bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 05: Association of 25-Year Body Mass Index Trajectories Throughout Early Adulthood With Nonalcoholic Fatty Liver Disease in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: VanWagner Lisa B , Khan Sadiya , NIng Hongyan , Siddique Juned , Lewis Cora E , Carr John Jeffery , Vos Miriam , Speliotes Elizabeth , Terrault Norah , Rinella Mary , Lloyd-Jones Donald M , Allen Norrina B
Published: July 2021

Background:
Nonalcoholic Fatty Liver Disease (NAFLD) has increased in parallel with obesity, is a risk factor for cirrhosis and liver cancer, and has few effective treatments. Identifying modifiable risk factors for NAFLD development is essential to effectively design prevention programs. We tested whether trajectories of body mass index (BMI) change throughout early adulthood were associated with risk of prevalent NAFLD in midlife independent of current BMI.

Methods:
Participants from the CARDIA study, a prospective multicenter population-based biracial cohort of adults (baseline age 18-30 years), underwent BMI measurement at exam years 0, 2, 5, 7, 10, 15, 20, and 25. At Year 25 (Y25, 2010-2011), liver fat was assessed by computed tomography. NAFLD was identified after exclusion of other causes of liver fat (alcohol/hepatitis). Latent mixture modeling was used to identify 25-year trajectories in BMI percent (%) change relative to baseline BMI over time. Multivariable logistic regression models were used to assess associations between BMI trajectory group and prevalent NAFLD with adjustment for baseline or current Y25 BMI.

Results:
Among 4,423 participants, we identified 4 distinct trajectories of BMI %change: stable BMI (26.2% of the cohort, 25-year mean BMI Δ=0.7 kg/m
2
), mild increase (46.0%, BMI Δ=5.2 kg/m
2
), moderate increase (20.9%, BMI Δ=10.0 kg/m
2
), and extreme increase (6.9%, BMI Δ=15.1 kg/m
2
) (Figure). NAFLD prevalence at Y25 was higher with increasing BMI trajectory: 4.1%, 9.3%, 13.0%, and 17.6% (p-trend <0.0001). At baseline, 34.6% of participants had overweight or obesity. After adjustment for confounders, trajectories of greater BMI increase were associated with greater NAFLD prevalence independent of baseline or current Y25 BMI (Figure).

Conclusion:
Weight gain throughout adulthood is associated with greater prevalence of NAFLD in midlife independent of baseline or current BMI. These findings highlight weight maintenance throughout adulthood as a potential target for primary prevention of NAFLD.
Abstract 08: Preterm Delivery and Maternal Cardiovascular Risk Factor Trajectories across the Life Course
Authors: Markovitz Amanda R , Haug Eirin B , Horn Julie , Fraser Abigail , Macdonald-Wallis Corrie , Tilling Kate , Romundstad Pål R , Åsvold Bjørn Olav , Rich-Edwards Janet W
Published: July 2021

Introduction:
Preterm delivery (<37 weeks) predicts 2 to 3-fold greater risk of cardiovascular disease in mothers. Development of subclinical cardiovascular risk in these women prior to and following pregnancy is not well understood.

Hypothesis:
Women who deliver preterm have an adverse cardiovascular health profile even prior to pregnancy.

Methods:
Linked data from the population-based, longitudinal HUNT study (1984-2008) and the Medical Birth Registry of Norway (1967-2012) yielded clinical measurements and pregnancy outcomes for 23,179 parous women. Women had up to 3 measurements of body mass index, waist circumference, blood pressure, non-fasting lipids and glucose, and high-sensitivity C-reactive protein (hs-CRP) during a follow-up period between 20 years before first birth to 41 years after first birth. We used mixed effects linear spline models, adjusting for age, pre-pregnancy smoking, education, and time since last meal, to compare risk factor trajectories for women with preterm versus term/postterm first births.

Results:
Women with a preterm first birth (n=1,402, 6%) had significantly higher triglyceride (Figure 1 A) and glucose levels prior to pregnancy. They also experienced steeper increases in systolic and diastolic blood pressure, non-HDL cholesterol, triglycerides, and hs-CRP from first birth to age 50 compared to women who delivered at term/post-term (Figure 1 A,B). Measures of adiposity were similar throughout the life course.

Conclusions:
These results are consistent with the hypothesis that preterm birth is an early marker of cardiometabolic impairment. A history of preterm birth may predict high cardiovascular risk well before the development of traditional risk factors.
Abstract 13: Adherence to Various Dietary Patterns and Risk of Recurrent Coronary Heart Disease and Mortality in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Shikany James M , Safford Monika M , Bryan Joanna , Newby PK , Richman Joshua S , Durant Raegan W , Brown Todd M , Judd Suzanne
Published: July 2021

Background:
We have shown that the Southern dietary pattern, characterized by added fats, fried foods, organ and processed meats, and sugar-sweetened beverages, is associated with a greater risk of incident CHD in REGARDS, a national, population-based, longitudinal cohort. We sought to determine if the Southern pattern, other dietary patterns, and the Mediterranean diet score were associated with CHD events and mortality in REGARDS participants who previously reported CHD.

Methods:
REGARDS enrolled white and black adults aged ≥45 years between 2003-2007. Data were analyzed from 3,562 participants with CHD at baseline. Participants completed an FFQ at baseline, from which 5 dietary patterns were derived through factor analysis (Table). The Mediterranean diet score was calculated for each participant. Expert-adjudicated CHD events included myocardial infarction and CHD death. Cox proportional hazards regression was used to model the association of the dietary patterns and score with CHD events and death, adjusting for sociodemographics, lifestyle factors, energy intake, anthropometrics, and medical conditions.

Results:
Over 7 years of follow-up, there were 581 recurrent CHD events and 1,098 deaths. In fully-adjusted analyses, the highest quartile of adherence to the alcohol/salads pattern and highest group of the Mediterranean diet score were associated with lower risk of recurrent CHD compared to the lowest quartile/group (HR: 0.76; 95% CI: 0.59 – 0.98, HR: 0.78; 95% CI: 0.62 – 0.98, respectively). The highest quartile of adherence to the Southern pattern was associated with higher mortality (HR: 1.57; 95% CI: 1.28 – 1.91), while the highest group of the Mediterranean diet score was associated with lower mortality (HR: 0.80; 95% CI: 0.68 – 0.95).

Conclusions:
While the Southern dietary pattern was not related to risk of recurrent CHD, it was associated with higher mortality in REGARDS participants with existing CHD. Greater adherence to a Mediterranean diet was associated with lower risk of recurrent CHD and mortality.
Abstract MP023: Changes in Systolic Blood Pressure Differs by Immigration History in a Cohort of Older Mexican Americans
Authors: To Tu My , Neuhaus John M , Sudhinaraset May , Albert Michelle A , Haan Mary N
Published: July 2021

Background:
Studies on immigrant health suggest that foreign-born individuals have better health outcomes than their native-born counterparts due to health selection. However, effects of immigration history on changes in cardiovascular conditions and risk factors are less well understood.

Objective and Hypothesis:
We examined the association between immigration history and change in systolic blood pressure (SBP). We hypothesized that Mexican Americans born outside the US and immigrated after age 30 (FB30+), would have lower SBP at baseline and have slower increase in SBP compared to people who were born in the US (US-B) or immigrated from Mexico before age 30 (FB<30).

Methods:
Participants come from the Sacramento Area Latino Study on Aging (n=1789), a longitudinal cohort of community-dwelling older Mexican Americans (mean age=70.6 years); 51% were born in Mexico. Immigration history was categorized as US-B, FB<30, and FB30+. SBP measures were available at baseline and at five follow-ups over ten years. A mixed effects linear model was used to examine the association between immigration history and SBP. Other covariates included gender, education, current hypertension medication use, and baseline measures of age, BMI, and diabetes. Follow up time was defined as time since enrollment. Quadratic time was included to account for non-linear change in SBP. Two interaction terms (immigration history x linear time and immigration history x quadratic time) were included to assess differences in SBP change by nativity.

Results:
The study included 1598 participants after exclusions. The figure shows the predicted average SBP by immigration history over the study period, derived from the mixed linear model. Compared to US-B, the FB<30 and FB30+ experienced an average of 7.3 (95% CI 2.0-12.7) and 7.9 (95% CI 2.2-13.5) mmHg increase in SBP over the study period, respectively.

Conclusions:
In contrast to current literature, immigrants appeared to be at greater risk for adverse cardiovascular risk factors.
Abstract MP033: Socioeconomic Disparities in the Risk of Developing Heart Failure: Prospective Findings from the Moli-Sani Study
Authors: Bonaccio Marialaura , Di Castelnuovo Augusto , Costanzo Simona , Persichillo Mariarosaria , Rago Livia , De Curtis Amalia , Donati Maria Benedetta , de Gaetano Giovanni , Iacoviello Licia ,   Moli-sani Study Investigators
Published: July 2021

Introduction:
The association between socioeconomic status (SES) and the risk of cardiovascular disease and all-cause mortality is well-established, while the impact of SES on heart failure (HF) incidence is less explored.

Hypothesis:
We tested the hypothesis of a SES gradient in the risk of HF.

Methods:
Population-based cohort study on 22,395 individuals (mean age 55.3±11.7, 47.7% men) free from HF at baseline randomly recruited from the general population included in the Moli-sani study (Italy). The cohort was followed up for a median of 7.6 years (168,031 person-years). Annual household income (Euros) and educational level were used as SES indicators. Presence of risk factors at baseline and a panel of health behaviours were tested as possible mediators of the association between SES and incident HF. Incident HF at follow-up was defined by HF hospitalization or HF death, according to the International Classification of Diseases-Ninth Revision (ICD-9). Hazard ratios (HR) with 95% confidence intervals were calculated by Cox-proportional hazard models.

Results:
We identified 757 first HF events. Both lowest education (middle and secondary schools) and household income (<60,000 Euros/y) were separately associated with increased risk of HF as compared with the highest category (Table). After simultaneous adjustment, the association of income appeared to be largely explained by education. The inclusion of traditional risk factors, biomarkers of heart failure and health-behaviors into the model attenuated the association of low education with HF incidence by 12%, 3.8% and 11.5%, respectively. Overall, the full explanatory model accounted for 23.8% of the educational gradient in the risk of HF (Table).

Conclusions:
Educational level, rather than income, is an independent predictor of HF development. Excess risk associated with low education was partially explained by traditional health risk factors, biomarkers of subclinical damage and health-behaviors.
Abstract MP042: Higher Levels of Sodium Density (mg/kcal) are Associated With Increased Blood Pressure Independent of Absolute Sodium (mg): the DASH Sodium Trial
Authors: Murtaugh Maureen A , Appel Lawrence J , Beasley Jeannette M , Guenther Patricia M , Greene Tom , McFadden Molly L , Tooze Janet A
Published: July 2021

Introduction:
Dietary recommendations for Na are expressed as absolute amounts, that is, mg of Na/d rather than as Na density (mg/kcal). The DASH-Na dose-response trial tested the impact of varying Na density on BP, that is, the absolute dose of Na received at the low, medium, and high levels depended on energy intake. For example, a dose of 3,600 mg was high density in individuals with average energy intake but was medium density in individuals with higher energy intake.

Objective:
Evaluate whether the effect of Na density on BP was independent of absolute Na.

Methods:
In the DASH-Na trial, participants with pre-or stage 1 hypertension were randomly assigned to a control or DASH diet; on both diets, participants were fed each of three Na levels in random order. We analyzed data from 378 Non-Hispanic Black and White participants (ages 23-76 yr, baseline BP 135/86). Using a mixed effects model, level of Na density (low, medium, or high) was added to a model of absolute Na on BP to determine if the effect of Na density on BP was independent of absolute Na, with adjustment for randomized diet, cohort, carryover, clinical center, age, sex, race, and interactions of diet with absolute Na and Na density.

Results:
At the same absolute amount of Na, higher Na density was associated with higher SBP and DBP (both p<0.0001) in the control diet arm (Figure 1). At the recommended upper limit of Na (2300 mg), the average SBP and DBP of those on a medium-Na-density diet was 7.2 mmHg (95% CI: 4.8, 9.7) and 3.9 mmHg higher (95% CI: 2.3, 5.5), respectively, than those on a low-Na-density diet. At 3600 mg, the average SBP and DBP of those on a high-Na-density diet was 6.0 mmHg (95% CI: 3.6, 8.5) and 3.1 mmHg (95% CI: 1.5, 4.7) higher, respectively, than those on a medium-Na-density diet. These differences were somewhat smaller, but still significant, in the DASH diet arm.

Conclusions:
The effects of Na on BP vary with energy needs. This suggests that Na density should be considered when designing and interpreting studies of Na and BP and when providing dietary guidance.
Abstract MP054: Associations of Monounsaturated Fat From Plant and Animal Sources With Coronary Heart Disease Risk
Authors: Zong Geng , Li Yanping , Wanders Anne , Zock Peter , Sampson Laura , Willett Walter , Hu Frank , Sun Qi
Published: July 2021

Background:
The association between monounsaturated fat (MUFA) intake and coronary heart disease (CHD) risk remains unclear. We aimed to investigate whether MUFA from plant foods (MUFA-P) and animal foods (MUFA-A) show different associations with CHD risk in two large prospective studies of U.S. men and women.

Method:
We calculated MUFA-P and MUFA-A among 60,931 women in the Nurses’ Health Study (1990-2012), and 28,445 men in the Health Professionals Follow-Up Study (1990-2010). Diet was assessed by validated food-frequency questionnaire every 4 years. CHD incidence was self-reported and confirmed by review of medical records or death certificates.

Result:
MUFA-A (median intake: 5.8-6.1% energy) was highly correlated with saturated fat (SFA; spearman correlation [
r
] =0.81-0.83) but not polyunsaturated fat (PUFA,
r
=0.04 -0.19), whereas MUFA-P intake (median: 5.3-5.4.9% energy) was strongly correlated with PUFA(r=0.61 for both cohorts) but not SFA (
r
=0.20-0.21; All P<0.001). In multivariate models adjusted for demographic, lifestyle, and dietary factors, hazard ratios of CHD (HR, 95% confidence interval[95%CI]) from low to high total MUFA quintiles were 1 (reference), 0.92 (0.83, 1.02), 1.03 (0.93, 1.05), 0.89 (0.79,1.00). 0.95(0.873, 1.08; P
trend
=0.42). For MUFA P these were 1(reference), 0.98 (0.89, 1.07), 0.90 (0.82, 0.99), 0.85 (0.77, 0.93), and 0.86 (0.78, 0.94; P
trend
<0.001) and for MUFA-A 1(reference), 1.09 (0.99, 1.20), 1.22 (1.11, 1.35), 1.26 (1.13, 1.39), and 1.33 (1.19, 1.48; P
trend
<0.001). In the energy-density model, CHD risk was lower when MUFA-P iso-calorically replaced 1% energy from total SFA (HR [95%CI]: 0.96[0.92, 1.00]; P=0.03), with no significant changes when MUFA-A replacing SFA (HR [95%CI]: 1.01[0.95, 1.07]; P=0.76). When grouping fat intake as the sum of animal MUFA plus saturated fat and the sum of plant MUFA plus PUFA, the HR (95%CI) of CHD was 0.96 (0.95, 0.98; P<0.001) for replacing 1% energy from the former with the latter.

Conclusion:
Because MUFA compositions of animal and plant origins are largely similar, our data suggested other components in plant and animal foods may lead to the observed different associations of MUFA-P and MUFA-A with CHD risk. These findings provided a possible explanation on current controversies regarding MUFA intake and CHD risk, and further support health benefit of MUFA intake.
Abstract MP058: Racial and Gender Differences in Acute Ischemic Stroke Pre-hospital Documentation: Last Known Well, Pre-alert Notification and Stroke Severity, Paul Coverdell National Acute Stroke Program, 2012-2015
Authors: Odom Erika , Coleman King Sallyann ,   the Paul Coverdell National Acute Stroke Program Team, Tong Xin
Published: July 2021

Stroke is the fifth leading cause of death in the United States and a major cause of adult disability. Documentation of stroke-related factors that occur before arrival to the hospital or immediately upon arrival may be critical in determining patient eligibility for life-saving measures, including receipt of thrombolytic therapy (e.g., alteplase) and other neurointerventional treatment. There is a need to describe differences in documentation of pre-hospital measures, in order to improve overall stroke patient care. De-identified data for 216,129 stroke patients were reported by hospital personnel during the 2012-2015 Paul Coverdell National Acute Stroke Program. Chi-square tests were performed to examine the differences on demographic and pre-hospital measures by gender and race. The median age was greater for females than males (75 vs 68 years) and for whites than blacks (74 vs 63 years). A higher percentage of females had Medicare coverage than males (67.8% vs. 57.4%, p<0.001), while blacks had higher Medicaid coverage than whites (12.8% vs. 4.2%, p<0.0001). Females (49.9%) and blacks (48.8%) had the highest percentage of arrival by EMS. Among patients who arrived by emergency services, the percentage of blacks with advance notification of stroke was lower than whites (49.8% vs. 58.2%, p<0.0001). Females (53.0%) were slightly less likely to have last known well time recorded than males (53.8%). Blacks were significantly less likely to have last known well time and stroke severity recorded compared whites (p<0.0001). The median time interval between last known well and emergency department arrival for blacks were 4.8 hours, significantly longer than median time of 4.0 hours for whites (p<0.001). Differences in documentation of pre-hospital measures, particularly between racial groups, suggest room for improvement in communication of information from the pre-hospital environment to emergency department staff, which may support access to critical links in the chain of stroke survival, including activation of stroke care teams who can provide swift access to life-saving treatment.
Abstract P005: Improving Heart Health in the Workplace: Results From the First Year of the American Heart Association’s Workplace Health Achievement Index
Authors: Calitz Chris , Pham Kristin , Santana Adela , Sanchez Eduardo , Arena Ross , Fonarow Gregg C
Published: July 2021

Background:
Comprehensive workplace wellness programs (CWWPs) have the potential to improve the heart health of the US workforce. To accelerate the adoption of these programs, the American Heart Association launched the Workplace Health Achievement Index (WHAI). The WHAI is an online scorecard that evaluates a workplace’s culture of health and the aggregate heart health score of its workforce as measured by Life’s Simple 7. Evidence from other workplace scorecards indicate that smaller companies achieve lower scores.

Objective:
To quantify differences in WHAI scores and score components between smaller (<250 employees) and larger (250+ employees) worksites.

Methods:
The total WHAI score is derived from 55 structure and process measures across seven best-practice domains and performance metrics based on employee Life’s Simple 7 data. Data from the first WHAI cycle (Feb 1 - June 30, 2016) were analyzed from 239 worksites that provided structure and process information. All data were stratified according to company size (smaller vs. larger). Differences in practice and performance measures were assessed across groups using Pearson chi-square tests or paired t-tests.

Results:
Overall, 5% of workplaces submitted the required amount of heart health metrics data (≥25% of employees) for eligibility. Smaller companies achieved a lower total WHAI score and lower scores across all domains except for Partnerships (Table 1).

Conclusion:
Lower WHAI scores for smaller companies may be due to limited resources and capacity to implement CWWPs. Low submission of performance metrics highlights the challenge of including these data in a comprehensive assessment of CWWPs. To meet its 2020 Goals, AHA should consider providing smaller companies with resources to implement CWWPs and develop strategies to increase submission of employee Life’s Simple 7 data.

Table 1: Differences in mean AHA Index scores between small and large companies

*Sample sizes too small for meaningful comparison.
Abstract P014: Lower eGFR and Proteinuria Were Independently Associated With Lower Cognitive Abilities in Community-dwelling Men in Japan: SESSA study
Authors: Fujiyoshi Akira , Ohkubo Takayoshi , Miura Katsuyuki , Shiino Akihiko , Miyagawa Naoko , Takashima Naoyuki , Saitoh Yoshino , Torii Sayuki , Kadota Aya , Kadowaki Sayaka , Hisamatsu Takashi , Miyazawa Itsuko , Tooyama Ikuo , Ueshima Hirotsugu
Published: July 2021

Introduction:
The relationship between chronic kidney disease (CKD) and cognitive function remains to be determined. Existing studies focused primarily on estimated glomerular filtration rate (eGFR) but not proteinuria in relation to cognitive function.

Hypothesis:
In a community-based sample, lower eGFR and presence of proteinuria are cross-sectionally independently associated with lower cognition.

Methods:
The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited and examined participants from Shiga, Japan in 2006-08 at baseline. Among 824 male participants in the follow-up exam (2010-12), we restricted our analyses to those who underwent the Cognitive Abilities Screening Instrument (CASI), age ≥65 years-old, free of stroke, with no missing pertinent covariates. We calculated eGFR (creatinine-based) according to the 2012-guideline by the Japanese Society of Nephrology. We then divided the participants into three groups by eGFR of ≥60, 59-40, and <40 (mL/min/1.73m
2
), and separately divided into three groups according to proteinuria using urine dipstick: (-), (-/+), and ≥(1+). We defined CKD as either eGFR <60 or proteinuria ≥ (-/+). In linear regression with CASI score being a dependent variable, we computed the score adjusted for age, highest education attained, smoking, drinking, body mass index, hypertension, diabetes, and dyslipidemia.

Results:
We analyzed 541 men. The mean [standard deviation] of age and unadjusted score were 72.6 [4.3] years and 89.7 [6.0]. Prevalence of CKD was 56%. The score was significantly lower in participants with CKD than those without it (P=0.03). eGFR and proteinuria categories were separately and jointly associated with lower CASI score in a graded fashion (Ps for trend <0.05 in all the models tested.
Table 1
).

Conclusions:
Lower eGFR and higher degree of proteinuria were independently associated with lower cognitive function in the community-based men. CKD even in its early phase may predispose to lower cognitive function.
Abstract P048: Risk Factors for Severe Hypoglycemia Differ in Black and White Older Adults With Diabetes: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Lee Alexandra K , Warren Bethany , Lee Clare J , Huang Elbert S , Sharrett A. Richey , Coresh Josef , Selvin Elizabeth
Published: July 2021

Introduction:
Blacks with diabetes have roughly twice the rate of severe hypoglycemia compared to whites with diabetes; it is unclear whether hypoglycemia risk factors identified in studies of white participants are similarly associated with hypoglycemia in blacks.

Methods:
We included ARIC participants aged 65+ at Visit 4 (1996-1998) who had Medicare fee-for-service Part B and diagnosed diabetes. We identified severe hypoglycemic events through 2013 using ICD-9 codes from hospitalizations, emergency department visits, and ambulance services. We evaluated previously identified risk factors: age, sex, chronic kidney disease (CKD), diabetes medication use, obesity, cognition, glycemic control, and number of comorbidities. We stratified Cox proportional hazards models by race and used Harrell’s C-statistic to compare discrimination.

Results:
There were 33 hypoglycemic events in 135 black participants and 43 hypoglycemic events in 319 white participants (incidence rate 2.8 vs. 1.5 per 100 person-years, p<0.01). Most risk factors had similar associations with risk of hypoglycemia in blacks and whites, with some notable exceptions. Obesity was associated with greater risk in blacks but not whites (
Table
). CKD was more strongly associated with risk in blacks than whites. Type of diabetes medication was associated with risk in whites but not in blacks. The C-statistic suggested better model discrimination in whites (C=0.795) than in blacks (C=0.759), but confidence intervals were wide.

Conclusion:
The direction and strength of risk factors for hypoglycemia may differ for blacks and whites. It is unclear why the relative importance of risk factors for hypoglycemia differ between whites and blacks. These data suggest that the mechanism by which CKD influences hypoglycemia risk may be decreased renal gluconeogenesis in blacks and reduced insulin clearance in whites. Additional research is needed to understand those factors that contribute to hypoglycemia risk in blacks and may underlie health disparities.
Abstract P053: Diabetes Risk Prediction and Sickle Cell Trait in African Americans From CARDIA and the Jackson Heart Study
Authors: Lacy Mary E , Wellenius Gregory A , Correa Adolfo , Carnethon Mercedes R , Leim Robert I , Luo Xi , Wilson James G , Gjelsvik Annie , Carson April P , Jacobs David R , Eaton Charles B , Wu Wen-Chih
Published: July 2021

Introduction:
Existing models to predict incident diabetes mellitus (DM) perform better in Whites than African Americans. In models that incorporate hemoglobin A1c (A1C) as a predictor of DM, the difference in model performance by race is more pronounced. In a recent study, we found that A1C was systematically underestimating glycemia in African Americans with sickle cell trait (SCT).

Hypothesis:
Given the poorer performance of DM prediction models in African Americans than Whites and the impact of SCT on the A1C-glycemia association, we hypothesized that incorporating sickle cell trait into DM prediction models would improve the ability of the model to predict future risk of DM.

Methods:
We pooled data collected from 2000-2012 on 3,122 African Americans (8.6% with SCT) from the Jackson Heart Study (JHS; n=2,065; mean age=54.71 years) and CARDIA (n=1,057; mean age=44.53). Over 5 years of follow-up in CARDIA and 10 years of follow-up in JHS, 85 CARDIA participants (8.1%) and 342 JHS participants (16.6%) developed DM. Using generalized estimating equations to account for correlation of repeated measures, we compared the discriminative ability and net reclassification improvement (NRI) resulting from the addition of SCT for a series of prediction models.

Results:
Overall, the addition of SCT to prediction models did not result in significant improvement in the discriminative ability. However, by the NRI index, the addition of SCT to measures of glycemia and to a fuller risk prediction model did improve prediction of DM. In the full model, adding SCT*A1C as a predictor resulted in 2% of events being reclassified as higher risk and 45% of non-events being reclassified as lower risk.

Conclusion:
Our results suggest that incorporating SCT into DM prediction for African Americans may result in modest improvement in model performance.
Abstract P078: Childhood Social Determinants Explain Ethnic Disparities in Obesity Among Black American Women
Authors: Barrington Debbie
Published: July 2021

Introduction:
Black American women have the highest prevalence of obesity in the United States (US). Ethnic disparities in this risk factor for cardiovascular disease have been found; Afro-Caribbean women have lower rates of obesity compared with African American women. Contributing factors of the ethnic disparity in adult obesity have yet to be fully elucidated. However, the emergence of the ethnic disparity in adolescence suggests a potential role for childhood social determinants.

Hypothesis:
Childhood social determinants are hypothesized to explain the ethnic disparity in obesity between African American and Afro-Caribbean women in the United States.

Methods:
Multiple logistic regression models were used to examine childhood social factors and adult social, health and lifestyle risk factors that explain the ethnic disparity in obesity between African American (N = 2299) and Afro-Caribbean women (N = 978), 18 years and older, in the National Survey of American Life (2001-2003). Adult socioeconomic factors included marital status, education, occupation, home ownership and poverty status. Adult health and lifestyle risk covariates included hypertension, diabetes, menopausal status, smoking, alcohol use and physical activity. Childhood social factors included measures of parental education, receipt of public assistance prior to 18 years of age, and type of high school attended (private/parochial vs. public). Odds ratios (OR) of the association between ethnicity and adult obesity were estimated after adjusting age and adult socioeconomic measures, adult health and lifestyle measures and childhood social factors within the models.

Results:
The prevalence of obesity was 40.5% among African American women and 30.8% among Afro-Caribbean women. Afro-Caribbean women had 34% lower odds of obesity than African American women; age-adjusted OR = 0.66; 95%CI: (0.52, 0.82). Adjusting for age and adult socioeconomic factors slightly decreased the ethnic disparity; adjusted OR = 0.70; 95%CI: (0.53, 0.94). Adjusting for age and adult health and lifestyle factors decreased the disparity by 11%; adjusted OR = 0.73; 95%CI: (0.55, 0.97). Adjusting for age and childhood social factors eliminated the ethnic disparity; adjusted OR = 1.00; 95%CI: (0.82, 1.23).

Conclusions:
These findings suggest that childhood social factors are key contributors to the ethnic disparities in obesity between African American and Afro-Caribbean women in the US.
Abstract P093: Analysis Commons: Team Science in a Big-data Environment for Genetic Epidemiology
Authors: Brody Jennifer A , Morrison Alanna , Bis Joshua C , O’Connell Jeffrey , Huffman Jennifer , Lewis Joshua P , Psaty Bruce M , Boerwinkle Eric , Cupples L A ,   on behalf of the TOPMed Hemostasis and the CHARGEAnalysis and Bioinformatics Working Groups
Published: July 2021

The growing volume and complexity of whole-genome sequence (WGS) and multi-omic data requires new analytic approaches beyond those developed for the GWAS era. In response to this challenge, we present an Analysis Commons, which brings together genotype and phenotype data from multiple studies along with a suite of powerful and validated analysis tools into a secure cloud-computing framework that is equitably accessible by associated investigators. This framework is designed to address the emerging challenges of multi-center WGS analyses—data sharing mechanisms, phenotype harmonization, -omics integration, annotation—and the need for flexible, secure, efficient, high-performance computing for numerous users.

The Analysis Commons is built on the DNAnexus cloud platform, which provides large parallel compute resources and robust security protocols. To permit multi-center data sharing, we implemented two parallel data sharing approaches: (1) a multi-lateral consortium agreement that enables data sharing across multiple studies, and (2) coordinated dbGaP applications among groups of institutions. Investigators with detailed knowledge of the phenotypes and contributing studies harmonize data from multiple sources for maintenance in a central database. The Analysis Commons supports multiple association-analysis software packages, as well as tools for annotation and visualization. Importantly, approved investigators have full access to the combined data sets, facilitating the rapid development and deployment of new methods.

We demonstrate the Analysis Commons model with an analysis of fibrinogen in 3999 participants from the Old Order Amish Study and the Framingham Heart Study with WGS from the Trans-Omics for Precision Medicine (TOPMed) Program. We performed and validated single-variant and SKAT analyses using GENESIS and MMAP pipelines, accounting for relatedness with linear mixed models. We confirmed a known association of a nonsynonymous variant in
FGG
(p=2.5e-9, MAF=0.34%, rs148685782)
.
No other single variant or SKAT association was significant after correcting for the number of tests. Analyses were run in parallel across 1408 cores and took less than one hour of wall-clock time.

The Analysis Commons offers the necessary infrastructure support for analysis of WGS and multi-omic data in a setting that empowers phenotype, analytic, and computational experts to transform raw data into knowledge of the determinants of cardiovascular health.
Abstract P098: An Epigenome-wide Study of Obesity in African American Youth and Young Adults: Novel Findings, Replication in Neutrophils and Relationship With Gene Expression
Authors: Wang Xiaoling , Pan Yue , Zhu Haidong , Hao Guang , Wang Xin , Huang Yisong , Harshfield Gregory , Barnes Vernon , Shi Huidong , Su Shaoyong
Published: July 2021

Background:
Several large-scale epigenome wide association studies on obesity-related DNA methylation changes have been published and in total identified 46 CpG sites. These studies were conducted in middle-aged and older adults of Caucasians and African Americans (AAs) using leukocytes. To what extend these signals are independent of cell compositions as well as to what extend they may influence gene expression have not been systematically investigated. Furthermore, the high prevalence of obesity comorbidities in middle-aged or older population may hide or bias obesity itself related DNA methylation changes.

Methods:
In this study of healthy AA youth and young adults, genome wide DNA methylation data from leukocytes were obtained from three independent studies: EpiGO study (96 obese cases vs. 92 lean controls, aged 14-21, 50% females, test of interest is obesity status), LACHY study (284 participants from general population, aged 14-18, 50% females, test of interest is BMI), and Georgia Stress and Heart study (298 participants from general population, aged 18-38, 52% females, test of interest is BMI) using the Infinium HumanMethylation450 BeadChip. Genome wide DNA methylation data from purified neutrophils as well as genome wide gene expression data from leukocytes using Illumina HT12 V4 array were also obtained for the EpiGO samples.

Results:
The meta-analysis on the 3 cohorts identified 76 obesity related CpG sites in leukocytes with p<1х10
-7
. Out of the 46 previously identified CpG sites, 36 can be replicated in this AA youth and young adult sample with same direction and p<0.05. Out of the 107 CpG sites including the 36 replicated ones and the 71 newly identified ones, 71 CpG sites (66%) had their relationship with obesity replicated in purified neutrophils (p<0.05). The analysis on the cis regulation of the 107 CpG sites on gene expression showed that 59 CpG sites had at least one gene within 250kb having expression difference between obese cases and lean controls. Furthermore, out of the 59 CpG sites, 6 showed significantly negative correlations and 1 showed significantly positive correlation with the differentially expressed genes. These CpG sites located in SOCS3, CISH, ABCG1, PIM3 and PTGDS genes.

Conclusion:
In this study of AA youth and young adults, we identified novel CpG sites associated with obesity and replicated majority of the CpG sites previously identified in middle-aged and older adults. For the first time, we showed that majority of the obesity related CpG sites identified from leukocytes are not driven by cell compositions and provided the direct link between DNA methylation-gene expression-obesity status for 7 CpG sites in 5 genes.
Abstract P110: Gene-Gene Interaction:
SERPINE1
Interacts with
ANRIL
in Association with Coronary Artery Disease and Coronary Artery Calcium in a Non-Hispanic Population
Authors: Pratte Katherine A , Lutz Sharon M , Fingerlin Tasha E , Bowler Russell P , Kinney Gregory L , Young Kendra A , Cho Michael H , Casaburi Richard , Silverman Edwin K , Crapo James D , Budoff Matthew J , Hokanson John E
Published: July 2021

Introduction:
Long non-coding RNAs (lncRNA) are important regulators of gene expression.
ANRIL
(
CDKN2B-AS1
) is an anti-sense lncRNA coded for at the Chr9p21 locus. GWAS have reported SNPs in the Chr9p21 to be associated with clinical coronary artery disease (CAD) and coronary artery calcium (CAC). A knockdown study of two isoforms of
ANRIL
reported the potential of
ANRIL’s
regulation of
SERPINE1
expression.
SERPINE1
encodes plasminogen activator inhibitor-1 (PAI-1) and has been reported to be associated with CAD and CAC. The 3’UTR of
SERPINE1
has been reported to bind miRNA and lncRNA suggesting
ANRIL
may modify
SERPINE1’s
association with CAD and CAC.

Hypothesis:
We hypothesized that rs7242 or rs1050955, covering the LD of the 3’ UTR of
SERPINE1,
will interact with SNPs within
ANRIL
to affect their association with self-reported CAD and CAC in non-Hispanic Whites (NHW, n=6103) and African Americans (AA, n=2549) in the COPDGene Study.

Methods:
Interaction of SNPs from Illumina HumanOmniExpress Beadchip for
ANRIL
, and rs7242 and rs1050955 were evaluated in an additive genetic model with a cross-product interaction term. Logistic regression was used to evaluate the association of CAD (Yes/No) and CAC (Yes/No) with the SNP-SNP interactions, while controlling for genetic ancestry, ascertainment, age, sex, BMI, diabetes, hypertension, high cholesterol and pack-years of smoking. Analyses were stratified by race.

Results:
A significant interaction between rs7242 (
SERPINE1
) and rs7049105 (
ANRIL
) and CAD (p=0.0004) and CAC (p=0.0023) were found in NHW (Figure 1). The risk estimates for the rs7242 G allele in
SERPINE1
were higher in those with the rs7049105 AA genotype in
ANRIL
but were lower in those with the rs7049105 GG genotype in
ANRIL
. We did not find any significant interactions in AA.

Conclusion:
In this study, the previously identified GWAS signal for CAD and CAC in Chr9p21 (
ANRIL
) interacts with a SNP in
SERPINE1
. This may be due to
ANRIL
lncRNA influences on gene expression of
SERPINE1
and increases the risk of both CAC and CAD.
Abstract P120: Relationship of Lipoproteins With Cardiovascular Disease in Persons With Chronic Kidney Disease
Authors: Bajaj Archna , Xie Dawei , Cedillo-Couvert Esteban , Charleston Jeanne , Chen Jing , Deo Rajat , Feldman Harold I , Go Alan S , He Jiang , Horwitz Edward , Kallem Radhakrishna R , Rahman Mahboob , Weir Matthew R , Anderson Amanda H , Rader Daniel J
Published: July 2021

Introduction:
Chronic kidney disease (CKD) is associated with dyslipidemia (particularly elevated triglycerides [TG] and reduced HDL-cholesterol [HDL-C]) and increased risk of atherosclerotic cardiovascular disease (CVD). However, the association between lipoprotein measures and CVD events in CKD is not well defined.

Hypothesis:
We hypothesize that high TG and low HDL-C are associated with increased risk for CVD (myocardial infarction [MI] and ischemic stroke) in CKD.

Methods:
The Chronic Renal Insufficiency Cohort (CRIC) is a prospective study of adults with CKD. We compared tertiles of TG, total cholesterol (TC), VLDL-cholesterol (VLDL-C), LDL-cholesterol (LDL-C), HDL-C, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I) with risk for MI and ischemic stroke using Fine and Gray methods with death as a competing risk. The lowest tertile was used as the reference category except for HDL-C and apoA-I, in which the highest tertile was used. In secondary analyses, we excluded participants with previous MI or stroke.

Results:
Among 3811 participants (55% men, 42% Caucasian) with mean age 57.7±11.0 years, 351 had an MI, 132 had an ischemic stroke, and 963 died over a median follow-up of 7.9 years. After adjusting for potential confounders, the hazard ratio (HR, 95% CI) for CVD was 1.04 (0.80-1.34) for high LDL-C, 1.31 (1.01-1.69) for high TG, 1.33 (1.04-1.70) for high VLDL-C, 1.30 (1.01-1.68) for high apoB, 1.65 (1.25-2.17) for low HDL-C, and 1.31 (1.01-1.70) for low apoA-I. In secondary analyses of 2751 participants with no CVD history, high TG (HR 1.46, 1.02-2.10), high VLDL-C (HR 1.56, 1.08-2.25), low HDL-C (HR 2.11, 1.40-3.16) and low apoA-I (HR 2.28, 1.54-3.37) were significantly associated with incident CVD.

Conclusions:
While high LDL-C is associated with increased CVD risk in the general population, we found no such association in CKD. Instead, high TG, high VLDL-C, low HDL-C and low apoA-I levels show strong associations with increased CVD risk and incident CVD events in CKD.
Abstract P132: Impact of Location and Social Context on the Probability of a Dietary Lapse Among Adults in Weight Loss Treatment
Authors: Burke Lora E , Shiffman Saul , Mendez Dara , Chasens Eileen , Smailagic Asim , Siewiorek Dan P , Ewing Linda J , Mancino Julie , Rathbun Stephen
Published: July 2021

Background:
Ecological momentary assessment (EMA) assesses individuals’ current experiences, location and social context in which behaviors occur. During a 12-mo behavioral weight loss intervention and using an EMA app, we asked participants to report any instances of temptations or a lapse from their weight management diet.

Objective:
Estimate the rate of temptations per unit time and the probability that a lapse will follow based on the location (restaurant, home, work) and the social context (
with others who are eating, completely alone
).

Methods:
Using a smartphone, participants initiated a report when they experienced a temptation and reported if this led to a lapse. Their location and the social context were recorded during the 5,211 self-reported temptations as well as during 106,960 random assessments over 12 mos.

Analyses:
A frailty model was used to estimate the rate at which temptations occurred per unit of time and a logistic regression model was used to estimate the probability that a temptation led to a lapse both as a function of location and social context.

Results:
The sample (N = 150) was predominantly female (90.7%) and White (80.7%), 56.4% were married with 16.4 (2.8) years of education and a mean BMI of 34.0 kg/m
2
(4.6). Temptations occurred most often in a restaurant and the person
was with others who were eating
or
in sight of others who were eating
(Fig 1). While temptations occurred infrequently in another person’s home, there was nearly a 65% probability that a lapse would occur there. When
with others who are eating
, the temptation rate and probability of a lapse were high.

Conclusions:
Temptations to eat in a manner that is inconsistent with a weight loss plan occur more frequently in certain locations, e.g., restaurants; however, the probability a temptation leads to a lapse is high in a variety of locations and social contexts, e.g.,
with others who are eating
. Interventions need to focus on empowering individuals trying to manage their weight to resist temptations in these at risk locations and social contexts.
Abstract P167: High vs. Standard Protein Diets in Obese Patients with Heart Failure: Effects on Chronic Disease Risks
Authors: Evangelista Lorraine S , Lombardo Dawn , Horwich Tamara , Hamilton Michele , Fonarow Gregg C
Published: July 2021

Background:
There is controversy over dietary protein’s effect on long-term chronic disease risks in overweight and obese patients with heart failure. The aim of this study was to compare the effects of two calorie-restricted diets differing in protein content on chronic disease risks (e.g., weight, adiposity, glycemic control, lipid profiles, and blood pressure).

Methods:
A total of 97 overweight and obese (mean body mass index [BMI], 37.0 ± 6.2 kg/m
2
) patients with heart failure, aged 58.8 ± 9.7 years, 70% males, consumed two diets, each for 12 weeks, in a randomized controlled design. The diets were: (1) a high protein diet (30% protein, 40% carbohydrates, and 30% fat) and (2) a standard protein diet (15% protein, 55% carbohydrates, and 30% fat). Their effects on weight (BMI) visceral fat (i.e. waist circumference), glycemic control (i.e. glycosylated hemoglobin [HgbA1C]), lipid profiles (total cholesterol [TC], low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides [TG]), and blood pressure at the beginning and end of each dietary intervention were analyzed.

Results:
Both diets were equally effective in promoting weight loss and visceral fat loss and in improving TC, but the high protein diet decreased to a greater extent HgbA1C levels (
P
< 0.001) when compared with the standard protein diet. The high protein diet improved significantly TG levels (
P
< 0.001) and both systolic and diastolic blood pressures when compared with the standard protein diet (
P
< 0.001 and
P
< 0.001, respectively, see figure). No differences were noted in LDL and HDL levels.

Conclusion:
Energy restricted diets facilitate weight loss and visceral fat loss and lower TC in overweight and obese patients with heart failure. However, the high protein diet promoted better improvements in TG levels, glycemic control, and blood pressure than the standard protein diet, and may be superior in reducing chronic disease risks and potentially slowing the progression of disease in this population.
Abstract P180: Impact of Intensive Systolic Blood Pressure Treatment on Cardiovascular Disease and Mortality in the US Population
Authors: Bundy Joshua D , Li Changwei , He Jiang
Published: July 2021

Introduction:
Hypertension is the most important risk factor for cardiovascular disease (CVD), the leading cause of morbidity and mortality among US adults. Clinical trials suggest that intensive systolic blood pressure (BP) management significantly reduces risk of CVD and mortality in patients at high risk for CVD. However, the impact of intensive BP lowering in the US population is uncertain.

Hypothesis:
More intensive treatment of systolic BP provides great benefits in the reduction of CVD and total deaths in the US population aged ≥40 years.

Methods:
We pooled follow-up data in 31,851 individuals from four US cohort studies (ARIC, CHS, Framingham Heart Study, and MESA) to estimate annual incidence rates of major CVD (combined stroke, coronary heart disease, and heart failure) by sex, race (white and non-white), and age groups (40-49, 50-59, 60-69, and ≥70 years). We retrieved mortality data from annual death statistics reported by the CDC. We combined nationally-representative survey data from three NHANES cycles (2009-2010, 2011-2012, 2013-2014) to estimate the proportions of US adults aged ≥40 years in each of 10 systolic BP categories (range <120 to ≥160 mm Hg). A Bayesian network meta-analysis of antihypertensive clinical trials was used to estimate relative risks for CVD and mortality comparing each of the 10 systolic BP categories, after adjusting for baseline risk in included trials. Using these data sources, we calculated the population attributable fractions and number of events (and deaths) that could be reduced by treating systolic BP ≥140 mmHg to more intensive systolic BP targets in the US population.

Results:
Treating systolic BP to 120-124 mm Hg showed the largest reduction in number of CVD events and total deaths compared to higher targets (Table).

Conclusions:
In conclusion, intensive treatment of systolic BP could prevent a large number of CVD events and total deaths in the US population.