bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP08: Whole Exome Sequencing Study Identified A Novel Variant For Kidney Function And Progression Of Chronic Kidney Disease
Authors: Li Changwei , Francis Michael , Westbrook Adrianna , Zhang Ruiyuan , Shen Ye , Ye Kaixiong , Chen Jing , He Jiang , Kelly Tanika N
Published: May 2021

Introduction:
Most genetic variants for chronic kidney disease (CKD) have been identified in non-coding regions, with functional roles that are difficult to interpret.

Hypothesis:
A whole exome sequencing study focusing on coding variants will reveal novel mechanisms of kidney function and CKD.

Methods:
We performed whole exome sequencing analyses of cystatin C among 29,789 UK Biobank (UKB) participants with further confirmation among 4,297 white and 607 African American participants of the Health and Retirement Study (HRS). Conditional analyses for loci achieving exome-wide significance (
P
<3.5х10
-7
) were conducted in UKB using both the exome (n=29,789) and imputed GWAS data (n=295,122). Genomic findings were tested for relevance to baseline estimated glomerular filtration rate (eGFR) and stringently adjudicated CKD progression events among participants of the Chronic Renal Insufficiency Cohort (CRIC) by race and smoking status, using a base model and a full model (
Table
).

Results:
We identified a common missense variant,
CST9
rs2983640, in a previously reported locus (
CST3
intron rs13038305), of which the minor G allele was associated with lower serum cystatin C level (UKB: beta=-0.03 mg/L,
P
=7.64х10
-92
; HRS whites: beta=-0.05 mg/L,
P
=4.71х10
-6
; HRS African Americans: beta=-0.03 mg/L,
P
=0.64; and multi-ethnic meta-analysis beta=-0.03 mg/L,
P
=2.46х10
-91
). After controlling for the
CST3
variant, the G allele was associated with higher cystatin C level (UKB exome: beta=0.003 mg/L,
P
=0.04; UKB GWAS: beta=0.003 mg/L,
P
=1.47х10
-10
). Similar associations were identified in white CRIC participants (direct effect: beta=-0.05 mg/L,
P
=0.005; conditional effect: beta=0.004 mg/L,
P
=0.86). The
CST9
rs2983640 G allele was associated with lower baseline eGFR (base model beta=-0.33 ml/min/1.73 m
2
,
P
=1.98х10
-6
) and higher hazard of developing CKD progression independent of the reported
CST3
variant (
Table
).

Conclusions:
We identified a novel missense variant influencing cystatin C level and CKD progression.
Abstract MP09: Untargeted
1
H Nmr Metabolomics Metabolomic Analysis Reveals Pathways Of Protection Between Mediterranean-style Diet And Incident Cardiovascular Disease In The Multi-ethnic Study Of Atherosclerosis.
Authors: Wood Alexis C , Saylor Georgina , Tzoulaki Ioanna , Greenland Philip , Tracy Russell P , Post Wendy S , Lindon John , Wassel Christina L , Phan Mimi , Momin Shabnam , Ebbels Tim , Boulange Claire , Graça Goncalo , Karaman Ibrahim , Gadghil Meghana , Chekmeneva Elena , Kaluarachchi Manuja , Elliott Paul , Herrington David M
Published: May 2021

Background:
The metabolites associated with a Mediterranean-style (AMED) diet may give insight into why AMED is robustly associated with protection against CVD. Previous investigations seeking to identify these have been limited by the use of modest sample sizes and targeted assays.

Methods:
Using samples from the Multi-Ethnic Study of Atherosclerosis (MESA), we conducted untargeted
1
H NMR spectroscopy (600 MHz) with internal and external annotation on the sera of ~3,698 participants, ages 45-84, who were free from overt CVD. We included data on baseline dietary intake (self-reported), and all incident CVD events (excluding stroke) over a 10-year period. From >100,000 spectral features, 845 significant associations (P<2.2*10
-6
) were identified via linear regression, and reduced to a putative list of 46 via elastic net regularized models. Hierarchical clustering identified 11 feature groups, from which cluster scores were constructed. The ‘mediate’ package in R used bootstrapping (1000 simulations) to partition the association between AMED and incident CVD into the effects of dietary intake on CVD which are mediated by the metabolomic cluster scores (the “indirect” / mediated effects) and those effects which are not (“direct effects”). All association analyses controlled for age, sex, ethnicity, data collection site and daily caloric intake.

Results:
AMED score was associated with reductions in the incidence of CVD (HR=0.95; 95% CI: 0.91 - 0.99; P=0.02). All metabolomic cluster scores were associated with AMED (all P<2*10
-06
;
Table 1
), with 6 significantly associated with incident CVD (all P<2.0*10
-4
) in the expected direction given their associations with AMED score. Four of these six significantly mediated the association of AMED score with incident CVD (P<0.05;
Table 1
).

Conclusions:
These preliminary data suggest that specific molecules, if replicated in other studies, hold promise to identify the underlying pathways by which an AMED diet offers protection against CVD.
Abstract MP10: A Novel Genetic Locus Influences Microvascular Reactivity To Acute Psychological Stress
Authors: Almuwaqqat Zakaria , Liu Chang , Kim Jeong Hwan , Lima Bruno B , Hammadah Muhammad , Alkhoder Ayman , Shah Amit J , Bremner James Douglas , Vaccarino Viola , Sun Yan , Quyyumi Arshed A
Published: May 2021

Background:
Excessive peripheral microvascular constriction during acute psychological stress, measured using peripheral arterial tonometry reflects similar changes in coronary blood flow.The ratio of digital pulse wave amplitude during stress compared to rest (sPAT) is used to estimate the degree of microvascular response to stress.

Hypothesis:
We hypothesized that genetic factors contribute to the degree of microvascular constriction during mental stress and that excessive vasoconstriction is associated with adverse cardiovascular outcomes.

Methods:
A total of 580 stable CAD subjects of European and African ancestries from two prospective cohort studies underwent mental stress testing with a standardized public speaking stressor. Digital pulse wave amplitude was continuously measured using PAT and the stress/rest PAT ratio (sPAT) of pulse wave amplitude during mental stress/baseline was calculated. Genotyping was performed using Illumina’s Multi-Ethnic Genotyping Array platform and imputed to the 1000 Genome reference panel. Ethnicity-specific genome-wide association studies (GWAS) of sPAT were conducted using linear regression of additive genetic mode adjusted for age, sex and population stratification in both cohorts. A trans-ethnic meta-analysis integrated the GWAS results from four sub-cohorts. Upon 5-year follow-up, Fine and Gray’s sub-distribution hazard ratios (sHR) were used to examine the association between sPAT ratio (> vs=< median) and the composite endpoint of cardiovascular death, myocardial infarction, revascularization, and hospitalization for heart failure.

Results:
Mean age was 63±9; 65% male, 35% African American. We identified three SNPs in linkage disequilibrium on chr7:111,666,943 T>C (rs6466396); chr7: 111,668,622 T>G (rs876170); chr7: 111,668,623 T>G (rs876169) that were associated with greater sPAT ratio by means of 0.13, 0.12 and 0.10, (
P
= 1.42E-08). The sPAT-associated locus was within
DOCK4
gene which encodes Dedicator of Cytokinesis 4, an essential protein for angiogenesis and brain development, and a known locus for obesity. After adjusting for demographic and cardiovascular risk factors, medications, and rate-pressure product change during mental stress, those with low sPAT ratio were at significantly higher risk of adverse outcomes (sHR 1.8 [95% CI 1.1 - 2.8]).

Conclusion:
We have identified a genetic basis for stress-induced vasomotion. Presence of allele C (rs6466396) is associated with increased vasoconstriction during mental stress, and thus may predispose CAD patients to a higher risk for adverse cardiovascular outcomes with stressful exposure.
Abstract MP13: Lipid Peroxidation And Inflammatory Response Differentiate With Changes In Liver Fat Among Obese Latino Youth Following Lifestyle Intervention
Authors: Pena Armando , Vander Wyst Kiley B , Soltero Erica , Olson Micah , Pimentel Janiel , Ayers Stephanie , Knowler William , Konopken Yolanda , Patrick Donald , Hu Houchun , Castro Felipe , Keller Colleen , Williams Allison N , Fernandez Arlene D , Shaibi Gabriel Q
Published: May 2021

Introduction:
Lipid peroxidation and inflammation are pivotal pathological processes involved in the progression of NAFLD, a prelude to cardiovascular disease. Lifestyle intervention is the cornerstone approach for preventing cardiometabolic disease among high-risk populations, yet studies have not examined the mechanisms by which lifestyle intervention may mediate changes in liver fat in youth.

Hypothesis:
Lifestyle intervention will decrease hepatic fat fraction (HFF), tumor necrosis alpha (TNF)-α, and malondialdehyde (MDA)-protein adducts.

Methods:
Latino youth with obesity (n=26, age 13.9±1.3, BMI% 98.1±1.1) and prediabetes completed a 6-month lifestyle intervention that included nutrition education (1 d/wk) and physical activity (3 d/wk). HFF was measured by MRI before and after intervention. Fasting serum samples were collected for measurement of lipid peroxidation, measured by MDA-protein adducts, and inflammation, measured by TNF-α. Repeated measures ANOVA models were used to examine the effect of lifestyle intervention on HFF, MDA-protein adducts, and TNF-α. Data are presented as Mean±SE.

Results:
The intervention led to significant decreases in HFF (from 7.0±1.1% to 5.4±0.7%, p=0.027) and TNF-α (from 1.7±1.0 to 1.5±0.1 pg/mL, p=0.050), but not MDA-protein adducts (from 266.4±28.4 to 253.8±29.3 pmol/mL, p=0.105). However, there was significant heterogeneity in changes in HFF whereby those with the greatest response (n=14) decreased HFF by -44.0% while non-responders (n=12) increased HFF by 67.5%. HFF responders exhibited significantly greater reductions in MDA-protein adducts (from 256.2±39.4 to 228.1±40.0 pmol/mL, Δ-10.1%) compared to HFF non-responders (from 278.4±42.5 to 283.7±43.2 pmol/mL, Δ2.0%; p=0.023). TNF-α was reduced in HFF responders (from 1.8±0.2 to 1.5±0.1 pg/mL, Δ-17.8%) compared to HFF non-responders (from 1.5±0.2 to 1.5±0.1 pg/mL, Δ-4.4%) but was not significant (p=0.231).

Conclusions:
Reductions in HFF through lifestyle changes were associated with greater reductions in markers of lipid peroxidation, but not inflammation. The effect of lifestyle intervention on HFF may be mediated by markers that extend beyond traditional clinical risk factors among high-risk youth.
Abstract MP22: Social Isolation, Social Support, And Cognitive Decline: The Atherosclerosis Risk In Communities Study
Authors: Liu Albert , Koton Silvia , Lutsey Pamela L , Walker Keenan , Palta Priya , Sharrett A Richey , Gottesman Rebecca F , Gross Alden L
Published: May 2021

Introduction:
Recent evidence supports relationships between social engagement and cognitive function, but the importance of social engagement decades before the onset of cognitive impairment is less well described. We examined associations of midlife social isolation and social support with mid-to-late life cognitive decline.

Methods:
In 14,083 participants in the Atherosclerosis Risk in Communities (ARIC) Study, social isolation was evaluated in 1990-92 by the Lubben Social Network Scale, discretized into: Isolated, and high, moderate, and low “risk” for isolation. Perceived social support, using the Interpersonal Support Evaluation List-Short Form, was discretized into tertiles. Linear mixed effects models with random intercepts and slopes were used to estimate the cross-sectional and longitudinal (1990-92 to 2011-13) associations of social isolation/social support with general cognitive performance. Models were adjusted for demographic factors and comorbidities, with effect modification explored by race and sex. We used multiple imputation by chained equations (MICE) to account for attrition.

Results:
Participants were on average 57.0 years old, 56% female, and 24% Black; 3% were “isolated” and 38% reported low social support. On average, men had a higher level of social isolation and lower level of social support. White participants had lower scored risk of social isolation. Socially isolated participants had on average a 0.253 standard deviation (SD) (95% CI 0.181, 0.324) lower baseline cognitive score, but a similar rate of cognitive decline in both the first 6 (difference: 0.002 SD/year, 95% CI -0.008, 0.012) and subsequent 15 years (difference: 0.001 SD/year, 95% CI: -0.006, 0.008), compared to those with lower social isolation level. Compared to participants with the highest level of social support, participants with the lowest level of social support had on average a 0.183 SD (95% CI 0.154, 0.212) lower baseline cognitive score, with a similar rate of cognitive decline in the first 6 years (difference: -0.001 SD/year, 95% CI -0.005, 0.003), but a 0.005 SD/year (95% CI 0.002, 0.007) slower rate of cognitive decline after 6 years, mainly driven by white and male participants. MICE-imputed results did not change.

Conclusions:
Although higher levels of social isolation and lower levels of social support in midlife were associated with worse cognitive function at baseline, these exposures had only a minimal impact on 20-year cognitive change. Some relationships differed by race and sex. Further studies are needed to better elucidate whether interventions addressing social isolation and support would be effective in the prevention of cognitive decline and dementia.
Abstract MP24: Sedentary Behavior (SB) In Mid-life And Structural Brain Magnetic Resonance Imaging (MRI) Markers Of Cerebrovascular Disease And Neurodegeneration In Late-life: The Atherosclerosis Risk In Communities Neurocognitive Study (ARIC-NCS)
Authors: Pettee Gabriel Kelley , Diaz Keith , Kumar Aarti , Sharrett A Richey , Evenson Kelly R , Gottesman Rebecca F , Mosley Thomas , Heiss Gerardo M , Palta Priya
Published: May 2021

Introduction:
Few prospective studies have examined the associations of SB on brain MRI markers. We tested the hypotheses that higher levels of, and persistence of mid-life television viewing, a cognitively passive SB, are associated with structural brain MRI markers in late-life, and that these associations are independent from physical activity (PA).

Methods:
ARIC participants (n=1,601, mean age: 76.2 years, 60.5% female, 27.2% Black) with reported television viewing at visits 1 (1987-89) and 3 (1993-95), and brain MRI in 2011-13 were included. Participants were categorized as low [never/seldom], medium [sometimes], or high [often/very often] television viewing. Persistent pattern of television viewing was quantified as the same frequency of reported television viewing at visits 1 and 3 (n=971). Imaging using 3T brain MRI quantified the presence of cerebrovascular lesions, white matter microstructural integrity and disease, and grey matter volumes using a standardized protocol. Models were adjusted for age, race-center, sex, education, APOE-ε4, smoking status, and total intracranial volume in volumetric analysis. Sampling weights were included to generalize MRI sample to the visit 5 cohort. Interactions by meeting (or not) 2018 PA guidelines were tested.

Results:
Compared to low television viewing, medium and high television viewing in midlife was significantly associated with smaller deep grey matter volumes in late-life after multivariable adjustment; associations were stronger for persistent television viewing (
Table
). All other associations of midlife, or persistent midlife, television viewing with structural brain MRI markers were statistically null. Interactions with meeting PA guidelines were also non-significant.

Conclusions:
Findings suggest an inverse association of mid-life television viewing with later-life deep grey matter volumes. Studies examining the associations of daily accumulated SB, and differences by SB type (active versus passive), with brain MRI markers are needed.
Abstract MP27: Changes In Cardiac Structure And Function Over 25 Years Are Associated With Lower Midlife Cognition: The Cardia Study
Authors: Rouch Laure , Hoang Tina , Xia Feng , Sidney Stephen , Lima Joao , Yaffe Kristine
Published: May 2021

Background:
Cardiovascular risk factors are associated with worse cognition, yet much less is known about the association of cardiac structure and function and decline over time with cognitive function, even as early as midlife.

Method:
We included 2256 subjects from the CARDIA (Coronary Artery Risk Development in Young Adults) study (60% women, 44% black). Echocardiograms were repeated at Years 5, 25, 30 (mean age 30, 50, 55 years, respectively) to assess left ventricular (LV) mass (LVM); LV systolic function with LV ejection fraction (LVEF); LV diastolic function with left atrial volume (LAV) and early peak mitral velocity (E)/early peak mitral annular velocity (e’) ratio. Five cognitive domains were assessed at Year 30: verbal memory, verbal fluency, processing speed, executive function, and global cognition. We investigated the association of (1) 25-year change and (2) Year 25 cardiac structure and function on midlife cognition using linear regressions.

Results:
Over 25 years, LVM and LAV increased with mean change (SD) of 5.7 g/m
2
(21.7) and 9.6 mL/m
2
(7.4) while LVEF decreased by mean (SD) change of 1.5% (9.0). Greater 25-year increase in LVM was associated with lower global cognition, processing speed, executive function, verbal memory, and verbal fluency. Similarly, greater 25-year increase in LAV was associated with lower cognition on most cognitive domains. Adjustment for (1) demographics, education and (2) hypertension, diabetes, smoking did not notably change the results. 25-year decrease in LVEF was not associated with cognition. In addition, higher Year 25 LVM, LAV and E/e’ ratio were significantly associated with worse cognition on most cognitive domains.

Conclusion:
Midlife altered cardiac structure and adverse changes from early to middle adulthood are associated with lower midlife cognition. Moreover, LV diastolic but not systolic dysfunction is linked to lower cognition. Our results provide novel information linking early to midlife cardiac structure and function to cognition.
Abstract MP31: Early Age At Menopause And The Association With Incident Heart Failure In The Southern Community Cohort Study
Authors: Pike Mindy , Akwo Elvis A , Robinson-Cohen Cassianne , Blot William J , Ikizler Talat A , Lipworth Loren
Published: May 2021

Introduction:
Reproductive factors might have an effect on the development of heart failure (HF). Early age at menopause has been linked with increased risk of cardiovascular disease; however, there is limited evidence on the relationship between early menopause and HF.

Hypothesis:
We assessed the hypothesis that earlier age at menopause is associated with increased risk of incident HF among women in the southeastern United States.

Methods:
The Southern Community Cohort Study enrolled ~86,000 low-income black and white adults in 12 southeastern states (2002-2009). Participants for this analysis were 11,948 women who were postmenopausal at enrollment, had no history of HF, and were using Centers for Medicare or Medicaid Services (CMS). HF events were ascertained using
International Classification of Diseases
, Ninth Revision, codes 428.x via linkage of the cohort with CMS Research Identifiable Files through December 31, 2016. Early menopause was defined as self-reported age at menopause less than 45 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed from multivariable Cox regression models, overall and by race, adjusting for demographic, lifestyle, and reproductive factors, including reason for menopause.

Results:
At baseline, median age was 58 years and 65% of participants were black. Among women with early menopause, 76% (n=4,836) had menopause due to hysterectomy or oophorectomy. In women with later menopause, 74% (n=4,102) reported natural menopause. During a median follow-up of 9.5 years (interquartile range 6.0-11.8), 3,808 incident HF events occurred. Compared to women with later onset of menopause, those with early menopause had increased HF risk (HR: 1.13, 95% CI: 1.04-1.23). Risk of HF associated with early menopause differed between white and black women (p-value for interaction: 0.02). In stratified analyses, white women with early menopause had an increased risk of HF compared to those with later onset of menopause (HR: 1.26, 95% CI: 1.11-1.43), although there was no association between early age at menopause and risk of HF in black women (HR: 1.07, 95% CI: 0.98-1.18).

Conclusions:
In conclusion, in this largely low-income population, early menopause is associated with an increased risk of developing HF and associations differ by race. Women with early menopause represent a potential target population for future interventions aimed to decrease risk of HF and cardiovascular risk factors.
Abstract MP32: The Level Of Adherence To The Dietary Approaches To Stop Hypertension Diet Is Associated With The Severity Of Insulin Resistance Among Community-Dwelling Heart Failure Patients: A National Health And Nutrition Examination Survey Analysis
Authors: Ishikawa Yuta , Laing Emma M , Anderson Alex K , Zhang Donglan , Trivedi-Kapoor Rupal , Sattler Elisabeth L
Published: May 2021

Introduction:
Heart failure (HF) patients are at risk of new-onset diabetes. In non-HF populations, adherence to the Dietary Approaches to Stop Hypertension (DASH) diet has shown to be associated with the delayed onset of insulin resistance; however, such effect remains unknown in HF patients without history of diabetes.

Methods:
Using data from 1999-2016 National Health and Nutrition Examination Survey cycles, we included 348 HF participants (20+ years) without history of diabetes or diabetes medication use and with data on at least one 24-hour dietary recall. Participants were classified by DASH dietary index score quartiles: quartile 1 indicated lowest DASH index scores and lowest DASH adherence, whereas quartile 4 indicated highest DASH index scores and highest DASH adherence. The severity of insulin resistance was examined using the Homeostatic Model Assessment of Insulin Resistance and was further classified by tertiles, where the upper tertile showed the most severe insulin resistance. Associations between the severity of insulin resistance and DASH dietary adherence and its linear trends were examined using logistic regression models.

Results:
Participants had a mean age of 65±1 (SE) years, 44.2% were female, and 10.5% were non-Hispanic black. The age-, gender-, and race/ethnicity-adjusted odds ratio for the most severe insulin resistance group in participants with highest DASH adherence was 0.32 (95% CI, 0.11-0.99), compared to participants with lowest DASH adherence. A significant trend of more severe insulin resistance was observed as participants showed less adherence to the DASH diet (p=0.02).

Conclusion:
Adherence to a DASH dietary pattern was associated with improved insulin resistance among community-dwelling HF patients in the U.S. Heart healthy dietary patterns may protect HF patients against new-onset diabetes. Future research is needed to test dietary interventions aimed at the prevention of HF complications and comorbidities.
Abstract MP35: Association Of Orthostatic Blood Pressure Response With Incident Heart Failure: The Framingham Heart Study
Authors: Shrout Tara A , Ramachandran Vasan S , Xanthakis Vanessa
Published: May 2021

Introduction:
Orthostatic hypotension (OH) and hypertension (OHT) are associated with cardiovascular disease and mortality. The relation of OH and OHT with heart failure (HF) in the community is not well explored, particularly among the elderly and those with hypertension. Moreover, there remains a paucity of longitudinal data on the development of HF subtypes (HF with reduced ejection fraction [HFrEF] and HF with preserved ejection fraction [HFpEF]) in those with OH and OHT.

Hypothesis:
We hypothesized that OH and OHT are associated with a higher risk of HF.

Methods:
We evaluated 1914 Framingham Heart Study participants (mean age 72 years, 1159 women [61%]), with available orthostatic blood pressure (BP) measurements. OH was defined as a decrease and OHT as an increase of 20/10 mmHg in systolic/diastolic BP from supine to standing position, respectively. We used a categorical variable (OH, OHT, absence of OH and OHT [referent]). Using Cox proportional hazards regression, we related OH and OHT to risk of HF and its subtypes (HFrEF, HFpEF), compared to the referent group, adjusting for age, sex, body mass index, systolic BP, diastolic BP, hypertension treatment, smoking, and diabetes.

Results:
There were 275 participants with OH (181 women, 66%) and 411 with OHT (236 women, 57%). On median follow-up of 13 years, 492 developed HF (292 women, 59%). In multivariable-adjusted analyses, OH was associated with higher risk of HF (Hazards Ratio [HR] 1.47; 95% CI, 1.13-1.92;
Figure
) compared to referent. Further, OH was associated with higher risk of HFrEF (HR 2.56; 95% CI, 1.46-4.48), but not HFpEF. OHT was not associated with incident HF.

Conclusions:
Assessment of orthostatic BP response in the elderly may identify future HF risk. Further studies are warranted to investigate mechanisms underlying the observed associations.
Abstract MP47: Maternal Trimethylamine-n-oxide Is Associated With Risk Of Gestational Diabetes Mellitus In A Low-income, Urban, Multi-ethnic Population
Authors: McArthur Kristen L , Zhang Mingyu , Hong Xiumei , Wang Guoying , Wang Xiaobin , Mueller Noel T
Published: May 2021

Introduction:
Trimethylamine-N-oxide (TMAO) is a metabolite influenced by gut microbiota composition and diet (e.g. eggs and red meat). While TMAO has been associated with type 2 diabetes in adults, it is still unclear whether TMAO is associated with risk of gestational diabetes (GDM). Results from the two case-control studies conducted on this topic in China were mixed, with one showing a U-shaped association and the other showing a linear association between TMAO and GDM. There is need to examine this association in a distinct population, in which the sources of TMAO may vary.

Hypothesis:
We hypothesized that higher TMAO concentration in both maternal and umbilical cord blood plasma (collected within 24-72 hours of birth) is associated with higher odds of GDM.

Methods:
We used data from the women in the Boston Birth Cohort (enrolled from 1998 to 2013) and fitted logistic regression models to examine the association of maternal and cord blood TMAO concentration with odds of GDM. TMAO was inversely normalized and was modeled in tertiles and as a continuous variable. GDM was diagnosed by a physician; women with pre-pregnancy diabetes were excluded from analyses. Final models were adjusted for covariates (see Table footnote).

Results:
Among our analytic sample (n=1405 participants), 1248 contributed maternal blood and 865 contributed cord blood. A total of 123 women developed GDM. Before and after adjustment for covariates, higher concentration of TMAO in maternal blood was associated with higher odds of GDM. After adjustment for potential confounders, the highest vs. lowest tertile of TMAO was associated with 1.75 times (95% CI 1.04, 2.96) the odds of GDM (Table). We found no association between cord blood TMAO and GDM (Table).

Conclusion:
In a population of predominantly low-income, urban mothers, higher maternal TMAO concentration measured in maternal blood (but not cord), was associated with higher odds of GDM. Our findings need to be replicated in prospective cohort studies that measure TMAO in early pregnancy.
Abstract MP48: Racial And Urban-rural Disparities In The Frequency Of Ischemic Stroke As First Manifestation Of Atrial Fibrillation
Authors: Guo Jingchuan , Gabriel Nico , Magnani Jared W , Essien Utibe , Gellad Walid , Brooks Maria M , Trinquart Ludovic , Benjamin Emelia J , Hernandez Inmaculada
Published: May 2021

Introduction:
Atrial fibrillation (AF) may be asymptomatic and remain undiagnosed until the development of complications, which precludes primary prevention efforts. We aimed to quantify racial and rural-urban disparities in the frequency of incident AF presenting with ischemic stroke in a nationally representative sample of Medicare beneficiaries.

Hypothesis:
Black patients have higher frequency of stroke as the first presentation with AF than White patients.

Methods:
We used a 5% random sample of Medicare claims data to identify patients newly diagnosed with AF in 2016. The primary outcome was stroke as first AF manifestation, and was defined by inpatient diagnosis of ischemic stroke within 7 days prior to the first AF diagnosis. We computed age- and sex-adjusted proportion of AF diagnosis manifesting as stroke and used multivariable logistic regression to quantify the association of race and urban/rural residence with the outcome, adjusting for demographic and clinical characteristics.

Results:
Among 39,437 patients newly diagnosed with AF, 2,821 (7.2%) had ischemic stroke as the first AF manifestation. In urban areas, age- and sex-adjusted proportions of AF diagnosis manifesting as stroke were 7.2(95%CI: 6.8,7.4)% for White and 9.5(8.4,10.8)% for Black, compared to 5.9(5.4,6.4)% and 8.1(5.8,11.1)% in rural areas (
Figure
). After adjusting for age, sex, CHA
2
DS
2
-VASc score, Alzheimer's disease, Medicaid enrollment, and receipt of low-income subsidy, Black race (adjusted OR [95%CI]: 1.21 [1.05, 1.40], vs. White) and urban residence (1.16 [1.06, 1.28], vs. rural) were associated with increased risk of stroke as first AF manifestation.

Conclusion:
We observed uneven distributions in the frequency of stroke as first manifestation of AF between White and Black patients and between rural and urban residents. Further research is needed to evaluate the effectiveness of AF screening efforts in reducing inequities in health outcomes associated with AF.
Abstract MP54: Retail Soda Purchases Decrease And Water Purchases Increase After Six Years Of A Healthy Beverage Campaign
Authors: Schwartz Marlene B , Schneider Glenn E , Xu Ran , Choi Yoon-Young , Atoloye Abiodun , Highsmith Vernick Nicolette , Appel Lawrence J
Published: May 2021

Introduction:
Sugary drink consumption is a major risk factor for excess weight gain. In 2013, Howard County, MD launched a multi-component campaign to decrease sugary drink consumption. A previously published difference-in-differences (DID) analysis of supermarket retail beverage sales from 2012 (baseline) to 2015 documented a significant decrease in regular soda and fruit drinks sales in intervention stores compared to matched control stores. The present study extends this evaluation through 2018.

Hypothesis:
Sugary drink sales will continue to decrease and sales of non-sugary drinks will increase through 2018.

Methods:
Prior to the intervention, a retail sales tracking company identified a sample of supermarkets (N=15) in Howard County (Intervention stores) and assessed 52-weeks of top brand sales for each beverage category. These data were used to identify a set of matched Control stores (N=17) in an adjacent state. DID analyses were used to compare the weekly volume sales of each product (brand and package size) within each beverage category in the Intervention and Control stores from baseline (2012) to Year 6 (2018). Models were adjusted for relevant variables, including average price/ounce; average competitor price/ounce; and weekly local temperature.

Results:
DID analyses identified a significantly larger net decrease in average weekly volume sales of regular soda, fruit drinks, and 100% juice in the Intervention stores compared to the Control stores over six years (p < .001). See Figure for regular soda sales. After 2015, intervention stores also exhibited significant increases in sales of plain bottled water (p < .0001) and carbonated water (p < .001). In contrast, sports drinks, diet soda, and flavored waters did not consistently differ between conditions.

Conclusion:
A locally implemented, multi-component campaign reduced regular soda and fruit drink sales over six years. Additional efforts to reduce sales of sports drinks are warranted.
Abstract MP55: Red And Processed Meat And Alternative Protein Sources In Relation To Risk Of Fatal Coronary Heart Disease: A Pooled Analysis Of 16 Prospective Cohort Studies
Authors: Al-Shaar Laila , Wang Molin , Willett Walter , Smith-Warner Stephanie
Published: May 2021

Background:
Red and processed meat intake have been associated with higher risk of fatal coronary heart disease (CHD). However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk.

Objective:
We estimated the associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD.

Methods:
This pooled analysis was conducted within the Pooling Project of Prospective Studies of Diet and Cancer and included participants with no prior self-reported history of cardiovascular diseases or cancer. Diet was assessed by cohort-specific food frequency questionnaires collected at baseline. Total red meat included processed meat and unprocessed red meat. Animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; plant protein sources included nuts and beans. After adjusting for dietary and non-dietary factors, study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models and then pooled using a random effects model. Isocaloric dietary substitution was evaluated by differences in coefficients in models including red meat and all alternative protein sources described above as continuous variables.

Results:
In preliminary analyses of 16 prospective cohorts including 1,364,211 participants (40% men and mean age of 57 ± 10 years) followed for a maximum of 32 years across studies, we identified 51,176 fatal CHD cases. A 100g/day increment in total red meat intake was associated with a 7% higher risk of fatal CHD, RR=1.07 (95% CI 1.04, 1.10). Substitutions of 200 kcal/day from nuts, low- and high-fat dairy products, and poultry for 200 kcal/d from total red meat were associated with 6-14% lower risks of fatal CHD. These associations were stronger when substituting the alternative protein sources for processed meat, especially among women (n=14,888 cases, 17-24% lower risk). Substituting 200 kcal/day from eggs for 200 kcal/day from total red meat and unprocessed red meat was associated with 8 and 14% higher risk of fatal CHD, respectively; this substitution for processed meat was weaker and not significant (4%). Results were similar after excluding the first 4 years of follow-up.

Conclusions:
Preliminary results from this international pooled analysis of 16 cohort studies provide more evidence about the risks of red and processed meat consumption. Replacement of red and processed meat with nuts, dairy products, or poultry may reduce the risk of fatal CHD.
Abstract MP61: Greater Late-life Physical Function Declines Among Older Adults With Higher Blood Pressure In Mid-life: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Skow Laura , Coresh J , Deal J , Gottesman Rebecca F , Schrack Jennifer , Sharrett A Richey , Palta Priya , Ghelani Kunali Parimal , Griswold Michael , Sullivan Kevin , Windham B Gwen
Published: May 2021

Introduction:
Greater late-life physical function decline is associated with incident adverse outcomes including disability and death. Hypertension is the strongest risk factor for stroke, the major cause of physical disability. Hypertension in mid-life has previously been associated with poor physical functioning in late-life; however, more evidence is needed to evaluate whether higher blood pressure in mid-life is associated with the rate of physical function decline during late-late in the absence of stroke. We hypothesized that elevated blood pressure in mid-life would be associated with greater physical function declines in late life.

Methods:
We studied 5,559 older adults in the ARIC Study (Visit 5; mean age: 75.8 years; range: 66.7-90.9 years; 58% women; 21% Black/79% White) without prior stroke or Parkinson disease who completed the Short Physical Performance Battery (SPPB, scored 0-12). Repeated SPPB assessments occurred at Visits 6 and 7 (median follow-up: 4.2 years). The exposure was a history of elevated blood pressure (BP) (Visit 1; mean age: 52.0 years; mean gap between mid- and late-life exams: 23.7 years). BP was modeled both categorically (hypertensive: SBP 140+ mmHg, DBP 90+ mmHg, or antihypertensive medication use; pre-hypertensive: SBP 120-139 mmHg or DBP 80-89 mmHg; else normotensive) and continuously. Random-slope, random-intercept mixed models with an independent covariance structure tested the association between BP and SPPB score change, adjusted for age, sex, race-site, BMI, education, heart disease and heart failure. Continuous analysis also adjusted for antihypertensive medication use.

Results:
SPPB scores declined an average of 1.60 points per 10 years (95% CI: -1.75, -1.46; p<0.001) among older adults who were normotensive in mid-life. Older adults with a previous measurement of hypertension declined an additional 0.94 points per 10 years (95% CI: -1.27, -0.60; p<0.001). Prehypertension was not statistically significantly associated with additional decline compared to mid-life normotension (estimate: -0.19 SPPB points/10 years; 95% CI: -0.53, 0.16; p=0.293). In the continuous analysis, each additional 10 mmHg higher mid-life systolic blood pressure above 120 mmHg was associated with an additional 0.24 point decline in SPPB per 10 years in late-life (95% CI: -0.31,-0.14; p<0.001).

Conclusions:
Elevated BP in mid-life provides insight into the rate of physical function decline decades later, with higher mid-life systolic blood pressure corresponding with steeper declines in late-life physical function even in the absence of stroke. Future research should investigate whether elevated blood pressure at multiple points in mid-life further informs the association.
Abstract MP65: Transgender Adolescents Have High Prevalence Of Atherosclerotic Cardiovascular Disease Risk Factors Before And After Taking Hormone Therapy For 1 Year
Authors: Staab Ambur M , Cizik Amy M , Mihalopoulos Nicole L
Published: May 2021

Introduction:
The United States has a growing population of transgender adolescents aged 12-21y presenting for medical transition via gender affirming hormone therapy (HT). Transgender people do not identify with their sex assigned at birth while cisgender people do. HT involves estrogen for trans females, those who identify as female, and testosterone for trans males, those who identify as male. Initiation of HT is beginning in adolescence and is a lifelong commitment for many transgender individuals. Little is known about how HT affects ASCVD risk factors in transgender adolescents. Studies of cisgender adults show cardioprotective effects of estrogen, and an estimated 37% of normal-weight cis gender adolescents have at least 1 ASCVD risk factor; but little investigation exists for transgender people, especially adolescents. Although some studies involving the transgender population have reproducible results, few include adolescents and comparison to acceptable ASCVD risk factor profiles. Guidelines for transgender health recommend laboratory assessment before starting HT and annually. This study expands on current knowledge and informs clinical practice by comparing ASCVD risk biomarkers of transgender adolescents taking HT to acceptable clinical values for adolescents.

Hypothesis:
Estrogen therapy for trans females will ameliorate ASCVD risk factors while testosterone therapy for trans males will worsen ASCVD risk factors.

Methods:
Retrospective chart review identified 300 transgender patients receiving HT at an academic adolescent medicine gender clinic. Of those 300, 50 trans female and 50 trans male were randomly selected for evaluation of ASCVD risk parameters at baseline and 1 year after initiating HT. ASCVD risk factors were compared to the International Diabetes Federation guidelines for metabolic syndrome. Parameters included lipids, glucose, and blood pressure. BMI ≥30 was used as proxy for obesity.

Results:
At baseline, at least one abnormal value was found for 50% (n=25, of these 5 had obesity) of trans females and 66% (n=33, of these 13 had obesity) of trans males. At 1 year, at least one abnormal value was found for 30% (n=15) of trans females and 70% (n=35) of trans males. At baseline, 50% (n=25) of trans females and 82% (n=41) of trans males, and at 1 year 20% (n=10) of trans females and 48% (24) of trans males had all parameters measured. Paired t-tests (α=.05) showed no significant change in ASCVD risk factors for trans females, and significant decrease in HDL and significant increase in BMI for trans males after 1 year of HT.

Conclusions:
The prevalence of having at least 1 ASCVD risk factor is greater among transgender adolescents than normal weight cisgender adolescents. HT may worsen HDL and BMI for trans males. We recommend baseline parameters for all and follow up and lab surveillance for patients with abnormal baseline parameters.
Abstract MP70: Short-term Fine Particulate Air Pollution Is Associated With Shorter Sleep Duration And Higher Sleep Variability In Adolescents
Authors: He Fan , Fernandez-Mendoza Julio , Yanosky Jeff D , Chinchilli Vernon M , Al-shaar Laila , Liao Duanping
Published: May 2021

Introduction:
Sleep deprivation and large sleep variability are potential risk factors for obesity and cardiovascular diseases. While it is plausible that particulate air pollution may contribute to these unfavorable sleep patterns, very few studies have been conducted to assess the association between fine particulate (PM
2.5
) air pollution and objectively measured sleep duration and its variability in an adolescent U.S. population.

Hypothesis:
We tested the hypothesis that higher individual-level short-term PM
2.5
exposure is associated with shorter sleep duration and higher sleep variability among adolescents.

Methods:
We analyzed the available data collected from 421 adolescents who participated in the follow-up examination of the population-based Penn State Child Cohort (PSCC) study. To estimate individual-level short-term PM
2.5
exposure, a personal nephelometer (Thermo pDR-1200) was used to measure real-time PM
2.5
concentration for 24 hours from the study participants. The 24-hour mean PM
2.5
concentration was used to quantify the short-term PM
2.5
exposure. To obtain objectively-measured habitual sleep duration (HSD) and habitual sleep variability (HSV), an actigraphy (GT3X+) was used to collect sleep data for 7 consecutive nights, including 1 night in parallel with the PM
2.5
monitoring and 6 nights thereafter. HSD and HSV were calculated as the intra-individual mean and standard deviation (SD) of the 7-night sleep duration, respectively. Participants with < 5 nights (70% of 7 nights) of data were excluded from the analyses. The associations between the individual-level PM
2.5
exposure and HSD/HSV were evaluated by using multi-variable adjusted linear regression models, controlling for age, race, sex, BMI percentile, environmental temperature, and relative humidity.

Results:
The mean (SD) age of the study population was 16.9 (2.2) years. The study sample consisted of 54% males and 78% whites. The 24-hour mean (SD) of PM
2.5
concentration was 16.9 (26.8) μg/m
3
, while the average HSD and HSV were 7.0 (0.9) hours and 1.2 (0.6) hours, respectively. We observed that a 10 μg/m
3
increase in the 24-hour mean PM
2.5
was associated with significantly lower HSD [β (SE): -0.06 (0.03) hours, p=0.02] and larger HSV [β (SE): 0.04 (0.02) hours, p=0.04]. The effect sizes were approximately 7% of their respective SDs.

Conclusion:
Individual-level short-term PM
2.5
exposure is associated with objective-measured shorter sleep duration and higher night-to-night sleep variability among U.S. adolescents. These observed associations suggest that particulate air pollution exposure in early life may impact habitual sleep pattern, which may in turn be associated with the risks of obesity and cardiovascular diseases in later life.
Abstract P001: Retirement Age And 20-year Cognitive Decline: The Atherosclerosis Risk In Communities Neurocognitive Study
Authors: Liu Albert , Patel Mehul D , Gross Alden L , Mosley Thomas , Rawlings Andreea , Schneider Andrea L , Kucharska-newton Anna , Sharrett A Richey , Gottesman Rebecca F , Koton Silvia
Published: May 2021

Background:
The effect of retirement on cognitive functioning is not clear. We examined the association between age at retirement, midlife occupation, and cognitive decline in the large Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort.

Methods:
Retirement status after ARIC visit 4 (1996-98) was reported in annual follow-up questionnaires administered in 1999-2007 (n= 8,426), and classified as occurring before or after age 70. Current or most recent occupation at visit 1 (1987-89) was categorized based on 1980 US census major occupation groups and tertiles of Nam-Powers-Boyd occupational status score (a measure of socioeconomic status of occupations, hereby used as a proxy for occupational complexity). Generalized estimating equation models were used to examine the associations of retirement with trajectories of a global cognitive factor score, assessed in 1990-92 (visit 2), 1996-98 (visit 4) and 2011-2013 (visit 5). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities. To account for attrition, we also performed multiple imputation by chained equations.

Results:
Retirement before age 70 is associated with higher educational level and higher occupational status score in white men and women, and in black men. We observed associations between retirement before age 70 and lower baseline cognitive scores, as well as slower cognitive decline in white men and women, and in black men (Figure). The results did not change substantially after adjusting for the occupational status score or accounting for attrition.

Conclusion:
Retirement before age 70 was significantly associated with lower baseline cognitive scores and slower cognitive decline in whites and in black men. The lack of similar associations in black women and the investigation of reasons for the observed associations warrant further research.