bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP20: The Discriminatory Characteristics of Neighborhood Socioeconomic Status in Predicting Cardiovascular Disease in Electronic Health Record Based Studies Differs by Age
Authors: Bhavsar Nrupen A , Gao Aijing , Pagidipati Neha , Phelan Matthew , Goldstein Benjamin
Published: July 2021

Introduction:
Recent studies report an association between neighborhood residence and health outcomes. There is less information on the relative utility of neighborhood socioeconomic status (nSES) in models that predict future health outcomes and the impact that age may have on this.

Objective:
To quantify if nSES data alone or in concert with electronic health record (EHR) data can improve risk prediction for myocardial infarction (MI) and stroke beyond current models.

Methods:
Neighborhood SES was derived using the AHRQ SES index. Clinical and demographic data was obtained from the EHR of patients seen at the Duke University Health System from 2009-2015; it was split into a training set (2009-2012) and testing set (2012-2015). Age (in yrs) was categorized as young (18-44), middle age (45-64), and old (≥65). Logistic regression models were fit for each outcome over 6 time horizons (30, 90, & 180 days; 1, 2, & 3 years) using machine learning methods (least absolute shrinkage and selection operator [LASSO]) for model selection to determine if nSES improved discrimination, as measured by the c-statistic.

Results:
Of 106703 patients, 63% were female, 41% were Black, 2.6% had CVD, 12% had diabetes, and 29% had hypertension at baseline with mean age of 47 years. The majority of the correlation between EHR variables and nSES (r
2
=0.31) was explained by demographic information within the EHR (r
2
=0.29; p<0.01). In LASSO models incorporating EHR and SES data, EHR variables (e.g., comorbidities) were frequently selected while nSES variables (e.g., AHRQ SES index) were rarely chosen. The c-statistic for predicting MI and stroke when using nSES data with and without EHR data was higher in middle aged and older patients as compared to younger patients (Figure).

Conclusions:
The added value of nSES was less than expected as much variability in nSES may be phenotyped through demographic information in the EHR. In discrete instances, nSES can improve risk prediction but varies by age, clinical outcome, and time horizon.
Abstract MP24: Comparison of on-site versus Remote Support for a Mobile-Device Pilot Study: A Collaboration Between the Framingham Heart Study and Health eHeart Study (FHS-HeH)
Authors: Spartano Nicole L , Sun Fangui , Lunetta Kathryn L , Trinquart Ludovic , Valentino Maureen , Manders Emily S , Pletcher Mark J , Marcus Gregory M , McManus David D , Benjamin Emelia J , Fox Caroline S , Olgin* Jeffrey E , Murabito* Joanne M
Published: July 2021

Background:
New “e-Cohort” study designs provide resource-effective methods for collecting participant data. It is unclear if implementing an e-cohort without direct, in-person participant contact can achieve successful participation rates. The FHS-HeH randomized pilot study compared two distinct implementation strategies for co-enrolling participants from the Framingham Heart Study (FHS) into the Health eHeart Study, a digital cohort with infrastructure for collecting mHealth data.

Methods:
FHS participants who had an email address and smartphone were randomized to one of two approaches:
remote
vs.
on-site
support. In the
remote
arm, participants received an email containing an enrollment URL, and, upon enrollment, were sent four Bluetooth sensor devices. Participants in the
on-site
arm were invited to visit FHS and were provided in-person support for enrollment and connecting the devices.

Results:
Compared to participants that declined, individuals that accepted an invitation to participate in our pilot study (n=101
remote
, n=101
on-site
) were more often women, highly educated, and younger (Figure 1). All
on-site
participants completed the consent, compared to 93% of the
remote
arm. Of participants who consented to participate, connection and initial use of devices was also higher in the
on-site
arm (100% connected the activity monitor, 94% the blood pressure cuff and scale, and 84% the electrocardiogram) compared to the
remote
arm (74%, 75%, 80%, and 42%). Roughly 75-78% of those that initially connected in both arms were still using the devices by the 3
rd
month and 58-60% were still participating by the 6
th
month.

Conclusions:
Our pilot study demonstrated that deployment of mobile devices among middle-aged and older adults in the context of an
on-site
clinic visit was associated with higher initial rates of device use as compared to offering only
remote
support. Once connected, drop-off rates were similar in both groups.
Abstract MP26: Obesity is Associated With Accelerated Epigenetic Aging in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Khan Sadiya S , Zheng Yinan , Colangelo Laura A , Zhang Wei , Lewis Cora E , Greenland Philip , Lloyd-Jones Donald M , Hou Lifang
Published: July 2021

Background:
Obesity is associated with increased risk of cardiovascular and other age-related diseases that may represent accelerated aging. As methylation levels in DNA change with aging, epigenetic age (EA), which integrates whole-genome methylation has emerged as a novel biomarker of aging and has been associated with mortality and age-related morbidity. Epigenetic age acceleration (EAA), is based on the residual value of 353 previously defined methylation markers regressed on chronologic age (CA), and is thus independent of CA. Therefore, we sought to examine the association of obesity and EAA in midlife.

Methods:
A subset of participants in the CARDIA cohort (n=1200) randomly selected (balanced on race and sex) underwent genome-wide DNA methylation profiling with the Illumina EPIC array from exam year 15 (2000-01 [age 33-45 years]) and 20 (2005-06 [38-50 years] for calculation of EAA. Body mass index (BMI) was measured at Y15 and Y20, respectively. We used linear regression to examine the association of obesity (independent variable) with EAA after adjusting for CA, race, sex, education, study center, smoking status, physical activity, and alcohol intake.

Results:
Participants were 52% female and 41% black and had mean BMI 28.5±6.2 kg/m
2
at Y15 and 29.2±6.4 kg/m
2
at Y20. At Y15, participants who were obese had 1.04 (0.38) years higher EAA compared to normal BMI participants (p<0.01,
Figure)
. Similar results were observed at Y20. Results were similar when evaluating the association of BMI continuously with EAA (p<0.05).

Conclusions:
EAA is a promising molecular biomarker of aging associated with obesity. Changes in DNA methylation may serve as an intermediate phenotype prior to the onset of age-associated pathologies related to obesity.
Abstract MP33: Association Between Twenty-year Trajectories of Physical Activity From Midlife to Old Age and Cardiovascular Disease Risk Factors: A 20-Year Cohort Study of British Men
Authors: Aggio Daniel , Papachristou Efstathios , Papacosta Olia , Lennon Lucy T , Ash Sarah , Whincup Peter H , Wannamethee Goya S , Jefferis Barbara
Published: July 2021

Introduction:
Maintenance of physical activity during later life is associated with reduced risk of cardiovascular disease; however, how long-term trajectories of physical activity into old age are associated with established and novel cardiovascular disease risk factors remains unclear. This study examined the association between 20-year physical activity trajectories and a wide range of cardiovascular disease biomarkers in early old age.

Hypothesis:
We assessed the hypothesis that persistent long-term physical activity from midlife to old age is associated with the lowest levels of cardiovascular disease risk factors in old age.

Methods:
7735 men (mean baseline age 50.2 ± 5.8 years) recruited in 1978-80 were followed up after 12, 16 and 20 years, reporting habitual physical activity levels at each wave. At the 20-year follow up, surviving men also attended a physical examination and provided a fasting blood sample. Initially, group-based trajectory modelling was used to identify the trajectories of physical activity. Then regression analyses were used to examine the association between trajectory group membership and a number of cardiometabolic, cardiac and inflammatory markers. Analyses were adjusted for a range of sociodemographic, health and lifestyle factors and use of blood pressure-lowering and antihypertensive drugs.

Results:
A total of 3228 men providing physical activity data at ≥3 time points with cardiovascular biomarker data were included in the analysis. Three distinct 20-year trajectories were identified: low decreasing (20.1%), light stable (52.7%) and moderate increasing (27.2%). In comparison to the low decreasing group, membership of the light stable and moderate increasing physical activity trajectory groups was associated with a more favourable cardiometabolic profile, including lower HbA1C and insulin; lower levels of inflammation, including lower levels of interleukin 6 and C-reactive protein; and lower levels of the cardiac marker high-sensitivity troponin T. The magnitude of the associations was similar for the light stable and moderate increasing groups.

Conclusion:
In conclusion, twenty-year trajectories of physical activity from midlife to old age were associated with established and novel cardiovascular disease risk factors. Effect sizes were similar for members following a light stable and a moderate increasing physical activity trajectory, suggesting that even relatively light but persistent physical activity into old age can be a determinant of lower cardiovascular disease risk.
Abstract MP53: 1,5-anhydroglucitol to Identify Older Adults with Diabetes at Risk of Hospitalization and All-cause Mortality
Authors: Warren Bethany , Rawlings Andreea , Sharrett A. Richey , Coresh Josef , Kottgen Anna , Selvin Elizabeth
Published: July 2021

Introduction:
Older adults with diabetes have variable prognosis. There is critical need to improve risk stratification among this population to understand who is most likely to experience adverse outcomes. Low 1,5-anhydroglucitol (1,5-AG) is a biomarker of glycemic variability and has demonstrated value for identification of middle-aged adults with diabetes at risk for major clinical outcomes. Total hospitalizations are a useful summary measure of poor health outcomes. It is unknown whether 1,5-AG can identify older adults at risk for hospitalizations and all-cause mortality.

Methods:
We included 2,061 participants from the Atherosclerosis Risk in Communities (ARIC) Study with diagnosed diabetes who attended the 2011-2013 visit. We dichotomized 1,5-AG (≥6μg/mL; <6μg/mL) and followed participants until December 31, 2015. We examined the associations of 1,5-AG with total and diabetes-related hospitalizations using negative binomial regression and all-cause mortality using Cox regression.

Results:
Participants ranged in age from 67-90 years, 57% were female, 30% were black, and 17% had 1,5-AG <6μg/mL. Median HbA1c was 6.2% in those with 1,5-AG ≥6μg/mL and 7.8% in persons with 1,5-AG <6μg/mL. During a median of 3.6 years of follow-up, there were 2,813 hospitalizations (1,689 diabetes-related) and 247 deaths. Compared to 1,5-AG ≥6μg/mL, individuals with 1,5-AG <6μg/mL had a significantly higher risk of hospitalizations, diabetes-related hospitalizations, and death (
Table
). After adjustment for diabetes medication use or HbA1c, associations with hospitalizations were attenuated and non-significant, while the relationship with all-cause mortality remained.

Conclusion:
Among older adults with diagnosed diabetes, glycemic variability may be an important risk factor for major short-term complications.
Abstract MP55: Associations Between Traffic-Related Air Pollution and Cardiovascular Disease Risk Factors Were Stronger in More Walkable Neighborhoods: The Cardiovascular Health in Ambulatory Care Research Team Cohort
Authors: Howell Nicholas A , Tu Jack V , Moineddin Rahim , Chu Anna , Chen Hong , Hystad Perry , Booth Gillian L
Published: July 2021

Introduction:
Studies suggest living in a more walkable neighborhood may protect against cardiovascular disease risk factors such as hypertension (HTN) and diabetes mellitus (DM) by encouraging physical activity. Walkable neighborhoods, however, often carry higher levels of traffic-related air pollution. Little is known regarding whether synergistic effects may exist between walkability and air pollution on these risk factors.

Hypothesis:
We hypothesized that the association between traffic-related air pollution, hypertension, and diabetes mellitus would be stronger in more walkable areas.

Methods:
We drew a cross-sectional sample of individuals ages 40-74 on January 1, 2008 from the CANHEART cohort. HTN and DM were ascertained using validated algorithms. Walkability (quintiles, Q5 highest, Q1 lowest) was measured using a validated index which has previously been shown to be inversely associated with obesity and diabetes. Exposure to nitrogen dioxide, a valid marker for traffic-related air pollution, was assessed using a land use regression models. The associations were tested using logistic regression with cluster-robust standard errors, adjusting for age, sex, area-level income, ethnicity, and comorbidities.

Results:
In total, 2,618,584 individuals were included in the analysis (mean (SD) age = 53.2 (9.2), 52% female). Walkability was inversely associated with odds for HTN (Q5 vs. Q1 OR = 0.80, 95% CI: 0.79, 0.82) and DM (Q5 vs. Q1 OR = 0.89, 95% CI: 0.87, 0.91), while NO
2
was positively associated with each (HTN: OR = 1.02 per 10 ppb (1.01, 1.03); DM: OR = 1.11 per 10 ppb (1.09, 1.13)). We observed significant interactions between walkability and NO
2
on odds for HTN and DM, with stronger NO
2
associations in the most walkable neighborhoods (Fig. 1).

Conclusions:
We observed significant interactions between traffic-related air pollution and walkability on odds for HTN and DM. This finding suggests that benefits from living in more walkable neighborhoods may be offset by stronger negative associations with air pollution.
Abstract MP63: Fine-mapping and Characterization of Adiponectin Gwas Loci Harboring Extensive Allelic Heterogeneity
Authors: Spracklen Cassandra N , Jackson Anne U , Iyengar Apoorva , Vadlamudi Swarooparani , Stringham Heather , Raulerson Chelsea K , Cannon Maren E , Currin Kevin W , Wu Ying , Fuchsberger Christian , Welch Ryan , Chines Peter , Narisu Narisu , Kuusisto Johanna , Pajukanta Paivi , Collins Francis , Boehnke Michael , Laakso Markku , Mohlke Karen
Published: July 2021

Background:
Elevated levels of adiponectin, an adipose-tissue derived hormone, are associated with a decreased risk for development of obesity, cardiovascular disease, and type 2 diabetes. We sought to fine-map and characterize loci from an adiponectin genome-wide association study (GWAS) to better understand the genes, variants, and mechanisms that contribute to adiponectin levels.

Methods:
We performed a GWAS of plasma adiponectin levels in 9,262 nondiabetic Finnish men from the Metabolic Syndrome in Men (METSIM) study using an efficient mixed model (EPACTS) to account for cryptic relatedness among the subjects. To identify multiple association signals within 1 Mb of each other, we used stepwise conditional analyses and Genome-wide Complex Trait Analysis (GCTA). We annotated association signals using regulatory elements based on chromatin marks from adipocyte nuclei (Epigenomic Roadmap) and ATAC-seq data from adipose tissue (METSIM) and SGBS preadipocyte cells. We also evaluated expression quantitative trait loci (eQTL) in subcutaneous adipose RNA-seq data from 387 METSIM samples. To test for allele-specific effects on transcriptional activity, we performed transcriptional reporter assays in HeLa cells.

Results:
We identified 5 loci associated with adiponectin (
P
<5x10
-8
):
CDH13, ADIPOQ
,
IRS1, PBRM1,
and
EPHA3.
Two loci (
CDH13
and
ADIPOQ
) contained 2 and 7 association signals (
P
<1x10
-5
), respectively. At
CDH13
, the first signal contained the lead adipose eQTL variant for
CDH13
. At the novel second signal at
CDH13
, rs4782722 is located in a regulatory element and the G-allele showed increased transcriptional activity compared to the T-allele, suggesting a functional role for this variant. At
ADIPOQ
, the first association signal also contained the lead adipose eQTL variant for
ADIPOQ.
All signals at
ADIPOQ
contained ≥1 variant in a putative enhancer, and the 7th signal includes rs62625753, a coding variant (G90S;

P
init

=3x10
-3
,

P
cond

=6x10
-4
) predicted to be deleterious (SIFT) and probably damaging (PolyPhen). Accounting for multiple signals resulted in a 1.6-fold increase in variance explained over the lead signals alone (5.9 vs 9.4%).

Conclusions:
Fine-mapping, annotation, and experimental validation of GWAS signals and variants provide novel insight into the molecular mechanisms underlying genetic association signals, leading to a clearer biological basis for disease.
Abstract MP64:
APOL1
Renal Risk Variants Associate With Heart Failure With Preserved Ejection Fraction in African-American Women
Authors: Franceschini Nora , Barac Ana , Martin Lisa , Rosamond Wayne
Published: July 2021

Introduction:
African origin coding variants in
APOL1
, encoding apolipoprotein L1, are strongly associated with various kidney diseases in African Americans, with odds ratio ranging from 7 to 89 for two renal risk allele carriers.
APOL1
renal risk genotypes may influence risk for cardiovascular disease and mortality, but findings have been inconsistent.

Hypothesis:
Given that African-American aging women are at high risk for cardiovascular disease and stroke, we asked whether
APOL1
risk genotypes affect these outcomes.

Methods:
We used data from 11,137 African-American postmenopausal women who participated in the Women’s Health Initiative prospective cohort, followed from enrollment (1993-1998) to 2014.
APOL1
genotypes were obtained directly or by imputation from whole exome sequencing data. Adjudicated outcomes were incident coronary heart disease, stroke and subtypes, heart failure and subtypes, and overall and cause-specific mortality obtained from hospital records and death certificates. End-stage renal disease status (ESRD) was obtained from the US Renal Data System. We estimated incident rates for each outcome and used Cox proportional hazard to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of
APOL1
high and low risk groups with outcomes.

Results:
Mean age was 61.7 years.
APOL1
high risk carriers (12.3% of participants) had higher prevalence of hypertension, use of cholesterol lowering medication, and reduced estimated glomerular filtration rate (eGFR), defined as <60 mL/min/1.73 m
2
. After 11 years mean follow-up
APOL1
high risk subjects had a higher incident rate of ESRD and hospitalized heart failure with preserved ejection fraction (HFpEF) than low risk carriers, but showed no difference in the incident rates of other outcomes. In adjusted models, there were a significant 43% increased hazard of ESRD (95% CI 1.01, 2.02), and a 58% increased hazard of hospitalized HFpEF (95% CI 1.03, 2.41) among high risk compared to low risk
APOL1
carriers. In sensitivity analyses restricted to the genome-wide association sample and accounting for population stratification (n=7,797), the associations remained significant for HFpEF. These associations were no longer significant after adjusting for eGFR.

Conclusions:
We identified novel associations of
APOL1
high risk status with hospitalization for HFpEF among postmenopausal women, which are likely mediated by
APOL1
-induced chronic kidney disease. We also showed lack of association of
APOL1
with incident coronary heart disease, stroke and mortality.
Abstract MP68: Association of Clinical and Subclinical Blood Pressure Elevation During Pregnancy With Maternal Health and Risk of Neonatal Low Birth Weight
Authors: Hu Jie , Li Jun , Peng Yang , Li Yuanyuan
Published: July 2021

Introduction:
Gestational hypertension is a leading cause of maternal mortality and fetal growth restriction (FGR). However, elevated maternal blood pressure at which trimester contributes to FGR is unknown, and whether gestational prehypertension (a systolic blood pressure [SBP] of 120 - 139 mmHg or a diastolic blood pressure [DBP] of 80 - 89 mmHg) is related with FGR and maternal health is not fully studied.

Methods:
We analyzed the relation of elevated gestational blood pressure with risk of neonatal low-birth-weight (LBW, birth weight < 2,500 g) and maternal health throughout pregnancy in 21,620 women from a birth cohort in Wuhan, China. Maternal health indicators, including SBP and DBP, were clinically measured during up to 22 antenatal visits. LBW were acquired from medical records. Linear mixed models were used to evaluate the relations of maternal SBP and DBP with LBW. Logistic regressions were used to assess the associations of SBP and DBP in late pregnancy (38.3 weeks) with LBW. Linear regressions were used to evaluate the association of prehypertension/hypertension with indicators of maternal health.

Results:
Gestational blood pressure increases throughout pregnancy, but a significant elevation of SBP and DBP between 15 and 25 gestational weeks were only observed for women who later delivered LBW newborns. High gestational SBP (≥ 140 mmHg) or DBP (≥ 90 mmHg) was associated with a 220% or 98% higher risk of LBW (
P
< 0.03). Notably, preclinical high SBP (120 - 139 mmHg) was also associated with a 40% higher risk of LBW (
P
= 0.036). At late pregnancy, elevated gestational SBP and DBP were associated with elevated liver enzymes, blood urea nitrogen, creatinine, and uric acid levels, and decreased activated partial thromboplastin time and prothrombin time.

Conclusions:
A fast blood pressure elevation in the second trimester may relate with increased risk of LBW. Pregnancy prehypertension was associated with not only LBW risk, but also impaired maternal liver, kidney, and coagulation functions.
Abstract MP69: How Well Do Cardiovascular Risk Factors Before and During Pregnancy Correlate? The International Childhood Cardiovascular Cohort (i3C) Consortium
Authors: Harville Emily W , Bazzano Lydia , Woo Jessica , Burns Trudy , Raitakari Olli , Urbina Elaine , Venn Alison , Jacobs David , Steinberger Julia , Sinaiko Alan , Dwyer Terry , Juonala Markus
Published: July 2021

Background:
Pregnancy complications such as gestational diabetes and pre-eclampsia predict later cardiovascular (CV) outcomes. However, it still is not clear whether pregnancy complications unmask preexisting impairments or instigate lasting injury. If pre-pregnancy and during-pregnancy CV risk factors are strongly correlated, it becomes more plausible that pregnancy unmasks an existing problem than creating a new one.

Methods:
Data from the i3C Consortium, a group of studies assessing the relationship between child/adolescent CV risk factors and adult outcomes, were used. 290 women from four cohorts had data on the same risk factor (blood pressure, lipids, glucose) from visits both prior to and during pregnancy. Correlation coefficients between the pre- and during pregnancy measures were calculated, and the mean difference between the measures modeled with adjustment for age, BMI, race, smoking, and study. Differences by gestational age and time between the pre-pregnancy visit and pregnancy visit were also examined.

Results:
All measures were strongly correlated at pre- and during-pregnancy visits (p<0.01), with r of between 0.3 and 0.55. The exception was glucose (r=0.11, p=0.15). These relationships held after adjustment for confounders. Interactions with gestational age indicated stronger correlations with measurements taken in the first and second trimesters than the third. The correlation did not differ by the time elapsed between the pre-pregnancy and pregnancy visits.

Conclusions:
Pre- and during-pregnancy CV risk factors are moderately well correlated. It is likely that women who develop pregnancy complications enter the pregnancy with higher risk rather than pregnancy inducing new vascular effects.
Abstract MP76: Trends in Adherence to Statin Therapy Among US Adults With Health Insurance Between 2007 and 2014
Authors: Colantonio Lisandro D , Rosenson Robert S , Deng Luqin , Monda Keri L , Dai Yuling , Farkouh Michael E , Safford Monika M , Philip Kiran , Mues Katherine E , Muntner Paul
Published: July 2021

Background:
Statins are effective for the primary and secondary prevention of coronary heart disease (CHD) events. However, studies from the early 2000s have suggested that many patients have low adherence to statin therapy.

Objective:
To analyze trends in adherence among US adults initiating treatment with a statin.

Methods:
We identified US adults 21-64 years of age with commercial health insurance in Marketscan and ≥65 years of age with government health insurance through Medicare who initiated statin therapy in 2007-2014. Three populations were analyzed, those initiating statin therapy 1) following myocardial infarction (n=52,828 in Marketscan, n=148,745 in Medicare), 2) with diabetes without a history of CHD (n=565,573 in Marketscan, n=42,411 in Medicare), and 3) without diabetes or a history of CHD (n=2,134,501 in Marketscan, n=105,948 in Medicare). Adherence to statin therapy was defined by having a statin available to take for ≥80% of the 365 days following treatment initiation.

Results:
Adherence to statin therapy increased in each population analyzed (
Figure
). In 2014, 68.1% and 62.7% of patients initiating treatment following myocardial infarction in Marketscan and Medicare, respectively were adherent to their statin. Less than half of patients initiating treatment with diabetes without CHD and without diabetes or CHD in Marketscan and Medicare were adherent to their statin. Adherence to statin therapy in the overall Marketscan and Medicare populations was higher among men (relative risk [95% CI] 1.16 [1.15, 1.18] and 1.10 [1.08, 1.12], respectively), and those with cardiologist visits (1.22 [1.21, 1.24] and 1.27 [1.25, 1.30], respectively), and lower among those with kidney disease diagnosed after treatment initiation (0.89 [0.85, 0.94] and 0.92 [0.88, 0.96], respectively).

Conclusion:
Adherence to statins improved slightly between 2007 and 2014 but remains suboptimal. Management by a cardiologist is associated with better adherence to statins.
Abstract MP78: Long-term Antibiotic Use and Risks of All-Cause and Cause-Specific Mortality among Women: Prospective Cohort Study
Authors: Heianza Yoriko , Ma Wenjie , Cao Yin , Chan Andrew T , Rimm Eric B , Hu Frank B , Rexrode Kathryn M , Manson JoAnn E , Qi Lu
Published: July 2021

Introduction:
Antibiotic exposure is associated with a long-lasting alteration in gut microbiota, and may be related to subsequent major chronic diseases such as cardiovascular diseases and cancer. No previous prospective cohort study has investigated associations between duration of antibiotic use during adulthood with mortality from major chronic diseases among populations at usual risk.

Hypothesis:
We investigated whether a longer duration of antibiotic use was associated with elevated risks of all-cause and cause-specific deaths among women.

Methods:
This study included 37,510 women aged ≥60 y who were initially free of cardiovascular diseases or cancer from the Nurses’ Health Study. The present analysis included women who reported data on antibiotic use on the 2004 questionnaire when the information was first assessed. We calculated hazard ratios (HR) for all-cause mortality, and deaths from cardiovascular disease (ICD-8 [international classification of diseases, eighth revision, ICD-8], codes 390 to 458) and cancer (ICD-8, 140-209) according to total days of antibiotic use per year (none, less than 15 days, 15 days to less than 2 months, or ≥2 months) in late adulthood (age 60 or older). Follow-up time was calculated from the return date of the 2004 questionnaire until the date of death, or end of follow-up (June 30, 2012), whichever occurred first.

Results:
During 287,474 person-years of follow-up, we documented 2908 deaths from any cause (including 474 cardiovascular deaths and 906 cancer deaths). Longer duration of antibiotic use was significantly associated with higher risk of death from any cause after adjusted for dietary intake, lifestyle factors, hypertension, hypercholesterolemia, diabetes (
P
trend
<0.0001), other medication use (such as aspirin, statin, H2 blockers, proton pump inhibitors) (
P
trend
=0.001), and other characteristics (
P
trend
=0.038). As compared to women who did not use antibiotics, those who used for ≥2 months in late adulthood had significantly increased risks of all-cause mortality (multivariate-adjusted HR 1.27; 95% CI, 1.07, 1.49) and cardiovascular mortality (HR 1.58; 95% CI, 1.02, 2.46), but not cancer mortality (HR=0.86; 95% CI, 0.63, 1.16). The association between long-term antibiotic use in late adulthood and an elevated risk of all-cause death was more evident among women who also used antibiotics in middle adulthood (during age 40-59) (
P
trend
=0.002) than among those who did not use during this life stage.

Conclusions:
Long-term duration of antibiotic exposure especially in late adulthood was associated with increased all-cause and cardiovascular mortality in women.
Abstract P005: Aspirin Use and Dementia: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Wu Aozhou , Sharrett A. R , Gottesman Rebecca F , Power Melinda C , Gross Alden L , Mosley Thomas , Rawlings Andreea M , Schneider Andrea L , Sharma Richa , Coresh Josef
Published: July 2021

Background:
Aspirin may help to prevent dementia through its antiplatelet and anti-inflammatory effects, but findings from previous studies are mixed. Considering the length of the preclinical phase of dementia, early initiation of regular aspirin use may be more protective against dementia than later initiation. In this study, we explored the association of regular aspirin use initiated during and after midlife with the risk of dementia.

Methods:
Using data from 1996 to 2013 on 10,398 ARIC participants, we assessed the association of self-reported prior duration of regular aspirin use which was collected during 1996-1998 (as the baseline of this study) with incident dementia after the baseline. Dementia cases were identified based on: in-person dementia ascertainment from 2011 to 2013; the Telephone Interview for Cognitive Status (TICS) or informant interviews on dementia; and hospital discharge codes/death certificate code by surveillance through 2013. The relative hazards of dementia across categories of the duration of regular aspirin use prior to baseline (<2 years, 2 to <5 years, and ≥ 5 years) were compared to no regular use by Cox proportional hazard models. We adjusted for potential confounders, including demographic variables and major dementia risk factors at baseline. In sensitivity analyses, propensity score weighting was applied. Subgroup analyses were conducted by age, gender, race, APOE, and diabetes status.

Results:
Participants had a median age of 62 (IQR: 58, 67) at baseline. 55.8% (5,805 of 10,398) were female and 20.6% (2,147 of 10,398) were African American. Lower but non-significant relative hazards (HR) were observed among participants with regular aspirin use for < 2 years (HR: 0.85; 95% CI: 0.69 to 1.04) and ≥ 5 years (HR: 0.87; 95% CI: 0.68 to 1.11), but not for the 2-5 year interval. With propensity score weighting, regular aspirin use < 2 years achieved marginal significance (HR: 0.79; 95% CI: 0.63 to 0.99), while the effect of regular aspirin use ≥ 5 years changed towards null (HR: 1.04; 95%CI: 0.75 to 1.46). Without a prior hypothesis, an interaction was found for diabetes status (p = 0.016) with a significant protective association of ever regular aspirin use compared to no regular use among non-diabetic participants (HR: 0.82; 95%CI: 0.69 to 0.98).

Conclusions:
We found a non-significant protective association of regular aspirin use at late-middle life with onward incident dementia in a community-dwelling population. Data suggest persons with fewer comorbidities, specifically without diabetes, might be more susceptible to the preventive effect of aspirin use on dementia. Our results are subject to confounding by indication, suggesting the need for additional studies in populations which have different covariate structures than ARIC.
Abstract P007: Arterial Stiffness is Associated With Increased Risk of Incident Dementia in the Older Elderly: The Cardiovascular Health Study Cognition Study
Authors: Cui Chendi , Sekikawa Akira , Kuller Lewis , Lopez Oscar , Newman Anne , Kuipers Allison , Mackey Rachel
Published: July 2021

Introduction:
Arterial stiffness is related to aging, hypertension, and obesity, and higher carotid-femoral pulse wave velocity (PWV) is associated with brain amyloid deposition. We hypothesized that higher cfPWV was associated with incident dementia in older adults (mean age 78) of the Cardiovascular Health Study Cognition Study (CHS-CS).

Methods:
Pittsburgh CHS-CS participants (n=532) without dementia at baseline (1998-99) had annual cognitive exams through 2013. CfPWV (m/sec) was measured from pulse velocity waveforms on 356 participants between 1996-2000, who were slightly younger, more educated, with less mild cognitive impairment (MCI) than those not included. Associations of cfPWV [continuous (transformed: -1/cfPWV) and quartile] with time-to-event [cfPWV measurement to dementia or death (competing event), or end of follow-up] were assessed in Cox proportional hazards model with competing risk of death.

Results:
Over 15-year follow-up, 212 (59.6%) dementia cases (median onset time=4 years) and 87 (24.4%) deaths occurred prior to dementia diagnosis. Adjusted for age and sex, incident dementia was related to higher cfPWV [hazard ratio (HR)=1.52 per -1/cfPWV, 95%CI=1.04, 2.24] (Table). Results were similar when further adjusted for education, race,
ApoE4
, hypertension, diabetes, MCI, and abnormal white matter (WMG) or ventricular grade (VG). Results persisted in separate models that excluded those with
ApoE4
+ (n=79), diabetes (n=40), MCI (n=65) or abnormal WMG or VG (n=136). In stratified models, results were stronger for age ≥80 vs. <80 and for hypertension vs. no hypertension. Pulse pressure (PP), another index of arterial stiffness, was not associated with incident dementia (age- and sex-adjusted HR=1.01 per mmHg PP, 95%CI=0.99, 1.01).

Conclusions:
Higher cfPWV, but not higher PP, was significantly associated with incident dementia in the older adults. Interventions to slow arterial stiffness with aging may reduce the risk of dementia among older individuals.
Abstract P015: Objectively Measured Step Counts Was Independently Associated With Higher Cognition in Apparently Healthy Japanese Men
Authors: Shibukawa Takeshi , Fujiyoshi Akira , Miura Katsuyuki , Miyagawa Naoko , Saito Yoshino , Zaid Maryam , Hisamatsu Takashi , Ohkubo Takayoshi , Arima Hisatomi , Tooyama Ikuo , Ueshima Hirotsugu ,   the SESSA Rsch Group
Published: July 2021

Introduction:
A positive association between physical activity and cognition has been reported. However, very few pertinent studies have evaluated physical activity by objective measures.

Hypothesis:
In a community-based sample of non-demented men, objectively measured step count was positively associated with higher cognitive function.

Methods:
The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited community-dwelling apparently healthy men aged 40-79 years from Shiga, Japan, and measured their step counts over 7 consecutive days using a pedometer (DIGI-Walker, DW-200) at baseline (2006-08). Among 853 mem who returned for follow-up (2010-12), we assessed their cognition using Cognitive Abilities Screening Instrument (CASI) score. The score can range from 0 to 100, and higher score indicates better cognition. We restricted our analyses to those with a valid 7-day average step count at baseline and who remained free of stroke (N=678). We calculated crude and adjusted mean CASI score according to quartile of average step count using linear regression models. All adjusting covariates used in models were asssessed at baseline including age, educational attainment, smoking, and drinking.

Results:
The mean [standard deviation] of age and unadjusted score were 63.8 [9.1] years and 90.8 [5.8]. Mean CASI score was higher in higher quartile of average step: 90.2, 90.4, 90.6, and 91.8 from the lowest to the highest quartile of average step (
P
for trend =0.004) in a model adjusted for age and education. Further adjustment for smoking, drinking and other cardiovascular risk factors resulted in similar pattern of association (Table 1).

Conclusions:
Apparently healthy Japanese men with greater 7-day average step count at baseline measured with pedometer was associated with a small but significantly higher CASI score than those with fewer step count. The finding is consistent with the hypothesis that physical activity is protective for cognition in non-demented individuals.
Abstract P022: The Association of Sleep Apnea With Atrial Fibrillation and Ectopy Using Ambulatory Electrocardiogram in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Gellert Kapuaola S , Alonso Alvaro , Chen Lin Y , Meyer Michelle L , Soliman Elsayed Z , Suzuki Takeki , Loehr Laura
Published: July 2021

Introduction:
Sleep apnea (SA) is associated with burden of atrial fibrillation (AF), but studies of SA and ectopic beats, potential triggers of AF, are sparse. Our study contributes by examining the association of SA with AF, premature atrial contractions (PACs), and premature ventricular contractions (PVCs) from 48-hour continuous ambulatory electrocardiogram (aECG) monitoring.

Methods:
The study population includes 716 black and 438 white participants from the ARIC 48-hour aECG ancillary study, after excluding those with a paced rhythm (n=43) or poor quality measures (n=8). SA was defined as self-reported physician diagnosis or hospital discharge records with ICD-9-CM codes for SA. Prevalent AF was defined using 48-hour aECG monitoring, study visit ECGs, or hospital discharge code (427.3) since study baseline in 1986-1987. PACs and PVCs were defined if ectopy was present 1-5% (occasional) and >5% (frequent) of the recording time versus <1% of the recording time (referent). Multivariable logistic regression was used to examine this association with inverse variance weighting to account for the sampling and non-response.

Results:
Participants with SA (unweighted N=217) were more likely to be female (55%), white race (52%), current smokers (57%), have hypertension (82%), and be obese (57%). Participants with SA were 7.3 (95% CI: 3.7, 14.5) times more likely to have AF compared to those without SA after adjusting for covariates. Compared to participants without SA, the relative odds of occasional and frequent PACs versus the referent was increased by 20% and 50% respectively among participants with SA after adjusting for confounders, although not statistically significant. The association was similar and not statistically significant for frequent PVCs.

Conclusions:
In a community-based population using standardized 48-hour aECG monitoring, SA was associated with prevalent AF, but not significantly associated with PACs or PVCs. Further study is needed to establish mechanisms that link SA and cardiac arrhythmias.
Abstract P028: High Framingham General Cardiovascular Disease Risk Scores in Victims of Out of Hospital Sudden Death
Authors: Khant Kyaw , Mirzaei Mojtaba , Joodi Golsa , Bogle Brittany M , Flowers Jessica P , Patel Samip M , Lin Feng-Chang , Simpson Ross J
Published: July 2021

Introduction:
Individuals with a history of cardiovascular disease (CVD) have a high risk of out-of-hospital sudden unexpected death (OHSUD). However, most OHSUDs occur in victims without a prior history of CVD. Information on CVD risk in these victims is scarce.

Hypothesis:
We hypothesized that OHSUD victims who had no prior diagnosis of CVD have higher 10-year CVD risk compared to a matched living control population.

Methods:
OHSUD cases were adjudicated from all emergency medical service attended out-of-hospital deaths aged 30-64 in Wake County, NC between 2013-2015. Age group and gender-matched controls were randomly selected from Wake County residents who visited a local healthcare facility over the same period (~3:1 match ratio). We obtained two years of medical records prior to death (cases) or last visit (controls). After excluding individuals with a history of CVD, we calculated the 10-year risk of CVD for each subject using the published general CVD algorithms by D'Agostino et al. Risk was classified into low (<6%), moderate (6%-20%), and high (>20%).

Results:
Among subjects without CVD, we included 106 cases and 414 controls who had sufficient data for calculating Framingham risk score. Gender distribution was similar in both case and control groups. The average 10-year risk of CVD was higher for OHSUDs than controls (29% vs. 16%, p=<0.0001). Similar results were found in both men (34% vs. 19%, p=<0.0001) and women (11% vs. 7.3%, p=0.0005). A larger proportion of OHSUDs were considered “high risk” compared to controls (57% (60 of 106) vs. 28% (114 of 414), p=<0.001). This finding remained significant when stratified by gender (Figure).

Conclusion:
The majority of out of hospital sudden death victims without known CVD are at high risk of cardiovascular disease. This finding bolsters the essential role of office-based risk assessment tools in identifying high risk patients antemortem. Targeted interventions for intensive CVD risk reduction may lead to a decrease in sudden deaths.
Abstract P035: Feasibility of Stretching Exercise for Prevention of Late-Onset Preeclampsia: A Pilot Trial
Authors: Caughey Melissa C , Cho Joyce S , Wu Ya-Ke , Nix W. B , Yeo SeonAe
Published: July 2021

Background:
Preeclampsia is a leading cause of maternal morbidity and perinatal mortality. Manifestations include hypertension, proteinuria, and end-organ dysfunction in the latter half of pregnancy. The United States Preventive Services Task Force recommends low-dose aspirin as a modestly effective preventive treatment; however, no conclusive prevention is currently available. Moderate to vigorous physical activity is reported to reduce preeclampsia risk, but is increasingly difficult by the 3
rd
trimester. Further, intense exercise may stimulate sympathetic overactivation, a precursor of late-onset (≥34 weeks gestation) preeclampsia associated with maternal obesity. Stretching exercise may be a feasible alternative to intense exercise, and more readily adopted by obese women at risk of late-onset preeclampsia. We hypothesized that stretching exercise would suppress sympathetic overactivity and enhance parasympathetic tone in pregnant women.

Methods:
Gravid women were recruited with informed consent for stretching exercise and cardiovascular testing during the 2
nd
to 3
rd
trimester of pregnancy. Exercises were standardized by video demonstration, and targeted 14 major muscle groups in the lower and upper extremities. Each muscle group was stretched for 20 seconds in 3 repetitions. Blood pressure, carotid-femoral pulse wave velocity (PWV), and heart rate variability (HRV) were acquired before and after stretching, with baseline values preceded by a 15 minute rest. Heart rate and HRV were averaged over 10 minute acquisitions. Total HRV variance was stratified into low frequency (LF; < 0.15 Hz) and high frequency (HF; ≥ 0 .15 Hz) domains, with HF reflecting parasympathetic nerve activity and LF dominated by sympathetic activity. Sympathovagal balance was estimated by the LF/HF ratio. Pre- and post-exercise measurements were compared by paired t-tests.

Results:
A total of 20 women consented to enrollment; all completed stretching exercise and cardiovascular testing without complications. On average, study participants were 32 years old, 27 weeks pregnant, and had a BMI of 29 kg/m
2
. Over a third (35%) had a BMI > 30 kg/m
2
. Significant reductions between pre- and post-exercise were observed for mean diastolic blood pressure (60 vs. 57 mmHg; p=0.02) and heart rate (78 vs. 75 bpm; p<0.0001). However, mean systolic blood pressure was not significantly changed (104 vs. 105 mmHg; p=0.2), nor was mean PWV (5.3 vs. 5.2 m/s; p=0.4). Although non-significant, the mean LF/HF ratio decreased (2.4 vs. 1.7 Hz; p=0.3), suggesting parasympathetic dominance post-exercise.

Conclusion:
This pilot study demonstrates stretching exercise is well-tolerated by pregnant women in the 2
nd
or 3
rd
trimester, and may be a feasible prevention for obese women at risk of late-onset preeclampsia. A randomized controlled trial investigating outcomes of routine stretching exercise in pregnancy is warranted.
Abstract P036: Effects of Exercise Training and Increasing Non-Exercise Physical Activity on Lipoprotein Subclass and Size: Results From the I-CAN Study
Authors: Swift Damon L , Sarzynski Mark A , McGee Joshua , Barefoot Savanna , Brophy Patricia M , Nevels Tyara , Lutes Lesley , Houmard Joseph
Published: July 2021

Introduction:
Previous studies have shown that lipoprotein particle size and lipoprotein subclasses are associated with cardiovascular and type 2 diabetes risk, and have independent prognostic value above traditional lipid concentrations. The impact of exercise training and increasing non-exercise physical activity on lipoprotein subclasses and size has not been previously investigated.

Methods:
In this pilot study, 35 obese adults were randomized to aerobic exercise training (50-75% of VO
2
max) (AERO, n=11), aerobic training and increasing non-exercise physical activity (AERO-PA, n=10, ~3,000 steps above baseline levels), or a non-exercise control group (n=14) for 6 months. Baseline and follow-up blood samples were analyzed for lipoprotein subclass, size, and lipoprotein insulin resistance score (LP-IR) using nuclear magnetic resonance spectroscopy (Liposcience, NC). Analysis of covariance was used to evaluate the change in outcome variables following the intervention across groups with adjustment for baseline value and age. Participants who changed lipid medications during the intervention (n=2) or who were non-adherent to exercise training (n=2) were excluded from the analysis.

Results:
Significant reductions were observed for mean VLDL size in the AERO-PA group (-4.7 nm, CI: -8.7 to -0.8) compared to control group (0.7 nm, CI: -2.7 to 4.4) and the AERO group (1.1 nm, CI: -2.9 to 5.0). Reductions in triglyceride concentrations were observed in the AERO-PA group (-28.3 mg/dL, CI: -50.3 to -6.4) compared to control (4.1 mg/dL, CI: -14.6 to 22.8). Additionally, we observed a trend for LP-IR index (p=0.055) and the concentration of small HDL particles (p=0.093) to decrease in the AERO-PA group compared to controls, with no differences compared to the AERO group (p>0.10). No significant changes were observed for other notable lipoprotein measures, such as LDL size, HDL size, concentration of small LDL particles, or chylomicron measures (p>0.05). In the AERO-PA group, the change in steps was associated with the change in LP-IR index (r= -0.71, p=0.013), but not with change in VLDL size (r= -0.24, p=0.463) or triglyceride concentrations (r=-0.28, p=0.388).

Conclusions:
Aerobic training combined with increasing non-exercise physical activity leads to favorable changes in the lipoprotein profile, specifically reductions in VLDL size and triglycerides, and may have promise for other lipoprotein traits (reductions in LP-IR and small HDL particles) that were not observed with aerobic training alone.