bluuebunny/crossref_metadata_2025 huggingface dataset:
РОЛЬ ІНТЕРАКТИВНИХ МЕТОДІВ В ОПТИМІЗАЦІЇ ПРОЦЕСУ ВИКЛАДАННЯ ДИСЦИПЛІНИ «ЕТИКА ТА ДЕОНТОЛОГІЯ У ФАРМАЦІЇ»
Authors: Stechyshyn I. P. , Denys A. I.
Published: March 2020

У статті наведено застосування методу «Інтерактивна дискусія» під час проведення семінарського обговорення з дисципліни «Етика та деонтологія у фармації» зі студентами фармацевтичного факультету першого року навчання. Зазначено, що використаний метод дав можливість всебічно розглянути поставлені проблеми та однаковою мірою залучити до їхнього обговорення всіх учасників, незалежно від їх рівня підготовки, здібностей, характеру тощо. Це є важливою перевагою, оскільки при традиційному підході до проведення заняття, враховуючи складність матеріалу, наповненість групи та тривалість заняття (1,5 год), досить складно якісно опитати та оцінити усіх студентів. Разом з тим, засвоєння усіма студентами навчального матеріалу у повному обсязі є важливим елементом при підготовці кваліфікованих фармацевтичних фахівців.

Сьогодні конкурентне середовище вимагає від провізорів знань та успішного застосування стандартів обслуговування, володіння комерційними технологіями, психологією продаж, навичок умілої презентації, вміння володіти конфліктною ситуацією та ін. Адже досить часто споживачі розлючені через відсутність потрібного препарату чи надмірно високу його ціну, створюючи конфліктну ситуацію. Успішне вирішення таких проблем можливе за умови етичної поведінки та культурного спілкування фармацевтичного фахівця у конкретній ситуації.

У статті описано обговорення ситуаційних задач як елементу методу «Інтерактивна дискусія». Для їх опрацювання учасники були поділені на групи і виконували послідовні кроки: «Робота в парах», «Рольова гра», «Пошук рішення» і «Написання есе». У відповідях студенти виявляли творчий підхід до вирішення ситуаційних задач, розглядаючи їх з різного ракурсу (пацієнта, провізора, керівника аптеки, лікаря). На завершення семінарського заняття проводилось опитування студентів («Плюси, мінуси, запитання») щодо доцільності використання даного методу у викладанні предмета «Етика та деонтологія у фармації». Студенти оцінили продуктивність роботи в команді позитивно.
Abstract 01: Retinal Microvascular Signs and White Matter MRI Findings: The Atherosclerosis Risk in Communities Neurocognitive Study
Authors: Deal Jennifer A , Power Melinda C , Bandeen-Roche Karen , Griswold Michael , Knopman David , Mosley Thomas , Walker Keenan , Gottesman Rebecca F , Sharrett A. Richey
Published: March 2020

Introduction:
Cerebrovascular small vessel disease, seen on brain imaging as lacunes and white matter hyperintensities (WMH), is a substrate for dementia in older adults. Diffusion tensor imaging (DTI) is thought to provide early signs of loss of white matter (WM) integrity due to microvascular disease and predicts WM hyperintensity volume. Retinal fundus photography provides surrogate measures of cerebral microvasculature. No studies have quantified the long-term association between retinal signs and DTI measures.

Hypothesis:
Microvascular retinal signs measured in midlife are associated with small vessel disease measured on brain magnetic resonance imaging (MRI) 18 years later, including reduced WM microstructural integrity (lower fractional anisotrophy [FA] and greater mean diffusivity [MD] by DTI), greater WM hyperintensity volume and greater lacune prevalence.

Methods:
In a biracial prospective cohort study, retinal signs were measured using fundus photography (1993-1995) with 3-T magnetic resonance imaging conducted in 2011-13. Multivariable-adjusted linear regression was used to quantify the relationships of retinal signs with WM measures. Prevalence of lacunar infarcts by retinal sign status was estimated using log binomial regression. Analyses were adjusted for age [linear and quadratic terms], education, sex, race, intracranial volume, body mass index, smoking, diabetes, hypertension, and ≥1
APOE
ε4 alleles.

Results:
In 1829 men and women (60% [N=1100] female, 27% [N=489] black race, aged 50-72 years when retinal signs were measured), a binary measure comprised of two retinal signs suggestive of arteriolar damage due to hypertension (focal arteriolar narrowing and/or arteriovenous nicking) was associated with worse (lower) FA (standardized β=-0.19, 95% confidence interval [CI]=-0.35, -0.02), worse (higher) MD (β=0.15, 95% CI=0.00, 0.30), greater WM hyperintensity volume (β=0.15, 95% CI=0.01, 0.30), and greater prevalence of lacunes (prevalence ratio=1.33, 95% CI: 0.99, 1.80). Generalized arteriolar narrowing, measured as the central retinal arteriolar equivalent (CRAE, narrowest quartile vs. widest three quartiles) was associated with worse FA (β=-0.13, 95% CI=-0.24, -0.01) and worse MD (β=0.12, 95% CI=0.01, 0.23). Results did not differ by sex, race, hypertension status or
APOE
ε4 genotype. No associations were found for retinopathy, but only 56 participants had retinopathy.

Conclusions:
Consistent with prior work, and as expected based on a common underlying pathology, retinal signs predicted WM disease and lacunar infarcts 18 years later. Novel to this study, we found that retinal signs related to arteriolar damage also predicted loss of white matter microvascular integrity measured using DTI.
Abstract 10: Serum Metabolomic Signatures of Multiple Healthful Dietary Patterns and Incident Cardiometabolic Diseases in US Hispanics/Latinos
Authors: Chen Guochong , Chai Jin Choul , Shan Zhilei , Yu Bing , Mossavar-Rahmani Yasmin , Sotres-Alvarez Daniela , Mattei Josiemer , DAVIGLUS Martha L , Burk Robert , Boerwinkle Eric , Kaplan Robert , Hu F , Qi Qibin
Published: March 2020

Introduction:
Healthful dietary patterns are associated with lower cardiometabolic risk, but the underlying mechanisms are not fully understood.

Hypothesis:
Healthful dietary patterns share widespread metabolomic signatures that are associated with altered risk of cardiometabolic diseases.

Methods:
We analyzed data from 2976 adult participants free of diabetes and CVD in the Hispanic Community Health Study/Study of Latinos. Scores of three USDA recommended dietary patterns, Healthy Eating Index (HEI)-2015, alternative Mediterranean diet (aMED), and healthful plant-based dietary index (hPDI) were calculated by averaging two 24-hour dietary recalls. Fasting serum metabolomics was performed using an untargeted approach. Dietary pattern associated metabolite modules were clustered using a weighted correlation network analysis, and their associations with 6-year incidence of diabetes and hypertension were further examined.

Results:
Of 624 known metabolites identified, some were uniquely associated with a single dietary score, while 51 metabolites were significantly associated with all dietary scores (
Figure A
). Eight metabolite modules were clustered based on 184 dietary pattern-related metabolites. Each dietary score was associated with one unique metabolite module, and two modules composed of antioxidants or polyunsaturated fatty acids (PUFA) were associated with all dietary scores (
Figure B
). After multivariable adjustment for demographics, socioeconomics, lifestyles, and BMI, the antioxidant module was significantly associated with lower risk of diabetes (per SD, relative risk (RR) = 0.80 [95% CI 0.69-0.96]) and risk of hypertension (per SD, RR= 0.85 [0.73-0.99]), whereas the PUFA module was not associated with either outcome.

Conclusions:
Metabolomic signatures positively relating to three common healthful dietary patterns are found to be associated with lower incident cardiometabolic diseases, providing some mechanistic insights into the cardioprotection of high-quality diets.
Abstract 15: Trends in Atrial Fibrillation-related Cardiovascular Mortality Rates in The United States: 1999-2017
Authors: Tanaka Yoshihiro , Shah Nilay , Passman Rod , Greenland Philip , Khan Sadiya
Published: March 2020

Background:
Atrial fibrillation (AF) is the most common sustained arrhythmia in adults and the prevalence is increasing due to the aging of the population and the growing burden of vascular risk factors. Although deaths due to cardiovascular disease (CVD) death have dramatically decreased in recent years, trends in AF-related CVD death has not been previously investigated.

Purpose:
We sought to quantify trends in AF-related CVD death rates in the United States.

Methods:
AF-related CVD death was ascertained using the CDC WONDER online database. AF-related CVD deaths were identified by listing CVD (I00-I78) as underlying cause of death and AF (I48) as contributing cause of death among persons aged 35 to 84 years. We calculated age-adjusted mortality rates (AAMR) per 100,000 population, and examined trends over time estimating average annual percent change (AAPC) using Joinpoint Regression Program (National Cancer Institute). Subgroup analyses were performed to compare AAMRs by sex-race (black and white men and women) and across two age groups (younger: 35-64 years, older 65-84 years).

Results:
A total of 522,104 AF-related CVD deaths were identified between 1999 and 2017. AAMR increased from 16.0 to 22.2 per 100,000 from 1999 to 2017 with an acceleration following an inflection point in 2009. AAPC before 2009 was significantly lower than that after 2009 [0.4% (95% CI, 0.0 - 0.7) vs 3.5% (95% CI, 3.1 - 3.9), p < 0.001). The increase of AAMR was observed across black and white men and women overall and in both age groups (FIGURE), with a more pronounced increase in black men and white men. Black men had the highest AAMR among the younger decedents, whereas white men had the highest AAMR among the older decedents.

Conclusion:
This study revealed that death rate for AF-related CVD has increased over the last two decades and that there are greater black-white disparities in younger decedents (<65 years). Targeting equitable risk factor reduction that predisposes to AF and CVD mortality is needed to reduce observed health inequities.
Abstract 17: Comparative Effectiveness of Implementation Strategies on Cardiovascular Risk Factor Control in Patients With Diabetes: The D4C Cluster Randomized Trial
Authors: He Jiang , Shi Xiulin , Lin Mingzhu , Liu Changqin , Yan Bing , Song Haiqu , Wang Caihong , Xiao Fangsen , Huang Peiying , Wang Liying , Zhang Mulin , Huang Yinxiang , Li Weihua , Yang Shuyu , Yao Guanhua , Li Xuejun
Published: March 2020

Objectives:
Uncontrolled blood glucose, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) are major risk factors for premature death and cardiovascular disease (CVD) in patients with diabetes. We compared the effectiveness of team-based care (TBC) with clinical decision support systems (CDSS) versus TBC alone on CVD risk factor control among patients with diabetes in China.

Methods:
In the Diabetes Complication Control in Community Clinics (D4C) cluster randomized trial, 38 community health centers were randomly assigned to TBC-CDSS (primary care physician-health educator-diabetes specialist collaborative care plus guideline-based treatment protocol implemented in CDSS) or TBC alone in Xiamen City, China. A total of 11,132 patients (5378 in TBC-CDSS and 5754 in TBC) aged ≥50 years with uncontrolled diabetes and additional risk factors (dyslipidemia, hypertension, or clinical CVD) were recruited. The intervention lasted for 18 months, and study data were collected at 6, 12, and 18 months after baseline.

Results:
Mean baseline age (62.6 vs. 63.1 years), body mass index (24.9 vs. 24.9 kg/m
2
), HbA1c (8.8 vs. 8.7%), LDL-C (121.2 vs. 121.1 mg/dL), systolic BP (136.6 vs. 136.9 mm Hg) and diastolic BP (79.7 vs. 79.8 mmHg) were comparable between TBC-CDSS and TBC alone groups. About 87.1% of participants in the TBC-CDSS group and 84.1% in the TBC alone group completed the 18-month intervention. Both TBC-CDSS and TBC alone significantly reduced HbA1c, LDL-C, and BP over the 18-month follow-up (all P<0.0001). Furthermore, the proportions of controlled HbA1c, LDL-C, and BP, as well as all 3 risk factors, were significantly higher in the TBC-CDSS group compared to the TBC alone group (Table).

Conclusions:
As compared with team-based care alone, team-based care plus a guideline-based treatment protocol implemented in clinical decision support systems further reduces CVD risk factors in patients with diabetes. (ClinicalTrials.gov number, NCT02835287)
Abstract 18: Gut Microbiome Modifies the Protective Effects of a Mediterranean Dietary Pattern Against Diabetes Mellitus in US Hispanics/ Latinos: The Hispanic Community Health Study/ Study of Latinos (HCHS/SOL)
Authors: Wang Dong , Qi Qibin , Wang Zheng , Usyk Mykhaylo , Sotres-Alvarez Daniela , Mattei Josiemer , Tamez Martha , Gellman Marc , DAVIGLUS Martha L , Hu Frank B , Knight Rob , Burk Robert , Kaplan Robert
Published: March 2020

Introduction:
Little is known about whether the effect of a healthy diet on diabetes mellitus (DM) is modified by the gut microbiome in human.

Hypothesis:
We hypothesize that the gut microbiome modifies the inverse association between the Mediterranean diet (MedDiet) and risk of DM.

Methods:
This study included 543 DM cases, 805 with impaired glucose tolerance (IGT) and 394 with normal glucose regulation (NGR) in adults 23-83yrs old from the HCHS/SOL. Fecal samples were profiled using 16s rRNA gene sequencing. We applied QIIME 2 to cluster sequences into OTUs and assign taxonomies, and PICRUSt to predict metagenomic gene functions. Adherence to the MedDiet was evaluated by a MedDiet index using the average of two 24-hr dietary recalls. We applied MaAsLin2 to quantify associations between the MedDiet index and microbial features with adjustment for confounding factors listed in the caption of Fig. 1.

Results:
MedDiet was associated with phylogenetically diverse, rare, and abundant gut microbes (Fig. 1a). For example, a higher MedDiet index was associated with a higher relative abundance of
Faecalibacterium Prausnitzii
[FDR-adjusted
p (q)
=0.002], but a lower relative abundance of
Collinsella aerofaciens
(
q
=0.009). We found that several microbial functions related to plant-derived polysaccharide degradation such as fructuronate reductase (
q
=0.02), and short-chain fatty acid fermentation such as butyryl-CoA dehydrogenase (
q
=0.002) were enriched in participants with higher MedDiet index. We found that the inverse association between MedDiet and risk of DM was more pronounced in participants with greater abundance of
Prevotella
copri
, but weaker in participants whose gut microbial communities were dominated by
Bacteroides
(
P
interaction
=0.02 for IGT/DM vs NGR, Fig. 1b).

Conclusions:
Adherence to the MedDiet is associated with diverse gut microorganisms and microbial functions. The inverse association between MedDiet and risk of DM might be modified by gut microbiome composition.

1
Abstract 19: Cost-effectiveness of the Stepwise Approach to Diabetes Prevention in India
Authors: Islek Duygu , Weber Mary Beth , Anjana Ranjit Mohan , Mohan Viswanathan , Staimez Lisa R , Harish Ranjani , Narayan K.M. Venkat , Laxy Michael , Ali Mohammed K
Published: March 2020

Introduction:
Expert guidelines recommend a stepwise approach (lifestyle modification followed by addition of metformin in those not meeting goals) in high-risk people to delay progression to diabetes. However, there is scant evidence on the cost-effectiveness of implementing stepwise diabetes prevention. We estimated the 3-year within trial cost-effectiveness of a stepwise diabetes prevention approach in the Diabetes Community Lifestyle Improvement Program (D-CLIP) study in Chennai, India.

Hypothesis:
We assessed the cost-effectiveness of a stepwise diabetes prevention approach in India.

Methods:
The D-CLIP study was a randomized, controlled, translation trial in 578 overweight/obese Asian Indian adults with isolated impaired glucose tolerance (IGT) and/or isolated impaired fasting glucose (IFG), comparing a 6-month lifestyle modification curriculum and stepwise addition of metformin vs. standard lifestyle advice. We assessed direct medical costs including costs to deliver the intervention, general health care utilization, and direct non-medical costs. We also calculated costs for screening which included identifying and recruiting eligible individuals with IGT and/or IFG. Health effects were measured as absolute reductions in cumulative diabetes risk and in quality adjusted life years (QALYs) gained. Generalized linear regressions models adjusted for age, sex and baseline levels were fitted to estimate incremental costs and health effects. Bootstrapping was applied to describe the uncertainty around incremental cost-effectiveness ratios (ICER).

Results:
Over 3 years, the intervention resulted in incremental direct medical costs of 211 USD; incremental direct non-medical costs of 34 USD, an absolute diabetes risk reduction of 10.2%, and incremental QALYs gained of 0.098 per person. The absolute diabetes risk reduction in people with IFG was 6.4%, with IGT was 9% and with both IFG and IGT was 8.1%. ICERs from a multi-payer perspective (including the screening costs) averaged 4,275 USD per diabetes case prevented/delayed. That figure was 5,220 USD in people with IFG, 2,627 USD with IGT and 3,312 USD with both IFG and IGT. ICERs from a multi-payer perspective (including the screening costs) averaged 4,472 USD per QALY gained. That figure was 4,589 USD in people with IFG, 4,270 USD with IGT and 4,335 USD with both IFG and IGT. ICERs from a societal perspective were slightly higher. In the sensitivity analysis, with the scenario of a 50% increase/decrease in screening and intervention costs, from a multi-payer perspective, the average of ICERs varied 1,907 to 6,420 USD per diabetes case prevented, from 1,995 to 6,715 USD per QALY gained.

Conclusions:
In conclusion, a stepwise approach for diabetes prevention is likely to be cost-effective over a three-year time horizon.
Abstract 28: Regular Aerobic Exercise Counteracts Endothelial Vasomotor Dysfunction Associated With Insufficient Sleep
Authors: Stockelman Kelly A , Bain Anthony R , Dow Caitlin A , Greiner Jared J , Stauffer Brian L , Desouza Christopher A
Published: March 2020

Insufficient sleep, defined as chronic short sleep duration (<7 h/night), is an independent risk factor for cardiovascular disease (CVD). We have previously demonstrated that insufficient sleep is associated with reduced endothelium-dependent vasodilation and enhanced endothelin (ET)-1-mediated vasoconstrictor tone. Impaired endothelial vasomotor regulation is thought to contribute mechanistically to the increased risk of atherosclerotic vascular disease incurred with chronic insufficient sleep. Regular aerobic exercise is an effective lifestyle strategy for improving endothelial function and, in turn reducing cardiovascular risk. It is currently unknown if regular aerobic exercise can counteract the negative impact of insufficient sleep on endothelial vasomotor regulation. We tested the hypotheses that regular aerobic exercise would: 1) improve endothelial vasodilation; and 2) decrease ET-1-mediated vasoconstrictor tone in middle-aged adults who chronically sleep less than 7 h/night. We studied 36 healthy, middle-aged adults: 16 with normal sleep duration (10M/6F; age: 57±2 yr; sleep duration: 7.4±0.1 h/night) and 20 with short sleep duration (11M/9F; 56±1 yr; sleep duration: 6.2±0.1 h/night). The 20 short sleepers completed a 3-month aerobic exercise training intervention. Forearm blood flow (FBF; plethysmography) was determined in response to intra-arterial doses of acetylcholine (ACh), sodium nitroprusside (SNP), BQ-123 (ET
A
receptor antagonist) and ACh + BQ-123 in both groups and after the exercise intervention in the short sleepers. As expected, forearm vasodilator responses to ACh were lower (20%; P<0.05) in the short (from 4.2±0.2 to 10.5±0.6 mL/100 mL tissue/min) vs normal (4.2±0.2 to 12.7±0.6 mL/100 mL tissue/min) sleepers. FBF responses to SNP were comparable between the groups. In response to BQ-123, short sleep group had a greater increase in resting FBF than normal sleep group (~25% vs ~8%; P< 0.05). ACh+BQ-123 resulted in an ~25% increase in the ACh-vasodilation in the short sleep group only. After exercise training, although nightly sleep duration was not affected (6.4±0.1 h/night), ACh-mediated vasodilation was ~20% higher (P<0.05), ET-1-mediated vasoconstriction was ~90% lower (P<0.05) and vasodilator response to ACh was not significantly increased with ET
A
receptor blockade. These results indicate that regular aerobic exercise can reverse the negative influence of insufficient sleep on endothelial vasomotor function, independent of changes in nightly sleep duration.
Abstract 29: Metabolomic Signatures of Sedentary Behavior and Cardiometabolic Traits in US Hispanics/Latinos: Hispanic Community Health Study / Study of Latinos (HCHS/SOL)
Authors: Chai Jin Choul , Moon Jee-Young , Yu Bing , Chen Guochong , Graff Mariaelisa , DAVIGLUS Martha L , Chan Queenie M , Thyagarajan Bharat , Castaneda Sheila , Grove Megan , Xue Xiaonan , Boerwinkle Eric , Kaplan Robert , Qi Qibin
Published: March 2020

Introduction:
Sedentary behavior is associated with cardiometabolic risk independent of physical activity, but the underlying mechanisms are not fully understood.

Hypothesis:
Sedentary behavior may influence serum metabolite profiles which are associated with cardiometabolic risk factors.

Methods:
The analyses included 2711 participants (43% men) of the HCHS/SOL aged 18 to 74 years, free of CVD and other major chronic diseases. Serum metabolomics was performed using an untargeted approach. Physical activity and sedentary behavior were measured by accelerometer (Actical) for a 7-day period. Survey linear regressions were used to examine associations between sedentary behavior and metabolites. Metabolite scores were calculated by summing up z-scores of significant metabolites within the same sub-pathway.

Results:
Of 624 known metabolites, 95 were significantly associated with sedentary behavior (
P
<0.05 after FDR correction), adjusting for socioeconomic and lifestyle factors including moderate to vigorous physical activity (
Figure 1A
). The majority of significant metabolites were clustered into 7 sub-pathways. Three sub-pathway scores (branched-chain amino acids [BCAA], acylcarnitine and medium-chain fatty acid metabolism) were positively associated with sedentary behavior, while the other 4 sub-pathway scores (acylcholine, plasmalogen, nicotinate, and arginine) were inversely associated with sedentary behavior. Among these scores, the BCAA score showed unfavorable correlations with all cardiometabolic traits including obesity measures, glycemic traits, blood lipids and blood pressure. The acylcholine score showed favorable correlations with obesity measures and glycemic traits, though positive correlations with blood lipids were observed (
Figure 1B)
.

Conclusions:
Our study identified multiple serum metabolites associated with sedentary behavior independent of physical activity, suggesting potential mechanistic links between sedentary behavior and cardiometabolic diseases.
Abstract 39: Development of a Hypoglycemia Prediction Model for Veterans With Diabetes Using Supervised Machine Learning Applied to Electronic Health Record Data
Authors: Raghavan Sridharan , Liu Wenhui , Baron Anna , Saxon David , Plomondon Meg , Ho Michael , Caplan Liron
Published: March 2020

Accurate assessment of hypoglycemia risk is critical for treatment selection in individuals with diabetes and cardiovascular disease (CVD) - patients for whom hypoglycemia is particularly harmful. We developed and validated a hypoglycemia prediction model in diabetes patients with and without CVD using data routinely available in electronic health records (EHR) and compared performance to a published prediction model. We studied 128,893 US Veterans with diabetes and angiographic assessment of CVD from 2005 to 2018. We used a random 2/3 of the sample for model development and the remaining 1/3 for validation. The primary outcome was severe hypoglycemia based on a previously validated algorithm that uses diagnosis codes and glucose measurements. We evaluated 33 potential predictors, including demographics, diabetes-related variables, comorbidities, and CVD risk factors. We sequentially used two machine learning algorithms for model development. First, we used multivariable adaptive regression splines, which can accommodate interactions and non-linearities for continuous variables, to select predictors. Second, we used adaptive elastic net, which can accommodate time-to-event outcomes, to fit a model with the selected variables. We tested model discrimination using the area under the ROC curve (AUC) and calibration by plotting predicted versus observed event rates in the independent validation cohort. The best-fitting prediction model included 18 predictors; a history of hypoglycemia was the strongest predictor (Table). In external validation, AUC was 0.729 for 2-year events, and the slope of the calibration curve was 1.05, exceeding performance of the published model in this patient population for both discrimination and calibration (Table).

Conclusions:
Applying supervised machine learning to EHR data may provide an efficient approach to tailoring prediction of preventable clinical outcomes, e.g., hypoglycemia, for high risk patients receiving care in an integrated healthcare system.
Abstract 40: Empirical Comparison of Approaches to Mediation Analyses in Nutrition Research With Applications to the Quality Cohort
Authors: Suissa Karine , Benedetti Andrea , Henderson Melanie , Gray-Donald Katherine , Paradis Gilles
Published: March 2020

Background:
Adiposity may mediate the effect of dietary glycemic load (GL) on lipid profile in children as studies have shown an association between dietary GL and adiposity and between adiposity and lipid profiles. While several approaches for conducting mediation analysis have been proposed, given the strict assumptions and restrictions for each method, it is not clear which method is ideal in nutrition research. Our objective was to compare the conventional approach and the causal approach using marginal structural models (MSM) with inverse probability weights (IPW) to examine adiposity as a mediator in the association between baseline dietary GL and lipid profile after 2 years.

Methods:
The QUALITY cohort included 630 children, 8-10 years at recruitment with at least one obese parent followed-up 2 years later. Three separate 24-hour dietary recalls were administered by a dietitian at baseline. Child and parent characteristics were obtained through direct measurement (blood lipids, anthropometrics) or questionnaires (socio-economic characteristics). Indicators of adiposity, including BMI z-score and percent fat mass, were the mediators of interest. A conventional approach of statistical adjustment for the mediator was used. As well, we used MSM to estimate the controlled direct effect (CDE) between GL and blood lipids 2 years later not mediated by adiposity. The MSM models were constructed using IPW truncated at 5-95 percentile.

Results:
Mean age of children at baseline was 9.6 years and 33% were overweight or obese. Both mediation analysis methods revealed that most of the effect of GL on blood lipids was mediated by adiposity. Results obtained from both methods differed; while the MSM with IPW did not show evidence of a direct effect of GL on TG not via percent fat mass (TG: β=0.06, 95%CI=-0.01, 0.12; HDL: β=-0.01, 95%CI=-0.04, 0.03), the conventional method did (TG: β=0.03, 95%CI=0.003, 0.06; HDL: β=-0.02, 95%CI=-0.03, -0.001).

Conclusion:
In conclusion, our results suggest that adiposity contributes substantially to the association between GL and blood lipids after 2 years. MSM with IPW may not be appropriate in nutritional studies with small sample sizes.
Abstract MP01: Multiple Social Determinants of Health Disparities Increase the Risk of Diabetes and Mortality in the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Ringel Joanna B , Carson April P , Cummings Doyle M , Pena Jessica , Gamboa Christopher , Schroff Praful , Safford Monika M
Published: March 2020

Introduction:
The Healthy People 2020 initiative proposed that social determinants contribute to disparities in health outcomes. While studies have documented the influence of individual social determinants of health (SDOH) on health outcomes, few studies have examined how the aggregation of multiple SDOH within the same person affect health.

Hypothesis:
We hypothesized that as the number of individual-level and neighborhood-level SDOH increased, the relative risk of incident diabetes and mortality also increased.

Methods:
This study included 15,310 black and white adults aged
>
45 years at baseline (2003-2007) who did not have prevalent diabetes and who completed the 10 year follow-up exam (2014-2016) or died prior to follow-up in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Exposures included 6 SDOH which have been associated with increased health risks: annual household income <$35,000, black race, < high school education, lack of health insurance, residing in a zip code with ≥ 25% poverty, and living in a state with poor public health infrastructure for 10 years prior to 2003. Outcomes were all-cause mortality or incident diabetes, defined as fasting glucose >126 mg/dL, random blood glucose >200 mg/dL, or taking diabetes medication or insulin. Multinomial logistic regression models examined associations of number of SDOH with death and incident diabetes, adjusting for other demographics, health behaviors, and medical conditions.

Results:
At follow-up, 1,170 (8.7%) had developed diabetes, and 3,790 (26.8%) had died. As the number of SDOH increased, the relative risk of both diabetes and death increased significantly (p for trend <0.001) in both crude and adjusted models (Figure).

Conclusions:
Counting the aggregate number of SDOH that an individual is exposed to may be a simple way to identify those at greater risk of developing incident diabetes or dying over 10 years. This approach has potential for application in both clinical practice and population health management.
Abstract MP09: Effect of Estradiol Therapy on Arterial Wall Echomorphology in the Early versus Late Intervention Trial With Estradiol(elite)
Authors: Karim Roksana , Xu Wenrui , Hodis Howard N , Kono Naoko , Sriprasert Intira , Li Yanji , Yan Mingzhu , Stanczyk Frank , MacK Wendy
Published: March 2020

Objective:
The effect of estradiol therapy (ET) has been evaluated on atherosclerosis progression measured by carotid artery wall thickness. Echogenicity of the arterial wall, a measure of lipid deposition, has not been investigated in relation to ET.

Methods:
This is a secondary analysis from ELITE. A total of 643 healthy postmenopausal women were randomized within time-since-menopause strata (early (<6 years) and late (>10 years) postmenopause) to daily 1 mg estradiol or placebo. The atherosclerosis outcome for the current analysis is grey scale median (GSM, unitless), a qualitative measure of atherosclerosis based on echogenicity obtained by high resolution ultrasonography of the common carotid arterial wall. Lower GSM values indicate more lipid deposition. GSM and serum concentrations of estradiol (E2) were assessed every 6 months over a median 5-year trial period. Linear mixed effects regression models were used to compare the rate of GSM progression between the randomized groups within time-since-menopause strata. The association of mean on-trial serum E2 levels with GSM progression was also tested using similar mixed effects model.

Results:
The effect of ET on the annual rate of GSM progression significantly differed between early and late postmenopause strata (p-value for interaction = 0.006). Annual GSM progression rate (95% confidence interval) among women in early postmenopause decreased by -0.30 (-0.63, 0.04) per year among women taking ET compared to -1.41 (-1.77, -1.06) per year among the placebo group (p<0.0001). In contrast, the annual GSM progression rate was not significantly different between ET and placebo among the late postmenopausal women (p=0.37). The positive association between mean on-trial E2 level (pg/ml) and GSM progression rate was stronger and significant among early postmenopausal women (0.008 (0.0007, 0.016)) compared to women in the late postmenopause group (0.003 (-0.006, 0.01)). However, this differential association between E2 level and GSM progression rate was not statistically significant (p-value for interaction = 0.33).

Conclusion:
Compared to placebo, oral ET significantly reduced progression of lipid deposition in the carotid arterial wall among women in early postmenopause. ET had no such beneficial effect in late postmenopause. Associations between serum estradiol levels and lipid deposition validated those findings. Qualitative assessment of subclinical atherosclerosis (GSM) complements the anatomic assessment by carotid artery intima-media thickness.
Abstract MP20: Evening Chronotype is Associated With Poor Cardiovascular Health and Adverse Health Behaviors in a Diverse Population of Women
Authors: Makarem Nour , Paul Jacob , Giardina Elsa-Grace , LIAO MING , Aggarwal Brooke
Published: March 2020

Background:
Chronotype is the behavioral manifestation of an individual’s innate circadian rhythm. Evening chronotype (i.e. being a “night owl”) is linked to elevated chronic disease and mortality risk in European and Asian populations. Evidence from US cohorts is limited, particularly among women, in whom evening chronotype prevalence becomes higher from midlife onward, coinciding with life stages and hormonal changes associated with higher cardiovascular disease (CVD) risk.

Hypothesis:
Being a definite evening chronotype would be associated with poor cardiovascular health (CVH) and elevated cardiometabolic risk factors.

Methods:
Participants were 506 diverse women (mean age=37±16y, 62% racial/ethnic minority) in the AHA Go Red for Women Strategically Focused Research Network at Columbia University. Chronotype was measured using the Morningness-Eveningness Questionnaire (MEQ), the most widely used validated tool by circadian biologists to ascertain chronotype. Higher scores reflected greater morningness. Participants were also categorized as “evening” vs. “intermediate/morning” chronotypes based on their MEQ scores. Health behaviors (diet, physical activity, sleep, and sedentary time) were assessed using validated questionnaires. Health factors (BMI, blood pressure, fasting glucose, and cholesterol) were assessed at the clinic visit. Overall CVH was evaluated using the AHA Life’s Simple 7 (LS7) score (0-8: poor, 9-14: moderate to high). Linear and logistic regression models adjusted for age, race/ethnicity, education, health insurance, and menopause were used to examine associations of chronotype with CVH, clinical risk factors, and health behaviors.

Results:
Overall, 13% of women identified as being evening chronotypes. Higher MEQ scores (i.e. greater morningness) were associated with higher AHA LS7 scores (β=0.02, p=0.01), indicative of more favorable CVH. Higher MEQ scores were also associated with having a lower Pittsburgh Sleep Quality Index, i.e. better sleep quality, (β=-0.07, p<0.0001), a lower Insomnia Severity Index (β=-0.14, p<0.0001), shorter time to fall asleep (β=-0.28, p=0.04), and less sedentary time (β=-0.11, p=0.001). In contrast, being an evening chronotype was associated with higher odds of poor CVH (OR (95%CI): 2.41 (1.20-4.85)), not meeting AHA diet (OR (95%CI): 2.89 (1.59-5.23)) and physical activity guidelines, (OR (95%CI): 1.78 (1.03-3.07)), and having short sleep (<7h) (OR (95%CI): 2.15 (1.24-3.73)) or insomnia symptoms (OR (95%CI): 2.69 (1.53-4.75)).

Conclusions:
Women with evening chronotypes have greater odds of having poor CVH and adverse health behaviors after adjustment for sociodemographic factors and menopausal status. Chronotype may be important to consider and target in lifestyle interventions aimed at CVD prevention, particularly among middle-aged and older women who are prone to sleep changes.
Abstract MP22: Association Of Intra-individual Daily Variability In Sleep With Metabolic Outcomes In Youth: Multidimensional Assessment Of Preschoolers Study (MAPS)
Authors: Carnethon Mercedes R , Wong Mandy , Hansell Charles , KNUTSON Kristen , McCabe Megan , Krefman Amy , Perak Amanda M , Lauren Wakschlag , Allen Norrina B
Published: March 2020

Background:
Average nightly sleep duration is associated with cardiometabolic health; both short- and long-sleep are associated with obesity, diabetes, hypertension and cardiovascular disease. An equally important measure of cardiometabolic health is an individual’s daily variability (DV) in sleep timing and duration. Greater intra-individual DV is associated with less favorable cardiometabolic health in adults, but less is known about the association of DV with cardiometabolic health in youth. We hypothesize that DV in sleep timing and duration is associated with less favorable body mass index (BMI), systolic blood pressure and waist girth among youth.

Methods:
Boys and girls aged 9-13 years old who wore the Actigraph GT-3X BT on their non-dominant wrist for a minimum of 4 days and had available measures of cardiometabolic health were included in the analysis (N=91). Validated algorithms from ActiLife software were used to determine daily total sleep time, sleep efficiency, sleep onset and time out of bed. We calculated DV in sleep onset, time out of bed and duration as the coefficient of variation (CV = standard deviation/overall mean). Average sleep measures were calculated across the days worn. We modeled the association of each sleep measure with metabolic outcomes using multivariable linear regression.

Results:
On average, participants slept for 7.23 (SD=1.4) hours per night, BMI percentile (BMI%) was 63.0 (SD=30.9), waist girth was 66.7 cm (SD=10.8) and systolic blood pressure percentile (SBP%) was 41.4 (SD= 21.4). Higher DV in sleep onset was associated with significantly higher BMI% and positively associated with SBP%. There was no association of average sleep measures with any outcomes. Findings were consistent by sex and age.

Conclusions:
Daily variability in time to sleep in youth was associated with higher BMI% and a modest association with SBP%. Future studies should test whether promoting consistent bedtimes can improve cardiometabolic health.
Abstract MP45: A Metabolome-wide Association Study of Plant Food Consumption With Blood Pressure
Authors: Oude Griep Linda M , Chekmeneva Elena , Stamler Jeremiah , Van Horn Linda , Chan Queenie , Daviglus Martha , Frost Gary S , Ebbels Timothy M , Holmes Elaine , Elliott Paul
Published: March 2020

Background:
Epidemiological evidence links blood pressure (BP) -lowering effects with fruit, vegetables, pulses, nuts but results are inconsistent and often rely on self-administered dietary assessment methods prone to random and systematic errors and potential under- or overestimation of relationships.

Objective:
To characterize urinary metabolic signatures of plant food intake (fruit, vegetables, pulses, and nuts) and subsequently to assess their associations with BP, validated across cohorts.

Methods:
We used untargeted metabolic profiling obtained by proton nuclear magnetic resonance spectroscopy (
1
H NMR) of two timed repeated 24-hour urine collections derived from 2,032 free-living US participants, and replicated among 449 UK participants, all part of the cross-sectional International Study of Macro- and Micronutrients and Blood Pressure (INTERMAP) study. Associations of plant foods intakes from four 24-hour dietary recalls with 7,100 NMR features were evlauted using univariate linear regression analyses. Significant metabolites were structurally identified using analytical and statistical approaches. We compared extensively adjusted associations of plant food intake and urinary metabolites with BP in the total population (N=2,481). All analyses were extensively adjusted for potential confounders and accounted for multiple testing.

Results:
We found consistent, reproducible relationships of NMR signatures with plant food intake across repeated urine collections and between populations. Eleven urinary metabolites were identified and two remained unknown (1: δ 2.80 (s); 2: δ 1.16(s), 1.67 (s)). Twelve metabolites were directly correlated with plant foods ranging from 0.15 (P≤1x10
-11
) to 0.49 (P≤5x10
-119
), and phenylacetylglutamine was inversely associated (r=-0.18, P≤1x10
-5
). In adjusted analyses, plant food intake was inversely associated with systolic BP (-1.29 mmHg; 95%CI: -2.38,-0.19), but not with diastolic BP. Metabolites inversely associated with systolic BP were hippurate (-2.67 mmHg;-3.71,-1.63), citrate (-2.50 mmHg; -3.55,-1.44), phenylacetylglutamine (-2.26 mmHg; -3.29,-1.23), unknown1 (-2.05 mmHg; -3.06,-1.04), 4-hydroxyhippurate (-1.45 mmHg; -2.44,-0.45), and unknown2 (-1.09 mmHg; -2.09,-0.09); with diastolic BP were phenylacetylglutamine (-1.12 mmHg; -1.84,-0.40), citrate (-1.02 mmHg; -1.76,-0.28), and unknown1 (-1.18 mmHg; -1.88,-0.47). Plant food-systolic BP associations were attenuated by further adjustment for citrate, hippurate, and unknown1, while hydroxyproline, proline and phenylacetylglutamine were potential effect modifiers.

Conclusion:
Urinary metabolites were consistently associated with plant food intake. Urinary metabolites that may underlie the plant food-BP association were gut-microbial co-metabolites and tricarboxylic acid cycle intermediates.
Abstract MP65: Occupational Complexity and Childhood Socioeconomic Environment Influence Mid-to-Late-Life 20-year Change in Cognitive Function; The Atherosclerosis Risk in Communities (aric) Study
Authors: Kucharska-newton Anna , Palta Priya , Patel Mehul D , Coker Laura , Meyer Michelle L , Koton Silvia , Mosley Thomas , HEISS Gerardo M
Published: March 2020

Background:
We tested the hypothesis that lower childhood SES is associated with greater age-and disease-related cognitive decline. We further examined potential protective effects of high adulthood occupational complexity in the association of childhood SES with cognitive decline.

Methods:
Childhood neighborhood SES (child nSES) was ascertained at midlife among 12440 ARIC participants using retrospective historical county-level census-based measures of median household income, value of owner occupied housing units, percent of households receiving interest, dividend, or net rental income, educational attainment, and proportion of adults in professional, management, or executive occupations. An occupational complexity index (OCI) was derived from self-reported occupational categories at baseline. Cognitive function was assessed at ARIC visits 2 (1990-1993), 4 (1996-1998), and 5 (2011-2013) according to performance on tests of memory, executive function/processing speed and language. A composite global cognition z-score was estimated, with missing data imputed using multiple imputation by chained equations. Linear mixed effects models, adjusted for baseline age, sex, and race-study center, were used to examine the association of distribution-based tertiles of the child nSES summary score with baseline and 20-year change in cognitive function. We further examined interactions by OCI tertiles.

Results:
Global cognitive z scores in adulthood were persistently higher at baseline among participants with high (Visit 2 β =0.545 (95% CI 0.514, 0.576) as compared to intermediate (Visit 2 β=0.348 (95% CI 0.317, 0.381)) and low (Visit 2 β = 0.007 (95% CI -0.030, 0.044) child nSES. Participants with high,as compared to low, OCI, had higher baseline cognitive function across all tertiles of child nSES (Figure, p<0.01).

Conclusion:
The positive association of child nSES with adult cognitive function is modified by adulthood occupational complexity. Child nSES is not associated with a 20-year cognitive change.
Abstract MP74: Association of Albuminuria With Incident Atrial Fibrillation: The Multi-ethnic Study of Atherosclerosis (MESA)
Authors: Tanaka Yoshihiro , Patel Ravi B , Michos Erin D , Szklo Moyses , Greenland Philip
Published: March 2020

Background:
Atrial fibrillation (AF) shares risk factors with atherosclerotic cardiovascular disease (CVD). Albuminuria (AU) is an established risk factor for renal failure and CVD. Endothelial dysfunction, inflammation and hemostasis underlie the pathogenesis of AU. However, the association of AU with incident AF and its effect modifiers are not fully understood.

Purpose:
To assess the association of AU with incident AF and to identify its effect modifiers.

Methods:
We studied MESA participants, free of clinical CVD and AF at baseline, with urine samples at exam 1. Participants were followed for incident AF ascertained by follow up visit ECGs, hospital discharge diagnoses or Medicare claims data. Participants were compared by the presence or absence of AU (albumin-creatine ratio of ≥30). Kaplan-Meier curves were used to estimate the cumulative rate of incident AF and log-rank test to evaluate statistical significance. Hazard ratio (HR) and 95% confidence interval (CI) were computed by Cox proportional hazard models. Final adjusted model included CHARGE-AF risk score covariates with socioeconomic variables, current alcohol use, renal function, and lipid lowering medication use.

Results:
A total of 6376 participants were analyzed (median age 62 years, male 47.4%, White race 38.8%, mean BMI 28.3 ± 5.5). During median follow-up of 13.9 years, there were a total of 924 AF events. Participants with AU had a higher incidence of AF than those without AU at 10 years (23.9% vs 10.4%, p < 0.05,
Figure 1A
). In fully adjusted model, AU was significantly associated with incident AF [HR 1.53 (95% CI 1.27 - 1.85, p < 0.01). Low high-density lipoprotein cholesterol (< 40 mg/dL) and high triglyceride (≥ 150 mg/dL) augmented the association between AU and incident AF (p-interaction < 0.05 for all,
Figure 1B
).

Conclusion:
AU was significantly associated with incident AF after adjusting for conventional risk factors in a multi-racial prospective cohort. Lipid markers were identified as effect modifiers in the association of AU with AF.
Abstract MP78: Progression of Valvular Calcification and Risk of Incident Stroke: The Multi-ethnic Study of Atherosclerosis (MESA)
Authors: Fashanu Oluwaseun , Bizanti Anas , Al-Abdouh Ahmad , Zhao Di , Budoff Matthew J , Thomas Isac C , Longstreth W T , Michos Erin D
Published: March 2020

Introduction:
Stroke is a leading cause of morbidity and mortality in the United States. Identification of individuals at risk for stroke is important for implementation of preventive therapies. Prevalent valvular calcification (VC) has been shown to be associated with stroke but less is known about associations of VC progression with stroke.

Methods:
Progression (interval increase >0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors.

Results:
We studied 5,606 multiethnic participants (39.6% White, 26.9% Black, 21.4% Hispanic, 12.2% Chinese) free of baseline CVD enrolled in MESA. Baseline mean ± SD age was 62 ± 10 years; 53% were women; 12% had prevalent AVC and 9% prevalent MAC at the baseline visit; 83% had no progression of VC, 14%, progression at one site (AVC or MAC), and 3% progression at both sites (AVC and MAC) at follow-up. Over a median of 12 years, 214 total and 170 ischemic strokes occurred. The number of sites with VC progression (range 0-2) was not associated with total and ischemic stroke (all p>0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratios (95% CI) 1.59 (1.11 - 2.27)] and ischemic stroke [1.64 (1.10 - 2.43)] in the whole cohort (model 3) and after further adjustment for baseline coronary artery calcification (model 4) (
Table
). Results remained significant for total stroke risk after excluding participants with interim atrial fibrillation or coronary heart disease [1.60 (1.01 - 2.54)]. In women, AVC progression was associated with ischemic stroke [1.87 (1.04 - 3.36)] (p-for-interaction=0.03).

Conclusion:
Progression of MAC over 2.4 years is associated with increased risk of total and ischemic stroke, and in women, AVC progression with higher ischemic stroke risk.