bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 008: Randomized Trial Of A Healthy Weight Intervention For Youth With Mental Illness: The Champion Trial
Authors: Daumit Gail , Findling Robert , Dalcin Arlene , Jerome Gerald , Appel Lawrence J , Goldsholl Stacy , Brady Tammy , Stepanova Ekaterina , Scheimann Ann , Getzoff Elizabeth , Dickerson Faith , Terry Alison , Fink Tyler , Cook Courtney , Thornton Rachel , Ozl-Price Rebecca , Gennusa Joseph , Lopez-Arvizu Carmen , Charleston Jeanne , Wang Nae-yuh
Published: April 2022

Introduction:
Overweight and obesity in youth with serious emotional disturbance (SED) is exceedingly common. In 2015 the AHA called attention to mental illnesses in youth as important risk conditions for early CVD and the need for transformational change in management of overweight and obesity in this group. Our objective was to test a 12-month, innovative healthy weight intervention in youth with SED.

Hypothesis:
The active intervention is more effective than control in decreasing BMI Z-score compared at 12 m.

Methods:
We conducted a two-arm randomized trial in 2 outpatient pediatric mental health settings in 112 youth, ages 8-18 yrs. The active intervention group was offered 12m of in-person and virtual individual weight management sessions led by health coaches who provided guidance on improving diet and increasing physical activity, and engaged parents.

Results:
At baseline, mean (SD) age was 13.0 (2.7) yrs with 46% ages 8-12 and 54% 13-18; 55% were male, 46% Black, 39% had household income less than $50K/yr and 31% lived in a single-parent household. Primary diagnoses were ADHD (41%), major depression (23%), and anxiety (23%). Mean BMI Z-score (SD) was 2.0(0.4), BMI 30.4 (6.4) kg/m
2
.Mean(SD) psychotropic medications were 2.1(1.4).

At 12m, 111 (99%) had a follow-up weight; 42 were collected after the onset of the COVID pandemic). The intervention group compared to the control group had 0.15 decrease in BMI Z-Score (95% CI 0.26 to 0.04), p<0.007) between baseline and 12 m (Figure) and a 1.43 kg/m
2
decrease in BMI (95% CI 2.43, 0.42, p<0.006). Estimated net effect on BMI Z-score for intervention vs. control was enhanced during the pandemic but not statistically different from net effects pre-pandemic (p=0.06).

Conclusions:
A weight control intervention designed for children with SED decreased BMI Z-score substantially over 12 months, including during the COVID-19 pandemic. These results provide empirical evidence in support of weight control programs in a population at high risk for early development of CVD risk factors.
Abstract 017: Clinical Utility Of Genetic Testing For Familial Hypercholesterolemia In A Pediatric Dyslipidemia Clinic
Authors: Ware Adam , Kemmou Nadaa , Sawyer Briana , Wells Layne , Ou Zhining , Yandell Mark , Williams Richard V , Tristani-firouzi Martin
Published: April 2022

Background:
Familial hypercholesterolemia (FH) in children is diagnosed by identification of a known FH pathogenic variant or clinical criteria. We sought to determine the number of pediatric probands undergoing genetic testing for FH that met clinical criteria, and to evaluate differences between genotype positive and negative probands.

Methods:
All children ≤18 years old undergoing genetic testing for suspected FH were included. Clinical FH was defined as LDL ≥160 mg/dL and family history of premature CAD in 1
st
/2
nd
degree relatives. Screening of 1
st
/appropriate 2
nd
degree family members was recommended at all visits (lipid panel or genetic test) and was complete if obtained within 1 year of proband testing. Probands were stratified based on the presence or absence of known FH pathogenic variants. Wilcoxon rank sum or chi-squared tests compared lipid panel, LP(a), BMI percentile, number of screening tests performed, and family members diagnosed with FH.

Results:
Of 76 probands (age 12.5±2.9 years, 57% males) with suspected FH and genetic testing; 41 (54%) were genotype positive. Genotype positive probands were more likely to meet clinical criteria (44% vs. 17%, p=0.01), but only 19/41 (46%) had a positive family history. Genotype positive probands had higher total cholesterol (mg/dL) [median (IQR): 260 (242-297) vs. 226 (215-245), p<0.01] and LDL [199 mg/dL (174-229) vs. 153 mg/dL (144-171), p<0.01]. Sex, BMI percentile, family history, HDL, triglycerides, and LP(a) were similar between groups. Genotype positive probands (adopted probands excluded) had more screening tests performed [median (IQR): 4 (2-6) vs. 2 (1-3), p<0.01] and more new family members identified [3 (1-4) vs. 0 (0-1), p<0.01].

Conclusion:
Clinical criteria alone underdiagnosed FH in children and a negative family history occurred in over half of pediatric FH patients. A positive genetic diagnosis increased the number of screening tests performed and improved identification of at-risk family members. Therefore, genetic testing should be performed in all suspected pediatric FH patients.
Abstract 019: Estimated Benefits And Risks Of Lowering Sodium Through Potassium-enriched Salt Substitution In India: A Modeling Study
Authors: Marklund Matti , Gupta Rachita , Tullu Fikru T , Neal Bruce , Wu Jason H
Published: April 2022

Objectives:
To estimate the overall health impact in India of nationwide salt substitution (i.e., replacement of regular salt used at home for cooking or at the table with potassium-enriched reduced-sodium salt substitute).

Methods:
We used a comparative risk assessment framework to estimate 1) the number of cardiovascular disease (CVD) deaths averted due to blood pressure reductions in all adults, 2) the potential number of hyperkalemia deaths from increased potassium intake in individuals with advanced chronic kidney disease (CKD, estimated glomerular filtration rate <60 mL/min per 1.73 m
2
), and 3) the net averted deaths (calculated as the difference of 1 and 2) from nationwide salt substitution in India. We evaluated a conservative scenario, deriving key model inputs and assumptions from a large, long-term pragmatic trial recently concluded in rural China; and an optimistic scenario informed by findings from our recent salt substitution trial in India. The models incorporated existing data and corresponding uncertainties from randomised trials, national surveys, the Global Burden of Disease Study, and the CKD Prognosis Consortium. Sensitivity analyses were conducted to assess the robustness of the findings to alterations in model inputs and assumptions.

Results:
In the conservative scenario, salt substitution was estimated to result in a net ~191 000 (95% uncertainty interval: 69 683; 329 147) fewer CVD deaths annually in the overall population, and ~30 000 (1 052; 58 409) fewer deaths among 28 million individuals with advanced CKD (Figure). In the optimistic scenario, the corresponding numbers were ~343 000 (120 035; 537 134) and ~57 000 (14 253; 96 606). Net benefits were consistent in deterministic sensitivity analyses (Figure).

Conclusions:
Nationwide salt substitution in India was consistently estimated to result in substantial net benefits, preventing around 8-14% of annual CVD deaths in India. Even considering risks of hyperkalaemia, net benefits were also projected for individuals with CKD
Abstract 022: Association Of Nutritionally-Rich Plant-Centered Diets With Gut Microbial Diversity And Composition Columbia Heart Failure-Microbiome Study
Authors: Choi Yuni , Yuzefpolskaya Melana , Bohn Bruno , Molinsky Rebecca , Pinsino Alberto , Braghieri Lorenzo , Johnson Abigail , Duprez Daniel , Colombo Paolo C , Jacobs David R , Demmer Ryan
Published: April 2022

Introduction:
A plant-centered diet is related to lower risk of cardiovascular disease. However, its association with the gut microbiome has not been well studied in populations with heart failure (HF), and mechanisms linking diet to improved outcomes among HF patients are poorly understood.

Hypothesis:
Consuming a more nutritionally-rich plant-centered diet is associated with increased microbial alpha diversity and with favorable taxonomic composition and features as compared to consuming less plant-centered diets.

Methods:
We conducted a cross-sectional analysis of 152 patients with NYHA class I-IV HF with reduced ejection fraction. Diet was assessed using a food frequency questionnaire. Plant-centered diet quality was evaluated using
A Priori
Diet Quality Score (APDQS) and the APDQS was classified into quintiles; high scores were characterized by higher consumption of nutritionally-rich plant foods with lower consumption of high-fat meats and unhealthy plant foods. Stool samples were analyzed using 16S rRNA gene sequencing. Associations of the APDQS with alpha (Shannon Index and Inverse Simpson) and beta diversity (defined via Bray-Curtis dissimilarity index) were evaluated by linear regression and permutational multivariate analysis of variance (PERMANOVA), respectively. Negative-binomial regressions using DESeq2 were used to study the association between the APDQS and the relative abundance of specific taxa at the phylum and genus levels. Adjustments for multiple comparisons were performed using the false discovery rate.

Results:
Mean Shannon Index and Inverse Simpson values were 6.28±0.5 and 407.7±183.37, respectively. Among patients aged <61y, after multivariable adjustment, the APDQS (per 12 units) was associated with higher Shannon Index (0.13±0.05; P for slope=0.007) and Inverse Simpson (46.87±15.5; P for slope=0.004); no associations were observed among those aged ≥ 61y (P for interaction <0.05 for each). APDQS quintiles were not associated with beta-diversity (PERMANOVA, P=0.54). At the genus level, the highest quintile of the ADPQS (vs the lowest quintile) was associated with higher abundance of Enterobacter and lower abundance of
Catenibacterium.

Conclusions:
Consuming nutritionally-rich plant-centered diets was significantly associated with higher gut microbiota diversity in younger HF patients, as well as significantly higher or lower abundance of certain bacterial taxa at the genus level.
Abstract 028: Microbiota Composition And Diversity Is Associated With Trunk Fat: Findings From Baltimore Longitudinal Study Of Aging
Authors: Tilves Curtis , Tanaka Toshiko , Differding Moira K , Spira Adam P , Ferrucci Luigi , Mueller Noel T
Published: April 2022

Background:
Gut microbes have been associated with overall obesity in humans, including in monozygotic twins discordant on obesity, and they are sufficient to cause weight gain in mice. Trunk fat mass (TFM) is a stronger predictor of cardiometabolic diseases than overall obesity, but there is a dearth of human studies that have examined the association between gut microbiota and TFM using high-resolution shotgun metagenomic.

Objective:
To examine the association of gut microbiota diversity and composition with TFM.

Methods:
Baltimore Longitudinal Study of Aging is a racially diverse longitudinal cohort of adults ages ≥20. From 2013 to 2017, a subset of N=829 participants with DEXA scans for body composition also provided fecal samples for shotgun sequencing. We examined associations of microbiota alpha and beta diversity with TFM using ANCOVA and PERMANOVA, respectively. We tested for differential abundance of bacterial species across quartiles of TFM using ANCOM-BC. We then examined species significantly associated with TFM using splines and linear regression. All statistical models were adjusted for age, sex, and race.

Results:
Our analytic sample had a mean age of 70.5 years and BMI of 27.4 kg/m
2
, was 55.4% female, and 65.9% identified as White. TFM was associated with beta diversity (Weighted UniFrac p<0.001), but not alpha diversity (Shannon p=0.93). A doubling in the
Bacteroidetes
:
Firmicutes
(
B
/
F
) ratio—a metric associated with obesity in prior studies—was associated with -0.55 kg (95%CI: -0.78, -0.31) lower TFM. After FDR-correction, four bacterial species (
R. gnavus, Clostridium, Blautia, Dorea spp.
) were associated with higher TFM, and in a monotonic fashion (
Figure
). These four species, but not the
B
/
F
ratio, remained significant after adjustment for BMI.

Conclusion:
In a large multiracial sample of US adults, four bacterial species were uniquely associated with abdominal fat independent of BMI. Future directions include verifying these associations in longitudinal models adjusting for lifestyle factors.
Abstract 029: Proteins Linking Chronic Kidney Disease To Incident Heart Failure In Adults With Chronic Kidney Disease: The Atherosclerosis Risk In Communities Study
Authors: Buckley Leo F , Dorbala Pranav , Grams Morgan , Coresh Josef , Matsushita Kuni , Claggett Brian , Demmer Ryan , Ballantyne Christie M , Hoogeveen Ron C , Yu Bing , Shah Amil M
Published: April 2022

Introduction:
Decreased estimated glomerular filtration rate (eGFR), a kidney dysfunction marker, associates independently with an increased incident heart failure (HF) risk. Identifying mechanisms linking kidney dysfunction to incident HF may reveal potential therapeutic targets. We performed a proteome-wide analysis to identify eGFR-related pathways associated with incident HF.

Methods:
We studied ARIC participants at Visit 3 (n=10412) and Visit 5 (n=4841) who were free of HF and had aptamer-based proteomic data (SomaLogic, Boulder, CO). Multivariable linear regression models identified proteins associated with eGFR at Visits 3 and 5 at Bonferroni-adjusted P < 1x10
-5
. Incident HF associations were assessed for eGFR-related proteins with multivariable Cox proportional hazards regression models at Bonferroni-adjusted P < 1x10
-5
. All regression models were adjusted for demographics, hypertension, diabetes, coronary artery disease, atrial fibrillation, smoking status, eGFR and albuminuria. Pathway analysis (g:Profiler/KEGG) was performed using proteins associated with incident HF at a false discovery rate (FDR) of < 0.05.

Results:
The mean age at Visit 3 was 62±6 years, 52% were women, 22% were Black, and 1127 incident HF events occurred post-Visit 3 (median follow-up: 14.8 years). The mean age at Visit 5 was 76±5 years, 58% were women, 18% were Black, and 488 incident HF events occurred post-Visit 5 (median follow-up: 7.2 years). One thousand and seventy-three proteins associated with eGFR at Visits 3 and 5 (P < 1x10
-5
). Of these eGFR-related proteins, 18 associated with incident HF at Visits 3 and 5 (P < 5x10
-5
) (
Figure
). Complement and coagulation cascades and cytokine-cytokine receptor interaction pathways were enriched within the 226 proteins associated with incident HF at FDR < 0.05.

Conclusions:
Kidney dysfunction-related changes in innate immunity and thrombosis associate with an increased risk of incident HF.
Abstract 036: Influence Of Physical Activity Measurement On The Association Between Life’S Simple 7 And Cardiovascular Disease In Older Women
Authors: Hyde Eric T , Nguyen Steve , Lamonte Michael J , Tinker Lesley , Lacroix Andrea Z , Bellettiere John
Published: April 2022

Introduction:
The AHA’s Life’s Simple 7 (LS7) includes physical activity (PA) as one of the metrics for assessing cardiovascular health. Using self-reported PA can misclassify those who meet the PA component of the LS7. Using accelerometer-measured PA may improve the utility of the LS7. Our study compares associations of LS7 and incident cardiovascular disease (CVD) associations using both self-reported and accelerometer-measured PA.

Methods:
Women’s Health Initiative (WHI) participants in the Objective Physical Activity and Cardiovascular Health Study (n=4075; mean±SD age = 79±7) with no history of CVD completed the WHI PA questionnaire (PAQ) and the Community Healthy Activities Model Program for Seniors (CHAMPS) PAQ prior to wearing a hip-worn accelerometer for up to 7 consecutive days. LS7 components (PA, diet, body mass index, smoking, blood pressure, fasting serum total cholesterol and glucose) were scored on a scale of 0-2 using AHA guidelines, resulting in an LS7 summary score ranging from 0-14 with higher scores reflecting more favorable status. Four LS7 summary scores were created using different PA measures: the WHI PAQ, the CHAMPS PAQ, and two accelerometer measures (MVPA min/week and mean steps/day). LS7 scores were analyzed using quartiles (LS7 scores 1-7, 8, 9, 10-14) and hazard ratios (HR) for incident physician-adjudicated CVD were estimated.

Results:
There were 500 incident CVD events (see Table) over an average 6 years of follow-up. Multivariable HRs (95% CI) comparing women with high (10-14) vs. low (1-7) LS7 scores were: WHI PAQ=
0.81
(0.60-1.09), CHAMPS PAQ=
0.80
(0.61-1.05), accelerometer (MVPA)=
0.61
(0.47-0.79), accelerometer (steps)=
0.65
(0.45-0.94; see Table).

Conclusions:
PA is just one component of the LS7, yet the LS7-incident CVD associations vary considerably by PA measurement. Accelerometer-measured PA, such as daily steps, improves the accuracy of the LS7 PA component used to classify cardiovascular health and may be feasible for practitioners to implement.
Abstract 043: Real-World Evidence Demonstrating The Association Of SGLT2 Inhibitors With Reduced Cardiovascular Disease In Patients With Type 2 Diabetes
Authors: Wang Wendy , Chen Lin Y , Walker Rob , Chow Lisa , Norby Faye L , Alonso Alvaro , Pankow Jim S , Lutsey Pamela L
Published: April 2022

Introduction:
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of antihyperglycemic drugs recommended to patients with type 2 diabetes (T2D) as a 2
nd
line therapy after metformin. Recent evidence suggests they may reduce the risk for cardiovascular disease (CVD); however, prior studies have been clinical trials, which do not reflect real-world data, and did not conduct head-to-head comparisons of SGLT2 inhibitors. Therefore, utilizing data from the US MarketScan administrative databases in 2013-19, we tested the hypothesis that patients with T2D taking SGLT2 inhibitors have a lower risk of CVD compared to those taking other 2
nd
line therapies.

Methods:
We included 313,626 patients with T2D who were taking metformin and a 2
nd
line therapy (SGLT2 vs. other). SGLT2 inhibitor users were matched with up to 5 users of other 2
nd
line therapies by age, sex, date of enrollment, and date of 2
nd
line therapy initiation. The primary CVD outcome was a composite of stroke, atrial fibrillation, myocardial infarction, and heart failure. Patients with prevalent CVD were excluded. We also conducted head-to-head comparisons of SGLT2 inhibitors. Cox proportional hazards models were used to estimate hazard ratios (HR).

Results:
Participants were on average age 53±10 years at baseline and 47% were female. Median follow-up time was 1.4 years. After multivariable adjustments, SGLT2 inhibitor users had a lower risk of CVD than those taking other 2
nd
line therapies [Table; HR (95% CI): 0.66 (0.62, 0.71)]. Significant associations were also observed when each CVD outcome was assessed separately, with the strongest associations for stroke and heart failure. No differences were observed when comparing individual SGLT2 inhibitors.

Conclusion:
Using MarketScan data in patients with T2D, we found that users of SGLT2 inhibitors had a lower risk of CVD compared to users of other 2
nd
line therapies. By using real-world data, these findings complement clinical trial results supporting the effectiveness of SGLT2 inhibitors in reducing risk of CVD.
Abstract 047: Effects Of The Dash Diet On Change In High-Sensitivity Cardiac Troponin I Over Time: Results From The Dash-Sodium Trial
Authors: Belanger Matthew J , Kovell Lara C , Turkson-Ocran Ruth-Alma , Mukamal Kenneth J , Liu Xiaoran , Appel Lawrence J , Miller Edgar R , Sacks Frank M , Christenson Robert H , Rebuck Heather , Chang Alex R , Juraschek Stephen P
Published: April 2022

Background:
The DASH (Dietary Approaches to Stop Hypertension) diet has been shown to reduce high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of subclinical cardiac injury. However, the time course of the DASH diet’s effects on this biomarker has not been determined.

Hypothesis:
The DASH diet lowers hs-cTnI within 4 weeks and the effects gradually increase over time.

Methods:
We analyzed data from the DASH-Sodium trial, a randomized controlled feeding study of healthy adults with systolic blood pressure 120 to 159 mm Hg and diastolic blood pressure 80 to 95 mm Hg. Participants were randomly assigned to the DASH diet or a typical American diet (control). Within each arm of the study, participants were assigned three sodium levels, in random order, changed every 4 weeks. Hs-cTnI was measured from serum collected at baseline and at 4, 8, and 12 weeks of feeding. Energy intake was adjusted to maintain body weight throughout the trial.

Results:
Of the 411 participants included in the final analysis, their mean age was 48 years, 56% were women, and 56% were Black. The mean baseline systolic/diastolic blood pressure was 135/86 mm Hg. Compared with baseline, the control diet did not have a significant effect on hs-cTnI at any of the measured time points. In contrast, the DASH diet reduced hs-cTnI by 0.18 ng/l (95% CI: -0.32, -0.04) at 4 weeks, 0.14 ng/l (95% CI: -0.29, 0.00) at 8 weeks, and 0.33 ng/l (95% CI: -0.48, -0.18) at 12 weeks (
Figure
;
P
-trend = 0.025). The %-difference in mean change from baseline of hs-cTnI for DASH vs. control was -13.30% (95% CI: -25.34, 0.69), -10.47% (95% CI: -23.08, 4.21), and -17.78% (95% CI: -29.51, -4.09) at 4, 8, and 12 weeks, respectively.

Conclusions:
The DASH diet reduced hs-cTnI within 4 weeks of feeding with greater diet effects occurring at 12 weeks of feeding. These results suggest that the DASH diet has both early and cumulative effects on subclinical cardiac injury.
Abstract 055: Neighborhood-Wide Association Study Of Hypertension In The Health And Retirement Study
Authors: Sims Kendra D , Hystad Perry W , Batty G. D , Smit Ellen , McGregor Jessina C , Odden Michelle C
Published: April 2022

Background:
Systematic evaluation of neighborhood factors which capture an array of characteristics -analogous to genome-wide-association studies- may identify important patterns in spatial determinants of blood pressure control.

Methods:
Our sample included Health and Retirement Study participants (N=13180; 58% women, 13% non-Hispanic Black, 4% Hispanic/Latino) with at least one sphygmomanometer reading taken between 2006 and 2016. Our main study outcome was at least one hypertensive blood pressure measurement over the study period. Participants were randomly assigned to either a training or test dataset. Using generalized estimating equations, we summarized multivariable associations between each of 51 standardized American Community Survey sociodemographic, housing, and income-related census tract variables (2005-09) and the period prevalence of measured hypertension. We adjusted for individual factors and accounted for multiple comparisons in the training set using the Simes significance test. Neighborhood-based factors that revealed statistically significant associations (Simes-adjusted p-value<=0.05) with hypertension in the training dataset were rerun in the test dataset to replicate findings. Lastly, in the full cohort, we evaluated main and race/ethnicity-stratified independent effects of each significant neighborhood factor on the likelihood of at least one hypertensive sphygmomanometer reading between 2006 and 2016. We hypothesized that residence in neighborhoods with worse housing or socioeconomic characteristics would be associated with a higher odds of hypertension, and that associations in the full sample would differ by racial/ethnic designation.

Results:
Thirty-two percent (4218 out of 13180) of participants had at least one hypertensive sphygmomanometer reading between 2006 and 2016. In the training set, two of the 51 census-tract level variables were independently associated with period prevalence of hypertension. In the full sample, we observed a lower likelihood of prevalent hypertension (OR: 0.95; 95% CI: 0.92, 0.99) among participants residing in a census tract with recent (since 2000) in-migration. A higher proportion of relatively recent (since 2000) renters in the census tract was associated with a lower hypertension prevalence (OR: 0.95; 95% CI: 0.91, 0.98). When stratified by racial/ethnic designation, these patterns were apparent among Non-Hispanic White and to some extent Hispanic/Latino but not Non-Hispanic Black participants. However, differences were not statistically significant by race or ethnicity.

Conclusion:
In conclusion, relatively more recent relocation to an area appears to be modestly associated with reduced prevalence of hypertension. These findings support possible differential cardiovascular health impacts of gentrification. Further investigation is needed to confirm these findings.
Abstract 056: Inflammatory Cytokines And Incident Hypertension In The REasons For Geographic And Racial Differences In Stroke (REGARDS) Study
Authors: Plante Timothy B , Juraschek Stephen P , Howard George , Howard Virginia J , Tracy Russell P , Judd Suzanne E , Kamin Mukaz Debora , Zakai Neil A , Long D Leann , Cushman Mary
Published: April 2022

Background:
Higher C-reactive protein (CRP) is a risk factor for incident hypertension, but this non-specific inflammatory biomarker does not provide insight into specific immune pathways of hypertension. Here, we studied the role of selected cytokines in risk of incident hypertension to better elucidate these pathways.

Objective:
To determine the risk for incident hypertension disease among adults by level of IL-1β, IL-6, TNF-α, and IFN-γ.

Methods:
REGARDS recruited 30,239 Black and White adults aged ≥45 years from the 48 contiguous states in 2003-07. The Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) substudy included 4,400 sex-race stratified REGARDS participants who also attendd a visit in 2013-16. We excluded those in BioMedioR with prevalent hypertension: 140/90 mm Hg threshold or self-reported antihypertensive medication use. Serum ELISAs assessed cytokines. Modified Poisson regression estimated relative risk (RR) of incident hypertension by detectable threshold (IL-1β; >0.06 pg/mL) or cytokine tertiles (tertile thresholds [33
rd
& 66
th
%iles] in pg/mL: IL-6, 0.56 & 0.94; TNF-α, 1.30 & 1.69; IFN-γ, 4.01 & 6.56). IL-1β was stratified on race because of a statistically significant interaction.

Results:
Among the 1,877 participants at risk for incident hypertension (mean [SD] age 62 [8] years, 36% Black race, 51% women), incident hypertension occurred in 31% of White adults and 45% of Black adults. With full adjustment (
Figure
), higher TNF-α and IFN-γ in everyone, and detectable IL-1β in White but not Black adults, were associated with greater incident hypertension risk. There was no association of higher IL-6 with incident hypertension.

Conclusions:
Among Black and White adults without prevalent hypertension, higher TNF-α, and IFN-γ, and detectable IL-1β (among White but not Black adults), were associated with greater risk of incident hypertension. Future basic and clinical research should study these inflammatory pathways toward developing hypertension prevention strategies.
Abstract 059: COVID-19 And Type II NSTEMI: A Comprehensive Overview
Authors: Patel Sahishnu , Visotcky Alexis , Devine Adam , Kode Vishwajit , Kotlo Srisha , Aljadah Michael , Sparapani Rodney , Kulinski Jacquelyn P
Published: April 2022

Introduction:
Data on the incidence of type 2 NSTEMI (T2MI) in hospitalized patients with COVID-19 infection has been limited to single-center studies. We propose to define the incidence of T2MI in a national cohort and identify pre-hospital patient characteristics associated with a diagnosis of T2MI in hospitalized patients with COVID-19. We will also examine the impact of T2MI on morbidity and mortality.

Methods:
We performed a retrospective analysis on data from the American Heart Association COVID-19 Cardiovascular Disease Quality Improvement Registry. This national registry contains data on tens of thousands of patients hospitalized with COVID-19 from at least 122 centers across the United States. From January 2020 through May 2021, there were 709 (2.2%) out of 32,015 patients with a coded diagnosis of T2MI. We performed Wilcoxon tests, chi-squared test, and multivariable logistic regression to (1) identify predictive pre-hospital patient characteristics (Table 1) of T2MI for patients hospitalized with COVID-19 and (2) investigate the impact of T2MI on mortality and morbidity.

Results:
Patients in the T2MI group were older (71 vs. 63 years, p<0.001), and in forward selection analyses, patients with a diagnosis of T2MI had higher odds of known HTN (OR 1.79 [1.01-3.1], p=0.026) and heart failure (OR 3.46 [2.24-5.34], p<0.001). Increased age, admission troponin, CRP, and d-dimer were also associated with higher odds of T2MI. Hispanic race (OR 0.517 [0.289-0.924], p=0.026) and use of antihyperglycemics (OR 0.562 [0.377-0.836], p=0.005) were both associated with lower odds of T2MI. T2MI led to increased mortality (HR 1.32, [1.17-1.5], P<0.001) and morbidity including cardiac arrest, major bleeding, and stroke.

Conclusion:
A history of heart failure was the strongest predictor of T2MI in hospitalized COVID19 patients. Patients with a T2MI compared to those without, had significantly higher mortality and morbidity. Limitations include the heterogenous ascertainment of the T2MI diagnosis across sites in this registry.
Abstract 065: Educational Attainment And Dementia Risk: Mediation By Vascular Risk Factors At Mid-life In The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Liu Chelsea , Ma Yuan , Hofman Albert , Waziry Reem , Koton Silvia , Pike James R , Windham B Gwen , Power Melinda C , Sharrett A R , Gottesman Rebecca F
Published: April 2022

Background:
Dementia prevention largely focuses on the modification of vascular risk factors and is particularly important among stroke survivors, who have the highest burden of vascular risk factors and are at elevated risk of dementia. Low educational attainment is a risk factor not only for worse vascular profiles at midlife but also for incident dementia. It is unclear to what extent the relationship between education and dementia is mediated through these vascular risk factors.

Methods:
In a cohort of 14,059 Black and White older adults in four U.S. communities, we assessed the relationship between education and dementia among all participants and, separately, among those with incident stroke. We used causal mediation analysis to assess multiple mediation by midlife hypertension, diabetes, BMI and smoking of the relationship between educational attainment and dementia.

Results:
Participants with less education had higher prevalence of mid-life risk factors. Lower education was associated with 60% higher risk of dementia and 40% higher risk of post-stroke dementia. About half of the association between education and dementia was mediated through vascular risk factors (Table 1).

Conclusion:
A substantial proportion of the relationship between education and dementia risk is indeed not mediated through mid-life vascular risk factors. The association between education and dementia was weaker in the high-risk participants who have had an incident stroke, indicating that more proximal causes such as vascular disease prior to the stroke superseded the distal cause of differences in educational attainment. As such, any mediated effect of education on dementia is likely through vascular risk factors earlier on in the life-course. Our findings suggest that dementia prevention efforts must also address disparities in socioeconomic resources as well as other mediating pathways.
Abstract 066: A Healthy Plant-based Diet Was Associated With Slower Cognitive Decline In African Americans: A Biracial Community-based Cohort Of Older Adults
Authors: Liu Xiaoran , Dhana Klodian , Barnes Lisa , Tangney Christy , Aggarwal Puja , Agarwal Neelum , Holland Thomas , Rajan Kumar
Published: April 2022

Background:
African Americans (AAs) are about twice as likely to develop dementia compared to non-Hispanic whites (NHWs). Dietary modification is an effective preventive strategy to reduce the rate of cognitive decline, a hallmark feature of dementia; however, evidence from diverse populations focusing on AAs is minimal.

Objective:
To evaluate the association between a plant-based diet and the rate of cognitive decline in a population-based sample of AAs and NHWs.

Method:
This study consisted of 4753 participants (62% African American, 63% female) in a biracial population-based study in the United States (Chicago Health and Aging Project, 1993 to 2012). Plant-based diet quality was evaluated by the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). Global cognition was assessed using a composite score of four tests of cognition. We used mixed models to examine the association between PDI, hPDI, and uPDI with the rate of decline in global cognition, perceptual speed, and episodic memory. Models were adjusted for age, sex, apoE genotype, education, cognitive activities, smoking status, calorie intake, risk factors of cardiovascular disease, time, and an interaction term of time with each covariate.

Results:
We demonstrated that there were distinct differences in the association of dietary patterns with cognitive decline in AAs and NHWs. AAs had higher intakes of egg, fish or seafood, sugar-sweetened beverages, and whole grains compared to NHWs (p<0.001 for all). Higher hPDI was associated with a slower rate of decline in global cognition, perceptual speed, and episodic memory in AAs but not NHWs. AAs in the highest quintile of hPDI had significantly slower rates of decline in global cognition, β = 0.0183 (p=0.032), perceptual speed β = 0.0179 (p=0.04), and episodic memory β=0.0183 (p=0.04) compared to individuals in the lowest quintile of hPDI. The rate of global cognitive decline in the highest quintile was slowed by 28.4% when compared to individuals in the lowest quintile of hPDI in AAs. There were no associations with either PDI or uPDI and the rate of cognitive decline in either racial group.

Conclusion:
AAs and NHWs have distinct dietary patterns. A healthy plant-based diet was associated with a slower rate of decline in global cognition, perceptual speed, and episodic memory in AAs. These results are informative in facilitating the development of tailored dietary recommendations for the prevention of cognitive decline in diverse populations.
Abstract 077: Association Between Key Family And Individual Factors And The Risk Of Obesity In Offspring: Findings From A Prospective Cohort Study
Authors: Wang Liang , Morelen Diana , Alamian Arsham
Published: April 2022

Purpose:
There remains a significant gap in our knowledge of the synergistic nature of family dynamics, child characteristics, and child-rearing features in the etiology of obesity from childhood through adolescence. We assessed the impact of family dynamics (poverty, family structure), child characteristics (child temperament), and child-rearing features (maternal depression, maternal sensitivity, and type of child care) on the development of childhood obesity.

Methods:
Children (n=1,240) whose weights and heights were measured at least once for ten time points (from 2 years through 15 years) from the NICHD Study of Early Child Care and Youth Development were included. Childhood obesity was based on standardized height and weight measures taken during the interviews and was defined according to appropriate 2000 CDC age and sex-specific body mass index percentiles. Maternal sensitivity was based on behavioral observations when children were 6 months of age, and all other measures were parental self-report. Generalized estimating equation (GEE) was used to examine the impact of family and individual factors on the childhood obesity after adjusting for covariates (child sex, race, birth weight).

Results:
Prevalence of obesity increased from 2 years (5.6%) to school ages (e.g., 19.5% at Grade 5 and 15.5% at age 15 years). Adjusted GEE models showed that living below poverty level was associated with an increased risk of obesity (odds ratio (OR)=1.62, 95% Confidence Interval (CI)=1.05, 2.53). Additionally, being nonwhite and higher birthweight were positively associated with an increased risk of obesity across time.

Conclusion:
Among these key family and individual factors, poverty status was observed to be the strongest predictor of obesity risk of offspring across time. Findings highlight the importance of systemic-level public health changes in obesity reduction efforts and suggest that poverty-reduction based prevention and intervention are likely more effective targets than more individual/family specific targets.
Abstract EP02: Identification Of Genetic Signals For “Diabesity” --- Type 2 Diabetes And Obesity -- Among African American And European American Participants In Four Cohorts Of The TOPMed Consortium
Authors: Chan Kei Hang Katie , Liu Qing , Reiner Alex P , De Vito Roberta , Kooperberg Charles , Brody Jennifer , Lange Leslie , Manson Joann E , Correa Adolfo , Cupples L. Adrienne , Flickinger Matthew , Li Jie , Lin Xiaochen , Madsen Tracy , North Kari E , Raffield Laura M , Manning Alisa , Meigs James B ,   NHLBI Trans-Omics for Precision Medicine (TOPMed)Consortium, Liu Simin
Published: April 2022

Background:
Diabesity defines the concurrent manifestation of type 2 diabetes (T2D) and obesity (BMI≥30 kg/m
2
) in the development of cardiovascular diseases, although the genetic basis for this joint phenotype remain poorly understood.

Objective:
This study aimed to identify the overlapping genetic patterns for diabesity incidence in 3,231 self-reported African American (AA) and 8,252 European Americans (EA) participated in four cohorts of the Trans-Omics for Precision Medicine (TOPMed) consortium.

Methods:
Using marker set enrichment analysis (MSEA) of whole genome sequencing data, specific gene sets (pathways) and key driver (KD) genes (important hub genes overrepresented in a network of pathways) were identified for diabesity incidence. Using multi-tissue and multi-species gene expression signatures as molecular indicators of drug functions, their potential drug signatures were also examined.

Results:
Testing genome-wide significance (P-value < 10
-8
) identified seven independent loci, six of which were replicated in the T2D Knowledge Portal
(https://t2d.hugeamp.org/
)(
NPFFR1, TRIO, G6PD, BCL11A, IGF1,
and
TCF7L2,
P<0.05) for diabetes and/or such obesity-related traits as blood pressure, lipids, glucose and insulin levels. One novel variant for diabesity, rs144540309, is an intronic region of
GPAT3
(G>A, AA MAF = 0.004, beta=3.66 and P=1.00e-8) whose enzyme plays important roles in dietary lipid absorption, enteric and hepatic lipid homeostasis, and entero-endocrine hormone production, along with 12 KEGG/Reactome/Biocarta pathways enriched for diabesity in AAs and 11 for EAs. In AAs, the top three pathways (ranked by P-value and false discovery rate [FDR]) were mitotic spindle checkpoint, resolution of sister chromatid cohesion, and rho GTPases activate formins, along with six KD genes (
NCKAP1L, CDCA8
,
BUB1
,
IRF5
,
FYB
, and
C15orf23
); in EAs, colorectal cancer, prostate cancer, and beta Catenin independent WNT signaling were the top 3 pathways (FDR≤0.25) including
LEF1
. Top repositioned drugs derived from diabesity-related gene sets (FDR≤0.25) included Benzbromarone, Fenofibrate, Interleukin-1β, and antihypertensive.

Conclusion:
Our study supports the notion that both pathway and network-based analytical approaches may identify novel signals from gene sets for highly clustering clinical phenotypes such as diabetes and obesity and improve their target validation for intervention.
Abstract EP03: 30-day Readmission Rates After Targeted Temperature Management For Cardiac Arrest
Authors: Mark Justin , Dodge Joshua , Belaunzaran Miguel , Wahood Waseem , Hardigan Patrick , abumoawad Abdelrhman
Published: April 2022

Background:
In its 2015 guidelines, the American Heart Association instituted a Class 1 recommendation for use of Targeted Temperature Management (TTM) in patients with cardiac arrest (CA) . Prior observational studies have suggested benefits using TTM in these patients, while many randomized control trials have failed to replicate these results. Regardless, there have been studies with contradictory conclusions addressing readmission rates in patients receiving TTM. Thus, we sought to ascertain this relationship further by identifying 30-day readmission rates in Out-of-Hospital Cardiac Arrest (OHCA) patients receiving TTM.

Methods:
We utilized the Healthcare Cost and Utilization Project (HCUP) National Readmission Database (NRD) for data collection and International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes to identify 353,380 cardiac arrest cases and clinical variables. The primary outcome includes all-cause readmission rates within 30 days from cardiac arrest index admission discharge. We then conducted a logistic regression analysis after accounting for variables to assess odds of 30-day readmission in these patients.

Results:
TTM following CA was associated with a decreased likelihood of readmission at 30 days(OR: 0.822, p = 0.006, 95% CI [0.716-0.945]). Comorbidities associated with an increased risk of readmission after controlling for the other variables include congestive heart failure(OR: 1.259, p = 0.027, 95% CI [1.207-1.313]) and renal failure (OR: 1.363, p = 0.031, 95% CI [1.304- 1.425]). Of these patients receiving TTM compared to those who did not receive TTM, there was a greater proportion of cardiogenic shock (23.7% vs. 12.3%, p < 0.001), acute heart failure (20.1% vs. 17.3%, p < 0.001), coronary artery disease (53.0% vs. 46.2%, p < 0.001), ischemic cardiomyopathy (61.7% vs. 53.1%, p < 0.001), ventricular tachycardia (9.6% vs. 8.6%, p = 0.045), and ventricular fibrillation (56.6% vs. 24.1%, p<0.001).

Conclusion:
TTM following CA is associated with decreased odds of readmission at 30 days. Prior long-term comorbidities represented most of the covariates for readmissions in this patient population.
Abstract EP07: A Longitudinal Lipidomics Profiling For Risk Of Chronic Kidney Disease In American Indians: The Strong Heart Family Study
Authors: Zeng Wenjie , Miao Guanhong , Subedi Pooja , Cole Shelley , Umans Jason G , Franceschini Nora , Lee Elisa T , Howard Barbara V , Fiehn Oliver
Published: April 2022

Background:
Dyslipidemia is associated with and often precedes the onset of chronic kidney disease (CKD). However, standard lipid panels fail to describe the full spectrum of blood lipidome. A longitudinal profiling of the full spectrum of blood lipidome associated with the risk of CKD is still lacking in any racial/ethnic group, including American Indians, a population that suffered a disproportionately high burden of CKD.

Objective:
To identify novel lipids and lipidomic signatures associated with risk of CKD in American Indians, independent of traditional risk factors.

Methods:
We included 1,910 American Indians who attended two examinations (~5.5 years apart) and were free of CKD and cardiovascular disease (CVD) at baseline. CKD was defined based on the estimated glomerular filtration rate (eGFR) calculated by the CKD-EPI formula. Fasting plasma levels of 1,542 lipids in 3,916 samples at two-time points were repeatedly measured by untargeted LC-MS. Machine learning (elastic net) was used to identify lipidomic predictors of CKD beyond traditional risk factors (age, sex, center, BMI, hypertension, diabetes, urinary albumin/creatinine ratio, HDL, triglyceride, and use of lipid-lowering medications). Mixed-effect linear models were used to examine the relationship between changes (baseline to 5-year follow-up) in lipidome and change in kidney function (eGFR), adjusting for traditional risk factors mentioned above, baseline lipid, and baseline eGFR. Multivariate analysis was conducted to identify discriminatory lipidomic signatures that can differentiate between high- and low-risk individuals.

Results:
Of 1,910 participants free of CKD and CVD (17.8% diabetic) at baseline, 55 (2.9%) developed incident CKD by the end of a 5-year follow-up. Elastic net identified 106 (24 known) lipids, largely glycerophospholipids (GPs), sphingomyelins (SMs), triacylglycerols (TAGs), fatty acids (FAs), and acylcarnitines (ACs), whose altered baseline levels were associated with the risk of CKD, independent of traditional risk factors. A composite lipid score composed of the 24 known lipids improved CKD risk prediction beyond traditional risk factors (AUROC improved from 0.944 to 0.963, P = 0.006). Longitudinal changes in 182 lipids (75 known) lipids, largely GPs, FAs, SMs, TAGs, ACs, and diacylglycerols (DAGs), explained up to 4.8% of the variation of the eGFR change. Multivariate analysis identified distinct lipidomic signatures that separated high- from low-risk participants.

Conclusion:
We identified novel molecular lipids that significantly predict CKD onset and progression among American Indians beyond traditional risk factors. Our findings shed light on the mechanisms by which dyslipidemia affects CKD and provide instrumental data for biomarker identification, risk prediction and stratification, prognosis, and potential therapeutics.
Abstract EP10: Obesity Is An Independent Risk Factor For Type 2 Myocardial Infarction-related Hospitalizations Without Significant Association With In-Hospital Mortality
Authors: Jain Akhil , Sultan Waleed , Ghadge Nitin , Moras Crystal , Yarrarapu Siva Naga , Dhaduk Kartik , Ijaz Hasnan , Qaryouti Mohammed Ghazi Moh'd , Desai Rupak
Published: April 2022

Background:
Contemporary data for the impact of obesity (BMI>30) on the risk of demand ischemia-related myocardial infarction (i.e. type 2; T2MI) and subsequent outcomes is lacking. We aimed to study the risk and outcomes of T2MI with obesity.

Methods:
We used National Inpatient Sample (2018) to identify adult hospitalizations with T2MI (excluded concurrent T1MI). Multivariable regression was performed to assess the risk of T2MI with obesity. Using propensity-matched analysis obese vs non-obese cohorts (1:1) were obtained to compare comorbidities and primary outcomes (in-hospital mortality/cardiogenic shock).

Results:
Obese had higher odds of T2MI (OR 1.11, 95%CI:1.05-1.17, p<0.001) when adjusted for confounders. Propensity-matched cohorts (

Table 1

, n=6220 obese & non-obese, each) were comparable for sociodemographics with higher rates of diabetes, hyperlipidemia, COPD, CKD, deficiency anemia, prior history of MI/CABG but lower hypertension, smoking, CHF, PVD, substance abuse, prior stroke than non-obese. Association of obesity did not reach a significant level of difference for all-cause in-hospital mortality (OR 0.93, 95% CI: 0.51-1.70) and cardiogenic shock (OR 1.42, 95%CI 0.75-2.69). Length of stay was similar (3 days) but obese patients with type MI had a higher mean cost of hospitalization.

Conclusion:
Obesity independently predicted a higher risk of developing T2MI but without any significant association with short-term all-cause in-hospital mortality or cardiogenic shock.