bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP17: Geographic Variations in Diet Quality Among Adults in the United States
Authors: Liu Junxiu , Chen Zhuo , Mu Lan , Li Yan , Thapa Janani R , Pagan Jose , Zhang Donglan
Published: March 2023

Introduction:
Prior studies of diet quality in the United States (US) have focused on national estimates and trends. Examining geographic variations in diet quality over time can provide actionable and targeted policy insights.

Hypothesis:
Diet quality is heterogeneously distributed across US geographical locations with higher diet quality in urban and western and eastern regions.

Methods:
We included a nationally representative sample of US adults aged 20 years or older with data on 24-hour dietary recall and geocode (N=19,607) from six cycles (2007-2018) of the National Health and Nutrition Examination Survey (NHANES).
Exposures
are geographic location by rurality, level of urbanization (large, medium, and small), and US census region and calendar year.
Outcomes
are diet quality measured by the American Heart Association dietary primary (range 0-50; based on total fruits and vegetables, whole grains, fish and shellfish, sugar-sweetened beverage, and sodium); secondary scores (range 0-80; adding nuts/seeds/legumes, processed meat, and saturated fat); the Healthy Eating Index (HEI) 2015 (range 0-50); major dietary components; and poor diet quality. Poor diet was defined according to the AHA secondary score as less than 40% adherence (score <32); intermediate, as 40% to 79.9% adherence (score 32-63.9); and ideal, as at least 80% adherence (score ≥64, respectively).

Results:
Among rural vs. urban residents, the primary AHA, secondary AHA, and HEI-2015 scores in 2017-2018 were 19.5 (95% CI, 18.9-20.1) vs. 20.6 (95% CI, 20.4-30.0); 35.1 (95% CI, 34.3-35.8) vs. 37.1 (95% CI, 36.7-37.6), and 51.8 (95% CI, 51.0-52.7) vs. 53.9 (95% CI, 53.9-54.4), respectively. The corresponding proportions having poor diet quality for rural vs. urban were 43.1% (95% CI, 40.8%-45.5%) vs. 36.2% (95% CI, 34.8%-37.5%). By region, the AHA secondary score was lowest (34.9; 95% CI, 34.1-35.6) for the South. Similar result patterns were found for the AHA primary and HEI-2015 scores. The proportion of adults having poor diet quality was highest in the South (43.2%; 95% CI, 40.8%-45.6%). Trends in diet quality remained stable from 2007 to 2018.

Conclusions:
Significant differences in diet quality by rurality, levels of urbanization, and region exist for adults in the US. These differences in diet quality have remained stable from 2007 to 2018. Geographic differences in diet quality—and the consistency of these differences over time—seem to be important in the development of targeted food policy strategies to address regional disparities.
Abstract MP19: An eGFR Polygenic Score Predicts Chronic Kidney Disease in African Americans
Authors: Jones Alana C , Patki Amit , Srinivasasainagendra Vinodh , Armstrong Nicole D , Chaudhary Ninad S , Hidalgo Bertha , Tiwari Hemant K , Limdi Nita , Arnett Donna K , Lange Leslie , Lange Ethan , Kiryluk Krzysztof , Khan Atlas , Irvin Marguerite M
Published: March 2023

Chronic kidney disease (CKD) is a risk factor for cardiovascular disease and early death. Genetic factors contribute to CKD, and recently, polygenic scores (PGS) have been developed to quantify risk for complex diseases, such as CKD. However, African ancestry populations are underrepresented in both CKD genetic studies and PGS development overall; moreover, European-ancestry derived PGSs demonstrate diminished predictive performance in African ancestry populations. This study aimed to develop a PGS for CKD using genotype and phenotype data from African American (AA) participants of observational cohort studies. We obtained score weights from a meta-analysis of genome-wide association studies (GWAS) for estimated glomerular filtration rate (eGFR) in the Million Veteran Program (MVP) and Reasons for Geographical and Racial Differences in Stroke (REGARDS) Study (total n~66,000). We then optimized the PGS in a cohort of AAs from the Hypertension Genetic Epidemiology Network (HyperGEN) Study (n~1,900) using the
PRS-CS
software and evaluated the predictive performance of the PGS at multiple global shrinkage parameters. We further adjusted the PGS for
APOL1
risk status. In HyperGEN, the eGFR-based PGS was significantly associated with the odds of prevalent CKD—defined as baseline eGFR <60 mL/min/1.73m
2
— in logistic regression models adjusted for age, sex, and population structure. Further, accounting for
APOL1
risk status—a putative variant for CKD unique to those of sub-Saharan African descent—improved the score’s accuracy, with the
APOL1
-adjusted PGS explaining 1.9% (1.1% without
APOL1
) of the variance in CKD and an area under the curve (AUC) of 58.9% [95% CI: 53.0%-64.9%] (without
APOL1
, 58.2% [95% CI: 52.3%-64.1%]). Sensitivity analyses and validation in external cohorts, as well as comparisons to previously published PGS, are ongoing. In this study, we developed a PGS that was significantly associated with CKD with improved predictive accuracy in AAs over previously published PGS.
Abstract MP22: Plasma Metabolomic Profiles Associated With Mortality and Longevity in a Prospective Study of 13,401 Individuals
Authors: Wang Fenglei , Tessier Anne-Julie , Liang Liming , Wittenbecher Clemens , Haslam Danielle , Eliassen A H , Rexrode Kathryn M , Tobias Deirdre K , Li Jun , Zeleznik Oana , Stampfer Meir J , Grodstein Francine , Martínez-González Miguel , Salas-Salvado Jordi , Clish Clary , Lee Kyu Ha , Sun Qi , Hu Frank , Guasch-Ferré Marta
Published: March 2023

Background:
Recent advances in metabolomic studies have shown promise in elucidating the biological pathways underpinning aging processes and mortality in animal models, but data in humans are lacking. We aimed to evaluate the associations between metabolite profiles, all-cause and cause-specific mortality, and longevity.

Methods:
Within three prospective cohorts (Nurses’ Health Study [NHS], NHSII, and Health Professional’s Follow-up Study), we measured plasma metabolites from 11,523 participants (mean age 54 years, 86% female) using high-throughput liquid chromatography-mass spectrometry. Participants were free of cardiovascular disease and cancer at blood collection. Metabolome-wide association analyses were conducted for all-cause, cardiovascular, and cancer mortality using Cox proportional hazards regression and longevity (attaining 85 years of age) using logistic regression. Both pre-defined and data-driven metabolite groups were also evaluated. We further developed a multi-metabolite profile score for all-cause mortality using an elastic-net regularized Cox model and assessed its associations with mortality and longevity. Results for all-cause mortality were replicated among 1878 participants (mean age 67 years, 58% female) from the PREDIMED trial.

Results:
We documented 4252 deaths (including 864 cardiovascular deaths and 1070 cancer deaths) and 3048 achieving longevity over a median follow-up of 22.6 years in the NHS/NHSII/HPFS, and 126 deaths during a follow-up of 4.7 years in the PREDIMED. Higher levels of three nucleosides (N2,N2-dimethylguanosine, pseudouridine, and N4-acetylcytidine), 4-acetamidobutanoic acid, triacylglycerols with ≤56 carbons and ≤3 double bonds, and several other lipids were associated with increased risk of all-cause mortality and corresponding decreased likelihood of longevity; whereas L-serine, L-glutamine, and TAGs with >56 carbons or >3 double bonds were associated with lower mortality risk and higher odds of achieving longevity. A multi-metabolite profile score comprising 73 metabolites was positively associated with all-cause (HR per 1-SD increment=1.25 [95% CI: 1.21, 1.30] in NHS/NHSII/HPFS and 1.47 [95% CI: 1.22, 1.78] in PREDIMED), cardiovascular (HR=1.34 [95% CI:1.24, 1.45]), and cancer mortality (HR=1.15 [95% CI:1.08, 1.24]) and inversely associated with longevity (OR=0.79 [95% CI: 0.74, 0.86]).

Conclusions:
We identified multiple metabolites associated with mortality and longevity. Our findings provide insights into the biological pathways that lead to death and open up new avenues to incorporate these metabolomic markers in clinical and research settings.
Abstract MP24: Atherogenic Gut Microbial Metabolite Scores and Risk of Coronary Heart Disease Among Women in the Nurses’ Health Study
Authors: Heianza Yoriko , Wang Xuan , Tiwari Saumya , Sun Qi , Rexrode Kathryn M , Watrous Jeramie , Jain Mohit , Manson Joann E , Qi Lu
Published: March 2023

Introduction:
Recent evidence suggests that dietary proteins modulate the microbial composition and metabolite production to influence host physiology. Gut-microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors, phenylacetylglutamine (PAGln) and p-tolyl (cresol) sulfate, have been recently implicated as atherogenic metabolites derived from the microbial metabolism of protein foods (such as red meat) and amino acids.

Hypothesis:
We tested a hypothesis that combined effects of atherogenic gut microbiota-related metabolites may be strongly related to the risk of incident coronary heart disease (CHD) among women.

Methods:
We conducted a prospective nested case-control study of 762 incident cases of CHD (fatal CHD and nonfatal myocardial infarction) and 762 matched controls identified over 10-14 years of follow-up. Plasma metabolites (TMAO, N,N,N-trimethyllysine, PAGln, and p-tolyl (cresol) sulfate) were measured at baseline. We regressed the CHD outcome against metabolites using conditional logistic regression and then calculated an atherogenic microbial metabolite score (AMMS) of CHD by summing the β effects of metabolites.

Results:
Every 1 SD increment of AMMS was associated with a matching factor-adjusted RR of 1.28 (95% CI: 1.15, 1.44) and a multivariable-adjusted RR of 1.26 (1.12, 1.42) for CHD controlling for demographic, dietary, and lifestyle factors, postmenopausal hormone use, and body mass index. Dose-response analysis showed a linear relation between AMMS and the risk of CHD (
P
<0.001). In addition, there was a 1.20 (1.06, 1.36) times increased risk of CHD per 1 SD of AMMS after adjusting for common metabolic comorbidities (diabetes, hypertension, and dyslipidemia). The highest quintile (Q5) group had an adjusted RR of 1.60 (1.08, 2.37) for CHD, as compared to the lowest quintile (Q1) (
Fig
).

Conclusions:
Atherogenic gut microbiota-related metabolite scores were significantly associated with risk of incident CHD among women without prior CHD.
Abstract MP26: Lifestyle, Genetic and Epigenetic Factors Associated With Serum Glyca Levels and Results From a Lifestyle Intervention Trial on This Cardiovascular Risk Biomarker
Authors: Coltell Oscar , Sorli Jose , Fernandez-Carrion Rebeca , Corella Dolores
Published: March 2023

Introduction:
GlycA is a novel biomarker of systemic inflammation and cardiovasculardisease (CVD) risk. It is measured by a signal in the proton nuclear magnetic resonance(NMR) spectra (from the N-acetyl methyl groups of N-acetylglucosamine residues).Epidemiological studies have reported associations between GlycA and increased CVD risk.However, there are few investigations examining the link between GlycA levels and lifestylefactors (diet, physical activity (PA), sleep, etc.), gut microbiota, or genetics at the genome-wide level (GWAS); and even fewer studies have analyzed serum GlycA and genome-widemethylation (EWAS) or the effect of lifestyle intervention on the reduction of GlycA.Therefore, our aims were: i) to investigate lifestyle, genetic, and epigenetic factorsassociated with serum GlycA; ii) to examine changes in serum GlycA after 1-y lifestyleintervention in a Mediterranean population.

Methods:
Cross-sectional and lifestyleintervention analyses were undertaken in a Mediterranean population at highcardiovascular risk (n=426 older subjects with metabolic syndrome in the PREDIMED-Plus-Valencia trial; ISRCTN89898870). Lifestyle variables were assessed by validatedquestionnaire and quantile-g-computation methods were used to analyze their jointcontribution. Serum GlycA was measured by NMR spectroscopy. Genome-wide genotypingand DNA-methylation were determined by Illumina arrays (OmniExpress and EPIC).Exploratory omics-wide and targeted analyses on GlycA (focusing on autophagy genes andmicrobiome-host-related genes) were undertaken. Changes in serum GlycA levels after a 1-y lifestyle intervention (intensive intervention group with Mediterranean diet and PA versusthe control group) were assessed in a subset of participants.

Results:
GlycA levels atbaseline (Mean: 1.49+/-0.20 mmol/L) were significantly associated with branched-chainamino acids and a highly atherogenic lipid profile. Also, we obtained an association withdietary factors and PA. Omics analysis suggested novel SNPs (in SFMBT2- DAB1 and TEK)and methylation sites (CpG in RAD50, PPP1R9B, ZDHHC4 and LSP1) associated with GlycA. We also obtained associations with host-microbiome related SNPs in FUT2 and withmethylation signals in selected autophagy genes (STX7, TAX1BP1, ATG9B and ATG10).Moreover, in the intervention trial we detected a significant (P<0.05) decrease in the GlycAlevels after 1 y of intensive lifestyle intervention in comparison with the control group.

Conclusions:
Serum GlycA levels were strongly associated with cardiometabolic risk factorsin this Mediterranean population and linked to lifestyle variables. Additionally, we haveidentified some genetic and epigenetic factors related to GlycA that may modulate theselevels.
Abstract MP28: The Association Between the Saliva Microbiome and Biomarkers of Cardiometabolic Disease in ORIGINS
Authors: Bohn Bruno , Roy Sumith , Marotz Clarisse , Knight Rob , Rosenbaum Michael , Paster Bruce , Yuzefpolskaya Melana , Colombo Paolo C , Papapanou Panos , Desvarieux Moise , Jacobs David R , Demmer Ryan
Published: March 2023

Introduction:
The present study sought to characterize taxonomic and functional characteristics of the saliva microbiome and their cross-sectional association with cardiometabolic biomarkers.

Hypothesis:
Features of the saliva microbiome will be associated with cardiometabolic risk.

Methods:
Saliva microbiome composition from 265 ORIGINS participants was defined with 16S rRNA sequencing (Illumina, DADA2). Functional composition (KEGG orthologs; KOs) was inferred with PICRUSt2. Alpha Diversity was computed with the Shannon Index. Blood pressure was defined as normal (SBP<120, DBP<80, and no antihypertensive medication) vs elevated/high (hypertension: SBP≥120, DBP≥80 and/or antihypertensive medication). Prediabetes was defined as 5.7≤HbA1≤6.4% or 100≤fasting plasma glucose≤125 mg/dL. HOMA-IR was calculated from insulin and glucose. HOMA-IR and CRP were dichotomized as high/low using thresholds of 3 mg/L and 1.9, respectively. Multivariable multinomial regression with cross-validation was conducted for each feature (species, KOs) and outcome, ranking regression coefficients from most positively to most inversely associated features. Microbiota and KO ratios (Micro-R, KO-R) were computed as the log-ratio of the sum of abundances of taxa/KOs in the top vs bottom tertiles of cross-validated ranks, such that higher ratios are potentially adverse. Adjusted multivariable logistic regressions produced ORs summarizing the association between Shannon, Micro-R, and KO-R and each cardiometabolic outcome.

Results:
Participants were 71% female, 22% Black, 40% Hispanic, and 18% white, with mean age of 33±10 years. Prevalence of hypertension was 36%, prediabetes was 17%, high CRP was 23%, and high HOMA-IR was 25%. Estimated ORs for the association between microbiome metrics and cardiometabolic outcomes are summarized in Figure 1.

Conclusion:
Microbiome scores based on specific taxa or KOs are associated with hypertension, prediabetes, and increased inflammation and insulin resistance.
Abstract MP31: Serum Metabolite Signatures for Metabolic Healthy and Unhealthy Obesity: The Bogalusa Heart Study
Authors: Li Changwei , Huang Zhijie , Sun Xiao , Pan Yang , Chen Jing , Kelly Tanika N , Li Shengxu , Chen Wei , Bazzano Lydia A , He Jiang
Published: March 2023

Introduction:
Mechanisms for metabolically healthy obesity (MHO) are not well studied.

Methods:
We performed cross-sectional analyses among 1,261 participants of the Bogalusa Heart Study 2013-2016 survey. A total of 887 known serum metabolites were profiled using an untargeted approach. Participants who met all the following five criteria were considered metabolically healthy, otherwise, unhealthy: 1) SBP <130 mm Hg and DBP <85 mm Hg; 2) fasting glucose <100 mg/dl; 3) triglycerides <150 mg/dl; 4) HDL ≥40 mg/dl in men and ≥50 mg/dl in women; and 5) not taking medications for hypertension, diabetes, or dyslipidemia. We tested associations of metabolites with metabolic health status, controlling for age, sex, race, education, smoking, drinking, and kidney function.

Results:
Among 648 obese participants (BMI≥30 kg/m
2
), 66 (10.2%) had MHO. After Bonferroni correction, 26 metabolites differed between MHO and metabolically unhealthy obesity (MUO) groups. Amino acids
serine
,
glycine,
and
histidine
, fatty acid
N-linoleoylserine
, 4 sphingolipids, and 3 plasmalogens were significantly higher among MHO individuals. These metabolites are functionally relevant to metabolic health (
Table
). Carbohydrates
mannose
,
lactate,
and
pyruvate
,
urate
, amino acids
glutamate
,
1-carboxyethylvaline
,
1-carboxyethylleucine
,
3-methyl-2-oxovalerate
, and
3-methyl-2-oxobutyrate
,
PE(18:0/18:2(9Z,12Z))
, and 5 diacylglycerols were significantly higher in the MUO group. These metabolites are mostly food additives or reduce gut microbiota diversity (
Table
). Furthermore,
histidine
was associated with metabolic health only among overweight and obese participants. Odds ratios of being metabolically healthy per SD increase of
histidine
among normal weight, overweight, and obese participants were 1.05 (95% CI: 0.83-1.32), 1.54 (95% CI: 1.10-2.14), and 2.12 (95% CI: 1.56-2.89), respectively (P for group difference=1.41E-4).

Conclusion:
We identified potential intervention targets to improve metabolic health in obesity.
Abstract MP33: Increases in the Ratio of Waist Circumference-Decile to Body Mass Index-Decile With Age: Findings From the National Health and Nutrition Examination Survey
Authors: Reges Orna , Test Tsafnat , Gaidishev Ira , Beshari Limor , Aharoni Shiraz , Greenberg Rinat , Melichov Maxim , Dicker Dror , Karpati Tomas
Published: March 2023

Introduction:
The predictive capability of waist circumference (WC) and body mass index (BMI) in cardiometabolic risk is well known. Both indices increase with age, yet the changes in WC relative to BMI, especially for a given BMI category, are not fully understand. This study aimed to assess changes with increasing age, of the ratio of WC-decile to BMI-decile (WC-d/BMI-d), stratified by sex and BMI categories.

Hypothesis:
WC-d/BMI-d increases with age, with significant differences within sex and BMI categories.

Methods:
For 29,256 participants (mean age: 47.8 years, 51% women) of the National Health and Nutrition Examination Survey during 2008-2017, WC-d and BMI-d (range 1-10 for both) were defined, and WC-d/BMI-d was calculated. Multivariable linear regression was used to assess the independent association of age with WC-d/BMI-d. The model was adjusted for sex, ethnicity, and comorbidities. The interaction terms
age x sex
and
age x BMI category
were incorporated into the model. Separate models were applied for males, females, and BMI categories.

Results:
In multivariable linear regression, WC-d/BMI-d increased with age among the total study population (0.006, p<0.001); and the interaction terms
age x sex
and
age x BMI-category
were significant (p<0.001for both). The increasing trend of WC-d/BMI-d with age was significant for males (0.008, p<0.001), females (0.004, p<0.001), and the BMI groups examined (normgal weight: 0.011, p<0.001, overweight: 0.007, p<0.001, and obesity: 0.002, p<0.001). Greater increases were found among males (Figure 1A) and among individuals with normal BMI level (Figure 1B).

Conclusion:
The increase in WC-d/BMI-d with age reflects a steeper increase in WC than in BMI, with greater changes among males and among individuals with normal BMI level. These results emphasize the importance of WC measurement in clinical practice, especially among males and individuals with normal BMI. It is worth considering WC-d/BMI-d as an additional measure in obesity management among adults.
Abstract MP34: Non-Alcoholic Fatty Liver Disease Modifies the Associations of Body Mass Index and Waist Circumference With Changes in Cardiometabolic Risk: The Cardia Study
Authors: Mathew Mahesh , Pereira Mark A , Pope Zachary C , Schreiner Pamela J , Jacobs David R , Terry James G , VanWagner Lisa B
Published: March 2023

Introduction:
Non-alcoholic fatty liver disease (NAFLD) is often unrecognized and untreated despite its high prevalence (~25% of adults) and implications for cardiometabolic diseases. We examined the potential for NAFLD to modify the associations between BMI and waist circumference (WC) with changes in cardiometabolic risk.

Hypothesis:
The associations of BMI and WC with CMR risk are modified by NAFLD.

Methods:
We analyzed data from Years 25 (2010/11) and 30 (2015/6) of the CARDIA cohort. NAFLD status was determined by noncontrast CT with a liver attenuation cut-off <51 HU after exclusions for other causes of liver fat. The outcome was 5-yr change in cardiometabolic risk score (CMR) derived by the mean Z-score score of fasting glucose, insulin, triglycerides [log], (-)HDL cholesterol, and systolic blood pressure. BMI and WC were directly assessed, and covariates included age, sex, race, center, education, smoking, alcohol, and medications for diabetes or CVD, and Year 25 CMR. Multivariable linear regression models included NAFLD status, BMI, and WC as the independent variables. Effect modification was assessed by interaction terms between NAFLD and continuous BMI and WC in separate models. Subsequent models were stratified by NAFLD status.

Results:
Our final sample size was 2366 (mean age: 50.1 y, males: 42.6%, Black race: 47.2%) with a NAFLD prevalence of 23% (n=539). Year 25 mean (± sd) CMR for those with and without NAFLD was -0.21 ± 0.58 and 0.50 ± 0.60, respectively. NAFLD status considerably modified the association of both BMI (interaction p<0.001) and WC (interaction p=0.002) with CMR change. BMI and WC were more strongly associated with CMR in participants
without
NAFLD compared to those
with
NAFLD (see Table). Within each BMI and WC category, CMR change was higher for those with NAFLD relative to those without NAFLD.

Conclusion:
NAFLD status modifies the association between BMI and WC with CMR changes. These findings have implications for routine clinical screening guidelines and risk stratification.
Abstract MP38: Higher Childhood Cardiovascular Risk Score is Associated With Worse Physical, Social and Emotional Functioning in Adulthood
Authors: Woo Jessica G , Bazzano Lydia A , Urbina Elaine M
Published: March 2023

Introduction:
Childhood cardiovascular risk factors have been associated with increased risk of adult cardiovascular disease, but how they are associated with adult physical, emotional and social functioning is not well understood.

Hypothesis:
We addressed the hypothesis that the International Childhood Cardiovascular Cohort (i3C) Consortium childhood risk score would be associated with worse physical, social and emotional functioning in adulthood.

Methods:
The i3C childhood combined risk score is the average of five childhood risk factors (body mass index, systolic blood pressure, youth smoking, total cholesterol and triglycerides) on the z-score scale. Self-reported measures of physical (e.g., pain, functioning, fatigue), social (e.g., social isolation, satisfaction with social role) and emotional functioning (e.g., anxiety, depression) were assessed in adulthood in a subset of two i3C cohorts, the NHLBI Growth and Health Study (NGHS) and the Princeton Lipid Research Study (PLRS). Potential covariates included cohort (as a proxy for age, given no overlap in ages between cohorts), sex, race (Black vs. White), own education, parental education, marital status, and self-reported hypertension, diabetes and cancer. Interactions between the i3C risk score and cohort (age) were evaluated.

Results:
Ninety-two NGHS (100% female, 46% Black, mean±SD age 44.5±0.6 years) and 75 PLRS (77% female, 31% Black, 60.6±3.4 years) participants were included in analyses. In adjusted models, a higher i3C risk score was associated with worse physical functioning, global pain score, pain interference with everyday activities, and fatigue in the older PLRS participants, but only with global pain score in the younger NGHS participants (all p[int]<0.05 except global pain). Higher i3C childhood risk score was associated with greater sleep-related impairment in PLRS, but with less impairment in NGHS participants (p[int]=0.03). Higher i3C childhood risk score was also associated with higher depression scores and less satisfaction with social roles in PLRS participants but not NGHS participants (p[int]=0.02 and 0.04, respectively). There was no significant relationship of i3C risk score with sleep quality, friendships, social isolation or anxiety.

Conclusions:
In conclusion, higher childhood cardiovascular risk factors are associated with worse physical, social and emotional health in adulthood, even in this limited sample of predominantly Black and White women followed from childhood. These effects are more prominent in older than younger adults, when issues such as pain and sleep problems become more prevalent.
Abstract MP44: Cardiovascular and Behavioral Correlates of Restless Leg Syndrome in the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Carnethon Mercedes R , Wong Mandy , Alexandria Shaina , Abbott Sabra , Chirinos Diana , Thomas S. Justin , Lewis Cora E , Feliciano Elizabeth C , Sidney Stephen , Schreiner Pamela J , Knutson Kristen
Published: March 2023

Background:
Restless Legs Syndrome (RLS) is a neurological condition characterized by uncomfortable sensations in the legs at rest that leads to sleep disruption and impaired quality of life. Correlates of RLS in prior studies are inconsistent but include many correlates of cardiovascular disease (CVD) risk factors. The objective of our study is to describe the burden and correlates of RLS in an epidemiological study of middle-aged adults.

Methods:
Participants in the CARDIA study completed the Cambridge-Hopkins RLS questionnaire between 2020-2022. Sociodemographic characteristics, cigarette smoking, physical activity, alcohol intake, depressive symptoms, parity and menopausal status were determined based on self-report. Waist circumference, body mass index (BMI) and blood pressure were measured using standard procedures. Serum glucose and creatinine were measured in fasting samples. A spot urine collection was used to determine urinary albumin and creatinine. Hypertension and diabetes were determined based on current clinical guidelines. We carried out univariate and multivariable logistic regression modeling to identify correlates associated with RLS.

Results:
In 2337 CARDA participants (44% Black and 60% female) with a mean age of 55.2 years old (SD=3.6), 120 (5.5%) participants (white women=78, black women=12, white men=26 and black men=4) endorsed symptoms of RLS. White participants and females were significantly more likely to endorse having RLS (Table). Health behaviors assessed in our study were not associated with RLS; however, the presence of diabetes and markers of adverse kidney function (i.e., serum creatinine, ACR) were associated with a higher odds of RLS and these associations persisted in a multivariable model.

Conclusion:
Metabolic disorders that lead to microvascular and peripheral nerve damage were associated with RLS in this sample. Future research should investigate whether RLS and peripheral neuropathy are overlapping conditions.
Abstract MP47: Sleep Disordered Breathing is Adversely Associated With Cardiac Autonomic Modulation in Adolescents
Authors: Fernandez-Mendoza Julio , Isely Alexis M , Morales-Ghinaglia Natasha , He Fan , Calhoun Susan , Liao Jason , Vgontzas Alexandros , Liao Duanping , Bixler Edward O
Published: March 2023

Introduction:
Sleep disordered breathing (SDB), as measured by the apnea/hypopnea index (AHI), is a known risk factor for cardiovascular disease (CVD) in adults. Although SDB is prevalent in pediatric populations, there has been less focus on SDB as a primary risk factor for CVD in youth. The recent AHA scientific statement on SDB and CVD in children and adolescents suggests that, in order to better understand the long-term CVD-related risk associated with SDB in youth, additional longitudinal studies incorporating noninvasive markers of CVD are needed. The current study aimed to fill this important gap.

Hypothesis:
We hypothesized that SDB is associated with decreased HRV in adolescents.

Methods:
We studied 421 subjects from the Penn State Child Cohort who were 8.7 (1.7) years old at baseline and were followed-up as adolescents 16.5 (2.3) years old. We estimated the AHI from 9-hour, in-lab polysomnography (PSG), and frequency and time-domain heart rate variability (HRV) indices from 24-h Holter EKG monitoring immediately following PSG. We stratified 24-h HRV data into daytime and nighttime periods. Linear regression analyses examined the association between AHI with 24-h HRV indices, while adjusting for age, sex, race/ethnicity, BMI percentile, and metabolic syndrome (MetS) score in adolescence as well as AHI and nighttime HRV indices in childhood.

Results:
While there were no significant associations between AHI and daytime (p=0.233) or nighttime (p=0.147) HR, there were significant associations with frequency and time-domain HRV indices. A higher AHI was associated with lower Log-HF, Log-LF, SDNN and RMSSD, yet higher LF/HF, for both daytime and nighttime periods (all p<0.05). For example, for each additional apnea or hypopnea per hour of sleep there was a decrease of -1.74ms (0.73) and -1.65ms (0.77) in SDNN during the daytime (p=0.018) and nighttime (p=0.033), respectively, even after adjusting for all covariates including MetS, childhood AHI and SDNN. More specifically, the 24-h SDNN of adolescents with an AHI≥5, indicative of moderate-to-severe SDB, was 10.9ms (4.4) lower than that of adolescents with an AHI=0 (p=0.014).

Conclusions:
SDB is associated with impaired cardiac autonomic balance in adolescence independently of MetS, prior SDB and prior HRV status. These data further support the role of SDB as an independent risk factor for CVD early in life.
Abstract MP48: Cross-Sectional and Prospective Associations Between Slow-Wave Sleep and Type 2 Diabetes: The Multi-Ethnic Study of Atherosclerosis
Authors: Kianersi Sina , Redline Susan , Mongraw-Chaffin Morgana , Huang Tianyi
Published: March 2023

Introduction:
Slow-wave sleep (also known as stage N3 sleep), a marker of deep restorative sleep, is implicated in the regulation of insulin resistance and glucose homeostasis and may impact cardiometabolic health.

Hypothesis:
We conducted both cross-sectional and prospective analyses to test the hypothesis that higher proportion and longer duration of N3 sleep are associated with reduced diabetes risk in older adults.

Methods:
A sub-sample of participants from the Multi-Ethnic Study of Atherosclerosis completed one-night polysomnography at Exam 5 (2010-2013) and were prospectively followed until Exam 6 (2016-2018). Continuous measures of N3 proportion (%) and duration (minutes) and their corresponding quartiles were used as primary exposures. Diabetes status was assessed in both Exams and was defined as fasting blood glucose≥126 mg/dl, HbA1c≥6.5%, antidiabetic medications use, or self-reported doctor diagnosis of diabetes. We used Modified Poisson regression to examine the cross-sectional associations of N3 proportion and duration with prevalent diabetes in Exam 5. Cox proportional hazards models were used to estimate risk of incident diabetes according to N3 measures. We sequentially adjusted for sociodemographic factors, lifestyles, adiposity measures, and multiple sleep-related factors, such as average sleep duration, apnea-hypopnea index, and insomnia symptoms.

Results:
In cross-sectional analyses (N=2,026, mean age: 69 years), diabetes prevalence was 28% (n=572). Compared to participants in the first quartile of N3 proportion (<2.0%), participants in the fourth quartile (≥15.4%) were 29% less likely to have prevalent diabetes (Prevalence ratio: 0.71; 95% CI: 0.58,0.87;
P
-trend: 0.0016]. The association was attenuated and not significant after adjusting for confounders, particularly BMI. In prospective analyses (N=1,251), there were 129 incident diabetes cases over 6,346 person-years of follow-up (mean follow-up time: 5.1 years). A curvilinear relationship was observed between N3 proportion and incident diabetes risk. The hazard ratio (95% CI) of developing diabetes versus the lowest quartile was 0.45 (0.25,0.81) for quartile 2, 0.31 (0.14,0.70) for quartile 3, and 0.30 (0.10,0.90) for quartile 4 (
P
-nonlinearity=0.0169, based on restricted cubic spline model). The association remained significant in the fully adjusted model (
P
-nonlinearity=0.0319). The results were similar for N3 duration.

Conclusions:
Higher N3 proportion and longer N3 duration were prospectively associated with lower diabetes risk in a nonlinear fashion among older American adults.
Abstract MP59: Host
LCT
Genotype Modifies the Relationship Between Milk Intake and Risk of Diabetes Partially Through the Gut Microbiome and Blood Metabolome: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Luo Kai , Chen Guochong , Xing Jiaqian , Moon Jee-Young , Wang Zheng , Yu Bing , Boerwinkle Eric , Hu Gang , Wang Tao , Knight Rob , Burk Robert , Kaplan Robert , Qi Qibin
Published: March 2023

Introduction:
The relationship between milk intake and risk of diabetes is controversial with substantial ethnical difference. Whether such difference can be partially explained by
LCT
genotype that varies by ethnical background is unknown.

Hypothesis:
Higher milk intake is associated with lower risk of diabetes only in lactase non-persistent (LNP) individuals (
LCT
rs4988235, GG) but not in LP individuals (AA/AG).

Methods:
We examined associations of milk intake with incident diabetes (n=7089, 768 incident cases over 6 years), 490 gut microbial species (n=1767) and 624 serum metabolites (n=3110), stratified by
LCT
genotype in US Hispanics from the HCHS/SOL. We related the identified microbial species and metabolites with metabolic traits and/or incident diabetes.

Results:
Higher milk intake was associated with lower risk of diabetes in LNP but not in LP individuals (Fig A). Milk intake was associated with different microbial species by
LCT
genotype, including 13 species specific to LNP individuals (Fig B), especially
Bifidobacterium sp.
(enriched), which were favorably associated with several metabolic traits (Fig C). In LNP individuals, milk intake was specifically associated with 20 metabolites (Fig D). Metabolites positively associated with milk, especially indolepropinate and β-cryptoxanthin, were favorably associated with metabolic traits and risk of diabetes (Fig E). Opposite patterns were found for metabolites negatively associated with milk, especially for several bile acids and branched chain amino acid metabolites (Fig E). Some of these metabolites are known microbiota related, were correlated with LNP specific milk-related bacteria, and partially mediated the milk-diabetes association in LNP individuals (Fig F). Such associations were not observed for LP specific milk-related bacteria or metabolites.

Conclusion
LCT
genotype may modify the relationship between milk intake and diabetes, with a beneficial association in LNP individuals, partially explained by gut microbiota and serum metabolites.
Abstract MP63: Higher Alternative Healthy Eating Index Scores Including Greater EPA and DHA Consumption Are Associated With Attenuated Platelet Function in the Framingham Heart Study
Authors: Pashek Robin , Nkambule Bongani , Chan Melissa , Thibord Florian , Lachapelle Amber , Cuhna Jason , Chen Ming-Huei , Jacques Paul , Ma Jiantao , Johnson Andrew
Published: March 2023

Introduction:
Dietary modification that reflects healthy eating is a notable strategy for CVD prevention on a population level. The cardioprotective role diet plays in hemostasis and thrombosis, particularly in respect to platelet function remains unclear.

Hypothesis:
Healthier Alternative Healthy Eating Index (AHEI) scores associate with attenuated platelet reactivity in a large-scale population cohort.

Methods:
Cross-sectional data was obtained from Framingham Heart Study participants (N=3,429). AHEI scores were derived from self-reported Harvard semi-quantitative food frequency questionnaires. Ranging from 0 to 110, higher AHEI scores reflect healthier overall diet quality. Five bioassays measured platelet reactivity traits across several agonists in whole blood and platelet-rich plasma samples. Linear mixed effects models adjusted for age, sex, aspirin use, family relatedness, daily energy intake, and BMI evaluated associations between platelet reactivity and AHEI scores and components.

Results:
Higher AHEI scores associated with attenuated platelet reactivity among 16 different traits (P<0.01), with notable decreased platelet aggregation to collagen, TRAP6 (PAR1 agonist), ADP, and ristocetin. Of the 11 AHEI components, higher EPA & DHA intake was most strongly associated to decreased platelet function with the greatest number of significant associations to platelet traits (18 traits, P<0.01) and moderate negative effect sizes (Figure 1).

Conclusions:
We report that higher AHEI scores associate with decreased platelet reactivity. Effects appear strongest for EPA & DHA intake consistent with several small randomized controlled trials. However, we found that a holistic AHEI score reflects a better interpretation of diet as a modulator of platelet function compared to individual components. Our results conclude that the impact of a healthier diet in preventing thrombosis may be partially mediated through a decline in platelet reactivity through multiple independent activation pathways.
Abstract MP65: Magnesium-Rich Diet Score is Inversely Associated With Incident Cardiovascular Disease: The Atherosclerosis in Communities (ARIC) Study
Authors: Copp Katherine L , Steffen Lyn M , Rebholz Casey M , Lutsey Pamela L , Yi So-Yun Y , Rooney Mary R
Published: March 2023

Background:
Numerous studies have shown inverse associations between serum magnesium (Mg) levels and risk of cardiovascular disease (CVD), but studies of dietary Mg have not been consistent.

Aim:
The association of a Mg-rich diet score with risks of incident CVD, coronary heart disease (CHD), and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study was examined.

Methods:
There were 15,022 Black and White adults without prevalent CVD included in this analysis. Diet was assessed at two visits using an interviewer-administered 66-item food frequency questionnaire. A Mg-rich diet score was created including whole grain products, nuts, fruits, vegetables, legumes, coffee, and tea. Cox proportional hazard regression evaluated the associations of incident CVD, CHD and stroke through 2019 across quintiles of Mg-rich diet score adjusted for demographic characteristics, lifestyle factors, and clinical characteristics.

Results:
Participants in the highest quintile of Mg-rich diet score compared to the lowest quintile consumed more servings of Mg-rich foods and fiber and less refined grains, red and processed meat, total fat and saturated fat. Over 30 years of follow up, a Mg-rich diet score was inversely associated with incident CVD (HR
Q5 vs Q1
=0.88, 95% CI 0.78-0.99, p
trend
=0.03) and CHD (HR=0.83, 95% CI 0.72-0.96, p
trend
=0.01); however the diet-stroke association was null (HR=1.08, 95% CI 1.07-1.09, p
trend
=0.93) (Table).

Conclusions:
Consuming a diet rich in whole grains, nuts, fruits and vegetables, legumes, coffee and tea is consistent with a lower long-term risk of CVD and CHD.
Abstract MP67: The Relationship of Cardiorespiratory Fitness, Physical Activity, and Coronary Artery Calcification to Incident Cardiovascular Disease Events in Cardia Participants
Authors: Gerber Yariv , Pettee Gabriel Kelley , Jacobs David R , Liu Jennifer Y. , Rana Jamal S , Sternfeld Barbara , Carr J. Jeffrey , Thompson Paul D. , Sidney Stephen
Published: March 2023

Introduction:
Coronary artery calcification (CAC) score, physical activity (PA), and cardiorespiratory fitness (CRF) are all associated with cardiovascular disease (CVD) risk. While a U-shaped relationship between PA and CRF with CAC has been reported, CAC presence among highly fit individuals was suggested to be benign.

Objective:
To determine interactive associations of PA/CRF and CAC with outcomes in a cohort of middle-aged adults and to evaluate the relationship of PA/CRF with CAC incidence.

Methods:
CARDIA participants with CT-assessed CAC at year 20 (2005-06) were included (n=3141, mean age 45y, 57% female, 45% Black). Moderate to vigorous intensity PA (MVPA) was assessed by self-report and accelerometer. CRF was estimated with a treadmill test. Incident CVD events were adjudicated, and mortality data were obtained through 2019. CAC was reassessed at year 25 (2010-11). Cox models assessed hazard ratios (HRs) for CVD and mortality in groups defined by CAC and MVPA/CRF. Logistic models assessed associations with CAC incidence.

Results:
At baseline, more favorable CVD risk was found among participants with higher MVPA, higher CRF (> median sex-specific duration), and absence of CAC. During a mean follow-up of 13 years, 166 CVD events and 171 deaths occurred. After multivariable adjustment, compared with no CAC and higher CRF (ref), the HRs (95% CIs) for CVD were 5.04 (2.49-10.20) for CAC and higher CRF, 2.26 (1.24-4.12) for no CAC and lower CRF, and 4.27 (2.24-8.14) for CAC and lower CRF (Figure, left panel). The respective HRs for mortality were 1.12 (0.45-2.77), 1.54 (0.91-2.60), and 3.23 (1.82-5.72) (Figure, right panel). Similar findings were observed with self-reported or accelerometer MVPA replacing CRF. Higher CRF and accelerometer MVPA were dose-responsively associated with a lower probability of developing CAC in a 5-year follow-up (P < .01).

Conclusions:
PA and CRF were inversely associated with CAC incidence in middle-aged adults. CAC presence eliminated the cardiovascular risk advantage of high PA or high CRF.
Abstract MP68: Adipokines as Mediators in the Association of Changes in Physical Activity With Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Wallace Amelia S , Ozkan Bige , Florido Roberta , Echouffo Tcheugui Justin B , Michos Erin D , NAMBI VIJAY , Aryee Ebenezer K , Hoogeveen Ron C , Ballantyne Christie M , Coresh Josef , Selvin Elizabeth , Ndumele Chiadi E
Published: March 2023

Background:
Physical activity (PA) patterns over time influence diabetes risk through incompletely understood mechanisms. Adipokines secreted by adipose tissue have myriad endocrine effects and are affected by PA. It is unknown the extent to which adipokines mediate the association between changes in PA and diabetes.

Methods:
We conducted a cross-sectional study of 10,908 ARIC participants (mean age 54; 55% female; 21% Black adults) who attended Visits 1 (V1; 1987-1989) and 3 (V3; 1993-1995) of the ARIC Study. We used mediation analyses to determine the extent to which the association of changes in PA from V1 to V3 and diabetes status at V3 was explained by adipokines. Analyses were stratified by obesity status. PA was defined using American Heart Association guidelines as inactive, intermediate, and recommended (150 minutes of moderate-vigorous activity/week); the intermediate group was further divided into low and moderate (below or above the median activity level). Participants were categorized by PA at V1 and V3 - (1) stable low: inactive or low at both visits; (2) increasing: higher category at V3 than V1; (3) decreasing: lower category at V3 than V1; and (4) stable high: moderate or high at both visits.

Results:
Increasing PA was associated with higher adiponectin and lower leptin at V3 compared to stable low PA, while decreasing PA was associated with lower adiponectin and higher leptin compared to stable high PA (p<0.01 for all comparisons). Decreasing PA was associated with 28% higher odds of diabetes compared to stable high PA (Table). Conversely, increasing PA was associated with 12% lower odds of diabetes compared to stable low PA. In mediation analyses, adjustment for leptin/adiponectin ratio explained 45% of the effect of increasing PA and 35% of the effect of decreasing PA. The directionality of associations was similar in obesity stratified analyses, but results were not statistically significant.

Conclusions:
The associations between changes in PA and diabetes may be mediated in part by adipokines.
Abstract MP71: Associations Between Physical Activity Trajectories and Nonalcoholic Fatty Liver Disease: The Cardia Study
Authors: de Brito Junia N , McDonough DJ , Mathew Mahesh , VanWagner Lisa B , Schreiner Pamela J , Pettee Gabriel Kelley , Jacobs David R , Terry James G , Jeffrey Carr John , Pereira Mark A
Published: March 2023

Introduction:
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in the US. Weight loss and lifestyle modifications, including increases in physical activity (PA), are the primary therapeutic recommendations for managing NAFLD. However, little is known about longitudinal physical activity patterns and NAFLD prevalence among a racially diverse population of adults. This study aimed to (1) identify distinct physical activity trajectories from young to middle adulthood and (2) examine the associations between physical activity trajectories and NAFLD prevalence in middle-aged adults.

Methods:
The analytic sample included 2833 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Physical activity was self-reported at eight examinations over 25 years (1985/1986 to 2010/2011), and separately scored for moderate- (MPA) and vigorous-intensity (VPA) physical activity. NAFLD was defined as liver attenuation values ≤51 Hounsfield units after exclusion of other causes of liver fat, measured using computed tomography in year 25 (2010/2011). Group-based trajectory modeling was used to identify MPA and VPA trajectories over 25 years. Modified Poisson regression models were used to estimate the risk ratios (RR) of NAFLD across the PA trajectories, adjusted for year 25 sex, age, CARDIA study center, race, education, smoking status, dietary pattern, and alcohol consumption.

Results:
We identified three distinct MPA and VPA trajectories. MPA: ‘very low stable’ (53%), ‘low stable’ (39%), and ‘moderate increasing’ (8%). VPA: ‘low stable’ (57%), ‘moderate stable’ (36%), and ‘high decreasing’ (7%). Year 25 NAFLD prevalence was 24%. Relative to participants with ‘moderate increasing’ MPA over time, those with lower levels of MPA had adjusted risk ratios of 1.11 (95% CI 0.87-1.43) for ‘low stable’ and 1.11 (95% CI 0.86-1.42) for ‘very low stable.’ Relative to participants with ‘high decreasing’ VPA over time, those with lower levels of VPA had adjusted risk ratios of 1.26 (95% CI 0.95-1.69) for ‘moderate stable’ and 1.62 (95% CI 1.21-2.16) for ‘low stable.’

Conclusions:
Our results suggest a higher risk of NAFLD in middle age for those with low levels of VPA from young to middle adulthood relative to those with the highest levels of VPA over time, with evidence of dose-response. Sustaining VPA throughout adulthood may be efficacious in the prevention of NAFLD, highlighting the importance of targeted delivery of prevention and management programs aimed at modifying lifestyle risk factors to reduce NAFLD risk.