bluuebunny/crossref_metadata_2025 huggingface dataset:
A responsabilidade do Estado e a tutela do contratado em decorrência da extinção do contrato administrativo pelo fato do príncipe
Authors: Barboza Olavo Sachetim
Published: March 2019

O presente artigo analisa, no âmbito de Portugal, a responsabilidade do Estado frente ao exercício do fato do príncipe, bem como a tutela do contratado em decorrência deste ato de poder. Durante todo o estudo, exemplificativamente, serão abordados os atos caracterizados e definidores do fato do príncipe, os quais o diferenciam das figuras afins, bem como o seu enquadramento na legislação portuguesa. Serão trazidas, num segundo momento, as considerações se a instabilidade do contrato administrativo em decorrência do fato do príncipe se encaixa como responsabilidade civil do Estado ou indenização pelo sacrifício, pois, se for uma ou outra, a indenização devida ao contratado será a reparação do dano ou a compensação pelo sacrifício, assim como quem é o responsável pelo pagamento da indenização.
Abstract 004: Novel Serum Metabolites Associate With Diastolic Function: Evidence From the Bogalusa Heart Study
Authors: Razavi Alexander C , Fernandez Camilo , Mi Xuenan , He Jiang , Bazzano Lydia , Nierenberg Jovia , Li Shengxu , Kelly Tanika N
Published: March 2019

Introduction:
Diastolic dysfunction is one key causal factor for heart failure with preserved ejection fraction (HFpEF). We conducted a metabolome-wide association study to identify novel diastolic function-related metabolites in relatively young and healthy adults.

Hypothesis:
We hypothesized that serum metabolites could predict diastolic function and thus potentially serve as biomarkers for subclinical disease.

Methods:
The study cohort consisted of 1,038 participants of the Bogalusa Heart Study (34.9% black, 57.3% females, aged 33.6-57.5 years). Diastolic function was assessed via 2D and tissue doppler echocardiography, and included peak early filling velocity (E), peak velocity caused by atrial contraction (A), medial mitral annular velocity (e’), left ventricular isovolumic relaxation time (IVRT), as well as deceleration time (DT). Untargeted metabolomic analysis of fasting serum samples was conducted. Multivariable-adjusted linear regression models were employed to assess the relationship of metabolites with echocardiographic measures of diastolic function.

Results:
Following quality control, 1202 metabolites were tested for association with E/A ratio, E/e’ ratio, IVRT, and DT. After Bonferroni correction, 9 novel metabolites, derived from amino acid, cofactor, energy, lipid, and nucleotide pathways, were significantly associated with diastolic function in blacks with nominal significance and consistent effect direction in whites (Table). Of these significant metabolites, 2 and 6 metabolites were associated with the E/A ratio and E/e’ ratio, respectively. No significant associations of metabolites with IVRT or DT were found. Fatty acid metabolism was the biological sub-pathway most represented in significant diastolic function-metabolite associations.

Conclusion:
The current study identified novel metabolites associated with diastolic function, suggesting that the serum metabolome, and its underlying biological pathways, may be implicated in HFpEF pathogenesis.
Abstract 006: Mapping Geographic Variation of Atherosclerotic Cardiovascular Disease Risk: 2013 Pooled Models Overpredict the Risk in United States Veterans
Authors: Ho Yuk-Lam , Vassy Jason L , Nguyen Xuan-Mai , Tarko Laura , Raghavan Sridharan , Galloway Ashley , Djousse Luc , Wilson Peter W , Gagnon David R , Cho Kelly
Published: March 2019

Introduction:
Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity in the U.S. We mapped ACC/AHA ASCVD risk in U.S. Veterans outpatients across U.S. geographic regions.

Methods:
We computed 10-year ASCVD risk using the 2013 ACC/AHA risk calculator with risk factor values derived from electronic health records and compared the estimates to observed ASCVD rates within Veterans Health Administration (VHA) population. We mapped the standardized differences in the observed and predicted risk at the county level using ArcGIS software.

Results:
There were 1.48 million VHA users between 2002-2007 aged 40 to 79 with median 10 years of follow-up. Mean age was 60 years, 96% were male, and 80% were white. The average 10-year predicted ASCVD risk after adjustment for true follow-up time at baseline was 13.8%, and the average observed risk was 6.6%, an overestimation of 7.2%. At baseline, 43.1% of patients were taking anti-hypertensive medications and 20.3% were taking statins. After updating risk factor statuses two years following baseline, 75.9% were taking anti-hypertensive medication, 42.6% were takings statins, and average predicted risk was dropped to 12.1%. In sex- and race-specific analyses the 2013 ACC/AHA risk calculator over-estimated 10-year ASCVD risk in white female, non-white female, white male, and non-white male by 2.0%, 2.0%, 8.1% and 4.8%, respectively. The greatest over-predictions in 10-year ASCVD risks were observed in western Arizona, southern California, southern Florida and Pennsylvania. These regions had higher percentages of white male VHA users compared to national averages.

Conclusion:
The 2013 ACC/AHA risk equation generally over-predicts ASCVD risk in the VHA population, particularly among white male Veterans. Increased anti-hypertensive and statin therapy with continual care at VHA was also associated with lower ASCVD risk. The mapping of these results allowed an overall visualization of the geographic variation across the U.S.
Abstract 010: Heart Disease and Arrhythmia in a Sample Experiencing Homelessness: Epidemiology, Prior History and Risk Factors
Authors: King Ben
Published: March 2019

Background:
Adults experiencing homelessness experience 40-50% greater mortality risk from heart disease than the general population. Research has identified several risk factors, including poor glycemic, hypertension, and hyperlipidemia control, high prevalence of cigarette smoking, and elevated homocysteine levels from smoking and poor nutrition. Implemented in 2014, the Vulnerability Index - Service Prioritization Decision Assistance Tool (VI-SPDAT v1) is a 50 question survey intended to proscribe appropriate levels of intervention, and prioritize the waiting list for housing services.

Method:
The VI-SPDAT was used to assess a cohort of individuals experiencing homelessness (n=4,739 unique participants) seeking subsidized housing services in a single county in Texas. The results of the self-report survey’s medical questions were validated through linkage to the community’s Health Information Exchange (HIE) for indigent populations. Confirmatory Factor Analysis tests were performed on all first-time assessments, and modification indices were used to optimize a 5 factor model of global vulnerability in the homeless population. Logistic regression was used to identify independent covariates associated with reported heart disease within various sections (explicit domains) within the measure.

Results:
One quarter of all individuals assessed with the VI-SPDAT reported a history of heart disease or arrhythmia (24.98%). Criterion validation of the tool using HIE data supported that this prevalence estimate was possibly even under-reported, with diagnostic data available for 3,240 participants and a 38.67% prevalence of heart disease or arrhythmia (26.44%, adjusted for full sample). Rates of the condition were elevated for females (27.5% vs 24.0%), non-Hispanic participants (25.7% vs 21.7%), and those experiencing chronic homelessness (HUD definition; 26.8% vs 22.5%). Behavioral and cognitive health conditions associated with heart disease included problems with concentration, history of traumatic brain injury, ED visits for mental health symptom management, and poor medication adherence (all p<0.001). Social risk factors such as being the victim of an attack, associating with perceived bad influences, having people they don’t like in their lives, and being forced or tricked into doing things by others were all associated with heart disease (all p<0.001).

Discussion:
This research presents a rare window into the complex interrelationships of social and medical vulnerability that surround cardiovascular diseases in a sample of extremely vulnerable individuals. Analytical techniques applied to this data show several relationships not previously explored in the literature, and support the existing evidence of heightened cardiovascular risk due to multiple exposures more common in those experiencing homelessness.
Abstract 014: Race and Sex-Based Disparities Associated With Carotid Endarterectomy in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Hicks Caitlin W , Daya Natalie , Black James H , Matsushita Kunihiro , Selvin Elizabeth
Published: March 2019

Introduction:
The indications and risks associated with carotid endarterectomy (CEA) are well established. We sought to investigate sex and race-based disparities in the incidence of CEA after adjusting for carotid artery stenosis risk factors.

Methods:
We conducted a prospective cohort analysis of 14,754 black and white participants in the Atherosclerosis Risk in Communities (ARIC) study who did not have a diagnosis of carotid artery stenosis at baseline (1987-1989). We estimated the cumulative incidence of CEA by sex and race using the Kaplan-Meier method. We used Cox proportional hazards models with adjustment for sociodemographic, cardiovascular, and disease severity risk factors to quantify the association of sex and race with incident CEA. Cardiovascular risk factors (hypertension, coronary heart disease, chronic kidney disease, diabetes), carotid intima media thickness(IMT), and symptomatic status (stroke or symptomatic carotid artery stenosis based on hospital diagnosis codes) were adjusted as time-varying exposures.

Results:
CEA was performed in 345 of 14,754 ARIC participants over a median of 27 years follow-up [incidence rate 1.04 (95%CI 0.93-1.15) per 1,000 persons-years]. The crude incidence of CEA varied significantly by sex [female vs. male: HR 0.58 (95%CI 0.47-0.72)] and race [black vs. white: HR 0.63 (95%CI 0.48-0.84)]. Adjustment for sociodemographic and cardiovascular risk factors, carotid IMT, and symptomatic status attenuated the association of sex with CEA [females vs. males HR 0.82 (95%CI 0.65-1.03)], but black participants had a persistently lower risk of incident CEA despite adjustment [HR 0.64 (95%CI 0.45-0.89)](
Figure
).

Conclusions:
While there are known sex and race-based differences in the prevalence of carotid artery stenosis, we found significant variation in the incidence of CEA based on race that is independent of traditional risk factors and carotid IMT. Whether this disparity is a reflection of differences in disease presentation or access to care deserves investigation.
Abstract 019: Changes in Gut Microbial Metabolites and Risk of Coronary Heart Disease in US Women: the Nurses’ Health Study
Authors: Heianza Yoriko , Ma Wenjie , DiDonato Joseph A , Sun Qi , Rimm Eric B , Hu Frank B , Rexrode Kathryn M , Manson JoAnn E , Qi Lu
Published: March 2019

Introduction:
Circulating levels of gut microbial metabolites, trimethylamine N-oxide (TMAO) and its nutrient precursors of choline and L-carnitine, have been suggested as risk factors for coronary heart disease (CHD). Whether changes in gut microbial metabolites are associated with the CHD incidence remains unknown.

Hypothesis:
We assessed the hypothesis that long-term (over 10 years) changes in plasma levels of TMAO, choline, and L-carnitine would be associated with the risk of CHD.

Methods:
This prospective nested case-control study included a total of 768 women (385 incident cases of fatal CHD and nonfatal myocardial infarction and 383 controls) who had data on blood concentrations of TMAO, choline, and L-carnitine at 2 time points, 10 years apart (1989-90, and 2000-01). We identified incident cases of CHD from the date of the second blood collection through 2014.

Results:
Higher TMAO levels at the second collection were associated with higher risk of CHD (relative risk (RR) 1.22 [95% CI: 1.05, 1.42] per 1 SD increment in log-transformed TMAO) in multivariate analyses controlling for traditional risk factors. Compared with women with low TMAO levels (lower two tertiles) at both time points, the RR was 1.74 (95% CI: 1.05, 2.89) for those with elevated levels of TMAO (the highest tertile) at both time points. Regardless of metabolite levels at the first collection, increases in TMAO or L-carnitine from the first to second collections were significantly associated with an increased risk of CHD (Fig. panels A-B). Women who had increases in both TMAO and L-carnitine had a particularly elevated risk of CHD (RR 2.12, 95% CI: 1.25, 3.59), as compared to those with decreases in both metabolites. Adherence to healthy dietary habits attenuated the associations of TMAO with CHD risk (Fig. panel C).

Conclusions:
Long-term increases in TMAO were significantly predictive of subsequent risk for CHD among women. The associations may be modified by the nutrient metabolite precursor, L-carnitine, and adherence to healthy dietary habits.
Abstract 21: Lipid Metabolites Are Associated With Epigenetic Aging Acceleration in the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Gao Tao , Zheng Yinan , Joyce Brian , Wilkins John , Greenland Philip , Lloyd-Jones Donald , Hou Lifang
Published: March 2019

Background:
Epigenetic aging measures including phenotypic aging (PA) and extrinsic epigenetic age acceleration (EEAA) have been associated with age-related diseases and conditions that include cardiovascular diseases, diabetes, and cancer. However, associations between epigenetic aging and lipids have not been widely investigated.

Hypothesis:
We hypothesized that adverse lipid metabolite profiles are associated with epigenetic age acceleration.

Methods:
We estimated measures of epigenetic age acceleration in 957 white and black participants from the CARDIA Study with whole-genome blood DNA methylation profiling by the Illumina EPIC array at Year 20 (Y20; ages 38-52). We used separate linear regression models to examine cross-sectional associations of PA and EEAA estimates with fasting triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels after adjusting for race, sex, education, alcohol intake, smoking status and physical activity.

Results:
Participants were 51% female (n=490) and 39% black (n=393) with mean chronological age 45±4 years. Compared with participants in the 1st tertile of TG, those in the 2nd tertile had 1.32 years older PA (95%CI 0.33-2.30) and 1.04 years older EEAA (95%CI 0.22-1.87); those in the 3rd tertile had 1.78 years older PA (95%CI 0.75-2.81) and 1.09 years older EEAA (95%CI 0.23-1.95). Compared to participants in the 1st tertile of HDL-C, those in the 3rd tertile had decreased EEAA by 1.21 years (95%CI -2.16--0.27). There were no significant differences of PA or EEAA among participants of LDL-C tertiles. (Figure 1.)

Conclusions:
Adverse lipid metabolites (TG and HDL-C) are associated cross-sectionally with accelerated epigenetic aging. Further studies are needed to understand the longitudinal associations between epigenetic aging and adverse lipid profiles as well as the potential mechanisms that underlie these associations.
Abstract 023: The Natural History of Cigarette Smoking From Childhood to Middle-Age: The International Childhood Cardiovascular Cohort (i3C) Consortium
Authors: Hu Tian , Gall Seana L , Widome Rachel , Bazzano Lydia A , Burns Trudy L , Daniels Stephen R , Dwyer Terence , Ikonen Johanna , Juonala Markus , Kahonen Mika , Prineas Ronald J , Raitakari Olli T , Sinaiko Alan R , Steinberger Julia , Urbina Elaine M , Venn Alison , Viikari Jorma , Woo Jessica G , Jacobs David R
Published: March 2019

Background:
Smoking is known to cause clinical cardiovascular disease. We report the natural history of smoking from childhood until average age 47 years in the large cohort followed in the International Childhood Cardiovascular Cohort (i3C) Consortium, which consists of seven long-standing cohorts in the US, Finland and Australia.

Methods:
Data on childhood smoking status were obtained from questionnaires answered during age 6-19 during the 1980s. Childhood smoking status was categorized as never smoker, tried smoking only a few times, tried more extensively (including quitters), and regular smoker. The i3C participants had follow-up visits until 2015-18 (Finland 2010-12), when they reported whether they were smokers during their 20s and/or 40s.

Results:
Of the 9977 participants, prevalence of regular smoking decreased from 35.5% in their 20s, to 20.5% in their 40s; cessation was unrelated to childhood smoking status. As shown in the Figure, among 1816 participants queried at age 18/19, prevalence of regular smoking in their 20s was 4.1% (36/886) in those who never smoked even during adolescence, 12% (22/183) in those who tried only a few times, 21.5% (40/186) in those who tried more extensively, and 76.5% (429/561) in those who were regular smokers during childhood. The pattern was similar among 860 whose last childhood smoking status was queried at age 16/17 (some probably experimented more during the remainder of childhood), but smoking in their 20s was more common for all smoking experimentation groups than in 18/19 year olds.

Conclusions:
These long-term follow-up data suggest that prevalence of adult smoking was significantly related to level of smoking experimentation during adolescence. However, cessation during adulthood does not depend on childhood smoking status. Policy change (such as taxes and restrictions on smoking indoors) has proven to be one of the most powerful tobacco control tools. These data support an emerging new policy strategy, namely raising the legal cigarette purchase age to 21 years
Abstract 024: The Timing of Cardiovascular Health Decline and Its Association With Subclinical Atherosclerosis in Adulthood
Authors: Pool Lindsay R , Krefman Amy E , Labarthe Darwin , Greenland Philip , Juonala Markus , Kähönen Mika , Lehtimäki Terho , Day Rena S , Bazzano Lydia , Van Horn Linda , Liu Lei , Alonso Camilo F , Webber Larry S , Pahkala Katja , Laitinen Tomi T , Raitakari Olli , Lloyd-Jones Donald M , Allen Norrina B
Published: March 2019

Introduction:
Declines in CVH beginning as early as childhood have been linked to development of subclinical atherosclerosis and CVD in adulthood; however, less is known about the timing and sequence. The objective of this study was to determine patterns for the loss of the health factors that comprise CVH and the associations with cIMT.

Methods:
We pooled data from five childhood/young adult cardiovascular cohorts including BHS, CARDIA, Young Finns, Project HB!, and STRIP. Available data allowed analysis of 4 of the 7 metrics that define CVH: BMI, blood pressure, total cholesterol, and blood glucose, categorized as ideal or non-ideal. We built a multi-trajectory model which fitted trajectory groups based on the simultaneous modeling of the loss of ideal CVH (defined as the probability of being ideal for a given health factor dropping below 50%), from childhood (ages 0-19) through early adulthood (ages 20-39) to middle adulthood (ages 40-59). Logistic regression was used to examine association of the trajectories and high cIMT.

Results:
There were 9,388 individuals included (55% female, 66% white), and 5 distinct trajectory groups were formed (Figure). As compared to those who maintained ideal levels of all four health factors, those who had a childhood loss of a single ideal health factor were about two times as likely to have high cIMT (cholesterol OR: 1.99; 95% CI 1.49-2.65; BMI OR: 1.91; 95% CI 1.45-2.53), while those with loss of more than one ideal health factors in childhood were 2.89 times more likely to have high cIMT (95% CI 2.21-3.78). The loss of ideal BMI and cholesterol during early adulthood was also associated with a higher likelihood of high cIMT than when ideal levels were retained to this age (OR: 1.47; 95% CI 1.10-1.97).

Conclusions:
Loss of multiple CVH factors in childhood was associated with the highest probability of developing subclinical atherosclerosis compared with retention of ideal levels into middle adulthood. These data add evidence of the importance of preserving ideal CVH beginning in childhood.
Abstract 027: The Menopausal Transition and Cerebrovascular Reactivity in the Coronary Artery Risk Development in Young Adults Study
Authors: Tahir Muna J , Schreiner Pamela J , Nasrallah Ilya M , Elbejjani Martine , Wellons Melissa F , Bryan R Nick , Launer Lenore J
Published: March 2019

Background:
Estrogen induces vasodilation in cerebral arteries and therefore increases perfusion to brain regions as needed. The menopausal transition, a state of variably declining endogenous estrogen levels, may be related to poorer cerebrovascular function. This study aims to investigate the association of menopausal status with cerebrovascular reactivity (CVR).

Methods:
The sample included women [N= 353] from the Coronary Artery Risk Development in Young Adults (CARDIA) Study who self-reported their reproductive histories and participated in the brain magnetic resonance imaging (MRI) sub-study at the year 25 follow-up examination. Menopausal status was classified as premenopause, perimenopause and postmenopause based on menstrual cycle regularity or cessation. CVR, a measure of vascular responsiveness to hypoxia, was calculated as mean percent change in blood-oxygen level dependent signals in activated voxels following a breath-hold test. Multiple linear regression models were used to examine the cross-sectional associations of menopausal status with total brain, gray matter and white matter CVR.

Results:
Women were mean age 50.4 ± 3.5 years; 42% were black; 56% were postmenopausal, 24% were perimenopausal and 20% were premenopausal. Following adjustment for hormone replacement therapy, and demographic, cardiovascular and behavioral risk factors, postmenopause versus premenopause was associated with less total, gray matter and white matter CVR (Table). Compared to premenopause, perimenopause showed no associations with CVR (Table).

Conclusions:
In this population-based sample of middle-aged women, postmenopausal status was associated with lower CVR, a marker for arterial stiffness and vascular aging, compared to premenopause; no difference was observed for perimenopause. While cross-sectional, these data suggest that interventions to prevent postmenopausal cerebrovascular function decline may still be initiated during perimenopause.
Abstract 031: County Poverty Disproportionately Effects Mortality in Heart Failure Compared to Coronary Heart Disease
Authors: Ahmad Khansa , Chen Edward , Nazir Umair , Trivedi Amal , Erqou Sebhat , Wu Wen-chih
Published: March 2019

Background:
Regional poverty has been associated with worse outcomes in stroke, myocardial infarction and overall cardiovascular mortality. There is paucity of data regarding regional socioeconomic (SE) factors and outcomes in heart failure (HF). We studied the association between SE factors and HF mortality and compared it with CHD mortality at a regional level.

Methods:
This is a cross sectional analysis of all US counties (n=3141) from 2010-2015. County level data for SE factors, risk factor prevalence and demographics were collected from CDC and Census Bureau. Counties (n=6) with insufficient mortality data were excluded. In 2014, poverty threshold was $11,670 for 1-person household. Mortality data was derived from death certificates, published by National Center for Health Statistics. Random sampling (n=50) was used to compare the strength of correlation for the strongest SE factor (poverty, employment, education and uninsured %) with HF and CHD mortality. Population weighted multivariate linear regression analyses were used to relate the strongest SE factor and HF mortality, adjusted for risk factor prevalence and demographics.

Results:
We studied 3,135 counties with median(IQR) of poverty (15.8% (12.4% - 20.1%)), male (49.5% (48.9% -50.4%)), white (84.6% (63.4% -93.1%), ≥ 65 yrs. (17.2% (14.7%-19.9%)), number of HF hospitalizations/1000 Medicare beneficiaries (13.9 (9.2-17.6)) and HF deaths/100,000 (189.5 (164.7-219.1)). Of all SE factors, poverty% has the strongest association with HF mortality, disproportionately higher for HF than CHD (p=0.000). Our final model explains 61.7% of variation in regional HF mortality. Poverty remains an independent risk factor despite adjusting for demographics, other SE factors and risk factor prevalence.

Conclusion:
County poverty disproportionately effects HF mortality as compared to CHD mortality, independent of demographics and risk factor prevalence. Future studies examining additional mechanism of this association are needed to reform health policy.
Abstract 032: Rural Versus Urban Living and Incident Cognitive Impairment in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS)
Authors: Harris Matthew L , Bennion Erica , MaWhinney Kristine , Howard Virginia J , Wadley Virginia G , McClure Leslie A , Levine Deborah A , Manly Jennifer J , Glymour Maria M , Wisco Jonathan J , Chaney Robert A , Thacker Evan L
Published: March 2019

Objective:
To estimate the association of rural vs urban living in the United States (US) with incident cognitive impairment (ICI), and to assess confounding, mediation, and effect heterogeneity by demographic, social, behavioral, and clinical risk factors.

Methods:
REGARDS is a cohort of 30,239 adults aged 45+ in the 48 contiguous states. We analyzed 20,592 participants who at baseline (2003-2007) were cognitively intact with no history of stroke and had cognition assessed an average of 7.1 years later. We used Rural-Urban Commuting Area (RUCA) codes to classify participants as urban (n = 16,436), large city/town (n = 2,420), or small/isolated rural (n = 1,736) at baseline. We defined ICI as falling ≥1.5 SD below the mean on at least two of three cognitive tests administered during follow-up: word list learning, word list delayed recall, and animal naming. Using urban as the referent, we estimated odds ratios of ICI for rural and for large city/town.

Results:
ICI occurred in 1,291 participants (6.3%). Rural residents had 49% higher odds of ICI adjusted for confounding by demographics (Model 2 in Table, OR = 1.49 [95% CI: 1.19, 1.85]). After further adjusting for potential mediators (Models 3-6), odds of ICI remained 25% higher for rural vs urban (Model 6, OR = 1.25 [0.99, 1.56]). In assessing effect heterogeneity, we found synergism of rural dwelling with black race, physical inactivity, and low self-rated health (all P < 0.1; see ORs in Table), but not for other ICI risk factors. We found no difference in ICI for large city/town vs urban (demographics-adjusted OR = 1.08 [0.88, 1.33]; fully adjusted OR = 0.95 [0.77, 1.18]), and no effect heterogeneity of ICI risk factors by large city/town (all P > 0.2).

Conclusion:
Rural living is an important social determinant of cognitive health in the US. ICI was significantly more frequent among rural dwellers than urban dwellers, partly due to confounding or mediation by ICI risk factors. Odds of ICI were highest for rural dwelling combined with black race, physical inactivity, or low self-rated health.
Abstract 035: Comparative Effectiveness of Long-term Lifestyle and Pharmacological Interventions for Primary Prevention of Type 2 Diabetes: a Network Meta-analysis of Randomized Controlled Trials
Authors: Tang Huilin , Xia Jin , Yang Keming , Song Yiqing
Published: March 2019

Background:
Lifestyle modification and some pharmacological interventions have been proven effective in preventing type 2 diabetes (T2D) in previous primary prevention trials. However, there is controversy regarding their comparative effectiveness because of the lack of head-to-head trials for all possible comparisons among different interventions. Network meta-analysis enables us to simultaneously evaluate the relative effectiveness among all interventions by synthesizing both direct evidence from head-to-head trials and indirect evidence through more than one common comparator while maintaining randomization.

Objective:
We performed a network meta-analysis of randomized controlled trials (RCTs) to directly and indirectly compare lifestyle modification and five commonly prescribed medications (insulin sensitizers, insulin secretagogues, alpha-glucosidase inhibitors, weight-loss drugs, and renin-angiotensin system blockade), and to rank their relative effectiveness for primary prevention of T2D among adults with prediabetes at enrollment.

Methods:
We systematically searched PubMed, Embase, and CENTRAL from inception to October 2018 and identified long-term RCTs (follow-up ≥ 1year) that evaluated the interventions for T2D prevention in adults with prediabetes (e.g. impaired fasting glucose and impaired glucose tolerance). A network meta-analysis using the frequentist approaches was conducted to calculate the summary odds ratio (OR) and 95% confidence interval (CI) for each active intervention in comparison with controls (i.e. usual care alone or with placebo or control pills) and rank the effectiveness of these interventions by the surface under the cumulative ranking curve probabilities.

Results:
Thirty-three RCTs involving 54,910 individuals with prediabetes and 13,189 diabetic cases were included. Network meta-analysis showed that lifestyle modification (OR, 0.53; 95% CI, 0.42 to 0.66), insulin sensitizers (0.44; 0.31 to 0.62), alpha-glucosidase inhibitors (0.60; 0.42 to 0.87), and weight-loss drugs (0.39; 0.23 to 0.66) were significantly associated with decreased risk of incident T2D as compared with the controls. Neither insulin secretagogues (0.80; 0.51 to 1.26) nor renin-angiotensin system blockade (0.93; 0.62 to 1.38) were significantly associated with lower risk of developing T2D. Ranking of these interventions revealed weight-loss drugs being the optimal intervention for preventing T2D (89.5%), followed by insulin sensitizers (84.1%), lifestyle modification (66.7%), and alpha-glucosidase inhibitors (54.4%).

Conclusions:
Among the four interventions (lifestyle modification, insulin sensitizers, alpha-glucosidase inhibitors, and weight-loss drugs) which showed significant benefits on the primary prevention of T2D, weight-loss drugs seem to be the most effective.
Abstract MP03: Aortic Stiffening and Intracranial Atherosclerosis: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)
Authors: Palta Priya , Qiao Ye , Wei Jingkai , Meyer Michelle , Tanaka Hiro , Knopman David , Heiss Gerardo , Wasserman Bruce
Published: March 2019

Introduction:
Stiffening of the aorta is associated with increased pulse pressure and transmission of pulsatile energy into the cerebral circulation. An association between increased aortic stiffening with intracranial atherosclerotic disease (ICAD) has not been widely studied. We tested the hypothesis that loss of aortic elasticity (i.e. higher aortic stiffness) is associated with a higher presence of ICAD.

Methods:
ARIC-NCS participants (n=1412; mean age: 76 years; 42% male; 30% Black) with measures of aortic stiffness and vascular brain magnetic resonance imaging (MRI) at the visit 5 (2011-2013) examination were included. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV) using the VP-1000 Plus device (Omron Co., Japan). cfPWV was discretized into high vs. low aortic stiffness based on the upper 25
th
percentile, 13.4 m/s. Brain MRI was performed on 3.0 Tesla scanners using a standardized protocol that included an MR angiography (MRA) and high isotropic resolution vessel MRI. Presence of ICAD was defined as eccentric wall thickening with or without luminal stenosis on MRA. We first examined the functional form relationship between continuous measures of cfPWV and ICAD. Comparing those with high vs. low aortic stiffening, we estimated the prevalence odds of ICAD using logistic regression. Models were adjusted for age, sex, race-center, education, smoking, heart rate, blood-pressure lowering medication, diabetes, LDL-cholesterol, and minutes/week of physical activity. Sampling weights were used for generalizability to the full ARIC cohort at visit 5. We tested for effect modification by race, sex, diabetes, central systolic blood pressure, and use of blood pressure-lowering medication.

Results:
The mean cfPWV was higher among participants with ICAD (12.6 ± 3.2 m/s) compared to those without ICAD (11.2 ± 2.9 m/s). cfPWV was associated with ICAD in a monotonic, linear fashion (p<0.05). The presence of ICAD was 50.6% among participants with high aortic stiffness (cfPWV above the upper 25th percentile; n=354) compared to 30.2% among participants with low aortic stiffness (n=1058). Compared to participants with low aortic stiffness, those with high aortic stiffness had two-fold higher odds of ICAD (odds ratio (OR): 1.97, 95% confidence interval (CI): 1.68, 2.33). No statistically significant modification of this association was observed. Results were robust to exclusions for prevalent stroke (n=43) and prevalent cardiovascular disease (n=153).

Conclusions:
Aortic stiffness, a highly prevalent trait among older men and women, is associated with ICAD presence quantified by magnetic resonance angiography. Aortic stiffness, its risk factors and the factors associated with the preservation of aortic elasticity, may play a role in modifying the risk of intracranial atherosclerosis.
Abstract MP04: Mean Heart Rate and Brain Morphology in Elderly Women Without a History of Cardiovascular Disease
Authors: Haring Bernhard , Liu Jingmin , Shimbo Daijchi , Padula Claudia B , Li Wenjun , Mozhui Khyobeni , Rapp Steve , Espeland Mark , Wassertheil-Smoller Sylvia
Published: March 2019

Background:
Low resting heart rate (RHR) has been shown to be predictive of a lower risk for cardiovascular events. Accumulating evidence suggests that RHR may also be related to cognition later in life. To this point, data on the relationship with brain morphology in populations with none or few modifiable cardiovascular risk factors are largely missing. The aim of this study was to assess the associations between mean RHR and brain volumes in elderly postmenopausal women without a history of cardiovascular disease.

Methods:
The study sample consisted of postmenopausal women without a history of diabetes, coronary heart disease, stroke, atrial fibrillation and hypertension who were enrolled in the MRI ancillary study of the Women’s Health Initiative Memory Study (WHIMS-MRI). Women with very low (<40 bpm) or very high (>120 bpm) heart rate, suffering from any cancer, emphysema, history of pulmonary embolism or current smokers were excluded. Heart rate readings were taken at baseline (WHI enrollment, 1996-1998) and each annual follow-up visit. Brain MRI scans were performed between 2004-2006. Our final sample consisted of 493 women with a mean age of 69 years who were followed over a median of 8 years with an average of 8 RHR assessments.

Results:
In multivariate regression models adjusting for age, education, WHI Hormone Trial Randomization assignment (HTR arm), depression, physical activity, alcohol intake, coffee intake, presence of ApoE4 allele, mean systolic blood pressure over time, anti-hypertensive medication use over time and incident cardiovascular disease over time, women in the highest tertile of mean RHR (71-92/min) exhibited significantly higher lesion volumes compared to women in the lowest tertile (51-66/min).

Conclusion:
In postmenopausal women without a history of cardiovascular disease, high mean RHR was associated with higher white and grey matter lesion volumes later in life reflecting higher volumes of neuronal dysfunction and degeneration.
Abstract MP05: Genetic Predisposition to Obesity and Healthful Plant-Based Diet in Risks of Hypertension and Cardiovascular Disease: Gene-Diet Interaction Analyses in the UK Biobank
Authors: Heianza Yoriko , Zhou Tao , Sun Dianjianyi , Qi Lu
Published: March 2019

Introduction:
Plant-based diets include beneficial nutrients for the prevention of obesity and cardiovascular disease (CVD). No study has assessed interactions between a new healthful plant-based diet index (hPDI) and genetic predisposition to obesity in relation to adiposity and its related metabolic abnormalities.

Hypothesis:
We assessed the hypothesis that adherence to healthy plant-based diets would modify the genetic risk of obesity, and people at genetically higher risk of obesity would be more susceptible to the healthy diets for improving obesity and cardiovascular health.

Methods:
This study included 160184 participants initially free of CVD (myocardial infarction or stroke), diabetes, and cancer. We calculated the hPDI in which healthy plant foods received positive scores and the other foods received negative scores based on previous studies. A genetic risk score (GRS) of obesity was created based on 75 SNPs for BMI. Outcome measures included differences in BMI and mean arterial blood pressure (MAB), untreated hypertension (systolic blood pressure ≥130 mmHg, diastolic blood pressure ≥80 mmHg without antihypertensive medication use), and the 5-year incidence of CVD.

Results:
Higher hPDI was related to lower risks of obesity and untreated hypertension among the total study participants. We found a significant interaction between GRS and hPDI for BMI (Pinteraction <0.0001) (Fig. panel A). For people at genetically high risk, higher hPDI was more strongly associated with lower BMI levels. The significant GRS-hPDI interaction was also found for MAB levels and the risk of untreated hypertension (panels B and C). The effect of GRS-hPDI interaction was also related to the subsequent risk of CVD (Fig. panel D).

Conclusions:
Adherence to the healthy plant-based dietary pattern significantly attenuated genetic association with obesity. People at genetically higher risk of obesity may be more susceptible to benefits of healthy plant-based diets in improving adiposity and cardiovascular health.
Abstract MP09: Indices of Kidney Tubular Health Improve Cardiovascular Disease Risk Prediction in Adults With Hypertension and Chronic Kidney Disease in SPRINT
Authors: Lee Alexandra K , Katz Ronit , Ambrosius Walter T , Cheung Alfred K , Garimella Pranav , Gren Lisa H , Jotwani Vasantha , Neyra Javier A , Punzi Henry , Raphael Kalani , Ix Joachim H , Shlipak Michael
Published: March 2019

Introduction:
While chronic kidney disease (CKD) is a strong risk factor for cardiovascular disease (CVD), traditional metrics of kidney function (eGFR and albuminuria) have not improved CVD risk prediction equations. We hypothesize that new measures of kidney tubular function and injury can improve CVD risk prediction.

Methods:
Of 1971 SPRINT participants with eGFR <60mL/min/1.73m
2
and without CVD at baseline, we analyzed 1858 with urine and serum biomarkers. We conducted factor analysis on 10 kidney tubule biomarkers using principal-component factor estimation and promax rotation. To examine the association between the factor scores and risk of subsequent cardiovascular events, we used adjusted Cox models. Using Harrell’s C-statistic, we compared a standard CVD risk prediction model to models adding 1) factor scores of kidney tubular health, 2) eGFR and albumin-to-creatinine ratio (ACR), and 3) factor scores, eGFR and ACR. We also conducted these comparisons using ASCVD predicted risk in place of CVD risk factors among those <80 years.

Results:
Mean age was 73, 44% female, 29% black, and mean±SD eGFR was 45±12 mL/min/1.73m
2
. Factor analysis identified 4 unique dimensions of kidney tubular health that correspond to hypothesized physiologic processes (
Table
). Three of four factors were associated with CVD in demographic models, and Factors 3 and 4 remained associated in the full model. The C-statistic of the base CVD risk equation was 0.670, and with inclusion of the four kidney tubule factors the C-statistic improved to 0.727 (p for difference <0.0001), a larger increase than addition of eGFR and ACR to the base model (c=0.711, p for difference=0.0007). Addition of eGFR and ACR to the kidney tubule model did not improve discrimination (c=0.730, p for difference=0.17). Results were similar with ASCVD predicted risk.

Conclusion:
Indices of kidney tubular health based on urine and serum biomarkers may improve CVD risk prediction in adults with hypertensive CKD. Further studies are needed in the general, non-CKD population.
Abstract MP10: Discontinuation of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Chronic Kidney Disease
Authors: Qiao Yao , Shin Jung-Im , Sang Yingying , Inker Lesley , Secora Alex , Coresh Josef , Alexander G. Caleb , Jackson John , Chang Alex , Grams Morgan
Published: March 2019

Introduction:
Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers (ACE-I/ARB) are commonly used antihypertensives, especially preferred when albuminuria is present. Common reasons for discontinuing ACE-I/ARB include hyperkalemia and acute kidney injury (AKI). We assessed real-world practice patterns of discontinuing ACE-I/ARB in the setting of chronic kidney disease (CKD).

Hypothesis:
Patients with more advanced CKD stage are more likely to discontinue ACE-I/ARB.

Methods:
We identified incident users of ACE-I/ARB from the Geisinger Health System between 2004 and 2015, with a baseline estimated glomerular filtration rate ≥15 mL/min/1.73 m
2
and no previous diagnosis of end stage renal disease. Discontinuation was defined as a therapy gap ≥60 days. Kaplan Meier curves were used to depict time to discontinuation since initiating ACE-I/ARB by CKD stage (i.e. G1, G2, G3a, G3b, and G4) (
Figure
). Multivariable Cox proportional hazards models were constructed to quantify the association between discontinuation and CKD stage, captured both as baseline and time-dependent.

Results:
54,588 patients met inclusion criteria. Adjusted hazard ratios (HR) of discontinuation were 1.06 [95% confidence interval (CI): 1.03-1.09], 1.24 [1.19-1.30], 1.49 [1.40-1.59], and 2.31 [2.09-2.57], comparing baseline G2-G4 respectively with G1. Effects were stronger when G-stage was treated as time-dependent. In adjusted analysis, risk of discontinuation was higher in 2008-2011 (HR=1.16 [95% CI 1.13-1.19]) and 2012-2015 (HR=1.28 [1.24-1.32]) than 2004-2007. Hospitalizations related and not related to AKI were both associated with higher risks of discontinuation (HR=17.34 [95% CI 16.01-18.78], and 4.11 [3.94-4.30], respectively). Among 29,029 discontinued users, 6,187 (21.3%) restarted therapy within six months of discontinuation.

Conclusions:
More advanced CKD stage was associated with a higher risk of ACE-I/ARB discontinuation with a trend toward greater discontinuation in more recent years.
Abstract MP18: Trajectories of Oral Anticoagulation Adherence After First Atrial Fibrillation Diagnosis
Authors: Hernandez Inmaculada , He Meiqi , Chen Nemin , Saba Samir , Gellad Walid
Published: March 2019

Introduction:
Regardless of the benefits of stroke prevention, only 50% of atrial fibrillation (AF) patients recommended for oral anticoagulation (OAC) actually use these medications. We identified groups of patients with similar OAC adherence patterns, and evaluated what patient characteristics affect group membership.

Hypothesis:
We hypothesized that patients continuously adherent to OAC would be more likely to reside in the Midwest and Northeast and have higher socioeconomic score (SES) than patients who never used OAC.

Methods:
Using Medicare claims data, we identified continuously enrolled beneficiaries with a first diagnosis of AF in 2014-2015 (n=36,185). We calculated the proportion of days covered with OAC in the first 12 months after first diagnosis. Using group-based trajectory models, we identified trajectories of OAC adherence. We constructed multinomial logistic regression to evaluated how a comprehensive list of demographics, system-level factors and clinical characteristics (list in figure) affected group membership.

Results:
We identified 4 trajectories of OAC adherence: patients who never used OAC (group 1, 43.6%), late OAC initiators (group 2, 7.6%), early OAC initiators who discontinued OAC (group 3, 8.9%), and continuously adherent patients (group 4, 39.9%). Black race, eligibility for low income subsidy, residence in segregated metropolitan areas (measured by index of dissimilarity), residence in the Southeast, Southwest or West, higher HAS-BLED score, and chronic kidney disease decreased the odds of belongings to the continuously adherent group.

Conclusions:
Trajectories of OAC adherence were highly variable, and were determined not only by demographics and clinical characteristics, but also system-level factors including income level, segregation measures, and region of residence. These trajectories may be useful in the implementation of targeted strategies to mitigate OAC underuse in stroke prevention.
Abstract MP20: Ethnic Differences in Coronary Heart Disease and Stroke Diagnosis Among Blacks in the United States
Authors: Patel Nishit , Dennison Himmelfarb Cheryl , Turkson-Ocran Ruth-Alma , Commodore-Mensah Yvonne
Published: March 2019

Introduction:
African-Americans bear a disproportionate burden of atherosclerotic cardiovascular disease than other racial/ethnic groups in the U.S. With current globalization trends, Black immigrants from Africa and Caribbean Islands contribute to the ethnic diversity of Blacks in the U.S. Despite the diversity in socioeconomic status, culture and genetic admixture, Black immigrants are traditionally combined with African Americans, therefore limiting opportunities to understand the health of Black immigrants.

Hypothesis:
Ethnic differences in coronary heart disease (CHD) and stroke prevalence exist among African-Americans (AAs), African-immigrants (AIs) and Afro-Caribbean (ACs).

Methods:
We conducted a cross-sectional study of the 2010-2016 National Health Interview Survey. CHD and stroke diagnoses were self-reported. We performed a descriptive and multivariable logistic regression analyses adjusting for demographic and health characteristics and stratified by sex.

Results:
We included 34,513 participants who were AAs (N=30,516), AIs (N=1,371) and ACs (N=2,626). Significant differences in sociodemographic characteristics were observed. AIs were the youngest (39 years) with the highest proportion of college graduates (51%). AAs (42%) were more likely to report hypertension diagnosis than AIs (19%) and ACs (36%) (p<0.05)Also, AAs (44%) were more likely to be overweight/obese than AIs (24%) and ACs (31%) (p<0.05). Diabetes prevalence was similar for AAs (13.7%) and ACs (12.8%), and lower for AIs (6.3%). Adjusted models showed that AAs were more likely to report CHD or stroke diagnoses than AIs and ACs (p<0.05). Sex-stratified models showed AA (4.2%) and AI (3.2%) women reporting similar rates of CHD diagnosis.
(Table)

Conclusion:
Ethnic differences were noted in the prevalence of CHD and stroke diagnosis and risk among Blacks. Future studies should examine the health advantage of AIs and ACs to inform interventions and policy to improve the health of AAs and maintain the health of foreign-born Blacks.