bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P367: Peripheral Artery Disease and Subsequent Risk of Hospitalized Infectious Disease in Older Individuals: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Mok Yejin , Ishigami Junichi , Lutsey Pamela L , Tanaka Hirofumi , Meyer Michelle , HEISS Gerardo M , Matsushita Kunihiro
Published: March 2020

Background:
Patients with cardiac disease and stroke have a high risk of infection, and several prevention programs target those patients. However, data among patients with peripheral artery disease (PAD) are lacking.

Methods:
In 5,055 ARIC study participants without a preceding infection within three months of visit 5 (age 71-90 years in 2011-2013), we assessed whether PAD (clinical history or ankle-brachial index [ABI] ≤0.90) was associated with subsequent hospitalization for infections. We ascertained infections using ICD-9 codes at discharge to identify overall infection as well as its major subtypes (i.e., cellulitis, bloodstream infection, pneumonia, and urinary tract infection). We also stratified participants with PAD by history of concomitant coronary heart disease (CHD) or stroke. Multivariable Cox regression models were used to estimate adjusted hazard ratio (aHR).

Results:
During the median follow-up of 5.4 years, 1103 (44.4 rate per 1000 person-years) had hospitalizations with infection. As compared to those with an ABI of 1.11-1.20, participants with PAD were at greater risk of overall infection (aHR 1.67 [95% CI 1.38, 2.02], as were those with borderline low ABI (0.91-1.00) (aHR 1.89 [1.54, 2.31]). Consistent results were observed when the major subtypes of infection were explored. When we compared four groups according to PAD and CHD/stroke, PAD alone had a higher risk of infection similar to those with PAD plus CHD/stroke compared to those without PAD or CHD/stroke (Figure). Of note, PAD alone showed the highest risk of bloodstream and urinary tract infections.

Conclusions:
PAD and borderline low ABI were independently associated with greater risk of hospitalized infection among older adults. The contribution of PAD to elevated infection risk appeared even larger than that of CHD/stroke. Our study suggests that PAD patients should be considered for preventive strategies for infection (e.g., vaccination).
Abstract P379: Features to Increase Primary Care Provider Referrals to Intensive Behavioral Counseling for Cardiovascular Disease Prevention
Authors: Omura John D , Watson Kathleen B , Loustalot Fleetwood V , Fulton Janet E , Carlson Susan A
Published: March 2020

Background:
The US Preventive Services Task Force recommends adults with certain cardiovascular disease (CVD) risk factors be offered or referred to intensive behavioral counseling to promote a healthful diet and physical activity for CVD prevention. However, only 1 in 12 primary care providers (PCPs) currently follow this recommendation. This study assessed system and programmatic features PCPs reported would increase their likelihood of referring patients at risk for CVD to intensive behavioral counseling and whether this varied by the percentage of at-risk patients with whom they discuss physical activity.

Methods:
DocStyles 2018, a web-based panel survey of PCPs, assessed the percentage of at-risk patients with whom PCPs discuss physical activity and the degree to which select features would increase their likelihood of referring to intensive behavioral counseling.

Results:
Overall, 60.8% of PCPs discussed physical activity with most of their at-risk patients; 21.8% did so with many and 17.4% with few or some. The proportion of PCPs identifying features as increasing their likelihood of referring to intensive behavioral counseling by a great extent ranged from 24.1% for an automated referral in electronic health records, 35.3% for patient progress reports, 41.5% for the program being accredited or evidence-based, to 67.2% for the program having no cost to the patient (Table). These proportions increased for each feature as the percentage of at-risk patients with whom they discuss physical activity increased.

Conclusion:
PCPs identified programmatic features (i.e. being accredited and of no cost) as having the greatest influence on their likelihood of referring patients at risk for CVD to intensive behavioral counseling, although this varied by the percentage of at-risk patients with whom they discuss physical activity. Findings suggest that the effectiveness of strategies to improve behavioral counseling referrals by PCPs may depend on their current physical activity counseling practices.
Abstract P380: Steps Per Day and Step Intensity are Associated With a Lower Risk of Diabetes. The Hispanic Community Health Study / Study of Latinos (HCHS/SOL)
Authors: Cuthbertson Carmen , Moore Christopher , Sotres-Alvarez Daniela , HEISS Gerardo M , Garcia-Bedoya Olga , Mossavar-Rahmani Yasmin , Isasi Carmen R , Carlson Jordan A , Gallo Linda , Goldsztajn Farelo David , Llabre Maria , Evenson Kelly R
Published: March 2020

Introduction:
Physical activity has been associated with a lower risk of diabetes but less is known about the association of steps per day (steps/d) and step intensity with incident diabetes.

Hypothesis:
We hypothesized an inverse association between both number of steps/d and time spent at a stepping rate corresponding to purposeful steps (
>
40 steps/min) with the risk of incident diabetes.

Methods:
We included 7247 participants free of diabetes at baseline in the prospective HCHS/SOL cohort of Latinos sampled from four communities in the United States. Steps/d and minutes per day (min/d) at a stepping rate
>
40 steps/min were assessed at baseline with the Actical accelerometer (2008-2011), and incident diabetes was ascertained at a follow-up visit (2014-2017). The association of steps with incidence rates (per 1,000 person-years) of diabetes and incidence rate ratios (IRR) was estimated using Poisson regression, accounting for the sampling design and adjusted for age, ethnicity, gender, education, smoking status, alcohol intake, and accelerometer wear time.

Results:
The average age at baseline was 38 years (range 18 - 74 years) and 52% were female. Over a median of 5.9 years, 850 participants (9%) developed diabetes. The median step count was 7360 steps/d and the median minutes per day at a stepping rate of
>
40 steps/min was 55 minutes. For each 1,000 step/d increment, the risk of diabetes was 5% lower (Table, IRR= 0.95(95% confidence interval (CI) 0.88, 1.02)). Compared to adults who engaged in 2,000 steps/d, those who engaged in 5,000 and 10,000 steps/d had a 13% and 26% lower risk of diabetes. The risk of diabetes was 5% lower (IRR=0.95 (95% CI 0.89, 1.00)) per 10 minute increase in time spent at a stepping rate
>
40 steps/min. Compared to adults who spent 10 min/d at
>
40 step/min, those who spent 30, 60, and 120 min/d had a 10%, 20%, and 32% lower risk of diabetes.

Conclusion:
The number of steps per day and time spent at a stepping rate that corresponds to purposeful steps are inversely associated with the risk of developing diabetes among adults.
Abstract P382: Impact Of Autoimmune Disease On Acute Venous Thromboembolism Incidence After Pregnancy
Authors: Walker Rob F , Mason Susan M , Zakai Neil A , Maclehose Richard F , Norby Faye L , Alonso Alvaro , Lutsey Pamela L
Published: March 2020

Introduction:
Venous thromboembolism (VTE) is a leading cause of mortality in the postpartum period. Several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus and Crohn’s disease, have been found to increase risk of VTE by upregulating the body’s procoagulants while decreasing physiologic anticoagulants via systemic inflammation. No existing studies have estimated the association of these risk factors exclusively among postpartum women.

Hypothesis:
Presence of autoimmune disease will be associated with increased risk of VTE among postpartum women.

Methods:
We identified a cohort of 755,722 women ages 15-45 with an international classification of disease code (ICD) for delivery in the 2011-2017 U.S. MarketScan Commercial administrative database. The exposure of prevalent autoimmune disease, represented by 29 endocrine, antibody positive, digestive and vascular diseases, was identified by two or more inpatient or outpatient ICD codes occurring before a woman’s delivery date. VTE events between the delivery hospital discharge and 12 weeks postpartum were defined using validated algorithms of ICD codes and confirmatory evidence of anticoagulant prescriptions. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) adjusted for age, hypertension, gestational diabetes, preeclampsia, multiple gestation and antepartum hemorrhage. Associations were also evaluated separately by specific autoimmune disease category (endocrine, antibody positive, digestive, vascular).

Results:
The average age of women was 30.7 years (SD: 5.4 years) and 27,322 out of the 755,722 deliveries (3.6%) occurred among women with prevalent autoimmune disease. Of these, 10,555 were endocrine diseases (1.4%), 12,851 were antibody positive diseases (1.7%), 4,634 were digestive diseases (0.6%) and 353 were vascular diseases (0.1%). There were 3,502 postpartum VTE events; among them 235 (6.7%) occurred in women with prevalent autoimmune disease. In the adjusted model, women with autoimmune disease had higher postpartum rate of VTE (HR: 1.54; 95%CI: 1.25, 1.90) relative to those without. When evaluating the subgroups separately, the rate of VTE was elevated among women with digestive (HR: 1.73; 95%CI: 1.09, 2.76) and antibody positive (HR: 1.82; 95%CI: 1.38, 2.39) autoimmune diseases.

Conclusions:
Women with autoimmune disease were at 50% greater risk of postpartum VTE as compared to women without these conditions. The association was more pronounced for women with digestive and antibody positive autoimmune disease. Given the importance of maternal mortality as an outcome, these findings suggest value for increasing VTE awareness among women with these autoimmune conditions and their healthcare providers.
Abstract P391: The Effects of Obstructive Sleep Apnea on Cardiac Arrhythmia Risk
Authors: Biben Emily , Burgess Lauren , Allen Julie , Jouett Noah , Burk John , Smith Michael
Published: March 2020

Background:
Over 20 million people in the United States suffer from Obstructive Sleep Apnea (OSA). Compared to the general population, OSA patients are 2.6 times more likely to experience sudden cardiac death (SCD), and it is suspected that this is due, in part, to QT prolongation leading to fatal dysrhythmias. OSA events have previously been shown to cause prolonged QT intervals compared to the post-apnea hyperventilation period, and studies have also observed increased QT dispersion in patients without cardiac disease. However, those with cardiac disease may be at the greatest risk for SCD, and it is not known what role QT prolongation plays and what factors influence these responses. Thus, the purpose of this study is to evaluate the factors that affect QT interval during periods of sleep apnea including OSA severity, time of night, and quantity of obstructive apneic events during sleep.

Methods:
We determined QTc intervals from the electrocardiograms of 36 patients undergoing polysomnography for diagnosis of OSA. Patients that were selected had an apnea hypopnea index >20/Hr and had no prior myocardial infarction or heart failure. Each patient’s ECG during their sleep study was analyzed to assess QT interval throughout the night. Baseline QT intervals were compared to QT intervals during obstructive apneas during the first 2 hours of sleep (Early) and last 2 hours of sleep (Late). In addition, apneas >40 seconds were analyzed in 11 patients for changes in QTc as the apnea progressed. Statistical comparisons were made with paired t tests and a one-way ANOVA analysis with repeated measures.

Results:
Early analyses of data showed QTc intervals in Early and Late apneas were significantly prolonged compared to awake baseline (p=0.04 and p=0.006 respectively). For patients with apneas >40 seconds, significant differences in QTc interval were observed at increasing time points during the apnea compared to the QTc immediately preceding the apnea (p<0.001). Furthermore, patients with longer apneas tend to have longer baseline QTc (p=0.07).

Conclusions:
Sleep apneic events are associated with periods of mild QTc prolongation despite some cardiac cycle shortening. The prolongation tends to become enhanced later in the night, implying that there is a cumulative effect of numerous prior apneas. Furthermore, prolongation tends to increase as the apnea duration progresses. Early data analyses also suggest that baseline QTc tends to be longer in patients who have more severe/longer apneic events throughout the night. Future studies will focus on QTc changes in OSA patients with prior heart disease, as these are the patients at greatest risk for serious arrhythmias during the night.
Abstract P392: Nocturia Frequency As A Novel Cardiometabolic Disease Risk Factor
Authors: Grandner Michael A
Published: March 2020

Introduction:
Nocturia causes sleep disturbances and is more common as people age. Therefore, it often overlaps with cardiometabolic risk factors. However, relationships between nocturia frequency and cardiometabolic risk as not been explored, over and above covariates such as age, sex, sleep duration, etc.

Methods:
Data from the 2015-2016 National Health and Nutrition Examination Survey was used. Nocturia was coded as 0 times/night, 1 time/night, 2-3 times/night, and 4-5+ times/night. Cardiometabolic disease risk factors examined included history of hypertension, taking antihypertensive medication, history of hypercholesterolemia, taking cholesterol-lowering drugs, diabetes, obesity, smoking, and poor diet. Covariates included age sex, education, race/ethnicity, income-poverty ratio, and habitual sleep duration category (very short, short, normal, and long). Logistic regression analyses were analyzed using NHANES sampling weights.

Results:
In adjusted analyses, the highest category of nocturia (4-5+ times per night) was associated with increased likelihood of hypertension (OR=2.12, 95%CI [1.34,3.38], p=0.001), antihypertensive medication (OR=2.52, 95%CI [1.56,4.09], p<0.0005), diabetes (OR=3.44, 95%CI [2.09,5.68], p<0.0005), hypercholesterolemia (OR=1.81, 95%CI [1.18,2.75], p=0.006), cholesterol-lowering medication (OR=2.25, 95%CI [1.38,3.68], p=0.001), poor diet (OR=2.17, 95%CI [1.41,3.34], p<0.0005), and obesity (OR=2.16, 95%CI [1.40,3.32], p<0.0005), but not smoking. Nocturia 2-3 times per night was also associated with increased likelihood of antihypertensive use (OR=1.40, 95%CI [1.04,1.88], p=0.025), diabetes (OR=1.85, 95%CI [1.27,2.71], p=0.001), hypercholesterolemia (OR=1.43, 95%CI [1.09,1.88], p=0.010), cholesterol-lowering medications (OR=1.81, 95%CI [1.31,2.51], p<0.0005), and obesity (OR=1.52,95%CI [1.18,1.96], p=0.001). When obesity was added as a covariate, significant relationships were still seen for hypertension, antihypertensive medication, diabetes, hypercholesterolemia, cholesterol-lowering medications, and poor diet.

Conclusions:
Frequent nocturia is associated with a wide range of cardiometabolic risk factors, after adjusting for age, sleep duration, and a wide range of other potential factors, as well as obesity. Complaints of nocturia might be considered an independent risk factor. Mechanisms, such as sleep fragmentation, should be explored.
Abstract P397: Social Determinants of Hypertension and Diabetes Among African Immigrants: The African Immigrant Health Study
Authors: Ogungbe Oluwabunmi , Turkson-ocran Ruth-alma N , Baptiste Diana , Koirala Binu , Dennison Himmelfarb Cheryl R , Davidson Patricia , Commodore-Mensah Yvonne
Published: March 2020

Introduction:
The differences in the risk of cardiovascular disease (CVD) among Black ethnic groups in the U.S. remain largely unexplained. African immigrants are particularly likely to have high rates of hypertension and diabetes, and less likely to be screened, diagnosed or receive treatment.

Objective:
To examine the association between social determinants of health (SDoH) and hypertension and diabetes among African immigrants.

Methods:
The African Immigrant Health Study was a cross-sectional study of 465 African immigrants living in the Baltimore-Washington metropolitan area. Data collection was performed through a combination of physical examinations and questionnaires. The outcomes were self-reported hypertension and diabetes. Elements of SDoH collected were education, income, health insurance, employment and marital status. Logistic regression analyses were used to assess the association between SDoH and hypertension/diabetes.

Results:
The mean age of participants was 46.8(±11.5) years and 60% were women; 64% had ≥ college degree, 83% were employed, 67% had health insurance, and 70% were married/co-habiting. Mean body mass index was 30.7 (±18.3) kg/m
2
. The prevalence of hypertension and diabetes was 32%, and 13% respectively. The odds of diabetes were higher amongst those who were unemployed [aOR: 2.86 (1.39-5.56)] (
Table
). Education, health insurance, income and marital status were not associated with hypertension or diabetes after accounting for age and sex.

Conclusion:
Among African immigrants, we observed that those who were unemployed had a higher likelihood of self-reported diabetes than those who were employed. Additional studies are needed to further study the contributions of social determinants of hypertension and diabetes as well as and developing health policy and interventions to improve cardiovascular health.
Abstract P401: Associations Between High-density Lipoprotein Subclasses and Coronary Artery Calcification Vary by Menopausal Stage. The Study of Women's Health Across the Nation Hdl Ancillary Study
Authors: El Khoudary Samar R , Nasr Alexis , Chen Xirun , Matthews Karen A , Orchard Trevor , Brooks Maria M , Billheimer Jeff , McConnell Dan , Janssen Imke , Everson-rose Susan A , Martin Deborah , Rader Dan
Published: March 2020

Objective:
Higher levels of high-density lipoproteins cholesterol (HDL-C) may not always be cardio-protective in midlife women. Nuclear magnetic resonance (NMR) spectroscopy HDL subclasses have shown strong associations with CVD risk beyond HDL-C. Preliminary work suggests significant declines in large HDL particles (HDL-P) and overall HDL size, but increases in small HDL-P during the perimenopause stage. Our objective was to assess whether associations between NMR HDL subclasses and risk of coronary artery calcification (CAC) vary by menopausal stage.

Design:
We assessed 283 women (at baseline : age 51.4 ± 3.0 years; 56.6% Pre-/Early peri-, 8.8% late peri-, 34.6% post-menopausal) who had NMR HDL subclasses and CAC Agatston score measured once (N=48 [17%]) or twice (N=235 [83%]) around menopause. CAC presence was defined as CAC>0. Effect modifications of menopausal stage on associations between HDL subclasses and CAC presence overtime were tested using generalized estimating equation for binary outcome. Final models were adjusted for study site, race and time varying: age, body mass index, physical activity, alcohol consumption, insulin resistance, triglycerides and low-density lipoprotein cholesterol.

Results:
In final models, menopausal stage modified the associations of small HDL-P (p=.009), large HDL-P (p=.05) and overall HDL size (p=.007) with CAC presence (
Table
). Higher concentration of small HDL-P, lower concentration of large HDL-P, and smaller overall HDL size significantly associated with greater risk of CAC presence during the late-peri stage compared to pre-/early peri-menopausal stage (
Table)
.

Conclusions:
Changes in HDL subclasses during the menopause transition may increase the likelihood of measurable CAC developing in women, particularly during the later peri-menopausal stage. Characterizing associations of HDL composition and function metrics with CVD risk over the menopause transition is critical to better understand the relationship of HDL to coronary disease in midlife women.
Abstract P405: Visceral Adipose Tissue Volume is Associated With Prevalent Coronary Plaque Independent of Total Adiposity in Psoriasis
Authors: Uceda Domingo E , Reddy Aarthi , Choi Harry , Lateef Sundus S , Abdelrahman Khaled M , Dey Amit K , Aksentijevich Milena , Scott Colin , Shukla Parag , Akbar Mohammed D , Argueta-Amaya Jenis , Rodante Justin , Teague Heather , Keel Andrew , Chen Marcus Y , Yao Jianhua , Zhou Wunan , Playford Martin P , Mehta Nehal N
Published: March 2020

Introduction:
Psoriasis (PSO) is a chronic inflammatory condition associated with accelerated atherosclerosis and increased risk of myocardial infarction in part mediated through high visceral adipose tissue (VAT) volume. VAT has been shown to be associated with increased coronary burden; however, the relationship with prevalent coronary plaque in PSO has not been explored.

Hypothesis:
We hypothesized that VAT would associate with coronary plaque in PSO beyond traditional risk factors.

Methods:
A total of 164 consecutive PSO patients underwent coronary computed tomography angiography (CCTA) as part of a large cohort study to assess presence of coronary plaque. Low-dose CT was utilized to quantify VAT and subcutaneous adipose tissue (SAT) volume from the level of the diaphragm to the pubic symphysis. Logistic regression was used to assess the association between the presence of coronary plaque and the ratio of VAT-to-total adiposity in adjusted models (STATA 12).

Results:
The cohort was middle-aged, predominantly male, relatively low CV risk by FRS and mild to moderate PSO (Table 1). Patients with increased VAT-to-total adiposity, had significantly increased coronary plaque presence (70% (45 of 65) vs. 31% (31 of 99), p<0.001) compared to those with low VAT-to-total adiposity. Moreover, increased VAT-to-total adiposity was associated with 3-fold higher odds of having a prevalent coronary plaque (adjusted OR 2.96 (1.22 - 7.22), p=0.016) after adjustment for Framingham risk score, body-mass-index, waist-to-hip ratio and lipid treatment.

Conclusions:
Having higher VAT was associated with higher prevalence of coronary plaque independent of total adiposity and cardiovascular risk factors. These findings suggest VAT contributes to coronary plaque in psoriasis and that weight loss efforts may improve outcomes in this high-risk population.
Abstract P407: Association of Obesity at Baseline and Change Over Time With 6 Minute Walk Distance: The Multi-ethnic Study of Atherosclerosis
Authors: Mongraw-Chaffin Morgana , Chen Haiying , Houston Denise K , Shah Sanjiv J , Bertoni Alain G
Published: March 2020

Introduction:
The 6 minute walk distance (6MWD) may be an indicator of frailty and is strongly associated with risk of mortality. Obesity is increasingly shown to be associated with decreased physical function, frailty, and disability, and is also associated with multiple major cardiometabolic comorbidities that cause early mortality. Studies of 6MWD have generally been limited in scope by the use of a single measurement of BMI for obesity, highly selected samples, and by lack of racial/ethnic diversity.

Methods:
6MWD was measured in participants at Visit 6 (2016-2018) of the Multi-Ethnic Study of Atherosclerosis (MESA) who were able to ambulate without assistance. MESA participants were diverse with 62% non-white and 50% female, aged 45-84 and free of CVD at Visit 1 (2000-2002). We used multivariable linear regression with robust standard errors that account for within person correlation to investigate the association of baseline BMI categories and BMI change over time (from Visit 1 to Visit 6) with 6MWD. We used normal weight (BMI 18.5 - <25.0kg/m
2
) and no BMI change (-1 to +1 kg/m
2
) as reference categories.

Results:
Among 2525 participants with 6MWD at Visit 6, mean Visit 1 BMI was 28.2 kg/m
2
, mean Visit 6 BMI was 28.4 kg/m
2
, mean BMI change was 0.22kg/m
2
, and mean 6MWD was 410 m. Average time between BMI measurements was 15.8 years. Baseline overweight and obesity were strongly and significantly associated with lower 6MWD, as was increase in BMI over time (
Figure
). Adjustment for potential confounders and mediators did not explain these associations, although significant interaction by age was found for BMI decrease ≥ -4kg/m
2
(p = 0.003) with those over 70 having lower 6MWD (-31.2 (-50.6, -11.8)) and younger participants having non-significantly higher 6MWD (17.2 (-8.2, 42.5)). There was no significant heterogeneity by sex or race/ethnicity.

Conclusion:
Even modest increase in BMI (1≤ change <4 kg/m
2
) with aging is associated with lower 6MWD in MESA. Consensus about the impact of weight loss in older adults remains a major challenge.
Abstract P427: Coronary Artery Calcium Assessed Years Before Was Positively Associated With Subtle White-matter Injury in Asymptomatic Middle-aged Men: The Framingham Heart Study
Authors: Suzuki Harumitsu , Davis-Plourde Kendra , Beiser Alexa , Miura Katsuyuki , DeCarli Charles , Maillard Pauline , Mitchell Gary F , Seshadri Sudha , Fujiyoshi Akira
Published: March 2020

Introduction:
Using magnetic resonance (MR) diffusion tensor imaging (DTI), we previously showed a cross-sectional association between carotid-femoral pulse wave velocity (CFPWV), a measure of aortic stiffness, and subtle white-matter injury in clinically asymptomatic middle-age adults. Although coronary artery calcification (CAC) predicted cerebral small vessel diseases evident in conventional MR technique in some studies, it remains unclear whether CAC predicts DTI-based subtle white matter injuries.

Hypothesis:
CAC and CFPWV are associated with global measures of subtle white-matter injury in middle-aged adults free of clinical brain diseases.

Methods:
We studied third-generation participants of the Framingham Heart Study who were assessed for CAC (2002-2005), CFPWV, and brain DTI (2009-2013). After excluding prevalent stroke, dementia, other neurological conditions, or those with missing data, 1052 participants (women, 45.4%, mean age: 45.4 years) were analyzed. Two DTI-based outcomes were examined (average within voxels from the white matter mask): free water (FW) and FW-corrected fractional anisotropy (FA). Using linear regression, we calculated slopes of the outcomes per 20-80
th
percentiles higher CAC (log-transformed Agatston score) or CFPWV (negative inverse) after adjustment for age and age squared at CAC or CFPWV, time between at CAC/CFPWV and DTI exam, systolic blood pressure, diabetes, total cholesterol, medication(s) for hypertension or dyslipidemia, smoking, and total cranial volume.

Results:
After multivariable adjustment, in men, CAC was associated only with FA (p=0.033), whereas CFPWV was associated only with FW (p=0.030) (
Figure
). No associations were observed in women.

Conclusions:
In men, CAC assessed at >7.5 years earlier was associated with worse FA, while CFPWV assessed at 1.7 years earlier was associated with worse FW. CAC may be a sensitive maker to predict subtle white-matter injury in asymptomatic middle-aged men.
Abstract P437: Early Insulin Resistance Responds To Lifestyle Interventions: The Premier Study
Authors: Cistola David P , Ard Jamy D , Brenner M. H , Dwivedi Alok K
Published: March 2020

Introduction:
Compensatory hyperinsulinemia (CH) is the metabolic response to early insulin resistance. Elevated blood insulin compensates for insulin resistance in tissues, maintaining normal fasting glucose and lipid levels. Therefore, CH is undetected by conventional screening tests for diabetes and cardiovascular risk. Our prior work showed that CH is prevalent in the U.S., especially in teenagers, young adults and Hispanic populations. Moreover, CH in young adults doubles the risk for diabetes later in life, independent of other known risk factors. The current study tested the hypothesis that markers of early insulin resistance improve with behavioral lifestyle interventions.

Methods:
The parent PREMIER study was a randomized controlled trial to evaluate the effect of lifestyle interventions on blood pressure. Many subjects also had insulin resistance, prediabetes (PreD) and/or metabolic syndrome (MetS). The interventions included increased physical activity, weight loss, reduced sodium and alcohol intake, and the DASH diet (Dietary Approaches to Stop Hypertension). A total of 810 subjects were randomized into three intervention arms: “established”, “established plus DASH” and “advice only”. Established refers to the above interventions, except for DASH. The subjects were 62% women and 34% African Americans; the mean age was 50.0±8.9 years. Inclusion criteria were age ≥25, elevated BP and BMI of 18.5-45.0 kg/m
2
. Exclusion criteria were diabetes, history of cardiovascular event, heart failure, cancer or psychiatric hospitalization within the last 2 years. Here, the analysis of covariance method was used to determine whether markers of insulin resistance at 6 months improved in the established or established plus DASH arms compared with the advice-only arm, after adjusting for baseline values. The results are reported as geometric means and 95% confidence intervals (CI).

Results:
Subjects in the lifestyle intervention arms showed reduced fasting insulin and increased insulin sensitivity compared with the advice-only arm. The mean fasting insulin levels after 6 months of the established and established plus DASH interventions were 9.8 μIU/mL (95% CI: 9.3, 10.3) and 10.1 (9.6, 10.7), respectively, compared with 12.0 (11.4, 12.6) for advice only. After excluding subjects with PreD and/or MetS at baseline, insulin levels for established and established plus DASH were 8.0 (7.3, 8.7) and 8.3 (7.3, 9.0), respectively, as compared with 9.8 (9.1, 10.6) for advice only. Likewise, HOMA2 %S increased to 101.2 (92.5, 110.6) and 93.3 (85.6, 101.8), respectively, compared with 79.0 (73.0, 85.5) in the advice-only arm.

Conclusion:
Markers of insulin resistance improved with the PREMIER lifestyle interventions, even in subjects who did not meet the clinical criteria for prediabetes or metabolic syndrome. Early screening and intervention may improve diabetes prevention outcomes.
Abstract P439: Generalizability of Heterogeneous Treatment Effects of Intensive Glycemic Control on All-cause Mortality Across Two Randomized Trials
Authors: Raghavan Sridharan , Josey Kevin , Bahn Gideon , Ghosh Debashis
Published: March 2020

Background:
Machine learning is an attractive tool for identifying patient subgroups that exhibit heterogeneous treatment effects (HTE) of an intervention. Whether HTE identified using machine learning methods generalize across clinical studies is unclear. Prior work using a causal forest machine learning approach identified hemoglobin glycation index (HGI), body mass index (BMI), and age as determinants of HTE of intensive versus standard glycemic control on all-cause mortality in the ACCORD randomized trial. We examined whether the same three variables defined HTE in the VA Diabetes Trial (VADT), an independent randomized trial of intensive versus standard glycemic control in type 2 diabetes patients.

Methods:
The VADT study randomized participants to intensive (median hemoglobin A1c [HbA1c] achieved of 6.9%) or standard (median HbA1c achieved of 8.4%) glycemic control. In this secondary analysis comparing results with the ACCORD trial, we included 1789 out of 1791 VADT participants who had non-missing data at baseline for fasting glucose, HbA1c, BMI, age, and lab values and comorbidities included in prior machine learning analysis of the ACCORD trial; median follow-up was 5.6 years. We examined the absolute risk difference in all-cause mortality in four subgroups with HTE for mortality in the ACCORD trial: group 1, HGI < 0.44, BMI < 30kg/m
2
, Age < 61 years; group 2, HGI < 0.44, BMI < 30kg/m
2
, Age ≥ 61 years; group 3, HGI < 0.44, BMI ≥ 30kg/m
2
; and group 4, HGI ≥ 0.44. We repeated the analysis after using inverse odds of sampling weights to standardize VADT study participants to the ACCORD study participants using individual-level data from both studies.

Methods:
The absolute all-cause mortality difference between intensive and standard glycemic control in all VADT participants included in this study was 0.8%. The absolute mortality difference did not vary significantly across subgroups: 2.2% (95% CI -6.0, 10) in group 1 (n=140), 3.4% (-7.3, 14.2) in group 2 (n=192), 2.4% (-2.9, 7.7) in group 3 (n=517), and -0.8% (-4.8, 3.1) in group 4 (n=940), where negative values indicate lower mortality in the intensive glycemic control intervention arm. The absolute mortality differences for the corresponding subgroups in the ACCORD trial were: -2.3% (-4.3, -0.2), 0.7% (-1.6, 3.1), 0.9% (0.4, 2.1), 3.7% (1.5, 6.0) in groups 1, 2, 3, and 4 respectively. The pattern of absolute mortality differences across groups 1 through 4 in the ACCORD study did not reproduce in the VADT study even after standardization of study population characteristics with the ACCORD study.

Conclusions:
Machine learning methods to define HTE subgroups from randomized trials may not be generalizable across study samples and are likely sensitive to variability in the intervention and differences in study populations. Additional work is needed to define consistent HTE that can guide individualized diabetes treatment.
Abstract P443: Association of Peripheral Neuropathy With All-cause and Cardiovascular Mortality in US Adults
Authors: Hicks Caitlin W , Wang Dan , Windham B Gwen , Matsushita Kunihiro , Selvin Elizabeth
Published: March 2020

Background:
Peripheral neuropathy (PN) is common in the general US adult population, especially in older adults even in the absence of diabetes. However, the clinical sequelae of PN have not been quantified in a nationally representative sample. We aimed to assess the associations of prevalent PN with all-cause and cardiovascular mortality using data from the National Health and Nutrition Examination Survey(NHANES).

Methods:
Prospective cohort analysis of 7,137 participants from NHANES (aged ≥40 yrs) who underwent standardized PN testing at baseline (1999-2004). We used survival analysis methods and Cox regression to evaluate the associations of PN with all-cause and cardiovascular mortality. Cox models were adjusted for demographic and cardiovascular risk factors.

Results:
The overall prevalence of PN was 17.7% (29.9% in adults with diabetes and 15.2% in adults without diabetes). In age-adjusted Kaplan-Meier analyses (median follow-up 13 yrs), the risk of all-cause and cardiovascular mortality was highest among adults with PN and diabetes, but PN was also associated with excess mortality risk in the absence of diabetes (
Figure
). After multivariable adjustment, PN remained significantly associated with all-cause and cardiovascular mortality in participants with diabetes (
Figure)
, although the association of PN with cardiovascular mortality was largely driven by participants with long-standing diabetes ≥10 yrs (HR 4.53, 95%CI 2.34-8.78). In participants without diabetes, PN was moderately associated with both all-cause and cardiovascular mortality after adjustment (
Figure
).

Conclusions:
PN was associated with mortality in the US population regardless of diabetes status, suggesting that screening for PN may be important for older adults both with and without diabetes. Adults with long-standing diabetes and PN were at a substantially elevated risk of cardiovascular-related mortality, potentially reflecting a higher burden of concomitant diabetic autonomic neuropathy in this high-risk population.
Abstract P444: Changes in Glucose-Lowering Medication Prescriptions After an Incident Cardiovascular Event Across eGFR Levels in an Integrated Health System
Authors: Shin Jung-Im , Selvin Elizabeth , Inker Lesley , Reider Jodie , CHANG Alex R , Grams Morgan
Published: March 2020

Introduction:
Cardiovascular disease is a major complication among patients with diabetes, and may merit changes in both antihypertensive medications (e.g., to beta blockers and ACE inhibitors) and glucose-lowering medications (e.g., to sodium-glucose cotransporter 2 inhibitors [SGLT2i] and glucagon-like peptide 1 receptor agonists [GLP1 RA], medication classes with evidence of cardiovascular outcome benefit). The objective of this study was to assess how glucose-lowering medication prescriptions changed after a cardiovascular event among persons with diabetes.

Hypothesis:
There are changes in glucose-lowering medication prescription following a cardiovascular event.

Methods:
We identified adult patients with diabetes and estimated glomerular filtration rate (eGFR)≥15mL/min/1.73 m
2
who experienced a cardiovascular event (myocardial infarction, stroke, or heart failure) from 2005-2018 in the Geisinger Health System (cases). We selected control patients with diabetes but without a cardiovascular event by 1:1 matching on demographics, diabetes duration, HbA1c, eGFR, and calendar year.

Results:
In 15,918 matched case and control patients with diabetes (mean age 65 years, 52% female, mean HbA1c 7.55%, median diabetes duration 5.6 years, and 28% eGFR<60 mL/min/1.73 m
2
), insulin prescriptions increased and metformin prescriptions decreased after a cardiovascular event among cases compared with controls in all eGFR categories (
Table
). There were no differences between cases and controls with respect to changes in SGLT2i, GLP1 RA, or dipeptidyl peptidase 4 inhibitors (DPP4i).

Conclusions:
In a real-world setting, insulin prescriptions increased and metformin prescriptions decreased, after a cardiovascular event regardless of eGFR level. Prescriptions for SGLT2i and GLP1 RA did not change following a cardiovascular event in all eGFR categories. More efforts are needed to provide optimal therapies for cardiovascular risk reduction in patients with diabetes and cardiovascular disease.
Abstract P445: Pulmonary Function is Associated With the Subendocardial Viability Ratio
Authors: Keshawarz Amena , Cech Martin , Westfeldt Elizabeth , Kinney Gregory L , Snell-bergeon Janet
Published: March 2020

Introduction:
Pulmonary function is reduced and arterial stiffening is increased in type 1 diabetes. While increased arterial stiffness is associated with greater risk of cardiovascular disease in type 1 diabetes, the association between reduced pulmonary function and health outcomes in this population is less understood. The subendocardial viability ratio (SEVR), a ratio comparing myocardial perfusion to cardiac workload, may provide useful information pulmonary function and myocardial hypoxemia in the context of pulmonary function in type 1 diabetes.

Hypothesis:
We tested the hypothesis that impaired pulmonary function (i.e., percent predicted forced vital capacity [FVCpp], forced expiratory volume at 1 second [FEV
1
pp], and FEV
1
/FVC), is associated with reduced SEVR in adults with and without type 1 diabetes.

Methods:
We conducted pulse wave analysis on 208 adults with type 1 diabetes (mean age 52±9 years) and 285 adults without diabetes (mean age 55±8 years) to obtain the outcome measure of SEVR. All participants underwent non-bronchodilated spirometry testing to obtain FVCpp, FEV
1
pp, and FEV
1
/FVC. Independent t-tests were used to test the difference by diabetes status in each pulmonary function measure and the SEVR. Linear regression models were used to test the association between each pulmonary function measure and SEVR after adjustment for age, sex, diabetes status, smoking status, and heart rate.

Results:
FVCpp and FEV
1
pp were both significantly lower in type 1 diabetes (87.5% and 85.6%, respectively) compared to controls without diabetes (95.6% and 94.9%, respectively; p<0.001 for both). There was no significant difference by diabetes status in FEV
1
/FVC (97.5% vs. 99.0%, p=0.07). SEVR was also significantly lower in type 1 diabetes (137.5 vs. 159.6, p<0.001). In an adjusted linear model, both FVCpp and FEV
1
pp were associated with SEVR. FVCpp was associated with 0.086 greater SEVR per SD (p=0.002), and FEV
1
pp was associated with 0.058 greater SEVR per SD (p=0.04). FEV
1
/FVC was not significantly associated with SEVR (p=0.37). In the model testing FVCpp, type 1 diabetes was associated with 0.18 lower SEVR (p<0.001). Similarly, in the model testing FEV
1
pp, type 1 diabetes was associated with 0.19 lower SEVR (p<0.001). After accounting for FEV
1
/FVC, type 1 diabetes was still associated with 0.20 lower SEVR (p<0.001).

Conclusions:
In conclusion, reduced pulmonary function was associated with reduced SEVR in cross-sectional analysis, but type 1 diabetes remained independently associated with reduced SEVR after accounting for reduced pulmonary function. The mechanism between pulmonary function and SEVR is unclear, but future research may reveal pathways or shared etiologies in type 1 diabetes.
Abstract P454: Impact of Air Pollution on Subclinical Atherosclerosis Risk in Middle Aged Women With and Without Polycystic Ovary Syndrome
Authors: Zhu Lei , Talbott Evelyn O , Youk Ada O.
Published: March 2020

Objective:
To study the association of ambient air pollution and subclinical atherosclerosis (SCA) risk in middle aged women with and without a history polycystic ovary syndrome (PCOS).

Background:
The harmful impact of air pollution relates to the increased risk in cardiovascular disease (CVD), a leading cause of mortality in the US. Atherosclerosis measured by coronary artery calcification (CAC) is highly correlated with the degree of atherosclerosis. Fine particulate matter (particles ≤ 2.5 μm in aerodynamic diameter [PM
2.5
]), is known to affect cardiovascular health, but no study has focused on the impact in middle aged women with PCOS, a heterogeneous disorder involving altered ovarian function and often with higher risk of CVD.

Methods:
We evaluated 310 women (at first visit: age 47.7 ± 6.3 years; BMI 30.1 ± 7.6; 46.4% PCOS) from the Cardiovascular Health and Risk Measurement III study, who had data on SCA measured by CAC Agaston score, PCOS measures and PM
2.5
levels. Logistic regression models were used to estimate the association between PM
2.5
exposures (categorized into quartiles) and CAC (categorized into a binary variable, where CAC Agaston score ≤ 10 as reference group), adjusting for age, BMI, and PCOS status. Subgroup analyses were conducted to test associations between PM
2.5
and CAC among the vulnerable population of women with PCOS.

Results:
Annual mean PM
2.5
levels were 16.8 ± 1.1 and 16.6 ± 1.3 μg/m
3
, respectively, among women with CAC Agaston score > 10 and ≤ 10 (N=76 vs. 234). In addition, women with PCOS had an annual mean PM
2.5
levels of 16.5 ± 1.3 μg/m
3
, and women without PCOS had an annual mean PM
2.5
levels of 16.8 ± 1.1 μg/m
3
(N=143 for PCOS cases vs. 165 for controls). In adjusted analysis, the odds ratio of CAC risk was 1.32 (95% CI: 0.54, 3.28) for the highest quartile of PM
2.5
vs. the lowest one (Q4: 17.5-18.9 VS. Q1: 12.7-16.0 μg/m
3
). Within the PCOS group, the likelihood of CAC was 4.78 times higher (95% CI: 1.37, 16.76) in the highest quartile of PM
2.5
levels, compared to the lowest.

Conclusions:
Women with PCOS appear to be at higher risk for the impact of PM2.5 exposure on SCA, compared to those without PCOS in this middle aged group. Replication of this work in other groups of women with PCOS would be of a high priority.
Abstract P457: Age Dependence of Genetic Risk Scores in Relation to Coronary Artery Disease
Authors: Liu Chang , Huang Yunfeng , Hui Qin , QUYYUMI Arshed A , Sun Yan
Published: March 2020

Background:
Coronary artery disease (CAD) is an age-related multi-factorial disease with a high public health burden. Genetic loci for CAD have been discovered and collectively predict CAD risk independent of traditional risk factors. It remains unclear whether age modifies the genetic predisposition to CAD.

Methods:
A total of 173,315 Caucasian subjects from the UK Biobank were included in this study, including 26,472 CAD patients with age of onset ranging from 32 to 78 years old, and 146,843 control subjects > 60 years old without CAD. CAD diagnosis was extracted from in-patient Hospital Episode Statistics (HES) and National Death Registry based on ICD-10 and OPCS-4 codes. CAD genetic risk score (GRS) was calculated based on the 161 known CAD loci. Sub-GRSs for body mass index (BMI, 16 loci), blood pressure (BP, 26 loci) and lipids (17 loci) were constructed to examine the genetic risk for CAD from certain intermediate trait. The CAD GRSs among onset age groups were compared to the controls using linear regression models, controlling for sex, BMI, creatinine, c-reactive protein, high density lipoprotein, low density lipoprotein, triglyceride, diabetes, heart failure history, hypertension and smoking status. The sub-GRSs were compared using the same models, excluding sub-GRS specific intermediate traits. Interactions of age groups and GRSs were tested using logistic regression models for CAD status, controlling for the same variables described above. Association analyses of each GRS were performed within each category of CAD age at onset comparing to controls.

Results:
Compared to the controls, the mean CAD GRS in CAD patients with age of onset ≤ 50 years was 0.58 standard deviations (SD) higher (95% CI 0.53-0.63), followed by CAD age of onset between 50 and 60 years (0.50 SD higher, 95% CI 0.48-0.52), between 60 and 70 years (0.35 SD higher, 95% CI 0.33-0.37), and > 70 years (0.25 SD higher, 95% CI 0.21-0.29). The sub-GRSs showed the similar trend. Age of onset stratified analysis revealed a significant CAD GRS-age interaction (p<0.001) on CAD risk where genetic effect is stronger among those early onset CAD patients - the odds ratios (OR) per CAD GRS SD among subjects with CAD onset age ≤ 50, 50 to 60, 60 to 70, > 70 years were 1.80 (95% CI 1.71-1.89), 1.66 (95% CI 1.62-1.70), 1.44 (1.41-1.47), 1.29 (95%CI 1.24-1.35), respectively. Among the three sub-GRSs, significant GRS-age interactions were observed for BP sub-GRS and lipids sub-GRS but not BMI sub-GRS.

Conclusion:
The observed gene-age interaction indicates that the genetic susceptibility for CAD decreases for older subjects. The contribution of the CAD GRS to CAD risk is almost 64% lower in those developing CAD at age > 70 years compared to those ≤ 50 years. Future considerations and applications of CAD genetic risk in precision medicine needs to include age of onset to accurately evaluate the genetic contribution.