. Hazard ratios (HRs) were calculated using weighted Cox proportional hazard modeling controlling for demographic and socioeconomic determinants of health. Results: Compared to NHW individuals (8.3%, 95% CI [8.2-8.4]), the prevalence of diabetes was higher in Filipino individuals (9.7%, 95% CI [8.9-10.6]) and Asian Indian individuals (7.7%, 95% CI [6.9-8.6]) but lower in Chinese individuals (4.7%, 95% CI [4.1-5.4]). Among individuals with diabetes, the adjusted hazard ratios for all-cause mortality rates were lower for Chinese (HR = 0.85, 95% CI [0.76-0.96]), Filipino (HR = 0.75, 95% CI [0.71-0.79]), and Asian Indian (HR = 0.65, 95% CI [0.45-0.93]) populations compared to NHW individuals. Conclusion: Asian Americans with diabetes experienced a lower mortality risk compared to NHW individuals with diabetes, despite some Asian subgroups having a higher prevalence of the disease. Variations in determinants of all-cause mortality, such as education, income, and nativity, likely contribute to these differences, underscoring the need for targeted interventions.
Abstract P2039: Disease Progression in patients with Chagas Disease treated with Benznidazole or Nifurtimox: A Systematic Review and Meta-analysis
Introduction: Most studies evaluated the efficacy of treatment for chagas disease with the reduction of parasite detection as a primary outcome. However, little is known about the mortality rate associated with benznidazole or nifurtimox in chagas disease patients. Thus, we aimed to investigate all-cause mortality and cardiovascular-related mortality among chagas disease patients treated with benznidazole or nifurtimox. Method: Systematic review and meta-analysis were conducted including randomized control trial studies and cohort studies in patients who received benznidazole or nifurtimox for chagas disease treatment, using online databases including PubMed, Embase, CENTRAL, LILAC, and sciELO up to May 1, 2024. The primary outcomes were all-cause mortality or cardiovascular-related mortality. Studies focused on patients with HIV-coinfection were excluded. Result: We included 15 studies involving 3837 patients, with 14 studies on benznidazole (n=3552) and 3 studies (n=285) on nifurtimox. Overall, all-cause mortality over follow-up was 1.96% [95% Confidence Interval (CI): 0.58-3.93], and 2.21% [95% CI: 0.45-4.89] for cardiovascular-related mortality. All-cause mortality was 1.04% [95% CI: 0.00-4.61] for the nifurtimox group and 2.07% [95% CI: 0.51-4.39] for the benznidazole group. Cardiovascular-related mortality was 3.03% [95% CI: 0.00-9.25] for the nifurtimox group and 2.10% [95% CI: 0.25-5.16] for the benznidazole group. Conclusion: This study is one of the first studies that conducted a meta-analysis to provide mortality outcomes in chagas disease patients. Our study estimated an increase in individuals of all-cause mortality and cardiovascular-related mortality over the study period. Further investigations are needed to understand mortality by phase of chagas disease, comorbidities, and cardiomyopathy-related signs to better understand the long-term effect of patients treated for chagas disease.
Abstract P2065: A Comparative Study Of Social Determinants, Hypertension, And Life Essential Factors In Alabama And Colorado From The 2021 Behavioral Risk Factor Surveillance System
Background: Hypertension is an important modifiable risk factor for cardiovascular disease, which disproportionately impacts racial/ethnic minorities in the US. Currently, Equity in Prevention of Hypertension (EPIPHANY, 2024) a program funded by the American Heart Association(AHA) is focusing on and engaging the Black belt of Alabama to mitigate hypertension by targeting adults with prehypertension, a new strategy to reduce the prevalence of hypertension. This project was meant to test the hypothesis of no difference in the risk of hypertension between two US States and to generate evidence for implementation. Objective: To compare the social determinant of health (SDOH), hypertension, and the AHA life's essential factors among adults in Colorado and Alabama in the 2021 Behavioral Risk Factor Surveillance System (BRFSS) Methodology: This was a cross-sectional survey of adults enrolled in the US 2021 BRFSS study. Data analysed compared Colorado and Alabama to determine the essential life factors among the two states. Elevated blood pressure (hypertension) and the included variables were based on the answers from the diagnosis of the healthcare professional given to the participants in the US BRFSS 2021. Data analysis used regression and risk ratios from the BRFSS WEAT to calculate the logistic regression and adjusted odds ratios (CDC, 2024). Results: In 2021, the racial proportion of adults with hypertension in Alabama was 41.8% for White vs 48.4% for the Black population (overall proportion=42.6 %), while in Colorado, 27.6% of White vs 36.1% of the Black adult population had hypertension(Overall proportion=25.9%) [Figure 1]. Compared to Colorado, AL has 1.83 times higher AOR of hypertension (p<0.0001). Fruit consumption, physical activity, and disability status significantly differed between Alabama and Colorado (p<0.0001)[Table 1, Figure 2]. Surprisingly, there was no difference in healthcare access between AL and CO (0.7872) [Table 1] Conclusion: Though Colorado has the lowest prevalence of hypertension in the United States, disparities still persist. However, Alabama demonstrated much higher disability status, lack of physical activity, and consumption of vegetables and fruits of <1 time/day (p<0.0001). Recommendations: The high burden of hypertension among ethnic minorities deserve attention and more evidence can be assessed to further understand the enabling factors that led to CO having the lowest proportion of hypertension.
<i>Dux</i> cluster duplication ensures full activation of totipotent genes
Zygotic genome activation (ZGA) confers to the mouse two-cell (2C) embryo a unique transcriptional profile characterized by transient up-regulation of many totipotency-related genes and MERVL retrotransposons. Intriguingly, those genes are duplicated and clustered in the genome during evolution, including Dux cluster, Obox, and Zscan4 family members in mice. However, the contribution and biological significance of the totipotency-related gene duplication events in early embryo development remain poorly understood. Here, we focus on Dux cluster, the master regulator of ZGA that is necessary and sufficient for the induction of 2C-like cells and activation of totipotency-related genes in mouse embryonic stem cells (mESCs). By reducing Dux gene copies from 31 to 0 or 1 through CRISPR-Cas9 technology, we generate Dux -KO and Dux (n = 1) mESC lines, respectively. We uncover that the totipotency-related gene transcriptional profile is awakened to a much lesser extent in Dux (n = 1) mESCs compared to wild type mESCs following global DNA demethylation reprogramming or induction of DNA damage, mimicking the intrinsic events in preimplantation development. Together, Dux cluster duplication is critically required for full activation of ZGA transcripts.
Abstract P2083: Lower Your LDL Cholesterol Now Initiative: Understanding Survivor LDL Awareness and Behaviors
Introduction: High cholesterol, and specifically high low-density lipoprotein cholesterol (LDL-C), is one of the major controllable risk factors for coronary heart disease, heart attack and stroke. About 1 in 4 U.S. adults have high LDL-C, which can be caused by lifestyle risk factors or genetics. More investigation is needed to understand the appropriate educational approach on LDL-C with heart attack and stroke survivors. Goals: The American Heart Association (AHA) is implementing a national 3-year initiative called Lower Your LDL Cholesterol Now TM to improve LDL-C understanding, testing and treatment adherence among survivors. We aim to understand survivors’ knowledge, motivators, and barriers to cholesterol testing and treatment to ultimately build an educational approach, supportive of cholesterol self-management skills. Methods: A 15-minute online survey was conducted with The Harris Poll on behalf of the AHA among nationally representative sample of 3,008 U.S. adults aged 18+ and an oversample of 503 U.S. adults aged 18+ who have experienced and survived a heart attack and/or stroke. Results: The survey revealed three out of four survivors (75%) reported having high cholesterol yet nearly half (47%) are unaware of their LDL-C number. Additionally, only about half (49%) prioritize their cholesterol, and 1 in 3 believe high cholesterol poses no or only a small increased risk for heart attack and stroke. However, 98% of survivors are willing to get their cholesterol measured if recommended by their health care professional (HCP). Conclusion: Nearly all survivors are receptive to having their cholesterol checked by their HCP if recommended, therefore, this initiative will focus on educating survivors to 1) know their LDL-C number, 2) understand the connection between high LDL and repeat events and 3) improve treatment adherence.
Abstract P3130: Peer Coaching Improves Cardiac Rehabilitation Participation and Reduces Perioperative Challenges in Cardiac Surgery Patients: A Pilot Study
Background: Cardiovascular disease remains the leading cause of death globally, with approximately 1.5 million patients undergoing cardiac surgery annually. Active participation in cardiac rehabilitation (CR) following cardiac surgery has been linked to a reduction in subsequent cardiovascular events and better survival. Despite these benefits, roughly 25% of patients nationally attend CR. Peer coaching, which involves guidance from individuals with similar experiences, may improve CR participation and has yet to be fully explored. The Peer Coaching for Cardiac Patients (PCCP) pilot program aimed to assess the benefits of peer coaching in improving participation in CR and perioperative anxiety and depression outcomes in cardiac surgery patients. Methods: This pilot study, conducted from November 2023 to April 2024, enrolled ten patients scheduled for elective cardiac surgery. Participants attended four 60-minute coaching sessions via Zoom, two before and two after surgery, by a coach who had undergone coronary bypass surgery in the past (Figure 1). Patient outcomes were evaluated through CR participation rates, pre- and post-program Patient Health Questionnaire (PHQ)-9 scores, and a post-program survey. Descriptive statistics and paired t-tests were used to analyze results, with p < 0.05 considered significant. Results: Seven of the ten patients completed the PCCP program. All participants who completed the program went on to attend CR for an average of 19.3 ± 8.70 sessions and 9.57 ± 3.0 weeks. No statistically significant difference in PHQ-9 scores was observed (p=0.341). Participants rated the program highly in its role in anxiety reduction (9.0 ± 1.2) and its likelihood of making them attend CR (9.43 ± 1.05) (Table 1). Conclusion: Our pilot study suggests that peer coaching in patients undergoing cardiac surgery is feasible and may improve CR participation rates. Moreover, it may increase patient readiness for surgery and support post-operative recovery in cardiac surgery patients. While we suspect the PCCP program may have mitigated some of the post-operative physiological challenges, further studies will need to be conducted to delineate the extent to which it does. Future studies with larger and more diverse patient populations with longer follow-up are warranted to confirm these preliminary findings and explore the broader applicability of peer coaching in cardiac surgery patients.
Abstract P1046: Positive and Adverse School Experiences and Cardiovascular Health (CVH) in the Young Hearts Study
Introduction: School environments play a crucial role in shaping the social and physical health of children, by promoting lifelong healthy habits. Therefore, we examined the association between harmful (peer-bullying) and positive (school connectedness) school-based experiences and behavioral CVH (bCVH) among children and adolescents. Methods: Data from 910 youth (14.9±1.9 years; 49.6% non-Hispanic White; 48% female) from the Young Hearts Study were analyzed. Self-reported experiences of peer bullying and school connectedness were measured via the School Experiences survey. Scores for bullying and school connectedness were derived by summing each of the four items pertaining to peer bullying and school connectedness, from their respective subdomain. A composite bCVH score was calculated by averaging scores for the four behavioral components of the American Heart Association Life’s Essential 8 [LE8; diet, physical activity (PA), sleep, and nicotine exposure] as well as body mass index (BMI), each scored on a 0 (poor) to 100 (ideal) scale. Linear regression was used to measure associations between school experiences and bCVH adjusting for age, sex, race, household income, and health insurance status. Results: Mean scores (±SD; range 0-16) for peer bullying and school connectedness were 1.65±2.53 and 12.3±3.8, respectively. Mean scores for the four components of the LE8 and BMI were: diet (39.4±22.0), PA (70.8±39.9), sleep (74.5±28.7), nicotine exposure (92.6±19.7), and BMI (77.9±32.3). In fully adjusted models, 1-unit higher score of connectedness or bullying were associated with 0.45-unit higher and 0.82-unit lower bCVH scores, respectively. Among individual bCVH components, connectedness was most strongly associated with BMI [0.77 (95% CI, 0.13, 1.41)] and nicotine exposure scores [0.76 (0.39, 1.12)], while higher bullying was associated with lower diet [-1.27 (-1.86, -0.67)] and nicotine exposure [-0.8 (-1.33, -0.27)] scores (Figure 1). Conclusions: Optimizing the school environment to promote social connectedness and anti-bullying practices may be an important strategy in promoting CVH among adolescents.
Abstract P3108: Pilot Evaluation of the Healthy Kids, Inc. Central Kitchen Food Project: Insights from a Childcare Center-Based Nutrition Program In West Virginia.
Introduction: Childhood obesity is a public health crisis that increases the risk of lifelong obesity and associated conditions like hypertension, sleep apnea, Type II diabetes, depression, and social stigma. Diet-related diseases are worsened by high intake of ultra-processed foods and insufficient whole foods rich in fiber. Addressing food insecurity and promoting a healthy diet in early childcare settings is critical, especially in West Virginia, where food insecurity and childhood obesity rates are among the nation's highest. In 2023, the American Heart Association’s (AHA) Social Impact Fund supported Healthy Kids, Inc. (HKI) to implement a Child Nutrition Program in childcare centers in Morgantown, West Virginia. The program provided children with healthy meals to improve dietary behavior and health outcomes. Hypothesis: Implementing HKI’s Program would increase children's fruit and vegetable (F&V) consumption. Methods: The AHA Evaluation team conducted a mixed-methods evaluation from February to July 2024. Retrospective surveys were completed by parents/guardians of children in participating childcare centers, with 54 eligible responses. Semi-structured interviews were conducted with five childcare center staff to assess the program's impact. Survey data were analyzed using descriptive statistics, and interviews were coded for themes related to outcomes and challenges. Results: Findings showed that over 90% of respondents (n=54) rated their child’s health as excellent or very good. Additionally, 60% of parents/guardians reported an increase in their child’s F&V consumption. The frequency of families eating healthy meals with their children increased, with 65% reporting they ate together more than five times a week after the program, compared to 44% before. Interviews with childcare center staff revealed positive experiences with the HKI Program, highlighting improved access to fresh, healthy meals, improved meal quality, and increased children’s willingness to try new foods. Conclusions: Findings from the pilot evaluation suggest that the HKI Program increased children’s F&V consumption and willingness to try new healthy foods. These findings indicate that community-driven nutrition programs can address children's and households' nutritional needs, highlighting the need for nutrition educational opportunities for families. Further research is needed to explore long-term effects and identify strategies for sustaining and scaling these outcomes.
Abstract P2117: Associations of cardiac biomarkers with physical activity and sedentary behavior in postmenopausal women
Background: Associations of physical activity (PA) and sedentary behavior (SB) with biomarkers of cardiac stress could have implications for cardiovascular resiliency in aging women but are understudied. Methods: Postmenopausal women (50-79 years old at Women’s Health Initiative enrollment) (a) without known CHD, (b) with available self-reported usual PA and SB information, and (c) with available blood biomarkers for high-sensitivity C-reactive protein (hsCRP mg/L; inflammation), tissue plasminogen activator (tPA ng/mL; fibrinolysis), N-terminal pro-brain natriuretic protein (NT-proBNP pg/mL; volume overload), and plasminogen activator inhibitor-1 (PAI-1 pg/mL; thrombosis/endothelial dysfunction) were included in this cross-sectional analysis (n=3,537 for hsCRP, tPA, NT-proBNP; n = 2,460 PAI-1). Adjusted means were estimated from linear regression models. All data was ascertained at study enrollment. Results: Controlling for age, race-ethnicity, history of stroke, heart failure, treated diabetes or hypertension, smoking, and postmenopausal hormone use, adjusted mean biomarker concentrations across incremental walking categories (0, >0-3.5, >3.5-8.33, >8.33 MET-hr/wk) were: hsCRP 4.1, 3.7, 3.2, 2.5, trend P<.001; NT-proBNP 162.9, 155.1, 148.2, 151.3, trend P=.05; tPA 8.9, 9.2, 8.3, 8.0, trend P=.01; PAI-1 16691, 16896, 15717, 14672, trend P<.001 ( Figures 1&2 ). Similar patterns were observed across strenuous activity categories, aside from NT-proBNP. Across incremental categories of SB (<4.6, 4.6-8.5, >8.5 hr/day) positive associations were seen for adjusted mean hsCRP 3.4, 3.6, 3.9, trend P<.01; tPA 8.2, 8.9, 9.9, trend P=.03; PAI-1 15552, 16407, 16639, trend P=.05. In stratified analysis, inverse associations were observed regardless of comorbid status (prevalent diabetes, hypertension, heart failure, or cancer). Associations were attenuated but significant among older women, and associations of PA measures with hsCRP were stronger in those with high BMI (30+ kg/m 2 ). Conclusion: In this cross-sectional study of postmenopausal women, higher levels of walking and strenuous PA were associated with lower concentrations of biomarkers related to inflammation (hsCRP), fibrinolysis (tPA), and thrombosis/endothelial dysfunction (PAI-1), while higher SB was positively associated with elevated levels. The findings highlight the role of PA in promoting cardiovascular resiliency during aging, and underscore the adverse impact of prolonged SB.
Abstract P3055: Longitudinal Associations of Dairy Derived Serum Fatty Acids with Early Type 2 Diabetes Mellitus Risk Phenotypes: Findings from the Prospective Metabolism and Islet cell Evaluation (PROMISE) Cohort
Background: Evidence suggests that dairy-derived saturated and trans fatty acids may contribute to observed inverse associations of dairy intake with risk of metabolically associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM). Longitudinal studies examining the association between circulating dairy fatty acids and phenotypes underlying these disorders are limited. This study aimed to investigate the 9-year longitudinal associations of 15:0 (pentadecanoic acid), t16:1n9 (trans palmitoleic acid), t18:1n11 (trans vaccenic acid) and c9,t11 CLA (conjugated linoleic acid) in four serum fractions with insulin sensitivity, beta cell function and alanine aminotransferase (ALT in U/L, a biomarker of liver function). Methods: In the PROMISE cohort (n=460), insulin sensitivity was assessed using Matsuda’s insulin sensitivity index (ISI) and the homeostasis model assessment of insulin sensitivity (HOMA2_S). Beta cell function was determined using the insulinogenic index divided by HOMA insulin resistance (IGI/IR) and the Insulin Secretion-Sensitivity Index-2 (ISSI-2). Serum ALT was measured at each visit. Baseline serum fatty acids (mol%) in the cholesteryl ester (CE), non-esterified fatty acid (NEFA), phospholipid (PL) and triglyceride (TG) pools were analyzed using gas chromatography flame-ionization detection. Longitudinal associations were analyzed using covariate-adjusted generalized estimating equations with P values adjusted using the Benjamini-Hochberg False Discovery Rate (FDR). Results: In the TG pool, 18:1n11t was significantly associated with logISSI-2 (β= 3.09, CI: [0.04, 6.24], p<0.05). Significant inverse associations were observed between 15:0 (CE) and logALT (β= -3.30, CI: [-5.33, -1.24], p<0.01). In the PL pool, 15:0 was positively associated with logISSI-2 (β=5.37, CI: [1.71, 9.16], p<0.01) and logIGI/IR (β=10.49, CI: [4.35, 16.99], p<0.01). After FDR adjustment, 15:0 (CE) continued to be inversely associated with logALT (p<0.05). Similarly, 15:0 (PL) was significantly associated with logISSI-2 and logIGI/IR (p<0.05). Fatty acids in the NEFA and TG pools were not significantly associated with outcomes. Conclusions: Longitudinal associations of dairy-derived serum fatty acids with liver health and beta cell function were detected across serum pools. Our findings expand the literature on the potential role of dairy-derived saturated and trans conjugate fatty acids in cardiometabolic phenotypes underlying MAFLD and T2DM.
Systematic identification of allosteric effectors in <i>Escherichia coli</i> metabolism
Recent physical binding screens suggest that protein–metabolite interactions are more extensive than previously recognized. To elucidate the functional relevance of these interactions, we developed a mass spectrometry–based screening method for higher throughput in vitro enzyme assays. By systematically quantifying the effects of 79 metabolites on the activity of 20 central Escherichia coli enzymes, we not only assess functional relevance but also gauge the depth of the current understanding of regulatory interactions within one of the best-characterized networks. Our identification of 50 inhibitors and 14 activators not only expands the range of known input signals but also uncovers novel regulatory logic. For instance, we observed that AMP inhibits malic enzyme to safeguard the cyclic operation of the tricarboxylic acid cycle, and erythrose-4-phosphate inhibits 6-phosphogluconate dehydrogenase to redirect flux from the pentose phosphate pathway into the Entner–Doudoroff pathway. Discrepancies between our standardized assays and existing database entries suggest that many previously reported interactions might occur only under specific, often nonphysiological conditions. Our dataset represents a systematically determined functional protein–metabolite interaction network, establishing a baseline for allosteric regulation in central metabolism. These results enhance our understanding of the regulatory logic governing metabolic processes and underscore its significance in cellular adaptation and growth.
Abstract P3138: Experiences of Discrimination in the Healthcare Setting and the Impact on Healthcare Utilization among Black Adults with Hypertension
Introduction: Experiencing discrimination in healthcare settings negatively impacts health care utilization and outcomes, contributing to health disparities. Discrimination is a psychosocial stressor, and when experienced in healthcare is linked with distrust of healthcare providers, fewer preventive screenings, and poorer physical well-being. These effects are particularly concerning for individuals with hypertension who require regular treatment from medical professionals. The objective of this study is to examine healthcare utilization among Black adults with hypertension who have experienced racial discrimination in healthcare settings. Hypothesis: We hypothesize that Black adults with hypertension, individuals that have experienced racial discrimination in the healthcare setting may be less likely to utilize the healthcare system. Methods: We conducted a cross-sectional analysis using 2020 California Health Interview Survey data. Participants were Black adults aged 18 or older with self-reported hypertension. To assess healthcare utilization we utilized survey items, including delays in seeking medical care, visits to the emergency room, and delays in prescriptions. Data was analyzed using descriptive statistics, chi-square tests, and ordinal logistic regression using STATA Version 18. Results: The study sample included 532 participants with an average age of 55 and the majority identified as women (62.4%). Eleven percent of participants reported experiencing discrimination in the healthcare setting. Approximately 15.7% of participants reported delays in seeking medical care in the past 12 months and 12.4% reported delays in refilling prescriptions. The adjusted analysis did not reveal a statistically significant relationship between discrimination in the healthcare setting and prescriptions delays (OR 1.11, p = 0.782) or having a usual source of health care (OR 0.79, p = 0.683). The findings revealed that participants reporting no delays in seeking medical care within the past 12 months (OR 3.19, p = <0.001) were less likely to experience discrimination in the healthcare setting. Conclusion: Within this sample of Black adults with hypertension, discrimination was associated with utilization of the ER and delays in medical care. In conclusion, the study findings underscore the persistent effects of racial discrimination and highlights a need for addressing discrimination in healthcare settings to create meaningful improvements in quality of care for Black patients.