bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP21: Feasibility of Electronic Health Records-based community surveillance of cardiovascular disease: Findings from the Atherosclerosis Risk in Communities Study.
Authors: Bogle Brittany M , Rosamond Wayne D , Folsom Aaron R , Sorlie Paul , Soliman Elsayed Z , Wagenknecht Lynne , Kucharska-Newton Anna , Moore Carlton , Haas Stephanie W , Heiss Gerardo
Published: July 2021

Background:
Accurate community surveillance of cardiovascular disease requires hospital record abstraction, which is typically a manual process. The costly and time-intensive nature of manual abstraction precludes its use on a regional or national scale in the US. Whether an efficient system can accurately reproduce traditional community surveillance methods by processing electronic health records (EHRs) has not been established.

Objective:
We sought to develop and test an EHR-based system to reproduce abstraction and classification procedures for acute myocardial infarction (MI) as defined by the Atherosclerosis Risk in Communities (ARIC) Study.

Methods:
Records from hospitalizations in 2014 within ARIC community surveillance areas were sampled using a broad set of ICD discharge codes likely to harbor MI. These records were manually abstracted by ARIC study personnel and used to classify MI according to ARIC protocols. We requested EHRs in a unified data structure for the same hospitalizations at 6 hospitals and built programs to convert free text and structured data into the ARIC criteria elements necessary for MI classification. Per ARIC protocol, MI was classified based on cardiac biomarkers, cardiac pain, and Minnesota-coded electrocardiogram abnormalities. We compared MI classified from manually abstracted data to (1) EHR-based classification and (2) final ICD-9 coded discharge diagnoses (410-414).

Results:
These preliminary results are based on hospitalizations from 1 hospital. Of 684 hospitalizations, 355 qualified for full manual abstraction; 83 (23%) of these were classified as definite MI and 78 (22%) as probable MI. Our EHR-based abstraction is sensitive (>75%) and highly specific (>83%) in classifying ARIC-defined definite MI and definite or probable MI (Table).

Conclusions:
Our results support the potential of a process to extract comprehensive sets of data elements from EHR from different hospitals, with completeness and accuracy sufficient for a standardized definition of hospitalized MI.
Abstract MP22: Feasibility of Electrocardiographic Identification and Classification of Myocardial Infarction Using Electronic Health Records. The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Baldassari Antoine R , Soliman Elsayed Z , Whitsel Eric A , Folsom Aaron R , Matsushita Kunihiro , Butler Kenneth , Bogle Brittany M , Zhang Zhu-Ming , Loop Matthew S , Heiss Gerardo
Published: July 2021

Background:
Standardized coding of 12-lead electrocardiograms (ECGs) enables an accurate classification of hospitalized myocardial infarction (MI). Although the costs of ECG coding are difficult to sustain in long-term community surveillance, automated protocols for identifying and classifying MI using electronic health records (EHR) have not incorporated ECG coding. We developed a process to retrieve and automatically code ECGs from EHR and compared its performance to ECGs coded at a specialized ECG reading center.

Methods:
Samples of EHR pertaining to hospitalizations previously included in hospital record abstraction and Minnesota coding of ECGs per the ARIC protocol were obtained. We assigned Minnesota codes (MCs) to the terms used by manufacturers of three ECG devices to interpret ECGs, extracted machine interpretation text from the EHR, and applied natural-language processing to match the interpretations to MCs. We defined MI by MCs as any major Q code (1.1.x, 1.2.x), or the co-occurrence of any minor Q (1.3.x) and major ST segment depression (4.1, 4.2) or T wave inversion code (5.1, 5.2). MI algorithmically ascertained from EHR was then compared to that based on MCs assigned by the ECG reading center.

Results:
Among 160 hospitalizations from 149 individuals admitted in 2014 to one hospital, ECG interpretations were matched to a median of three Minnesota-coded terms. There was moderate-to-substantial agreement between EHR-derived and ARIC-assigned MI by MC (
κ
=0.60, 95% CI: 0.41, 0.79). Thirteen (81%) of the 16 ECGs with ARIC-assigned MCs defining MI also had EHR-derived MCs defining MI (Table 1). The corresponding specificity, positive predictive value, and negative predictive value were 0.92±0.02, 0.56±0.12, and 0.97±0.01.

Conclusion:
Novel, EHR-based automated approaches to electrocardiographic identification and classification of MI are feasible, relatively accurate even without pending refinements, and promise to reduce the effort and costs associated with population-based MI surveillance.
Abstract MP23: Completeness in the Abstraction of Cardiac Biomarkers and Cardiac Pain Data From Electronic Health Records (EHR). Findings From the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kucharska-Newton Anna , Bullo Manuela , Loop Matthew , Moore Carlton , Haas Stephanie W , Rosamond Wayne , Futrell Wendell , Luo Kehan , Yadav Harish , Bogle Brittany
Published: July 2021

Background:
Calibration of case-finding algorithms from electronic health records (EHR) against established disease surveillance protocols is key to avoiding misclassification bias when using EHR data in epidemiological research. We examined the agreement in the classification of troponin I levels and identification of cardiac pain in hospital EHR data against manually abstracted charts for hospitalizations observed by the ARIC community surveillance of cardiovascular events.

Methods:
A structured data request for laboratory data and provider notes was submitted to hospitals in the ARIC community surveillance program. Computer programs were developed to extract dates of service, type of laboratory assays performed, and individual assay values for days 1-4 of each hospitalization. Presence of cardiac pain was extracted from provider notes using natural language processing protocols. We calculated percent agreement for troponin I values, kappa statistics for their classification as abnormal (values ≥ twice upper limit normal (ULN)), equivocal (values ≥ULN, but < twice ULN) normal (<ULN), and incomplete, and validity statistics for cardiac pain. Abstraction of information from the medical records by trained abstractors was considered the “gold standard” for comparisons. The analysis sample consisted of all events eligible for full abstraction discharged from one hospital in 2014. Analytical code was created using a “training” dataset randomly-selected from the analysis sample, with the final results computed using a validation sample.

Results:
Of the 126 EHRs, 104 were eligible for abstraction of cardiac biomarkers and pain information. Agreement in the troponin I values was 75.5% (95%CI: 65.8%, 83.6%) for day 1 of the hospitalization, decreasing thereafter to 62.5% (95%CI: 24.5%, 91.5%) for Day 4. The kappa coefficient for the classification of troponin I values was 0.96 (95% CI: 0.90, 1.00), We observed a high sensitivity in the abstraction of information on cardiac pain (0.99 (95%CI: 0.94, 1.0)). The specificity of cardiac pain information was 0.24 (95% CI: 0.16, 0.35) when extracted from all note types, increasing to 0.90 (95%CI: 0.75, 0.97) if extracted from discharge notes.

Conclusion:
Troponin I values and manifestation of ischemia such as cardiac pain are critical to the classification of acute coronary events. Therefore, the observed excellent agreement with the gold standard ARIC abstraction shows promise for the use of EHRs in the surveillance of acute cardiovascular disease.
Abstract MP25: Obesity, Heart Failure Risk & Cardiorespiratory Fitness
Authors: Kokkinos Peter F , Narayan Puneet , Faselis Charles , Myers Jonathan , Lavie Carl , Aiken Monica , Ahmed Ali , Mordini Federico , Moore Hans , Karasik Pamela
Published: July 2021

Introduction:
Obesity, defined as body mass index (BMI) ≥30 kg/m
2
, is associated with increased incidence of heart failure (HF). Increased cardiorespiratory fitness (CRF), as indicated by increased exercise capacity, is associated with lower risk of cardiovascular disease and HF. However, the CRF-BMI-HF interaction has not been fully explored.

Hypothesis:
We assessed the hypothesis that the risk of HF associated with increased BMI is moderated by increased CRF.

Methods:
We identified 19,881 Veterans (mean age: 58.0±11.3 years) who completed an exercise tolerance test (ETT) to assess either CRF status or suspected ischemia at two VA Medical Centers (Washington DC and Palo Alto, CA). None had documented HF at baseline or evidence of ischemia during the ETT. We established four BMI categories: <25 kg/m
2
; 25-29.9 kg/m
2
; 30-34.9 kg/m
2
; and ≥35 kg/m
2
. In addition, we established four CRF categories based on age-stratified quartiles of peak metabolic equivalents (METs) achieved (mean ± SD): Least-Fit (4.5±1.2 METs; n=4,743); Low-Fit (6.6±1.3; n=5,103); Moderate-Fit (8.0±1.3 METs; n=5,084); and High-Fit (11.1±2.4 METs; n=4,951). Multivariable Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals [CI] for incidence of HF across BMI categories for the entire cohort, using BMI 25-29.9 kg/m
2
(lowest HF rate) as the reference group. We then stratified the cohort by the four BMI categories and assessed HF risk across CRF categories within each stratum, using the Least-fit category as the reference group. The models were adjusted for age, race, gender, cardiac risk factors, sleep apnea, alcohol dependence, medications.

Results:
During follow-up (median=11.8 years), 2,193 developed HF (10.5 per 1,000 person-years of follow-up). The HF risk for normal weight individuals (18.5-24.9 kg/m2) was 10% higher (p=0.93). For obese individuals, the HF risk was 22% higher in those with BMI 30-34.9 kg/m
2
(HR=1.22; 95% CI: 1.09-1.35) and 50% higher (HR=1.50, 95% CI: 1.32-1.72) for those with BMI ≥35 kg/m
2
. When CRF (peak METs achieved) was introduced in the model, the risk for those with BMI 30-34.9 was reduced from 22% to 16% (HR=1.16; 95% CI: 1.04-1.29) and from 50% to 29% (HR=1.29; 95% CI: 1.13-1.48) among those with ≥35 kg/m
2
. For every 1-MET increase in exercise capacity, HF risk was 15% lower (HR=0.85; 95% CI: 0.83-0.87). We then assessed the impact of CRF on the risk of HF within each of the four BMI categories. The HF risk declined progressively (range: 25% to 69%; p<0.01) with increasing fitness within all BMI categories.

Conclusions:
The obesity-associated increased risk of HF was attenuated by increased CRF. The HF risk was progressively decreased with increased CRF within all BMI categories.
Abstract MP27: Weight Change, BMI, and Mortality Among Survivors of Myocardial Infarction: Analysis of Two Prospective US Cohort Studies
Authors: Al-Shaar Laila , Li Yanping , Rimm Eric , Manson JoAnn E , Hu Frank , Willett Walter
Published: July 2021

Background:
The relation between BMI, weight change and mortality among survivors of Myocardial Infarction (MI) remains controversial, with some studies reporting favorable survival outcomes among overweight and obese patients, as compared to those with normal weight. We aim to examine the relationship between BMI reported shortly before and after MI diagnosis in addition to weight change with all-cause and cardiovascular disease (CVD) mortality among MI survivors.

Methods:
Using the data from Nurses’ Health Study (NHS) and Health Professionals Follow up Study (HPFS) cohorts, we studied 4278 participants who were free of CVD and cancer before their MI. Weight change (in BMI units) was categorized as loss of (> 4, 2-4, <2-0 (reference)), or gain of (0.1-2, or >2) units. Multivariable Cox models were used to estimate hazard ratios and 95 % confidence interval for mortality across BMI/weight change categories.

Results:
During up to 36 (NHS) and 28 (HPFS) years of follow-up post-MI, there were 2071 all-cause and 835 CVD deaths. Overweight patients with BMI before or after MI of 25-27.49 kg/m
2
had decreased mortality as compared to normal weight patients (22.5-24.9 kg/m
2
). All-cause mortality increased progressively with higher BMI. Obese patients (BMI≥30) had the highest risk of CVD mortality (HR=1.35; 95% CI, 1.06-1.73). Among MI patients who had never smoked (N=1484) or were younger than 65 years of age at the time of diagnosis (N=1873), no survival advantage was observed for overweight/obese patients. Compared to stable weight (a BMI reduction of 0-1.99 units) from before to after MI, a reduction of 2-4 or >4 BMI units was associated with increased mortality (HR=1.12; 95% CI, 0.96-1.29 and 1.42; 95% CI, 1.17-1.71 respectively, Figure).

Conclusions:
We observed a J-shaped association between BMI and mortality among all MI patients, but not among those who had never smoked or were younger than 65 years of age. Weight loss associated with acute MI, potentially related to disease severity, is an important predictor of higher mortality.
Abstract MP28: Cardiorespiratory Fitness Attenuates Risk of Cancer in Obese
Authors: Narayan Puneet , Kokkinos Peter F , Faselis Charles , Myers Jonathan , Kumar Anubhav , Karasik Pamela , Moore Hans
Published: July 2021

Introduction:
An association exists between being overweight and obese and an increased risk of certain types of cancers. In recent years even though there has been a decline in cancer rates in the general population, cancer rates in the overweight and obese have increased. Specific factors that may protect obese individuals against cancer have not been identified.

Hypothesis:
We assessed the hypothesis that improved cardiorespiratory fitness (CRF) will attenuate the risk of obesity associated cancer.

Methods:
We studied a total of 6,830 obese Veterans aged 56.2 ±10.4 years, of whom 67.2% (6471 of 6830) were African-American, 94.7% (4581 of 6830) males, 57.4% (3921 of 6830 smokers, 94.4% (6439 of 6830) with a past history of alcohol or drug use and 60.0% (4100 of 6830) were on statins. Obesity was defined as body mass index (BMI) ≥30.0 kg/m
2
and mean BMI for the cohort was 34.4±4.2 kg/m
2
. None of the patients had a diagnosis of cancer at baseline. Participants completed a maximal exercise tolerance test (ETT) as a part of clinical evaluation at either the Department of Veterans Affairs Medical Centers in Washington, DC or Palo Alto, CA and metabolic equivalents (METs) were estimated based on peak exercise time and treadmill grade. Based on these METs achieved on ETT, patients were divided into 4 age-based CRF categories (mean ± SD): least-fit (4.8±1.3 METs; n=1978), low-fit (6.8±1.2 METs; n=2210), moderately-fit (8.3±1.2 METs; n=1674), and high-fit (11.1±2.2 METs; n=968). Multivariable Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incidence of cancer across these age-based fitness categories for the entire obese cohort, using least-fit as the reference group. The models were adjusted for age, race, gender, smoking, alcohol and drug use.

Results:
During a median follow-up of 11.1 years, 9.5% (646 of 6830) of the cohort developed cancer with an event rate of 8.0 per 1000-person years of follow-up. An inverse and graded association was observed between CRF and cancer rates. The adjusted risk of cancer was 15% lower for each 1-MET increase in exercise capacity (HR=0.85; CI: 0.82-0.89). When incidence rates were assessed across CRF categories using the least fit as the referent group, the incidence of cancer was 31% lower in the moderately-fit group (HR=0.69; 95% CI: 0.56-0.86) and 81% lower in the high-fit group (HR=0.19; 95% CI: 0.12-0.29).

Conclusions:
CRF was inversely associated with rate of cancer in obese Veterans. For each 1-MET increase in fitness, cancer rate was 15% lower.
Abstract MP29: Factors Associated With Stability of Metabolically Healthy Obesity: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Camhi Sarah M , Must Aviva , Gona Philimon N , Hankinson Arlene , Odegaard Andrew , Reis Jared P , Gunderson Erica P , Jacobs David R , Carnethon Mercedes
Published: July 2021

Background:
The demographic, behavioral or lifestyle factors associated with transitioning from metabolically healthy (MHO) to metabolically unhealthy obesity (MUO) are unknown.

Methods:
CARDIA participants (n=735) were included if they were not obese (BMI <30 kg/m
2
) at baseline and developed obesity at exams 7, 10, 15, 20, or 25 years. MHO was defined as the presence of obesity and 0-1 risk factor: SBP/DBP ≥130/85mmHg; glucose ≥100mg/dL; triglycerides (≥150mg/dL); and HDL-C (men <40, women <50mg/dL) or on relevant medication. MUO was defined as obesity and 2+ risk factors. Duration of MHO and obesity were estimated (yrs). Phenotypes were categorized by MHO duration (%; MHO duration÷obesity duration): stable MHO (100%); transient MHO (1-99%); MUO (0%). Factors were compared between phenotypes using linear or logistic regression (adjusted for sex, race, baseline BMI, age). Multinomial logistic regression analysis was used to determine which factors [obesity duration, BMI change (ΔBMI), obesity onset age, physical activity (PA), alcohol intake, smoking] associated with transient MHO and MUO, relative to stable MHO.

Results:
Participants were 55% black and 72% women. Relative to transient MHO (n=184, 25%), stable MHO (n=347, 47%) had 5.4±0.5 yrs later obesity onset, 3.4±0.4 kg/m
2
smaller ΔBMI, 5.6±0.5 yrs shorter obesity duration, and 2.4±0.5 yrs longer MHO duration (all p<0.0001), with no significant differences for PA (moderate, vigorous or total), alcohol or smoking. Relative to stable MHO, transient MHO were less likely to be female, but more likely to smoke, have increased obesity duration and ΔBMI. Relative to stable MHO, MUO (n=204, 28%) were less likely to be female or black, more likely to smoke, have lower total PA, lower alcohol, and increased ΔBMI (Table 1).

Conclusion:
Obesity duration, ΔBMI and smoking were the strongest correlates of transition from MHO to MUO. MUO were more likely to have adverse health factors. Additional research should explore the cardiovascular consequences of the transition of MHO to MUO.
Abstract MP30: Longitudinal Tracking of Obesity From Childhood and Adolescence Into Adulthood: The International Childhood Cardiovascular Cohort (i3C) Consortium
Authors: Ryder Justin R , Sinaiko Alan R , Jacobs David R , Hu Tian , Burns Trudy , Woo Jessica G , Urbina Elaine M , Bazzano Lydia , Venn Alison , Dwyer Terrence , Juonalla Markus , Raitakari Olli , Prineas Ronald , Steinberger Julia
Published: July 2021

Obesity in childhood and adolescence tracks into adulthood. However, limited longitudinal data exist on variation in tracking in relation to pediatric development periods, race, and gender. The study objective was to relate adult (age>30) weight status to that in childhood (3-11, mean 8.5 yrs; adult 36.6 yrs; N=4,511) and adolescence (12-17, mean 14 yrs; adult 39.9 yrs; N=7,215) from seven i3C cohorts. Overall tracking of BMI into adulthood was highly significant (p<0.0001) and similar from childhood and adolescence. Almost all obese children (74.3%) and adolescents (81.6%) became obese adults, and few obese children (6.5%) or adolescents (4.2%) became normal-weight adults. Overweight children and adolescents also were more likely to become obese adults (60.7% and 65.2%, respectively), and few became normal weight (11.7% and 6.6%). Normal weight children and adolescents tended to remain normal weight into adulthood (43% and 40.3%), but 22.7% of both normal-weight children and adolescents became obese. Patterns differed by race and gender (both p<0.001). Obese adolescent females had the highest persistence of obesity in adulthood (84.2%), followed by obese adolescent males (79.3%), obese male children (78.1%) and obese female children (70.6%). Normal weight male and female children and adolescents had a similar low prevalence of obesity as adults (22-23%), but females were more likely than males to remain normal weight from childhood (51.2% and 33.1%) and adolescence (48.7% and 30.6%). Tracking by race (see Table) showed that blacks had greater risk of adult obesity regardless of childhood or adolescent weight category. The results show that: 1) almost all obese and most overweight children and adolescents became obese adults; 2) one-fifth of white normal weight children and adolescents became obese adults; 3) even normal weight black children and adolescents are at significant risk of becoming obese adults. These data strongly suggest the need for early intervention to prevent adult obesity-related morbidity.
Abstract MP35: Physical Activity Before and After Cancer Diagnosis and Total and Cause-Specific Mortality
Authors: Chandler Paulette D , Tobias Deirdre , Buring Jule E , Lee I-Min , Chasman Daniel , Hall Kathryn T , Cook Nancy R , Giovannucci Edward L , Hazra Aditi , Sesso Howard D
Published: July 2021

Background:
Given the increased prevalence of cancer survivors in the United States, it is imperative to define risk factors for potential reductions in total and cause-specific mortality. Physical activity (PA) represents a promising target for intervention.

Design:
We prospectively evaluated PA from questionnaires before and after cancer diagnosis with total and cause-specific mortality among 13,297 subjects diagnosed with invasive cancer combined from the Physicians’ Health Study (PHS) (n=6328), Physicians’ Health Study II (PHS II) (n=912), and Women's Health Study (WHS) (n=6057). WHS and PHS participants were free of baseline cancer; PHS II participants reported no active cancer at baseline. We ascertained PA before and after an incident cancer diagnosis based on reports on repeated follow-up questionnaires. Death was ascertained by medical records and death certificates. Cox regression estimated combined hazard ratios (HRs) of mortality by PA adjusted for age, randomized treatments, BMI, and other lifestyle/demographic factors. We evaluated the interaction between PA before and after cancer diagnosis by comparing PA ≤1 versus ≥2 times/wk.

Results:
The mean follow-up after cancer diagnosis was 8.0, 7.5, and 5.2 y for WHS, PHS, and PHS II, respectively, during which there were 5623 deaths (WHS, 2164; PHS, 3269; PHS II; 190). Higher PA before cancer diagnosis was associated with significantly lower mortality. Compared with PA ≤ once/wk, the HRs (95% CIs) associated with PA 2-4 and >4 times/wk were 0.87 (0.82-0.93) and 0.88 (0.82-0.94) for total mortality; 0.77 (0.63-0.95) and 0.79 (0.62-0.997) for CVD mortality, and 0.90 (0.83-0.98) and 0.90 (0.83-0.98) for cancer mortality. Higher PA after cancer diagnosis was associated with significantly lower total and cancer mortality and non-significantly lower CVD mortality, with HRs (95% CIs) of 0.65 (0.58-0.72) and 0.66 (0.59-0.73) for total mortality; 0.78 (0.59-1.03) and 0.82 (0.61-1.10) for CVD mortality, and 0.66 (0.57-0.77) and 0.64 (0.55-0.74) for cancer mortality. There was a significant interaction of PA before and after cancer diagnosis for total (p
int
=0.02) and cancer (p
int
=0.007) mortality, but not CVD mortality (p
int
=0.38).

Conclusions:
Greater PA both before and after cancer diagnosis were significantly associated with lower total and cancer mortality. Higher PA before cancer diagnosis was also associated with lower CVD mortality. PA may be an important target for lower mortality after cancer diagnosis.
Abstract MP50: Serum Metabolomic Profile of Incident Diabetes
Authors: Rebholz Casey M , Yu Bing , Zheng Zihe , Chang Patrick , Tin Adrienne , Köttgen Anna , Wagenknecht Lynne E , Coresh Josef , Boerwinkle Eric , Selvin Elizabeth
Published: July 2021

Background:
Metabolomic profiling offers the potential to reveal metabolic pathways relevant to diabetes pathophysiology and to improve diabetes risk prediction.

Methods:
We prospectively analyzed metabolites and incident diabetes from baseline (1987-1989) through December 31, 2015 in a subset of 2,939 Atherosclerosis Risk in Communities (ARIC) Study participants with metabolomics data and without diabetes at baseline. Metabolomic profiling was conducted in stored serum specimens collected at baseline using a reverse phase, untargeted ultra-performance liquid chromatography tandem mass spectrometry approach.

Results:
Among the 245 named compounds we identified, 7 metabolites were significantly associated with incident diabetes after Bonferroni correction and covariate adjustment (age, sex, race, center, batch, education, blood pressures, body mass index, lipids, smoking, physical activity, history of cardiovascular disease, eGFR, fasting glucose). These 7 metabolites consisted of a xenobiotic (erythritol) and compounds involved in amino acid metabolism [isoleucine, leucine, valine, asparagine, 3-(4-hydoxyphenyl)lactate] and glucose metabolism (trehalose). Higher levels of the metabolites were associated with an increased risk of incident diabetes, with the exception of asparagine which was associated with a lower risk of diabetes (HR per 1 SD increase: 0.78, 95% CI: 0.71, 0.85; p=4.19x10
-8
). The 7 metabolites improved the prediction of incident diabetes beyond fasting glucose and established risk factors (C statistic for model with vs. without 7 metabolites, respectively: 0.744 vs. 0.735; p-value for difference in C statistics=0.001).

Conclusions:
Branched chain amino acids may play a role in diabetes development. Our study is the first to report asparagine as a protective biomarker of diabetes risk. The serum metabolome reflects known and novel metabolic disturbances that improve diabetes prediction.
Abstract MP52: Population Health Impact of Sodium Glucose Co-Transporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in US Adults With Type 2 Diabetes
Authors: Nadkarni Girish , Poojary Priti , Ferrandino Rocco , Saha Aparna , Chauhan Kinsuk , Mazumdar Madhu , Coca Steven , Ferket Bart S
Published: July 2021

Introduction:
Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) receptor agonists have been introduced as novel antidiabetic agents, but their potential health impact in the US is unknown. We assessed the number of potentially eligible type 2 diabetes (T2D) patients, as well as projected changes in death and complication rates for nationwide use.

Methods:
Based on inclusion criteria of SGLT2i and GLP-1 receptor agonist RCTs, we determined eligibility in a weighted sample of 69.2M T2D patients from 2007-2014 National Health and Nutrition Examination Survey (NHANES) data. We employed a validated microsimulation model based on the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to simulate virtual life courses of eligible US patients. Pooled hazard ratios from meta-analyses of published RCTs were applied to model death and non-fatal adverse event rates with SGLT2i and GLP-1 receptor agonist use.

Results:
The proportion eligible in NHANES was 9.2% (95% CI 7.3-11.1), which translates into ~6.4M US adults. Simulated 10-year mortality (32.5%) decreased by 4.6% (95% CI 2.7-7.3) with SGLT2i and by 2.9% (95% CI 1.6-4.8) with GLP-1 receptor agonists. Mean life expectancy was 16.5 y, and increased by 1.3 y (95% CI 0.6-2.2) with SGLT2i and by 0.8 y (95% CI 0.4-1.5) with GLP-1 receptor agonists. With SGLT2i, lifetime heart failure risk decreased by 7.4% (95% CI 4.1-12.3) and end-stage renal disease (ESRD) risk decreased by 0.4% (95% CI -0.1-0.9). Improvements in these event risks were uncertain with GLP-1 receptor agonist use (Figure). With lifetime SGLT2i use, fracture risk increased from 16.9 to 22.4% (95% CI of Δ 2.5-9.6) and amputation risk rose from 5.7 to 11.2% (95% CI of Δ 2.3-9.5).

Conclusions:
Nationwide use of SGLT2i or GLP-1 receptor agonists may save over 8 or 5M life years, respectively. Moreover, SGLT2i may avoid over 470K new cases of heart failure and over 28K ESRD cases. Further research should illuminate whether these benefits outweigh additional costs and harms.
Abstract MP66: Lipidomics Profiling and Progression of Carotid Artery Atherosclerosis in HIV-infected Individuals
Authors: Chai Jin Choul , Hua Simin , Clish Clary B , Deik Amy A , Wang Tao , Hanna David B , Haberlen Sabina A , Shah Sanjiv J , Post Wendy S , Hodis Howard N , Landay Alan L , Anastos Kathryn , Kaplan Robert C , Qi Qibin
Published: July 2021

Background:
Lipid metabolism disruption and excess cardiovascular disease (CVD) risk have been associated with HIV infection, yet plasma lipidomics profile and its relationship with CVD risk has been rarely examined in HIV-infected individuals.

Methods:
Using liquid chromatography tandem mass spectrometry, 211 plasma lipid species from 13 classes were profiled in 737 women and men aged 35-55 years (520 HIV+, 217 HIV-) from the Women’s Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained in 2004-2013. Poisson regression and network analysis were used to examine associations of baseline lipids with incident carotid plaque over 7 years (112 cases, 90 HIV+ and 22 HIV-).

Results:
Adjusted for demographic and behavioral factors, 120 individual species from 11 lipid classes showed significant associations with incident carotid plaque (all
P
<0.05 FDR adjusted). The risk ratios were 1.22 to 1.44 per standard deviation increment for top significant lipids from 11 classes. Further adjustment for HIV serostatus and conventional CVD risk factors did not change the results. No evidence of effect modification by HIV serostatus was observed. Network analysis identified 2 lipid modules (Blue and Pink), which included triacylglycerols (TAGs) and phosphatidylcholines of higher acyl carbon number and greater double bond content, showing the strongest associations with incident carotid plaque (
Figure
). Of note, the Blue module, but not the Pink module, also showed a strong positive association with HIV infection. Most lipids in the Blue module had higher levels in HIV+ compared to HIV- individuals, and were associated with increased risk of carotid plaque (
Figure
).

Conclusions:
Lipidomics profiling identified that multiple lipids, especially, TAGs, are increased in HIV infection and associated with progression of atherosclerosis. Our data provide new insights into early lipid metabolism alterations preceding the development of CVD in HIV infection.
Abstract MP75: Geographic Variation in Stroke Rates and Oral Anticoagulation Use among Medicare Beneficiaries with Atrial Fibrillation
Authors: Hernandez Inmaculada , Saba Samir , Zhang Yuting
Published: July 2021

Background:
Recent studies have shown strong geographic variation in oral anticoagulation (OAC) use in atrial fibrillation (AF); however, it remains unknown how this contributes to the geographic variation in ischemic stroke observed across the US. The objective of the present study was to evaluate the relationship between the geographic variation in the initiation of OAC and the incidence of ischemic stroke in a cohort of Medicare beneficiaries newly diagnosed with AF.

Methods:
Using 2013-2014 claims data from a 5% random sample of Medicare beneficiaries, we identified patients newly diagnosed with AF in 2013-2014 and categorized them according to their initiation of OAC. Our sample included 21,226 OAC initiators and 20,068 patients who did not initiate OAC therapy. We assigned each patient to one of the 9 US Census Divisions using the zip code, and collected their medical claims with a diagnosis of ischemic stroke. We constructed logistic regression models to estimate the average adjusted probability of OAC initiation and Poisson models to estimate the average adjusted rate of ischemic stroke, in each Census Division. Both estimates were adjusted for demographics, eligibility for Medicaid coverage and for low-income subsidy, enrollment in a Medicare Advantage Part D plan, and a comprehensive list of clinical characteristics. We computed the correlation between the average adjusted probability of OAC initiation and the average adjusted rate of ischemic stroke at the Census Division level.

Results:
The probability of OAC initiation was lowest in the West South Central (0.47) and highest in the West North Central (0.54) and New England (0.54). The average adjusted rate of ischemic stroke was lowest in the West North Central (0.09) and highest in the South Atlantic (0.14) and South West Central (0.14). The average adjusted probability of OAC initiation at the Census Division level and the average adjusted rate of ischemic stroke were inversely correlated, with R=-0.576, p-value=0.10. This suggests that variation in OAC initiation likely explains at least a third of geographic variation in ischemic stroke [R
2
=(-0.576)
2
=0.332].

Conclusions:
Our results suggest that geographic variations in OAC initiation within the U.S. explain, in part, variations in the incidence of ischemic stroke among AF patients. Further mechanistic research using advanced causal mediation models is warranted.
Abstract MP77: Patient, Provider, and Insurance Predictors of Oral Anticoagulation Initiation and Dosing in Atrial Fibrillation
Authors: Hernandez Inmaculada , Zhang Yuting , Saba Samir
Published: July 2021

Background:
Recent research has shown strong provider-level variation in oral anticoagulation (OAC) use in atrial fibrillation (AF). The objective of the present study was to examine predictors of prescribing OAC to newly diagnosed AF patients, with special attention to prescribing low-dose direct oral anticoagulant agents (DOACs) to patients with no diagnosis of chronic kidney disease (CKD).

Methods:
Using 2013-2014 Medicare claims data, we identified patients newly diagnosed with AF who had CHA2DS2-VASc score≥2. Our sample included 19,390 patients who did not initiate OAC, and 22,299 OAC initiators, among whom 12,786 initiated warfarin, 5,984 high-dose DOACs and 3,529 low-dose DOACs. We constructed logistic regression models to estimate the effect of patient demographics, clinical characteristics, provider specialty, and insurance factors on OAC initiation and likelihood of prescribing low dose DOAC in patients with no CKD.

Results:
As shown in the table, age, gender, heart failure, and a history of bleeding affected the initiation of OAC as well as DOAC dosing. White patients were more likely to initiate OAC, but race did not affect DOAC dosing. Use of antiplatelet agents decreased the odds of OAC initiation by 27% (95%CI, 23%-31%), but did not impact DOAC dosing. The odds of OAC initiation decreased by 10% (95%CI, 6%-15%) for each point increase in the Geographic Practice Cost Index for malpractice. The odds of initiating low-dose DOACs were 30% (95%CI, 11%-38%) lower for patients seen by cardiologists than for those seen by internists or family practitioners.

Conclusions:
In addition to demographics and clinical characteristics, provider and insurance factors have a strong impact on initiation and dosing of OAC.
Abstract P010: Mid-life Vitamin D Levels and Later Life Performance on Neuropsychological Testing: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Fashanu Oluwaseun E , Zhao Di , Schneider Andrea L , Rawlings Andreea M , Sharrett Richey A , Lutsey Pamela L , Gottesman Rebecca F , Gross Alden L , Guallar Eliseo , Alonso Alvaro , Mosley Thomas H , Michos Erin D
Published: July 2021

Background:
Prior cross-sectional studies among older adults have found associations between low vitamin D (vitD) levels and reduced cognitive performance but were unable to distinguish the temporal order between vitD and the onset of dementia. We examined the association between mid-life vitD levels, assessed by serum 25-hydroxyvitD, with later life performance on neuropsychological testing.

Methods:
We conducted a non-concurrent cross-sectional analysis of 5,887 white and black participants enrolled in the ARIC Neurocognitive Study. We included participants who had serum vitD concentrations measured at visit 2 (1990-1992; age range 47-69 years) and who had neuropsychological and functional testing at visit 5 (2011-2013; age range 67-91 years). Neuropsychological tests were grouped into memory, language, and executive function domains and were standardized. We categorized vitD using clinical cut points as deficient (<20 ng/mL), intermediate (20-<30 ng/mL), or sufficient (≥ 30 ng/mL). We used Poisson and linear regression models adjusted for demographic and socioeconomic factors to examine the associations between vitD with prevalent dementia and performance on neuropsychological testing.

Results:
In mid-life, the mean (SD) age of participants was 56 (5) years, 60% were female, and 22% black. Mean (SD) vitD was 24.6 (8.4) ng/mL; 30% had deficient, 46% intermediate, and 24% sufficient vitD levels. Compared to participants with sufficient vitD levels, the prevalence ratios (95% CI) of late-life dementia were 1.35 (0.99, 1.84) and 1.27 (0.90, 1.80) for participants with intermediate and deficient vitD levels, respectively. We found no significant association between mid-life vitD and late-life performance on neuropsychological testing (
Table
). Further adjustments for cardiovascular, genetic, and metabolic factors yielded similar results.

Conclusion:
In this cohort, mid-life serum vitD levels were not associated with prevalent dementia or with performance on neuropsychological testing 20 years later.
Abstract P013: Elevated Resting Heart Rate in Mid-Life is Associated With Cognitive Change Over 20-years: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Wang Stephanie Z , Fashanu Oluwaseun E , Zhao Di , Guallar Eliseo , Gottesman Rebecca F , Schneider Andrea L , McEvoy John W , Norby Faye L , Alonso Alvaro , Aladin Amer I , Michos Erin D
Published: July 2021

Background:
Resting heart rate (RHR) is an easily measured marker that is independently associated with cardiovascular disease (CVD) risk. There are several potential mechanisms by which RHR could affect cognitive function, but little is known about the relation of RHR and cognitive decline. We examined the association of RHR with 20 year cognitive decline in a community-based cohort.

Methods:
We studied 13,720 middle-aged white and black participants without a prior history of stroke or atrial fibrillation. RHR was obtained from a 12-lead resting electrocardiogram at baseline (1990-1992). Cognitive testing was measured at baseline and at up to two additional visits (1996-1998 and 2011-2013). A 3-test combined cognitive score was summed from these tests: delayed word recall, digit symbol substitution and word fluency. RHR was categorized into groups as < 60 (reference), 60-69, 70-79 and ≥80 bpm. We examined the association of RHR with cognitive decline using linear mixed-effects models adjusted for demographic, socioeconomic, CVD risk factors, and AV nodal blockade use. ApoE genotype was included as a possible predictor. Imputation methods were used to account for attrition over follow-up.

Results:
Mean (SD) age of participants at baseline was 58 (6) years; 56% were women, 24% black. Average (SD) RHR was 66 (10) bpm, with RHR distribution: <60 (28%), 60-69 (40%), 70-79 (23%), >80 (9%) bpm. Over a mean follow-up of 20 years, participants in each RHR group exhibited cognitive decline (Table Part A). However, there was relatively greater global cognitive decline for those with RHR 70-79 and >80 bpm compared to <60 bpm (Part B). Results were consistent when excluding participants on AV nodal blockade medications.

Conclusion:
Elevated RHR is independently associated with greater cognitive decline over 20 years. Further studies are needed to determine whether the association is causal or secondary to another underlying process. If causal, future studies can determine whether modification of RHR can reduce cognitive decline.
Abstract P017: Childhood Food Insufficiency and Adulthood Cardiometabolic Health Among a Population-based Sample of Elderly Adults in Puerto Rico
Authors: McClain Amanda C , Mattei Josiemer
Published: July 2021

Objective:
Childhood food insufficiency is associated with poor physical health and psychosocial development in children, but less is known about long-term health implications. The objective of this study was to elucidate the association of childhood food insufficiency with cardiometabolic risk factors and health outcomes in later life among a sample of elderly adults.

Methods:
We conducted cross-sectional analysis of data from the Puerto Rican Elderly: Health Conditions Project (n=2,712), a longitudinal, population-based sample of elderly adults (>60 y) living in Puerto Rico. Participants reported childhood food insufficiency at wave 2. Prevalence of cardiometabolic health outcomes was self-reported at wave 1 or 2, and included hypertension, diabetes, and cardiovascular disease (heart attack, heart disease, and stroke). Obesity was assessed at wave 2 using objective measurements. Multivariate-adjusted complex survey logistic regression models tested the associations of childhood food insufficiency with each condition, as well as with total number of cardiometabolic conditions (0-6).

Findings:
Nearly a third (31.8%) of the sample reported childhood food insufficiency; 71.0% reported hypertension, 33.0% reported diabetes, 34.3% reported cardiovascular disease, and 29.5% had obesity. Over half (55.2%) had two or more cardiometabolic conditions. In models adjusted for age, sex, childhood socioeconomics and health factors, and current socioeconomic status and smoking status (current/former/never), childhood food insufficiency was associated with increased odds of hypertension (Odds Ratio (OR), 95% Confidence Intervals (CI): 1.65 (1.03, 2.63)) and of having 1 (2.52 (1.36, 4.67)), 2 (2.38 (1.35, 4.20)), or 3 or more (2.36 (1.34, 4.17)) cardiometabolic conditions compared to no cardiometabolic conditions. Childhood food insufficiency was not significantly associated with cardiovascular disease (1.19 (0.82, 1.74)), diabetes (1.33 (0.92, 1.93)), or obesity (0.82 (0.54, 1.26)).

Conclusions:
Childhood food insufficiency may increase the likelihood of having hypertension or multiple cardiometabolic conditions in adulthood, independent from socioeconomic factors. Creating strategies to prevent and reduce food insufficiency in childhood may be a way to prevent eventual cardiovascular-related diseases.
Abstract P019: Insulin resistance indexes and lower heart rate variability in older adults: the Atherosclerosis Risk in Communities Study (ARIC)
Authors: Poon Anna K , Whitsel Eric , Heiss Gerardo , Soliman Elsayed , Wagenknecht Lynne , Suzuki Takeki , Loehr Laura
Published: July 2021

Introduction:
Lower heart rate variability (HRV) is an indicator of cardiac autonomic dysfunction which is associated with cardiovascular disease in diabetes. Whether pre-diabetes insulin resistance contributes to lower HRV is not clear; insulin resistance (IR) indexes reflect different aspects of IR, including dysregulation of glucose, insulin, and lipids. We hypothesized that IR indexes are inversely associated with HRV.

Methods:
We analyzed 48-hour ambulatory electrocardiograms on 759 adults in a sample of the ARIC Study, excluding diabetes, antiarrhythmic medications, and missing/poor quality recordings. Insulin resistance indexes were defined as quartiles for the homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride to HDL-C ratio (TG/HDL-C), and triglyceride-glucose index (TyG). Low HRV was defined as <25
th
percentile for time domain measures -- including the standard deviation of all NN intervals (SDNN) and square root of the mean squared differences of successive NN intervals (RMSSD), and frequency domain measures -- including the high-frequency (HF) and low-frequency (LF) spectral components. Logistic regression with weights for sampling and nonresponse was used to estimate odds ratios and 95% confidence intervals (OR, 95% CI).

Results:
Mean age was 75 years [993 (63%) women, 688 (43%) African American]. The following results are reported for TyG. For time domain measures, high IR indexes were significantly associated with low SDNN (OR 1.83, 95% CI 1.09, 3.07), but not with low RMSSD (OR 1.48, 95% CI 0.89, 2.46). For frequency domain measures, high IR indexes were not associated with low HF (OR 1.62, 95% CI 0.96, 2.74), but significantly associated with low LF (OR 1.95, 95% CI 1.15, 3.30). Although results for other indexes were in the same direction, most were not statistically significant.

Conclusions:
Insulin resistance indexes may be inversely associated with HRV. An understanding of this relationship informs public health strategies for prevention of cardiovascular risk.
Abstract P020: Atrial Fibrillation and White Matter Microstructural Integrity: The Atherosclerosis Risk in Communities Neurocognitive Study
Authors: Shao Iris Yuefan , Power Melinda , Mosley Thomas , Gottesman Rebecca , Chen Lin , Norby Faye , Soliman Elsayed , Alonso Alvaro
Published: July 2021

Background:
Evidence suggests atrial fibrillation (AF) is associated with increased risk of cognitive decline and dementia, even in the absence of stroke. Pathways such as AF-induced brain hypoperfusion and small vessel disease resulting in white matter abnormalities may also compromise cerebrovasculature and brain tissue, which would lead to cognitive impairment and dementia. However, mechanisms responsible for the association between AF and cognitive impairment independent of stroke and cerebral infarcts remain relatively unexplored. The study aims to assess the cross-sectional association between prevalent AF and white matter microstructural integrity (WMMI) as a marker for cerebrovascular disease.

Methods:
We performed a cross-sectional analysis of 1937 participants attending the ARIC-Neurocognitive Study (ARIC-NCS) in 2011-2013 that were either black or white and with brain magnetic resonance imaging (MRI). Prevalent AF was defined by a history of AF based on study ECG and hospitalization record. WMMI was defined using regional average fractional anisotropy and mean diffusivity from Diffusion Tensor Imaging measurements in the MRI. We excluded participants with a prior history of stroke or cerebral infarct. A multivariable regression model was used to assess the association between AF and WMMI measures.

Results:
Among 1943 participants (mean age = 76 years, 28% black, 60% female), 7% (N= 133) had prevalent AF. After multivariable adjustment, prevalence of AF was not associated with WMMI measurements (Table).

Conclusion:
In a community-based study, prevalent AF was not independently associated with WMMI in the absence of stroke or cerebral infarct. However, the reduced sample size of the AF population as well as the cross-sectional study design are important limitations. Further longitudinal studies are needed to investigate prospectively the association of AF with early markers of white matter disease.