bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 042: Accelerometer-Derived Daily Life Movement Classified by Machine-Learning and Incidence of Cardiovascular Disease in Older Women: The OPACH Study
Authors: LaCroix Andrea Z , Bellettiere John , Di Chongzhi , Rosenberg Dori , LaMonte Michael J
Published: March 2019

Background:
OPACH study evidence has shown that both accelerometer-measured light (LPA) and moderate-vigorous physical activity (MVPA) are associated with CVD mortality and morbidity in older women. However, accelerometer-measured PA exposures have been limited to measuring time and intensity of movement, without providing any information about which physical activity behaviors produced the movements. This study examines associations of a validated, machine-learned classification of “daily life movement” (DLM) in relation to incident CVD events.

Methods:
Women (n=5416, mean age=79±7, 33% Black, 17% Hispanic) without prior myocardial infarction or stroke wore accelerometers for up to 7 days from May 2012-April 2014 and were followed for incident CVD through February 2018 (n=667 events). Machine-learned algorithms were developed in a sample of 39 free-living older women who simultaneously wore small cameras (SenseCam) capturing images of daily activities (used as the ground truth) and hip-worn accelerometers to measure movement. DLM was defined as standing and moving in a confined space such as around the house or garden. The DLM algorithm had 66% sensitivity and 94% specificity compared to SenseCam images and was further validated in 2 other populations. Cox models estimated hazard ratios (HR) and 95% confidence intervals for CVD across quartiles of DLM adjusting for age, race-ethnicity, smoking, alcohol use, education, co-morbidity score, physical function, and self-rated health. We then examined the DLM association with CVD after adjustment for MVPA.

Results:
Fully-adjusted HRs (95% CIs) for CVD across DLM quartiles were: [Q1-ref
1.00
; Q2
0.74
(0. 60,0.91); Q3
0.76
(0.61,0.94); Q4
0.56
(0.44,0.72); p-trend<0.001]. Hazard ratios for continuous DLM show that associations were independent of MVPA (Figure).

Conclusions:
Older women who spend more time in DLM had reduced risks of incident CVD. Increasing levels of DLM is an achievable behavioral target for reducing CVD risk in older women.
Abstract MP11: Role of Modifiable and Non-Modifiable Risk Factors in the Association of Kidney Function With Dementia Incidence in Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Sedaghat Sanaz , Bancks Michael , de Boer Ian H. , Kramer Holly , Gutierrez Orlando , Longstreth WT , Kershaw Kiarri N. , Carnethon Mercedes
Published: March 2019

Introduction:
As many as 20-50% of persons with chronic kidney disease have mild-to-moderate cognitive impairment or overt dementia. Shared risk factors, such as aging, sex, hypertension, and diabetes have been suggested to play a role in this association. Our objective was to examine the contribution of non-modifiable and modifiable risk factors to this association.

Hypothesis:
We hypothesize that non-modifiable and modifiable risk factors could explain part, but not all, of the association between worse kidney function with incidence of dementia.

Methods:
We included 6025 CVD free participants (mean age 62 yrs, 51% women, 38% white). Kidney function was assessed by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Participants were followed for an average of 12±4 yrs for dementia ICD code hospitalization. Multiple Cox regression models, adjusted for baseline non-modifiable (age, sex, race, and
APOE4
carriership) and modifiable risk factors (BMI, smoking, SBP, diabetes, cholesterol, alcohol intake, education, physical activity, and healthy diet score) were used to estimate the association of worse kidney function with incidence of dementia hospitalization.

Results:
During follow-up, 268 (4.4%) participants were hospitalized for dementia. Non-modifiable risk factors vs. modifiable risk factors were associated with greater reduction in HRs from a crude model for association between each SD lower eGFR and risk of dementia (70% vs. 8%). Non-modifiable risk factors explained a higher percentage of the association of doubling ACR with risk of dementia than modifiable risk factors (14% vs. 7%) (Figure). Adjusting for all factors, worse kidney function remained associated with incident dementia.

Conclusions:
Findings suggest that conventional modifiable and non-modifiable risk factors cannot fully explain higher risk of dementia in relation to worse kidney function. This finding warrants exploring other potential novel vascular and nonvascular mechanisms of this association.
Abstract MP13: Plasma Homocysteine is Causally Associated With Ischemic Stroke in a Han Chinese Population: A Mendelian Randomization Study
Authors: Zhu Zhengbao , Kelly Tanika N. , Zhang Yonghong , Li Changwei , Wang Aili , Xu Tan , Sun Xiao , Shi Mengyao , Bu Xiaoqing , Chen Jing , He Jiang
Published: March 2019

Introduction:
Observational studies identified plasma homocysteine as a risk factor for ischemic stroke, but randomized controlled trials of folate supplementation reported inconsistent findings. The methylenetetrahydrofolate reductase (
MTHFR)
gene encodes an enzyme critical for homocysteine metabolism and can serve as an unconfounded proxy for plasma homocysteine levels.

Hypothesis:
We assessed the hypothesis that there was a causal association between plasma homocysteine and risk of ischemic stroke by Mendelian randomization method.

Methods:
We examined the association between the
MTHFR
gene and ischemic stroke among 11,753 Chinese participants. The discovery stage included 999 ischemic stroke cases and 1,001 controls with no history of atherosclerotic disease. The
MTHFR
gene was sequenced using the SOLiD 4hq platform. Variants with minor allele count >10 were each tested for association with stroke using logistic regression models. Interactions between significant variants and alcohol drinking on stroke were also tested. Aggregate analysis of rare variants (minor allele count <20) used the sequence kernel association test. Variants achieving P<1х10
-4
were tested for replication among 4,724 ischemic stroke cases and 5,029 controls from the China Stroke Project.

Results:
An association between
MTHFR
rs1801133, a missense variant known to reduce enzyme activity and increase plasma homocysteine level, and ischemic stroke was identified in discovery, replication and joint analyses (P=2.10х10
-8
, 2.65х10
-11
, and 6.93х10
-17
, respectively). Each copy of the rs1801133 risk allele conferred respective odds ratios (95% confidence interval) of 1.44 (1.27, 1.64), 1.21 (1.15, 1.28), and 1.25 (1.18, 1.31). This variant also interacted with alcohol intake on stroke risk (P for interaction=7.82х10
-9
, 1.86х10
-10
, and 1.46х10
-18
, respectively). Odds ratios (95% confidence interval) of stroke associated with the risk allele were 1.66 (1.40, 1.96), 1.26 (1.18, 1.36), and 1.32 (1.23, 1.40) in non-drinkers and 1.17 (0.92, 1.49), 1.12 (1.01, 1.23), and 1.12 (1.03, 1.23) among alcohol drinkers in discovery, replication and joint analyses, respectively. No additional variants were identified.

Conclusions:
In conclusion, this is the first large scale genomic study to implicate the etiologic relevance of plasma homocysteine in ischemic stroke. An attenuating effect of alcohol intake on this relation was also observed.
Abstract MP15: Validation of Phenotyping Algorithms for Stroke From Electronic Health Records Using Natural Language Processing
Authors: Zhao Yiqing , Fu Suyang , Larson Nicholas B , Decker Paul A , Chamberlain Alanna M , Roger Veronique L , Liu Hongfang , Bielinski Suzette J
Published: March 2019

Background:
Accurate identification of stroke cases from electronic health record (EHR) is needed for efficient and valid clinical and epidemiology research. A number of studies have evaluated the validity of using ICD-9 and ICD-10 codes for stroke identification. Previous research results show that sensitivity and positive predictive value (PPV) for stroke identification is the lowest among all other cerebrovascular diseases, with notable differences observed by stroke pathological subtypes. While most prevalent cerebrovascular disease cases can be detected using 430-438/I60-I69 collectively, more accurate and comprehensive stroke phenotyping algorithm is needed to identify incident stroke cases from EHR. In our work, we compared case identification results using ICD-codes exclusively with ICD plus a natural language processing (NLP) algorithm.

Methods:
We developed the NLP part of our stroke algorithm using a list of expert provided stroke-related keywords, which covers transient ischemic attack (TIA), ischemic stroke, and hemorrhagic stroke. We validated the hybrid (ICD+NLP) algorithm and compared it with ICD-exclusive algorithm in a previously established atrial fibrillation cohort (n=5,062). Clinical notes and ICD codes of all patients after the incident AF event were reviewed by two nurse abstracters to confirm new stroke incidences. All past clinical notes and ICD codes of a subset of patients (n=402) were reviewed to confirm lifetime (prior and current) stroke cases. Manual abstraction results were considered the gold standard for evaluation of ICD only and ICD+NLP automatic extraction. Sensitivity and positive predictive values (PPV) of both algorithms were calculated.

Results:
Among 5,062 patients, 593 patients were confirmed to have suffered a stroke after atrial fibrillation while 4,469 patients were confirmed with no EHR evidence of stroke after AF. The ICD-exclusive algorithm had a sensitivity of 47.2% and a PPV of 47.8% for detecting new stroke incidences. The hybrid stroke algorithm achieved a sensitivity of 92.4% and a PPV of 60.6% for extraction of incident stroke. For extraction of lifetime stroke cases, the hybrid approach achieved a sensitivity of 93.9% and a PPV of 88.7%. Performance of new stroke incidence extraction is limited because past/current stroke mentions in clinical notes are difficult to distinguish by our NLP algorithm (may be a future direction).

Conclusions:
We developed and validated a stroke algorithm that performed well for identifying incident and lifetime stroke cases. The addition of NLP into the stroke algorithm improved the sensitivity and PPV of compared to an ICD-exclusive algorithm.
Abstract MP17: Comorbidity Type and Risk of Hospitalization and Death in Patients With Atrial Fibrillation
Authors: Chamberlain Alanna M , Alonso Alvaro , Noseworthy Peter , Jiang Ruoxiang , Weston Susan , Lutsey Pamela , Chen Lin , O’Neal Wesley , Bengtson Lindsay , Norby Faye , Claxton J’Neka , MacLehose Richard , Roger Veronique
Published: March 2019

Background:
Multimorbidity is common in atrial fibrillation (AF); however, the impact of the number and type of comorbid conditions on death and hospitalizations is uncertain.

Methods:
The prevalence of 17 chronic conditions was obtained in 1430 patients with incident AF from 2000-2010 from Olmsted County, MN. Chronic conditions were ascertained electronically prior to AF and were classified into 3 groups: cardiovascular (CV), other physical, and mental. All hospitalizations and deaths were obtained through 12/31/2014. Associations of the number and type of condition and each individual condition with hospitalizations and death were determined using Andersen-Gill and Cox regression, respectively.

Results:
Among the 1430 patients with AF (median age 76 years, 48.6% men), the mean (SD) number of chronic conditions was 4.7 (2.7). A total of 4496 hospitalizations and 812 deaths occurred over a mean (SD) follow-up of 5.4 (4.1) years. An increase in the number of conditions of each type was associated with increased risks of death and hospitalizations (Table). Mental conditions (which included depression, anxiety, dementia, schizophrenia, and substance abuse) exhibited the strongest association with death, whereas other physical conditions exhibited the strongest association with hospitalizations. Individual predictors of death included heart failure (HF), hypertension, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), depression, dementia, and substance abuse. Predictors of hospitalizations included HF, coronary artery disease, diabetes, COPD, CKD, arthritis, osteoporosis, and substance abuse.

Conclusions:
Patients with AF have many comorbid conditions which are associated with death and hospitalizations. Although conditions of each type were associated with outcomes, mental conditions exhibited strongest association with death. These data highlight the importance of management of not only CV comorbidities but other physical and mental comorbidities in patients with AF.
Abstract MP23: Heart Failure is Associated With Incident Venous Thromboembolism: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Norby Faye L , Fanola Christina L , Shah Amil M , Chang Patricia P , Lutsey Pamela L , Rosamond Wayne D , Cushman Mary , Folsom Aaron R
Published: March 2019

Background:
Heart failure (HF) hospitalization places patients at increased short-term risk of venous thromboembolism (VTE). However, the degree to which incident HF is a long-term risk factor for VTE is less clear, and it is unknown if the association differs by type of HF. We assessed the association between HF and VTE in the ARIC study.

Methods:
Our analysis included 10,495 participants (22% black race, 59% female, mean age 62) who were initially free of HF, cancer, and VTE in 2005. We identified incident HF from hospitalization records starting in 2005, and when possible HF was further subcategorized from hospital record review as HF with preserved ejection fraction ≥50% (HFpEF) or reduced ejection fraction of <50% (HFrEF). Incident VTE was adjudicated by physician review and classified as pulmonary embolism (PE) or deep venous thrombosis (DVT), and provoked or unprovoked. We used Cox proportional hazards models to evaluate the association between time-dependent HF and incident VTE. Follow-up time accrued from 2005 until date of VTE, loss to follow-up, death, or the end of 2015, whichever came first.

Results:
During a mean follow-up of 10 years, we identified 1005 participants who developed hospitalized HF (28% HFpEF; 27% HFrEF) and 262 who had incident VTE events. Incident HF was associated with a significantly higher risk of subsequent incident VTE: multivariable hazard ratio (HR) 5.15, 95% confidence interval (CI) 3.80-6.98. The risk of VTE was similar for HFpEF and HFrEF; HR (95% CI) = 4.71 (2.94-7.52) and 5.53 (3.42-8.94), respectively. The risk was similar when the VTE outcome was subclassified as PE or DVT or as provoked or unprovoked.

Conclusion:
In this large population-based study, incident HF was associated with a greatly increased risk of VTE, and the risk was similar in participants with HFpEF and HFrEF. Health care providers should consider possible evidence-based strategies to prevent VTE in HF patients, regardless of HF classification.
Abstract MP38: Association of Changes in Plant-Based Diet Indices with Total and Cause-Specific Mortality
Authors: Baden Megu Y , Liu Gang , Satija Ambika , Li Yanping , Sun Qi , Fung Teresa T , Rimm Eric B , Willett Walter C , Hu Frank B , Bhupathiraju Shilpa N
Published: March 2019

Introduction:
Plant-based diets have been associated with health benefits, including lower risk of type 2 diabetes (T2D) and coronary heart disease (CHD). However, the association between plant-based diets and mortality remains unclear as previous studies did not take into account the quality of plant-based foods. To overcome this limitation, we recently developed three plant-based diet indices—an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI, emphasizing processed carbohydrates and fats)—and reported that hPDI and uPDI were differentially associated with T2D and CHD. In this study, we investigate associations between long-term changes in plant-based diet indices and subsequent total and cause-specific mortality in the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS).

Hypothesis:
We hypothesized that improved plant-based diet quality is associated with lower total and cardiovascular disease (CVD) mortality.

Method:
We included 47,983 women, aged 63±7y (mean±SD) in the NHS and 25,737 men, aged 63±9y in the HPFS who had no history of CVD or cancer on or before 1998 (baseline). We used multivariable Cox proportional-hazards regression to assess the association between 12-y pre-baseline changes (1986-1998) in three plant-based diet indices and subsequent total and cause-specific mortality (1998-2014). We adjusted for age, race, initial corresponding plant-based diet index score, BMI, family history of diabetes, myocardial infarction, or cancer, history of hypertension, hypercholesterolemia, or T2D, medications, postmenopausal status and postmenopausal hormone use in women, initial and 12-y pre-baseline changes in weight and other lifestyle-related factors.

Results:
Compared with those participants whose diets remained relatively stable during the pre-baseline 12-year period, among participants with the greatest increase in plant-based diet indices, the pooled hazard ratio (95% confidence interval [CI]) for total mortality was 0.92 (95% CI, 0.87 to 0.97) for PDI, 0.90 (95% CI, 0.86 to 0.95) for hPDI, and 1.11 (95% CI, 1.05 to 1.16) for uPDI. For CVD-specific mortality, a 10-point increase in hPDI was associated with a 10% lower risk (95% CI, 5 to 15), while a 10-point increase in uPDI was associated with a 6% higher risk (95% CI, 0 to 12). We found no evidence for changes in plant-based diet indices and subsequent risk of cancer mortality.

Conclusions:
Improved plant-based diet quality over a 12-year period was associated with a lower risk of total and CVD mortality, whereas increased consumption of an unhealthful plant-based diet was associated with a higher risk of total and CVD mortality.
Abstract MP46: Fasting Glucose Variability in Young Adulthood and Incident Diabetes, Cardiovascular Disease, and Mortality: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Bancks Michael , Carson April , Lewis Cora , Gunderson Erica , Reis Jared , Schreiner Pamela , Yano Yuichiro , Carnethon Mercedes
Published: March 2019

Introduction:
Whether long-term variability in fasting glucose (FG) independent of incident diabetes mellitus (DM) is associated with incident cardiovascular disease (CVD) and mortality is unclear.

Hypothesis:
Higher variability of FG would be associated with higher risk for incident CVD and mortality as compared with lower FG variability, independent of increases in FG over time and the development of DM.

Methods:
We studied 4210 black and white CARDIA participants, ages 18 to 30 years (1985-1986) at baseline and calculated 2 measures of long-term glucose variability, the coefficient of variation about the mean (CV-FG) and the absolute difference between successive FG measurements (average real variability; ARV-FG) before the onset of DM. We estimated hazard ratios (HR) for incident CVD and mortality over 30 years of follow-up with adjustment for time-varying CVD risk factors.

Results:
There were 417 incident cases of DM, 195 incident CVD events (122,279 person-years) and 237 deaths (123,505 person-years). The HR for incident CVD per 1-standard deviation (1-SD) higher CV-FG was 1.24 (95% confidence interval [CI]: 1.08, 1.42) and for ARV-FG was 1.14 (95% CI: 1.01, 1.28) after adjustment for demographics, baseline FG, change in FG, and time-varying education, smoking, alcohol consumption, body mass index, physical activity, systolic blood pressure (BP), BP medications, low-density lipoprotein cholesterol, cholesterol medications, incident DM, and DM medications (Figure 1A and 1B). HRs for mortality were similar in magnitude for 1-SD ARV-FG (HR: 1.22, 95% CI: 1.10, 1.35) and slightly weaker for CV-FG (HR: 1.12, 95% CI:0.98, 1.27) after adjustment for time-varying CVD risk factors. The majority of mortality and the variability-mortality association was due to non-CVD mortality. Associations were similar in magnitude when restricted to individuals without incident DM.

Conclusion:
Higher intra-individual FG variability during young adulthood before the onset of DM was associated with incident CVD and mortality.
Abstract MP48: Control of Cardiovascular Risk Factors Among Older Adults With Incident Diabetes: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Malla Gargya , Cherrington Andrea , Zhu Sha , Cummings Doyle M , Clay Olivio , Brown Todd M , Lee Loretta T , Kimokoti Ruth , Cushman Mary , Safford Monika M , Carson April P
Published: March 2019

Background:
Control of risk factors is important for the primary prevention of cardiovascular disease among adults with diabetes. The objective of this study was to determine whether management of clinical (hemoglobin A1c <8%; BP <130/80 mm Hg; and statin use) and lifestyle factors (not currently smoking; physical activity on 4+ days/week; and moderate or no alcohol use) varied by race and sex among older adults with incident diabetes.

Methods:
This study included 1,420 Black and White adults from the REGARDS Study with incident diabetes at the follow-up exam (2014-16). Incident diabetes was defined as fasting glucose>=126 mg/dL, random glucose>=200 mg/dL, or use of diabetes medications among those without diabetes at baseline (2003-07). Modified Poisson regression was used to obtain prevalence ratios (PR) for the control of risk factors for Black versus White adults and assess race-sex interactions.

Results:
The mean age was 71.5 years, 53.6% were female, 46.1% were Black and 85.7% reported they were aware of their diabetes. BP control was lower for Black males than White males (p=0.0036), whereas statin use was lower for Black females than White females (p=0.0241). For lifestyle factors, not smoking was lower for Black males than White males (p=0.0187), whereas moderate or no alcohol use was higher for Black females than White females (p<0.0001). (Figure) Race-sex interactions were not statistically significant. In age and sex-adjusted models, Black adults were less likely to have BP controlled (PR=0.89; 95% CI=0.81, 0.99) or use statins (PR=0.88; 95% CI=0.80, 0.97) and more likely to report moderate or no alcohol use (PR=1.05; 95% CI=1.03, 1.07) than White adults. Control of other factors was similar.

Conclusion:
Although control of individual risk factors was generally high among older adults with incident diabetes, racial differences in BP control and statin use were apparent. Assessment and management of cardiovascular risk factors in this high-risk population remains important for prevention.
Abstract MP51: Sleep Characteristics and Adverse Social Exposures Elevate Blood Pressure in Young Black Females
Authors: Scott Jewel , Silva Susan , Simmons Leigh Ann
Published: March 2019

Introduction:
The prevalence of hypertension (HTN) in Black females is 46%, which is higher than males and other females in the United States. Among Black females, HTN develops at younger ages and often is more difficult to treat. Research suggests that sleep quality and quantity may have sex- and race-specific implications for CV health. Further, sleep characteristics may be a behavioral response to adverse social exposures (e.g., discrimination, financial stress), and this response may be amplified among young adults.

Hypothesis:
We assessed the hypothesis that sleep characteristics and adverse social exposures may contribute to elevated blood pressure in Black women.

Methods:
Participants included 634 Black females who participated in the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative study of youth in the U.S. initially enrolled between 7
th
-12
th
grades and followed over 2.5 decades. Adverse social exposures included child abuse, discrimination, perceived stress, social isolation, and subjective social status. Self-reported sleep characteristics included measures of duration, latency, continuity, and snoring. Applying 2018 AHA guidelines, participants were classified as having elevated BP (>120/80) or not in early adulthood (age 24-32 years). Bivariate and multivariable logistic regression was used to evaluate the influence of social exposures, sleep characteristics, and their interactions on elevated BP.

Results:
Despite a mean age of 28.9 years, 58% (374 of 634) of the sample had elevated BP. In bivariate analyses, lack of sleep continuity, snoring, less social isolation, and less perceived stress predicted elevated BP, but sleep duration and latency did not. Multivariable analyses that adjusted for demographics, BMI, and depression indicated that elevated BP was associated with snoring (OR 1.458, p=0.03), frequent awakening (OR 1.904, p=0.0005), less social isolation (OR 0.691, p=0.05), and lower perceived stress (OR 0.646, p=0.02). Interactions between sleep characteristics and social exposures were insignificant in predicting elevated BP.

Conclusions:
Sleep characteristics may represent a key risk factor for HTN that could be addressed in targeted interventions beginning in adolescence. Given the unexpected inverse relationship between social isolation, perceived stress, and elevated BP, future research should examine how current paradigms and measures of social connectedness and stress may need to be adapted to better elucidate the impact of these factors on Black women’s long-term CV health.
Abstract MP57: Genetics of Chronic Kidney Disease Stages Across Ancestries: The PAGE Study
Authors: Franceschini Nora , Lin Bridget M
Published: March 2019

Background:
Chronic kidney disease (CKD) is common, disproportionally burdens ethnic minorities in the US, and is associated with increased cardiovascular mortality. Our prior trans-ethnic genetic research has identified approximately 100 loci for kidney function. We now extend this research to CKD stages in studies of diverse populations. To uncover genetic factors associated CKD stages, we performed genome-wide association studies in diverse populations within the Population Architecture using Genomics and Epidemiology (PAGE) study.

Methods:
We assembled multi-ethnic data on CKD non-overlapping cases (4,690 mild to moderate CKD, 1,105 advanced CKD [stage 5] including end-stage kidney disease) and non-CKD controls for up to 46,263 PAGE participants (African Americans, Hispanics/Latinos, East Asian, Native Hawaiian and American Indians). We implemented a generalized estimating equation approach for single test genome-wide association analyses using ancestry combined data and adjusting for age, sex, principal components, study and ethnicity.

Results:
The analyses identified two associated loci at p < 5.3 x 10
-8
, including a novel association with mild to moderate CKD on chromosome 9, which is driven by an intronic variant of
TYRP1
(rs186208070, allele frequency 0.01 in our combined sample, 1000 Genomes: 0.02 in AFR, 0.003 AMR, 0.001 EUR, p=4.4 x 10
-8
). Several genome-wide associated variants at the
APOL1
locus were associated with advanced CKD. The most significant finding was for
APOL1
G1 rs73885319 (p=1.19 x 10
-9
). Additional variants with suggestive associations at p<10
-6
for advanced CKD included an intronic low frequency variant in
FTO
(rs7189997) and a variant nearby
IRX3
(rs8050506). Both variants are more common in African ancestry and these loci were previously associated with obesity traits.

Conclusions:
Our study on the genetics of CKD identified a novel locus for mild to moderate CKD and showed for the first time strong associations of African-ancestry
APOL1
variants with advanced CKD across multi-ethnic populations.
Abstract MP62: Associations of Timing of Complementary Feeding Introduction and Adiposity Throughout Childhood and Adolescence
Authors: Gingras Veronique , Aris Izzuddin M , Rifas-Shiman Sheryl L , Switkowski Karen M , Oken Emily , Hivert Marie-France
Published: March 2019

Introduction:
Complementary feeding includes introducing food or beverages other than breastmilk or formula to infants. We previously showed associations of early complementary feeding (<4 months old) with higher obesity risk at 3 years old in formula-fed children only.

Hypothesis:
We hypothesized that associations with adiposity would persist into early adolescence.

Methods:
Among 991 children from Project Viva, a pre-birth prospective cohort, we examined associations of complementary feeding timing with later body mass index (BMI) z-scores, waist circumference, and dual-energy radiograph absorptiometry (DXA) measured adiposity in mid-childhood (mean: 7.8, SD 0.8 years old; N=681) and in early adolescence (mean: 13.2, SD 0.9 years old; N=637). We used linear regression models adjusted for socio-demographic characteristics, parental BMI, and change in weight-for-age z-score from 0 to 4 months (as a marker of early infant growth); the reference group for all analyses was complementary feeding initiation between 4 to <6 months. We ran separate models for infants who were breastfed for ≥4 months (breastfed) and infants who were never breastfed or weaned <4 months of age (formula-fed). As a secondary analysis, we fitted individual BMI trajectories using mixed-effect models with natural cubic spline functions (N=952), and then examined the association of timing of complementary feeding with age at BMI rebound derived from the trajectories, using linear regression models, adjusting for previously listed covariates.

Results:
At 4 months of life, 66% (654 of 991) of children were breastfed and 34% (337 of 991) were formula-fed. Complementary feeding was introduced <4 months for 19% (188 of 991), between 4 to <6 months for 68% (674 of 991; reference group), and ≥6 months for 13% (129 of 991) of children. Complementary feeding <4 months was associated with higher waist circumference in both formula-fed (β 2.60, 95% CI [0.35, 4.86] cm) and breastfed children (1.98 [0.07, 3.89] cm) in mid-childhood, while in early adolescence, it was associated with higher BMI z-score (0.36 [0.04, 0.68]) in formula-fed children, and with higher waist circumference in both formula-fed (4.99 [1.14, 8.84] cm) and breastfed children (3.12 [0.02, 6.21] cm). Complementary feeding <4 months was additionally associated with an earlier age at BMI rebound (-7.6 [-12.6, -2.5] months) in breastfed children. Complementary feeding initiated ≥6 months was associated with higher BMI z-score (0.50 [0.04, 0.97]) in mid-childhood and with an earlier age at BMI rebound (-11.5 [-20.0, -2.9] months) in formula-fed children only.

Conclusions:
We found associations of both early and late introduction of complementary feeding with BMI z-score in formula-fed infants and with waist circumference in breastfed and formula-fed infants throughout childhood.
Abstract P001: Greater Time Spent in Ideal Cardiovascular Health in Adulthood is Associated With Lower Risk of Cardiometabolic Outcomes and Death: the Framingham Heart Study
Authors: Corlin Laura , Short Meghan I , Vasan Ramachandran S , Xanthakis Vanessa
Published: March 2019

Introduction:
The AHA ideal cardiovascular health (CVH) metric evaluated on a single occasion is associated with risk of cardiovascular disease (CVD). It is unclear if greater time spent in ideal CVH during midlife influences morbidity and mortality.

Hypothesis:
We hypothesized that maintenance of ideal CVH for a longer duration in midlife is associated with lower risk of hypertension, diabetes mellitus, chronic kidney disease (CKD), atrial fibrillation, CVD, CVD sub-types (coronary heart disease, stroke, congestive heart failure, and peripheral artery disease), and all-cause mortality.

Methods:
We evaluated 2609 Framingham Offspring Study participants (mean age 61 years; 54% women) who attended examination cycle 7 [1998-2001]. CVH scores were calculated using smoking status, diet, physical activity, total serum cholesterol, resting blood pressure, body mass index, and fasting blood glucose for a total score of 0-14 (score of 0-7 = poor; 8-11 = intermediate; 12-14 = ideal). We determined time spent in each CVH score category during midlife (using data from examination cycles 5 [1991-1995] through 7 (6426 person-exams). Incident hypertension, diabetes, and CKD were assessed at sequential follow-up examinations whereas incident atrial fibrillation, CVD, CVD sub-types, and mortality were assessed based on continuous surveillance through 2015. Years spent in a given CVH score category were related to each outcome using proportional hazards regression with discrete (for hypertension, diabetes, and CKD) or continuous (other outcomes) time, adjusted for age, sex, and baseline values (e.g., fasting blood glucose for diabetes).

Results:
At examination 7, participants mostly had poor (40%) or intermediate (54%) CVH scores. For each 5-year duration that participants had poor CVH, they were more likely to develop adverse outcomes (Figure).

Conclusions:
Maintenance of ideal CVH for a longer duration in midlife may have salutary cardiometabolic benefits and be associated with a lower risk of all-cause mortality.
Abstract P008: Pulse Pressure Following a Brief Patient Rest Period: Age and Gender Variations
Authors: Nguyen Landai , Sachdev Sarina , Tahir Hassan , Omar Bassam , Rahimi Farnoosh , Malozzi Christopher , Awan G. Mustafa
Published: March 2019

Background:
Increased pulse pressure (PP) is an independent determinant of cardiovascular disease. The effect of rest period on office-based systolic blood pressure has been previously reported, but not on PP in particular. Whether such rest period impacts the measured pulse pressure, and the variability of such response with age and gender remains unknown.

Methods:
Patient charts reviewed in University-based cardiology clinic identified 170 encounters which contained blood pressure (BP) re-measurement data due to elevated initial BP of > 130/80 mmHg. BP was measured initially by the nurse, with the patient in a sitting position and the arm resting at the level of the heart. If BP was > 130/80 mmHg, it was repeated by the physician after resting the patient for 15 minutes. There were 112 (66%) elderly patients ≥ 60 years of age and 58 (34%) younger patients < 60 years of age. Among the elderly patients, there were 51 males (46%) and 61 females (54%).

Results:
Among all encounters, after a brief rest period, initial pulse pressure (PP) of 67 ± 2 mmHg decreased to 62 ± 1 mmHg (5 mmHg; P < 0.01). PP decreased by 8 mmHg in the elderly (72 ± 2 to 64 ± 2 mmHg; P < 0.01) but did not significantly change in the young (56 ± 3 to 58 ± 3 mmHg; P = NS). PP decrease among the elderly was more pronounced in females (11 mmHg; 76 ± 4 to 65 ± 2 mmHg; P < 0.01) compared with males (4 mmHg; 68 ± 3 to 64 ± 2 mmHg; P = 0.03).

Conclusion:
Hypertension is a challenging public health problem. The new ACC/AHA High Blood Pressure Guidelines have decreased the range for Stage 1 hypertension to systolic blood pressure of 130-139 mmHg, and diastolic blood pressure of 80-89 mmHg, with normal blood pressure as less than 120/80 mmHg. Blood pressure guidelines recommend that prior to BP measurement, persons should be seated quietly for at least 5 minutes in a chair, with feet on the floor, and arm supported at heart level; which resulted in significant decrease in pulse pressure in our patients. We show that while a decrease in pulse pressure was confined to the elderly, elderly females had a more pronounced PP decrease compared to males; both, however, fell to the same level. White coat hypertension may explain this observation, since it is more frequent in elderly females. The implication of this observation is that physicians should take extra care in re-measuring the blood pressure and pulse pressure, especially in elderly females, in whom a more pronounced drop in pressure may be observed after a brief rest period, and thereby, result in reclassifying their risk and need for treatment.
Abstract P009: Association Between Intracranial Subclinical Vessel Diseases and Cognition in a Community-Based Sample of Japanese Men: Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA)
Authors: Ito Takahiro , Fujiyoshi Akira , Ohkubo Takayoshi , Shiino Akihiko , Nozaki Kazuhiko , Miyagawa Naoko , Torii Sayuki , Hisamatsu Takashi , Miura Katsuyuki , Ueshima Hirotsugu
Published: March 2019

Background and Purpose:
Intracranial subclinical vessel diseases are considered important indicators of cognitive impairment. However, comprehensive assessment on various types of vessel disease is lacking. We aim to compare various types of intracranial vessel disease in association with cognitive function among a community-based male population.

Method:
The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited and examined participants from Shiga, Japan in 2006-08 at baseline. Among 824 male participants in the follow-up exam (2010-12), we restricted our analyses to those who underwent the Cognitive Abilities Screening Instrument (CASI), cranial magnetic resonance imaging/angiogram (MRI/MRA, 1.5-Tesla), and free of stroke or neurodegenerative disease. Using MRI/MRA, we assessed intracranial arterial stenosis and four types of small vessel diseases: lacunar infarction and microbleed, periventricular hyperintensity (PVH), deep and subcortical white matter hyperintensity (DSWMH). We graded each vessel disease into 3 grades by severity. Cerebral artery stenosis was graded according to the presence of most stenotic lesions in the major 11 vessels: no stenosis (grade 1), 1-50% stenosis at least 1 vessel (grade 2), ≥ 50% stenosis at least 1 vessel (grade 3). Lacunar infarct was graded according to number of infarct: 0 (grade 1), 1-2 (grade 2), >2 (grade 3). Microbleed was graded according to number of microbleed: 0 (grade 1), 1 (grade 2), ≥2 (grade 3). PVH and DSWMH were graded according to Shinohara’s scale (a modified Fazekas scale): scale 0 to 1 (grade 1), scale 2 (grade 2), scale ≥3 (grade 3). Using linear regression, CASI score (ranging from 0 to 100 with a higher score indicating better cognition) was calculated according to the grade of each vessel disease adjusted for age and education year attained.

Results:
We analyzed 693 men. Mean (standard deviation) age and CASI score was 67.9 (8.1) years, and 91.2 (5.4), respectively. Significant inverse trends were observed between disease grade and CASI score for DSWMH and PVH: adjusted CASI scores of grade 1, 2, and 3 were 91.7, 91.2, and 90.4 (P
trend
0.015) for DSWMH, and 91.5, 90.4, and 89.8 (P
trend
0.007) for PVH. No clear trend across the grade was observed in other vessel diseases.

Conclusion:
Among various types of intracranial subclinical vessel diseases assessed with MRA/MRI, white matter hyperintensity (PVH, and DSWMH) had significant dose-response relationships to cognitive function in a community-based male sample that has a relatively well-preserved cognition level. Our finding suggests that white matter hyperintensity is an important early predictor of cognitive functions among subclinical vessel diseases.
Abstract P010: Do the Pooled Cohort Equations Accurately Predict Cardiovascular Disease Risk in Older Adults?
Authors: Nanna Michael , Peterson Eric , Wojdyla Daniel , Navar Ann Marie
Published: March 2019

Background:
The ACC/AHA Pooled Cohort Equations (PCE), derived using data from adults ages 40-79, have not been evaluated for accuracy among older adults.

Methods:
We evaluated 2,667 adults aged ≥75 years without known ASCVD in the NIH pooled cohorts (Framingham, Framingham offspring, MESA, & CHS), stratified by number of major risk factors [smoking, diabetes, lipids (LDL≥130 mg/dL or on lipid-lowering therapy), and BP (≥140/90 mmHg or on BP medication)]. Observed vs. predicted 5-year ASCVD event rates were compared across strata. We also evaluated 5-year PCE model performance overall.

Results:
At the group level, the PCE somewhat overestimated risk across all strata in Kaplan Meier analysis: observed versus expected was 7.0% vs. 11.0%, (p=0.005) for those with no risk factors (N=429), 12.5% vs. 15.4%, (p<0.001) for those with 1 risk factor (N=1,179), 14.7% vs. 18.4 % (p=0.003) for those with 2 risk factors (N=908), and 24.2% vs. 25.1 % (p=0.54) for those with 3+ risk factors (N=151). The Figure shows the performance of the PCE by decile of predicted risk. In the figure, risk-overestimation appears to be driven by over-estimation of risk in the highest deciles of risk, rather than those at low predicted risk.

Conclusion:
The PCE can be used to risk-stratify older adults. However, it may over-predict risk, especially in those at the top quartile of risk.
Abstract P027: Perceived Discrimination and Trajectory of High-Sensitivity C-Reactive Protein: The Jackson Heart Study
Authors: Sims Kendra D , Sims Mario , Glover LáShauntá , Smit Ellen , Odden Michelle C
Published: March 2019

Introduction:
Perceiving discriminatory treatment against oneself may induce a stress response, and over time contribute to cardiovascular pathophysiology. The study evaluated the association of self-reported discrimination and changes in high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation predictive of incident cardiovascular disease.

Hypothesis:
We assessed the following hypotheses: 1) higher levels of perceived discrimination are associated with higher serum hs-CRP at baseline, 2) over 13 years of follow-up, greater mean increases in hs-CRP are observed among those with higher levels of baseline discrimination than those with lower levels of discrimination, and 3) body composition mediates the longitudinal trajectory.

Methods:
The sample included 5145 African American participants, aged 21-92, in the Jackson Heart Study. Multiple imputation addressed missingness in baseline sociodemographic (e.g, age, sex, education), behavioral (e.g., AHA smoking and physical activity categorizations) and clinical covariates (e.g, estimated glomerular filtration rate, diastolic blood pressure, hemoglobin A1c) as well as in hs-CRP taken at all three study examinations. Everyday, lifetime, and burden from perceived discrimination -attributed to reasons including race, gender, age, or weight- comprised primary predictors in three sets of multivariable linear regression models of baseline (2000-2004) discrimination and ln(hs-CRP). Linear mixed models (LMMs) were fitted to assess mean changes in ln(hs-CRP) between three study examinations (2000-2013).Mediation was quantified by percent changes in estimates adjusted for the adiposity measures BMI, waist circumference, or waist-to-height ratio.

Results:
In the cross-sectional analyses, those in the highest tertile of lifetime discrimination had adjusted ln(hs-CRP) levels 0.08 ln(mg/dL) lower than those in the lowest tertile (95% CI= -0.16, -0.01). However, the ln(hs-CRP) increases among those reporting more frequent everyday discrimination were 0.07 ln(mg/dL) higher per examination than those reporting no everyday discrimination (95% CI=0.01, 0.12) A similar trend emerged for lifetime discrimination and changes in ln(hs-CRP) (adjusted mean increase per visit: 0.04 ln(mg/dL), CI=0.01, 0.08). BMI, waist circumference, or waist-to-height ratio did not mediate the longitudinal associations between any discrimination measure and hs-CRP. In sensitivity analyses, the magnitude of these estimates did not change before or after multiple imputation.

Conclusion:
Everyday and lifetime discrimination were associated with significant hs-CRP increases over 13 years of follow-up. These conclusions build upon the existing research that indicates the physiological response to discrimination may lead to systemic inflammation and in turn cardiovascular disease.
Abstract P028: Gut Microbiota-Related Metabolites and Long-Term Bone Health in Response to Weight-Loss Diets: The POUNDS Lost Trial
Authors: Zhou Tao , Heianza Yoriko , Chen Yuhang , Sun Dianjianyi , Pei Xiaofang , Bray George , Sacks Frank , Qi Lu
Published: March 2019

Introduction:
Weight-loss diet interventions affect gut microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors (choline and L-carnitine), and improve cardiometabolic status. However, little is known about how these metabolites may affect bone mineral density (BMD) during weight loss.

Hypothesis:
We assessed the hypothesis that changes in gut microbiota-related metabolites are related to changes in BMD during weight loss.

Methods:
A total of 264 overweight and obese participants with measurement of BMD by dual-energy X-ray (DEXA) scan were included in the present analysis. The participants were randomly assigned to one of four diets varying in macronutrient intakes. We investigated the associations of changes in plasma levels of TMAO, choline, and L-carnitine from baseline to 6 months with changes in BMD.

Results and Conclusions:
We found that changes in plasma levels of TMAO from baseline to 6 months were positively related to changes of whole body (
P
=0.011) and spine (
P
=0.002) BMD over the 2-year intervention, independent of weight change. The association with whole body BMD was also significant at 6 months. The correlations between changes in TMAO and BMD were not modified by dietary macronutrients; while changes in TMAO precursor L-carnitine showed interactions with dietary fat intake on changes of spine and trochanter BMD (all
P
<0.05). Participants with the least L-carnitine decrease showed less BMD reduction by eating a low-fat diet (

P
spine

=0.031 and

P
trochanter

=0.017). In conclusion, our results suggest that decrease in TMAO during weight loss may be related to reduction in BMD.
Abstract P031: Plasma Xanthine Oxidoreductase Activity is Associated With Edothelial Dysfucntion and Increased Arterial Stiffness in a General Japanese Population: the Iwate Tohoku Medical Megabank Project
Authors: Kotozaki Yuka , Tanno Kozo , Ohmomo Hideki , Tanaka Fumitaka , Otomo Ryo , Shimizu Atsushi , Sakata Kiyomi , Hitomi Jiro , Sasaki Makoto , Satoh Mamoru
Published: March 2019

An increase in xanthine oxidoreductase (XOR) activity is related to various diseases such as diabetes, hypertension and obesity has been reported. However, so far the association with XOR activity and pathogenesis of atherosclerosis in a general Japanese population are not known. The purpose of this study is to investigate the association between XOR activity and progression of atherosclerosis including pulse wave velocity (PWV) and flow mediated dilation (FMD) in a general Japanese population.

The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture (n = 810, male / female = 271 / 539, age = 67.6 ± 7.2).

Plasma levels of XOR activity in males were marginally higher than in females (89.6 ± 187.0 vs. 64.8 ± 145.8 pmol / h/ mL, p = 0.06). Arterial stiffness by PWV after log10 transformation was significantly higher in quartiles III and IV of XOR compared to quartiles I in females (F =4.768, p < 0.01) (quartiles I vs. III, 3.187 ± 0.088 vs. 3.214 ± 0.081, p < 0.01; quartiles I vs. IV, 3.187 ± 0.088 vs. 3.213 ± 0.080, p < 0.05). Endothelial function as assessed by FMD was significantly lower in quartiles III and IV compared to quartiles I in females (F = 6.074, p < 0.001) (quartiles I vs. III, 6.02 ± 3.19 vs. 4.90 ± 2.66 %, p < 0.01; quartiles I vs. IV, 6.02 ± 3.19 vs. 5.04 ± 2.76 %, p < 0.01). XOR activity was related to progression of atherosclerosis (FMD, OR = 0.930, p = 0.06) and the high risk for CVD in females (Suita Score ≥ 41, OR = 1.92, 95% confidence interval (CI) = 1.04 - 3.54, p < 0.05). XOR activity was no significant association with progression of atherosclerosis and the high risk for CVD in males. The area under the curve (AUC) for XOR activity combined with Suita score was 0.66 (95% CI = 0.52 - 0.77, p < 0.05).

In conclusion, XOR activity is associated with endothelial dysfunction and increased arterial stiffness suggesting that elevated XOR activity may relate to progression of atherosclerosis and indicate the CV risk.