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Abstract P2048: Comparison of Incident Cardiovascular Diseases Between Asian American, Native Hawaiian and Other Pacific Islanders in Hawaii vs. Northern California: The PANACHE Study

Circulation Yihe Daida, Rishi Parikh, Andrew Ambrosy et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p2048

Introduction: Hawaii (HI) and California (CA) are home to the largest and fast-growing Asian American, Native Hawaiian, and other Pacific Islander (AANHPI) populations in the U.S., yet our understanding about the influence of factors related to geographic location on cardiovascular disease (CVD) risks within the AANHPI population is limited. We compared incident CVD rates for eight AANHPI subgroups between HI and California CA. Methods: We identified AANHPI members of Kaiser Permanente Hawaii and Northern California aged ≥30 years with no prior CVD from 2012-2022. Outcomes included incident acute myocardial infarction (MI), stroke, heart failure (HF) and atrial fibrillation (AF) using validated diagnosis codes in electronic health records. Cox proportional hazards models stratified by AANHPI subgroup were performed to evaluate the association between geographic region (CA vs. HI) and each CVD outcome, after patient-level adjustment for age, sex, body mass index, census tract-level education and income, diabetes, hypertension, dyslipidemia, chronic kidney disease stage, depression, alcohol use, and smoking status. Results: Among 677,563 AANHPI adults with no prior CVD, mean age was 47±14 years, with higher proportion of women at both sites (53.0% HI, 58.8% CA), and a mean BMI of 28.2 in HI and 25.8 in CA. In stratified multivariable models that adjusted for demographic and CVD risk factors, rates of incident MI, stroke, HF and AF varied between CA and HI depending on the CVD outcome and AANHPI subgroup. Among Filipino adults, those living in CA had a higher adjusted rate of MI (adjusted hazard ratio [aHR] 1.35, 1.21-1.51), HF (aHR 1.14, 1.06-1.23) and AF (aHR 1.16, 1.07-1.25) than those living in HI. Among Native Hawaiian/Pacific Islander adults, those living in CA had a higher adjusted rate of MI (aHR 1.30, 1.13-1.49) but a lower adjusted rate of stroke (aHR 0.81, 0.68-0.98), HF (aHR 0.86, 0.77-0.95) and AF (aHR 0.71, 0.64-0.80) than those living in HI. In addition, the adjusted rate of stroke was lower for Japanese (aHR 0.77, 0.66-0.90) and Korean (aHR 0.58, 0.40-0.85) adults in CA. Conclusions: We observed varying rates of incident CVD events across AANHPI subgroups between HI and CA that were not explained by measured sociodemographic and clinical risk factors. Further investigation into environmental, structural, and behavioral risk factors that may contribute to the observed CVD outcome variation within AANHPI subgroups is needed.

Abstract P1013: Ideal cardiovascular health is associated with reduced epigenetic aging: cross-sectional findings from the INSPIRE-T cohort

Circulation Mathilde Strumia, Vanina Bongard, Samuel Thuriot et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1013

Introduction: Chronological age is the main non-modifiable risk factor for morbidity, but it cannot be the only factor responsible for these age-related changes. Several teams have taken an interest in the biological mechanisms underlying ageing and have developed biological clocks, in particular epigenetic clocks such as DNAm GrimAge. These clocks could help to identify factors protecting against accelerated ageing and associated diseases. In this context, our aim was to assess the association between ideal cardiovascular health and reduced epigenetic ageing. Method Our cross-sectional analysis included participants from the INSPIRE-T human translational cohort. Cardiovascular health (CVH) was assessed using the Life’s Essential 8 composite score (0 to 100 points, higher means better) and calculated as the average of 8 component metric scores (healthy diet, physical activity, avoidance of nicotine, healthy sleep, healthy weight, and healthy levels of blood lipids, glucose and blood pressure). Overall CVH scores of 80-100 points were considered high CVH, 50-79, moderate CVH; 0 to 49, low CVH. Epigenetic aging was derived from the residuals of a linear regression of epigenetic age calculated using the GrimAge epigenetic clock and chronological age. Linear regression models were used in the analyses. Results We included 937 subjects (age range 20-100, mean age 60 years, 67% men). On average, the subjects had an LE8 score of 68 points (± 9.7) and 11.7% had a high CVH. After adjustment for chronological age and sex, compared to those with low to moderate CVH, subjects with high CVH had reduced epigenetic aging (β = -1.1 ± 0.4, p =0.002). Among LE8 components and per 1-unit increase in scoring (0 to 100) physical activity (β = -0.9 ± 0.4, p =0.02), BMI (β = -1.3 ± 0.2, p <0.001), diabetic status (β = -0.4 ± 0.1, p =0.001), smoking status (β = -3.6 ± 0.3, p <0.001) and blood pressure level (β = -0.9 ± 0.3, p =0.004) were significantly associated with a reduction in epigenetic ageing. This association was not found for dietary score, lipid levels or sleep. Discussion Our study reported an association between ideal global CVH and optimal levels of multiple health behaviors and health factors with reduced epigenetic aging after adjustment for chronological age and sex. This suggests that epigenetic aging is potentially modifiable by healthy lifestyle and control of cardiovascular risk factors although a potential underlying causal relationship remains to be established.

Abstract 006: Mid- and late-life exposure to cardiovascular risk factors and subsequent risk of dementia

Circulation Sanaz Sedaghat, Hongyan Ning, Katherine Giorgio et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.006

Introduction: Dementia has a long preclinical phase, with pathological and brain changes emerging decades before clinical symptoms appear. Cardiovascular risk factors throughout life contribute to dementia risk, but their effects vary based on their timing and duration. Identifying critical periods of influence is key for developing targeted prevention strategies. Hypothesis: We hypothesize the association between cardiovascular risk factors and dementia varies across the lifespan. Methods: We pooled data for 39,524 individuals from seven cohort studies (Whitehall II, ARIC, CHS, HAAS, MESA, SALSA, and FHS) as part of the Dementia Risk Prediction Pooling Project. We imputed trajectories of body mass index (BMI), systolic blood pressure (SBP), fasting glucose, and cholesterol for each participant starting from age 40 years. Time-weighted average exposures during midlife (ages 40-64 years) and later life (ages 65+ years) were calculated, and hazard ratios for dementia incidence were estimated using Cox proportional hazards models. These models accounted for competing risks of death and were adjusted for sex, race, cohort, educational level, and depressive symptoms. Results: Over a median follow-up of 14 years, there were 5,654 dementia cases and 10,819 deaths. Joint modeling of midlife and late-life risk factors revealed higher BMI, fasting glucose, and cholesterol in midlife were each independently associated with elevated risk of dementia. In contrast, higher late-life values for these factors were associated with lower risk of dementia (Figure). For example, compared to BMI < 20, a BMI ≥ 30 in midlife was associated with a 70% higher risk of dementia, while in late life, it was associated with a 50% lower risk. No association was found between late-life SBP and dementia, but higher midlife SBP was linked to higher risk of dementia. Using rank-based cut offs for risk factors instead of clinical ones did not change the findings. Conclusion: Midlife, but not later-life, levels of cardiovascular risk factors have a stronger effect on dementia risk, highlighting a critical period for intervention.

Performance evaluation of Rayto RT-7600Vet hematology analyzer in side-by-side comparison with manual hematological methods for apparently healthy Cholistani cattle blood

PLoS ONE Umer Farooq, Mushtaq Hussain Lashari, Zia Ur Rehman et al. Mar 11, 2025 DOI: 10.1371/journal.pone.0302617

The present study is the first from Pakistan being reported with an objective to assess performance of Rayto RT-7600Vet hematology analyzer (HA) for Cholistani cattle blood (n = 134), in comparison to the manual hematological methods. The four hematological attributes viz. total erythrocyte count (TEC), hemoglobin (Hb), packed cell volume (PCV) and platelet count (PLT) were deduced through HA (A) and manual (M) methods. Various statistical tests were implied to ascertain level of interrelationship, accuracy and level of agreement between the two methods. All attributes attained through manual methods had high positive, leptokurtic distribution (having many outliers) except for PLT-M and PCV-M. The coefficient of variation for attributes attained through HA and manual methods ranged from 16–24% and from 16–59%, respectively. Comparison between the overall results revealed that all the studied attributes, except TEC, were significantly (P≤0.05) different for both methods. A weak relationship was noticed between the attributes attained through two methods as indicated by weak r-values and adjusted r-square values. The reliability level of estimating Hb and PCV had highest intraclass correlation coefficient value of 0.722 and 0.555 for average measures, respectively. However, accuracy level, as determined through Lin’s concordance correlation coefficient was highest for TEC (0.9504) for both analytical methods. Poor level of agreement, in general, was shown for the two methods of analysis regarding all four hematological attributes through Bland and Altman test. In conclusion, the Rayto RT-7600Vet) may present data having higher skewness, kurtosis, and CV%, however, they are valid for multi-species hematological analysis. Caution must however, be taken in interpreting their results with corrected reference intervals and CV% for each machine and for each tested attribute.

Abstract P2002: Cardiovascular Diseases Risk Assessment in the Adult Population: the Italian Health Examination Survey 2023-2024 - CUORE Project

Circulation Chiara Donfrancesco, Cinzia Lo Noce, Anna Di Lonardo et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p2002

Introduction: The reduction of non-communicable diseases premature mortality is pursued by the WHO; risk conditions targets are recommended as well as population-level monitoring of cardiovascular disease (CVD) risk. The Italian Ministry of Health (MoH) has strengthened prevention/health promotion and supported periodic CVD risk assessment through national health examination surveys (HESs), technically and financially supported by the Ministry of Health - National Centre for Disease Prevention and Control, and conducted within the CUORE Project. Hypothesis: The aim of assessment is the monitoring of the cardiovascular risk distribution in the Italian general population. Methods: In 2023 a new HES started including the 10-year fatal and non-fatal CVD risk assessment based on the knowledge of sex, age, smoking habit, measured systolic blood pressure and fasting total and HDL serum cholesterol, and presence of diabetes (on measured fasting serum glycemia and/or treatment) and anti-hypertensive therapy. Up to now, data from random samples of residents in 12 Regions (of 20 regions) distributed in North, Centre and South of Italy, aged 35-69 years, without previous CVD, are available (1029 men, 1064 women). Determinations were assayed by a central lab. CUORE Project functions developed on and for the Italian adults were used. Results: Mean values of the CVD risk assessment resulted 6.7% (95% CI: 6.3-7.1) in men and 2.2% (2.1-2.4) in women. For men aged 35-44 years risk was 1.6% (1.5-1.7), for 45-54 years 3.9% (3.6-4.2), for 55-64 years 9.3% (8.7-10.0), for 65-69 years 17.1% (16.1-18.1); for women was 0.4% (0.4-0.5), 1.1% (1.0-1.2), 3.1% (2.8-3.4) and 5.8% (5.4-6.2) respectively. Prevalence of CVD risk less than 5% was 56% (50-62) in men and 88% (85-92) in women, of 5-10% risk were 23% (19-28) of men and 10% (6-13) of women, of 10-15% risk were 4% (2-7) of men and 0% of women, of over 15% risk were 1% (0-2.5) of men and 0% of women. Conclusions: Compared to 2008, these data showed stable mean levels of CVD risk both in men and women at any age-classes and stable prevalence of CVD risk classes. CVD risk perception represents a challenge in primary prevention especially for young age groups and women.

Abstract P1126: Cognitive Decline is Associated with Fewer Daily Steps and More Sedentary Behaviors Among Older Adults in Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation Erin Dooley, Bjoern Hornikel, Alexandra Munson et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1126

Introduction: Despite known benefits of physical activity (PA) on cognition, little is known about how cognitive decline may relate to PA patterns. Hypothesis: We hypothesized that cognitive decline is associated with lower levels of PA and higher sedentary behaviors (SED) and differing patterns of accumulation across the week. Methods: Data are from 700 MESA participants (ages 70.1 ± 6.7 years; 55% women) with a cognitive battery at Exam 6 (2016-18) and Exam 7 (2022-24) and a hip accelerometer (valid wear: ≥4 of 7 days with ≥10 hrs) at Exam 7. The cognitive battery included the Cognitive Abilities Screening Instrument (CASI), a global measure of cognitive function (range 0-100). We calculated change in CASI test scores (△ = Exam 7 – Exam 6). Evenson vector magnitude (VM) cutpoints for older adults were used to estimate minutes by intensity category. We used linear mixed models to examine daily patterns of steps and minutes of SED, low light intensity PA, high light intensity PA, and moderate/vigorous intensity PA (MVPA) by cognitive change. Models were adjusted for age, sex, race/ethnicity, center, education, income, employment status, obesity, hypertension, diabetes, smoking status, and Exam 6 CASI score. Results: On average (± SD), participants spent 9.1 ± 3.2 hours in SED, 4.4 ± 1.3 hours in low light intensity PA, 2.0 ± 0.8 hours in high light intensity PA, and 45.2 ± 35.1 minutes in MVPA per day. Sunday was the least active/most sedentary day across the week (Figure). Average change (± SD) in CASI score was -1.2 ± 4.8 items. For every 1 item reduction in CASI score, there was 4.6 minutes (95% CI: 1.2, 8.0) higher SED and 95 fewer steps (95% CI: 24, 165) per day. No statistically significant interactions between cognitive change and gender or race/ethnicity with PA patterns were observed. Conclusions: In an ethnically diverse cohort of older adults, decline in 6-year cognitive performance was associated with more sedentary time and less steps. Consequences of cognitive decline on movement suggests need to support sit less, move more strategies.

Abstract P1075: Computer-based Technology Enhancing Cardiovascular Disease Risk Assessment by Health Workers in Rural Communities in Thailand: A Preliminary Analysis

Circulation Boonsub Sakboonyarat, Jaturon Poovieng, Kanlaya Jongcherdchutrakul et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1075

Introduction: In 2019, the revised WHO CVD risk prediction charts for 21 global regions, including Southeast Asia, were developed. These charts provide a non-laboratory-based risk score and are practical for implementation in resource-limited areas. We used this chart to develop a web-based application for assessing CVD risk prediction scores. We aimed to evaluate the effectiveness of computer-based technology in enhancing CVD risk assessment by health workers in rural communities across four geographic regions in Thailand. Methods: In a preliminary analysis of a randomized controlled trial conducted between July and September 2024, we enrolled 16 health workers working in primary care units in rural areas. These health workers included registered nurses and public health technical officers aged 27–52. They were randomly assigned to either the intervention group (web-based application) or the control group (traditional chart-based tool). Each health worker used the assigned tool to assess ten simulated patients' CVD risk. The primary outcome was a reduction in the duration of the CVD risk assessment. The secondary outcomes were the reduction of error in predicted CVD risk scores and predicted CVD risk group. We performed mixed-effects regression models to evaluate the primary and secondary outcomes. Furthermore, the two groups' usefulness, satisfaction, and ease of use (USE) scores (ranging from 1-7) were compared using a t -test. Results: The mean duration of CVD risk assessment per one simulated patient in the intervention group was 26.2±0.5 seconds, while it was70.9±2.4 in the control group. The mean reduction was 44.8 seconds with the intervention effect size (95% CI: 34.4 to 55.2; p<0.0001), which reduced the duration of CVD assessment by 63.1%. The error in predicted CVD risk scores and predicted CVD risk group in the intervention group demonstrated a significant reduction of 27.5% (95% CI: 15.1% to 39.9%; p <0.0001) and 17.5% (95% CI: 8.4% to 26.6%); p<0.0001), respectively, compared to the control group. The mean overall USE score in the intervention group was 6.8±0.1, significantly higher than 5.0±0.3 in the control group (p<0.0001), indicating a more satisfying user experience. Conclusion: For health workers in Thai rural communities, computer-based technology significantly reduced the duration of CVD risk assessment and errors in predicted CVD risk scores and groups. Additionally, users reported higher scores for usefulness, satisfaction, and ease of use.

Using statistical modelling and machine learning in detecting bone properties: A systematic review protocol

PLoS ONE Osama Abdelhay, Rand Alshoubaki, Sana Murad et al. Mar 11, 2025 DOI: 10.1371/journal.pone.0319583

Introduction Osteoporosis, a common condition characterised by decreased bone mass and microarchitectural deterioration, leading to increased fracture risk, is a significant health concern. Traditional diagnostic methods, such as Dual-energy X-ray Absorptiometry (DXA), have limitations in sensitivity and accessibility. However, the emergence of artificial intelligence (AI) and machine learning (ML) has brought promising tools capable of analysing complex medical data to enhance the detection and prediction of osteoporosis-related bone properties. This systematic review protocol outlines the methodology to evaluate the application and effectiveness of AI and ML methods in detecting bone properties and osteoporosis. It underscores their potential to revolutionise healthcare by providing more accurate and accessible osteoporosis detection and prediction tools. Methods This systematic review, which will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines, will be comprehensive in its approach. A thorough search will be conducted across PubMed, Embase, IEEE Xplore, Scopus, Cochrane Library, and GitHub from their inception to March 2025. Studies involving adults aged 40 years and older that utilise AI/ML techniques to detect or predict bone density or other bone-related properties will be included. Two independent reviewers will perform screening, data extraction, and risk of bias assessments using appropriate tools such as RoB 2, ROBINS-I, QUADAS-2, PROBAST, and NOS. The comprehensive nature of this review ensures that no relevant study is overlooked. Data synthesis will involve narrative synthesis and, if applicable, meta-analysis using Review Manager (RevMan) and R software. Discussion This systematic review will comprehensively evaluate current AI and ML applications in detecting bone properties and osteoporosis. By identifying and analysing various AI/ML models and comparing them with traditional diagnostic methods, the review aims to highlight the effectiveness and potential of these technologies in clinical practice. The findings are expected to significantly impact healthcare professionals, researchers, and policymakers regarding advancements in AI/ML for bone health assessment and guide future research directions. Understanding the strengths and limitations of existing studies will be crucial in developing standardised protocols and facilitating the integration of AI/ML tools into routine osteoporosis screening and management. Systematic review registration This Systematic Review Protocol was registered in PROSPERO (CRD42024587326).

Abstract MP15: Different Questions Lead to Different Answers: Comparing Different Survey Methods for Assessing Relationships between Sleep Duration and Cardiometabolic Health Risk Factors

Circulation Michael Grandner Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.mp15

Introduction: Sleep Duration is part of Life’s Essential 8, and sleep duration items are included in surveys. Yet, sleep duration can be assessed in several ways. The present study examined the degree to which assessing sleep duration using different survey items produces different results when examining associations with cardiometabolic health. Methods: Data from the Sleep and Healthy Activity, Diet, Environment, and Socialization (SHADES) study was used. SHADES is a community-based study of adults in southeastern Pennsylvania (N=1007). Habitual sleep duration was assessed in four ways: the National Health and Nutrition Examination Survey (NHANES) item assessed hours on a typical weeknight, the Behavioral Risk Factor Surveillance System (BRFSS) item assessed typical hours in 24h, the Pittsburgh Sleep Quality Index (PSQI) item assessed hours on a typical night, and the Sleep Timing Questionnaire (STQ) computed typical weeknight and weekend sleep from self-reported bed and wake times. These were evaluated continuously and categorized as short (≤6h), normal (7-8h, reference), and long (≥9h). Correlations among variables were computed. Binary logistic regression analyses adjusted for age and sex examined each of these sleep continuously and categorically relative to obesity, hypertension, hypercholesterolemia, and arrhythmia. Results: Although questions were asked of the same participants at the same time, there was notable variability in responses. No pairs were collinear in either Pearson or Spearman correlations; most correlations were weak to moderate. The Table shows results of regression analyses. As a continuous variable, increased sleep duration was associated with decreased likelihood of obesity and hypertension, but this was only observed using some variables. Also, short and long sleep were associated with obesity and hypertension, and long sleep was associated with increased likelihood of hypertension, hypercholesterolemia, and arrhythmia, but these results were only observed using certain variables. Conclusions: Despite similarly-worded self-report items, there was a high degree of inconsistency regarding whether sleep duration variables were associated with cardiometabolic disease risk factors. This has implications for epidemiologic studies attempting to assess Life’s Essential 8. Assessments that differentiate time in bed vs sleep, and nighttime vs 24-hour sleep, may produce differing results.

Abstract P1172: From adverse pregnancy outcome to preventive care: insights from patient interviews on barriers to primary care after adverse pregnancy outcomes, and how to overcome them

Circulation Mara Murray Horwitz, Grayce Bredy, Lillian Rupert et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1172

Introduction: Primary care is needed to assess and address cardiovascular risk after adverse pregnancy outcomes (APOs) like preeclampsia and gestational diabetes. Yet 40% of individuals with APOs do not connect with primary care post-pregnancy, a gap that is pronounced among individuals who identify as Black or have low incomes. Understanding barriers and facilitators to primary care after APOs can inform interventions to improve women’s cardiovascular health and health equity. Hypothesis: We hypothesize that patient and health system factors impede access to primary care after APOs. Methods: We conducted semi-structured interviews with individuals who experienced APOs and delivered at our urban safety-net hospital 1-2 years prior. Purposive sampling was based on patient language (English, Spanish, Haitian Creole) and linkage to primary care (yes/no) to achieve a diverse sample (goal n=30). Two researchers independently coded the transcripts using an inductive-deductive approach, informed by the Patient-Centered Access to Health Care model. Results: Recruitment was challenging; from 9/2023-8/2024 we completed 15 interviews (9 in English, 3 in Spanish, 3 in Haitian Creole) with individuals with recent APOs, all of whom had linked to primary care in the first postpartum year. Despite universal linkage, every interviewee expressed confusion or frustration with the transition from pregnancy-based care to primary care. They cited numerous patient-level barriers (e.g., competing priorities) and system-level barriers (e.g., scheduling difficulties). Figure summarizes their suggestions for improving postpartum care transitions. Conclusions: In conclusion, individuals with APOs note an abrupt and unsupported transition to primary care after pregnancy, with barriers at multiple levels. They provide concrete and actionable recommendations for health system changes to improve linkage to primary care after APOs.

Abstract P1023: Temporal Changes in High-Sensitivity C-Reactive Protein and Risk of Atrial Fibrillation in African Americans: The Jackson Heart Study

Circulation Hiroto Yagasaki, Wondwosen Yimer, Daisuke Kamimura et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1023

Background: Atrial fibrillation (AF) is associated with significant morbidity and mortality. Inflammation plays an important role in AF pathogenesis. The relationship between high-sensitivity C-reactive protein (hs-CRP), a key biomarker of chronic inflammation, and incident AF in African Americans (AAs), remains unclear. This study aimed to examine the association between baseline and serial hs-CRP levels and incident AF in AAs in the Jackson Heart Study (JHS). Methods: Participants of the JHS with hs-CRP assessment and without previous AF at baseline were included in the study. hs-CRP measurement at Visit 1 (baseline) and Visit 2 were used. Elevated hs-CRP was defined as 3 mg/L per guidelines. Incident AF was defined as having 12 lead electrocardiogram evidence at a subsequent follow up, or a documented diagnosis code at the time of hospital discharge from 2000 to 2016. Cox proportional hazards models were used to evaluate the association between baseline hs-CRP as a continuous variable and AF risk (t 0 =Visit 1), and the risk of AF in those with elevated hs-CRP at Visit 1 or 2, compared to those who had never had elevated hs-CRP (t 0 =Visit 2). Results: Of the 4,169 participants followed for a median of 13.7 years, 351 participants developed AF (6.7 cases per 1,000 person-years). 1,089 participants (44.1%) never had elevated hs-CRP, while 1,379 (55.9%) had elevated hs-CRP at Visit 1 or 2. hs-CRP at baseline was significantly associated with incident AF in Model 1 (age and sex-adjusted), but not in Model 2 (further adjusted) (Table). Elevated hs-CRP at Visit 1or 2 was associated with higher risk of AF incidence in both Model 1 (HR 1.81, 95% CI 1.28-2.58, P < 0.005) and Model 2 (HR 1.61, 95% CI 1.11-2.32, p<0.05). Conclusion: In a community AA cohort, baseline hs-CRP was not associated with incident AF. On the other hand, individuals with elevated hs-CRP at Visit 1 or 2 had a higher risk of AF incidence. This might suggest usefulness of serial hs-CRP measurements to identify those with lower AF risk.

Stress and stiffness as predictors of shear wave velocity in peripheral nerve

PLoS ONE Chelsea L. Rugel, Seth D. Thompson, Colin K. Franz et al. Mar 11, 2025 DOI: 10.1371/journal.pone.0319439

Shear wave elastography (SWE) is a promising non-invasive indicator for diagnosing peripheral neuropathy. Emerging validation studies using ultrasound-based measures of shear wave velocity (SWV) in other biological tissues, such as muscle, demonstrate there is a concern of whether SWE is an accurate measure of tensile stress or stiffness. Distinguishing between these two parameters and their relationship with SWV is crucial if SWE is to be used as a biomarker for peripheral neuropathies, where changes in mechanical properties are known to occur. In this study, we use cat sciatic nerves to first evaluate SWV in situ at knee positions known to reduce (90° flexion) or increase (180° extension) stress, and then excise nerves to directly quantify the relationships between SWV, stress, and stiffness with ex vivo tensile testing. Our ex vivo findings show that although SWV can be predicted using either stress or stiffness, stress explains more variability in sciatic nerve SWV. However, while stress remains the better predictor of SWV ex vivo, within the SWV range established in situ, stiffness improves its accuracy at estimating SWV, especially when also accounting for factors related to nerve viscoelasticity. Therefore, if SWE is to be used in clinical settings as an indicator of nerve stiffness in peripheral neuropathy, it is essential to standardize parameters such as limb positioning and nerve preloading, which could potentially mask pathological changes in nerve stiffness.

Abstract P1020: Relationship Between CHA <sub>2</sub> DS <sub>2</sub> -VASc, Health Literacy, and Atrial Fibrillation Knowledge

Circulation Tanvi Nayak, Preeti Kansal, Kenzie Cameron et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1020

Introduction: It is unknown how comorbid diagnoses affect patients’ disease-specific knowledge or how patients’ health literacy or numeracy affects this relationship. In patients with atrial fibrillation (AF), comorbidities can be quantified by the CHA 2 DS 2 -VASc score. We explore the association of AF/stroke knowledge with CHA 2 DS 2 -VASc score, health literacy, and numeracy for usual care participants in the multi-center Randomized Evaluation of Decision Support Interventions for Atrial Fibrillation (RED-AF) trial evaluating decision aids to initiate (initiation cohort) or continue (monitor cohort) oral anticoagulation (OAC) in AF patients. Methods: This study was conducted at six academic medical centers in the United States. Participants were aged ≥18, diagnosed with non-valvular AF, and at risk for stroke (CHA 2 DS 2 -VASc ≥1 for men, ≥2 for women). Patient demographics were obtained via questionnaires after a baseline clinical encounter; knowledge was evaluated by patient responses to 7 questions about OAC and AF. Health literacy was measured by a validated self-reported screening tool; numeracy by a validated subjective numeracy scale; CHA 2 DS 2 -VASc was calculated from medical records. We applied generalized estimating equations for a binomial outcome to jointly relate patient knowledge to CHA 2 DS 2 -VASc score, health literacy and numeracy, controlling for 5 additional patient factors and accounting for clustering by clinician. Results: We report on 306 patients randomized to the usual care group across six participating sites. Average age 68.7 9, 61.6% male, mean CHA 2 DS 2 -VASc 2 1.5. Patient knowledge was independently associated with numeracy (5% higher odds of correct response per 1 unit increase in numeracy, 95% CI 0-10%, p=0.05) and membership in the monitor cohort (40% odds of correct response, 4-89%, p=0.03) but not health literacy or increased stroke risk. Conclusion: In the RED-AF study , although health literacy and increasing stroke risk were not independently associated with patient knowledge about AF, numeracy had a minimal positive association. Those already on OAC had greater disease knowledge than patients newly starting OAC. These results suggest a need to broadly increase patient education regardless of baseline comorbidity burden and degree of health literacy. Future studies should be performed to better understand other factors that drive patient knowledge regarding AF and stroke.

Abstract P1039: Inhibition Of Drug Metabolizing Enzyme Cytochrome P450 2C8 By Acyl-Glucuronide Metabolites Of Gemfibrozil And Clopidogrel.

Circulation Manish Shah Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1039

Human cytochrome P450 (CYP) enzymes are a superfamily of heme-containing oxidoreductases essential in the metabolism of various xenobiotics. CYP2C8 is responsible for the oxidative metabolism of many important drugs including cerivastatin, repaglinide, pioglitazone, enzalutamide, dasabuvir, imatinib, etc. and has generated research interest due to its involvement in drug-drug interactions (DDI). The glucuronide metabolites of the antilipemic drug gemfibrozil and the antiplatelet drug clopidogrel are known as strong inhibitors of CYP2C8 leading to several DDIs. Most of the gemfibrozil dose is primarily metabolized as glucuronide conjugate or gemfibrozil acyl-glucuronide, which is a known mechanism-based inhibitor of CYP2C8 that leads to clinical DDIs with the substrates of CYP2C8. For example, the co-administration of gemfibrozil with the CYP2C8 substrate pioglitazone inhibited the metabolism and increased the concentration of pioglitazone leading to DDIs. In addition, the clopidogrel acyl-glucuronide metabolite is a known strong time-dependent inhibitor of CYP2C8 leading to marked clinical DDIs with the substrates of this enzyme. Patients on clopidogrel and concurrently taking cerivastatin, or the anti-diabetic repaglinide, are at increased risk of rhabdomyolysis. It is not clear how a glucuronide metabolite of these drugs binds in the active site of CYP2C8 and inhibit the enzyme. CYP2C8 enzyme was recombinantly expressed and purified. A biophysical method Surface Plasmon Resonance (SPR) was used to elucidate the binding of the acyl-glucuronide metabolites of gemfibrozil and clopidogrel with CYP2C8. The representative dissociation constant (K D ) of CYP2C8 binding with gemfibrozil acyl-glucuronide was 227.5 ± 38.5 µM, whereas the K D of CYP2C8 binding with clopidogrel acyl-glucuronide was ten-fold lower, in the range of 3 to 25 µM indicative of higher affinity. The purified protein was also used for crystallization with these acyl glucuronides of gemfibrozil and clopidogrel with an aim to determine the three-dimensional structure. Overall, the characterization of CYP2C8 with gemfibrozil acyl-glucuronide and clopidogrel acyl-glucuronide yielded insights into the binding and inhibition of an important drug metabolizing enzyme.

Abstract 028: The Role of Low Physical activity in Exacerbating Global Ischemic Heart Disease: A Three-Decade Global Comprehensive Analysis

Circulation Hardik Dineshbhai Desai, Anusha Parisapogu, Rutvij Patel et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.028

Introduction: Ischemic heart disease (IHD) remains one of the leading causes of morbidity and mortality worldwide, with physical inactivity identified as a key modifiable risk factor. This is the first ever study estimating the burden of IHD attributable to low physical activity (LPA) including first 2 years of COVID-19 pandemic. Method: Using Standardized GBD 2021 methodology, we estimated deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), years of life lost (YLLs) due to IHD attributable to LPA stratified by age, sex, year and location across the 204 Countries and territories from 1990-2021. Non-fatal health outcomes were estimated using cause of death ensemble model (CODEm). Results are shown in absolute counts, unadjusted and age-standardized rate per 100,000. Results: From 1990-2021, the average annual percentage change (AAPC) the absolute death count rose by 2.00%, 1.79% for DALYs, 2.81% for YLDs, and 1.77% for YLLs. The highest increase in APC was observed in deaths among countries with a middle socio-demographic index at 2.06%, followed by DALYs at 1.60%. According to health system grouping levels, the highest death rate in 2021 was observed in countries with advanced health systems at 4.38 per 100,000 (95% UI: 1.8-7.3). Over the last three decades, males continued to show a higher burden compared to females, with APCs in deaths of 1.10% for males versus 0.74% for females, 0.89% for DALYs versus 0.65%, and 0.88% for YLLs versus 0.64%. Conclusion: Deaths due to IHD accounted for 2.58% of all IHD related deaths globally in 2021. Our findings underscore the need for public health strategies that address the complex socio-technological landscape influencing physical activity levels and suggest pathways for integrating more movement into daily life to mitigate the IHD burden. The need for action is urgent if we are to reverse the trends that have placed so many at risk in our increasingly sedentary world.

Utility of UAS-LIDAR for estimating forest structural attributes of the Miombo woodlands in Zambia

PLoS ONE Hastings Shamaoma, Paxie W. Chirwa, Jules C. Zekeng et al. Mar 11, 2025 DOI: 10.1371/journal.pone.0315664

The ability to collect precise three-dimensional (3D) forest structural information at a fraction of the cost of airborne light detection and ranging (lidar) makes uncrewed aerial systems-lidar (UAS-lidar) a remote sensing tool with high potential for estimating forest structural attributes for enhanced forest management. The estimation of forest structural data in area-based forest inventories relies on the relationship between field-based estimates of forest structural attributes (FSA) and lidar-derived metrics at plot level, which can be modeled using either parametric or non-parametric regression techniques. In this study, the performance of UAS-lidar metrics was assessed and applied to estimate four FSA (above ground biomass (AGB), basal area (BA), diameter at breast height (DBH), and volume (Vol)) using multiple linear regression (MLR), a parametric technique, at two wet Miombo woodland sites in the Copperbelt province of Zambia. FSA were estimated using site-specific MLR models at the Mwekera and Miengwe sites and compared with FSA estimates from generic MLR models that employed combined data from the two sites. The results revealed that the model fit of site-specific MLR models was marginally better (Adj-R2: AGB =  0.87–0.93; BA =  0.88–0.89; DBH =  0.86–0.96; and Vol =  0.87–0.98 than when using a generic combined data model (AGB =  0.80; BA =  0.81; DBH =  0.85; and Vol =  0.85). However, the rRMSE (2.01 – 20.89%) and rBias (0.01-1.03%) of site specific MLR models and combined data model rRMSE (3.40-16.71%) and rBias (0.55-1.16%) were within the same range, suggesting agreement between the site specific and combined data models. Furthermore, we assessed the applicability of a site-specific model to a different site without using local training data. The results obtained were inferior to both site-specific and combined data models (rRMSE: AGB =  36.29%–37.25%; BA =  52.98–54.52%; DBH =  55.57%–64.59%; and Vol =  26.10%–30.17%). The results obtained from this indicate potential for application in estimating FSA using UAS-lidar data in the Miombo woodlands and are a stepping stone towards sustainable local forest management and attaining international carbon reporting requirements. Further research into the performance of UAS-lidar data in the estimation of FSA under different Miombo vegetation characteristics, such as different age groups, hilly terrain, and dry Miombo, is recommended.

Abstract 010: Peripheral Neuropathy is Detected in More than Half of Very Old Adults

Circulation Yuan-Haw Andrew Wu, Jiahuan Helen He, Dan Wang et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.010

Objectives: Emerging evidence suggests peripheral neuropathy (PN) may be more common in older individuals than previously reported, even in the absence of diabetes. However, most studies define PN by loss of protective sensation alone, a late form of PN. We aimed to quantify the prevalence and risk factors for PN in community-dwelling adults aged 80-100 years using the Michigan Neuropathy Screening Instrument (MNSI), a validated screening tool that includes a questionnaire and physical examination. Methods: We conducted a cross-sectional analysis of participants in the Atherosclerosis Risk in Communities Study (2022–2023) who completed the MNSI. Using age-, sex-, site-adjusted logistic regression, we quantified associations between various risk factors and PN, including education, height, body mass index, Short Physical Performance Battery (SPPB) score, lifestyle habits, and comorbidities. PN was defined by a score &gt; 2 on the physical examination or ≥ 7 on the questionnaire portion of MNSI. Results: Among 993 participants (median age 84 years, 40% male, 18% Black, 30% with diabetes), 44.1% screened positive for PN. Risk factors associated with PN included advanced age (≥ 95 years vs 80-85 years, aOR 2.60), male sex (aOR 1.47), taller height (height quartile 2 and 4 vs quartile 1, aOR 1.69 and 1.54), low physical function score (SPPB 0-6 vs 10-12, aOR 2.12), former alcohol consumption (vs no alcohol drinking history, aOR 1.64), and prevalent cardiovascular disease (aOR 1.47) ( Figure ). Diabetes and prediabetes were not significantly associated with PN based on the MNSI, but diabetes was associated with PN based on monofilament testing for loss of protective sensation (aOR 1.51, 95% CI 1.08-2.13). Conclusions: PN detected by the MNSI is highly prevalent among very old adults, regardless of diabetes status. In contrast, PN in adults with diabetes is associated with loss of protective sensation. Routine screening of older adults using the MNSI may be warranted to facilitate early detection and management.

Abstract P3009: Biomarkers and Risk of Cognitive Impairment in Atrial Fibrillation: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort

Circulation Vinh Le, Samuel Short, Katherine Wilkinson et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p3009

Introduction: Atrial fibrillation (AF) is highly prevalent, and its health effects outside of stroke are under intense study. AF increases dementia risk, but underlying mechanisms are unknown. Stroke or cerebrovascular pathophysiology, possibly attenuated with anticoagulation, may be contributory. Hypotheses: We assessed two hypotheses: (1) that higher levels of 9 circulating biomarkers (see Figure) would be associated with greater risk of incident cognitive impairment (ICI) in REGARDS participants with AF, and (2) that associations would be attenuated after adjusting for oral anticoagulant use. Methods: REGARDS enrolled 30,239 persons &gt; 45 years old in 2003-07. AF was defined by self-report or ECG. ICI was defined during follow-up by robust cognitive norms based on the Montreal Cognitive Assessment and Six-Item Screener. Biomarkers were measured at baseline in participants with AF and no prior stroke. HRs of time to ICI by biomarkers were calculated by Cox proportional hazards models, with covariates shown in the Figure. Interaction testing by baseline oral anticoagulant use was also performed. Results: Among 2,261 participants with baseline AF, mean follow-up was 10.6 years (mean age 66.5 years, 51% women, 28.7% Black), and there were 149 ICI cases (7%). Higher NT-proBNP, FVIII, and GDF15 were each associated with ICI (Figure), with the largest association for FVIII (HR adj 2.41 per SD higher FVIII). Added adjustment for anticoagulant use did not attenuate associations, but the association of GDF15 was lower among those on anticoagulation (HR 1.0, 95% CI 0.4-2.6 compared to HR 1.8, 95% CI 1.1-3.0 without anticoagulation; p interaction 0.07). Conclusion: Higher NT-proBNP, FVIII, and GDF15 were associated with ICI in this biracial cohort with AF. Risk associated with GDF15, an inflammation marker, might be reduced with anticoagulation, but further study is needed.

Abstract P1053: Impact of Adversity and Birth Outcomes on the Prevalence of Heart-Related Conditions in Children

Circulation Jenil Patel, Deep Shah, Anna Holdiman et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1053

Background: Adverse childhood experiences (ACEs), social determinants of health, and adverse birth outcomes significantly impact children's well-being. Stress, psychological distress, and adverse birth outcomes contribute to various health issues, including heart-related conditions. This study explores the relationship between these factors and heart health in children to inform interventions and policies. Methods: Data from the National Survey of Children’s Health (NSCH) from 2016 to 2019 were analyzed. The NSCH provides comprehensive data on children's health. US households were randomly contacted by mail, and one child from each eligible household was selected. The overall weighted response rates ranged from 37.4% to 43.1%, with 131,774 children aged 0 to 17 years included. Key variables included bullying, emotional support from family, peers, and healthcare providers, parental divorce, birth weight, preterm birth, and heart conditions. Logistic regression analysis evaluated the relationship between these factors and heart-related conditions, controlling for confounders. Results: The prevalence of heart-related conditions was 2.40%. Bullying was reported by 4.15% of children as definitely true, 18.87% as somewhat true, and 76.98% as not true. Emotional support from family was reported by 89.44%, from peers by 12.65%, and from healthcare providers by 28.70%. Parental divorce was experienced by 22.43% of children. Very low birth weight was reported in 1.18%, low birth weight in 6.50%, and preterm birth in 10.83% of the sample. Logistic regression showed bullied children were 1.93 times more likely to have a heart condition. Emotional support from healthcare providers was associated with a 1.34 times higher likelihood of heart conditions. Low birth weight and preterm birth were associated with higher likelihoods of heart conditions (OR: 1.50 and 1.54, respectively). Emotional support from family, peers, and parental divorce were insignificant predictors. Conclusion: Adverse experiences such as bullying and adverse birth outcomes significantly increase the likelihood of heart-related conditions in children. Emotional support from healthcare providers also plays a crucial role. Interventions targeting bullying, enhancing emotional support, and addressing risks associated with adverse birth outcomes can mitigate long-term health impacts. Early intervention strategies are essential to improve children's health outcomes and prevent long-term cardiovascular issues.

Cancer screening prevalence and preference among hospitalized women with and without diabetes mellitus

PLoS ONE Margaret A. Mallari, Amteshwar Singh, Jocelyn Shubella et al. Mar 11, 2025 DOI: 10.1371/journal.pone.0319681

Objective To determine the prevalence of nonadherence to breast cancer and colorectal cancer screening, associated risk factors, and screening preference among hospitalized women with and without diabetes aged 50–75 years who were cancer-free at baseline. Methods A prospective study compared women with and without diabetes who were cancer-free (except for skin cancer) at baseline and between 50 and 75 years of age, admitted to the general medical service at an academic center were approached for study participation from December 1, 2014, to May 31, 2017. The study evaluated breast and colorectal cancer screening nonadherence prevalence, preference for screening locale, sociodemographic and clinical variables associated with nonadherence using multivariable logistic regression model. Results Of 510 women, 39% had a prior diagnosis of diabetes mellitus, and 36% were African American. Women with diabetes were more likely to have obesity, reliance on assistive devices for ambulation, inability to work (have a disability), and a greater average number of comorbidities compared to women without diabetes. Women with or without diabetes were equally nonadherent with BRC (28% vs 36%, p = 0.6) and CRC (25% vs 28%, p = 0.51) screening guidelines. After adjustment for sociodemographic and clinical risk factors, only high risk for CRC (OR = 3.20, 95%CI; 1.03–9.91) was an independent risk factor associated with nonadherence to BRC among hospitalized women with diabetes. Whereas after similar adjustment, age younger than 60 years (OR = 2.91, 95%CI; 1.15–7.35) and current or prior smoking (OR = 2.80, 95%CI; 1.14–6.86) were associated with nonadherence to CRC among women with diabetes. 46% of women with diabetes expressed a preference for in-hospital screening for BRC, while 45% expressed a similar preference for CRC. Conclusion Hospitalizations may offer additional screening opportunities as almost half of the women with diabetes preferred undergoing breast and colorectal cancer screening during a hospital stay.