bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P211: Response to a School-based Health Intervention in High- and Low-income Communities
Authors: Rogers Robert , Corriveau Nicole , Lee Alexander , Pew Alexandra , Wei Wen-Ching , Foti Alisa , Vuong Belinda , Kline-Rogers Eva , Jiang Qingmei , Goldberg Caren , DuRussel-Weston Jean , Eagle Kim A , Jackson Elizabeth A
Published: July 2021

Introduction:
Childhood obesity is associated with increased cardiovascular disease risk and is a major health issue in the United States. Previous studies show higher rates of obesity in low socioeconomic status (SES) communities. The efficacy of school-based interventions in these communities is not as well documented.

Hypothesis:
We hypothesized that low SES would be less healthy at baseline and show greater improvement than high SES.

Methods:
Project Healthy Schools (PHS) is a school-based intervention targeted at middle-school students in lower Michigan. We studied body mass index (BMI), blood pressure (BP), lipid profiles, resting and recovery heart rate (HR), and behavioral characteristics in 3147 middle-school students. Students were stratified into 2 groups: high SES and low SES. Ann Arbor (median family income=$53,377) students were included in the high SES cohort (n=1840) while Ypsilanti ($33,699) and Detroit ($27,862) were considered low SES (n=1307). Chi-square, Wilcoxon, and t-tests were conducted to compare baseline and baseline-to-follow-up data. Median household income was based on US Census Bureau data.

Results:
At baseline, those students in the low SES cohort performed significantly worse than the students in the high SES cohort in nearly every category, most notably: BMI, systolic and diastolic BP, resting and recovery HR, fried food consumption, exercise, and screen time. Upon follow-up, post-intervention examination, low SES improved recovery HR, screen time, fried meat and snacks, and sugary beverages significantly more than high SES. High SES improved fruit, BP, and total cholesterol significantly more than low SES.

Conclusions:
The PHS intervention was more efficacious in a number of categories in higher-risk, low SES communities. This suggests a need for the implementation of similar school-based programs in low SES areas.
Abstract P226: D-Dimer Levels and Risk of Stroke: Findings from the EPICOR Study
Authors: Di Castelnuovo Augusto , Agnoli Claudia , de Curtis Amalia , Giurdanella Maria Concetta , Grioni Sara , Mattiello Amalia , Matullo Giuseppe , Panico Salvatore , Sacerdote Carlotta , Tumino Rosario , de Gaetano Giovanni , Donati Maria Benedetta , Iacoviello Licia
Published: July 2021

Background:
Elevated D-dimer levels are reportedly associated with higher risk of vascular diseases. We investigated the association of baseline D-dimer levels with stroke events occurred in the European Prospective Investigation into Cancer and Nutrition-Italy cohort.

Methods:
Using a nested case-cohort design, a center-stratified random sample of 832 subjects (66% women, age range 35 to 71) was selected as subcohort and compared with 289 strokes in a mean follow-up of 9 years. D-dimer was measured on fresh citrated plasma by an automated latex-enhanced immunoassay (HemosIL-IL, Milan). The hazard ratios and 95% confidence intervals, adjusted by relevant confounders and stratified by center, were estimated by a Cox regression model using Prentice method.

Results:
Individuals in the second, third or fourth quartile compared with the lowest quartile of D-dimer had significantly higher risk of stroke (Table). The association was independent from several potential confounders, including C-Reactive protein (Table). It was evident starting from the second quartile (D-dimer >100 ng/ml) and persisted almost unchanged for higher D-dimer levels (Table). No differences were observed in men and women. The increase in risk was essentially the same both for ischemic and hemorrhagic strokes (Table).

Conclusions:
Our data provide a clear evidence that elevated levels of D-dimer are potential risk factors for ischemic or hemorrhagic strokes.
Abstract P234: Diabetes as Risk Factor for Coronary Heart Disease in Women Compared with Men
Authors: Peters Sanne A , Huxley Rachel R , Woodward Mark
Published: July 2021

Introduction:
A previous pooled analysis suggested that women with diabetes are at substantially increased risk of fatal coronary heart disease (CHD) compared with affected men. Additional findings from larger and more contemporary studies have since published on the sex-specific associations between diabetes and incident CHD. We performed a systematic review with meta-analysis so as to provide the most reliable evidence of any sex difference in the effect of diabetes on subsequent risk of CHD.

Methods:
PubMed MEDLINE was systematically searched for prospective population-based cohort studies published between on January 1, 1966 and February 13, 2013. Eligible studies had to have reported sex-specific estimates of the relative risk (RR) for incident CHD associated with diabetes, and its associated variability. Random effects meta-analyses with inverse variance weighting were used to obtain sex-specific RRs and their ratio (RRR).

Results:
Data from 64 cohorts including 858,507 individuals and 28,203 incident CHD events were included. The RR for incident CHD associated with diabetes compared with no diabetes was 2.83 (95% confidence interval [CI]: 2.37, 3.38) in women and 2.11 (95% CI: 1.79, 2.50) in men. The multiple-adjusted RRR for incident CHD was 44% greater in women with diabetes than it was in men with diabetes (95% CI: 27; 63) with no significant heterogeneity between studies (I2=20%).

Conclusions:
Women with diabetes have more than a 40% greater risk of incident CHD compared with men with diabetes. Sex disparities in pharmacotherapy are unlikely to explain the excess risk in women. Instead, a greater deterioration in cardiovascular risk profile combined with more prolonged exposure to adverse levels of cardiovascular risk factors among pre-diabetic women compared with their male equivalents may be responsible for the excess risk of diabetes-related CHD in women. Future studies are warranted elucidate the mechanisms responsible for the substantial sex-difference in diabetes-related risk of CHD.
Abstract P235: Association of Lipid Related Genetic Variants and Hypertriglyceridemia in Type 2 Diabetic Patients from a Chinese Population
Authors: Kong Xiaomu , Zhang Xuelian , Zhao Qi , He Jiang , Chen Li , Zhao Zhigang , Li Qiang , Ge Jiapu , Chen Gang , Guo Xiaohui , Lu Juming , Weng Jianping , Jia Weiping , Ji Linong , Xiao Jianzhong , Shan Zhongyan , Liu Jie , Tian Haoming , Ji Qiuhe , Zhu Dalong , Zhou Zhiguang , Shan Guangliang , Yang Wenying
Published: July 2021

Previous studies have showed that hypertriglyceridemia may be a stronger risk factor for coronary heart disease in diabetic patients than non-diabetic individuals. Multiple genomic loci have been identified to be associated with lipid levels among general populations by genome-wide association studies. It is unclear about their effects on lipid levels among type 2 diabetes (T2D) patients. The present study aimed to investigate the associations of lipid related genomic loci and hypertriglyceridemia (defined as triglycerides ≥ 1.70mmol/L or taking lipid-lowering medications) among 5,338 T2D patients from China. We genotyped 9 single nucleotide polymorphisms (SNPs) within or near
ABCA1
,
DOCK7
,
TOMM40
,
GCKR
,
HNF1A
,
HNF4A
,
LDLR
,
BAZ1B
and
BUD13
genes. Under an additive genetic model, logistic and linear regression models were used to examine the associations of these genomic loci with hypertriglyceridemia and the triglycerides level (among 4,908 individuals without taking any lipid-lowering medications) with adjustment for age, sex, and body mass index, respectively. Five SNPs near
ABCA1
(rs3890182),
TOMM40
(rs157580),
GCKR
(rs780094),
BAZ1B
(rs2240466) and
BUD13
(rs28927680) genes were significantly associated with hypertriglyceridemia among T2D patients (OR [95% CI] = 0.79 [0.67, 0.93] for per A allele of rs3890182,
P
= 4.03х10
-3
; 1.13 [1.04, 1.22] for per A allele of rs157580,
P
= 2.81х10
-3
; 0.87 [0.80, 0.94] for per G allele of rs780094,
P
= 4.26х10
-4
; 0.77 [0.68, 0.87] for per T allele of rs2240466,
P
= 1.28х10
-5
; 3.83 [1.39, 10.50] for per C allele of rs28927680,
P
= 9.27х10
-3
). Six SNPs within or near
ABCA1
,
GCKR
,
BAZ1B
, TOMM40
,
HNF1A
and
LDLR
were significantly associated with the triglycerides level. For example, minor alleles of
GCKR
and
BAZ1B
were associated with lower triglycerides level (β [SE] = -0.025 [0.005] for per G allele of rs780094,
P
= 7.88х10
-7
; -0.035 [0.007] for per T allele of rs2240466,
P
= 2.03х10
-6
). To test the robustness of these findings, we conducted a sensitivity analysis to only include newly diagnosed T2D patients (2,646 out of 4,908 patients without taking any lipid-lowering medications). The associations between
ABCA1,
TOMM40
,
GCKR
and
BAZ1B
with hypertriglyceridemia maintained significant (
P
value ranged from 7.79х10
-4
to 1.29х10
-2
), as well as their associations with the triglycerides level (
P
value ranged from 2.76х10
-5
to 2.89х10
-2
). In conclusion, our study provides the first data for the effects of lipid-related genomic loci on hypertriglyceridemia and the triglycerides level among T2D patients of the Chinese population. Further studies were warranted to replicate these findings.
Abstract P237: Improved Cardio-metabolic Risk Profile through Targeted Life Style Modification Program
Authors: Das Sankalp , Rouseff Maribeth , Tran Thinh H , Nasir Khurram , Bou-Khalil Josette , Mora Joseph , Guzman Henry , Brown Doris , Santiago-Charles Joann , Ochoa Teresa C , Gilliam Cynthia , Lehn Virginia , Castillo Beatriz , Aneni Ehimen , Roberson Lara , Veledar Emir , Oni Ebenezer , Post Janisse
Published: July 2021

Introduction:
Workplace wellness programs are part of the American Heart Association’s (AHA) strategy at improving cardiovascular health. Data suggest that most cost and risk borne by employers is with metabolic syndrome (MS). The current study aimed to ascertain the primary to short-term (12 weeks) efficacy of a lifestyle intervention improvement program (My Unlimited Potential (myUP), among employees of a health care system in improving metabolic status as well as associated degree of vascular inflammation as measured by high sensitivity C-reactive protein (hs-CRP).

Methods:
The MyUP enrolled high risk individuals with at least 2 of the following cardio-metabolic risk factors, total cholesterol ≥ 200 mg/dl, systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, hemoglobin A1C ≥ 6.5%, and body mass index (BMI) ≥ 30. Improvement in cardio-metabolic risk was assessed by the change in number of metabolic risk components and C-reactive protein (CRP) from baseline to 12 week follow-up.

Results:
Overall 203 (48±10 years, 78% females) employees were enrolled. The retention of subjects was high with 89% (n=181) of subjects following up at 12 weeks. There were significant changes in the distribution of the number of components of the metabolic syndrome from baseline to 12 weeks follow up, see figure 1. Overall only 25% met criteria for MS at 12 week as compared to 48% at baseline. There were changes in the overall median hsCRP at 12 weeks follow-up compared to baseline, 3.6(1.8-7.9) vs. 4.4(2.0-8.4). We also noticed improvement in median hs-CRP levels across the categories of improving metabolic risk factors. Among individuals who had improvement in 1-2 MS risk factors, the median hsCRP at follow-up compared to baseline was 4.6(2.2-8.8) vs. 5.2(2.7-8.9) p=0.6090 and those with improvements in >2 MS components it was 3.3(2.5-5.3) vs. 5.0(3.5-7.14) p=0.1614.

Conclusion:
Measurable cardio-metabolic risk reduction was achieved, benefiting participant of a targeted Life style modification intervention program.
Abstract P240: Increased Aerobic Fitness is associated with Cardiometabolic Risk Reduction in a High Cardiovascular Disease Risk Occupational Cohort Independent of Significant Weight Loss
Authors: Aneni Ehimen C , Oni Ebenezer , Roberson Lara , Rouseff Maribeth , Guzman Henry , Tran Thinh H , Das Sankalp , Brown Doris , Santiago-Charles Joann , Ochoa Teresa C , Mora Joseph , Gilliam Cynthia , Lehn Virginia , Bou-Khalil Josette , Castillo Beatriz , Veledar Emir , Feldman Theodore , Agatston Arthur S , Post Janisse , Nasir Khurram
Published: July 2021

Background:
Studies have demonstrated that improving physical fitness is associated with weight loss and improvement in cardio-metabolic risk profile. However, the effect of improvement in aerobic fitness on metabolic risk in the absence of significant weight loss in a high risk working population is poorly understood. We examined efficacy of both weight reduction and increased aerobic fitness on metabolic syndrome in an ongoing multicomponent lifestyle intervention improvement program (My Unlimited Potential (myUP)), among employees of Baptist Health South Florida (BHSF).

Methods:
The study population included 158 participants who had at least 2 metabolic risk factors at baseline. An advanced nurse practitioner, registered dietician, exercise physiologist, certified diabetic educator, and registered nurse met with participants to provide one-on-one counseling and fitness training. During the first 12 weeks the multidisciplinary team rigorously supervised participants.

Results:
Over the 12 week period, there was a significant increase in METS (median difference 2.7; IQR 1.4 to 3.4 p<0.001). Over the same period the prevalence of metabolic syndrome reduced from 48% to 25% (p <0.001). The increase in METS was greater among those with significant weight loss defined as weight loss at least 5% of baseline body weight (median difference = 1.30, P<0.001). In a fully adjusted logistic regression model, there was markedly significant reduction in the risk of metabolic syndrome at 3 months among those who had shown improvements in fitness alone (OR 0.15, p=0.025) and among those who had both improvements in fitness and significant weight loss (OR 0.14, p=0.030).

Conclusion:
Improvements in respiratory fitness as can be seen with exercise, even in the absence of significant weight loss, is associated with significant reduction in cardiometabolic risk. In an intensive lifestyle modification interventional program aimed at CVD risk reduction, emphasis should be placed at increasing physical fitness, not only on weight loss.
Abstract P241: The Impact of Dietary and Metabolic Risk Factors on Cardiovascular Diseases and Type 2 Diabetes in Brazil
Authors: de Oliveira Otto Marcia C , Micha Renata , Khatibzadeh Shahab , Singh Gitanjali , Afshin Ashkan , Fahimi Saman , Danaei Goodarz , Mozaffarian Dariush
Published: July 2021

Background:
Brazil, the 5th largest country in the world, is undergoing a nutrition transition toward unhealthy diets and greater incidence of cardiometabolic diseases (CM). However, little is known about the quantitative impact of major dietary and metabolic risk factors on current burdens of CVD and diabetes in Brazil.

Aims:
To quantify using consistent and comparable methods the CVD and diabetes mortality attributable to suboptimal diet and metabolic factors in Brazil.

Methods:
Based on data from 2010 Global Burden of Disease Study, we used a comparative risk assessment framework to develop consistent and comparable methods to identify dietary and metabolic risk factors with evidence for etiologic effects on CVD and diabetes; estimate current national intake levels and their uncertainty, by age and sex; quantify etiologic effects of each diet-disease relationship, by age; and characterize optimal consumption levels. We combined these inputs with national data on disease-specific deaths to estimate overall burdens attributable to each dietary factor, and by age, sex, and disease. We quantified uncertainty using probabilistic simulation analyses, incorporating uncertainty in dietary exposure data and etiologic effects by age, and sex. Missing exposure data was imputed using a multi-level hierarchical Bayesian model based on non-missing exposure data from other regions. Robustness of findings was evaluated by sensitivity to varying inputs including effect sizes and feasible optimal levels.

Results:
Among dietary factors, low intake of fruits and whole grains had highest impacts on CM mortality, each responsible for ~12% of total CM deaths (62,800 and 61,400 deaths, respectively) (Figure). Hypertension and high fasting plasma glucose were responsible for 32% (163,000) and 28% (141,700) of CM deaths respectively. Other dietary and metabolic risk factors also caused substantial numbers of deaths among Brazilians.

Conclusion:
Our findings inform priorities for policy measures to reduce CVD and diabetes in Brazil.
Abstract P242: Abdominal Adipose Tissue Distribution and Metabolic Syndrome Burden in Adolescents - Penn State Child Cohort (PSCC) Study
Authors: Liao Duanping , He Fan , Rodriguez-Colon Sol , Fernandez-Mendoza Julio , Vgontzas Alexandros , Bixler Edward O
Published: July 2021

Objectives:
To investigate the association between abdominal adipose tissue distribution and metabolic syndrome burden in a population-based sample of adolescents.

Methods:
We used available data from 400 adolescents who completed the follow up examinations in the PSCC study. We used whole body low-dose dual energy absorptiometry (DXA) to assess and calculate the following abdominal and body fat distribution measures: Android/Gynoid Fat ratio, Android/whole body fat ratio, Gynoid/whole body fat ratio, visceral fat area, and subcutaneous fat area in the abdominal region. . Metabolic syndrome burden was assessed by using continuous metabolic syndrome score (cMetS) - the sum of the age and sex adjusted standardized residual (Z-score) of five established metabolic syndrome components: waist circumference, mean arterial pressure, homeostatic model assessment of insulin resistance (HOMA-IR), triglycerides, and HDL cholesterol. Linear regression models were used to data analysis.

Results:
The mean age was 16.9 yrs (SD=2.19), with 54% male and 77% white. The average cMets score was 0.04 SD (3.01). The regression coefficients on cMets score per one SD increase in abdominal adipose tissue measures are shown in Table 1. In summary, higher abdominal adipose tissue, especially in the android (visceral) area, of the abdomen is associated with higher cMetS score.

Conclusion:
Obesity, especially visceral obesity, is associated with higher metabolic syndrome burden in adolescent population, which may result in increased metabolic syndrome risk in adulthood.
Abstract P256: Association of Genetic Variants on the Metabochip With Urine Albumin-Creatinine Ratio in African Americans: The Population Architecture using Genomics and Epidemiology (PAGE) Study
Authors: Wassel Christina L , Wong Quenna , Li Man , Goodloe Robert J , Graff Misa , Tao Ran , Shao Yaming , Crawford Dana C , Buyske Steve , Buzkova Petra , Jenny Nancy S , Bielinski Suzette J , Pankow James S , Rich Stephen S , Chen Ida , Taylor Kent D , Mychaleckyj Josyf , Wise Anastasia , Ix Joachim H , Rifkin Dena , Junkins Heather , Fornage Myriam , Kao Linda , North Kari E , Franceschini Nora
Published: July 2021

Several loci have been discovered and replicated for urine albumin-creatinine ratio (ACR), a measure of kidney function, in European populations; however, other ethnic populations such as African-Americans have been less studied for this trait. We examined the association of genetic variants on the Metabochip with natural log transformed ACR (ln(ACR)) in 4,629 African-Americans from the Population Architecture using Genomics and Epidemiology (PAGE) Study which includes participants from the Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health Study (CHS), Coronary Artery Risk Development in Young Adults (CARDIA), and Epidemiologic Architecture for Genes Linked to the Environment (EAGLE-BioVU) studies. We then replicated our findings in 1,533 African-American participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Linear regression models were used to examine associations, assuming additive effects of the SNPs. Within each study, models were adjusted for age, field center (where applicable), and principal components of ancestry, and stratified by sex. Fixed effects inverse variance weighted meta-analysis was used to combine results from contributing studies. Array-wide statistical significance was concluded for SNP associations of p-value less than 2.8 x 10-7. Mean ln(ACR) ranged from 1.4 to 2.9 mg/g, average age ranged from 44 to 77 years, and percent female participants ranged from 59-65% in the contributing studies. Four SNPs were significantly associated array-wide with ACR in the discovery sample: rs17399841 in GRHL2 (β=-0.67, MAF=0.01, p=2.7x10-9), rs153914 near SPATA9/RHOBTB3 (β=-0.59, MAF=0.01, p=1.0x10-7), rs17439845 in LEF1 (β=-0.49, MAF=0.02, p=1.3x10-7), and rs11836243 near ZNF641/ANP32D (β=0.23, MAF=0.12, p=1.8x10-7). Of these four loci, only the association of rs17439845 with ACR replicated in MESA (β=-0.36, p=0.038), with a combined discovery-replication beta of -0.46 and p value of 1.8x10-8. Combined discovery-replication for rs17399841, rs153914, and rs11836243 no longer achieved array-wide significance (p-values 9.84x10-7, 1.98x10-5, and 1.32x10-4, respectively). LEF1 is a mediator in the Wnt signaling pathway, and has been previously implicated in systemic lupus erythematosus and osteoporosis, as well as previously associated with waist circumference, echocardiographic traits, bone mineral density, and blood count traits. Continuing studies in diverse populations are warranted to identify a set of loci important in contributing to the variation in ACR.
Abstract P260: Genome-wide Pathway and Network-based Approaches Identify Novel Genetic Loci and Pathways for Cardiovascular Disease and Diabetes in an Ethnically Diverse Cohort of American Women
Authors: Chan Kei Hang K , Huang Yen-Tsung , Hsu Yi-Hsiang , Song Yiqing , Hevener Andrea , Meng Qingying , Wu Chunyuan , Reiner Alexander , Sobel Eric M , Tinker Lesley , Yang Xia , Liu Simin
Published: July 2021

Introduction:
Despite the success of recent genome-wide association studies (GWAS) in identifying genetic loci associated with cardiovascular disease (CVD) and diabetes (T2D), a comprehensive examination of GWAS data for identifying biological pathways underlying their specific or shared genetic mechanisms is lacking, especially in an ethnicity-specific manner.

Hypothesis:
We hypothesized that genetic variation clustered in biological pathways is associated with an increased risk of CVD and T2D.

Methods:
We applied a pathway and network-based approach to characterize GWAS signals in sets of biological pathways for their contribution to CVD and T2D in two separate nation-wide populations of ethnically diverse women from the Women’s Health Initiative (WHI) Cohort, the WHI SNP Health Association Resource(WHI-SHARe) and the Genomics and Randomized Trials Network(WHI-GARNET), involving 8,155 African American, 3,494 Hispanic American, and 3,697 Caucasian American women.

Results:
Eight pathways were identified to be significantly enriched for CVD, T2D, and combined CVD and T2D across the three ethnic groups at false discovery rate <0.001, including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, calcium signaling pathway, axon guidance, cell adhesion molecules, focal adhesion, and ECM-receptor interaction pathways. We also identified disease- and ethnicity-specific pathways, such as cell cycle (specific for Hispanic and Caucasian Americans) and tight junction (CVD and combined CVD + T2D in Hispanic Americans).

Conclusions:
By applying pathway- and network-based analyses to two large GWAS from three ethnic groups of American women, we identified shared biological pathways for CVD and T2D and disease- and ethnicity-specific pathways. These results provide evidence for multiple pathways underlying the pathogenesis of CVD and T2D in three genetically distinct populations and implicate the complex etiology of cardiometabolic disease.
Abstract P261: Methylation Status of VKORC1 and Warfarin Dose
Authors: Finkelman Brian S , Bershaw Luanne , Chen Jinbo , Brensinger Colleen M , Li Ron C , Kimmel Stephen E
Published: July 2021

Introduction:
It is well known that genetic variants, especially in the
VKORC1
and
CYP2C9
genes, can be associated with warfarin maintenance dose. However, currently known genetic variants fail to explain a large portion of the observed variability in warfarin dose, especially in African American patients. Methylation is a heritable epigenetic modification in which conversion of cytosine residues within “CpG islands” to 5-methylcytosine is associated with reduced gene expression. To our knowledge, the effect of methylation status on warfarin dose has never been studied.

Hypothesis:
We hypothesized that higher rates of methylation near the start region of
VKORC1
in whole blood would be associated with lower required maintenance dose in warfarin patients.

Methods:
We conducted a prospective cohort study of patients initiating warfarin at three anticoagulation clinics. All individuals with available methylation data who reached maintenance dose were included in the analysis (N = 237). Methylation status was assessed in the region from 1500bp upstream to 500bp downstream of the
VKORC1
start site using the Sequenom EpiTYPER assay on DNA extracted from whole blood. Linear regression was used to assess the association between methylation levels at individual CpG sites (66 total) and required warfarin maintenance dose. Visual inspection of univariable results was used to identify potentially important CpG clusters, which were subsequently examined using univariable and multivariable linear regression, with the latter adjusting for the effects of race, presence of
VKORC1
variant, and other well-known predictors of warfarin dose.

Results:
Two of 66 CpG sites were nominally associated with lower maintenance dose requirement on univariable analysis. These CpG sites were identified as part of a CpG cluster located approximately 330 to 226bp upstream of the
VKORC1
start site. Median methylation levels in this cluster was 16% (IQR 15%, 17%). A 1% increase in methylation in this cluster was associated with a 2.8 mg/wk reduction in weekly warfarin maintenance dose (P = 0.02). No significant interaction between methylation status and African American race was observed (P = 0.77). This association was substantially attenuated with the inclusion of
VKORC1
variant status in the model (P = 0.33).

Conclusions:
Preliminary evidence suggests that methylation levels in a CpG cluster in
VKORC1
may be moderately associated with warfarin maintenance dose, although this association may not be independent of
VKORC1
variant status. However, these results require confirmation from additional epidemiological studies and possibly functional assays in liver tissue.
Abstract P262: Evidence for association between SH2B1 gene variants and glycated hemoglobin in non-diabetic European American young adults: The Add Health study
Authors: Lange Leslie A , Graff Misa , Lange Ethan M , Young Kristin M , Harris Kathleen M , Richardson Andrea S , Mohlke Karen L , North Kari E , Gordon Larsen Penny
Published: July 2021

Introduction:
Glycated hemoglobin (HbA1c) is a marker of long-term glycemic control, and elevated HbA1c is a risk factor for type 2 diabetes and cardiovascular disease. Few genome-wide association studies(GWAS) have been performed for HbA1c, although very large scale GWAS for obesity, a related trait, have identified multiple loci that have been widely replicated. We tested 43 single nucleotide polymorphisms (SNPs) from 41 well-established obesity susceptibility gene regions for association with HbA1c in a nationally representative sample of European American (EA), African American (AA) and Hispanic American (HA) young adults.

Methods:
We performed association analysis in race-stratified models using data from participants (age 24-34 years, median age=28 years) from the National Longitudinal Study of Adolescent Health (Add Health) Study (n = 5641 EA; n = 1740 AA; n = 1444 HA) without type 2 diabetes. We tested for additive genotype effects at each locus using linear mixed models, including a random intercept for school and family clusters, and two levels of covariate adjustment (model 1: age, sex, smoking, and geographic region; model 2: model 1 covariates plus BMI). We used Bonferroni adjustment for 43 SNPs and considered P < 0.0011 to be statistically significant.

Results:
Means (SD) for HbA1c % across the sample were 5.4(0.3) in EA, 5.7(0.4) in AA, and 5.5(0.3) in HA. We observed significant evidence for association with HbA1c for two SNPs near
SH2B1
in EAs (rs4788102, P = 2.2x10-4; rs7359397, P = 9.8x10-4) for the model 1 adjustment, although both results were slightly attenuated after additional adjustment for BMI (rs4788102, P = 1.7x10-3; rs7359397, P = 4.6x10-3). No SNPs reached statistical significance after multiple test correction in either AAs or HAs.
SH2B1
rs4788102 was nominally significant in AAs for the BMI-adjusted model (P = 0.02), although the estimated direction of effect was in the opposite direction as that observed in EAs.

Conclusions:
These results suggest that polymorphisms in the obesity gene
SH2B1
, for which rare deletions and mutations have been observed in obese individuals with extremely high insulin resistance, are associated with HbA1c in EA young adults. Our findings further suggest these associations are largely independent of BMI.
Abstract P265: Association of Dietary Fatty Acid Intake with Serum High-density Lipoprotein Particle Concentration
Authors: Zaid Maryam , Miura Katsuyuki , Fujiyoshi Akira , Okayama Akira , Nakagawa Hideaki , Sakata Kiyomi , Saito Shigeyuki , Okuda Nagako , Yoshita Katsushi , Choudhury Sohel , Rodriguez Beatriz , Masaki Kamal , Willcox Bradley , Miyagawa Naoko , Stamler Jeremiah , Ueshima Hirotsugu
Published: July 2021

Background:
Studies have found that HDL particle (HDL-P) concentration is inversely associated with risk of CVD, independent of HDL cholesterol (HDL-C). Dietary factors (such as fatty acid intake) have been found to affect levels of HDL-C and influence risk of CVD. However, little is known about the associations of dietary fatty acid with serum HDL-P levels.

Hypothesis:
We hypothesized that dietary fatty acid associations with HDL-P are independent of HDL-C in men.

Methods:
Data were from 463 male participants in the 1996-98 cross-sectional INTERLIPID Study, ages 40-59 years, randomly selected from five populations; four in Japan (n=386) and one in Hawaii (n=77). Fatty acid intake was estimated from the mean of four in-depth 24-hour dietary recalls (% kcal per day). Individuals were excluded due to missing data on HDL-P or HDL-C and use of lipid lowering medication. Serum HDL-P was measured using nuclear magnetic resonance and HDL-C was measured using standard methods. Multiple linear regression models were used to assess the association between dietary fatty acid and each of the lipid measures.

Results:
In men, HDL-P and HDL-C were moderately correlated (r = 0.52, p<0.001). In Model 1 (Table), adjusted for age, country, alcohol intake, BMI, diabetes, hypertension, smoking status, and physical activity, most dietary fatty acids were significantly (p<0.05) associated with HDL-P and HDL-C levels. In Model 2, further adjusted for HDL-C, almost all fatty acids maintained a significant association with HDL-P. In contrast, most associations of fatty acids and HDL-C ceased to be significant after adjustment for HDL-P. Total SFA and omega-3 PUFA remained associated with HDL-C.

Conclusion:
HDL-P was significantly associated with fatty acid intake, independent of HDL-C. Associations of dietary fatty acid intake and HDL-C level were weaker and generally not independent of HDL-P in men.
Abstract P271: Relationship among Dietary Patterns, Apolipoproteins, C Reactive Protein and Other Lipids in Adult Populations in Four Cities of the Southern Cone of Latin America
Authors: Poggio Rosana , Elorriaga Natalia , Gutierrez Laura , Irazola Vilma , Rubinstein Adolfo
Published: July 2021

Background:
In the last decades, the nutrition transition in Latin America turned to diets with higher total caloric intake and lower consumption of vegetables, cereals and fruits. An unhealthy dietary pattern affects plasma levels of apolipoprotein (Apo) AI, Apo B and C-reactive protein (CRP) which are independently associated with the incidence of coronary heart disease and stroke). There is no data regarding these biomarkers in relation to dietary patterns from the Southern Cone of Latin America. Therefore the objective of this study is to analyze these biomarkers in relation to our traditional dietary patterns.

Methods:
CESCAS I study is an observational prospective cohort study with a multistage probabilistic sample of 7,600 participants from general population of 4 sites in Argentina, Chile and Uruguay. We conducted a cross-sectional analysis in a randomly selected subsample of 988 subjects. Subjects with previous cardiovascular event or under lipid lowering agents were excluded. Diet was assessed using a previously validated 126-item food frequency questionnaire. We used a factor analysis to derive the major dietary patterns by gender. Linear regression model were used to examine the independent associations among Apo AI, B, CRP, other lipids by tertiles of dietary pattern scores.

Results:
The population sample included 418 men and 570 women. Higher scores of “Prudent pattern”, characterized by intake of fruits, vegetables, low fat dairy products, fish, seafood and whole cereal was independently and significantly associated in men with the reduction of Apo B (β -4,4), low density lipoprotein (LDL) (β -7,2), Apo B/A ratio (β -0,03) and a non-significant reduction of CRP (β -0,6). In women, we observed a significant reduction in Apo B (β -1,3), LDL (β -2,1), total cholesterol (TC) /high density lipoprotein (HDL) ratio (β -0,1) and a non-significant reduction of triglycerides (β -4 mg/dl). The “Western like pattern” (WLP) was characterized by meat, processed foods, pizza, empanadas, sweets and desserts, refined grains, vegetables oils and other fats. Higher scores of WLP showed in men a non-significant increment of Apo B (β 0,7), TC/HDL ratio (β 0,1), CRP (β 0,1), LDL (β 3), triglycerides (β 1,3) and a non-significant reduction of Apo AI (β -1,7) and HDL (β -0,7). In women, we observed a significant increment of TC/HDL ratio (β 0,2) and triglycerides (β 12). We also found a non-significant increment of Apo B and LDL and to reduce HDL and CRP.

Conclusion:
Our findings confirm that diet has an important role on health. Prudent diet pattern was associated with a healthier lipid profile especially in men. The WLP showed a trend to adversely affect the lipids profile and CRP.
Abstract P274: A meta-analysis of meta-analyses: Is "reverse Epi" OK or not?
Authors: Williams Ken , Sniderman Allan D
Published: July 2021

Introduction:
Applications of observational risk models assuming “all else equal” to estimate the effect on risk of interventions expected to change the level of one or more independent variables have been criticized as “reverse Epi” since clinical trials provide better estimates of treatment effects.

Hypothesis:
The purpose of this analysis is to assess how reasonable it is to use “reverse Epi” to project the number of events avoided under different scenarios in which different markers are used for determining to whom to prescribe and how to target preventative treatment. We pursued this aim by comparing two different meta-analyses which compared HRs for apoB and non-HDL-C. One meta-analysis included 12 published observational studies. In 11 of these studies all subjects were at primary CHD risk. The other meta-analysis included 7 placebo-controlled statin trials (3 primary and 4 secondary).

Methods:
We calculated the reciprocal of each observational study’s HR per 1-SD increase (36 mg/dl for non-HDL-C and 27 mg/dl of apoB) to compare with each trials’ HR per 1-SD decrease; calculated the percentage difference (95% CI) in standard HRs for each report assuming a correlation between the two markers of 0.93 (calculated from NHANES 2005-2010 to be representative of adult US residents); and compared the resulting statistics using standard subgroup meta-analysis.

Results:
The overall geometric mean point estimate (95% CI) of the difference favoring apoB over non-HDL-C for all observational studies was 11.1% (7.7%, 14.4%) versus 5.4% (2.9%, 9.2%) for all 7 trials (p = 0.007). However these same point estimates are 9.5% (7.3%, 14.0%) versus 10.6% (7.3%, 14.0%) (p=0.714) when only primary studies or trials were included. The geometric mean treatment effect HR among the 4 secondary trials was 0.732 (0.689, 0.792) versus 0.599 (0.504, 0.714) among the 3 primary trials (p = 0.035).

Conclusion:
Meaningful differences between primary and secondary observational and interventional studies warrant stratified analysis. Among subjects at primary CHD risk, “reverse Epi” application of primary observational results may provide projections similar to those from applying primary trial results.
Abstract P279: A High Fiber Nutrient Dense Supplement Moves the Metabolome in Obese Parent[[Unable to Display Character: −]]Teen Dyads
Authors: Suh Jung H , Narayanan Nisha , Laine-Graves Kirsten , McCann Joyce C , Shenvi Swapna V , Shigenaga Mark K , Ames Bruce N , Mietus-Snyder Michele
Published: July 2021

Objective:
To determine whether twice daily intake of a low-calorie (110 kcal), high-fiber, fruit and dark chocolate based nutrient-dense bar with supplemental vitamins/minerals, β-glucan, and docosahexaenoic acid might serve as an effective adjunct to lifestyle counseling for weight management in an inner city population.

Methods:
18 overweight, predominantly female adolescent/parent guardian dyads and 2 triads (21 adults, 22 teens, randomized as 12 intervention (INT, with bars), 8 control (C) family units were recruited from a pediatric obesity clinic. The cohort was 48.7% Nonhispanic Black, 34.1% Hispanic, and 17.0% Caucasian. Two adults dropped out. The remaining 41 subjects participated in six identical weekly exercise and nutrition sessions by group. Full assessment of physical (BMI, blood pressure), behavioral (diet, activity), metabolic (cardiovascular and diabetes risk biomarkers), and metabolomic status was conducted at baseline and end-of-study.

Results:
There was excellent attendance in both INT and C groups with all family units participating in more than 80% of group sessions and 100% of baseline and follow-up assessment visits. Compliance with nutrition bar intake was 86 ± 11% and 87 ± 14% among INT group adults and teens respectively. There was considerable obesity, hypertension, dyslipidemia, inflammation, and insulin resistance in all subjects and baseline diets were universally poor. Self-report activity increased and dietary habits improved in both INT and C groups, adults and teens, most notably decreased saturated fat and total carbohydrates (especially added sugars). Weight was stable, even in the INT group despite the addition of 220 additional kcal in two daily nutrition bars. In paired analyses, systolic blood pressure (SBP) improved significantly in INT teens (-6.7 ± 9.2 mm Hg, p = 0.02), and worsened in C teens (+6.3 ± 7.7 mm Hg, p = 0.04); p = 0.002 for unpaired comparison by teen group. Plasma homocysteine levels and two amino acids, citrulline and sarcosine, implicated in the arginine-urea cycle pathway fell in both INT parents and teens, but not in controls. The drop in citrulline was more significant in INT teens (
p
= 0.005) than in adults (
p =
0.047). In a diet-induced obesity mouse model, elevated plasma citrulline has been associated with cardiometabolic complications attributed to decreased systemic arginine bioavailability that may affect capacity to produce nitric oxide. The observed metabolomic changes are consistent with more efficient mitochondrial processing and may relate to the systolic BP improvement observed in teens.

Conclusions:
A nutritional supplement bar may be a valuable adjunct for weight management, resulting in early favorable metabolomic changes.
Abstract P291: Psychosocial Factors are Associated with Cardiovascular Disease among African Americans in the Jackson Heart Study
Authors: Sims Mario , Bruce Marino , Wyatt Sharon , Mosley Tom , Sarpong Daniel , Mount David , Taylor Herman
Published: July 2021

Introduction:
African Americans (AA) have a higher risk for cardiovascular disease (CVD) than Whites. This disparity has been attributed to risk factors such as hypertension, diabetes, and obesity. This disparity has also been attributed to psychosocial factors across groups. Using Jackson Heart Study (JHS) data, we examined the associations of negative affect and stress measures with CVD risk factors and prevalent CVD among AA.

Hypothesis:
Negative affect and stress measures are associated with prevalent CVD risk factors and CVD among men and women in the JHS.

Methods:
Cross-sectional associations of negative affect (cynicism, anger in, anger out, and depressive symptoms) and stress (global stress, weekly stress, and major life events) with prevalent BMI, hypertension, diabetes and CVD were examined among 5,301 participants 34-85 years old (women=3,360; men=1,941). We estimated mean differences in BMI and prevalence ratios (PR) of hypertension, diabetes and CVD with measures of negative affect and stress and adjusted for demographic and clinical risk factors.

Results:
Men had higher cynical distrust and anger in scores than women (p<.05). Women had higher depressive symptoms, global stress, weekly stress and major life event scores than men (p<.05). After adjustment for age, sex, education, behaviors and risk factors, each psychosocial factor (except anger out and weekly stress-event) was associated with an increased mean average of BMI. For example, the mean difference in BMI increased by 41% for each 1 SD increase in cynical distrust (p<.01); and the mean difference in BMI increased by 45% for each 1 SD increase in global stress (p<.01). In fully-adjusted models, global perceived stress was associated with prevalent hypertension and diabetes (PR for hypertension: 1.07, 95%CI 1.00,1.07; PR for diabetes: 1.24, 95%CI 1.04, 1.47). Major life events were also associated with hypertension and diabetes. Each psychosocial measure (except cynicism and anger in) was associated with prevalent CVD.

Conclusion:
Efforts to reduce disparities in CVD may need to address environmental and psychosocial factors that place AA at higher risk.
Abstract P294: Urinary Sodium and Potassium Excretion and Progression of Chronic Kidney Disease
Authors: He Jiang , Mills Katherine T , Appel Lawrence J , Yang Wei , Chen Jing , Rosas Sylvia E , Porter Anna , Makos Gail , Weir Matthew R , Hamm L L , Kusek John ,   CRIC Study Investigators
Published: July 2021

Introduction:
Chronic kidney disease is a major risk factor for end-stage renal disease, cardiovascular disease, and premature death. There are scarce data on the effects of dietary sodium and potassium intake on the development and progression of chronic kidney disease.

Hypothesis:
We investigated the prospective association of urinary sodium and potassium excretion with the risk of chronic kidney disease progression and all-cause mortality among patients with chronic kidney disease.

Methods:
The Chronic Renal Insufficiency Cohort study is a prospective, longitudinal cohort study among 3,939 patients with chronic kidney disease from 7 clinical centers in the US. Dietary sodium and potassium intake are accessed by averaging three 24-hour urinary measures and calibrating to sex-specific mean 24-hour urinary creatinine excretion. Estimated-glomerular filtration rate was obtained annually. Chronic kidney disease progression was defined as a composite end point of incident end-stage renal disease or halving of estimated-glomerular filtration rate from baseline.

Results:
A total of 905 events of chronic kidney disease progression and 540 deaths from all-causes were identified during follow-up. Overall, a 100-mmol/24 hours higher adjusted sodium excretion was associated with an increased hazard ratio of 1.28 (95% confidence interval 1.17, 1.41; p<0.0001) for chronic kidney disease progression, 1.35 (1.21, 1.50; p<0.0001) for all-cause mortality, and 1.30 (1.21, 1.41; p<0.0001) for the composite outcome. Similar, a 50-mmol/24 hours higher adjusted potassium excretion was associated with increased hazard ratio of 1.56 (1.36, 1.78; p<0.0001) for chronic kidney disease progression, 1.36 (1.15, 1.62; p=0.0004) for all-cause mortality, and 1.51 (1.35, 1.69; p<0.0001) for the composite outcome after adjustment for important covariables, including baseline kidney function, diuretics, and other antihypertensive medication use.

Conclusions:
High dietary sodium and potassium intake are associated with increased risk of chronic kidney disease progression and all-cause mortality in patients with chronic kidney disease. These results suggest that a moderate reduction in dietary sodium and potassium intake might slow the progression of chronic kidney disease and reduce all-cause mortality in patients with chronic kidney disease.
Abstract P295: Exercise Capacity and Rate of Progression to Chronic Kidney Disease
Authors: Kokkinos Peter , Tsimploulis Apostolos , Faselis Charles , Myers Jonathan , Zhang Jiajia , Sui Xuemei , Blair Steven , Kheirbek Raya , Narayan Puneet , Palant Carlos
Published: July 2021

Introduction:
Increased exercise capacity is associated with better health outcomes. It is not known if increased fitness can attenuate the progression to chronic kidney disease (CKD).

Hypothesis:
We assessed the hypothesis that increased exercise capacity is associated inversely with the rate of progression to CKD.

Methods:
A routine exercise stress was performed on 6,452 veterans (mean age: 58±12) with normal kidney function at VA Medical Centers in Washington DC. We used Cox proportional hazards model with spline function of MET to define the MET level associated with no increase in rate of progression to CKD (hazard ratio (HR)=1.0). We used this MET level to guide the formation of the following four fitness categories based on intervals of 2 METs achieved above and below this threshold: Least-Fit (<5.5 METs; n=1,392); Low-Fit (5.5-7.5 METs; n=2,270); Moderate-Fit (7.6-9.5 METs; n=2,192) and High-Fit (>9.5 METs; n=714). We then performed Cox proportional hazards analysis adjusted for age, BMI, cardiac risk factors, sleep apnea, alcohol dependence and medications. We used the Least-fit category as the reference group.

Results:
The MET threshold for the entire cohort was defined at 7.5 METs. During the follow-up period (median 8.8 years; 50,371 person-years of follow-up), 925 individuals developed CKD based on an estimated glomerular filtration rate <60 ml/min/1.73m
2
. Cox proportional hazards analysis revealed that exercise capacity was inversely associated with the rate of progression to CKD. More specifically, the rate of progression was lower by 25% (HR=0.75; CI: 0.64-0.87; p<0.001) for Low-Fit individuals, 40% (HR=0.60; CI: 0.48-0.73; p<0.001) for the Moderate-Fit and 68% (HR=0.42; CI: 0.28-0.64; p<0.001) for High-Fit individuals.

Conclusions:
Exercise capacity is inversely associated with the rate of progression to CKD.