bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multicentre, Randomized Trial in Adults with de novo Philadelphia Chromosome-Positive Acute Lymphoblastic Leukaemia to Assess the Efficacy of Ponatinib versus Imatinib in Combination with Low-Intensity Chemotherapy, to Compare End of Therapy with Indication for Stem Cell Transplantation versus Tyrosine Kinase Inhibitor, Blinatumomab, and Chemotherapy in Optimal Responders, and to Evaluate Blinatumomab in Suboptimal Responders (GMALL-EVOLVE)
Authors: Lang Fabian , Pfeifer Heike , Brüggemann Monika , Hermann Eva , Serve Hubert , Goekbuget Nicola
Published: May 2024

Introduction: Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL) is treated as standard of care (SoC) by imatinib-based treatment combined with induction and consolidation chemotherapy followed by allogeneic stem cell transplantation (SCT) in first remission. The German Multicenter ALL Study Group for Adult ALL (GMALL) reports about a trial to evaluate the impact of ponatinib-based therapy, blinatumomab treatment for suboptimal responders, and the possibility of omission of SoC Allo SCT in optimal responders entitled GMALL-EVOLVE. Methods: Herein, imatinib is randomized versus ponatinib as frontline treatment combined with chemotherapy, optimal responders also get randomized between SCT and chemo-immunotherapy, and suboptimal responders receive immunotherapy before SCT. The trial is registered under the EudraCT number 2022-000760-21. Conclusion: This trial will answer several major questions in the treatment of Ph+ALL.
Abstract 06: Residential Segregation and Thrombo-Inflammatory Biomarkers Related to Hypertension in Black and White Americans
Authors: Kamin Mukaz Debora , Sparks Andrew , Judd Suzanne E , Howard Virginia J , Carson April P , Plante Timothy B , Long D. Leann , Cheung Katharine L , Cushman Mary
Published: May 2024

Background:
Thrombo-inflammation is involved in hypertension pathogenesis. Black people have higher thrombo-inflammatory biomarkers and hypertension burden than White people. It is unclear whether residential segregation, a driver of health inequities, has a differential impact on thrombo-inflammation in Black and White Americans.

Hypothesis:
Higher residential segregation is associated with adverse levels of thrombo-inflammatory biomarkers, and this association is greater among Black relative to White adults.

Methods:
This cross-sectional study included 4,362 participants of the biracial REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. County-level segregation was measured with the (1) dissimilarity index (DI, the difference in racial distribution of census tracts relative to their county), (2) isolation index (ISI, the degree to which Black people are exposed only to one another in a county), and (3) interaction index (ITI, the degree to which Black people are exposed to White people in a county). Linear regression was used to assess correlations of residential segregation indices with 7 thrombo-inflammatory biomarkers associated with hypertension risk: C-reactive protein (CRP), D-dimer, E-selectin, Factor IX, interferon (IFN)-γ, interleukin (IL)-6, and tumor necrosis factor (TNF)-α.

Results:
Worse ISI, ITI, and DI were associated with adverse levels of most biomarkers even with Bonferroni adjustment (Table). For example, CRP was 12% (95% CI: 9-16%) higher per SD higher ISI, 5%(95% CI: 1- 8%) higher per SD higher DI, and 9% (95% CI: 6-12%) higher per SD lower ITI. None of the associations differed significantly by race (p race* residential segregation index >0.1).

Conclusions:
Several thrombo-inflammatory biomarkers important in hypertension were more adverse with greater residential segregation by three metrics, regardless of race. This indicates that residential segregation, a manifestation of structural racism, may become embodied in thrombo-inflammatory processes.
Abstract 16: County-Level Racial Residential Segregation and Sedentary Behavior in US Adults
Authors: Mohammad Moniruzzaman , Deng Yangyang , Shariful Islam Sheikh Mohammed , Jones Kelly , Berrigan David , Matthews Charles , Tamura Kosuke
Published: May 2024

Introduction:
Sedentary behavior (SB) is highly prevalent and shows an increasing trend in United States (US) adults, resulting in adverse health outcomes, such as cardiovascular disease, cancer, and diabetes. Yet, potential environmental determinants of SB, including racial residential segregation, remain understudied.

Hypothesis:
County-level segregation will be associated with sedentary time in a nationwide sample of US adults, and this relationship will be moderated by sex.

Methods:
We analyzed data from 2637 US adults aged 20-75 years (mean age [45.1 years], female [50.6%] from the population-based AmeriSpeak panel in 2019. Participants completed the Activities Completed over Time in 24-hours (ACT24) previous-day recall, a validated population-level measure of total daily SB (hours/day). County segregation was expressed as the isolation index at the county level for non-Hispanic (NH) White, NH Black, and Hispanic adults (vs all other races/ethnicities). The isolation index ranges from 0 to 1, with a higher value indicating higher segregation and therefore, a higher average probability of contact among residents of the minority group and, thus, a lower probability of contact among residents of the minority group and all other races/ethnicities. We used survey-weighted linear regression models to assess the relationships of race-specific isolation index with time spent in SB, adjusting for age, sex, marital status, education, occupation, household income, body mass index, census region, and county-level poverty. Additionally, we stratified these relationships by sex.

Results:
Overall, US adults reported a mean of 9.5 hours/day of sedentary time. Counties with higher NH White isolation showed a significant inverse relationship with sedentary time (β = -1.52, 95% confidence interval [-2.75, -0.29], p = 0.017). Counties with higher NH Black isolation showed a non-significant inverse relationship with sedentary time (β = -0.30 [-2.53, 1.94], p = 0.790), and counties with higher Hispanic isolation showed a non-significant positive relationship (β = 0.32, [-1.64, 2.28], p = 0.743). In sex-stratified analysis, only NH White isolation among White females showed a significant inverse relationship with sedentary time (β = -2.14 [-4.19, -0.09], p = 0.041).

Conclusions:
NH White adults, particularly females, residing in more segregated counties reported less sedentary time in this population-based nationwide sample of US adults. SB was not strongly associated with isolation for NH Black and Hispanic adults. Future studies could aim to replicate (or not) our findings with larger samples of underrepresented minority populations and further explore potential mechanisms for sex related variation in the association between residential segregation and sedentary behavior.
Abstract 24: Actigraphy-Measured Sleep Irregularity Increases the Risk of Incident Cardiovascular Disease and Cardiovascular Mortality in Older Women
Authors: Full Kelsie M , Nguyen Steven , LaMonte Michael J , Lacroix Andrea Z
Published: May 2024

Background:
Cardiovascular disease (CVD) is the leading cause of death for U.S. women. Our understanding of how poor sleep health contributes to CVD is limited by reliance on cross-sectional studies, self-reported sleep measures, and predominately non-Hispanic white samples. Our objective was to prospectively investigate actigraphy-measured sleep health and incident CVD and CVD mortality in a cohort of older multiethnic women.

Methods:
Women (n=3,992; mean age: 78.5 years, 33% African American, 17% Hispanic/Latino) enrolled in the Women’s Health Initiative OPACH (Objective Physical Activity and Cardiovascular Health) study wore an Actigraph GT3X+ accelerometer for 7 days in May 2012-April 2014 and were followed through February 2022 for physician-adjudicated incident CVD (definition in Table footnote) and CVD mortality. Sleep duration, timing, efficiency, irregularity, and continuity were derived from accelerometers (definition in Table footnote). Women with prior CVD at baseline were excluded from analyses. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Minimally adjusted models included age, race and ethnicity. Models were additionally adjusted for education, smoking, alcohol consumption, comorbid conditions, self-rated health, and CVD risk factors.

Results:
Over a median of 8.3 years of follow-up, 636 incident CVD cases occurred, including 395 CVD deaths. In minimally adjusted models, longer sleep duration, greater sleep irregularity, and more wake after sleep onset were associated with increased CVD risk (Table 1). In models further adjusted for CVD risk factors, the HR (95% CI) for a 60-minute increase in sleep irregularity was 1.18 (1.01-1.37) for incident CVD and 1.30 (1.07-1.58) for CVD mortality.

Conclusions:
Greater sleep irregularity was associated with higher risk of incident CVD and CVD mortality in a diverse cohort of older women. These results support the importance of maintaining regular sleep for cardiovascular health.
Abstract 36: Clinical Guidelines May Help Mitigate the Impact of Physician Implicit Bias on Patient Care and Treatment
Authors: Beidelman Erika T , Kalbaugh Corey A
Published: May 2024

Introduction:
We previously found that physician pro-White implicit bias was associated with the performance of low-value revascularization procedures for Black patients with claudication. These treatments are commonly considered risk greater than benefit but are not expressly discouraged by guidelines. We sought to investigate whether implicit bias is less likely to impact care in settings with well-defined Class Ia-supported guidelines.

Hypothesis:
We hypothesized that a physician’s implicit bias would not be associated with the performance of clinical practices as outlined in the 2016 AHA/ACC Guidelines on the Management of Patients with Lower Extremity Peripheral Artery Disease.

Methods:
We measured implicit bias via the race Implicit Association Test (IAT) using a sample of physicians from the Society for Vascular Surgery’s Vascular Quality Initiative (VQI). The IAT asks participants to classify sequential images of Black and White faces to positive and negative attributes. Based on reaction times and responses on the IAT, physicians were categorized as having no bias, pro-Black bias, or pro-White bias. IAT results were then weighted to reflect the overall VQI demographics and linked to peripheral revascularization data. We used mixed effects logistic regression models to assess the association of physician implicit bias category with pre-operative prescriptions of antiplatelets (ASA, P2Y12) and statins, as well as current smoking status (reported as aORs). All models included a random intercept for the physician and were adjusted for year, physician race/ethnicity, and patient factors of race/ethnicity, diabetes, and hypertension. We examined effect modification by patient race/ethnicity through the inclusion of an interaction term with physician implicit bias category. Finally, we calculated a summary index across the four primary clinical practices and assessed the association with physician implicit bias category via a mixed effects Poisson model (reported as IRRs).

Results:
A total of 218 physicians successfully completed the IAT and were linked to 6,588 peripheral revascularizations they completed for claudication. We found no significant associations between the physician’s implicit bias category and the performance of any of the assessed guideline metrics for their Black or White patients (Summary Index - IRR: 1.02, 95% CI: 0.98-1.06). Additionally, we found no evidence of effect modification by patient race/ethnicity (ASA - aOR: 0.91, 95% CI: 0.61-1.34; P2Y12 - aOR: 1.22, 95% CI: 0.88-1.69; Statin - aOR: 1.12, 95% CI: 0.76-1.67).

Conclusions:
The performance of guideline-driven practices were not associated with a physician’s measured racial implicit bias. We provide preliminary evidence that appropriately designed guidelines could be successful in combatting Black-White health inequities stemming from the implicit bias of physicians.
Abstract 56: Associations Between the Plasma Proteome and a Polygenic Risk Score for Venous Thromboembolism: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Li Aixin , Guan Weihua , Pankow Jim S , Pankratz Nathan , Lutsey Pamela L , Moser Ethan , Cushman Mary , Folsom Aaron R , Tang Weihong
Published: May 2024

Introduction:
Venous thromboembolism (VTE) is a leading cause of cardiovascular morbidity and mortality. While coagulation system variation causes VTE, other novel biological pathways remain underexplored. This study aims to provide a comprehensive understanding of the plasma proteomics signature associated with genetic susceptibility for VTE, as captured by a polygenic risk score (PRS).

Methods:
We constructed a race-specific PRS for VTE for participants in the ARIC, an ongoing community-based prospective cohort, based on the two newest large genome-wide association studies (GWAS) reports: one reported 93 risk loci in individuals of European ancestry (PMCID: 36658437); another identified 135 risk loci from a cross-ancestry GWAS (36154123). We selected one SNP for each gene locus from each study, retaining a single SNP when the same gene was identified by both studies. These SNPs were then clumped within a 250kb window with an r
2
threshold of 0.1. We included 139 SNPs in the PRS calculation in ARIC European American (EA) and African American (AA) participants using SNP dosage and race-specific estimates when possible. A total of 4,955 plasma proteins were measured by SOMAscan v4 from samples collected at ARIC visit 2 in 1990-92. We then employed race-specific linear regression to associate the VTE PRS with levels of all 4,955 proteins, controlling for potential confounders. We treated the analysis in EAs (n=7,402) as discovery and that in AAs (n=1,933) as replication, applying Bonferroni correction to account for multiple testing. We then conducted pathway analysis using the Ingenuity Pathway (IPA) to identify enriched biological signaling pathways for the top PRS-protein associations based on FDR<0.01.

Results:
In the EA participants, 90 proteins were statistically significantly associated with the VTE PRS (p<5x10
-5
). Among these, 15 were replicated in the AA participants (p<0.00056) with the consistent direction of associations and 7 of these 15 proteins at p<5x10
-5
. Beyond the well-documented proteins for VTE, such as VWF and coagulation factors VIII, and XI, novel proteins were also identified, such as sulfhydryl oxidase 2, interleukin-3 receptor subunit alpha, ephrin type-A receptor 4, and insulin receptor. The IPA analysis indicated enrichment of the coagulation system, IL-15 pathways, and heparan sulfate biosynthesis pathways.

Conclusion:
This comprehensive proteomic analysis offers valuable insights into the circulating proteomics signature and biological pathways underlying the genetic predisposition for VTE, potentially enhancing our understanding of VTE etiology and prevention.
Abstract MP04: Socioeconomic Spatial Social Polarization and Blood Pressure at Three Spatial Levels
Authors: Abdel Magid Hoda S , Jaros Samuel , Lovasi Gina S , Judd Suzanne E , Odden Michelle C
Published: May 2024

Spatial social polarization (SSP) indices measure how a population is distributed at extremes of privilege and deprivation. The choice of spatial level for analysis impacts the results of studies of SSP, resulting in a bias known as the Modifiable Areal Unit Problem (MAUP). The objective of this study is to examine the association between participant SSP with systolic and high blood pressure among Black and White adults in the CHS and REGARDS studies across three spatial levels: ZCTA, census tract, and county. We used the Index of Concentration at the Extremes (ICE) to measure SSP across socioeconomic domains including race/ethnicity, income, joint race/ethnicity with income, and home ownership using ZCTA-, census tract-, and county-level data. We computed quintiles for each geographic level, with quintile 1 representing the most deprived area and quintile 5 representing the most privileged for each SSP domain measured. High BP was defined as a treated or untreated blood pressure >140/90 mmHg. Multilevel mixed-effects regression models were adjusted for source study and a priori defined covariates with a random intercept for spatial level. The magnitude of the association between spatial privilege and blood pressure was higher at more local levels. We found that study participants who resided in the most polarized and disadvantaged quintile for race/ethnicity had an odds ratio of 1.01 (95% CI: 0.87, 1.16), 1.20 (95% CI: 1.06, 1.35), and 1.24 (95% CI: 1.09, 1.40) at the county, ZCTA, and tract level respectively for high blood pressure compared to those in the most polarized privileged groups for race/ethnicity. Similar results were found for systolic blood pressure, though results varied by the ICE domain examined. These varying effects as a result of MAUP may be functions of the larger area units not capturing the underlying granular SSP distributions of deprivation and privilege and washing out the total effects of spatial polarization on blood pressure.
Abstract MP18: Comparative Assessment of Proteomics, Phenotypic, and Genomic Data on Visceral Adipose Tissue Volume Using Machine Learning in UK Biobank: Advancing Precision Medicine
Authors: Azizi Zahra , Gupte Trisha , Kho Pik Fang , Nzenkue Kevin , Zhou Jiayan , Guarischi-Sousa Rodrigo , Panyard Daniel , Chen Ming-Li , Abbasi Fahim , CLARKE Shoa L , Tsao Philip S , Assimes Themistocles L
Published: May 2024

Background:
Adiposity is a key modulator for Insulin resistance (IR); a strong risk factor for type 2 diabetes and cardiovascular diseases. The blood proteome is a crucial indicator of biological processes associated with complex disorders. In this study, we investigate the associations between plasma proteomics and visceral adipose tissue volume (VAT), and their intersection with phenotypic and genomic data to identify critical proteins for adiposity linked to IR.

Methods:
We examined UK biobank participants with proteomic data generated using the Olink proximity extension antibody assay (PEA). Interactions between, polygenic scores, biomarkers, socio-behavioral, and fitness factors were investigated to identify the most important proteins associated with VAT (Figure). Multi-step machine learning algorithms including separate models for each feature type, followed by a combined model were employed. We used R2 as an indicator of the variance of VAT explained by the features in each model and reported SHAP values for the top 30 features.

Results:
We analyzed a cohort of 5,342 participants (females: 52.2%, mean age: 54.8 ± 7.9 years). Significant variation of VAT with plasma proteins was observed. Polygenic scores, phenotypic, proteomics, and the combined model explained 1%, 62%, 64%, and 67% of the variation in VAT, respectively. The top proteins in the combined model were CDHR2, ACY1, PRSS8, PSPN, LPL, PLAT, FABP4, COL4A1, CPM, CTSD, SSC4D, PON3, CDH15, DSG2, CNTN3, IGFBP2, CCL16, ADM< WFDC12, OXT, CNTN5, PRCP, ADGRG2, and LEP. The model that included only the top 30 features explained 66% of the variation in VAT.

Conclusion:
A small number of plasma proteins measured with the PEA explain a significant portion of the variance of VAT beyond non-proteomic measures. Further validation and incorporation of additional protein-phenotype models may enable a single-source, personalized measurement of adiposity that is easily accessible and may facilitate further understanding the biology of IR and adverse health outcomes.
Abstract MP41: Associations Between Reallocations of Daytime Movement Behaviors and Self-Reported Sleep Quality and Insomnia Severity in Desk Workers
Authors: Kline Christopher E , Sanders Rachel M , Cheruka Caitlin A , Kubala Andrew G , Egeler Mara E , Perera Subashan , Patel Sanjay R , Barone Gibbs Bethany
Published: May 2024

Introduction:
While moderate- to vigorous-intensity physical activity (MVPA) is commonly associated with better sleep, few studies have considered the influence of sedentary behavior (SB) or light-intensity PA (LPA) on sleep or how reallocation of these daytime movement behaviors are associated with sleep.

Purpose:
To examine the association of reallocating time spent in daytime movement behaviors (SB, LPA, MVPA) with self-reported sleep quality and insomnia severity.

Methods:
Using baseline data from a clinical trial, 170 adults with desk jobs were included in analyses (84.1% white; 51.2% female; body mass index [BMI]=31.1±6.6 kg/m
2
; age=44.7±10.8 y). Daily SB and MVPA were measured with activPAL and ActiGraph GT3x accelerometers, respectively, over ~7 days; SB was categorized into short- and long-bout SB (time spent in <30 or ≥30 min bouts, respectively). Daily LPA was calculated as activPAL-assessed wear time minus SB and MVPA. The Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) assessed sleep quality and insomnia severity, respectively. Isotemporal substitution analyses utilized linear regression to demonstrate the effects of replacing one movement behavior (short-bout SB, long-bout SB, LPA, MVPA) with an equivalent amount of another movement behavior on sleep. All analyses adjusted for age, sex, BMI, and device wear time.

Results:
On average, participants spent 4.7±1.3 h/day in short-bout SB, 6.3±2.2 h/day in long-bout SB, 4.3±1.6 h/day in LPA, and 37.3±21.8 min/day in MVPA. Mean PSQI and ISI scores were 5.5±3.0 and 7.2±4.8, respectively; 42.4% had poor sleep quality (PSQI>5) and 40.6% had at least mild-severity insomnia (ISI≥8). Reallocating time from short-bout SB to MVPA was significantly associated with better sleep quality (-0.73±0.37 unit change in PSQI score per 30-min reallocation [P=.05]); reallocations from long-bout SB or LPA to MVPA trended toward significantly better sleep quality (P=.08 and P=.09, respectively). Reallocating time from SB or LPA to MVPA was not significantly associated with lower insomnia severity (each P>.16).

Conclusions:
Increasing moderate-vigorous physical activity at the expense of sedentary behavior or light-intensity physical activity was associated with better sleep quality, though the strengths of these associations were mild at best.
Support:
NIH R01 HL134809, R01 HL147610.
Abstract MP48: Consumption of Low-Calorie Sweeteners Among Infants, Toddlers, and Preschoolers in the United States, NHANES 2013-2018
Authors: Zhu Xinyu , Sylvetsky Allison C , Welsh Jean A
Published: May 2024

Introduction:
Research has highlighted the rising consumption of low-calorie sweeteners (LCSs) and their possible negative health implications. While the American Academy of Pediatrics advises against beverages with LCSs for children under 5y, little is known about current consumption patterns among infants and young children in the United States.

Objectives:
To estimate the prevalence, frequency, and top sources of LCS intake among U.S. infants and young children and to investigate associations between LCS consumption and energy and macronutrient intake.

Methods:
We used one 24-h dietary recall from 3117 children aged 0-5y in the National Health and Nutrition Examination Survey (NHANES) 2013-18 to describe the prevalence and their frequency of consuming foods and beverages containing LCSs. We also compared total energy and macronutrient intake as a proportion of total energy intake (TEI) between LCS consumers and non-consumers. Complex survey procedures and sample weights were applied for all analyses. F-tests were used to compare consumption estimates across sociodemographic subgroups.

Results:
Thirty percent of all U.S. children aged 0-5y consumed foods and/or beverages with LCSs, including 17.5% of infants (0-1y), 34.3% of toddlers (2 and 3y), and 34.5% of preschoolers (4 and 5y). Prevalence of LCS consumption tended to be highest among non-Hispanic Blacks children and those from households with higher educational attainment or a higher family income. Among consumers, mean frequency of any LCS product, LCS beverages (LCSBs) only, and LCS foods (LCSFs) only was 1.4, 1.4, and 1.1 times/day, respectively, and did not differ by age. The most consumed of all LCSBs were
fruit drinks
(71.9%) and the most consumed of all LCSFs was
yogurt (not-Greek)
(59.5%). Compared to non-consumers, LCS consumers had higher intake of total energy, 1516 vs. 1316 kcal/day (p<.0001), carbohydrates, 54.0% vs 52.4% TEI (p=.0005), and added sugar, 3.3% vs. 2.1% TEI (p<.0001) but significantly lower intake of total fat and saturated fat, 33.1% vs 34.9% TEI (p<.0001) and 12.0% vs 13.1% TEI (p<.0001), respectively.

Conclusions:
LCS consumption is prevalent among infants and young children in the U.S. and fruit drinks and yogurt are the main sources. These results highlight the need for further research to understand long-term implications of this consumption.

Funding sources:
None.
Abstract MP59: Associations of Plasma Inosine With Lipid Profiles in the Bogalusa Heart Study
Authors: Sun Yixi , Zhang Ruiyuan , Tian Ling , Pan Yang , Sun Xiao , Huang Zhijie , Fan Jia , Chen Jing , Zhang Kai , Li Shengxu , Chen Wei , Bazzano Lydia A , Kelly Tanika N , He Jiang , Bundy Joshua D , Li Changwei
Published: May 2024

Introduction:
Inosine, a naturally occurring purine nucleotide, has been used as a dietary supplement to enhance overall health. An emerging study in a rat model has indicated that inosine holds promise as a potential treatment for atherosclerosis by reducing cholesterol-driven inflammation and improving vascular function, providing a foundational concept for further investigation in humans.

Hypothesis:
We hypothesize that inosine can improve lipid profiles among humans.

Methods:
We profiled inosine and 886 known metabolites using plasma samples from 1,261 participants of the Bogalusa Heart Study (BHS) 2013-2016 survey. Linear regression models were used to evaluate the relationship between inosine and four lipid phenotypes, including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, while controlling for age, sex, race, education, smoking, drinking, BMI, lipid medication, and total physical activity. Statistically significant findings in the BHS were validated in the Protein and Blood Pressure (ProBP) study, where 80 adults with available stored samples underwent 8-week dietary supplementation of carbohydrate, milk protein, and soy protein in a random order with 2-week washouts. Inosine and lipids were measured at baseline and post-intervention. We tested associations of longitudinal changes of inosine with changes in lipids profile. We also performed formal mediation analyses in the BHS to identify metabolites and metabolic pathways that might mediate inosine’s association with lipids.

Results:
In the BHS, inosine was significantly associated with HDL cholesterol (β=1.85, 95% CI: 0.72- 2.98) but not with LDL cholesterol, triglycerides, or TC. In the ProBP trial, inosine change was positively associated with HDL cholesterol change during the soy protein intervention (β=2.13, 95% CI: 0.59-3.66). Our mediation analysis identified 74 metabolites that nominally mediated (p<0.05) the inosine-HDL association. After Bonferroni correction for 228 independent metabolite clusters, three metabolites, including PC(18:2(9Z,12Z)/20:4(5Z,8Z,11Z,14Z)), arachidonic acid, and LysoPC(18:2/0:0) were significant mediators (p<0.05/228). The 74 nominally significant metabolites were enriched in the sphingolipid metabolic pathway (False Discovery Rate= 0.00312).

Conclusion:
Inosine appears to enhance HDL cholesterol, possibly through the sphingolipid metabolic pathway.
Abstract P125: Association of Cardiology Encounters for Underrepresented Racial and Ethnic Groups With Human Immunodeficiency Virus With Subsequent Lipid and Blood Pressure Control
Authors: Durstenfeld Matthew S , Hill C. Larry , Chiswell Karen , Sanders Gretchen , Okeke Nwora Lance , Meissner Eric , Thomas Kevin L , Morse Caryn , Bloomfield Gerald S , Pettit April , Longenecker Chris T
Published: May 2024

Background:
People with HIV (PWH) are at elevated atherosclerotic cardiovascular disease (ASCVD) risk. Underrepresented racial and ethnic groups (UREGs) with HIV in the Southern U.S. are disproportionately affected, yet whether cardiology specialist care for this at-risk group improves blood pressure and lipid control is unknown.

Methods:
We evaluated a cohort of UREGs with HIV at elevated ASCVD risk without known cardiovascular disease. Participants received HIV-related care from 2015-2018 at four academic medical centers in the Southern United States with follow up through 2020. To create the cardiology and non-cardiology comparator groups, we divided the study into 6-month intervals, creating 8 cohorts and identified eligible patients with a new cardiology encounter during the interval. We included those without a cardiology encounter in that interval or any prior as controls. Primary outcomes were blood pressure control (<140/90 mmHg) and lipid control (LDL-C ≤ 100 mg/dl) assessed during 2 years of follow-up. Statistical analyses were adjusted for cohort, patient factors, HIV measures, and comorbidities, and used random effects to account for repeated use of patients across cohorts.

Results:
Among 4096 included individuals, 411 (10%) had a cardiology encounter (Table 1). Cardiology encounters were associated with subsequent lipid control (OR 2.55, 95% CI 1.17-5.55, p=0.02), but not blood pressure control (OR 0.94, 95% CI 0.46-1.92, p=0.86). Compared to those without a cardiology encounter, those with a cardiology encounter did not subsequently have lower LDL-C (0.46 mg/dl higher per month, p=0.03) or systolic blood pressure (0.05 mm Hg higher per month, p=0.07).

Conclusions:
Cardiology encounters are associated with lipid control for UREGs with HIV. The lack of a decrease in LDL or systolic blood pressure suggests cardiology encounters may not be adequate to improve blood pressure and lipid control, two major modifiable risk factors for atherosclerotic cardiovascular disease among PWH.
Abstract P137: Patient Level Determinants of Glycemic Control Among Patients With Type 2 Diabetes Mellitus in Primary Health Facilities in Ghana
Authors: Hinneh Thomas , Ogungbe Oluwabunmi V , Metlock Faith , Abeiku Mensah Bernard , Baptiste Diana , Commodore-Mensah Yvonne
Published: May 2024

Background:
Glycemic control among patients with type 2 diabetes mellitus (T2DM) has implications for the risk of complications. Despite the increasing burden of T2DM in sub-Saharan Africa, research on glycemic control remains scanty.

Objective:
To assess individual-level determinants of glycemic control among patients with T2DM who were on treatment.

Methods:
A retrospective review of medical records of patients with T2DM in four primary health clinics in the Bono Region of Ghana was conducted. Glycemic control was classified as controlled (fasting blood glucose [FBG] <7.0 mmol/l) and uncontrolled (FBG ≥7 mmol/l) using WHO guidelines for glycemic control. Patient-level characteristics were selected as predictors based on their potential association with glycemic outcomes. A multivariable logistic regression model was fitted to examine the association between patient-level characteristics and glycemic control.

Results:
Medical records of 637 patients were included, mean age of 61 (±12.2) years, 77% females and 59% farmers. Prevalent complications were Peripheral Neuropathy (17%) and Retinopathy (4%). The mean FBG was 9.7mmol/l (±3.9). Twenty-seven percent (27%) of the patients had glycemic control, with a higher proportion among middle-aged patients (36-65). Patients older than 65 years had higher odds of glycemic control compared to those between 20-35 (adjusted odds ratio OR = 1.83, [95% CI: (1.13 3.54)] p=0.049). Patients without any complications had higher odds of glycemic control compared with those with complications (adjusted OR (AOR) 1.80 [95% CI: 1.07 3.02] p=0.029) (Table)

Conclusions:
Age and diabetes-related complications were significantly associated with glycemic control. Intensive treatment strategies should be implemented to improve glycemic control among younger adults to reduce the risk of complications. Health system interventions for people with diabetes must recognize the age dimension of glycemic control in Ghana.
Abstract P141: T2D-DNA Methylation Score and Changes in Glycemic Traits in Response to Weight-Loss Dietary Interventions: The MACRO Trial
Authors: Li Xiang , Kou Minghao , Ma Hao , Wang Xuan , Bazzano Lydia A , Qi Lu
Published: May 2024

Introduction:
Epigenome-wide association studies (EWAS) have identified several CpGs associated with type 2 diabetes (T2D). A previous study has shown that a DNA methylation score provided more comprehensive information related to T2D risk than individual CpGs. However, whether such T2D-DNA methylation score is associated with changes in glycemic traits in response to weight loss dietary interventions remains unknown.

Hypothesis:
We hypothesized that a T2D-related DNA methylation score was associated with changes in glycemic traits in response to weight-loss dietary interventions; and may modify the effect of the interventions.

Method:
The current study included 147 participants from the MACRO trial, who were randomly assigned to a low-fat diet or a low-carbohydrate diet. A weighted DNA methylation score was created by 5 CpGs (cg19693031 at
TXNIP
, cg11024682 at
SREBF1
, cg02650017 at
PHOSPHO1
, cg18181703 and
SOCS3
, and cg06500161 at
ABCG1
) from a previous EWAS at baseline. One-year changes in glycemic traits were calculated.

Results:
We found that a higher DNA methylation score was significantly associated with greater reductions in glucose (β: -3.20, SE: 1.08, p=0.003), insulin (β: -2.29, SE: 0.86, p=0.009), and homeostasis model assessments of insulin resistance (HOMA-IR, β: -0.86, SE: 0.30, p=0.005). The DNA methylation score was more strongly associated with changes in glycemic traits than any individual CpG sites (
Figure
). In addition, DNA methylation score significantly interacted with dietary interventions (low-fat vs. low-carbohydrate). The beneficial associations appeared to be stronger among participants with the low-carbohydrate diet (p-interaction=0.009 for glucose, 0.003 for insulin, and 0.004 for HOMA-IR).

Conclusions:
Our data indicate that a higher DNA methylation score was significantly associated with greater reductions in glycemic traits in response to weight-loss dietary interventions; such beneficial associations were stronger among those who consumed a low-carbohydrate diet.
Abstract P148: Prevalence and Correlates of Overweight and Obesity Among Adults in an Urban HIV Clinic in Uganda
Authors: Assefa Redeat L , Aizire Jim , Nsibirwa Sara , Ocama Ponsiano , Kirk Gregory
Published: May 2024

Background:
Obesity has become a major comorbidity faced by people living with HIV (PLH). This study aimed to estimate the prevalence and correlates of overweight and obesity among PLH in Uganda.

Methods:
From June 2016 and February 2020, we conducted a cross-sectional analysis among PLH receiving comprehensive HIV care in a large urban clinic in Kampala, Uganda. We collected data on socio-demographic and behavioral anthropometry, and included variables such as age, marital status, occupation (farmer/other), migration history (rural to urban, urban to rural, consistently rural, consistently urban), contraceptive use history (pills, injections, implants), previous pregnancies (categorized as 0-2, 3-5, ≥6), and socioeconomic status (SES) index variable developed for Ugandan settings. Standardized weight and height assessments were performed with BMI categorization into normal, overweight and obese categories. We performed sex-stratified analysis employing multinomial logistic regression (Stata 18.0) to estimate adjusted relative risk ratios (aRRR) and 95% confidence intervals (CIs) for overweight and obesity compared to under or normal weight., focusing on correlates of overweight in males due to the limited number of obese male participants (n=15).

Results:
Of 1939 participants aged 18-80 years, 60.2% were female and the median age (IQR) was 43 (35-50) years for females and 47.5 (40-54) years for males. Median body mass index (BMI) was 24.27(21.09-27.99) kg/m2 for females and 21.63 (19.69-24.11) kg/m2 for males. 27.1% and 17.2% were overweight and 16.7% and 2% were obese among females and males, respectively.

In adjusted analysis among females, factors positively associated with being overweight were older age (36-50 years: aRRR=1.84; 95% CI:1.26-2.68, >50 years: aRRR=2.16; 95% CI:1.34-2.46), being married (aRRR=2.00; 95% CI:1.46-2.73), middle SES (aRRR=1.47; 95% CI:1.01-2.13), upper SES (aRRR=2.05; 95% CI:1.44-2.90), and rural-to-urban migration (aRRR=1.52; 95% CI:1.05-2.22). Being a farmer was negatively associated with overweight (aRRR=0.42; 95% CI:0.22-0.77). Similar associations were observed with obesity, with ever use of contraception and having had >2pregnancies also significantly associated with increased risk of obesity. For males, being older (36-50 years: aRRR=2.09; 95% CI:1.06-4.11, >50 years: aRRR=2.04; 95% CI:1.01-4.08) and having high SES (aRRR=2.38; 95% CI:1.53-3.70) were positively associated with overweight, while being a farmer was inversely associated (aRRR=0.43; 95% CI:0.20-0.93).

Conclusions:
High prevalence of overweight and obesity were observed among PLH in Uganda, notably among females. Migration, SES, and reproductive factors were strongly associated with higher BMI. Identified sociodemographic risk factors can guide targeted interventions in this region.
Abstract P161: Association Between Kidney Function and Pre-Heart Failure: Insights From the Echocardiographic Study of Latinos (Echo-SOL)
Authors: Hadavi Cyrus , Duran Luciano Priscilla , April-Sanders Ayana K , Yuan Yawen , Escalera Cristian , Lee Un Jung , Peralta Carmen A , Rosas Sylvia E , Sotres-Alvarez Daniela , Hurwitz Barry E , Talavera Gregory A , Kansal Mayank M , Hanna David B , Daviglus Martha L , Lash James , Cai Jianwen , Abramowitz Matthew , Rodriguez Carlos J
Published: May 2024

Background:
Impaired kidney function is an independent risk factor for heart failure (HF), but its association with pre-HF is not as well studied. We assessed kidney function in relation to pre-HF in a diverse Hispanic/Latino population in the US.

Methods:
Echocardiographic data from visit (V) 1 and 2 of Echo-SOL were analyzed (unweighted n=1643). Prevalent pre-HF was defined as any abnormal echocardiographic parameter at V1: left ventricular (LV) systolic dysfunction (LVSD) [ejection fraction <50%, global longitudinal strain >15%]; LV diastolic dysfunction (LVDD) >grade 1; and LV remodeling (LVR) [LV mass index >115 g/m2 in men, >95 g/m2 in women, relative wall thickness >0.42]. Incident pre-HF was defined at V2 among those without pre-HF at V1 (unweighted n=588). Kidney function was assessed by cystatin C (per 10 mg/L), eGFR (MDRD-traditional and CKD-EPI, per 5 mL/min/1.73 m2), and urine albumin creatinine ratio (UACR, per 10 units). Survey logistic regression analyses were used to examine the association of kidney function measures with prevalent and incident pre-HF and its domains (LVSD, LVDD, LVR), unadjusted and adjusted for age and sex and accounting for the complex survey design.

Results:
At V1 (mean age 56 years, 55% female), 66.7% had prevalent pre-HF; at V2, 66.3% had incident pre-HF. UACR was significantly associated with prevalent pre-HF and LVR in all models (Table 1-2). Higher cystatin C was significantly associated with incident pre-HF, LVDD, and LVR in all models; whereas eGFR (CKD-EPI) showed a marginal inverse relation with prevalent and incident pre-HF, LVDD and LVR, but only remained associated with LVR in adjusted models (Table 1-2).

Conclusion:
Declining kidney function (higher UACR and cystatin C) is associated with prevalent and incident pre-HF, diastolic dysfunction, and cardiac remodeling. Lower eGFR is also associated with cardiac remodeling in this population. Screening for kidney function could help us identify pre-HF and start protective therapies earlier to most effectively prevent overt HF.
Abstract P162: Projected Reduction in Incident Non-Ischemic Heart Failure by Controlling Risk Factors in Individuals With Diabetes
Authors: Hennessy Susan , Penko Joanne , Coxson Pamela G , Boylan Ross , Bellows Brandon K , Zhang Yiyi , Sims Kendra D , Moran Andrew E , Bibbins-Domingo Kirsten , Kazi Dhruv S
Published: May 2024

Background:
Individuals with diabetes have an elevated risk of non-ischemic heart failure (NIHF), and comorbidities such as hypertension, obesity, and smoking exacerbate this risk. Compared with the status quo in US adults with diabetes, we projected the decrease in NIHF incidence and prevalence that could occur if hypertension, overweight/obesity, and smoking status were treated to evidence-based thresholds.

Methods:
The Cardiovascular Disease (CVD) Policy Model is a computer simulation that provides nationally representative estimates of CVD burden for the US population aged 35-94 years. We used National Health and Nutrition Examination Survey (2015-2018) data to determine diabetes prevalence (i.e., “ever been told you have diabetes”, HbA1c ≥6.5%, fasting glucose ≥126mg/dl, or non-fasting glucose ≥200mg/dl) in individuals without prior CVD. Incident NIHF rates were estimated from pooled epidemiologic cohorts. We modeled the impact of treating hypertension (SBP ≥130mmHg), overweight or obesity (BMI ≥25Kg/m
2
), and current smoking to evidence-based thresholds (SBP <130mmHg, BMI <25Kg/m
2
, and smoking cessation) on incident and prevalent NIHF over ten years (2023-2032).

Results:
An estimated 28.4 million US adults aged 35-94 years have diabetes and no prior CVD. Of these, 50% have hypertension, 89% are overweight or obese, and 13% are current smokers. In ten years under the status quo, the projected incidence of NIHF would be 604,000 cases per year and the prevalence of NIHF would be 4.7 million individuals. Treating risk factors to evidence-based thresholds across the whole population would reduce NIHF incidence to 528,000 cases per year, a 13% decline, and prevalence to 4.4 million individuals, an 8% decline. Achieving a BMI ≤25Kg/m
2
among those with overweight/obesity would have the greatest independent effect on projected HF incidence and prevalence (
Table
).

Conclusions:
Weight loss, blood pressure control, and smoking cessation in patients with diabetes could substantially reduce the US burden of incident NIHF.
Abstract P164: Patient-Reported Awareness and Understanding of the Diagnosis of Heart Failure With Preserved Ejection Fraction
Authors: Khodneva Yulia , Arora Pankaj , Hearld Larry , Nordberg Megan , Cherrington Andrea
Published: May 2024

Background:
Heart failure with preserved ejection fraction (HFpEF) accounts for half of all HF cases, is difficult to diagnose and manage, and represents the fastest growing subtype of HF in the US. Lack of awareness about the HFpEF diagnosis among patients contributes to delays in seeking care, reduced participation in self-management, and worse health outcomes.

Methods:
This study explored HFpEF-related knowledge among patients using semi-structured interviews guided by the “Integrated Health Literacy Model”. Patients were asked to describe 1) their heart condition, as they understand it; 2) where they currently learn about their heart condition; 3) what they want to learn more about; and 4) who can help them learn more.

Results:
In this study, 10 patients with HFpEF were recruited from a local health care system (
Table
). All patients were unaware of having HFpEF; 8 out of 10 thought they had "congestive HF." Patients learned about their condition from cardiologists, primary care physicians and clinic staff. All reported using the Internet to seek information, though in some cases information was confusing or contradictory to what they were told before. Patients noted that they had symptoms for a long time before learning the symptoms were HF-related. Patients wish to know more about the prognosis, factors that can help or make their condition worse, signs and symptoms to monitor, use of wearable devices to monitor, how to live longer and non-pharmacological treatment options. Most patients wanted to learn more about their condition from cardiologists, however, some faced challenges in their current cardiology care, citing lack of time during the clinic visit, difficulty with medical terminology and inability to ask follow-up questions. Patients emphasized a need for more emotional support at the time of diagnosis and help addressing mental health.

Conclusion:
Patients were not aware they had HFpEF, expressed multiple needs for education and support, and identified cardiologists as the most credible source of education.
Abstract P165: Home- and Center-Based Cardiac Rehabilitation Utilization Among Adults With Heart Failure in Kaiser Permanente Southern California
Authors: Mefford Matthew T , Yang Su-Jau , Reynolds Kristi , Funahashi Tadashi T , Elkoustaf Rachid , Batiste Columbus D , Lahti Debora A , Nkonde-Price Chileshe
Published: May 2024

Background:
Cardiac rehabilitation (CR) is guideline-recommended for patients with chronic, stable heart failure (HF). Despite benefits in reducing the risk of outcomes and improved quality of life, referrals to and participation in CR are low. This study describes sociodemographic variability in referrals and participation in center-based CR (CBCR) and home-based CR (HBCR) among adults with HF in Kaiser Permanente Southern California.

Methods:
Adults ≥ 18 years of age with a history of HF, who were eligible for CR referral between April 2018 and April 2019 were identified. HF was defined using diagnosis codes and required to occur ≤ 30 days prior to their first CR session. Participation was defined as completing ≥ 1 session. Sociodemographics and comorbidities were described across four mutually exclusive groups: (1) no referral, (2) referral and non-participation, (3) participation in CBCR and (4) participation in HBCR.

Results:
Among 7,801 adults with HF eligible for CR, the mean age was 74 years, with the majority male (58%), non-Hispanic white (50%), and English-speaking (90%), and having high burden of comorbidities including atrial fibrillation (50%), chronic kidney disease (49%), and hypertension (82%). (Table) Only 326 (4%) adults received a referral for CR, with 128 (39%) not participating, 97 (30%) participating in CBCR, and 101 (31%) participating in HBCR. Those not receiving a CR referral had the highest proportion of older individuals and comorbidities. Those referred to CR but who did not participate were most likely to be male (70%) and single (16%). Household income was highest among those participating in CBCR and HBCR ($83,000 and $80,000, respectively, compared with overall median $77,000) but this was not statistically significant.

Conclusion:
Less than 5% of eligible HF patients were referred to CR and variability by age, income, marital status, and comorbidities were noted for referrals and participation. Reducing disparities in CR utilization may improve outcomes in this high-risk group.