bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P062: Impact of Second-line Antidiabetic Treatments on the Risk of Microvascular Complications: Analysis of Real-world Data for 94,685 Patients Type 2 Diabetes
Authors: Ha Kyoung Hwa , Kim Bongseong , Choi Hansol , Kim Dae Jung , Kim Hyeon Chang
Published: July 2021

Objective:
To compare the risk of microvascular complications associated with second-line anti-diabetic medications by analyzing the national health insurance claim database.

Methods:
The Korean National Health Insurance (NHI) Service is the single payer which covers all Korean citizens and residents. We identified all patients who used sulphonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP4I), or thiazolidinedione (TZD) as a second-line oral anti-diabetic medication added to metformin (MET) therapy between January 2011 and June 2015 in the NHI database. Cox’s proportional hazard regression model was used to estimate hazard ratio and its 95% confidence interval for developing microvascular complications according to the types of second-line medications. Age, gender, calendar index year, duration of metformin treatments, comorbidities of hypertension and dyslipidemia, and Charlson Comorbidity Index were adjusted as potential confounders.

Results:
A total of 94685 initiators of a second-line add-on to MET of either a SU (n = 28887), DPP4I (n = 60780) or TZD (n = 5018) were identified. Diagnoses of diabetic retinopathy (n=7139), diabetic nephropathy (n=5290), and diabetic neuropathy (n=4265) were identified from the NHI claim database over a mean of 1.3 years of follow-up. Compared to the SU+MET, adjusted hazard ratio (95% confidence interval) for diabetic retinopathy was 1.03 (0.96-1.10) for the DPP4I+MET and 1.26 (1.10-1.44) for the TZD+MET. Adjusted hazard ratio (95% confidence interval) for diabetic nephropathy was 1.30 (1.19-1.42) for the DPP4I+MET and 1.63 (95% CI: 1.40-1.91) for the TZD+MET, compared with the SU+MET. Adjusted hazard ratio (95% confidence interval) for diabetic neuropathy was 0.78 (95% CI: 0.71-0.85) for the DPP-4i+MET and 0.81 (95% CI: 0.66-0.99) for the TZD+MET, compared with the SU+MET.

Conclusion:
In this analysis of nationwide real-world data, DPP4I+MET and TZD+MET therapies were associated with higher risk of diabetic retinopathy and nephropathy, but lower risk of diabetic neuropathy compared to SU+MET therapy.
Abstract P084: Racial Variation in Stroke Risk by Stroke Risk Factors
Authors: Jimenez Monik C , Manson JoAnn E , Cook Nancy , Kawachi Ichiro , Wassertheil-Smoller Sylvia , Haring Bernhard , Nassir Rami , Rhee Jinnie J , Sealy-Jefferson Shawnita , Rexrode Kathryn M
Published: July 2021

Background:
Black American adults exhibit a greater risk of stroke and disproportionate burden of stroke risk factors; however, it is unclear whether these stroke risk factors differentially impact stroke risk by race.

Methods:
In total, 126,018participants of the Women’s Health Initiative (11,389 black women and 114,629 white women), free of stroke and coronary heart disease at baseline (1993-1998), were followed for up to 17 years through 2010. Participants completed baseline clinical exams with standardized measurements of blood pressure and anthropometrics, medication inventory and self-reported questionnaires on socio-demographic, lifestyle/behaviors, diet and medical history. Incident total strokes were updated annually by questionnaire and confirmed by medical records. Multivariable Cox models estimated racial disparities in stroke overall and by across stroke risk factors.

Results:
We observed 4,344 stroke events over 1,496,314 person-years (py). In age-adjusted analyses, black women exhibited a 47% greater risk of total stroke compared to white women (hazard ratio [HR]=1.47, 95% CI: 1.33-1.63), which was attenuated toward the null (HR=1.05, 95% CI: 0.94-1.17) by further adjustment for stroke risk factors, which may be considered to be on the biological causal pathway. Disparities in stroke were two-fold higher for younger black (50-<60 years) compared to white women, with an incidence rate difference (RD) of 119/100,000 py. These disparities remained statistically significant after adjustment for stroke risk factors. For those 60-<70 years, the risk of stroke was 34% higher among black compared to white women, with a RD of 81/100,000 py No significant variation by other stroke risk factors was observed.

Conclusions:
Black women exhibited a significantly greater risk of total stroke compared to white women. Importantly, racial disparities were greatest among younger women aged 50-<60 years. Interventions targeted at younger black women may provide the greatest benefit in reducing disparities.
Abstract P104: Genetic Factors Influence Glycated Hemoglobin, Fasting Glucose, and Fasting Insulin Levels in the Population Architecture Using Genomics and Epidemiology Consortium
Authors: Highland Heather M , Bien Stephanie , Patel Yesha , Vishnu Abhishek , Schurman Claudia , Lin Bridget M , Tao Ran , Lin Danyu , Liu Simin , Phillips Lawrence , Qi Qibin , Rotter Jerome I , Laurie Cathy C , Hindorf Lucia , Buyske Stephen , Matise Tara , North Kari E , Kooperberg Charles , Pankow James S , Loos Ruth J , Haiman Christopher
Published: July 2021

Elevated levels of fasting glucose and fasting insulin precede the development type 2 diabetes (T2D). While T2D and cardiovascular disease share common risk factors, dysregulation of glucose metabolism is of particular concern because it can result in end-organ damage including the heart, nerves, kidneys, and eyes. The prevalence of diabetes is higher in American minority populations. Through genome-wide association studies, approximately 60 loci have been identified for fasting glucose, fasting insulin, and glycated hemoglobin. To better understand the genetic basis of glucose dysregulation, the Population Architecture using Genomics and Epidemiology (PAGE) Consortium genotyped 12,801 Hispanic/Latinos, 5,696 African Americans, 1,405 Native Hawaiians, 398 Native Americans, and 1,727 Asians without diabetes using the approximately 1.3 million variants on the Multi-Ethnic Global Array (MEGA), which is enriched for coding variation and ancestral diverse content. Through ancestry-combined single variant association testing with fasting glucose, fasting insulin, and glycated hemoglobin (HbA1c), we identified a novel potential association between decreased HbA1c and the minor A allele of rs11887523 (
p
= 4.51x10
-9
,
MFSD2B
p.A60T, minor allele frequency (MAF) 7% in African Americans, MAF 2% in Hispanics). Other associations with HbA1c included hemoglobin genes, further highlighting the importance of considering variation in hemoglobin and red-blood cell lifespan when using HbA1c as a measure of glucose control. We also replicated several known associations including between fasting glucose and variants near
G6PC2, GCKR, MTNR1B,
and
FOXA2
; and between fasting insulin and the
GRB14/COBLL1
locus. Further analyses including imputing the data out to 1000 Genomes phase3 and gene-based tests of rare variants are underway. These will increase power to detect associations with ancestry-specific rare variants.
Abstract P109: Detection of Haplotypes Underlying a Coronary Artery Calcification Linkage Peak in the Family Heart Study
Authors: Hicks James E , Province Michael A
Published: July 2021

Coronary artery calcification (CAC) is the buildup of calcium deposits in the arteries leading to the heart, and is an indicator of atherosclerosis. CAC is known to have a genetic component, and a genome-wide linkage screen in the Family Heart Study identified significant evidence of linkage on chromosome 9 in the area near rs13293430, but no common variant in the linkage region showed significant evidence of association.

Linkage screens attempt to identify covariance due to common ancestry at a genomic locus. This is robust to the presence of rare variation or multiple variants in a region, but is unable to identify the genomic feature causing the signal and additional research is needed to identify potential causative variants.

Pairs of individuals who have inherited a locus from a common ancestor will share an identical sequence of alleles (a haplotype) within the region. To identify haplotypes influencing the trait in the region, a mixed effects model was used. CAC was modeled as a trait influenced by polygenic effects and locus-specific haplotype effects. This model has the benefit of jointly estimating the effect of each haplotype while separating the haplotype effect from the background polygenic effect.

From the study, 2,687 individuals of European descent from 508 pedigrees with CAC scores were genotyped on the Illumina Human 1M-DuoV3 single nucleotide polymorphisms (SNP) array. Of these, 180 individuals from 23 pedigrees were for subsequent analysis due to membership in a pedigree contributing to the linkage signal. CAC scores were determined by cardiac CT scan and adjusted for age, sex, and principal components before analysis. Phased haplotypes were generated for 906,856 common SNPs across the genome using SHAPEIT. The region between 25Mb and 35Mb (3,500 SNPs) was divided into 250kb sections, and within each section haplotypes were created based on 24 evenly spaced SNPs. Statistical significance for each region was determined by likelihood ratio test.

Haplotype analysis identified two regions showing strong evidence of association (p<10
-7
) with CAC. The region 28-28.25Mb is located completely within the gene LINGO2, which has been associated with BMI and cholesterol. The region 27.5-27.75Mb contains MOBKL2B, IFNK and C9orf72. Additional work will be needed to validate haplotypes used in the model and identify the particular haplotype influencing the trait.
Abstract P112: Genes in Genome-wide Association Study-identified Loci and Risk of Atherosclerosis in Adolescents and Young Adults
Authors: Li Changwei , Li Shengxu , Hixon James E
Published: July 2021

Background:
Genome-wide association studies (GWASs) have identified multiple genomic loci associated with atherosclerotic diseases. However, specific genes underlying the observed associations are largely unknown.

Objectives:
We aimed to examine the associations between genes that harbor variants in high LD with index variants in GWAS-identified loci and pathologically determined atherosclerosis in major arteries from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study.

Methods and Results:
Data for 1,938 single nucleotide polymorphisms (SNPs) from 28 genes were retrieved from whole exome sequence data. Atherosclerosis was confirmed by postmortem examination of major arteries from 1,005 young persons (aged 15-34 years) who died from non-cardiovascular causes. Logistic regression was used to evaluate associations between common SNPs and atherosclerosis controlling for age and sex. Gene-based analysis was conducted using Sequence Kernel Association Test (SKAT) method to test the combined effect of rare and common variants on atherosclerosis controlling for age and gender. All analyses were performed separately in blacks and whites. Statistical significance was determined by false positive discovery rate (FDR) method. In gene-based analyses,
BUD13
(
P
=1.11х10
-2
) and
COL4A1
(
P
=3.58х10
-2
) were associated with atherosclerosis among young blacks; none of the 28 genes was associated with atherosclerosis in whites. In single marker analysis of common SNPs,
LRP1
missense variant rs7397167 (
P
=8.50х10
-3
),
COL4A1
variant rs16975492 (
P
=4.60х10
-3
),
STK32B
variant rs168985 (
P
=4.00х10
-3
), and
SMARCA4
variant rs8104480 (
P
=1.20х10
-3
) were associated with atherosclerosis in blacks;
MIA3
variant rs17465637 (
P
=8.00х10
-3
),
DUS4L
missense variant rs6957510 (
P
=6.4х10
-3
),
BOLL
variant rs771018 (
P
=6.2х10
-3
),
BUD3
missense variant rs11820589 (
P
=2.1х10
-3
), and
COL4A1
variant rs1133219 (
P
=1.8х10
-3
) were associated with atherosclerosis in whites.

Conclusion:
Genes in GWAS-identified loci may play a role in the development of atherosclerosis at a young age.
Abstract P113: Lipid-related Genetic Variants and Lipid Outcomes in a Cohort of Chilean Children
Authors: Von Holle Ann , Justice Anne , North Kari E , Angel Bárbara , Blanco Estela , Gahagan Sheila , Graff Misa , Santos José
Published: July 2021

Dyslipidemia is an important risk factor for chronic cardiometabolic diseases. Lipid traits are highly heritable and there are currently >185 established loci influencing lipid levels in adults. Recent studies have confirmed that variants associated with lipids influence lipid levels across the lifecourse, and in ancestrally diverse populations. Given that Hispanic/Latinos (HL) shoulder much of the cardiometabolic burden in the United States, it is important to identify genetic variants that contribute the greatest risk for elevated lipid levels across life stages. Thus, our primary aim is to examine the association of known lipid variants with lipid traits identified in large study of adult participants from a Chilean infancy cohort of primarily European-descent. The sample assessed from 2008 to 2013 (n=546) had genotyping and well-measured lipid phenotypes (median age: 16.8 years, interquartile range: 16.6, 16.9). We assessed single variant associations using linear regression for high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG), assuming an additive genetic model, adjusted for sex. Additionally, we regressed phenotypes onto weighted trait-specific polygenic risk scores (PRS). Only six variants from the Chilean sample met the
a priori
threshold of power > 0.8. We found statistically significant effect sizes (mmol/l (se)) for four of the six variants: rs3764261 (0.16 (0.04)) and rs1532085 (0.05 (0.04)) for HDL and rs1260326 (0.34 (0.15)) and rs964184 (0.33 (0.15)) for TG. For each significant variant, direction of effect matched the multiethnic adult GWAS from which SNPs were selected. We compared our findings to a previous study in Finnish children at age 18 years (n=1,216) and found an opposite direction of effect for our significant HDL variants. Likewise, when comparing coefficients for the PRS between the Chilean and Finnish youth sample we found the association to be stronger in the Chilean sample for every trait and gender group with the exception of LDL for males. The lipid loci explained the least amount of total variance for LDL (males=4% and females=5%) and the most amount of variance for HDL (males=20% and females=14%). In conclusion, there is evidence that lipid loci from a HL sample of adolescents contain similar associations as those from European children and adults. Despite the small sample size and possibility for bias with different ancestral groups we found meaningful and statistically significant associations relating lipid loci in a HL cohort of Chilean adolescents with those found in European ancestral groups. These associations emphasize the importance of adolescence as a time for disease prevention given studies demonstrating both the persistence of associations between PRS and lipids over the life course and the increasing role PRS plays in predicting disease.
Abstract P115: Better Methodologies to Compare Coronary Heart Disease Mortality Trends in Latin American Countries: Argentina, Colombia and Mexico From 1985 to 2012
Authors: Arroyo Quiroz Maria C , O’Flaherty Martin , Lamadrid-Figueroa Hector , Guzman-Castillo Maria L , Capewell Simon , Barrientos-Gutierrez Tonatiuh
Published: July 2021

Introduction:
Coronary heart disease (CHD) is the leading cause of death worldwide. CHD mortality rates have decreased in most high-income countries, but increased in some Latin-American countries. CHD mortality rates have plateaued among young adults (<55 years) in the US, UK and Australia, but trends in Latin-America are largely unknown. Few studies have analyzed trends in age and sex-specific CHD mortality rates in this region, and almost none has assured data quality by correcting for garbage codes (ICD codes for nonspecific causes of death) as recommended by WHO.

Objective:
To describe and compare standardized, age-specific and garbage-code corrected mortality trends for coronary heart disease (CHD) from 1985 to 2012 in three contrasting Latin American countries.

Methods:
CHD deaths (1985-2012) in Argentina, Colombia and Mexico were grouped by calendar year, sex and 10-year age bands to calculate the overall age-adjusted and age and sex specific mortality rates for adults aged ≥25 years. We corrected for garbage-codes for the three countries (1997-2012) using the Global Burden of Disease (GBD) methodology. We then fitted Joinpoint regression models, using the original and garbage code corrected rates, to estimate the annual percent change (APC) and detect points in time when significant changes in the trends occurred.

Results:
In 2012, age-standardised mortality rates per 100,000 were 65.3 in Argentina, 132.4 in Colombia and 130.3 in Mexico. Compared to 1985, by 2012 mortality fell by 17.5% in Colombia and 52.5% in Argentina. The largest annual decreases in mortality rates were observed in Argentina from 1988-1994 (APC=-5.7 p-value<0.01). The declines in Colombia were constant and smaller for the full period (APC=-0.4 p-value<0.01). CHD mortality rose by 48.9% in Mexico, particularly after 2000. Mortality rates increased in both men and women, particularly in younger men (<39 years) and older women (>60 years). Application of the garbage code corrections produced dramatic increases in mortality rates, more in women than men, and particularly in Argentina: approximately 80 additional deaths per 100,000 (compared with just 14 additional deaths per 10
5
in Colombia and 13 per 10
5
in Mexico).

Conclusions:
Different Latin American countries demonstrate dramatically different CHD epidemiology. Mortality rates increased after correcting for garbage code misclassification. Although CHD mortality is falling in Argentina, the modest falls in Colombia and substantial rises in Mexico highlight the region’s urgent need for effective, population-wide prevention policies.
Abstract P116: The Impact of Diet Low in Fruits and Vegetables on Cardiovascular Disease Burden Across 195 Countries in 2015
Authors: Sur Patrick J , Afshin Ashkan
Published: July 2021

Introduction:
While cardio-protective effects of fruits and vegetables are well-established, the impact of their suboptimal intake on the CVD burden across nations and levels of development has not been evaluated.

Objective:
To systematically quantify the burden of CVD attributable to low intake of fruits and low intake of vegetables in 195 countries by age, sex, country, and development status in 2015.

Methods:
We obtained data on consumption of fruits and vegetables from nationally or subnationally representative nutrition surveys and data on their national availability from the UN FAO. Etiologic effect sizes of fruits and vegetables on CVD endpoints were obtained from meta- analyses of prospective cohort studies. The optimal level of intakes for each was determined based on the levels associated with lowest risk of mortality in prospective observational studies. A comparative risk assessment analysis was conducted to quantify the proportion of disability- adjusted life years (DALYs) attributable to low intake of each. The variation of this burden was further evaluated across different levels of our newly developed socio-demographic index (SDI).

Results:
In 2015, low intake of fruits accounted for 57.3 (95% UI: 37.1- 78.4) million DALYs due to CVD globally (41.5% from IHD and 58.5% from stroke). Low intake of vegetable caused 44.6 (23.6- 68.8) million CVD DALYs (67.3% IHD and 32.7% stroke). The highest burden of CVD attributable to low intake of fruits and vegetables was seen in the middle and low-middle SDI quintiles (17.2 and 14.3% of total DALYs), while the lowest burden for each was seen in high and high-middle SDI quintiles (12.7 and 11.2%). At the country level, the attributable CVD burden ranged from 5.1% of total DALYs (Rwanda) to 23.2% (Bangladesh) for low intake of fruit and from 5.9% (North Korea) to 19.4% (Mongolia) for low intake of vegetable.

Conclusion:
Our findings suggest that population inventions to increase consumption of fruits and vegetables at population level could save millions of life years globally.
Figure.
Age-standardized proportion of disability-adjusted life years attributable to low intake of fruits (A) and vegetables (B) from cardiovascular disease among adults (> 25y) in 2015.
Abstract P127: Dose-dependent Effects of Comprehensive Lifestyle Changes on Blood Lipid Levels: Results From the PREMIER Trial
Authors: Dudum Ramzi , Juraschek Stephen P , Appel Lawrence J
Published: July 2021

Introduction:
Low-density lipoprotein (LDLc) is a major risk factor for cardiovascular (CV) disease. While comprehensive lifestyle change (CLC) lowers LDLc, little is known about how CLC adherence affects LDLc levels.

Hypothesis:
The PREMIER trial demonstrated CLC reduced LDLc levels. We hypothesized those undergoing CLC will exhibit dose dependent reductions in LDLc proportional to the number of intervention sessions attended.

Methods:
PREMIER was a multicenter randomized trial in adults with pre-hypertension or stage 1 hypertension. The current analyses were limited to participants randomized to CLC interventions, excluding those who were assigned to control, those on lipid-lowering medication, or those missing follow-up lipid data. One intervention, “Established” (Est.), was a CLC that emphasized increased physical activity, weight reduction, reduced sodium intake, and a reduced fat/calorie diet. A second CLC intervention, “Established+DASH” (Est.+DASH), also included counseling on the DASH diet. Behavioral counseling was delivered via 18 sessions in the first 6 months and 15 sessions in the following 12 months (total 33 sessions).

Results:
Among the 450 participants, mean age was 50.4, 63% were women, and 31% were black. Baseline LDLc was 134 mg/dL in Est. and 134.8 mg/dL in Est.+DASH. Mean attendance in the first 6 months was 14.2 sessions in Est. and 14.6 in Est.+DASH, and in the last 12 months was 9.6 sessions in Est. and 10.1 sessions in Est.+DASH. There was no difference in attendance by intervention. After adjustment for factors associated with LDLc, every 10 CLC sessions were associated with a 6 mg/dL (P=0.003) lower LDLc (
Table
). This association was attenuated when adjusted for weight change. Similar patterns were noted for triglycerides and total cholesterol.

Conclusions:
Better attendance at CLC sessions was associated with larger reductions in LDLc over an 18 month period with evidence that weight loss mediated this relationship.
Abstract P136: Cardiometabolic Burden in Adolescents is Associated with DNA Methylation in Genes Related to Cardiovascular Disease Risk
Authors: He Fan , Berg Arthur , Bixler Edward O , Fernandez-Mendoza Julio , Imamura Kawasawa Yuka , Salzberg Anna C , Whitsel Eric A , Liao Duanping
Published: July 2021

Background:
Metabolic syndrome is related to increased cardiovascular disease (CVD) risk. Although continuous metabolic syndrome score (cMets) is a marker of cardiometabolic burden in adolescence, the relationship between cardiometabolic burden and DNA methylation has been rarely assessed at this stage of the life course.

Hypothesis:
Cardiometabolic burden is related to methylation levels in genes related to CVD risk in adolescents.

Methods:
A sample of 263 independent adolescents from the population-based Penn State Child Cohort follow-up exam (N=421) was used in this analysis. cMets was calculated as the sum of standardized residuals of five established cardiometabolic risk factors, namely waist circumference, mean arterial pressure, homeostatic model assessment of insulin resistance, triglycerides, and high density lipoprotein cholesterol (HDL) concentration. cMets was log-transformed to improve the distribution. Peripheral leukocyte DNA was extracted and subjected to enhanced, reduced representation bisulfite sequencing. The assay provided single nucleotide resolution of DNA methylation in cytosine-phosphate-guanine (CpG) sites and surrounding regions. Bases with < 10x coverage were excluded, resulting a total of 1,609,424 methylation sites. Linear regression was used to model the association between site-specific methylation level and cMets. All models were adjusted for age, race, and sex. A p < 10x10
-8
was used to determine statistical significance. The significant sites were mapped to the hg19 assembly and subjected to Ingenuity Pathway Analysis (IPA) wherein mapped gene sets were examined for enrichment of downstream function and diseases. Permutations were further performed to confirm the robustness of our findings.

Results:
On average, the sample was 55% male, 79% white, and aged 16.7 (standard deviation = 2.2) years. cMetS was significantly associated with 52 sites within 43 genes. Among the genes, three were related to glucose tolerance, two to endothelial function, and two more to oxidative stress. IPA indicated that genes associated with these functions were significantly enriched for glucose tolerance (p=0.029), endothelial function (p=0.009), and oxidative stress (p=0.028). Indeed, high cMetS was associated with hypermethylation of
PRKCD
, which is related to diabetes risk, and
PRDX5
, which encodes anti-oxidant peroxiredoxin-5. Higher cMetS also was associated with hypomethylation of
ID3
.

Conclusion:
Despite validation is pending, these preliminary findings suggest that cardiometabolic burden in adolescents is related to DNA methylation in genes related to CVD risk factors in adulthood, including glucose tolerance, endothelial function, and oxidative stress.
Abstract P145: Association Between Birth Weight and Childhood and Maternal Cardiovascular Disease Risk Factors in Full Term Birth Infants
Authors: Umer Amna , Hamilton Candice , Britton Cris , Cottrell Lesley , Giacobbi Peter , Kelley George , Innes Kim , John Collin , Neal William , Lilly Christa
Published: July 2021

Introduction:
Reported associations between birth weight (BTW) and childhood cardiovascular disease (CVD) risk factors have been inconsistent. The relationship between infants’ BTW and later maternal CVD is also a more recent and active area of research. We aimed to examine the association between BTW and subsequent childhood and maternal CVD risk factors 11 years post-partum.

Methods:
The study used longitudinally linked data from three cross-sectional datasets in West Virginia (N=19,583). The outcome variables included blood pressure for children and lipid levels for both mothers and children. The exposure was BTW of the infants born full-term. The role of the child’s current body mass index (BMI) was assessed as a potential mediator.

Results:
Unadjusted analyses showed a positive association between BTW and the child’s systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL), and a negative association with triglycerides (TGs). When adjusted for the child’s BMI, the association became non-significant for SBP and DBP but remained significant for HDL [β= 0.14 mg/dL (95% CI: 0.11, 0.18) per1000g increase in BTW] and TGs [β= -0.007 mg/dL (-0.008, -0.005) per 1000g increase in BTW]. Low-density lipoprotein cholesterol (LDL) and non-HDL became significant and negatively associated with BTW in the adjusted analysis [LDL (β = -0.1 mg/dL (-0.19, - 0.16) per 1000 g increase in BTW; non-HDL (b = - 0.18 mg/dL (-0.28, -0.09) per 1000 g increase in BTW]. There was a positive association between infant’s birth weight and maternal total cholesterol (TC) levels, which became non-significant in the adjusted analysis [β = 0.4 (95% CI: -0.01, 0.90) mg/dL per1000g increase in birth weight]. None of the other maternal lipids levels (LDL, HDL, and TG) were significant in the unadjusted or the adjusted analysis.

Conclusion:
Low BTW was associated with higher LDL, non-HDL, and TGs, and lower HDL levels in fifth grade children independent of the current weight status. As childhood CVD risk factors persist and are often amplified over time, these small effect sizes can have potential unfavorable consequences on lipid levels in later adulthood.
Abstract P147: Glycemic Control and Weight in a Pediatric Diabetes Clinic Over Time: Gender Differences in Children With Type 1 Diabetes Between the Ages of 9-17 Years
Authors: Bodan Alexandra
Published: July 2021

Research shows women with type 1 diabetes (T1D) face a disproportionately increased risk for development of cardiovascular disease (CVD) compared to men. We posit, adolescence may be a critical time period for CVD risk development. Our study examined the effects on gender differences in Hemoglobin A1c (HbA1c) and Body Mass Index z-score (BMIz) across puberty in children with T1D in a large pediatric diabetes specialty clinic. A total of 733 T1D children (M=355, F=378) aged 9-17 with a total of 21,534 visits from the Barbara Davis Center were suitable for this retrospective cohort study. To exam HbA1c and BMIz overtime by gender we used a linear mixed model with SAS version 9.4. HbA1c increased with age in both genders (p<0.0001), but there was a greater increase in girls across adolescence (sex by age interaction, p<0.0007). BMIz increased with age in girls only (sex by age interaction, p<0.0001). Teenagers had worse glycemic control than younger children, and girls had worse glycemic control with greater obesity rates than boys. This gender difference in glycemic control and obesity during puberty may explain the increased CVD risk seen in women with T1D compared to men.
Abstract P151: Comparison of Standard Definitions and Sagittal Abdominal Diameter as a Measure of Excess Adiposity When Defining Metabolic Syndrome in Adolescents
Authors: Gaston Symielle A , Tulve Nicolle S , Ferguson Tekeda F
Published: July 2021

Introduction:
Metabolic syndrome (MetS) is the cluster of several clinical symptoms that together represent the strongest risk factor for cardiovascular disease. The prevalence of MetS in adolescents is difficult to estimate given that there are several, but no agreed upon definition of MetS for this age group. It is important to estimate MetS and identify at-risk adolescents early in order to provide effective interventions prior to the development of diabetes and coronary heart disease.

Objective:
Study objectives are to: (1) estimate the prevalence of MetS in U.S. adolescents using three widely adopted definitions and (2) compare changes in prevalence of MetS when utilizing sagittal abdominal diameter (SAD) as a component of MetS.

Methods:
Data from U.S. adolescents ages 12-19 years (N=970) in the NHANES (2011-2014) were analyzed. MetS standard definitions developed by Cook et al. (2003), deFerranti et al. (2007), and the International Disease Federation (IDF, 2007) were applied to estimate the sex-stratified, weighted prevalence of MetS and its individual components (i.e., high waist circumference (WC), hypertension, blood lipid abnormalities, and high fasting blood glucose (FBG)). The definitions were modified by substituting SAD for WC, and weighted MetS prevalence was re-estimated.

Results:
Regardless of gender and definition, abnormal blood lipids and high WC were the most prevalent MetS components. For both sexes, estimated prevalence of components varied greatly by definition (e.g., boys’ prevalence of high fasting blood glucose: IDF-27.2% vs. Cook and deFerranti-both 2.7%). MetS prevalence in boys using standard and SAD-modified definitions were 4.5% and 5.0%; 10.6% and 9.4%; and 4.6% and 3.3% for the Cook, deFerranti, and IDF definitions, respectively. Among girls, the standard-defined and SAD-modified MetS prevalence were 2.4% and 2.4%; 8.5% and 8.2%; and 4.3% and 2.8% for the Cook, deFerranti, and IDF definitions, respectively.

Conclusions:
Though the most prevalent MetS components were similar, the estimated prevalence values of individual components varied greatly across MetS definitions. With the risk of false positives, the deFerranti definition of MetS may identify the greatest number of adolescents at potential risk for MetS. Cook and deFerranti definitions may miss the identification of adolescents who could benefit from additional health promotion programs. Compared to WC, use of SAD resulted in similar yet slightly attenuated estimated MetS prevalence.
Abstract P159: In-Hospital Lifestyle Interventions to Prevent Secondary Stroke Among At-Risk Patients Varies by Patient Characteristics and Over Time: Analyses From a Large, Multi-Hospital Network
Authors: Baraban Elizabeth , Lucas Lindsay , Spinelli Kateri
Published: July 2021

Introduction/Objective:
Recent studies show that targeted interventions on lifestyle factors such as weight management and diet can be successful in reducing ischemic stroke (ISC) and transient ischemic attack (TIA) rates. The objective of this study was to examine which subpopulations of patients at risk for secondary stroke presenting to a hospital with an ISC or TIA were more likely to receive interventions in a multi-hospital health system.

Methods:
Data from 26 hospitals participating in a multi-state healthcare system stroke registry, from January 2009 to December 2015, were used. Patients admitted with a diagnosis of ISC or TIA discharged to home were included. Patients on comfort care or those not discharged home were excluded. At-risk groups included patients with Body Mass Index (BMI) ≥ 25 and those prescribed medication for hypertension or high cholesterol in-hospital. Risk-related interventions included educational material given to patients during admission. Mixed effects logistic regression models with backward elimination were used to identify significant predictors of receiving the intervention from the following variables: year of discharge, age, insurance (private, Medicare, other/self-pay), BMI grouping, ambulation status, length of stay, stroke severity, and medical histories of family stroke, previous stroke or TIA, atrial fibrillation, coronary artery disease, heart failure, dyslipidemia, hypertension, and drug/alcohol abuse.

Results:
A total of 19,661 patients met the inclusion criteria. Of the 8,334 patients with a BMI ≥ 25, 57% (n=4,717) received weight management intervention. Of the 9,676 prescribed medication for hypertension, 55% (n=5,348) received information on antihypertensive diet. Of the 10,999 patients prescribed medication to lower cholesterol, 64% (n=7,088) received cholesterol lowering diet information. From 2009 to 2015, interventions increased for patients with a BMI ≥ 25 (40% to 66%), prescribed medication for hypertension (37% to 53%), and prescribed medication to lower cholesterol (39% to 67%). The mixed effects logistic regression models showed that all risk groups were significantly less likely to receive intervention if they had lower BMIs, were unable to ambulate versus able to ambulate alone, and had no family history of stroke. For those on medication for cholesterol, patients with Medicare were significantly less likely to receive the intervention compared to those on private insurance or other payment types (AOR=0.78, p<0.001).

Conclusions:
This large patient cohort demonstrates there are improvement opportunities for in-hospital secondary stroke prevention efforts. Over time, prevention efforts have increased for at-risk patients, but many are still not receiving it. The disparity in intervention rates suggest that a more targeted strategy to educate at-risk populations may need to be developed.
Abstract P161: Variation in Five-Year Weight Loss Patterns Following Bariatric Surgery by Insurance Status
Authors: Takemoto Erin , Wolfe Bruce , Nagel Corey , Boone-Heinonen Janne
Published: July 2021

In the general population, bariatric surgery facilitates sustained weight loss and remission of comorbidities (e.g., CVD). The effectiveness among Medicaid beneficiaries, a population with a disproportionately high burden of obesity, remains unclear. We sought to determine if patterns of weight change following bariatric surgery differed in patients with Medicaid compared to commercial insurance.

Data were obtained from the Longitudinal Assessment of Bariatric Surgery, an observational cohort study of adults undergoing bariatric surgery (2006-2009) at one of 6 geographically diverse centers. We used group-based trajectory models (PROC TRAJ, SAS) to identify discrete groups of individuals with similar weight trajectories over 5-years; we considered cubic trajectory models with between 1 and 6 groups. We selected the 6-group model based on Bayesian Information Criteria, visual fit and statistical significance of parameter estimates. We tested demographic predictors against trajectory group membership; Medicaid (n=174) vs. Commercial (n=991) was our primary predictor of interest.

Medicaid participants had higher mean weight at baseline compared to the commercially insured (307.9 vs. 291.2 lbs), but lost a similar amount of weight over time (74.8 vs 85.0 lbs). All groups experienced the most weight loss in year 1 (Figure). Group 6 was the heaviest at baseline and began to regain weight after year 1; groups 1-5 continued to lose weight through year 2. Group’s 1 & 2 weight remained stable over 5 years while groups 3-6 began to slowly regain weight. Medicaid beneficiaries were more likely to be in group 4 (OR 3.2, 95% CI: 1.2, 8.6), group 5 (OR 5.7, 95% CI: 2.0, 16.1) and group 6 (OR 7.9, 95% CI: 2.5, 25.1) compared to group 1.

Medicaid beneficiaries experience substantial long term weight loss. However, they had higher baseline weight and tended to be in groups with less long-term weight loss compared to the commercially insured. Focusing on tailored interventions to specific patient groups could help maintain weight loss.
Abstract P163: Racial, Gender and Regional Variation in Rates of Cardiovascular Hospitalization Among 9 Million US Veterans
Authors: Krishnamurthi Nirupama , Whooley Mary A
Published: July 2021

Introduction:
Little is known about population-level trends in rates of cardiovascular hospitalizations among U.S. Veterans. Recent adoption of a centralized Corporate Data Warehouse in the Veterans Health Administration (VHA) provides a new opportunity to evaluate trends in national rates of hospitalization among Veterans. We sought to determine the leading causes of cardiovascular (CV) hospitalization, and to compare national rates of CV hospitalization by age, gender, race, ethnicity, geographical distribution and year, among U.S. Veterans.

Methods:
We evaluated the electronic health records of all Veterans ≥18 years old that accessed VA healthcare services between January 1 2010 and December 31 2014. Among these 9,066,693 patients, we identified the 5 leading causes of CV hospitalization and compared rates of hospitalization by age, gender, race, ethnicity, geographical distribution and year.

Results:
The top 5 causes of CV hospitalization in VA hospitals were: chest pain (3.23 per 1,000 Veterans per year), coronary arteriosclerosis in native artery (2.36), congestive heart failure (1.82), atrial fibrillation (1.34) and acute sub-endocardial infarction (0.99). Overall, the rate of Veterans hospitalized for one or more of these CV conditions decreased over time, from 9.9 per 1000 Veterans in 2010 to 8.3 per 1000 Veterans in 2014. The odds of hospitalization due to any of the 5 conditions were higher in men vs. women (OR 1.73, p<0.0001), in urban vs. rural areas (OR 1.15, p<0.0001), and in the Southeast vs. Pacific regions (OR 1.08, p<0.0001). As compared with Whites, odds of CV hospitalization were higher in Blacks (OR 1.34, p<0.0001) but lower in Asians (OR 0.50, p<0.0001). Racial, geographic and temporal differences in rates of hospitalization were also observed for each of the individual CV conditions.

Conclusions:
Among U.S. Veterans enrolled in the VA healthcare system, there is substantial variation in rates of CV hospitalization by age, gender, race, geographical distribution and year.
Abstract P169: Health Literacy and Outcomes in Heart Failure: a Prospective Community Study
Authors: Fabbri Matteo , Yost Kathleen , Finney Rutten Lila , Manemann Sheila , Weston Susan , Jiang Ruoxiang , Roger Veronique L
Published: July 2021

Background:
Growing evidence documents the association between low health literacy and poorer health outcomes. However, less is known about the relationship between health literacy and outcomes among patients with heart failure (HF). We examined the association of health literacy with risk of hospitalization and mortality in patients with HF.

Methods:
Residents in an 11-county region in southeastern Minnesota with incident HF from 1/01/2013 to 3/31/2015 were identified using the International Classification of Diseases, Ninth Revision code 428 (n=3715) and prospectively surveyed to measure health literacy using established screening questions. A total of 1992 patients returned a survey (response rate 54%); 1779 patients with complete clinical data and adequate follow up were retained for analysis. Health literacy, measured as a composite on three 5-point scales, was categorized as adequate (≤ 10) or low (> 10). Cox proportional hazards regression and Andersen-Gill models were used to determine the association of health literacy with mortality and hospitalization.

Results:
Among 1779 patients (mean age 74, 53% male), 10% had low health literacy. After a mean follow-up of 8±4 months, 72 deaths and 600 hospitalizations occurred. Low health literacy was associated with increased mortality and hospitalizations (Figure). After adjusting for age, sex, comorbidity, education and marital status, the hazard ratio for death and hospitalization in patients with low health literacy was 2.84 (95% CI: 1.63, 4.96) and 1.43 (95% CI: 1.04, 1.96) respectively, compared to patients with adequate health literacy.

Conclusions:
Low health literacy is associated with increased risk of hospitalization and death among patients with HF. Health literacy is critical to the self-management demands of living with heart failure. Evaluation of health literacy in the clinical setting may guide inventions to target patients with low literacy.
Abstract P178: Cost-Effectiveness of Intensive versus Standard Blood Pressure Goals by Baseline Systolic Blood Pressure Levels in SPRINT-Eligible US Adults
Authors: Bellows Brandon K , Bress Adam P , King Jordan B , Ruiz-Negrón Natalia , Hess Rachel , Beddhu Srinivasan , Zhang Zugui , Berlowitz Dan R , Weintraub William S , Moran Andrew E
Published: July 2021

Background:
In high-risk adults, intensive systolic blood pressure (SBP) goals (<120 mmHg) reduced cardiovascular disease (CVD) events and mortality, when compared to standard SBP goals (<140 mmHg), in the Systolic Blood Pressure Intervention Trial (SPRINT). While average benefit of reduced CVD risk with intensive SBP goals outweighs the average risk of serious adverse events (SAEs) and treatment costs, net intensive SBP goal benefits may vary by baseline SBP. We hypothesized that intensive SBP goals would be cost-effective vs. standard SBP goals when stratified by baseline SBP level in SPRINT-eligible US adults from the payer’s perspective.

Methods:
Using CVD event, death, and SAE risks, a microsimulation model compared direct healthcare costs and quality-adjusted life-years (QALYs) in the SPRINT intensive and standard SBP goal arms over patients’ remaining lifetimes. Published literature and national estimates were used for model parameters. The model assumed that, after the planned duration of SPRINT, adherence to treatment goals decayed over time. To estimate the effect of baseline SBP on the cost-effectiveness of intensive SBP goals, baseline SBP was stratified into the following groups: 130-139 mmHg, 140-149 mmHg, 150-159 mmHg, 160-169 mmHg, and 170-180 mmHg.

Results:
With higher baseline SBP, patients in both arms experienced higher rates of CVD events or CVD deaths and accrued higher costs compared with patients starting with lower baseline SBP. However, with higher baseline SBP, there were slightly more incremental QALYs gained with intensive SBP treatment, from 0.29 to 0.31. This led to a modestly better incremental cost-effectiveness ratio (ICER) for intensive vs. standard SBP goals, decreasing from approximately $50,000 to $43,000 per QALY gained as baseline SBP increased. If SPRINT treatment effects and in-trial adherence persisted for the remaining lifetime, the ICER for intensive SBP goals decreased to approximately $25,000-$26,000 per QALY gained across baseline SBP groups.

Conclusions:
Treatment of all SPRINT-eligible patients led to lifetime cost-effectiveness below accepted willingness-to-pay thresholds and lifetime net benefit and cost-effectiveness varied only modestly by baseline SBP. However, this analysis was based on summary data and did not account for individual patient risks. Multiple predictors, in addition to baseline SBP, may be needed to identify which SPRINT-eligible patients derive maximal benefit from intensive SBP treatment.
Abstract P183: Minimal Impact of JAMA 2014 Guidelines on Blood Pressure Control in a Large Health System
Authors: Chang Alex R , Hartle J E , Appel Lawrence , Grams Morgan
Published: July 2021

Background:
JAMA 2014 blood pressure (BP) guidelines raised BP goals for adults older than 60 years (from <140/90 to <150/90) and adults with chronic kidney disease (CKD) or diabetes (from < 130/80 to <140/90). It is unknown whether there were changes in BP control at the health system level after guideline publication.

Methods:
Using data from 288,962 adults receiving primary care in the Geisinger Health System, we compared blood pressure control over 1-year time periods before and after the February 2014 publication of the JAMA 2014 BP guidelines (i.e. Aug 2012-July 2013 vs Aug 2014-July 2015). Mixed effects models were used, allowing intercepts to vary by individual, adjusted for age, gender, and race.

Results:
Mean age was 49.2 ± 18.3 y, 56.7% were female, and 2.5% were black. Prevalence of diagnoses for hypertension, diabetes, and CKD were 40.0%, 15.1%, and 11.4%, respectively. Overall, distributions of systolic BP were similar before and after JAMA 2014 BP guidelines (Figure). BP control <140/90 was also similar between the two periods for adults 18-59 y (90.9% vs. 90.3%; OR 1.01, 95% CI: 0.99-1.02; p=0.3), adults ≥ 60 y (81.8% vs 82.2%; OR 1.01, 95% CI: 1.00-1.03; p=0.05), and adults with diabetes (83.2% vs. 82.7%; OR 1.00, 95% CI: 0.99-1.02; p=0.7) whereas BP control <140/90 improved slightly for adults with CKD (81.7% vs. 82.1%; OR 1.06, 95% CI: 1.04-1.08; p<0.001). BP control <130/80 was marginally worse after JAMA 2014 BP guidelines in patients with diabetes (53.5% vs. 51.8%; OR 0.98, 95% CI: 0.96-0.99; p=0.01). Trends were similar in analyses only including patients with hypertension diagnoses (overall 78.6% vs. 78.2%, OR 1.00, 95% CI: 0.99-1.02; p=0.5), and when using a goal of < 130/80 for patients with CKD (53.3% vs. 53.5%; OR 1.06, 95% CI: 1.04-1.08; p<0.001).

Conclusion:
There was little change in blood pressure control in a large integrated health system after publication of the JAMA 2014 BP guidelines. These findings are reassuring given recent findings from the SPRINT trial supporting lower BP goals.