bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P316: Orthostatic Hypertension, Standing Hypertension, and Risk of Cardiovascular Disease
Authors: Dooley Sean W , Col Hannah , Turkson Ruth , Ngo Long H , Cluett Jennifer , Lipsitz Lewis , Malek Natalie R , Selvin Elizabeth , Coresh Joseph , Lutsey Pamela L , Windham B Gwen , Zhang Mingyu , Mukamal Ken J , Larbi Kwapong Fredrick , Juraschek Stephen P
Published: May 2024

Background:
There is substantial controversy over how to define orthostatic hypertension (OHTN), an increase in blood pressure (BP) after standing. Recent consensus statements combine both orthostatic and standing hypertension. This could be problematic if their individual associations with cardiovascular disease (CVD) differed as one phenotype would subsume the risk attributes of the other.

Objectives:
To compare the association between OHTN or standing HTN with CVD.

Methods:
The Atherosclerosis Risk in Communities Study measured supine and standing BP during visit 1 (1987-1989). OHTN was defined as a rise in SBP ≥20 mm Hg or DBP ≥10 mm Hg (standing minus supine BP). We also examined a new consensus statement definition of a rise of ≥20 mm Hg in SBP (systolic OHTN) and standing SBP of ≥140 mm Hg. We excluded participants with a history of CVD. We determined risk associations with incident CHD, heart failure, stroke, fatal CHD, and all-cause mortality using Cox models adjusted for CVD risk factors (see Table footnote).

Results:
Of 11,369 participants (56% female, 25% Black adults, mean age 54 years), 10% had OHTN, 20% had standing systolic HTN, and 1% had systolic OHTN with standing SBP ≥140 mm Hg. Over a range of 25-28 years of follow-up, OHTN was not significantly associated with any of the outcomes, while standing systolic HTN was significantly associated with all outcomes. In joint models comparing systolic OHTN and standing HTN, standing HTN was significantly associated with CVD and associations differed significantly from systolic OHTN (Table).

Conclusions:
Unlike OHTN, standing HTN was strongly associated with CVD and death. These differences in CVD risk raise important concerns about combining OHTN and standing HTN in a consensus definition.
Abstract P319: Effects of Environment and Noise on Blood Pressure Readings: The (Decibel(s)) Trial
Authors: Ishigami Junichi , Liu Hairong , Sabit Ahmed , Zhao Di , Pathiravasan Chathurangi H , Charleston Jeanne , Miller Edgar R , Matsushita Kuni , Appel Lawrence J , Brady Tammy M
Published: May 2024

Background:
While guidelines emphasize quiet settings for blood pressure (BP) measurement, large-scale hypertension screening is often conducted in noisy, public spaces (e.g., health fairs). However, the influence of noise and environment on BP readings is unknown.

Methods:
We conducted a randomized crossover trial of community dwelling adults in Baltimore, MD to determine the BP effect of noise and public environment. Participants were randomly assigned to the order of triplicate BPs in 3 spaces: private quiet office (private quiet
1
[reference]); noisy public space (public loud); noisy public space + earplugs (public quiet). To account for intrinsic BP variability, all participants underwent a 4th set of BP measurements in a private quiet office (private quiet
2
). Between each set of triplicate BPs with a WelchAllyn ProB 2000 device and appropriately sized cuff, participants walked for ≥2 minutes, rested for 5 minutes, and had arm/back/feet supported. We conducted difference in difference analysis, overall and stratified by baseline SBP (≥ vs. < 130mmHg) and age (≥ vs. <60yrs).

Results:
N=108, mean age 56 (SD 17) yrs (55% ≥60 years), 91% Black race, and 44% female. 45% had SBP≥130mmHg. Mean private quiet
1
and private quiet
2
BP was 129/74 and 127/74 mmHg (SBPΔ -1.6 (SD 7.1)/DBPΔ -0.2 (SD 4.0)). The average noise level in public loud was 74 db and in private quiet was 37 db. Public loud and public quiet BPs were slightly different than private quiet
1
BPs, with difference in differences minimal (Table): [Public loud: SBPΔ 0.97 mmHg (95%CI: -0.61, 2.55)/DBPΔ 1.86 mmHg (95%CI: 0.94, 2.78); Public quiet: SBPΔ 1.72mmHg (95%CI: 0.05, 3.39)/DBPΔ 1.66 mmHg (95%CI: 0.79, 2.54)]. The patterns were generally consistent across subgroups by SBP and age.

Conclusion:
BP readings in noisy public spaces resulted in small overestimation of BP compared to readings in a quiet private office, but the difference was minimal. Large-scale hypertension screening programs in public loud places may be an acceptable option, especially in low resource settings.
Abstract P321: Clinical Correlates of Medication Adherence to Antihypertensives and Bipolar Medications in Individuals With Hypertension and Bipolar Disorder
Authors: Levin Jennifer B , Moore David J , Briggs Farren , Rahman Mahboob , Montoya Jessica , Depp Colin , Machado-Vieira Rodrigo , Weise Celeste , Maniglia Taylor , Yala Joy , Howard Griggs Gracie , Barigye Richard , Adeniyi Clara , Sajatovic Martha
Published: May 2024

Introduction:
Individuals with bipolar disorder (BD) have high rates of suboptimal medication adherence, medical illness, and premature mortality largely from cardiovascular causes. In the current analysis, we examined screening and baseline data from an ongoing randomized controlled trial and assessed clinical correlates of adherence to antihypertensives and BD medications in 55 patients with bipolar disorder and hypertension.

Hypothesis:
We assessed the hypothesis that adherence to antihypertensives would correlate with systolic blood pressure (SBP) and adherence to BD medication would correlate with psychiatric symptoms.

Method:
Inclusion criteria were a BD Type 1 or 2 diagnosis, being prescribed antihypertensives, and uncontrolled hypertension (SBP ≥130mmHg). Adherence was measured for the prior week with 1) self-reported Tablets Routine Questionnaire for antihypertensives (TRQ-HTN) and BD (TRQ-BD) with higher percentage reflecting worse adherence and 2) objective electronic monitoring using an eCAP
©
for one antihypertensive medication. Average SBP was calculated from 12 readings over one week. Symptoms of BD were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Psychiatric Rating Scale (BPRS).

Results:
Mean age of the sample (N=55) was 53.91±9.97, a majority female (61.8%), 49.1% Black and 45.5% White. Mean years of education was 14.09 ±2.83 and 95% had Bipolar Type I. At screen, TRQ-HTN was 35.80% ± 21.78 (N=55); at baseline, mean TRQ-HTN was 12.94 ± 16.88%. At screen, TRQ-BD was 29.61% ±28.02 (N=55); at baseline, TRQ-BD was 19.43% ±28.54 (N=50). At baseline, eCAP (N=43) was 39.53 ± 35.11%. There was a significant improvement in TRQ-HTN from screen to baseline (t(52) = -6.75 r <0.001) and a trend for TRQ-HTN (t(49) = 1.80, p = 0.078). There was a significant correlation between TRQ-HTN and eCAP at baseline (rs=0.307, p<.05, N= 43) yet eCAP reported more missed days than TRQ-HTN (Mean = -25.581 t(42) = -4.903 p<0.001). TRQ-BD was significantly correlated with BPRS (
r
= 0.313,
p
<.05, N = 50) but not with MADRS. Neither TRQ-HTN nor eCAP were correlated with SBP. SBP significantly decreased from screen to baseline (t(53) = 2.357 p<.05).

Conclusion:
In conclusion, adherence levels vary widely and objective measurement identified rates of missed medications that were approximately 26% higher than self-report. Self-reported BD adherence was related to global psychiatric symptoms but not depression while antihypertensive adherence did not relate to SBP. Greater BD symptom severity may be a clinical indicator to assess for adherence problems and medication and BP monitoring alone may improve adherence and SBP.
Abstract P328: Hepatocyte Growth Factor and Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS)
Authors: Campbell Avery J , Wilkinson Katherine , Plante Timothy B , Olson Nels , Palermo Brittney , Irvin Ryan M , Sawyer Russell P. , Cushman Mary
Published: May 2024

Background:
Cognitive impairment is a major public health burden in the U.S., and Black adults experience a disproportionate burden of cognitive impairment, including dementia. Hepatocyte growth factor (HGF) is a tyrosine kinase receptor MET agonist with neuroprotective properties, including peptide synthesis, neuronal regeneration, and inflammation reduction. Recombinant HGF aids endothelial repair and combats tissue fibrosis in mice. A positive HGF/MET pathway modulator (fosgonimeton) is in Phase 2 clinical trials for mild to moderate Alzheimer’s disease. We investigated the link between circulating HGF and incident cognitive impairment (ICI) in a national cohort study.

Methods:
REGARDS enrolled a cohort of 30,239 Black and White adults aged ≥45 in 2003-2007. ICI was identified using a 3-test battery administered every 2 years. Excluding participants with baseline cognitive impairment or stroke, with a mean follow-up of 3.5 years, 432 ICI cases and 520 controls were identified and HGF was measured in their baseline blood samples. Logistic regression estimated odds ratios (OR) of ICI by continuous HGF and also per quartile of HGF, controlling for known confounders. We assessed sex*HGF and race*HGF interactions on ICI. Restricted Cubic (RC) splines illustrated potential non-linear relationships.

Results:
Higher HGF was not associated with greater ICI risk in any model (
Figure
). There was no observed significant sex*HGF (P=0.58) or race*HGF interactions (P=0.19). RC splines visualized a possible non-linear relationship between lower HGF and higher risk of ICI relative to the median HGF level.

Conclusions:
In a prospective study of HGF in adults free from stroke or cognitive impairment, there was no clear association between higher HGF and ICI, though possible nonlinear associations might exist at low levels. This suggests that pharmaceuticals augmenting HGF pathways may benefit in primary prevention of ICI. Confirmatory studies are needed.
Abstract P330: The Association Between APOE Genotype and Dementia in the Dementia Risk Pooling Project
Authors: Lakomski Natalia A , Giorgio Katherine , Stephen John , Mansolf Maxwell , Soumare Aicha , Gross Alden , Aiello Allison , Singh-Manoux Archana , Ikram Mohammad A , Helmer Catherine , Tzourio Christophe , Satizabal Claudia L , Levine Deborah A , Lloyd-Jones Donald M , Briceno Emily M , Sorond Farzaneh , Wolters Frank , Himali Jayandra , Launer Lenore J , Zhao Lihui , Lopez Oscar L , Debette Stephanie , Seshadri Sudha , Judd Suzanne E , Hughes Timothy M , Gudnason Vilmundur , Zmora Rachel , Peterson Elizabeth , Scholtens Denise , Allen Norrina B , Sedaghat Sanaz
Published: May 2024

Introduction:
Apolipoprotein E (
APOE
) is a glycoprotein that mediates and regulates lipid transport and uptake. The
APOE e4
allele is associated with increased risk of mortality and Alzheimer’s Disease and related dementias. It has been suggested that the
APOE e2
allele is associated with increased survival and serves as a protective factor for cognitive decline and dementia. However, due to the rarity of the
e2
allele, this association is not fully understood. Furthermore, the association between
APOE
genotypes and dementia may differ by race/ethnicity.

Methods:
Data from six large, community-based, prospective cohort studies from the Dementia Risk Pooling Project (DRPP) were used. Cumulative incidence estimates for dementia and mortality by race and
APOE
genotype (combining one or two
e2
or
e4
alleles:
24, 22/23, 33, 34/44
) were estimated. Cox regression models were used to estimate the
APOE
genotype (
22, 23, 33, 34, 44
) cause-specific hazard ratios (HRs) for dementia and mortality adjusting for age, sex, and cohort.

Results:
The sample consisted of 43,404 participants (average age 54, 52% female, 16% Black participants). Overall, the 5-year cumulative incidence of dementia was higher in White participants across different genotypes, while mortality rate was higher in Black participants (Figure 1). The 5-year cumulative incidence of dementia was higher among both Black and White participants with one or two
e4
alleles. Using the
APOE e2/e4
genotype as a reference, the dementia HRs for the
e2/e2
and
e2/e3
genotypes were 0.73 (95% CI 0.51-1.06) and 0.64 (95% CI 0.53-0.76), respectively.
e3/e4
and
e4/e4
genotypes were associated with higher HRs of 1.32 (95% CI 1.12-1.56) and 2.68 (95% CI 2.20-3.27), respectively. There was no association between
APOE
genotypes and mortality.

Conclusion:
In this large, pooled cohort, the presence of an
e2
allele was associated with lower risk of dementia, while the presence of an
e4
allele was associated with higher risk in both Black and White adults.
APOE
genotype was not associated with mortality.
Abstract P337: Clonal Hematopoiesis of Indeterminate Potential and Cognitive Decline in Chronic Kidney Disease Patients
Authors: Xiao Cissy , Kurella Tamura Manjula , Vlasschaert Caitlyn , Pan Yang , Missikpode Celestin , Rao Varun , Uddin Md Mesbah , Kim Do-Kyun , Sun Xiao , Huang Zhijie , Li Changwei , Taliercio Jonathan , Anderson Amanda H , Chen Jing , Deo Rajat , Bhat Zeenat , Rao Panduraga , Xie Dawei , Lash James , He Jiang , Hixson James , Natarajan Pradeep , Yaffe Kristine , Kelly Tanika N
Published: May 2024

Introduction:
Patients with chronic kidney disease (CKD) are at substantially increased risk of dementia. Clonal hematopoiesis of indeterminate potential (CHIP), caused by clonal expansion of blood cells with somatic mutations in certain driver genes, is an established risk factor for cardiovascular diseases, including cerebral vascular disease. In contrast, CHIP was recently shown to be associated with a decreased risk of Alzheimer’s disease. Given emerging evidence of a key role of vascular compared to neurodegenerative mechanisms in CKD-related dementia, the relation of CHIP with cognitive decline in CKD patients needs clarity. We investigated the prospective associations of CHIP with cognitive impairment in a cohort of patients with CKD.

Methods:
Our study included 1989 participants aged 65 years or older from the Chronic Renal Insufficiency Cohort. Participants underwent high-depth targeted gene sequencing to ascertain CHIP status. Cognitive function was assessed by four cognitive tests (see
Table
). For each test, incident cognitive impairment was defined as a test score one standard deviation worse than the baseline group mean. Sequential Cox proportional hazards models tested associations between CHIP and cognitive impairment after adjusting for demographics (model 1), clinical measures (model 2), and
APOE
genotype in a subset with available data (model 3).

Results:
CHIP carriers were significantly less likely to experience impairment in attention (Trails A) and executive function (Trails B) in our fully adjusted models (
Table
). There were no significant associations between CHIP and impairment in global cognition (3MS) or verbal memory (Buschke). There were no differences in the associations of CHIP with cognitive impairment across sex or race groups (data not shown).

Conclusions:
In patients with CKD, we observed markedly reduced risks of impairment in cognitive domains of attention and executive function. Further studies are needed to confirm our findings and evaluate mechanisms of these relations.
Abstract P347: Variability in Predictive Error of Waist Circumference Models: A Stratified Analysis Based on Body Mass Index, Waist Circumference, and Their Ratio
Authors: Karpati Tomas , Test Tsafnat , Reges Orna
Published: May 2024

Introduction:
Waist circumference (WC) independently predicts cardiovascular risks, yet clinical measurements are sporadic. Some models have been developed for WC prediction, with body mass index (BMI) as a key predictor. While these models are generally efficient, variability in error across distinct subpopulations is possible. This study aimed to assess the prediction error (PE) variability of WC models across different strata of BMI, WC, and their ratio, and to evaluate the role of BMI for WC prediction.

Hypothesis:
1) PE varies across BMI, WC, and their interrelated strata. 2) BMI is a key feature for WC prediction.

Methods:
Data from 30,298 individuals from the National Health and Nutrition Examination Survey (2007-2018) were analyzed. After outlier removal and kNN-imputation for missing values, machine learning predictive models for WC were developed. The base model included age, gender, ethnicity, height, weight, and BMI. A non-BMI model was also formulated, incorporating demographics and clinical variables selected via a feature-selection process. Root Mean Square Error (RMSE) across BMI, WC, and ratio of BMI-decile to WC-decile categories were assessed.

Results:
The base model's RMSE for the entire cohort was 5.70. Stratification by BMI revealed higher error rates for obesity classes II (5.88) and III (12.28), contrasting with lower RMSEs in participants with normal BMI (3.95), overweight (4.63), and obesity class I (5.41). Individuals with high WC had an increased RMSE (6.28) compared to those with low WC (5.04). Those with a BMI-decile/WC-decile below one had elevated error (6.98) compared to those with ratios equal to (4.60) or above one (5.52). Across all categories, the base model outperformed the non-BMI model (Figure 1).

Conclusion:
WC model PE demonstrated variability across BMI, WC, and their respective ratios, underscoring the predictive significance of BMI for WC. Considering population-specific variations in predictive WC modeling is important within clinical and research sets.
Abstract P369: Patterns of American Heart Association "Life's Essential 8" Scores in Children With Down Syndrome
Authors: Tirado Boris , Merrill Robert , De Ferranti Sarah D , Lambert Linda M , McCrindle Brian W , Williams Richard V , Ware Adam L
Published: May 2024

Introduction:
Children with Down syndrome (DS) have unique cardiovascular (CV) risk profiles. AHA’s “Life’s Essential 8” (LE8) scores were developed to track comprehensive CV health over the life span. LE8 scores have not been described for children with DS.

Methods:
Children 8-18 years old with DS were enrolled in a multi-site, cross-sectional study. LE8 measures were obtained prospectively and scored as described previously. Controls were obtained from published National Health and Nutrition Examination Survey (NHANES) data. Table 1 describes components of each composite score (not all components available in NHANES). Results are presented by age group (8 to <12, ≥12 to 19 years). Statistics were descriptive with 1 sample t tests to compare the cohort with population means.

Results:
A total of 54 patients with DS, 28 (52%) females, mean age 14.3. years (range 8-18 years) were enrolled. Table 1 lists LE8 scores by age group and LE8 component. The composite LE8 score for children with DS is worse at ages 8-11 and similar at 12-19 compared to the general population. At 8-11 years patients with DS had worse activity, and non-HDL cholesterol scores. At 12-19 years patients with DS had better diet and tobacco scores, but worse non-HDL-C scores.

Conclusion:
Children with DS have unique cardiovascular risk profiles compared to the general population. Composite LE8 scores are worse for young children with DS due to inactivity and cholesterol scores. Composite scores improved in older children with DS compared to the general population based on a stable diet score and less tobacco exposure, but cholesterol scores remained low. Variability in LE8 components can be used to guide preventive practices and health counseling in children with DS.
Abstract P387: Research Participation Rates and Characteristics in Underrepresented Groups in a West Virginia-Based Pregnancy Cohort Study
Authors: Wilhite Katrina L , Barone Gibbs Bethany , Whitaker Kara M , Williamson Carly , Marshall Elly , Morris-Neuberger Lindsay
Published: May 2024

Introduction:
Individuals living in rural areas, identifying as underrepresented racial minorities, and with low socioeconomic status tend to be poorly represented in research. Each underrepresented group experiences unique barriers that may prevent them from participating in research.

Objectives and Hypothesis:
This study aimed to test the hypotheses that 1) in a West Virginia-based pregnancy cohort study, individuals identifying as rural, an underrepresented racial minority, or receiving Medicaid/Medicare (as a surrogate for socioeconomic status) would have lower participation rates than typically better represented populations; and 2) that people from each underrepresented group would have different characteristics associated with screening for and consenting to participate in the pregnancy cohort study.

Methods:
Potentially eligible participants were sent recruitment messages via MyChart, a patient facing app linked to their electronic medical record. Upon receiving the message, participants could express their interest to participate in the study by filling out an eligibility screening form and, eventually, consent to participate at a study visit. Screening and consenting rates were calculated, stratified by rurality (i.e., urban, micropolitan rural, small town rural), race (i.e., white, underrepresented racial minority), and insurance status (i.e., Medicaid/Medicare, private). Logistic regression was used to test which characteristics were associated with screening for and participating in the study in each group.

Results:
Between October 2022 - April 2023, 1024 potential participants were sent recruitment messages. Screening rates (7.3% urban, 7.6% micropolitan rural, 8.8% small town rural; 7.3% White, 10.1% underrepresented racial minorities; 7.9% private insurance, 7.1% Medicaid/Medicare) and consenting rates (2.5% urban, 2.1% micropolitan rural, 4.6% small town rural; 2.8% White, 1.4% underrepresented racial minorities; 3.6% private insurance, 1.9% Medicaid/Medicare) were similar between different underrepresented groups and their better represented counterparts. For small town rural participants, preterm births (OR 6.85 [2.04 - 33.7]) and number of children (OR .24 [.05 - .71]) were associated with participating in the study. Those who identified as an underrepresented racial minority were more likely to screen for the study if they had private health insurance (OR 16.81 [1.53 - 500]). People with Medicaid/Medicare were more likely to participate in the study if they lived in a small town rural area (OR 7.71 [1.57 - 58.97]).

Conclusion:
Differences in characteristics associated with research participation suggest that researchers may need to tailor recruitment strategies to better consider characteristics of different underserved groups.
Abstract P396: Life’s Essential 8 Cardiovascular Health Metrics Are Deteriorating In South Korea: A Nationwide Survey 2007-2021
Authors: Son Dasom , Seo Yeeun , Lee Hyeok-Hee , Kim Hyeon Chang , Lee Hokyou
Published: May 2024

Introduction:
The American Heart Association (AHA) recently updated the “Life’s Essential 8” (LE8) metrics for quantification of cardiovascular health (CVH). We investigated temporal trends of CVH status by LE8 metrics among Korean adults, using nationwide survey data.

Methods:
We analyzed data from the Korea National Health and Nutrition Examination Survey (KNHANES), 2007-2021, including 93,092 participants aged 20 years or older. The LE8 CVH score was calculated as the average score of 8 metrics: diet, physical activity, nicotine exposure, sleep health, body mass index (BMI), blood lipids, blood glucose, and blood pressure, each scaled 0 to 100 points. The CVH scores of 80 to 100 were categorized as high CVH, 50 to <80 as moderate CVH, and 0 to <50 as low CVH. All statistical analyses accounted for the complex survey design of the KNHANES data.

Results:
From the 4
th
(2007-2009) to 8
th
(2019-2021) cycle of the KNHANES, the mean LE8 CVH score declined from 68.9 to 66.6 in the Korean population. The proportion of adults with high CVH decreased from 22.5% to 16.9%, while the proportion of adults with low CVH increased from 8.4% to 10.6% (Figure A). Most adults had already lost ideal CVH by young adulthood; only 25% of adults aged 20-39 attained high CVH, and the proportion was lower at older ages. By individual metrics (Figure B), the score decreased in terms of physical activity (51.2 to 32.8), BMI (77.3 to 74.2), blood lipids (70.1 to 65.9), blood glucose (87.5 to 82.0), and blood pressure (75.9 to 72.3), remained stable in terms of sleep health (80.7 to 80.8), and increased in terms of diet (46.7 to 52.0) and nicotine exposure (63.6 to 73.3). The time-trends were similar across sex and age groups, although CVH scores were generally lower among men and older age.

Conclusions:
The CVH status of Korean adults has deteriorated over the past 15 years, especially in terms of physical activity, BMI, blood lipids, blood glucose, and blood pressure.
Abstract P397: Choline Metabolites Are Associated With Non-Alcoholic Fatty Liver Disease: A Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Sprinkles Jessica K , McRitchie Susan U , Rushing Blake U , Terry James G , Du Xiuxia U , Huo Yuankai Z , Avery Christy L , North Kari E , Gordon-Larsen Penny Z , VanWagner Lisa B , Lloyd-Jones Donald M , Carr J. Jeffery Z , Sumner Susan U , Meyer Katie A
Published: May 2024

Background:
Non-alcoholic fatty liver disease (NAFLD), a common cause of chronic liver disease, has become increasingly prevalent. Choline deficiency has long been a model for the study of accelerated NAFLD, in preclinical and small-scale human studies. More recently, NAFLD has been associated with choline metabolites betaine (inversely) and trimethylamine N-oxide (TMAO) (positively). There has been a paucity of research on circulating choline metabolites and NAFLD in diverse and population-based cohort studies.

Methods:
We used data from 2,413 CARDIA participants who did not self-report liver disease or heavy alcohol intake at Y15, had stored plasma available from Y15, and chest computed tomography (CT) measures from Y25. NAFLD was defined as a mean CT-derived liver attenuation score <51 Hounsfield units; severe NAFLD was <40 Hounsfield units. Liquid chromatography mass spectrometry was used to quantify choline, betaine, and TMAO concentrations from stored plasma samples. Plasma metabolite concentrations were standardized for analysis. Plasma TMAO was natural log transformed for normality. Multivariable-adjusted logistic regression models quantified associations between plasma choline metabolites and NAFLD.

Results (Table):
In fully adjusted models, plasma betaine was inversely associated with NAFLD, and plasma TMAO was positively associated with NAFLD. Plasma choline was not associated with NAFLD in fully adjusted models.

Conclusions:
Our findings support an inverse association between plasma betaine and NAFLD in a diverse, population-based US cohort, and a positive association between plasma TMAO and NAFLD. Circulating betaine reflects dietary intake of betaine, as well as conversion from choline. TMAO reflects an alternative fate of choline, through metabolism by the gut microbiota. These results contribute to a growing literature on choline metabolism and cardiometabolic risk.
Abstract P404: Food Insecurity Has a Moderation Effect in the Association Between Neighborhood Deprivation and Obesity Among Children
Authors: Labisi Titilola , Sidell Margo , Li Xia , Koebnick Corinna
Published: May 2024

Background:
Childhood obesity tracks into adulthood and is a risk factor for non-communicable diseases such as cardiovascular diseases and diabetes. The relationships between socioeconomic status (SES) (including food security, financial stability, and living conditions) and obesity among children have been well established. However, there is limited research on the heterogeneity of the role of food insecurity or insufficiency and neighborhood deprivation (ND) on obesity risk in children. We aimed to investigate the moderating effect of food insecurity in the association between ND, health insurance, race/ethnicity, and Body Mass Index (BMI) among children aged 3-11 years old.

Methods:
For this cross-sectional study of 223,653 children aged 3-11 years who were members of Kaiser Permanente in Southern California, weight and height were collected during routine annual medical visits and extracted from electronic health records. ND index (NDI) was based on patients’ addresses using 2021 regional data. Higher indices represent a higher deprivation. The risk of food insecurity was assessed using the Hunger Vital Sign™ tool on the well-child visit questionnaire. A multivariate linear regression analysis was performed with the absolute distance from the median BMI-for-age and sex based on the 2000 CDC growth charts. Models included age, sex, race/ethnicity, state-subsidized health insurance, self-reported risk food insecurity, and 2-way interaction terms for NDI and state-subsidized health insurance with food insecurity.

Results:
The cohort included children with a mean age of 7.9 years (SD 2.4), males (51.2%), Hispanics (50.3%), living with obesity (24.1%), resided in neighborhoods above the average deprivation (39.6%), and were enrolled in state-subsidized health insurance (25.6%). The risk of food insecurity and insufficiency were reported at 5.0% and 3.3%, respectively. In adjusted models, a higher NDI quintile, state-subsidized health insurance, race/ethnicity, and food insecurity were all associated with a higher BMI (p<0.0001). Food insecurity also moderated the association between NDI and BMI (p = 0.0244) and between state-subsidized health insurance and BMI (p = 0.0034). The effect of food insecurity was highest among those with the least ND and with private health insurance. In a separate model, food insecurity had no moderating effect in the association between race/ethnicity and BMI (p = 0.1).

Conclusion:
Food insecurity showed a moderating effect on high BMI risk among children in higher deprived neighborhoods and enrolled in state-subsidized health insurance. This study highlights the possible effects of food insecurity on obesity among children regardless of race/ethnicity. Future studies are recommended to investigate the moderating role of food insecurity in health outcomes, specifically obesity-associated conditions among children with low SES.
Abstract P407: Decreased Peripheral Mitochondrial Respiration in Pre-Adolescent Hispanic Children With Hepatic Steatosis
Authors: Ramirez Tovar Ana , Sanchez Torres Cristian , Huneault Helaina , He Zhulin , Welsh Jean A , Vos Miriam B
Published: May 2024

Introduction:
Mitochondria plays a significant role in the functioning of the liver. Its function and structure have been associated with diseases outside the organelle by producing reactive oxygen species (ROS), causing generalized oxidative stress, improper function to several metabolic pathways, and perpetuating a pro-inflammatory state in conditions like obesity, diabetes, and metabolic dysfunction associated steatotic liver disease (MASLD). These diseases are on the rise and increase future atherosclerotic cardiovascular disease. Little is known regarding the pathophysiology of the earliest stages of hepatic steatosis, although mitochondrial dysfunction has been shown in later stages. In young children with and without MASLD, we aimed to measure mitochondrial respiration and compare it to hepatic steatosis and other cardiometabolic parameters. The hypothesis of the sub-study was that children with MASLD will have a decreased mitochondrial function compared with healthy children.

Methods:
We report data on 9 subjects, (all Latino subjects, mean age of 8.1 years, mean BMIp of 78%) who participated in screening for an ongoing clinical trial (ClinicalTrials No. NCT05292352). After consent and assent, procedures included drawing whole blood and transferring it immediately to the lab. Monocyte isolation was performed using RosetteSep™ Cocktail and measurement of fatty acid oxidation and glycolysis using the Seahorse Bioscience XFp extracellular flux analyzer. We measured the Oxygen Consumption Rate (OCR) as a proxy for mitochondrial respiration. Association with the mitochondrial parameters was evaluated with the percentage of hepatic steatosis (Hepafat), levels of ALT, insulin, and BMI percentile (BMIp). Data were analyzed using the R software program version 4.2.3

Results:
Mean hepatic steatosis (HS) was 5.97% with a low of 2.4% and a high of 13%. The mean OCR for the subjects without MASLD (n=4, HS ≤5% by MRI) was 404.64 and the mean for subjects with MASLD (n=5, HS ≥5% by MRI) was 349.88. The mean OCR of subjects with a normal, overweight, and obese BMIp was 441.58, 397.45, 309.08, respectively. We found peripheral mitochondrial respiration tends to decrease as hepatic steatosis, BMIp, ALT and insulin levels increase.

Conclusion:
Hepatic steatosis is associated with decreased mitochondrial respiration and perhaps perpetuates an inflammatory state at very young ages in this vulnerable population. More subjects from the NAFLD prevention study will increase the significance of the study in the future.
Abstract P413: Epigenetic Age Acceleration Measures Predict Cardiovascular Outcomes in Diabetic Kidney Disease
Authors: Aronov Avi , Pan Yang , Sun Xiao , Susztak Katalin , Lash James , Kelly Tanika N
Published: May 2024

Introduction:
Cardiovascular disease (CVD) remains the leading cause of mortality in the US, highlighting the need for novel approaches to its prediction, prevention, and management. Epigenetic age acceleration (EAA), or increased DNA methylation-based age relative to chronological age, is a promising biomarker of disease risk. While previous studies have prospectively linked EAA to CVD, recent work in patients with end-stage kidney disease showed no association between EAA and mortality from CVD, underscoring a need for more research across patient populations.

Hypothesis:
EAA measures, specifically intrinsic epigenetic age acceleration (IEAA), extrinsic epigenetic age acceleration (EEAA), phenotypic epigenetic age acceleration (PhenoAA), and Grim epigenetic age acceleration (GrimAA), are associated with incident CVD in diabetic kidney disease (DKD).

Methods:
In a subset of 496 participants from the Chronic Renal Insufficiency Cohort with DKD, selected based on kidney function decline over follow-up (large versus small), we examined four EAA measures: IEAA, EEAA, PhenoAA, and GrimAA. GrimAA is comprised of eight DNA methylation-based biomarkers, including plasminogen activator inhibitor-1 age acceleration (PAI-1
AA
) and tissue inhibitor of matrix metalloproteinase (TIMP-1
AA
), which were also assessed. Primary outcomes were incident CVD, atherosclerotic CVD, and CVD mortality; secondary outcomes included myocardial infarction, congestive heart failure (CHF), cerebrovascular accident, and peripheral artery disease (PAD). Cox proportional models tested associations between the EAA measures and CVD endpoints after adjusting for baseline demographics, clinical center, kidney function decline as a study design feature, lifestyle, and clinical risk factors.

Results:
Participants were predominantly male (63%), with a median age of 57 years, median eGFR of 44 mL/min/1.73m
2
, and mean hemoglobin A1c of 8.0%. After adjusting for multiple testing, each standard deviation increase in GrimAA was associated with incident CVD (HR=1.27; 95% confidence interval [CI], 1.08-1.50; p=0.012) and PAD (HR=1.65; 95% CI, 1.15-2.37; p=0.006). Likewise, PAI-1
AA
was significantly associated with incident CVD (HR=1.24; 95% CI, 1.06-1.44; p=0.006) and PAD (HR=1.46; 95% CI, 1.17-1.81; p=0.001), while TIMP-1
AA
was associated with CHF (HR=1.32; 95% CI, 1.09-1.60; p=0.005). Nominally significant associations between IEAA and atherosclerotic CVD were also identified (HR=1.24; 95% CI, 1.00-1.53; p=0.049). Similarly, EEAA was nominally associated with incident CVD (HR 1.22; 95% CI, 1.01-1.47, p=0.039).

Conclusion:
EAA measures, notably GrimAA, are promising CVD biomarkers in DKD patients. Associations of GrimAA components PAI-1
AA
and TIMP-1
AA
with incident CVD add to the accumulating evidence of their predictive and therapeutic potential.
Abstract P417: A Cumulative Score Approach to Evaluating the Impact of Five Modifiable Lifestyle Factors on Kidney Function
Authors: Laurenzi Martino W , Cirillo Massimo , Terradura Vagnarelli Oscar
Published: May 2024

Background:
Data from the Gubbio population study were used to investigate the impact of a cumulative score combining physical activity, intake of alcohol, sodium, potassium and protein on the decline of kidney function.

Methods:
The Gubbio Study is a longitudinal study on the population of Gubbio, a town in central Italy; it started in the year 1983, and addressed the resident population aged 5 +. Three exams were performed: Exam 1 (baseline) Exam 2 (6-year follow-up) and Exam 3 (20-year follow-up); this analysis is on the 3,039 adult individuals (Age 18+ at baseline) who participated in Exam 2 (1989-92) and Exam 3 (2001-07). Kidney function was estimated as glomerular filtration rate (eGFR) with the CKD-Epi equation (mL/min x 1.73 m
2
). Habitual physical activity and alcohol intake were assessed by standard questionnaires. Dietary intake of protein, sodium and potassium were measured by urinary markers. Each factor received score 0 for the tertile associated with greater eGFR decline, score 1 for the tertile associated with intermediate decline and score 2 for the tertile associated with greater decline. A cumulative score (CS) was then calculated for each individual and used as main independent variable.

Results:
After correction to avoid low-n bias, the CS ranged from 1 (low risk for all factors) to 9 (high risk for all factors). The mean was 5+/-2, with skewness = 0.016. Multiple linear regression showed a relation with the annualized decline in eGFR (slope = - 0,027, 95% CI = - 0.039/ - 0.014, p < 0.001). Incidence of low eGFR was higher in the groups with higher CS, ranging from 2% in the group with CS = 1 to 12.9% in the group with CS = 9. Multivariate logistic regression analysis confirmed the correlation (p < 0.001).

Conclusion:
These data indicate a significant independent association between a score comprising five modifiable lifestyle factors and the long-term decline of kidney function, providing a tool for the quantification of its impact on the long-term incidence of low eGFR.
Abstract P423: Individual and Combined Effects of Diet, Exercise, and Metformin on Risk of Microvascular Complications in Older Type 2 Diabetes Patients: Post-Hoc Analysis of Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial Data
Authors: Parab Kaustubh , Gao Xiaotian , Gothe Neha , Wilund Kenneth , Singleton Chelsea R
Published: May 2024

Introduction:
Microvascular complications are a major burden on the health of type 2 diabetes (T2D) patients. The literature has yielded mixed results regarding synergistic effects of common diabetes treatments (i.e., metformin, exercise, and diet) on microvascular complication risk. Some trials demonstrated that the combination of metformin and exercise diminished beneficial effects. We aimed to explore this ambiguity in findings by examining the effects of metformin, exercise, and diet on microvascular complication risk over time among T2D patients in the U.S. and Canada.

Hypothesis:
We hypothesize that the combined effects of metformin, exercise, and diet would be better than their individual effects on microvascular complication risk.

Methods:
We analyzed data from 923 participants [mean age: 62.6; 39.2% female; mean years with diabetes: 10.7] of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) (2003-2009) trial. Adequate exercise was defined as > 150 mins of moderate-intensity physical activity per week. Metformin use was defined as yes vs. no. An adequate diet score was ≤ 2.4 of the summary fat intake score (range: 0 - 5). We defined composite outcomes for microvascular complications (i.e., nephropathy, retinopathy, and neuropathy) based on several measurements including serum creatinine doubling, decrease in estimated glomerular filtration ratio (≥ 20 ml/min/1.73 m2 decrease), vision loss, Michigan Neuropathy Screening Instrument. We performed longitudinal analysis with synergy factor (SF) approach using multinomial logistic regression models adjusted for sex, diabetes years, education, alcohol, treatment arm, and baseline outcome.

Results:
Among individuals with poor diet score, those taking metformin but not adequate exercise had an odds ratio of 1.12 (95% CI: 0.65 - 1.94, p = 0.68) for microvascular complication. Those not taking metformin but had adequate exercise had an odds ratio of 2.71 (95% CI: 1.12 - 6.59, p < 0.05). However, taking metformin and having adequate exercise produced an odds ratio of 0.90 (95% CI: 0.49 - 1.67, p = 0.75), which was 0.30 times less than the predicted odds of the joint effect (SF = 0·30, 95% CI: 0 - 0.59, p = 0·05). Individuals with an adequate diet, adequate exercise, and taking metformin had an odds ratio of 0.85 (95% CI: 0.48 - 1.49, p = 0.57). However, we did not find these associations to be statistically significant. A similar pattern holds for individual microvascular complication outcomes.

Conclusion:
Additional randomized controlled trials are needed to confirm the potential additive beneficial effect of metformin, adequate exercise, and adequate diet combination over their individual effects on odds of microvascular complications.
Abstract P427: Vitamin D Deficiency and Cardiovascular Disease (CVD) Risk Factors in American Indian Adolescents: The Strong Heart Family Study
Authors: Reese Jessica A , Willis Carson , Davis Erin , Peck Jennifer D , Fretts Amanda M , Ali Tauqeer , Lee Elisa T , Umans Jason G , Zhang Ying
Published: May 2024

Introduction:
Vitamin D deficiency (VDD) may be associated with CVD risk factors, such as obesity, diabetes, and dyslipidemia and is amenable to successful interventions through changes in diet and vitamin supplementation.

Aims:
To describe the prevalence of VDD among American Indian adolescents from SHFS and determine its association with obesity, diabetes, and dyslipidemia incidence in follow-up exams.

Methods:
We included adolescents (<20 years) from the SHFS, who had serum vitamin D measured on stored samples collected at the baseline examination, 2001-2003 (n=307). We defined VDD as ≤20ng/mL and obesity as baseline Body Mass Index (BMI) ≥95%, follow-up BMI ≥30kg/m
2
, waist-hip-ratio (WHR) ≥0.9 for males, or WHR ≥0.85 for females. Diabetes was defined as measured fasting plasma glucose level ≥126 mg/dL or taking hypoglycemic medication. We defined dyslipidemia as abnormal total cholesterol, LDL-C, HDL-C, non-HDL-C, triglycerides, or taking medication. We used log binomial generalized estimating equations to determine if the prevalence or incidence of obesity, diabetes, or dyslipidemia differed according to VDD, while controlling for age, gender, and center (Arizona, Oklahoma, or Dakotas).

Results:
VDD prevalence was 50.8% in AI adolescents, and it was associated with the prevalence of BMI≥95%, high WHR, and dyslipidemia. By the first follow-up, 28.8% developed a BMI≥30kg/m
2
, 58.8% developed high WHR, 6.2% developed diabetes, and 62.6% developed dyslipidemia. By the second follow-up, 11.4% developed diabetes. The risk of high WHR (RR=1.28, CI=1.04-1.58, follow-up=5.8 years), and the risk of diabetes (RR=2.32, CI=1.05-5.12, follow-up=13.3 years) was higher in those with baseline VDD while controlling for covariates (Table 1).

Conclusions:
These data suggest that VDD in adolescence may contribute to the development of high WHR and diabetes later in life, which are strongly associated with CVD. Thus, the results of this analysis may provide a critical step toward reducing or controlling CVD at an early age.
Abstract P428: Risk-Based Approach to Defining Prediabetes Among Middle-Aged Adults in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Rooney Mary R , Wallace Amelia S , Echouffo Justin B , Coresh Joe , Selvin Elizabeth
Published: May 2024

Introduction:
Current prediabetes definitions, based on fasting blood glucose (FG) or HbA1c, are broad and capture many individuals who will never develop diabetes. Other risk factors including age, sex, body mass index (BMI), systolic blood pressure (SBP), and family history of diabetes, are not part of current definitions but are highly predictive of progression from prediabetes to diabetes. We evaluated whether approaches to defining prediabetes that incorporate standard clinical measures can improve 10-year diabetes risk prediction.

Methods:
We conducted a prospective analysis of 11,322 participants in the Atherosclerosis Risk in Communities (ARIC) Study aged 46-70 years (55% women, ~20% Black adults) without diabetes at baseline (1990-1992). We used logistic regression to develop risk equations for incident diabetes over ~10-year based on combinations of HbA1c, FG, and/or clinical measures (age, sex, BMI, SBP, family history of diabetes). We calculated area under the curve (AUC) for 10-year diabetes risk, comparing American Diabetes Association (ADA) prediabetes definitions (HbA1c 5.7-6.4%, FG 100-125 mg/dL, either, or both) with our new risk equations.

Results:
Over ~10 years of follow-up, there were 1230 incident cases of diabetes. The ~10-year absolute diabetes risk for persons with HbA1c 5.7-6.4% was 27% (AUC=0.66) and for persons with an FG of 100-125 mg/dL was 16% (AUC=0.64). Risk equations combining FG and HbA1c yielded an AUC of 0.76. The additional inclusion of all 5 clinical measures increasing the AUC to 0.78 (ΔAUC=0.02; p<0.001). Simple clinical measures, primarily BMI, led to modest improvements in risk discrimination when added to HbA1c alone (ΔAUC=0.03; p<0.001) or FG alone (ΔAUC=0.03; p<0.001).

Conclusions:
Defining prediabetes based on both an elevated FG and elevated HbA1c (confirmatory definition) or using clinical variables (age, sex, BMI, SBP, family history) added to either FG or HbA1c can substantially improve our ability to identify middle-aged adults who will progress to diabetes.
Abstract P432: Validation and Optimization of the American Diabetes Association Score for Undiagnosed Type 2 Diabetes Risk in Hispanic or Latino Adults
Authors: Varghese Ben T , Girardo Marlene E , De Filippis Elena , Vella Adrian , Bailey Kent R , Dugani Sagar B
Published: May 2024

Background:
The prevalence of type 2 diabetes (T2D) is increasing in Hispanic or Latino adults. The American Diabetes Association (ADA) score to identify
current risk
of T2D was developed with limited Hispanic or Latino representation. Therefore, we sought to validate the ADA score in a cohort of Hispanic or Latino adults.

Methods:
At enrollment in the Sangre Por Salud Biobank, 3,625 Hispanic or Latino adults from Phoenix, Arizona completed a baseline questionnaire. Current risk of undiagnosed T2D was based on non-laboratory risk factors and ADA score ≥5 (Table). Participants also completed T2D screening (ie, fasting glucose, 2-hour oral glucose tolerance test, and/or hemoglobin A1c). Undiagnosed T2D was based on 'no self-reported T2D but meeting T2D diagnostic’ criteria. Multivariable logistic regression analyzed associations of ADA risk factors and undiagnosed T2D, and model performance was based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Results:
At enrollment, 7.3% of participants had undiagnosed T2D (n=265/3,625). In multivariable analysis, most risk factors described for the ADA score were significantly associated with T2D, except for sex, which showed no association. ADA score ≥5 had sensitivity 50%, specificity 79%, PPV 18%, and NPV 95%. However, ADA score ≥4 had sensitivity 72%, specificity 61%, PPV 14%, and NPV 96%. ADA score ≥4 vs ≥5 identified 22% (n=59) additional cases of undiagnosed T2D. Furthermore, using the revised definition for elevated blood pressure (>120/80 mmHg) vs ≥140/90 mmHg (current ADA score) further improved the ADA score ≥4 (sensitivity 81%; specificity 52%). Other scores had lower performance using both hypertension definitions.

Conclusion:
In Hispanic or Latino adults, a lower ADA score than currently recommended identified additional cases of undiagnosed T2D. The ADA score requires validation and recalibration, including for the updated hypertension guidelines.