bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P581: Body Mass Index Variability in Relation to Heart Failure and Outcomes
Authors: Liu Chang , Chiang Yiyun , Hui Qin , Wilson Peter , Joseph Jacob , Sun Yan
Published: March 2023

Introduction:
Heart failure (HF) is a disease with high morbidity and mortality, and affects an estimated total of 6.2 million HF patients in the US. Obesity is an established risk factor for HF, and fluctuation in body mass index (BMI) has shown a negative effect in health.

Hypothesis:
We assessed the hypothesis that BMI variability is associated with incident HF.

Methods:
This study used data from the UK Biobank, which is a prospective cohort study with a median follow-up of 12.5 years. After excluding prevalent HF or cancer at enrollment, a total of 99,368 White participants with ≥ 3 BMI measures from primary care records within > 2 years before and at enrollment were included. The within-participant variability of BMI was evaluated using standard deviation (SD) and coefficient of variation (CV), which were converted to z scores for further analysis. HF prevalence and incidence were ascertained based on in-patient Hospital Episode Statistics using ICD-9 and -10 codes and self-report at enrollment. The association of BMI variability with incident HF was assessed using Fine and Gray's competing risk model, treating death events obtained from the National Death Registry as competing risk. Two multi-variate models were used: Model 1 adjusted for age, sex, smoking history, alcohol consumption, diabetes, hypertension, history of heart attack or stroke, lipids, estimated glomerular filtration rate; Model 2 additionally adjusted for mean BMI across multiple measures per individual. Sex-stratified analyses were also conducted.

Results:
The cohort was 43% male, with mean age 57.5 (SD 7.8) years. A total of 3,406 incident HF cases were observed during the follow-up. Per SD higher in BMI variability measured in SD and CV were associated with higher risk in HF incidence, with stronger associations observed among females,
Figure 1
.

Conclusions:
BMI fluctuation is linked with HF incidence. Future studies are warranted to explore the mechanisms in changes of BMI such as body composition, and the possible causal pathways leading to HF.
Abstract P582: Race, Social Determinants of Health, and Comorbidity Patterns Among Participants With Heart Failure in the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Enogela Ene M , Goyal Parag , Safford Monika M , Clarkson Stephen , Buford Thomas W , Jackson Elizabeth A , Brown Todd , Long Leann , Durant Raegan W , Levitan Emily B
Published: March 2023

Introduction:
Heart failure (HF) is often accompanied by comorbid conditions that impact outcomes. We examined racial differences in comorbidities among patients with HF and the mediating role of social determinants of health (SDOH).

Hypothesis:
Comorbidities among people hospitalized with HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) will differ by race, and SDOH will partly explain the disparities.

Methods:
Black and White US community-dwelling participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study aged ≥ 45 years with an adjudicated HF hospitalization between 2003 and 2017 (n = 506 HFpEF and 742 HFrEF, 4.1% of the REGARDS cohort) were included in this cross-sectional analysis. Comorbidities were abstracted from HF hospitalization records. We estimated age- and sex-adjusted prevalence ratios (PR) for comorbidities comparing Black to White participants. Guided by the Healthy People’s 2030 framework, SDOH including income, education, marital status, rural residence, ZIP code-level poverty, healthcare provider shortage area and poor public infrastructure were considered as potential mediators using the inverse odds weighting method.

Results:
Among participants with a HF hospitalization, the median age was 79 (IQR: 73 – 85) years and 74 (67 – 80) years for White and Black adults, respectively. There were racial differences in the prevalence of some comorbidities between Black and White participants (Table). In HFpEF, low income and education explained 27% of the excess diabetes experienced by Black adults compared to White adults (P < 0.05). There was no significant mediation of other associations by SDOH.

Conclusions:
There were racial differences in the patterns of comorbidities among REGARDS participants with HF, with low income and education partly explaining the higher prevalence of diabetes among Black adults with HFpEF.
Abstract P583: Cardiac Sarcoidosis is an Under-Recognized Cause of Heart Failure Admissions in the United States: A Population Based Epidemiologic Study
Authors: Khalid Yaser , Dasu Kirti , Dasu Neethi , Kadiyala Bhavana
Published: March 2023

Background:
Progressive heart failure is the cause of mortality for almost 25% of patients with cardiac sarcoidosis (CA). However, there are limited studies on the impact of heart failure (HF) on mortality, hospital length of stay (LOS), and total hospital charges for patients with cardiac sarcoidosis.

Methods:
Data were extracted from the National Inpatient Sample (NIS) 2016-2019 Database. The NIS was searched for hospitalizations for adult patients with cardiac sarcoidosis as the principal discharge diagnosis with and without different types of heart failure as secondary diagnosis using ICD-10 codes. Multivariate analysis via STATA was used to adjust for confounders.

Results:
6,560 patients were identified with a diagnosis of cardiac sarcoidosis. Only 0.08% of patients with heart failure were identified with a diagnosis of cardiac sarcoidosis, of which 15.8% had systolic HF, 3.7% diastolic had HF, and 14% had combined systolic and diastolic HF. There were more males than females (60.0% vs. 40.0 %, p<0.01).

Mortality was increased for combined systolic and diastolic HF (OR 1.98, p<0.04). LOS was increased for patients with any type of HF(+2.48 days, <0.001), systolic heart failure (+2.14 days, p<0.017), combined systolic and diastolic HF (+1.96 days, p<0.010). Total hospital charges were increased with any type of HF ($44,214.43, p<0.004), and systolic heart failure ($58,298.90, p<0.015). Interestingly, patients with cardiac sarcoidosis did not have increased mortality with all types of HF(OR 1.04, p=0.928), systolic HF (OR 0.98, p=0.973), diastolic HF (OR 0.35, p=0.179), and combined systolic and diastolic HF (OR 1.34 experienced a 51% increased odds of mortality (OR 1.51, 95%CI 1.41-1.62, p<0.01), a longer LOS with a mean difference of 1.4 days (95%CI, 1.16-1.57, p<0.01), and a more costly overall hospitalization with a mean difference of $12,841 (95%CI $9,705-$15,976, p<0.01).

Conclusion:
Cardiac sarcoidosis remains a widely under-recognized cause of HF hospitalizations in the United States.
Abstract P585: Impact of Thrombocytopenia on the Outcomes of Patients Admitted With Heart Failure: Analysis of the National Inpatient Sample
Authors: Karki Sadichhya , Deenadayalan Vaishali , Atluri Ramtej , Soon-Shiong Raquel
Published: March 2023

Background:
Thrombocytopenia is known to be a marker of adverse clinical outcomes in acute coronary syndromes, pulmonary hypertension and critically ill patients. Its impact on heart failure (HF) patients has not been well characterized. We aim to compare the clinical outcomes in patients admitted for HF with and without thrombocytopenia.

Methods:
A retrospective cohort study was designed using data obtained from the 2016-2019 National Inpatient Sample (NIS) database. Adult patients (age >18) with a principal diagnosis of Heart Failure (HF) were identified using the International Classification of Diseases code, tenth revision (ICD-10), and were divided into two cohorts based on a secondary diagnosis of Thrombocytopenia. Primary outcomes evaluated were in-patient mortality, Length Of Stay (LOS) and Total Hospitalization Charges(THC). Secondary outcomes included a blood transfusion, AKI, Pneumonia, Sepsis and GI bleed.

Results:
Out of 1,276,429 adult patients admitted with HF, 70,755 (5.5%) were found to have a diagnosis of thrombocytopenia. The mean age was 72 years for the thrombocytopenia group vs 71 years for the other group. On a multivariate regression analysis after adjusting for confounders, HF patients with thrombocytopenia had double the odds of inpatient mortality (aOR 2.0 , 95% CI 1.84-52.16, p<0.01) and LOS (aOR 2.38 , 95% CI 2.19-2.58 p<0.01) compared to the other group .THC was also increased by 43,376$ ( 95%CI 38,842-47,910 ,p<0.01). Among the secondary outcomes, the rate of blood transfusion (6.4% vs 2.1%, aOR 2.19, 95% CI 2.02-2.38, p<0.01), AKI (37.4% vs 25.0%, aOR 1.5, 95% CI 1.44-1.56, p<0.01), Pneumonia (16% vs 13%, aOR 1.18, 95% CI 1.12-1.25, p<0.01),Sepsis (3.08% vs 1.13, aOR 2.5 ,95% CI 2.22-2.78, p<0.01) and GI Bleed (0.9 %vs 0.4 %, aOR 1.68, 95% CI 1.38-2.05, p<0.01) was also significantly elevated in the thrombocytopenia group.

Conclusion:
HF patients with thrombocytopenia had worse clinical outcomes compared to those without. Very few studies have explored this impact of thrombocytopenia on HF and concluded with similar outcomes, probably related to abnormal platelet activity in this population and its consequence on cardiac function. This finding highlights the need for future studies to elucidate the pathophysiology and include platelet level in prognostic tools.
Abstract P587: Patients With Diabetes Mellitus and Atrial Fibrillation Affected by Non-Alcoholic Fatty Liver Disease Have Greater Risk of Mortality and Worse Clinical Outcomes
Authors: Khokhlov Leonid , Aboelnasr Amr , Fatuyi Michael , Pereira Leanne , Ali Mehnaaz , Hussain Fatima , Brown Amanda , Shemisa Kamal
Published: March 2023

Background:
Patients with diabetes mellitus (DM) are increasingly affected by AF. Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging disease and risk factor of interest that predisposes to adverse outcomes. Nevertheless, there is limited scientific evidence of clinical outcomes of NAFLD in patients with AF&DM. Therefore, we sought to investigate this population.

Methods:
We queried NIS between 2016-2019 for adult patients who were hospitalized with AF&DM and had NAFLD. The primary outcome was inpatient mortality. The secondary outcomes were cardiogenic shock, cardiac arrest, gastrointestinal bleeding (GIB), invasive mechanical ventilation, length of stay (LOS) and total hospital charge. Multivariable logistic and Poisson regression analyses were used to estimate clinical outcomes. P-value < 0.05 was significant.

Results:
There were 6,723,293 patients with AF&DM and 253,639 (3.7%) had NAFLD. NAFLD and non-NAFLD cohorts were with mean age of 70.4 vs. 73.8 yrs; males 57.2% vs 55.6%; Caucasians 70.5% vs 73.9%; HTN 20.3% vs 29.2%; HF 61.4% vs 56%; CKD 53.4% vs 45.2%; obese 26.9% vs 27.1%; dyslipidemia 49.8% vs 61.9%; anemia 24.8% vs 19.2%; history of MI 10.9% vs 13.3%; stroke 2.4% vs 4.1%, COPD 28.8% vs 31.1%; alcohol use 5.2% vs 2.2%, respectively. NAFLD cohort had significantly higher mortality and worse clinical outcomes (Table 1).

Conclusion:
AF&DM patients with NAFLD demonstrated significantly worse clinical outcomes and higher resource utilization. They were younger, with greater comorbid HF, anemia, CKD. Cardiogenic shock, cardiac arrest and GI bleed were all higher in the NAFLD subgroup. NAFLD may therefore raise the risk for ventricular dysfunction and coagulopathy. Awareness of this risk factor is essential in the AF&DM population. Further research is necessary to assess long-term outcomes.
Abstract P593: Urinary Nitrate Was Not Associated With Prevalence of Dyslipidemia Among Adults in the National Health and Nutrition Examination Survey, 2009-2016
Authors: Hwang Andrew Y , Carriker Colin R
Published: March 2023

Introduction:
Exogenous dietary sources of nitrate (green leafy vegetables) and endogenous oxidation of nitric oxide are potential sources of urinary nitrate. While nitrate exposure elicits a profound impact on vascular health and higher levels of urinary nitrate correlate with reduced blood pressure, less is known about its association with blood cholesterol.

Hypothesis:
Higher urinary nitrate levels are inversely related to dyslipidemia prevalence.

Methods:
Cross-sectional 2009-2016 National Health and Nutrition Examination Survey (NHANES) was used to identify participants aged ≥20 years. Participants were categorized into four quartiles based on urinary nitrate levels (ng/mL) - Q1: ≤26,300; Q2: 26,300-45,800; Q3: 45,800-72,200; Q4: >72,200. Primary analysis was survey-weighted logistic regression modeling to estimate the association of urinary nitrate with dyslipidemia prevalence (defined as self-report, total cholesterol [TC] ≥200 mg/dL, high-density lipoprotein cholesterol [HDL-C] <40 mg/dL for men or <50 mg/dL for women, low-density lipoprotein cholesterol [LDL-C] ≥100 mg/dL, triglycerides [TG] ≥150 mg/dL, or non-HDL-C ≥130 mg/dL). The model was adjusted for age, sex, race/ethnicity, smoking status, income level, hypertension, and diabetes. Secondary analysis included comparison of TC, HDL-C, LDL-C, TG, and non-HDL-C stratified by urinary nitrate quartiles. Survey-weighted ANCOVA, adjusted for the same co-variates, was performed at a significance level of 0.05; if significance level was met, post-hoc multiple comparison test using the Dunnett-Hsu method was performed, with Q1 as the reference.

Results:
Across the 8-year NHANES survey, 3,099 participants (74.7% aged <60 years, 50.5% women, and 65.6% non-Hispanic white) were included in the study. Hypertension and diabetes prevalence were 24.5% and 9.3%, respectively. Urinary nitrate was not significantly associated with hypercholesterolemia prevalence (Q2 vs. Q1, OR 0.87 [95% CI, 0.62-1.23]; Q3 vs. Q1, OR 1.09 [95% CI, 0.71-1.68]; Q4 vs. Q1, OR 0.89 [95% CI, 0.59-1.37]). No statistically significant trends in TC, HDL-C, LDL-C, TG, or non-HDL-C were observed with urinary nitrate quartiles.

Conclusion:
Higher urinary nitrate excretion, a marker of nitrate exposure and elevated nitrate levels, was not associated the prevalence of dyslipidemia. Therefore, while a healthy diet may lead to changes in cholesterol, such changes may be independent of dietary nitrate intake.
Abstract P598: Highly Purified Eicosapentaenoic Acid Use Can Reduce Neurological Severity at the Onset of Ischemic Stroke in Patients With Hyperlipidemia
Authors: Mori Takahisa , Yoshioka Kazuhiro , Miyazaki Yuichi
Published: March 2023

Introduction:
Functional outcomes after acute ischemic stroke (AIS) are related to initial neurological severity (NS). Therefore, neuroprotective drugs against ischemic injury are promising. Not only statins but also eicosapentaenoic acid (EPA) have neuroprotective effects.

Hypothesis:
Highly purified EPA (hp-EPA) pre-stroke may reduce NS at the onset of AIS.

Methods:
We retrospectively included patients with AIS and hyperlipidemia admitted to our institution between July 2012 and March 2019 from the prospectively and consecutively enrolled institutional stroke registry database. Hyperlipidemia was defined as serum values of low-density lipoprotein cholesterol (LDL-C) at arrival ≥140 mg/dl or triglycerides ≥150 mg/dl. We excluded patients: (1) admitted to our institution 24 h after AIS onset, (2) who did not stay in the hospital, and (3) in whom dyslipidemia drugs pre-stroke except the hp-EPA were administered. We collected data on age; sex; pre-stroke statin use, antiplatelets, anticoagulants, antihypertensives, and antidiabetic drugs; serum albumin, glucose, glycated hemoglobin (HbA1c), cholesterol, triglycerides, and c-reactive protein levels; pre-stroke modified Rankin scale and the National Institutes of Health Stroke Scale (NIHSS) scores; stroke subtypes at admission; hospitalizations; and home discharge. We performed a multivariable linear regression analysis to identify significant variables of NIHSS scores at arrival.

Results:
Of the 2,199 patients with AIS and hyperlipidemia during the study period, 691 met our inclusion and exclusion criteria, their median age was 75 years, and 18 (2.6%) received pre-stroke hp-EPA. In patients with and without pre-stroke EPA use, the median NIHSS scores were one and three, respectively. Multivariable regression analysis showed that the glucose, mRS, age, LDL-C, and anticoagulants increased the NIHSS score, albumin, HbA1c, high-density lipoprotein cholesterol, antihypertensives, antidiabetic drugs, and hp-EPA use decreased the NIHSS score.

Conclusion
Pre-stroke hp-EPA use reduced NS at the AIS onset in patients with hyperlipidemia and without other dyslipidemia drugs.
Abstract P599: Should Regression Calibration or Multiple Imputation Be Used When Calibrating Different Devices in a Longitudinal Study?
Authors: Loop Matthew S , Lotspeich Sarah C , Garcia Tanya P , Meyer Michelle L
Published: March 2023

Objective:
In longitudinal studies, devices used to measure exposures, like pulse wave velocity (PWV), can change from visit to visit. Calibration studies, where a subset of participants receive measurements from both devices at follow-up, are often used to assess differences in the device measurements. Regression calibration and multiple imputation are common statistical methods to correct for those differences, but no study yet exists to compare the two when the quantity of interest is change in the exposure over time. We compared both methods in a hypothetical study of change in PWV and its association with total brain volume.

Methods:
We simulated true values of PWV at baseline and follow up, as well as imperfect measurements of PWV using an “old” device and “new” device. Two statistical methods were compared:
regression calibration
, which calibrates the new device measurements at follow up to the old device using linear regression in a calibration study; and
multiple imputation
, which imputes the (mostly) missing old device measurements at follow up.We varied the bias and measurement error of each device and for each scenario simulated 1,000 datasets of size n=2,500. Two percent of participants in each iteration were chosen to participate in the calibration study, and thus had measurements on the old and new devices at follow up. We used 200 bootstrap replicates to calculate the standard errors for the regression calibration method and 50 imputed datasets for the multiple imputation method. To compare the methods we used bias of the estimated association and how well the standard errors approximated the empirical standard errors.

Results:
Regression calibration was virtually unbiased for the association between change in PWV and total brain volume when the old device had larger measurement error than the new device. The maximum bias for regression calibration across all scenarios was still small (6%). When the old device had more measurement error or the two devices had equal measurement error, multiple imputation underestimated the association by more than 10%. This underestimation was reduced to approximately 2% when the new device had a larger measurement error than the old device. In all scenarios, regression calibration underestimated the empirical standard error by approximately 35%, while multiple imputation underestimated it by only 2-5%.

Conclusions:
In analyses of change in PWV and total brain volume, when unbiased estimation is the main objective, regression calibration is favorable to multiple imputation. When null hypothesis significance testing is the main objective, multiple imputation may be favorable in order to not underestimate the standard errors. We expect these conclusions to apply to other change in exposure and outcome relationships with similar ratios between the association’s magnitude and the amount of measurement error.
Abstract P601: Death Certificate-Based Screening Methodology is an Efficient and Accurate Methodology for Identifying Sudden Death Victims
Authors: Day Gabriella , Cesmat Andrew , Keen Susan , Capone Alia , Simpson Ross J
Published: March 2023

Introduction:
Out-of-hospital sudden death accounts for over 10% of all deaths among working age adults. Traditional methods of identifying victims by screening Emergency Medical Services (EMS) reports and clinical adjudication are labor intensive. We hypothesize death certificates may provide efficient and reliable information to identify victims of sudden death. This study aims to compare a death certificate-based sudden death screening algorithm to a more time-intensive EMS-screened and cardiologist-adjudicated sudden death method.

Methods:
Death certificates from four North Carolina counties (Guilford, Mecklenburg, Surry, Wake) were screened by written protocol. Cases were excluded if age under 18 or over 64, hospital death, non-free living, or non-natural cause of death (overdose, gunshot wound, suicide, drowning, cancer, traumatic death without evidence of coronary disease). Census tract data was determined from victim home address. These 2013 death certificate cases were compared to our preexisting dataset of EMS-screened, cardiologist-adjudicated cases identified in Wake County 2013-2015. Demographic data was compared between datasets using Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical variables.

Results:
Death certificate cases included 518 victims and EMS-screened/cardiologist-adjudicated cases included 399 victims. There were 99 overlapping cases in both datasets which were excluded from this comparative analysis. Demographic and social data were similar in the two groups (Table 1).

Conclusion:
Like previous methods have shown, sudden death occurs predominantly among unmarried individuals and is more common among black race and male sex. Death certificate screening methods are sufficient to identify sudden death victims to allow for efficient, population-based assessment of the epidemiology of sudden death. These methods may allow for identification of high-risk communities to facilitate intervention to reduce the incidence of sudden death.
Abstract P602: Complete Blood Count Analysis in the Risk Underlying Rural Areas Longitudinal (RURAL) Cohort Study With a Point of Care Instrument
Authors: King Margaret , Perry April , Cornell Elaine S , Boyle Rebekah , Judd Suzanne E , Rhodes James D , Ramachandran Vasan S , Tracy Russell , Durda Jon P
Published: March 2023

Background:
The RURAL cohort study is a uniquely designed study using a Mobile Examination Unit (MEU) to study heart and lung disorders in rural counties in the southeastern US. Complete blood counts (CBC) are included in the participant baseline examination. We wanted to use an instrument in the MEU for onsite blood counts and chose the Pixcell Hemoscreen, a point-of-care instrument using a unique technology. Before using the Hemoscreen in the RURAL study, it was necessary to ensure that the CBC results would be comparable to laboratory generated results.

Methods:
We compared CBC results from the Hemoscreen to those from the Sysmex XN9000 at the University of Vermont Medical Center. CBC measurements include erythrocyte count (RBC), white blood cell count (WBC), hemoglobin concentration (HGB), hematocrit value (HCT), and platelet count (PLT). Blood from ten volunteers was analyzed on the Hemoscreen and the Sysmex. Statistics included average, standard deviation, and coefficient of variance (CV) for each of the parameters analyzed. Blood from ten volunteers was assayed on both the Hemoscreen and the Sysmex to compare for accuracy. Blood from three volunteers was analyzed ten times on the Hemoscreen to assess variability.

Results:
The Hemoscreen and Sysmex reported similar values for WBC, RBC, HCT, HGB and PLT counts, as shown in Figure 1. Between repeat measures conducted on the same sample on the Hemoscreen WBC, RBC, HCT, HGB and PLT showed little variance (%CV = 5.9, 2.7, 2.8, 2.7, and 4.0 respectively).

Conclusions:
The Hemoscreen data correlated with data generated in a hospital laboratory on the same samples. Variability between multiple measures of the same samples on the Hemoscreen showed acceptable variance. To date over 730 RURAL participants have been seen and the Hemoscreen has proven to be quick, accurate, and reliable.
Abstract P603: Diet Quality Scores Measured With Standard and Modified Component Weights Are Associated With Mortality Risk in the Multiethnic Cohort
Authors: Parker Haley W , Buchanan Ashley , Oaks Brietta , Vadiveloo Maya
Published: March 2023

Introduction:
The Dietary Patterns Methods Project reported higher scores of four selected dietary indices were all inversely associated with mortality risk. Diet quality components are generally weighted equally but previous meta-analyses and NHANES analyses suggest some may be more integral for mortality risk reduction. Thus, we examined if modified weight (vs. standard) Healthy Eating Index (HEI)-2015 scores were differently associated with all-cause and cardiovascular (CVD) mortality risks.

Hypothesis:
High modified weight (vs. standard) HEI-2015 scores will be associated with stronger mortality risk reduction.

Methods:
Data from adults (n=156,863) enrolled in the Multiethnic Cohort (MEC) Study recruited between 1993-96 from Hawaii and California with vital status and dietary data were analyzed. Baseline diet quality was assessed with the HEI-2015 using a food frequency questionnaire. Standard component weights of 5 or 10 points on 9 adequacy and 4 moderation components were reweighted creating two modified HEI scores, the Key Facets HEI with equally weighted fruits, vegetables, whole grains, and plant proteins and the Machine Learning (ML)-weighted HEI, calculated using weights reflecting relative component contributions to mortality risk from a prior analysis of NHANES III adults using LASSO models. All 3 HEI scores were assigned to deciles; sex-stratified, adjusted Cox models evaluated associations of HEI deciles with all-cause and CVD mortality risk.

Results:
Participants represented 5 ethnic groups (24% White, 16% African American, 23% Latino, 29% Japanese American, and 7% Native Hawaiian), and 55.3% were women. The mean age was 59.1 years, mean BMI was 26.4 kg/m
2
, and 27.3% were college graduates. For men and women, high scores (≥90th, vs. <10th percentile) on all HEIs were significantly associated (p<0.05) with 10% to 24% reduced all-cause and CVD mortality risks.

Conclusions:
Similar mortality risk reductions were observed for standard and modified weight diet quality scores in this sample.
Abstract P606: Effectiveness of Randomized Dietary Interventions for the Primary Prevention of Incident Cardiovascular Disease and Type 2 Diabetes
Authors: Shah Alisha , Kim Suryun , Hamaya Rikuta , Manson JoAnn E , Tobias Deirdre K
Published: March 2023

Objective:
Randomized controlled trials (RCTs) provide opportunities to estimate the causal effects of interventions on disease risk; however, large-scale, long-term RCTs of diet for the prevention of major chronic disease endpoints are sparse. We sought to summarize RCTs comparing the effectiveness of dietary interventions for the primary prevention of clinical cardiovascular disease (CVD) events and type 2 diabetes (T2D) in adults.

Methods:
We conducted a systematic review and meta-analysis (PROSPERO #CRD42021283728) of RCTs exclusively with dietary interventions with outcomes of incident primary CVD events and/or T2D among adults. We searched MEDLINE and other databases and references. Eligible interventions included those providing instruction, education, and/or provisions to modify intakes of nutrients, foods, or overall dietary patterns. We excluded meal replacement products, dietary supplements, interventions with concomitant comprehensive lifestyle programs, exercise regimens, etc., trials in secondary prevention populations, and trials assessing risk factor or biomarker changes only, rather than clinical events. Two investigators performed screening and data extraction in parallel. We conducted a random effects meta-analysis to estimate the pooled effectiveness of dietary interventions compared with usual diet or low-fat control groups for CVD and T2D outcomes, separately.

Results:
Among the 5365 citations generated in our searches, we identified 4 eligible RCTs, representing 56,721 participants with mean ages ranging from 44.7 to 67.9 years. Mean intervention duration was 2.3 to 8.1 years, resulting in 3,151 CVD events and 3,603 T2D cases. Compared with the control diets, the various healthy dietary patterns were related to a combined 7% (relative risk [RR] = 0.93, confidence interval [CI] = 0.87-1.00) lower CVD risk and 8% (RR = 0.92, CI = 0.86-0.98) lower T2D risk.

Conclusion:
Despite major morbidity and mortality from CVD and T2D, there have been few large, population-based, long-term RCTs assessing the exclusive effectiveness of dietary modification for the primary prevention of clinical CVD events or T2D. Results, however, indicate that various healthy diets may be modestly effective for primary prevention.
Abstract P607: What Do Consumers See? Nutrients Listed on Packaged Foods and Beverages in Addis Ababa, Ethiopia
Authors: Henry Megan E , Chen Mengkun , Marklund Matti , Fasil Nebiyou , Berhane Hanna Y , Beyan Seada , Foti Kathryn , Khandpur Neha , Appel Lawrence J
Published: March 2023

Introduction:
Noncommunicable diseases (e.g. type 2 diabetes, hypertension, cardiovascular disease) are the leading cause of death globally and among adults in Ethiopia. Suboptimal diet (with high intake of sugar, salt, and saturated fat) is a major risk factor for such diseases and the consumption of processed foods rich in these nutrients is rising globally. Mandatory nutrition information on packaged foods, potentially with warning labels, can guide consumers and create healthier food environments. However, such information is lacking in many countries, including Ethiopia.

Hypothesis:
We assessed the hypothesis that the display of nutrition information (including sugar, sodium, and saturated fat) would be low on packaged foods and beverages in Ethiopia.

Methods:
A database of packaged foods was created in 2021 from an assessment across 18 markets within Addis Ababa, Ethiopia. The analysis included 1388 products in four major food categories (cereals; snack foods; sweets; and beverages).

Results:
In total, 880 (63%) products displayed nutrient content information. This was most common among cereals (73%), and least common in snack food (43%) (Table 1). For specific nutrients, the display of sodium/salt (38%) was similar to sugar (35%) and saturated fat (34%). This discrepancy was highest in the beverages category.

Conclusion:
Nutrition labeling was incomplete in four major packaged food categories in Ethiopia. Fewer than half of snack foods displayed any nutrient content information, and while nearly three-fourths of cereals had some label, data on all three nutrients (sugar, sodium, and saturated fat) was missing on more than half of these products. Mandatory warning labels will allow consumers to assess the nutrient content of packaged foods and may encourage reformulation by industry to meet consumer demand and avoid placement of warning labels on their products.
Abstract P616: Implementing a Dietary Energy Density Intervention in Preschool Children
Authors: Robson Shannon M , Sundermeir Samantha M , Fultz Amanda K , Verdezoto Alvarado Adriana , Raynor Hollie A , Filigno Stephanie S , DiGuglielmo Matthew , Bodt Barry
Published: March 2023

Introduction:
The preschool years have been identified as a critical time to intervene on energy balance behaviors to halt the progression of obesity. In children, strategies for achieving physical activity recommendations are well established. Less clear are strategies for implementing an optimal dietary approach—one that maintains a healthy body weight and improves diet quality. Energy density (ED), the amount of energy per unit weight of food (kcal/g), may be a promising dietary approach.

Hypothesis:
We tested the hypothesis that a lower ED dietary approach will lower ED and energy intake and demonstrate better maintenance of body mass index (BMI z-score) than standard dietary recommendations in young children at risk for obesity.

Methods:
Thirty-six preschool children (3.5±1.1 years; 52.8% female; 52.8% White; 16.7% Hispanic or Latino; BMI percentile 56.8±22.2) and their parent (35.4±6.2 years; 86.1% female; 55.6% White; 13.9% Hispanic or Latino; BMI 38.2±5.4 kg/m
2
) participated in a 6-month, 14-session, family-based behavioral intervention. Participants were randomized to a low-ED dietary approach (consume ≥10 foods/day with an ED ≤1.0 kcal/g and ≤2 foods/day with an ED ≥ 3.0 kcal/g; LOW-ED), or standard dietary recommendations (meet recommended daily servings of fruits, vegetables, and whole grains; STANDARD). Both interventions had physical activity goals of 60 minutes/day for children and 150 minutes/week for adults. Dietary and anthropometric assessments occurred at baseline and 6-months. Completer and intent-to-treat (ITT) analyses, with outliers removed, used repeated measures general linear mixed models to examine child change in ED (calculated as both all foods and beverages and food only), kcals, and BMI z-score from baseline to 6 months.

Results:
ITT analyses showed that the change in ED did not differ between the LOW-ED condition and STANDARD condition when calculated as for foods and beverages (LOW-ED: Δ-0.1 kcal/g vs. STANDARD: Δ+0.1 kcal/g, p = 0.12) or food only (LOW-ED: Δ-0.2 kcal/g vs. STANDARD: Δ+0.1 kcal/g, p = 0.06). There was a significant time by condition interaction with kcals/d decreasing in LOW-ED and increasing in STANDARD over time for completers (LOW-ED: Δ-98 kcals vs. STANDARD: Δ+212 kcals, p = 0.04), but not when using ITT (LOW-ED: Δ+5 kcals vs. STANDARD: Δ+211 kcals, p = 0.09). Under ITT BMI z-score had a main effect of time, with both LOW-ED and STANDARD conditions significantly increasing over time (p=0.03).

Conclusion:
In conclusion, these data suggest a LOW-ED dietary approach is an alternative way to lower ED and energy intake in young children at risk for obesity.
Abstract P619: DNA Methylation at
SREBF1
and Long-Term Changes in Body Composition: The POUNDS Lost Trial
Authors: Li Xiang , Shao Xiaojian , Xue Qiaochu , Kou Minghao , Grundberg Elin , Bray George A , Sacks Frank M , Qi Lu
Published: March 2023

Introduction:
A previous epigenome-wide association study has causally linked DNA methylation (DNAm) at the
SREBF1
gene (cg11024682) with obesity and lipids. However, little is known about whether DNAm at
SREBF1
is associated with long-term changes in body adiposity and composition.

Hypothesis:
We hypothesized that participants with different DNAm at
SRBF1
might respond differently to dietary weight-loss interventions on changes in body adiposity and composition.

Methods:
The current study included 314 individuals with overweight or obese, who participated in POUNDS Lost: a 2-year randomized dietary weight-loss trial. The blood DNAm level was profiled by methylC-capture sequencing at baseline. Regional DNAm at
SREBF1
was calculated as the average methylation level over CpGs within ±250 bp of cg11024682. Body composition, including total fat mass (FM), percentage of FM (FM%), total fat-free mass (FFM), percentage of FFM (FFM%), and percentage of trunk fat (TF%) were measured by dual-energy X-ray absorptiometry (DEXA) at baseline, 6 months, and 2 years.

Results:
Lower regional DNAm at
SREBF1
was significantly associated with changes in body composition across 2 years (
Table
). At 6 months, per SD lower regional DNAm at
SREBF1
was significantly associated with greater reductions in FM (β [SE] -0.23 [0.07], p=0.002), FM% (-0.30 [0.09], p<0.001), and TF% (-0.44 [0.13], p<0.001), and greater increases in FFM (0.18 [0.08], p=0.028) and FFM% (0.30 [0.09], p<0.001), regardless of dietary intervention groups and independent of concurrent weight loss. Such association remained at 2 years: FM (β [SE] -0.21 [0.10], p=0.045), FM% (-0.32 [0.11], p=0.004), TF% (-0.36 [0.16], p=0.026), FFM (0.22 [0.12], p=0.07) and FFM% (0.32 [0.11], p=0.004).

Conclusions:
Overweight and obese individuals with a lower regional DNAm at
SREBF1
achieved greater improvement in body composition across the 2-year intervention, independent of concurrent weight loss, suggesting DNAm at
SREBF1
is predictive of individuals’ response to treatment.
Abstract P621: Visceral Adipose Tissue Attenuation: A Marker of Liver Fat Content Beyond the Body Mass Index and Visceral Adipose Tissue Area
Authors: Chartrand Dominic , Almeras Natalie , Lemieux Isabelle , Despres Jean-Pierre
Published: March 2023

Introduction:
Body mass index (BMI) and visceral adiposity cannot fully discriminate individuals at risk of presenting non-alcoholic fatty liver. Discordant visceral adiposity/liver fat phenotypes highlight the need for a better understanding of mechanisms involved in liver fat (LF) accumulation independent of BMI and visceral adipose tissue (VAT) quantity.

Hypothesis:
As VAT attenuation is a marker of VAT quality, we hypothesized that this marker would be an important determinant of LF accumulation and that a lower VAT attenuation would be associated with an increased LF accumulation irrespective of BMI and VAT area.

Methods:
Analyses included 3002 participants (51% men) aged 40 to 70 years with BMI values between 18.5 and 40.0 kg/m
2
of INSPIRE ME-IAA, a prospective observational study conducted in 29 countries in America, Asia, and Europe. Computed tomography was used to measure subcutaneous adipose tissue (SAT) and VAT area and attenuation (a marker of adipocyte size) and liver attenuation (a marker of LF content). Participants’ cardiometabolic health profile was assessed in the fasting state. Partial Pearson correlation coefficients were computed to document the associations between VAT area and attenuation and liver attenuation. Multivariable regression analyses were performed to quantify the contribution of SAT and VAT area and attenuation to LF attenuation. A mixed-model ANOVA was used to compare liver attenuation according to VAT area and attenuation, and to compare VAT attenuation according to LF level and VAT area. A generalized linear mixed model was used to compare the prevalence of type 2 diabetes according to LF content and VAT area.

Results:
VAT attenuation was associated with liver attenuation in women (r=0.34, p<0.0001; r=0.38, p<0.0001; r=0.36, p<0.0001) and men (r=0.42, p<0.0001; r=0.30, p<0.0001; r=0.24, p<0.0001) within each BMI category (normal weight, overweight, obesity), respectively. VAT attenuation better explained LF attenuation than SAT and VAT area. A low VAT attenuation was associated with a lower liver attenuation within each VAT area tertile in all BMI categories (p<0.05). Furthermore, an increased LF content was associated with a lower VAT attenuation (p<0.05) independent of SAT and VAT area in both sexes in all BMI categories. An increased LF content was also associated with a higher prevalence of type 2 diabetes (p<0.05) in individuals with normal weight and overweight beyond VAT area.

Conclusion:
A low VAT attenuation reflecting larger adipocytes is associated with an increased LF content and risk of type 2 diabetes independent of BMI and VAT area. These results suggest that VAT attenuation as a marker of adipose tissue quality might be involved in the development of non-alcoholic fatty liver disease.
Abstract P625: Differences in Urban/Rural Oral Anticoagulation and Mortality Among People With Incident Venous Thromboembolism: Medicare 20% Sample 2016-2018
Authors: Walker Rob F , Zakai Neil A , Maclehose Richard F , Norby Faye L , Wang Wendy , Alonso Alvaro , Lutsey Pamela L
Published: March 2023

Introduction:
Oral anticoagulants (OAC) are a standard and highly efficacious treatment for venous thromboembolism (VTE), with newer direct oral anticoagulants (DOACs; rivaroxaban and apixaban) equivalent or preferred over warfarin for many patients. Rural residents often lack easy access to medical care, which may cause differences in OAC use and outcomes in people with incident VTE.

Hypothesis:
People enrolled in Medicare who reside in rural locations will be less likely to be prescribed DOACs for primary treatment of incident VTE and will experience higher 6-month mortality compared to patients residing in urban areas.

Methods:
We used the Medicare 20% sample to identify a cohort of individuals aged ≥65 years with incident VTE and prescribed an OAC from 2016-2018. Risk factors, demographics, and ZIP codes to create urban/rural categories based on rural-urban commuting area codes were defined at time of VTE diagnosis. All-cause mortality and death date were ascertained via Medicare linkage to the Social Security Administration. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of urban/rural status and 6-month mortality rates, adjusting for demographics, comorbidities and medications. Urban/rural status and OAC choice were tested for multiplicative interaction.

Results:
Among 37,954 beneficiaries with VTE (mean age 76.7, SD 8.1), 82% were urban and 18% were rural. There were 3,778 deaths within 6 months of VTE diagnosis; 3,130 among urban residents while 649 among rural residents (83% vs. 17%). Overall, warfarin was prescribed more often in rural areas than urban areas (34% vs. 27%), rivaroxaban prescriptions were less common in rural versus urban areas (32% vs. 36%), and apixaban did not differ by rural versus urban status (35% vs. 37%). In multivariable-adjusted analyses, risk of mortality was not significantly different in rural versus urban areas (HR: 1.08 (0.99-1.17)). The HRs for mortality with rivaroxaban versus warfarin was 0.85 (95% CI: 0.79, 0.93), for apixaban versus warfarin it was 0.96 (95% CI: 0.89, 1.04), while for apixaban versus rivaroxaban it was 1.14 (95% CI: 1.05, 1.23). There was no interaction between OAC prescribed and urban/rural status for all comparisons of OACs (p-interaction rivaroxaban vs. warfarin: 0.50; apixaban vs. warfarin: 0.54; apixaban vs. rivaroxaban: 0.27).

Conclusions:
Rural versus urban residence resulted in less prescription of DOACs versus warfarin or oral anticoagulation treatment of VTE, but not a significant difference in 6-month mortality. The reasons for different prescribing patterns are unclear, whether due to comorbid conditions or provider knowledge. Greater attention to understanding rural-urban treatment differences is needed to ensure high quality care for everyone.
Abstract P630: Dietary Sodium Intake Increases the Risk of Developing Type 2 Diabetes Mellitus in the Million Veteran Program
Authors: Mahbub Hasan , Nguyen Xuan-Mai , Li Yanping , Ward Rachel , Hu Frank , Willett Walter , Gaziano John M , Djousse on behalf of the VA Million Veteran Progra Luc
Published: March 2023

Background:
Type 2 Diabetes Mellitus (T2DM) affects 10.5% of the US population (~34.2 million people). While previous studies have shown that high intake of sodium is associated with the worsening of the T2DM parameters, it is unclear whether dietary sodium intake is associated with incidence of T2DM. We prospectively examined the association of sodium and potassium intake and risk for T2DM among participants of the Million Veteran Program (MVP).

Methods:
Between 2011 to 2020, 379,852 participants from the MVP completed a semi-quantitative food frequency questionnaire (sFFQ). Incidence of T2DM was ascertained using ICD-9 code 258.xx from electronic health records. We used Cox proportional hazards model to calculate hazard ratio (HR) with 95% confidence intervals (CIs) for T2DM adjusting for confounding factors.

Results:
Among the 234,721 veterans analyzed, mean age was 65 years (age range 19-106), 91% were male, and 88% were Caucasian. The observed energy-adjusted mean sodium intake was 1222 mg/day (1103 for females, 1234 for males) and potassium intake was 2596 mg/day (2534 for females, 2602 for males). During a mean follow-up of 4.4 years, 8,753 participants developed T2DM. After adjusting for confounding factors, a higher sodium intake was associated with 11% higher risk of T2DM (HR: 1.11, 95% CI: 1.04, 1.19, p-trend=0.0006); while a higher potassium intake was associated with a 6% lower risk of T2DM (HR: 0.94, 95% CI: 0.92, 0.97) (Figure).

Conclusion:
Higher intake of dietary sodium and lower intake of dietary potassium were each associated with a higher risk of developing T2DM among US veterans.
Abstract P631: Association Between Suboptimal Sleep Duration and Cardiovascular Disease Prevalence Among Asian Americans
Authors: Nadarajah Santhosh , Akiba Risa , Maricar Isabelle , Vohra Sanah , Jamal Armaan , Yano Yuichiro , Elfassy Tali , Srinivasan Malathi , Kim Gloria , Palaniappan Latha , Kim Karina , Yang Eugene
Published: March 2023

Importance:
Cardiovascular disease (CVD) risk and prevalence is widely varied among Asian Americans. The American Heart Association recently added healthy sleep to its metrics used to define ideal cardiovascular health. Little is known about the association between sleep and CVD prevalence among Asian subgroups.

Hypothesis:
The association between suboptimal sleep duration and CVD risk prevalence will differ by Asian American subgroup.

Methods:
We analyzed results from the National Health Interview Survey (2012-2018, N=234,126), a nationally representative sample. Participants (age>40 years old) included 214,956 non-Hispanic Whites (NHWs), 3,043 Asian Indians, 3,993 Chinese, 4,719 Filipinos, and 7,603 other Asians. Suboptimal sleep was self-reported and defined as <7 or >9 hours. CVD was defined as self-reported stroke, heart attack, coronary artery disease, or angina. We used multivariable logistic regression models to ascertain the association. All analyses included complex survey design considerations.

Results:
Suboptimal sleep duration was associated with higher CVD prevalence for NHWs and all Asians, but in Asian subgroup stratified analyses, suboptimal sleep was only associated with higher CVD prevalence among Other Asians.

Conclusions:
Our results show heterogeneity in the association between sleep duration and CVD prevalence among Asian subgroups, however further research is needed to better understand these relationships.
Abstract P635: Poverty, Sodium Intake and Abnormal Blood Pressure Among Youth 13 to 18 Years of Age
Authors: Baker-Smith Carissa M , Akins Robert E , Lennon Shannon , Alvarado Christian
Published: March 2023

Hypertension (HTN) is a primary cause of cardiovascular disease (CVD) and begins in youth. Among adults, low socioeconomic status (SES) is a demonstrated risk factor for HTN. Low SES has been associated with increased sodium intake and obesity. In this study, we assess the impact of family income, obesity and sodium intake during adolescence on average systolic blood pressure (SBP) to determine if these factors are associated with HTN and elevated BP during adolescence.

Methods:
Using 2007-2018 National Health and Nutrition Examination Survey data, representative of the non-institutionalized civilian population 13 to 18 years of age, we employed multivariable logistic regression (proc survey logistic) to assess the relationship between abnormal BP diagnosis (HTN or elevated BP), family income, obesity, and sodium intake. Poverty was defined as a family income less than 5-times the poverty level. Sodium intake was estimated based upon a combined 1-day total dietary and 1-day diet supplement recall and was adjusted for total caloric intake per day. The upper quartile of adjusted sodium intake was used to distinguish high from low sodium intake. Abnormal BP was defined as an average systolic blood pressure (SBP) at or above 120mmHg. Multivariable logistic regression was carried out.

Results:
2.4% and 13% of the adolescent population had average SBP at or above 130mmHg (HTN) or at or above 120mmHg (elevated BP), respectively. According to multivariable logistic regression, predictors of the HTN/Elevated BP were overweight status (OR: 2.4, 95%CI: 1.8, 3.2), obesity (OR: 3.6 95%CI: 2.8, 4.7), male sex (OR:3.6, 95%CI: 2.7, 4.9), non-Hispanic black race (OR: 1.8, 95%CI: 1.2, 1.4) and age (OR: 1.3, 95%CI: 1.2, 1.4). Poverty status (OR: 1.2, 95%CI: 0.74, 1.9), Hispanic ethnicity (OR 1.2, 95%CI: 0.87, 1.5), and sodium intake (OR: 1.1, 95%CI: 0.86, 1.4) were not associated with HTN/elevated BP.

Conclusion:
While SES factors contribute to abnormal BP, sodium intake and family income were not associated with HTN/elevated BP in adolescents using a single day dietary intake recall. According to our results, additional SES factors contribute to HTN/elevated BP in adolescents and should be further explored.