bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P071: Moderate Exposure to Inorganic Arsenic in Drinking Water is Associated with Elevated Pulse Pressure: Results from Chihuahua, Mexico
Authors: Mendez Michelle A , González-Horta Carmen , Sánchez-Ramírez Blanca , Ballinas-Casarrubias Lourdes , Hernández Cerón Roberto , Viniegra Morales Damian , Baeza Terrazas Francisco Andres , Gutiérrez-Torres Daniela , Ishida María Cecilia , Drobna Zuzana , Buse John , García-Vargas Gonzalo G , Del Razo Luz M. , Stýblo1 Miroslav
Published: March 2022

Background:
Though levels of arsenic >100 μg/L in drinking water have been consistently associated with increased risk of cardiovascular disease (CVD), evidence of an association at lower levels of exposure is more inconsistent. We used data from a cohort from Chihuahua Mexico to examine whether relatively low levels of arsenic in drinking water were associated with elevated pulse pressure, a marker linked to arterial stiffening and CVD risk.

Methods:
We used concentrations of arsenic in household drinking water from 931 adults not taking hypertensive medication to examine the association between water arsenic categories as low as 25-50 μg/L and mean increases in systolic, diastolic and pulse pressure (systolic - diastolic pressure). We also examined the association between water arsenic categories and elevated pulse pressure, defined as >70 mm Hg. Associations between arsenic exposure and blood pressure measures were obtained from multivariable linear or logistic regression models that adjusted for age, gender, education level, ethnicity, BMI, waist circumference, smoking status and alcoholic beverage intake.

Results:
After multivariable adjustment, compared to lower levels, water arsenic concentrations of 25-50 μg/L and above were associated with statistically significant increases in systolic blood pressure (SBP) and pulse pressure, but were not associated with diastolic blood pressure (DBP). Multivariable-adjusted associations [β (95% confidence interval)] with water arsenic concentrations of 25-50 μg/L were: 4.3 (1.2-7.4) mm Hg for SBP; 3.3 (0.8-5.7) mm Hg for pulse pressure; and 1.3 (-0.6-3.3) mm Hg for DBP. For elevated pulse pressure (16.1% of the sample), the association [odds ratio (95% CI)] with water arsenic levels of 25-50 μg/dL was 2.5 (1.3-4.9).

Conclusions:
Results support potential adverse effects of exposure to moderate levels of arsenic in drinking water on CVD risk through pathways that may involve widening pulse pressure.
Abstract P095: Diet Quality and Genetic Association With Body Mass Index
Authors: Ding Ming , Ellervik Christina , Huang Tao , Jensen Majken , Curhan Gary , Pasquale Louis , Kang Jae Hee , Wiggs Janey , Hunter David , Willett Walter , Rimm Eric , Kraft Peter , Chasman Daniel , Qi Lu , Hu Frank , Qi Qibin
Published: March 2022

Background:
Whether dietary quality modifies genetic association with body mass index (BMI) is unknown.

Methods:
We examined the interactions prospectively of a genetic risk score (GRS) based on 97 BMI-associated variants with three diet quality scores (alternative healthy eating index 2010 (AHEI-2010), Alternative Mediterranean Diet score (AMED) and Dietary Approach to Stop Hypertension (DASH) diet score) on BMI in 30,904 participants from three large US cohorts. According to the enrichment of genes near the BMI-associated loci in the central nervous system (CNS), we further created two subsets of GRSs: CNS GRS based on 54 variants and non-CNS GRS based on 43 variants.

Findings:
We found significant interactions between total GRS and all three diet scores on BMI assessed after 2 to 3 years, with an attenuated genetic effect observed in individuals with healthier diets (AHEI: P for interaction = 0.003; AMED: P = 0.001; DASH: P = 0.004). For example, the difference in BMI per 10 unit increment of the GRS was smaller among participants in the highest tertile of AHEI score compared to those in the lowest tertile (0.84 [95% CI: 0.72, 0.96] vs. 1.14 [0.99, 1.29] kg/m
2
). Results were consistent across the three cohorts with no significant heterogeneity. The interactions with diet scores on BMI appeared more significant for CNS GRS (AHEI: P = 0.009; AMED and DASH: P < 0.001) than for non-CNS GRS (AHEI: P = 0.10; AMED: P = 0.50; DASH: P = 0.68). Among individual components of diet scores, higher consumption of red/processed meat, sugar-sweetened beverages, and
trans
fat accentuated genetic associations with BMI (P <0.01), while higher consumption of fruit and moderate alcohol attenuated genetic associations with BMI (P < 0.01).

Interpretation:
A higher diet quality may mitigate genetic predisposition to obesity. These findings provide insights into complex interplays between diet and genetic influences and underscore the importance of adopting a healthful diet for the prevention of obesity, particularly those individuals with a strong genetic predisposition to obesity.
Abstract P099: A Methylome- and Transcriptome-Wide Study of Dietary Fructose Intake in Humans
Authors: Aslibekyan Stella , Do Anh N , Irvin Marguerite R , Hidalgo Bertha A , Zhi Degui , Tiwari Hemant K , Absher Devin M , Ordovas Jose M , Arnett Donna K
Published: March 2022

Background:
Animal model studies reported robust associations between fructose intake, a known determinant of metabolic health across species, and DNA methylation/ gene expression patterns. To date, these associations have not been comprehensively investigated in humans.

Methods:
Using DNA methylation data on ~470,000 cytosine-phosphate-guanine (CpG) sites in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n=991) quantified in CD4+ T-cells, we have interrogated the cross-sectional relationships between fructose intake (ascertained using a validated food frequency questionnaire) and epigenome-wide methylation. We fit linear mixed models adjusted for age, sex, study site, technical covariates (fixed effects) and family relatedness (random effect). We have supplemented the methylation analyses with a transcriptome-wide scan on 98 unrelated GOLDN participants with available RNASeq data in whole blood. For the RNASeq data analysis, we used negative binomial models of read counts as a function of fructose intake, adjusted for age, sex, study site, technical covariates (including differential white blood cell counts).

Results and Conclusions:
The top loci differentially methylated with respect to fructose intake mapped to
SNED1
(regression coefficient +/- SE= 0.002 +/- 0.0005, P=5x10-6) and
FARSB
(regression coefficient +/- SE= 0.002 +/- 0.0004, P=5x10-6) on chromosome 2.
SNED1
is an insulin responsive transcription factor that has previously been shown to be downregulated in the setting of metabolic syndrome.
FARSB
encodes an aminoacyl-tRNA synethetase implicated in cell growth. Additionally, two genes reached transcriptome-wide significance in the RNASeq analysis:
MTATP8P1
(P=1x10-7) and
PDXDC1
(P=6x10-7). Sequence variation in
PDXDC1
(pyridoxal-dependent decarboxylase isoform) has previously been linked to lipid metabolism, while
MTATP8P1
is a pseudogene for a mitochondrially encoded ATP synthase. Upon future replication and functional validation, our preliminary findings offer promising insights into the link between fructose intake and metabolic health.
Abstract P125: Reverse Causality of the Relationship Between Dietary Cholesterol and Serum Low Density Lipoprotein Cholesterol Associated With Education and Employment: the INTERLIPID Study
Authors: Okami Yukiko , Ueshima Hirotsugu , Nakamura Yasuyuki , Okuda Nagako , Nakagawa Hideaki , Sakata Kiyomi , Saitoh Shigeyuki , Okayama Akira , Yoshita Katsushi , Miyagawa Naoko , Choudhury Sohel R , Chan Queenie , Elliott Paul , Stamler Jeremiah , Miura Katsuyuki ,   the INTERMAP and INTERLIPID Rsch Groups
Published: March 2022

Introduction:
The upper limit of recommended dietary cholesterol has been abolished recently from guidelines in Japan and US even though high intake is known to increase serum cholesterol levels. Reverse causality has been involved, reflecting availability of widespread information with consequent lifestyle modifications among knowledgeable people. People with higher serum cholesterol are more likely to modify diet than those with lower serum cholesterol, especially among more educated; if enough people do this, dietary cholesterol will not relate to serum cholesterol or will relate inversely.

Hypothesis:
We assessed the hypothesis that lifestyle modifications separately by those with high education level and employment status reverse the positive relationship between dietary cholesterol and serum low density lipoprotein cholesterol (LDL-C); therefore, the positive relationship between dietary cholesterol and LDL-C would prevail after adjustment for education level and employment status.

Methods:
A population-based, random sample, cross-sectional study (INTERLIPID) which was an ancillary study of the International Study of Macronutrients and Blood Pressure (INTERMAP), conducted a survey between 1996 and 1999. Among 1,145 Japanese individuals ages 40-59 years, 106 were excluded because of special diets, use of lipid lowering drugs, hormone replacement, and missing data, leaving 1,039 individuals (533 men and 506 women). Dietary cholesterol was assessed from four 24-h dietary recalls and LDL-C was measured by enzymatic methods on an auto-analyzer. A standard questionnaire inquired about years of education and employment status.

Results:
Linear regression analysis revealed an inverse association between dietary cholesterol and LDL-C in men (coefficient, -0.04 [95%CI, -0.08 to -0.01]), no significant association when adjusted for education and its interaction term with dietary cholesterol in men (coefficient, 0.05 [95%CI, -0.03 to 0.14]), and a significant positive relation when adjusted for employment and its interaction term in men (coefficient, 0.13 [95%CI, 0.01 to 0.26]). With adjustment for education and employment and their interactions, a significant positive relation was recorded again in men (coefficient, 0.16 [95%CI, 0.03 to 0.29]). These relationships were not observed in women.

Conclusions:
In Japanese men, education, employment, and their interaction terms with dietary cholesterol reversed an observed inverse relationship between dietary cholesterol and LDL-C. A positive relation prevailed between dietary cholesterol and LDL-C after adjustment for education level and employment status.
Abstract P130: Ideal Cardiovascular Health and Incident Cardiovascular Disease: Heterogeneity Across Event Phenotype and Contribution of Multiple Biomarkers. The Prime Study
Authors: Gaye Bamba , Tafflet Muriel , Arveiler Dominique , Montaye Michèle , Aline Wagner , Ruidavets Jean Bernard , Kee Frank , Evans Alun , Amouyel Philippe , Ferrieres Jean , Empana Jean philippe
Published: March 2022

Background:
To which extent the association between ideal cardiovascular health (CVH) and incident vascular events differ by main coronary heart disease (CHD) and main stroke phenotype is currently unknown. Furthermore, data on potential mediating factors underlying the association of ideal CVH with outcomes are lacking.

Aims:
We aimed to 1) quantify the association between ideal CVH and incident CHD and stroke, 2) to assess for potential heterogeneity across main CHD and main stroke phenotypes and between CHD and stroke; and 3) to assess the mediating effect of a selected panel of key circulatory biomarkers from different relevant disease pathways.

Methods and Results:
A total of 9312 men middle-aged men (50-59 years) free of CHD and stroke were recruited in the framework of WHO MONICA centres in Lille, Strasbourg, Toulouse (France) and Belfast (Northern Ireland) between 1991 and 1993 and enrolled in the PRIME study. According to the American Heart Association, men with 0-2, 3-4 and 5-7 metrics at the ideal level were categorized as having poor, intermediate and ideal CVH respectively. Hazards ratios (HRs) were estimated using Cox proportional hazards regression and were adjusted for age, centre, education, living alone, marital status, family history of CHD and blood fibrinogen. The contribution of baseline circulating, endothelial inflammatory and haemostatic biomarkers was explored in a case control study nested within the PRIME cohort and settled after 10 years of follow-up. An ideal CVH was observed in 7% of the participants. After a median follow-up of 10 years, 614 first CHD events (myocardial infarction, angina, coronary death) and 117 first stroke events (ischaemic and non ischaemic) were adjudicated. Compared to those with poor CVH, those with an ideal CVH at baseline had a 72% lower risk of CHD (HR=0.28; 95% CI: 0.17; 0.46) and a 76% lower risk of stroke (HR=0.24; 95% CI: 0.06; 0.98) in multivariate analysis. No heterogeneity was detected across main CHD and main stroke phenotypes. While significantly lower mean concentrations of hs-CRP, IL-6, ICAM-1, fibrinogen and von Willbrandt factor were noted in subjects with ideal or intermediate as compared to poor CVH status in the controls, none of these biomarkers contribute to the association of CVH with future CHD.

Conclusion:
In this study ideal CVH was associated with a substantially lower risk of CHD and stroke, without any difference across phenotypes. Neither inflammatory, endothelial nor haemostatic biomarkers explained the lower risk of CHD in men with ideal CVH.
Abstract P135: Abdominal Obesity is Associated With DNA Methylation in Cardiovascular Health Related Genes Among Adolescents
Authors: He Fan , Berg Arthur , Bixler Edward O , Fernandez-Mendoza Julio , Imamura Kawasawa Yuka , Salzberg Anna C , Whitsel Eric A , Liao Duanping
Published: March 2022

Background:
Obesity, especially abdominal obesity, is a risk factor for coronary artery disease (CAD) in various populations. Little is known regarding the role of epigenetics in the association between abdominal obesity and cardiovascular health in adolescents.

Hypothesis:
Abdominal and especially visceral obesity is associated with DNA methylation in genes related to cardiovascular health among adolescents.

Methods:
We used data from a sample of 263 adolescents participating in the population-based Penn State Child Cohort follow-up exam (N=421). Dual-energy X-ray absorptiometry was used to measure visceral and subcutaneous fat areas (VAT; SAT, in cm
2
) in each participant. We extracted DNA from peripheral leukocytes and subjected it to enhanced, reduced representation bisulfite sequencing. A high-throughput assay provided single nucleotide resolution of DNA methylation in cytosine-phosphate-guanine (CpG) sites and surrounding regions. We excluded bases with < 10x coverage or available from < 20 individuals. We analyzed a total of 1,609,424 methylation sites. We used linear regression models to assess the association between site-specific methylation level (expressed as %) and VAT and SAT. We adjusted all models for age, race, sex, and body mass index (BMI) percentile. We used Bonferroni-adjusted statistical tests to identify sites significantly related to VAT and separately, SAT. We mapped the VAT- and SAT-associated sites to the hg19 assembly and subjected them to Ingenuity Pathway Analysis (IPA) wherein mapped gene sets were examined for enrichment of downstream function and diseases.

Results:
On average, the sample was 55% male, 79% white and aged 16.7 (standard deviation = 2.2) years. VAT and SAT were significantly associated with methylation at 296 sites within 193 genes and 101 sites within 87 genes, respectively. Among them, seven genes related to VAT and five related to SAT were associated with CAD. IPA revealed that CAD-related genes were significantly enriched in both gene sets (for VAT: p=1.97x10
-2
; SAT: p=9.67x10
-3
). Genes related to VAT also were significantly enriched in endothelial activation (p=8.16x10
-3
), fibrogenesis (p=5.01x10
-5
), and dyslipidemia (p=7.99x10
-3
). Indeed, higher VAT was associated with hypomethylation of
CD14
and hypermethylation of
GNMT
, while higher SAT was associated with hypermethylation of
ADRB1
and hypomethylation of
TUBB4A
.

Conclusion:
If externally validated, our data would suggest that (1) abdominal obesity in adolescence is associated with DNA methylation of genes related to cardiovascular health, independent of BMI; and (2) visceral adiposity has a more prominent association with cardiovascular health through DNA methylation of genes with roles in atherogenesis.
Abstract P154: Short-Term Health Care Expenditures Increase After Workplace Wellness Program
Authors: Levy Douglas E , Regan Susan , Thorndike Anne N
Published: March 2022

Introduction:
A major goal of workplace wellness programs is to improve employee health and lower health care costs. Research on wellness program effectiveness is often limited by either a lack of a control comparison groups or confounding when the intervention and control groups differ on baseline health. Our study objective was to assess the effect on health expenditures of an employee wellness program (BeFit), already shown to improve diet, physical activity, cholesterol, and BP. We compared participants to a matched non-participant control group.

Hypothesis:
We hypothesized that health care costs would be lower for participants than for non-participants.

Methods:
BeFit is a 10 week nutrition/exercise program that includes measurement of cardiovascular risk factors, weekly meetings with a nutritionist and personal trainer, gym membership, and team competition to achieve weight and exercise goals. For this study, participants were matched by age, sex, period of employment, and pre-participation Diagnostic Cost Group (DCG) risk score (a predictor of future health care use based on past-year use), to two non-participant control employees. Health expenditures were gathered from claims data obtained by the employer’s human resource department. Subjects in the analysis had at least 12 months pre- and post-program claims data. Within-subject quarterly health care cost trends were compared after subjects’ BeFit start dates using multivariable generalized least squares regression controlling for age, sex, and baseline health. Control subjects were assigned the start date of the subject to whom they were matched. Expenditures were capped at the 99
th
percentile ($42,393) so results were not unduly influenced by extreme events unlikely to be affected by a wellness program. We analyzed overall, domain-specific (outpatient, inpatient, pharmaceutical), and diagnosis-specific costs.

Results:
From 2010-2014, 412 BeFit participants and 824 controls met the inclusion criteria (77% female, mean age 41 [range 23,78], mean baseline DCG risk score of 92.3 [range 3, 2315]). After participation in BeFit, the regression-adjusted health expenditures decreased by $15/quarter among BeFit participants compared to $85/quarter among control subjects (95% CI for difference $27, $113). Trends were significantly more negative in the control group for outpatient, inpatient, and pharmaceutical costs, as well. There were no differences in trends for cardiovascular or diabetes-related costs.

Conclusions:
Contrary to our hypothesis, trends in health expenditures decreased more for the matched control group than for participants in the employee wellness program. This result may be due to increased attention to health and higher health care use spurred by participation in the program. Further work is necessary to understand the long-term impact of wellness programs on health and health expenditures.
Abstract P157: Sex Disparities in High Intensity Statin Use Following Myocardial Infarction
Authors: Tanner Rikki M , Rosenson Robert , Monda Keri , Safford Monika , Taylor Ben , Dai Yu Ling , Zhao Hong , Muntner Paul , Bittner Vera
Published: March 2022

Background:
High intensity statins have been shown to lower the risk of major cardiovascular events after an index myocardial infarction (MI). Studies have shown that women are less likely than men to receive cardiovascular risk reduction therapies but little is known about sex differences in high intensity statin use following hospital discharge for MI.

Methods:
We compared high intensity statin use following hospital discharge for MI in 2014 between men and women 19 to 64 years with commercial health insurance in the Marketscan database (n=7,089 men and 2,318 women) and Medicare beneficiaries ≥66 years (n=20,202 men and n=18,937 women). Patients were included if they filled a statin of any intensity within 30 days following hospital discharge. Statin fills were identified through pharmacy claims and high intensity statins included atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg.

Results:
Among patients not taking statins prior to having an MI (n=6,303 in Marketscan and n=17,763 in Medicare), 69.4% of men and 62.4% of women (p-value <0.001) in the Marketscan database and 55.2% of men and 48.1% of women (p-value <0.001) with health insurance through Medicare initiated treatment with a high intensity statin. Among patients taking low or moderate intensity statins prior to having an MI (n=2,234 in Marketscan and n=16,818 in Medicare), 58.0% of men and 49.2% of women (p-value <0.001) in the Marketscan database and 38.2% of men and 31.7% of women (p-value <0.001) in Medicare titrated to a high intensity statin within 30 days of hospital discharge. After multivariable adjustment, women were less likely to initiate treatment with a high intensity statin (relative risk: 0.92; 95% CI 0.88-0.96 in Marketscan and 0.92; 95% CI 0.90-0.95 in Medicare) or titrate from low/moderate to high intensity statin (relative risk: 0.89 95% CI 0.81-0.95 in Marketscan and 0.89; 95% CI 0.86-0.93 in Medicare). Among those taking a high intensity statin prior to their MI (n=870 in Marketscan and n=4,558 in Medicare), 92.0% and 87.4% of men and women, respectively, in Marketscan (adjusted relative risk 0.95; 95% CI 0.90-1.01) and 91.5% and 88.1% of men and women, respectively, in Medicare (adjusted relative risk 0.97; 95% CI 0.95-0.99), remained on a high intensity statin following hospital discharge.

Conclusions:
Women are less likely than men to receive high intensity statins following hospital discharge for MI.
Abstract P165: Lifestyle Counseling Practices and Referrals for CVD Prevention by Primary Care Providers
Authors: Omura John D , Watson Kathleen B , Loustalot Fleetwood , Kumar Gayathri , Carlson Susan A
Published: March 2022

Background:
The US Preventive Services Task Force recommends that adults who are overweight or obese and have additional cardiovascular disease (CVD) risk factors be offered or referred to intensive behavioral counseling interventions to promote a healthful diet and physical activity for CVD prevention. However, it is unknown what resources primary care providers (PCPs) refer patients to for this service. This study determined the proportion of PCPs who referred patients to different health sector and community resources to receive intensive behavioral counseling and whether this differed by physical activity counseling frequency.

Methods:
DocStyles 2016, a Web-based panel survey of 1256 PCPs (response rate=64.5%), assessed physical activity counseling practices for those patients at risk for CVD(overweight or obese and with hypertension, dyslipidemia, impaired fasting glucose, or metabolic syndrome).

Results:
Overall, 78.0% (SE=1.2) of PCPs referred any of their at risk patients to intensive behavioral counseling. The providers and services to which these PCPs referred patients to ranged from 25.4% to a healthcare worker within their practice or group to 41.3% to an organized program in a medical facility (TABLE). PCPs who discussed physical activity with many or most of their at risk patients were more likely to refer to an organized program within the community setting and less likely to refer to a healthcare worker outside their practice or group than their respective counterparts.

Conclusion:
Differences in the providers and services PCPs referred to for intensive behavioral counseling were observed by physical activity counseling frequency. Future work could explore the influence that the availability of different resources, especially community programs, has on improving PCPs’ physical activity counseling practices.
Abstract P173: Hyperthyroidism Increases the Risk of Takotsubo Cardiomyopathy Among Hospitalized US Patients
Authors: Akinjero Akintunde M , Adegbala Oluwole , Akinyemiju Tomi
Published: March 2022

Background:
The association between hyperthyroidism and Takotsubo Cardiomyopathy (TTCM) has only been reported in isolated case reports and a recent single center study with inconclusive results. It is known that elevated thyroid hormone causes an increased sympathetic modulation of heart rate. It has also been shown that TTCM occurs in the setting of acute stressful illnesses involving excess catecholamine release. What is unclear is whether hyperthyroid states can predispose to TTCM. This is the first nationwide study of this association.

Methods:
We used ICD-9 CM codes to extract data from the Nationwide Inpatient Sample database from 2007-2011. Patients with TTCM and coexisting hyperthyroidism were compared with TTCM patients without coexisting hyperthyroidism. We excluded persons below the age of 18 as well as patients diagnosed with TTCM who later underwent percutaneous coronary intervention (PCI). Multivariate logistic regression was used to assess the independent effect of coexisting hyperthyroidism on the occurrence of TTCM.

Results:
A total of 33,639,230 patients were included, where 123,923 patients had hyperthyroidism while 32,400,000 did not have hyperthyroidism. There were 101 (0.08%) TTCM patients with coexisting hyperthyroidism compared to 13,893 (0.04%) without (p<0.0001). In adjusted models, patients with hyperthyroidism had a higher risk of TTCM in the index hospital admission (aOR=1.43, 95% CI=1.18-1.74), independent of potential demographic, comorbid and lifestyle confounders. Hispanics with hyperthyroidism had the highest risk of TTCM (OR=1.41, 95% CI=1.39-1.44).

Conclusion:
In this large, nationwide study, hyperthyroidism was associated with increased risk of TTCM. This association was strongest among hispanics. Further research is needed to understand the mechanisms behind this association.
Abstract P182: Risk for Hypertension Extends Across Generations in the Community: a Multi-generational Cohort Study
Authors: Niiranen Teemu , McCabe Elizabeth , Larson Martin , Lakdawala Neal , Vasan Ramachandran , Cheng Susan
Published: March 2022

Background:
Hypertension is a major risk factor for cardiovascular disease, and parental hypertension is known to predict high blood pressure (BP) in children. However, the extent to which risk for hypertension is conferred across multiple generations, notwithstanding the impact of environmental factors, is unclear. Our objective was therefore to evaluate the degree to which risk for hypertension extends across multiple generations.

Methods:
We studied three generations of Framingham Heart Study participants with objectively ascertained, uniform BP measurements performed at serial examinations spanning 5 decades: First Generation cohort (1948-2005), Second Generation cohort (1971-2008), and Third Generation cohort (2002-2005). We examined the simultaneous associations of early-onset hypertension (prior to age 55 years) in parents or grandparents with normotension (BP <120/80; reference), prehypertension (BP 120-139/80-89 mmHg), and hypertension (BP ≥140/90 mmHg, or use of antihypertensive medication) in the Third Generation cohort. We estimated odds ratios (OR) and 95% confidence intervals (CI) for prehypertension and hypertension per additional parent or grandparent with early-onset hypertension using multinomial logistic regression adjusting for standard environmental factors.

Results:
Our final dataset for analyses included BP measurements collected from 2280 First Generation participants (i.e., grandparents), 3122 Second Generation participants (i.e., parents), and 3608 Third Generation participants (mean age 39 years, 53% women). In Third Generation participants, risk for elevated BP was conferred simultaneously by both parental (OR for prehypertension 1.72 [CI, 1.42-2.08]; OR for hypertension 2.22 [CI, 1.72-2.86]) and grandparental (OR for prehypertension 1.24 [CI, 1.05-1.46]; OR for hypertension 1.38 [CI, 1.11-1.73]) early-onset hypertension. In a secondary analysis with a subset of 3319 Third Generation participants with all covariates available, results were also similar in models additionally adjusting for physical activity and daily dietary intake of sodium.

Conclusions:
A predisposition for developing hypertension is conferred from grandparents to grandchildren, even after adjusting for parental history of hypertension and lifestyle factors. Additional studies are warranted to elucidate how identifying transgenerational risk for early-onset hypertension can improve the care of individuals at risk. Our results also suggest that when assessing an individual’s risk for hypertension, more accurate risk stratification could be achieved by considering both parental and grandparental history of hypertension.
Abstract P203: Building Cardiovascular Risk Prediction Models by Applying Machine Learning Methods to Right-Censored Electronic Health Data
Authors: Kotalik Ales , Vock David , Wolfson Julian , O’Connor Patrick
Published: March 2022

Background:
Cardiovascular (CV) risk prediction is useful in prioritizing resources and guiding treatment decisions. Most risk prediction equations are constructed using data from cohort studies. However, these cohorts often suffer from lack of diversity or generalizability. Therefore, there is an increasing interest in using electronic health data (EHD) to construct CV risk models. Given the size and complexity of EHD, machine learning (ML) techniques are an appealing alternative to time-to-event regression. However, the nature of EHD is such that subjects have varying duration of follow-up and some event times may be right censored. However, many ML techniques do not accommodate censoring.

Methods:
We propose a simple and universal method that allows any ML technique to accommodate right-censored data by averaging predictions over a set of weighted bootstrap samples, where the sampling weights are computed using inverse probability of censoring weighting (IPCW). IPCW is a method that reweights the observed data to represent the underlying population by assigning more weight to observed subjects who were likely to be censored. After resampling from the fully observed data, we fit a model and produce predictions in each iteration. Lastly, we offset computational times by using an ensemble. We consider the problem of predicting 5-year CV risk using EHD from a large health system (N=87,348), where 50% of subjects are censored. We compare our method to other ways of handling censoring.

Results:
Our technique consistently improved calibration by about 70-90% than approaches which ignored censoring (see below). However, there were no differences in discrimination. In conclusion, we show that miscalibration due to censoring can affect real-world treatment decisions, as demonstrated using the 2013 ACC/AHA treatment recommendation for statins. In such a scenario, one does not aim to identify for example top 10% highest risk patients, but rather the actual magnitude of risk for a single patient.
Abstract P218: Longitudinal Changes in Berry Intake and the Risk of Cardiovascular Disease in Women
Authors: Rautiainen Susanne , Wang Lu , Lee I-Min , Buring Julie E , Sesso Howard D
Published: March 2022

Background:
High intake of polyphenols has been linked to a lower risk of cardiovascular disease (CVD). Berries are high in polyphenols, including anthocyanins, along with other key nutrients. However, few studies have investigated the association between longitudinal changes in berry intake and long-term risk of CVD. The aim of this study was to investigate whether longitudinal changes in berry intake are associated with the risk of major CVD endpoints.

Methods:
Longitudinal changes in berry intake (sum of blueberries and strawberries) were assessed from two 131-item food-frequency questionnaires (FFQ) completed in 1992-1995 (FFQ1) and 2004 (FFQ2) among 29,598 middle-aged and older women free of CVD from the Women’s Health Study. Women also provided self-reports of a wide range of lifestyle, clinical and dietary factors at both timepoints. For each FFQ, women were categorized into two categories of total berry, blueberry, and strawberry intake: never/rarely and ≥1 time/month. Women were then categorized as having consistent low intake (never/rarely), consistent any intake (≥1 time/month), any increase in intake, and any decrease in intake between FFQ assessments. We used Cox proportional hazards models to calculate age and multivariable-adjusted hazard ratios (HRs) (95% confidence intervals (CI)). We included age, randomization assignments, smoking status, body mass index, physical activity, hormone replacement therapy, family history of myocardial infarction (MI), hypercholesterolemia, hypertension, diabetes, fruit and vegetable intake, saturated fatty acid intake, and omega-3 intake as covariates at the FFQ2 assessment.

Results:
During a mean follow-up of 9.9 years, we identified 851 cases of incident major CVD (MI, stroke, and CVD death). The intakes of total berries at FFQ1 were 23% (never/rarely) and 77% (≥1 time/month). Corresponding intakes at FFQ2 were 15% and 85%, respectively. In multivariable-adjusted models, consistently having any berry intake (HR: 1.00 (0.78-1.28)), any increase (HR: 0.89 (0.66-1.19)), or any decrease (HR: 0.84 (0.60-1.18)) in total berry intake over 10 years were not significantly associated with the risk of major CVD compared to women with consistently having no intake. A similar lack of association was observed for changes in strawberry intake. Increasing blueberry intake was associated with a lower risk of major CVD (HR: 0.83 (0.69-0.99)), whereas consistently having any blueberry intake (HR: 1.09 (0.91-1.29)) and any decrease in blueberry intake (HR: 0.97 (0.75-1.27)) were not associated with CVD.

Conclusions:
The results from this prospective study of middle-aged and older women initially free of CVD suggest that increasing blueberry intake over time may lower the risk of subsequent CVD.
Abstract P225: Obesity Genetic Risk Alleles Do Not Substantially Contribute to the Association Between Gestational Diabetes Exposure and Childhood Adiposity
Authors: Raghavan Sridharan , Zhang Weiming , Yang Ivana V , Fingerlin Tasha , Dabelea Dana
Published: March 2022

Background:
Prior work has demonstrated a strong association between gestational diabetes mellitus (GDM) exposure and childhood adiposity. However, it is unknown whether this association is attributable to specific intrauterine effects or merely to genetic transmission of risk alleles associated with obesity or other metabolic traits. We aimed to assess whether obesity and insulin resistance associated genetic risk alleles explain the association between gestational diabetes exposure and childhood adiposity.

Study Population:
Children aged 7 to 12 years enrolled in the Exploring Perinatal Outcomes in Children (EPOCH) Study who have genome-wide common variant genotyping (n=282), 82 of whom were exposed to GDM in utero and 200 of whom were not.

Methods:
Genetic risk scores (GRS) for body mass index (BMI) and insulin resistance (IR) were calculated by summing the count of 91 BMI-raising or 10 insulin resistance-raising risk alleles, respectively. Multivariable linear and logistic regression were used where appropriate to estimate associations between offspring GRS and maternal exposures (GDM and pre-pregnancy overweight/obesity [BMI >= 25]), as well as offspring GRS and childhood obesity traits (BMI and childhood waist circumference), adjusting for clinical and demographic covariates. Contribution of offspring GRS to association between maternal GDM or pre-pregnancy overweight/obesity and childhood adiposity was estimated by comparing the regression coefficient for the exposure variable in models with and without GRS.

Results:
The offspring BMI GRS was weakly associated with GDM (p=0.05), and more strongly associated with maternal pre-pregnancy overweight/obesity (p=0.001). Offspring BMI GRS was also strongly associated with childhood BMI (p=0.006) and waist circumference (p=0.02), whereas the insulin resistance GRS was not associated with GDM, maternal pre-pregnancy overweight/obesity, childhood BMI, or waist circumference. Offspring BMI genetic risk explained only 7.7% (95% CI -3.3, 18.8; p=0.2) and 5.8% (95% CI -3.1, 14.8; p=0.2) of the associations between GDM and childhood BMI and waist circumference, respectively. Similarly, offspring BMI genetic alleles explained only 4.8% (95% CI -5.4, 14.9; p=0.4) and 4.0% (95% CI -5.4, 13.4; p=0.4) of the associations between maternal pre-pregnancy overweight/obesity and childhood BMI and waist circumference, respectively.

Conclusions:
Genetic risk for obesity does not substantially explain the association between GDM exposure and childhood adiposity. The association between GDM and childhood adiposity is likely explained through alternative pathways, either through direct intrauterine effects or through shared postnatal environment.
Abstract P229: Prenatal Development and Obesity: Two Distinct Pathways to Diabetes in Adulthood
Authors: Boone-Heinonen Janne , Sacks Rebecca M , Hooker Elizabeth , Dieckmann Nathan F , Harrod Curtis S , Thornburg Kent L
Published: March 2022

Background:
Adverse prenatal development, often indicated by low birthweight, is associated with elevated risk of cardiometabolic disease, but the mediating role of obesity is not well understood.

Methods:
We used data from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative sample of adolescents followed 14 years over 4 waves into adulthood (1994-95, 1995-96, 2001-02, 2008-09; n=14,180). In gender-stratified path analysis, we examined pathways from birth weight [BW (kg); linear (BW) and quadratic (BW
2
)], to latent trajectories in body mass index (BMI) from adolescence to adulthood, to prevalent diabetes or prediabetes (DM; HbA1c, diagnosis, medication) in adulthood (Figure), adjusting for sociodemographic characteristics.

Results:
Direct associations between BW and DM (not through BMI) indicated that increasing BW was associated with non-significantly lower likelihood of DM in women [coeff (95% CI): BW: -0.30 (-1.23, 0.63); BW
2
: 0.01 (-0.14, 0.16)] and unrelated to DM in men. We identified distinct, gender-specific indirect pathways from greater BW to higher BMI and DM. In girls, the association between BW and BMI in adolescence was J-shaped, by which girls born lower and higher BW exhibited elevated BMI in adolescence [coeff (95% CI): BW: -2.10 (-3.96, -0.24); BW
2
: 0.44 (0.13, 0.75)]; higher BW predicted marginally faster BMI gain from adolescence to adulthood. Higher adolescent BMI and faster BMI gain was associated with diabetes in women [coeff (95% CI): BMI intercept: 0.09 (0.06, 0.12); BMI slope: 0.12 (0.08, 0.17)]. In boys, BW was not associated with BMI at adolescence or BMI gain thereafter; in turn, adolescent BMI was unrelated to diabetes, while faster BMI gain was associated with higher likelihood of adult DM [coeff (95% CI): 0.29 (0.20, 0.37)].

Conclusions:
Findings suggest that in girls, slowing BMI gain prior to adolescence and from adolescence to adulthood is critical for diabetes prevention, yet may not address distinct pathology stemming from early life.
Abstract P234: The Relationship Between Polyphenols and Body Composition within the Hispanic Community Health Study/Study of Latinos Nutrition and Activity Study
Authors: Makarem Nour , Mossavar-Rahmani Yasmin , Sotres-Alvarez Daniela , Hua Simin , Wong William W , Van Horn Linda , Daviglus Martha L , Franke Adrian , Beasley Jeannette M
Published: March 2022

Background:
Polyphenols have antioxidant properties that may protect against chronic disease.Epidemiological evidence regarding potential impact on body composition and obesity is limited, particularly among Hispanics/Latinos who are disproportionately prone to obesity.

Hypothesis:
Polyphenols are associated with lower percent body fat (%BF) and prevalence of obesity, with moderate intra-class correlations between repeated measures.

Methods:
Participants were 442 adults from SOLNAS aged 18-74y. Doubly labeled water, a recovery biomarker, estimated Total Energy Expenditure . Polyphenol excretion from 24-hour urine samples was assessed for enterolactone, enterodiol, resveratrol, daidzein, urolithin A, naringenin, hesperetin, and quercetin (nmol/liter). Measures were repeated in a subsample (N=90) to provide a reliability measure. Anthropometric measures were obtained by trained personnel, and %BF was measured by
18
O dilution. Diet was assessed using two 24-hour recalls. Linear regression models were used to evaluate the multivariable associations between body composition and polyphenols. Spearman correlations between BMI and %BF with polyphenols and intra-class correlation coefficients (ICCs) between repeated polyphenol measures were computed.

Results:
Resveratrol and %BF were weakly correlated (r=-0.11, p=0.02), but 69% of urinary resveratrol levels were below detectable limits. Hesperetin was associated with a 12% lower odds of obesity in models unadjusted for TEE (Table 1), while enterolactone was associated with 16% higher odds in fully-adjusted models. Repeated polyphenol measures were moderately correlated (ICCs:0.11-0.65). Urinary polyphenols and their main food sources were weakly correlated (r=0.10-0.17, p<0.03).

Conclusions:
Hesperetin and quercetin were inversely while enterolactone was positively associated with obesity. Findings are indicative of an immigrant group in transition. Repeated measures of urinary polyphenols could help clarify impact on obesity.
Abstract P237: Sex and Body-mass Index Specific Percentiles for Neck and Waist Circumference in the Longitudinal Study of Adult Health: ELSA Brasil
Authors: Baena Cristina P , Moura Bruno , Goulart Alessandra , Lotufo Paulo , Santos Itamar , Benseñor Isabela
Published: March 2022

Background:
Waist circumference (WC) and neck circumference (NC) have been linked with higher cardiovascular risk, which cannot be explained only by the association with higher BMI. Therefore, the distributions of predicted neck circumference and waist circumference values according to BMI may be a useful measurement of fat distribution.

Aim:
To describe percentiles for WC and NC according to BMI and stratified by sex in a large non-clinical based sample of middle-aged Brazilians.

Methods:
From the 15105 participants from ELSA-Brasil, 15085 partcipants with complete data were included in this analysis. Height and weight were measured using a standardized scale, and BMI was calculated by dividing body weight with the squared height in meters (kg/m2). Waist circumference (cm) was measured using standardized procedures and equipment. Neck circumference was measured with an inelastic tape (mm) immediately above the cricoid cartilage and perpendicular to the long axis of the neck, with the participant in a sitting position. We determined the estimated distribution function in men and women, with special interest in the 25
th
, 50
th
, 75
th
and 90
th
percentiles for neck and waist circumferences in ELSA-Brasil baseline fitting spline quantile regression models. Sex-specific nomograms were also built. Analyses were performed using R software and SPSS analytical package.

Results:
We evaluated 6880 men (52.2 ± 9.3 years old) and 8205 women (52.0 ± 8.9 years old). Among men, mean WC, NC and BMI were 95.3 ± 11.7 cm, 39.5 ±2.9 cm and 27.0 ± 4.3 kg/m2, respectively. Among women mean WC, NC and BMI were 87.8 ± 12.6 cm, 34.0 ±2.6 cm and 27.0 ± 5.1kg/m2, respectively. Table 1 shows respective 25
th
, 50
th
, 75
th
and 90
th
percentiles with correspondent 95% prediction interval in cm for NC and WC by BMI and sex.

Conclusion:
In this study, we describe sex-specific centile values for NC and WC according to BMI. This distribution may be useful in the study of body fat distribution as a marker of cardiovascular risk beyond BMI values.
Abstract P255: Use of Novel Oral Anticoagulants Among Patients With Atrial Fibrillation Increased Even in Those With Severely Impaired Kidney Function
Authors: Shin Jung-Im , Secora Alex , Coresh Josef , Chang Alex R , Grams Morgan E
Published: March 2022

Novel oral anticoagulants (NOACs) are increasingly prescribed as substitutes for warfarin in patients with atrial fibrillation (AF). All of the NOACs are at least partially renally cleared, but most trials excluded patients with severe kidney dysfunction. Despite this, labels include dosing for creatinine clearance 15-30 ml/min. The objective of the study was to estimate the prevalence of NOAC use over time among people with AF, stratified by stage of chronic kidney disease (CKD). Study population included 17,280 patients with AF and at least one prescribed anticoagulant (warfarin, dabigatran, rivaroxaban, or apixaban) between 2010 and 2016 in the Geisinger Health System, a large rural health care system in Pennsylvania. Medication information was obtained from both medication orders and records. Average age of the study population was 73.6 years, 46.6% (N=8,044) were women, 98.4% (N=17,009) were Non-Hispanic White, and average estimated glomerular filtration rate (eGFR) was 70.2 ml/min/1.73 m
2
. Over the course of 2010-2016, 3.0% (N=513), 6.9% (N=1,184) and 4.6% (N=792) received at least one prescription for dabigatran, rivaroxaban, or apixaban. NOAC ever-users (N=2,392) were younger (69.1 vs. 74.3 years,
P
<0.001) and had a higher eGFR (77.7 vs. 69.9 ml/min/1.73 m
2
) than warfarin-only users (N=14,888). Prescription of NOACs increased from 0% to 14.7% from 2010 to 2016 (
P
<0.001). Prescription of NOACs increased in each category of CKD (G1-2, G3 and G4-5, all
P
<0.001) (Figure 1). The most frequently prescribed NOAC in 2016 was rivaroxaban (8.2%) among those with eGFR>60 ml/min/1.73 m
2
and apixaban (5.9% and 4.9%) among those with eGFR 30-60 ml/min/1.73 m
2
and eGFR<30 ml/min/1.73 m
2
, respectively. Among the 22 patients prescribed apixaban with eGFR<30 ml/min/1.73 m
2
in 2016, 22.7% (5 of 22) had eGFR<15 ml/min/1.73 m
2
. In conclusion, NOAC prescriptions increased among patients with AF in all stages of CKD. Further studies to quantify the effectiveness and safety of NOACs compared to warfarin by stage of CKD are warranted.