bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P365: Psychosocial Factors and Subsequent Risk of Peripheral Artery Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Honda Yasuyuki , Mok Yejin , Mathews Lena , Van’t Hof Jeremy , Daumit Gail , Kucharska-newton Anna , Selvin Elizabeth , Mosley Thomas , Coresh Josef , Matsushita Kunihiro
Published: March 2020

Background and aims:
Psychosocial factors such as depression, character traits, and lack of social support have been associated with increased risk of cardiovascular disease (CVD). However, data of peripheral artery disease (PAD) in this regard are sparse. Since risk factor profiles differ across atherosclerotic CVD (ASCVD) subtypes, to appreciate the contribution of psychosocial factors to overall ASCVD, we aimed to comprehensively explore the association of psychosocial factors with the risk of PAD and ASCVD in a community cohort.

Methods:
We included 12,090 participants from the Atherosclerosis Risk in Communities (ARIC) Study (mean age 56.7 [SD 5.7] years) free of PAD and ASCVD at baseline (1990-1992). Depressive symptom was evaluated by the Maastricht Questionnaire (MQ). Trait anger was assessed by the Spielberger Trait Anger Scale. Social support was measured by the Interpersonal Support Evaluation List, while the extent of social networks was evaluated by the Lubben Social Network Scale. PAD events were defined as hospitalizations with PAD diagnosis and procedures. ASCVD included adjudicated myocardial infarction, fatal coronary disease, and ischemic stroke events.

Results:
We observed 429 PAD and 2,539 ASCVD events during a median follow-up of 23.1 years. The cumulative incidence of PAD was highest in the highest quartile of MQ score. This association remained after adjusting for traditional CVD risk factors, socioeconomic status, and physical activity. A weaker association was observed for ASCVD. Social support also showed independent association with incident PAD, but not with ASCVD. Trait anger and social network were not significantly associated with either PAD or ASCVD (Table).

Conclusions:
Psychosocial factors demonstrated more evident associations with PAD than ASCVD. Our results suggest the importance of considering PAD when assessing the overall impact of those factors on CVD. Future studies are needed to explore potential mechanisms behind our observation.
Abstract P378: Higher Non-exercise Estimated Cardiorespiratory Fitness in Midlife is Associated With Lower Risk of Cardiovascular Disease and Mortality in Later Life: The Framingham Heart Study
Authors: Lee Joowon , Vasan Ramachandran S , Xanthakis Vanessa
Published: March 2020

Introduction:
Studies have demonstrated that higher cardiorespiratory fitness (CRF) is associated with a lower risk of cardiovascular disease (CVD) and mortality. However, exercise CRF test is not routinely performed in clinical settings because it requires specialized equipment and trained personnel. Therefore, non-exercise estimated CRF (eCRF) using easily accessible health indicators in clinical practice may be a time- and cost-effective alternative for evaluating fitness.

Hypothesis:
We hypothesized that higher eCRF in midlife will be associated with a lower risk of CVD and all-cause mortality in later life.

Methods:
We evaluated 2,501 Framingham Offspring cohort participants (mean age 65 yrs., 52% women). We used a longitudinal non-exercise algorithm that includes age, sex, body mass index, waist circumference, resting heart rate, physical activity, and smoking status. We then used SAS PROC TRAJ to identify sex-specific latent patterns of eCRF (low, moderate, and high eCRF categories) between exam 2 and 8 (1979-2008). Multivariable Cox proportional hazards regression models were used to relate the long-term trajectories of eCRF to incident CVD and all-cause mortality on follow-up.

Results:
We identified three distinct trajectories of eCRF (Low [n=268, 10.7%] vs. moderate [n=1,273, 50.9%] vs. high [n=960, 38.4%]). Overall, 265 participants developed CVD and 429 died during 10 years of median follow-up. Participants in the “high eCRF” group were at lower risk of CVD and all-cause mortality compared to those in the “low eCRF” group, after adjustment for potential confounders (
Table
).

Conclusions:
Our findings suggest that lower eCRF during midlife may be a marker of risk of CVD and mortality in older adulthood.
Abstract P386: Pregnancy-related Risk Factors May Signal Additional Risk For Future Cardiovascular Disease
Authors: Reddy Shivani M , Moraes Tsujimoto Tamy H , Nicholson Wanda , Fine Jason
Published: March 2020

Introduction:
Emerging data suggest that pregnancy may be a window on the future of women’s cardiovascular health. Cardiovascular disease (CVD) guidelines recommend using the Pooled Cohort Equation (PCE) to assess 10-year CVD risk based on traditional risk factors. Less is known about the role of pregnancy-related factors, such as a history of small for gestational age (SGA) infants or breastfeeding, and the risk of CVD events in addition to the PCE.

Hypothesis:
We hypothesize that pregnancy-related complications and breastfeeding can affect the risk of future CVD risk in addition to traditional risk factors currently accounted for by the PCE.

Methods:
Using NHANES 1999-2006, a weighted sample of 3,913 women (representing 27,102,057 women in the US population), ages 40-79, with a history of pregnancy, but no prior CVD, was identified. Variables for SGA infants and breastfeeding were abstracted along with traditional risk factors. Less than 5% of women were missing data on these variables. CVD outcomes were defined as a composite of (1) CVD death and (2) surrogates for CVD death, in which diabetes or hypertension were a secondary cause of death. CVD outcomes and survival time were obtained from the NHANES Linked Mortality File. The PCE was used to estimate 10-year CVD risk. Bivariate and survival analyses using Cox proportional hazards models adjusting for PCE risk score were performed. For survival analysis, the cause-specific hazard function was estimated considering the time of death as censoring for women dying from causes other than CVD outcomes, as well as the time of follow-up for women that did not present the death event.

Results:
Among the sample, 504 (11.8%) women had a SGA infant and 2133 (54.5%) reported a history of breastfeeding. 198 (5.1%) women had the composite CVD death outcome. CVD outcomes were lower in women with a history of breastfeeding (97 of 2133) compared to those who did not breastfeed (96 of 1629). (2.6% vs. 4.2%, p=0.002) The opposite relationship was observed for women with a history of SGA infant (4.2% (29 of 504) vs. 3.2% (161 of 3232), p=0.2). PCE scores were associated with breastfeeding and SGA, potentially confounding those effects. Survival analyses, adjusting for continuous PCE risk scores, showed an inverse association of breastfeeding and CVD outcomes (HR 0.7, 95% CI 0.5 to 1.0) and a positive association of history of SGA infant and CVD outcomes. (HR 1.4, 95% CI 0.8 to 2.2)

Conclusion:
Specific pregnancy-related complications and breastfeeding may provide additional, relevant information about the risk of CVD risk events beyond traditional risk factors. While further research is needed to incorporate pregnancy outcomes into risk prediction models, it may be helpful for clinicians to counsel women about the potential impact of pregnancy-related factors and breastfeeding on future cardiovascular health.
Abstract P411: Longitudinal Association Between Frailty and Arterial Stiffness in Community-dwelling Older Adults: The Atherosclerosis Risk in Communities Study
Authors: Thomas Alvin G , Kucharska-Newton Anna , Wei Jingkai , Palta Priya , Burgard Sheila , Meyer Michelle , Stoner Lee , Tanaka Hirofumi , Nadruz Wilson , Windham B Gwen , Wagenknecht Lynne E , Heiss Gerardo M
Published: March 2020

Introduction:
Frailty is predictive of cardiovascular disease and is suggested to co-occur with arterial stiffening, the hallmark of vascular aging. However, the temporal relationship is uncertain. Using the ARIC study, we examine the association of baseline frailty with cross-sectional and 5-year change in carotid-femoral pulse wave velocity (cfPWV) in older adults.

Methods:
Participants at visit 5 (2011-2013) were classified as frail (≥3 criteria), prefrail (1-2 criteria), or robust using the Fried frailty phenotype criteria (unintentional weight loss, exhaustion, grip strength, slow walking speed, and low physical activity). We measured cfPWV at visits 5 and 6/7 (2016-2019). We used linear regression with inverse-probability of attrition weights to estimate the association between frailty and 5-year change in cfPWV while accounting for loss-to-follow-up among survivors. Models were adjusted for age, sex, race-center, mean arterial pressure, height, heart rate, smoking, and time between visits.

Results:
Of 5,096 participants at visit 5 (58% female, 21% black, mean age 75 [SD 5.1] years), 296 (6%) were frail and 2403 (47%) prefrail. In adjusted analyses at visit 5, frail participants had 30 cm/s (95% CI: -9, 69; p=0.1) higher cfPWV and prefrail participants had 12 cm/s (95% CI: -5, 30; p=0.2) higher cfPWV than those classified as robust (Table 1). In longitudinal analyses adjusted for attrition, we observed a 3 cm/s (95% CI: -11, 19; p=0.6) and 6 cm/s (95% CI: 0, 12; p=0.05) greater annualized increase in cfPWV over ~5 years among frail and prefrail participants, respectively, relative to the rate of arterial stiffening among robust participants (26 cm/s per year).

Conclusions:
Compared to robust older adults, greater aortic stiffness was observed among frail community-dwelling adults. Changes in aortic stiffening over the course of 5 years were not materially influenced by frailty status at baseline. Frail older adults may present with greater arterial aging and its associated hemodynamic effects on target organs.
Abstract P417: Relationship Between Blood Pressure Variability and Sleep Architecture
Authors: Liu Xiaoyue , Logan Jeongok G , Kwon Younghoon , Lobo Jennifer , Kang Hyojung , Kim Soyoun , Sohn Min-Woong
Published: March 2020

Introduction:
Blood pressure (BP) variability (BPV) is a novel marker for cardiovascular disease (CVD) independent of high BP. Sleep architecture represents the structured pattern of sleep stages consisting of rapid eye movement (REM) and non-rapid eye movement (NREM), and it is an important element in the homeostatic regulation of sleep. Currently, little is known regarding whether BPV is linked to sleep stages. Our study aimed to examine the relationship between sleep architecture and BPV.

Methods:
We analyzed in-lab polysomnographic studies collected from individuals who underwent diagnostic sleep studies at a university hospital from 2010 to 2017. BP measures obtained during one year prior to the sleep studies were included. BPV was computed using the coefficient of variation for all individuals who had three or more systolic and diastolic BP data. We conducted linear regression analysis to assess the relationship of systolic BPV (SBPV) and diastolic BPV (DBPV) with the sleep stage distribution (REM and NREM sleep time), respectively. Covariates that can potentially confound the relationships were adjusted in the models, including age, sex, race/ethnicity, body mass index, total sleep time, apnea-hypopnea index, mean BP, and history of medication use (antipsychotics, antidepressants, and antihypertensives) during the past two years before the sleep studies.

Results:
Our sample (N=3,565; male = 1,353) was racially and ethnically diverse, with a mean age 54 ± 15 years and a mean BP of 131/76 ± 13.9/8.4 mmHg. Among the sleep architecture measures examined, SBPV showed an inverse relationship with REM sleep time after controlling for all covariates (
p
= .033). We subsequently categorized SBPV into four quartiles and found that the 3
rd
quartile (mean SBP SD = 14.9 ± 2.1 mmHg) had 3.3 fewer minutes in REM sleep compared to the 1
st
quartile (
p
= .02). However, we did not observe any relationship between DBPV and sleep architecture.

Conclusion:
Greater SBPV was associated with lower REM sleep time. This finding suggests a possible interplay between BPV and sleep architecture. Future investigation is warranted to clarify the directionality, mechanism, and therapeutic implications.
Abstract P424: Low Liver Enzymes, Cognitive Performance and Dementia. The Atherosclerosis Risk in Communities Neurocognitive Study (aric-ncs)
Authors: Lu Yifei , Thomas Alvin G , Selvin Elizabeth , Palta Priya , Sharrett A Richey , Mosley Thomas , Knopman David , Pike James , Loehr Laura R , HEISS Gerardo M
Published: March 2020

Introduction:
Low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) among older adults are associated with mortality, and reportedly with lower cognitive performance, biomarkers of neurodegeneration, and dementia. We tested the associations of liver enzymes with cognition in ARIC-NCS.

Methods:
We studied 3191 participants (mean age 79 years, 59% female, 23% black) free of chronic liver disease and cirrhosis, and with AST:ALT ratio ≤2 at visit in 2016-2017. Serum ALT and AST were examined continuously and by quintiles, with the 3
rd
quintile as the distribution-based modal reference range. Cognitive status (normal, mild cognitive impairment [MCI], dementia) was ascertained by an expert adjudication panel. A composite global cognition score was estimated from memory, executive function, and language tests. We used demographic and ApoE4 adjusted multinomial logistic and linear regressions.

Results:
Participants were classified as cognitively unimpaired (2375), MCI (602) or dementia (214). Lower levels of ALT and AST, and a higher AST:ALT ratio were associated with higher prevalence of dementia and lower global cognition scores (
Figure
). The prevalence odds ratio of dementia and MCI for the 1
st
quintile, vs 3
rd
quintile of ALT, were 1.73 (95% CI:1.06-2.81) and 1.27 (0.92-1.76), respectively. The corresponding estimates for AST were 1.71 (1.03-2.84) and 1.17 (0.87-1.59). Global cognition scores were lower in the 1
st
vs 3
rd
quintiles of ALT and AST by 0.13 (0.06-0.21) and 0.08 (0-0.15) standard deviation units, respectively. Additional adjustment for alcohol intake did not change the results.

Conclusions:
Liver hypometabolism is linked to reduced brain glucose metabolism, impaired production of neurotransmitters and synaptic maintenance, systemic insulin resistance and inflammation, while hepatic metabolite profiles are altered in dementia. Prospective assessments are warranted to characterize the role of hepatic metabolic dysfunction in cognitive impairment among older adults.
Abstract P428: A Polyexposomic Risk Score for Hypertensive Disorders of Pregnancy Using External Exposome Data
Authors: Hu Hui , Zhao Jinying , Bian Jiang , Zheng Yi , Pearson Thomas A
Published: March 2020

Hypertensive disorders of pregnancy (HDP) are one of the most common pregnancy complications that lead to increased maternal and infant morbidity and mortality. While effective prevention of HDP can be attained using low-dose aspirin in high-risk pregnant women, identification of these high-risk women has been ineffective. Existing risk assessment models of HDP predominantly rely on biomarkers such as angiogenesis-related factors which are not routinely tested at the population level. The external environment has been shown to play an important role in the development of HDP, yet no predictive model of HDP has been developed considering the totality of the external environment, or the external exposome. To address this, we developed a polyexposomic risk score of HDP using external exposome-wide data among 6,989 women from the 2007-2012 linked Florida Vital Statistics Birth Records and Pregnancy Risk Assessment Monitoring System data. A total of 5,510 external exposome factors characterizing women’s surrounding natural, built, and social environment during pregnancy (i.e. climate, air pollution, noise, greenness, walkability, food access, socioeconomics, social capital, housing, and safety) were collected, harmonized, integrated, and spatiotemporally linked to pregnant women based on their geocoded residential addresses and pregnancy periods. The data were randomly divided into training (80%) and testing (20%) sets. A gradient boosting decision trees model was trained using the CatBoost library with hyper-parameters tuned by a grid search based on 5-fold cross validations. The model has a test-AUC (areas under curve) of 0.735. The most important features for predictions include neighborhood socioeconomic status, housing characteristics, meteorology factors, and air pollutants. External exposome data can provide important predictive information to identify individuals at high risk of HDP. The model is feasible for implementation at the population level to help guide precision preventions. Future efforts are warranted to integrate external exposome data with electronic health record data to further improve the model performance.
Abstract P440: Diabetes and the Long-term Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities Study
Authors: Matsushita Kunihiro
Published: March 2020

Introduction:
Diabetes mellitus is known to be related to lower risk of abdominal aortic aneurysm (AAA). However, the full spectrum of glycemic status including prediabetes and the duration of diabetes have not been extensively investigated in the context of AAA risk.

Methods:
We prospectively studied incident AAA (defined using outpatient records, hospitalization discharge, or death certificate) according to the baseline glycemic status defined using physician diagnosed diabetes, self-reported anti-diabetic medication use and glucose or hemoglobin A1c (diabetes, pre-diabetes, vs. normal glycemia) in 13,116 participants (1990-1992) and the time-varying exposure of duration of incident diabetes in 11,675 participants (1987-1989) using Cox models. We cross-sectionally explored ultrasound-based abdominal aortic diameter by glycemic status and cumulative duration of diabetes in 4,710 participants (2011-2013) using linear regression models.

Results:
There were 489 incident AAA cases during a median follow-up of ~20 years. Diabetes but not pre-diabetes (vs. normal glycemia) at baseline was independently associated with lower risk of AAA (HR: 0.71 [95%CI 0.51 - 0.99]). The association was largely driven by long-standing diabetes (≥10 years duration: HR: 0.58 [95%CI 0.38 - 0.87]). Longer duration of diabetes was associated with lower risk of AAA (Figure 1A), with 30-50% lower risk in 8 years after incident diabetes diagnosis, as well as smaller aortic diameter measured cross-sectionally (Figure 1B) compared to non-diabetes. Pre-diabetes consistently showed relatively greater diameter (e.g., +0.26 mm [-0.03, +0.54]).

Conclusions:
Diabetes (but not prediabetes) and its longer duration were independently associated with lower risk of AAA and smaller aortic diameter. Our findings suggest that the cumulative effects of hyperglycemia may play a role in the counterintuitively lower AAA risk. Reduced aortic diameter might be a structural mechanism of decreased AAA risk in diabetes.

Figure 1A.
Adjusted hazard ratio of incident AAA according to the duration of diabetes among incident cases as a time-varying exposure;
Figure 1B.
Adjusted difference in maximum diameter (mm) for diabetes vs. non-diabetes by cumulative duration of diabetes. Both models adjusted for age, sex, race, education, BMI, height, total cholesterol, HDL cholesterol, systolic blood pressure, diastolic blood pressure, anti-hypertensive medication, cholesterol-lowering medication, cigarette smoking pack-years, alcohol drinking, eGFR, prevalent peripheral artery disease, prevalent coronary heart disease, and prevalent stroke (time-varying covariates for Figure 1A and baseline covariates for Figure 1B).
Abstract P442: Periodontal Disease is Associated With Risk of Incident Diabetes Among Non-obese Individuals
Authors: Adam Hamdi S , Zhang Shaoping , Philips Kamaira , Moss Kevin , Wu Di , Selvin Elizabeth , Norby Faye L , Pankow James S , Demmer Ryan , Mustapha Indra , Beck James D
Published: March 2020

Background:
Strong evidence suggests that diabetes is a risk factor for periodontal disease and that periodontal disease, once established in the diabetic state, then contributes to worsened glycemic control. Recent studies suggest that periodontal disease is also associated with diabetes development.

Hypothesis:
Incident Type 2 Diabetes (T2D) rates will be higher among participants with baseline periodontal disease vs. those with periodontal health. The relationship is modified by Body Mass Index (BMI).

Methods:
We included 5586 diabetes-free eligible participants (aged 52-75 years) from Visit 4 (1996-1999) of The Atherosclerosis Risk in Communities (ARIC) Study. Participants received full-mouth periodontal exams and periodontal disease status was classified using Periodontal Profile Classes (PPC-Stages). T2D was defined based on participant-self report of physician diagnosis during annual telephone follow-ups. Time-to-event was computed from baseline through 2018. Competing risk, multivariable Cox proportional hazard models examined T2D and All-Cause Mortality risk according to baseline periodontal disease status. We tested the interaction with BMI. Multivariable adjustment was performed for race/center, age, gender, smoking and education.

Results:
Participants were mean age (SD) 62.4 (5.6), 55.0% female, 16.7% African American. During the average 21.1 years of follow-up there were 1,359 incident T2D cases and 1,531 deaths. Cumulative incidence rates were 24.3% and 27.4% for T2D and deaths, respectively. Among underweight participants, the hazard ratios[95%Cis] for incident diabetes among severe periodontitis or severe tooth loss (vs. periodontally healthy) were 1.84[1.14-2.96] and 2.29[1.57-3.33], respectively. Hazard ratios[95%Cis] among normal weight participants were 1.54[1.06-2.23] and 1.88[1.41-2.51], respectively. There were no significant associations with T2D in obese participants (p for interaction = 0.06.

Conclusion:
Severe periodontal disease was associated with a modestly increased risk for T2D among a multi-racial community-based sample. Two periodontal disease stages in the PPC-Stages index system are significantly associated with increased risk for incident diabetes. This periodontal disease-associated risk is modified by BMI levels and only associated with incident diabetes in study participants with lower BMI.
Abstract P448: Neighborhood Built Environment is Associated With Odds of Chronic Disease Death Among Participants in the Bogalusa Heart Study
Authors: Anderson Christopher E , Bazzano Lydia A , Broyles Stephanie , Wallace Maeve E , Chukwurah Queendaleen , Gustat Jeanette
Published: March 2020

Relationships of the built environment (BE) with physical activity (PA) and health outcomes have been reported, though data is limited in rural settings. This study was conducted to assess relationships between BE around the residence and death from chronic disease in rural residents. We hypothesized that BE more conducive to PA would be associated with lower odds of chronic disease death. Participants in the Bogalusa Heart Study, a long-running cohort study in rural Louisiana, with a valid address of residence and either deceased of a chronic disease (cases) or observed (controls) since 1998 were included (N=2,052). Cases were identified in the National Death Index (N=111). BE features on the street segment of residence were assessed with the Rural Active Living Assessment tool and Google Street View. Scores for walkability, overall and in domains (including path features, aesthetics, land use), were calculated for street segments and in buffers of 0.25, 0.50, 1.00 and 1.50 miles. Associations of BE scores with chronic disease death were assessed with generalized estimating equations logistic regression models that accommodated clustering in street segments and census tracts, and were adjusted for age, sex, race, census tract population density and percent living in poverty. Cases were of similar age (45 at death vs 44 at last visit), more likely to be male (59 vs 43%) and less likely to be white (52 vs 66%) than controls. Significant associations were observed between scores for path features, aesthetics and land use and odds of chronic disease death in buffers of 0.25, 0.50, 1.00 and 1.50 miles. In 0.25 mile buffers, 1-point higher scores for path features, aesthetics and land use were associated with 1.12 (95% CI 1.02, 1.23), 0.66 (95% CI 0.53, 0.82) and 0.49 (95% CI 0.32,0.76) times the odds of chronic disease death, respectively. Significant associations highlight the importance of land use development conducive to PA (i.e. higher density and better condition residential settlement) and improved community aesthetics (i.e. greenspace presence and maintenance) to improved health in rural populations. More research is needed to identify a mechanism for the unexpected association between path features (i.e. presence of a path) and increased odds of chronic disease death. Rural BE improvements face barriers (lower population density), and these reported associations may guide feasible approaches to improved rural health.
Abstract P449: Associations of Unhealthy Food and Physical Activity Environments With Adverse Cardiac Function: The Coronary Artery Risk Development in Young Adults (Cardia) Study
Authors: Patel Ravi B , Colangelo Laura A , Gordon-Larsen Penny , Yancy Clyde W , Lloyd-Jones Donald M , Kershaw Kiarri N , Khan Sadiya S
Published: March 2020

Background:
Substantial disparities in risk of heart failure (HF) exist by race, which may be driven by certain social or environmental factors. The relationship between the neighborhood built environment, including food and physical activity facilities, and risk of HF is unclear. The associations of the built environment and subclinical cardiac dysfunction may offer insight into mechanisms that lead to increased HF risk.

Methods:
In the CARDIA study, we evaluated the associations between measures of the neighborhood built environment and echocardiographic indices of cardiac function at the Year 25 exam (Y25). Built measures were assessed within a 3-km Euclidean distance from participant residence and included: 1) proportion of fast food restaurants or convenience stores relative to total food outlets and 2) number of public or commercial physical activity facilities.

Results:
Among 2,363 participants (44% male, 51% black) with available data from Y25, higher proportions of fast food restaurants and convenience stores were independently associated with lower left ventricular (LV) diastolic function (lower e’ tissue velocities and higher E/e’) (
Table
). Lower number of public and commercial physical activity facilities were independently associated with lower LV systolic function (LV longitudinal strain) and diastolic function.

Conclusions:
Food environments with higher proportions of fast food and convenience stores are associated with lower diastolic function, and environments with less physical activity facilities are associated with worse systolic and diastolic function. These findings suggest relationships between the built environment and subclinical HF.
Abstract P458: Genetically Determined Reproductive Aging and Cardiovascular Risk Factors and Coronary Heart Disease Risk: A Two-sample Mendelian Randomization Study
Authors: Onland-Moret N. Charlotte , Dam Veerle , van der Schouw Yvonne T ,   EPIC-CVD consortium
Published: March 2020

Introduction:
Accelerated reproductive aging, in women indicated by early natural menopause, is associated with an increased risk of coronary heart disease (CHD) in observational studies. Conversely, an adverse CHD risk factor profile has been suggested to accelerate menopause. We conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors. Genomic variants for age at natural menopause (ANM) have been implicated in genome stability, immune function and mitochondrial biogenesis, which are not sex-specific processes. We used ANM variants as a measure for genetically determined reproductive aging in women and also in men, since genome-wide association studies (GWAS) for reproductive aging traits in men are lacking.

Hypothesis:
Reproductive ageing is causally related to CHD in both women and men.

Methods:
We conducted a bidirectional two-sample Mendelian Randomization, using both cohort data as well as summary statistics, with four methods: simple median-based, weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression.

Exposures:
Genetically determined reproductive aging, CHD and CHD risk factors.
Main outcomes:
CHD, CHD risk factors and age at natural menopause.

Results:
Summary statistics were pooled from three studies with together 417,579 participants from European descent, including 49,150 CHD cases. Publicly available GWAS and EPIC-CVD were pooled for total cholesterol, high density lipoprotein cholesterol, triglycerides, HbA1c, and glucose. Across different MR methods genetically determined reproductive aging was not causally related to CHD risk in women (Relative Risk Estimate (RRE)
IVW
=0.99, 95% confidence interval (CI): 0.97;1.01), or any of the CHD risk factors. Also, no associations were found in men. Furthermore, CHD was not causally related to reproductive ageing.

Conclusions:
Reproductive aging is not causally related to CHD risk or CHD risk factors in women, nor in men. We found no evidence for a reverse association. The associations between early menopause and CHD risk in observational studies might be the result of residual confounding, reverse causation, or reflect a shared etiology that results in both earlier menopause and higher CHD risk.
Abstract P459: Milk Intake, Host LCT Genotype and Gut Bifidobacteria in Relation to Obesity: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Moon Jee-Young , Wang Zheng , Usyk Mykhaylo , Vazquez-baeza Yoshiki , Isasi Carmen R , Mossavar-Rahmani Yasmin , McDonald Daniel , Sotres-Alvarez Daniela , DAVIGLUS Martha L , Cai Jianwen , Knight Rob , Kaplan Robert , Qi Qibin , Burk Robert D
Published: March 2020

Background:
Previous studies in Europeans found that gut
Bifidobacterium
genus was elevated in lactose intolerant individuals. However, the interrelationship between milk intake, host lactase (
LCT
) genotypes and different
Bifidobacteria
species, and their implications for human diseases have not been well-studied.

Methods:
This study included 2141 participants aged 23-83 years with microbiome, genetics and 24 hour dietary recall data from the HCHS/SOL, a population-based cohort of US Hispanics/Latinos. Stool samples were analyzed by shotgun metagenomics sequencing.

Results:
A GWAS on
Bifidobacterium
genus confirmed the genome-wide significant
LCT
locus (rs4988235,
P
=3.7х10
–21
) (
Fig A
), and 3 major
Bifidobacteria
species were also significantly associated with
LCT
(
B. longum
P
=
4.4х10
–17
,
B. adolescentis
P=2.9х10
–13
,
B. bifidum
P=3.1х10
–5
). 779 adults with lactose tolerant genotype (GG) had higher milk intake but lower
Bifidobacteria
compared to 1372 lactose intolerant adults (AA/AG). There was a significant interaction between milk intake and
LCT
variant on
Bifidobacterium
(P
int
=0.0003), with a positive association between milk intake and
Bifidobacterium
only in lactose intolerant but not in tolerant people (
Fig B
). The association of
Bifidobacterium
with obesity was also modified by
LCT
genotype. In lactose intolerant people, higher
Bifidobacterium
was associated with lower BMI, waist circumference and fat mass index, whereas in tolerant people higher
Bifidobacterium
was associated with higher obesity measures (
Fig C
). Species-level analyses indicated that
B. longum
may account for the positive association with milk intake and inverse associations with obesity measures in lactose intolerant people, while other major species,
B. adolescentis
and
B. bifidum
, may contribute to the positive association with obesity measures in lactose tolerant people.

Conclusion:
Our data indicate that diet and
LCT
genotype may alter the
Bifidobacterium
composition in gut, with different associations with obesity.
Abstract P460: Genetic Risk for Obesity Across the Transition From Young to Older Adulthood: A Pathway Based Analysis
Authors: Hou Ruixue , Howard Annie Green , Tien Hsiao-Chuan , Graff Mariaelisa , Huang Wei , Shi Jinxiu , Wang Haifeng , Gordon-larsen Penny
Published: March 2020

Background:
Genetics and lifestyle behaviors are key contributors to obesity. However, few studies explicitly examine the differential genetic association with BMI across critical lifecycle periods between young adulthood and later adulthood.

Hypothesis:
We anticipate that genetic risk will be directly associated with BMI in young adulthood and there will be a strong indirect association with BMI later in life, as a result the increased risk of BMI associated with young adulthood.

Methods:
For 7,397 Chinese adult participants (age 18 to 65y) of the China Health and Nutrition Survey (CHNS; 1991-2015), we calculated an obesity polygenic risk score (PRS) based on BMI-related SNPs selected from the largest BMI GWAS in 700,000 individuals of European ancestry from UK biobank and GIANT consortium, weighted by effect size estimated from the GWAS study. We used linear mixed models to estimate BMI across all periods of adulthood, adjusting for calendar time and sex. In a subsample of participants with three measurements across 24 years (n=1220), we used pathway based analysis to estimate the direct effects of genetic risk in association with BMI during young (18-35y), middle (35-45y), and later (45-65y) adulthood as well as the indirect genetic effects of at later adulthood through BMI at each of these earlier periods in life.

Results:
In the full sample, the linear mixed model-adjusted mean BMI (Standard Error (SE)) was 22.4 (0.04) kg/m
2
at young adulthood, 23.1 (0.04) kg/m
2
at middle adulthood and 23.2 (0.04) kg/m
2
at later adulthood, adjusting for sex and calendar year. In the subsample, a one standard deviation higher obesity PRS was directly associated with a 0.38 (0.07 SE) and 0.21 (0.06 SE) kg/m
2
higher BMI in young and middle adulthood, respectively. We found no evidence of a direct estimated effect of PRS in later adulthood (age 45-64y), but evidence of an indirect association between obesity PRS and BMI in later adulthood (age 45-64y). For example, we found a one standard deviation higher PRS was indirectly associated with 0.31 (0.06 SE) kg/m
2
higher BMI at age 35-45y through BMI at age 18-35y, and a 0.25 (0.05 SE) kg/m
2
higher BMI at age 45-65y through BMI at age 18-35y and subsequently BMI at age 35-45y.

Conclusion:
We observed a strong direct association between polygenic risk for obesity in young adulthood (age 18-35y), with persistence through age 35-45y and into age 45-65y.
Abstract P463: Objectively Measured Moderate-to-Vigorous Physical Activity is Associated With Decreased Myosteatosis in African Caribbean Adults
Authors: Miljkovic Iva , Kuipers Allison , Cvejkus Ryan , Wheeler Victor , Zmuda Joseph
Published: March 2020

Increased skeletal muscle fat infiltration (i.e. myosteatosis) is now recognized as a major risk factor for cardio-metabolic diseases. Therefore, a lifestyle modification that reduces myosteatosis would be of great public health importance. However, studies examining the association of relevant lifestyle factors with this ectopic fat depot are lacking, particularly in African ancestry populations who have a very high burden of cardio-metabolic diseases.

The aim of this study was to examine the relation between objectively measured physical activity and sedentary behavior with computed tomography measured calf muscle attenuation among middle-aged and elderly African-Caribbeans from the population-based Tobago Health Study. Preliminary analyses were conducted among 134 women (mean age 59 yrs, mean BMI 31.6 kg/m
2
) and 355 men (mean age 62 yrs, mean BMI 28 kg/m
2
). Physical activity was measured using the SenseWear Pro armband worn for 4-7 days. We calculated the mean duration of waking time engaged in light physical activity (LPA), moderate to vigorous activity (MVPA), and sedentary behavior (SB) per day. Skeletal muscle attenuation (mg/cm
3
) reflects the fat content of the muscle such that greater skeletal muscle fat infiltration is reflected by lower attenuation.

Women spent less time in LPA (146 vs. 270 min/day) and MVPA (15 vs. 41 min/day), but more time in SB (789 vs. 647 min/day) than men (all p<0.0001) after adjustments for gender differences in age. Muscle attenuation was lower among women compared with men (70.5 vs. 72.7 mg/cm3; age and BMI adjusted p<0.0001). In both women and men, muscle attenuation was positively correlated with the LPA and MVPA, and inversely with time spent in SB (spearman correlation coefficients (r) ranged from 0.21 to 0.39, all p<0.006 adjusted for age). Upon additional adjustment for BMI, in both women and men, the association of muscle attenuation with MVPA remained significant (r=0.21 and r=0.18, respectively, both p<0.03), but there was no association with LPA. Percent time spent in SB was associated with muscle attenuation only among women after additional adjustment for BMI (women: -0.16, p=0.052), and we also found a significant sex interaction effect of SB on muscle attenuation (p=0.035).

Our preliminary findings suggest that there is significant association between MVPA and myosteatosis among middle-aged and elderly African Caribbeans. However, SB may only be relevant for myosteatosis among women. Future analyses will be conducted in a larger sample from this cohort to confirm our findings and to test for independence from other potential confounding factors, such as diet, sleep patterns, adiposity distribution, and diabetes.
Abstract P491: Serum Fatty Acids Concentrations and Compositions, Lipids Concentrations and Their Correlation in Acute Ischemic Stroke Patients Aged 50 Years or Older
Authors: Mori Takahisa , Yoshioka Kazuhiro
Published: March 2020

Background:
Compositions of serum fatty acids (s-FAs), such as palmitic acid (PA), oleic acid (OlA), linoleic acid (LiA) and docosahexaenoic acid (DHA), and their correlation with serum lipids (s-LPs), such as total cholesterol (T-CHO) and triglycerides (TG), have been reported in healthy young or middle subjects. However, little is known about s-FAs features in acute ischemic stroke (AIS) patients.

Hypothesis:
Serum FAs features in AIS elderly patients are different from those in healthy young subjects and concentrations of s-FAs provide different correlation with s-LPs from compositions.

Methods:
We conducted a cross-sectional study of patients aged 50 years or older who were admitted to our institution between August 2016 and July 2019 within 24 hours of first AIS onset. We evaluated concentrations and compositions of s-FAs and their association with s-LPs, age and ischemic stroke subtype.

Results:
Three hundred sixty-six patients met our inclusive criteria. Their average age was 74.7 years, median T-CHO and TG were 203.5 and 102 mg/dl, respectively and median concentrations of PA, OlA, LiA and DHA were 642.5, 566.0, 723.0 and 129.8 μg/ml, respectively, and their median or mean compositions were 23.6, 20.9, 26.5 and 4.7 %, respectively. Concentrations of s-FAs had positive correlation with s-LPs. Concentrations of s-LPs and most of s-FAs had negative correlation with age. In stroke subtype of large-artery atherosclerosis or small-vessel occlusion (LAA_SVO) and in stroke subtype of cardioembolism or others (CE_O), mean age was 72.6 and 76.4 years (p<0.001), median TCHO was 214 and 194 mg/dl (p<0.0001), median TG was 113 and 95 mg/dl (p<0.05), median PA was 678.8 and 611.2 μg/ml (p<0.0001), median OlA was 613.8 and 532.4 μg/ml (p<0.001), median LiA was 767.2 and 696.1 μg/ml (p<0.001), and mean DHA was 131.4 and 127.9 μg/ml (ns). Compositions of PA, OlA, LiA and DHA had no correlation with T-CHO and compositions of PA and OlA had positive correlation with TG, whereas compositions of LiA and DHA had negative correlation with TG. Compositions of OlA had negative correlation with age, whereas DHA composition had positive correlation with age. There was little difference of compositions between stroke subtypes.

Conclusions:
In first AIS elderly patients, concentrations of most of s-FAs had positive correlation with s-LPs. In LAA_SVO, patients were younger and their concentrations of s-LPs and most of s-FAs were larger than in CE_O. On the other hand, correlation of s-FAs compositions with s-LPs was not constant and there was little difference of compositions between ischemic stroke subtypes.
Abstract P502: Deep Learning-powered Wearable Electrocardiogram Big Data Monitoring for Precision Cardiac Health
Authors: Zhang Qingxue
Published: March 2020

Smart health technologies are bringing exciting possibilities to the cardiac healthcare area. Wearable electrocardiogram (ECG) monitoring is expected to establish cardiac big data towards precision cardiac health. However, there are two key obstacles here. Firstly, how to conveniently measure the standard 12-lead ECG in our daily lives is an open question, since the traditional 12-lead ECG is mainly used in clinics or hospitals. The Holter ECG monitor is actually not convenient and comfortable enough for daily and long-term use. The Apple Watch only provides finger-touch-based single lead ECG measurement, neither supporting 12-lead ECG nor continuous tracking. In this study, a long short-term memory neural network-based ECG monitoring system is proposed, which can generate the remaining 9-lead ECG from only 3-lead ECG, offering a very high wearabilty, usability and convenience. Secondly, how to maintain a high ECG quality even when the user has different physical activities is another critical challenge. Usually, the ECG morphology may be contaminated by diverse motions artifacts induced by sensor-to-skin contact variations. This has to be addressed to guarantee the obtained ECG is usable and interpretable. We have introduced bidirectional long short-term memory to deal with these noisy fluctuations, by learning the temporal consistent dynamics among 3-lead ECG. The system has been evaluated on ten human subjects to demonstrate the effectiveness. Compared with the ground truth, the reconstructed 12-lead ECG has a correlation as high as 0.88 and a root mean square error of 0.059 mV, far superior to the traditional linear regression method. The proposed novel monitor is expected to greatly advance precision cardiac health.
Abstract P506: Dietary Self-monitoring Using An App: Are Frequency, Consistency And Completeness Related To Weight Loss?
Authors: Payne Jason E , Turk Melanie T , Pellegrini Christine A , Kalarchian Melissa A
Published: March 2020

Background:
Approximately 70% of the U.S. adult population has obesity and/or overweight and thus increased risk for heart disease, stroke, and type II diabetes mellitus. Standard obesity treatment includes a behavior modification technique, dietary self-monitoring, which entails recording all foods and beverages consumed with calorie amounts and time of consumption. Greater adherence to dietary self-monitoring using a paper diary is associated with weight loss. Self-monitoring via a mobile phone application (app) is an appealing, convenient alternative to paper-based techniques; however, few studies have examined the relationship between adherence to a dietary self-monitoring app and weight loss.

Objectives:
The objectives of the study were to 1) examine if there is an association between app-based dietary self-monitoring and weight change and 2) explore the relationships between the frequency, consistency, and completeness of app-based dietary self-monitoring and weight change at 8 weeks among adults with overweight or obesity. Frequency was the percentage of days that any self-monitoring occurred during the study; consistency was the recording of any dietary intake on
>
3 days each week; completeness was the recording of 50% or more of the weekly individual calorie goal.

Methods:
Ninety participants interested in weight loss were recruited to self-monitor dietary intake for 8 weeks using the app Calorie Counter by FatSecret. Participants were assigned a daily calorie goal to achieve a one-pound weight loss per week. Paired sample t-test and linear regression were used to examine the relationships between app-based self-monitoring and weight change as well as the frequency, consistency and completeness of self-monitoring and weight change at 8 weeks.

Results:
The sample [N = 90, mean (
M
) age = 42 ± 10 years (SD)] was employed (100%), primarily female (96.7%), White (90%), and married (63.3%) with a Bachelor’s or Associate’s degree (60%). Paired-sample t test revealed a significant mean difference [
t
(89) = 6.59,
p
< .001] between baseline and 8-week weight in pounds (
M
=
-3.26 ± 4.70). Linear regression analysis revealed an association [
F
(1, 88) = 7.18,
p
= .009] between total weeks of consistently self-monitoring (
M
= 4.44 ± 2.77) and percent weight loss (
M
= -1.54 ± 2.26) as well as an association (
F
(1, 88) = 6.42,
p
= .013] between the frequency of self-monitoring (
M
= 50.14 ± 33.0) and percent weight loss. Completeness of self-monitoring was not associated with percent weight loss.

Conclusion:
Results suggest that consistent (
>
3 days/week) and frequent (
>
50% of days) app-based self-monitoring aids weight loss. Clinicians may wish to emphasize frequent and consistent self-monitoring, rather than complete self-monitoring, when providing weight loss counseling. Future research should examine app-based self-monitoring in men as well as ethnically and racially diverse populations.

.
Abstract P514: A Healthy Beverage Score and Risk of Chronic Kidney Disease Progression, Cardiovascular Disease, and All-Cause Mortality in the Chronic Renal Insufficiency Cohort
Authors: Hu Emily , Anderson Cheryl A , Grams Morgan , Appel Lawrence J , Coresh Josef , Crews Deidra , He Jiang , Shou Haochang , Mills Katherine T , Taliercio Jonathon , Jena-Mohanty Madhumita , Bhat Zeenat , Rebholz Casey M
Published: March 2020

Background:
The association between an overall healthy beverage pattern and chronic disease outcomes is unknown. We created the Healthy Beverage Score (HBS) to characterize the healthfulness of participants’ beverage profiles and examined its association with chronic kidney disease (CKD) progression, cardiovascular disease (CVD), and all-cause mortality among individuals with CKD.

Methods:
We conducted a prospective analysis of 2,275 participants aged 21-74 years with an estimated glomerular filtration rate (eGFR) between 20 and 70 mL/min/1.73 m
2
from the Chronic Renal Insufficiency Cohort. Diet was assessed using a 124-item food frequency questionnaire at visit 1 (2003-2008). The HBS (7-28) consisted of 7 components. Each component was scored 1-4 based on rank distribution by quartile. Participants were given more points for higher consumption of low-fat milk, coffee and tea, moderate consumption of alcohol, and lower consumption of 100% fruit juice, full-fat milk, artificially-sweetened beverages, and sugar-sweetened beverages. CKD progression, CVD, and all-cause mortality were ascertained through January 2018. We conducted multivariable Cox proportional hazards models.

Results:
There were 815 cases of CKD progression, 285 cases of CVD, and 725 deaths over a median of 7, 10, and 12 years of follow-up, respectively. Compared with participants in the lowest tertile of the HBS, participants in the highest tertile had a 27% lower risk of CKD progression (hazard ratio, HR: 0.73, 95% confidence interval, CI: 0.61-0.87) (
P
-trend<0.001) and 17% lower risk of all-cause mortality (HR: 0.83, 95% CI: 0.69-1.00) (
P
-trend=0.05) after adjusting for covariates (
Table
). There was no significant association for CVD comparing tertile 3 with tertile 1 (HR: 0.93, 95% CI: 0.70-1.23) (
P
-trend=0.70).

Conclusions:
A healthier beverage pattern was associated with lower risk of CKD progression and all-cause mortality. Beverage intake may be an important modifiable dietary target in managing outcomes for individuals with CKD.