bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P004: Association Between The Liver Fibrosis-4 Score And Incident Atrial Fibrillation In A General Japanese Population Of Middle-aged To Older Adults
Authors: Tanaka Yoshihiro , Chuzi Sarah , Morikawa Nagisa , Tada Hayato , Hayashi Kenshi , Greenland Philip , Vanwagner Lisa B , Khan Sadiya
Published: May 2021

Background:
There is increasing evidence that end-organ liver dysfunction is an important risk factor for atrial fibrillation (AF). Whether a non-invasive, laboratory-based marker of liver fibrosis, the fibrosis-4 score (FIB-4), is associated with incident AF is not known.

Aim:
To examine the longitudinal association of FIB-4 with incident AF in a general Japanese population with public health insurance.

Methods:
We used data from the National Japanese Health Check-Up performed in Kanazawa City, which included unemployed or retired participants aged ≥ 40 years. The baseline examination occurred in 2013 and participants were invited for annual routine examinations with follow-up data available through 2018. We excluded participants with pre-existing AF or missing data at baseline or follow-up. Incident AF was based on 12-lead electrocardiogram. We calculated the FIB-4 score (composed of age [years], aspartate and alanine aminotransferase, and platelet levels) for each participant and estimated the cumulative incidence of AF stratified by FIB-4 score quartiles. We also examined the association between quartiles of FIB-4 and incident AF using Cox proportional hazard models adjusted for risk factors with the lowest FIB-4 quartile as referent.

Results:
Of 37,892 participants, 37% were male and mean age was 72.4±9.6 years. Median (interquartile range [IQR]) of the FIB-4 score was 1.75 (IQR 1.38, 2.27). During a median (IQR) follow-up period of 5.0 years (4.0, 5.0), 707 cases of incident AF were identified. Cumulative incidence in the highest quartile of FIB-4 was 3.9% compared with 1.0% in the lowest quartile (log-rank p<0.001,
Figure A
). Higher quartiles of the FIB-4 score had a dose-dependent increased risk of AF with adjusted HR of 1.70 (1.29, 2.23) in the highest quartile compared with the lowest quartile (
Figure B
).

Conclusion:
FIB-4 was independently associated with incident AF in a general, older Japanese population and may reflect risk of AF, in addition to traditional cardiovascular risk factors.
Abstract P009: Growth Differentiation Factor 15 And The Subsequent Risk Of Atrial Fibrillation: The Atherosclerosis Risk In Communities Study
Authors: Chen Mengkun , Ding Ning , Mathews Lena , Hoogeveen Ron C , Ballantyne Christie M , Chen Lin Yee Y , Matsushita Kunihiro
Published: May 2021

Introduction:
Growth differentiation factor 15 (GDF-15) is a marker of oxidative stress and inflammation and has been associated with several cardiovascular disease (CVD) phenotypes. However, conflicting results have been reported regarding the association of GDF-15 with incident atrial fibrillation (AF) in the general population.
Hypotheses:
Higher GDF-15 level is associated with increased risk of incident AF independent of potential confounders.

Methods:
In 10,101 White and Black ARIC participants (mean age 60 years and 20.9% Blacks) free of AF at baseline (1993-95), we quantified the association of GDF-15 and incident AF using three Cox proportional hazards models. GDF-15 was measured by SOMA scan assay. AF was defined by hospitalizations with AF diagnosis or death certificates (ICD-9 codes: 427.31-427.32; ICD-10 codes: I48.x) or AF diagnosis by ECG at subsequent ARIC visits.

Results:
There were 2165 cases of incident AF over a median follow-up of 20.7 years (incidence rate 12.1 cases/1,000 person-years). After adjusting for demographic characteristics and cardiovascular risk factors, log GDF-15 was significantly associated with incident AF (hazard ratio 1.42 (1.25-1.63) for top vs. bottom quartile) (Model 1 in
Table
). The result was robust even further adjusting for history of other CVD phenotypes and cardiac markers (Models 2 and 3 in
Table
). In Model 3, quartiles of high-sensitive cardiac troponin T (hs-cTnT) did not demonstrate significant associations with incident AF.

Conclusions:
In community-based population, elevated GDF-15 level was independently and robustly associated with incident AF (even more strongly than troponin). These results suggest the involvement of GDF-15 in the development of AF and the potential of GDF-15 as a risk marker to identify individuals at high risk of AF.
Abstract P015: Serum Thrombospondin-2 Of Cardiovascular Risk Factor Is Strongly Associated With Liver Fibrosis In A General Population
Authors: Morikawa Nagisa , Adachi Hisashi , Enomoto Mika , Fukami Ako , Sakaue Akiko , Toyomasu Kenta , Yamamoto Maki , Fukumoto Yoshihiro
Published: May 2021

Background:
Non-alcoholic fatty liver disease is increasing in decades and has been recently reported to be associated with cardiovascular disease (CVD). However, the underlying pathophysiology has not been elucidated. Thrombospondin(TSP)-2 is a cardio-protective extracellular matrix, while some clinical studies showed that high serum TSP-2 is a good predictor for adverse events in patients with heart failure. We previously found that in healthy people, serum TSP-2 was associated with insulin resistance, N-terminal pro-brain natriuretic peptide and atrial fibrillation, which suggested a potential CVD risk factor. Therefore, serum thrombospondin-2 can affect on the association between liver fibrosis and CVD.

Hypotheses:
Serum TSP-2 levels were associated with liver fibrosis in a general population.

Methods:
We performed a cross-sectional study with a health-check up in 224 participants (mean age: 69.0±7.8 years, men: 42.0%) in Uku, Japan in 2019. Serum TSP was measured by ELISA. Liver fibrosis was defined by the Fibrosis-4 (FIB-4) index ≥2.67, where FIB-4 was calculated as {(ageхaspartate aminotransferase)/(plateletх(alanine aminotransferase)
0.5
)}/10. Continuous serum TSP-2 was modeled using restricted cubic splines with 3 knots (5
th
, 50
th
, 95th) to allow a nonlinear association with the log odds ratio of liver fibrosis.

Results:
Mean FIB-4 was 1.92±0.89 and 14.3% of total had liver fibrosis. Age and sex adjusted log odds ratios (ORs) for liver fibrosis was associated with serum TSP-2 non-linearly and the risk accelerate when serum TSP-2 ≥29.5ng/mL(Figure 1). ORs(95% CI) for 29.5 and 31.0 of serum TSP-2 compared to 23.0(median) were 1.57(1.11-2.21) and 1.86(1.25-2.78), respectively.

Conclusion:
Serum TSP-2, which is a CVD biomarker, was strongly associated with liver fibrosis in the pathological range in a general population. This finding provides a new insight into the pathology in the link between liver fibrosis and CVD.
Abstract P019: A Single Model For Predicting Major Adverse Cardiovascular Events In Individuals With And Without History Of Atherosclerotic Cardiovascular Disease: The Atherosclerosis Risk In Communities (aric) Study
Authors: Mok Yejin , Mathews Lena , Hoogeveen Ron C , Blaha Michael J , Ballantyne Christie M , Coresh Josef , Rosamond Wayne D , Matsushita Kunihiro
Published: May 2021

Background:
In the 2018 AHA/ACC Cholesterol guideline, risk stratification is an essential element. The use of a Pooled Cohort Equation (PCE) is recommended for individuals without atherosclerotic cardiovascular disease (ASCVD), and the new dichotomous classification of very high-risk vs. high-risk has been introduced for patients with ASCVD. These distinct risk stratification systems mainly rely on traditional risk factors, raising the possibility that a single model can predict major adverse cardiovascular events (MACEs) in persons with and without ASCVD.

Methods:
We studied 11,335 ARIC participants with (n=885) and without (n=10,450) a history of ASCVD (myocardial infarction, ischemic stroke, and symptomatic peripheral artery disease) at baseline (1996-98). We modeled factors in the PCE and the new classification for ASCVD patients (Figure legend) in a single CVD prediction model. We examined their associations with MACEs (myocardial infarction, stroke, and heart failure) using Cox models and evaluated the discrimination and calibration for a single model including those factors.

Results:
During a median follow-up of 18.4 years, there were 3,658 MACEs (3,105 in participants without ASCVD). In general, the factors in the PCE and the risk classification system for ASCVD patients were associated similarly with MACEs regardless of baseline ASCVD status, although age and systolic blood pressure showed significant interactions. A single model with these predictors and the relevant interaction terms showed good calibration and discrimination for those with and without ASCVD (c-statistic=0.729 and 0.704, respectively) (Figure).

Conclusion:
A single CVD prediction model performed well in persons with and without ASCVD. This approach will provide a specific predicted risk to ASCVD patients (instead of dichotomy of very high vs. high risk) and eliminate a practice gap between primary vs. secondary prevention due to different risk prediction tools.
Abstract P020: Triglyceride-lowering Lipoprotein Lipase Gene Variants And Improvements In Lipids And Lipoprotein Subspecies Defined By Apolipoprotein C-iii: Pounds Lost Trial
Authors: Heianza Yoriko , Zhou Tao , He Hua , Bray George , Sacks Frank M , Qi Lu
Published: May 2021

Introduction:
Triglyceride-lowering variants in the lipoprotein lipase (
LPL
) gene have been associated with a lower risk of coronary heart disease. Lipoproteins are heterogeneous, and lipoprotein subspecies containing apolipoprotein C-III (ApoCIII) have adverse effects on cardiovascular disease (CVD) risk.

Hypothesis:
We examined associations of triglyceride-lowering
LPL
gene variants with long-term improvement in lipids and lipoprotein subspecies with ApoCIII in patients with obesity. We also investigated whether the
LPL
gene variants were significantly related to the improvement of the 10-year CVD risk estimated using the Framingham risk score in the participants of a weight-loss dietary intervention trial.

Methods:
This study included 382 overweight and obese adults of white European ancestry in a 2-year weight-loss dietary intervention, the POUNDS Lost trial. We evaluated changes in lipids (triglycerides and cholesterol) and lipoproteins (such as very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) subfractions defined by the presence or absence of ApoCIII from baseline to 2 years after the intervention. A genetic risk score of
LPL
(LPL-GRS) was calculated by summing triglyceride-lowering alleles of five independent single nucleotide polymorphisms (SNPs). We calculated the Framingham risk score and estimated changes in the 10-year CVD risk after the intervention.

Results:
At baseline, higher scores of triglyceride-lowering LPL-GRS were significantly associated with higher levels of HDL cholesterol (p= 0.0065) and lower levels of triglycerides (p= 0.017). Higher LPL-GRS was also associated with more decreases in total triglycerides (p= 0.028) and triglycerides in VLDL with ApoCIII (p=0.018) at 2 years. The LPL-GRS was also predictive of 2-year improvements in other atherogenic lipoprotein subtypes, such as cholesterol in VLDL with ApoCIII (p= 0.037) and cholesterol in LDL with ApoCIII (p= 0.027) after the intervention. Further, the LPL-GRS was significantly associated with a 2-year reduction of the estimated CVD risk, regardless of the initial risk status (p=0.034).

Conclusion:
The triglyceride-lowering LPL-GRS was significantly predictive of improvements in unfavorable lipid profiles, including lipoprotein subtypes containing ApoCIII after consuming a weight-loss diet in patients with obesity. The reduction of the estimated CVD risk after the dietary intervention was predicted by the LPL-GRS at the pre-intervention.
Abstract P022: Self-reported Polycystic Ovary Syndrome Is Associated With Higher Odds Of Metabolic Syndrome In Women Aged 18-76 Years From The Hispanic Community Health Study/Study Of Latinos
Authors: Rao Hridya C , Fernandez-Rhodes Lindsay , Meyer Michelle , Kominiarek Michelle , Gallo Linda , Syan Raveen , Perreira Krista
Published: May 2021

Introduction:
Polycystic Ovary Syndrome (PCOS) is associated with increased Metabolic Syndrome (MetS), however, these findings have not been characterized in Hispanic/Latina women who are disproportionately burdened by obesity and cardiovascular disease risk compared to non-Hispanic whites. It is also unclear if this association is moderated by elevated high-sensitivity C-Reactive Protein (hs-CRP) levels, a marker for inflammation and a predictor of cardiovascular disease.

Hypothesis:
In Hispanic/Latina women, we hypothesized that 1) PCOS (self-reported diagnosis and signs) is associated with a higher prevalence of MetS compared to those not reporting PCOS 2) elevated hs-CRP is associated with MetS, and 3) the PCOS-MetS association is moderated by elevated hs-CRP.

Methods:
We used information from reproductive and economic questionnaires and venous blood measurements collected in Hispanic Community Health Study/Study of Latinos (2008-2017), a U.S. community-based cohort study of Hispanic/Latino adults. PCOS was operationalized as either 1) signs of PCOS (e.g., menstrual cycles >35 days, irregular cycles (at age 20 to 40 years old when not using birth control pills or other hormone medications and not pregnant or breastfeeding) or 2) having answered “yes” to a self-reported question on PCOS. MetS was operationalized as ≥3 elevated subcomponents of MetS (i.e., waist circumference, hypertension, insulin resistance, lipid profile, and triglycerides). A hs-CRP value ≥3.0 mg/L was considered elevated. We adjusted for the complex survey study design, age, study center, Hispanic/Latina background, and age at immigration in all models.

Results:
The overall (unweighted N=9582) age ranged from 18 to 76 years (mean=41.74, SD=14.18). The prevalence of PCOS (self-reported diagnosis and signs) was 12% (1008/7366), prevalence of MetS was 40% (2380/3495), prevalence of elevated-hsCRP was 44% (3704/4667). PCOS was associated with a significantly higher odds of MetS before (OR 1.35, 95% CI: 1.06-1.71) and after adjusting for elevated-hsCRP (OR 1.29, 95%CI: 1.02-1.65). Elevated hs-CRP is significantly associated with MetS (OR 2.31, 95%CI: 1.95-2.76). There was no significant interaction effect of hs-CRP in the PCOS-MetS association.

Conclusions:
Prevalence of PCOS (self-reported and signs) was 12% in our sample of Hispanic/Latina women, which is consistent with the previous findings in non-Hispanic whites. Both PCOS (self-reported diagnosis and signs) and elevated hs-CRP were significantly associated with higher prevalence of MetS and could indicate women at metabolic disease risk.
Abstract P023: Leukocyte Count, Adiposity And Incident Diabetes In A Biracial Cohort
Authors: Kamin Mukaz Debora , Koh Insu , Carson April P , Joseph Joshua J , Long Leann , Plante Timothy B , Cushman Mary
Published: May 2021

Background:
Diabetes is one the costliest diseases in the U.S, and excess inflammation associates with greater diabetes risk. Greater adiposity is associated with higher leukocyte count, but the interrelations of body size phenotype, leukocytes, and incident diabetes is unknown.

Hypothesis:
Body size phenotype and incident diabetes can be further understood using leukocyte count in Black and White people.

Methods:
The study included 8075 Black and White participants without diabetes at baseline (2003-2007) in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Body size phenotypes included metabolically healthy non-obese, metabolically healthy obese, metabolically unhealthy non-obese, and metabolically unhealthy obese. The interaction of leukocyte count with body size phenotype was assessed. As an exploratory analysis, data were further stratified by race.

Results:
The interaction of leukocyte count with body size phenotype was significant (p=0.02). In metabolically healthy individuals with or without obesity, the risk of diabetes increased across leukocyte quartiles. In healthy non-obese individuals, the risk of diabetes was 3 times higher in the top compared to the bottom quartile of leukocyte count and 4.5 times higher in unhealthy obese individuals. In contrast, there was no association in metabolically unhealthy participants with or without obesity. Considering race differences, in metabolically healthy non-obese persons, the association was 4 times higher for Black individuals and 2 times higher among White individuals. In the healthy obese group, these associations was larger in White than Black people.

Conclusions:
Higher leukocyte count is associated with the risk of diabetes in metabolically healthy individuals with or without obesity, but not among metabolically unhealthy individuals. Inflammation, as assessed by leukocyte count, does not identify added risk among those who are already classified as metabolically unhealthy.
Abstract P025: Atrial Fibrillation Associated With Worsened Postoperative Outcomes In Patients Undergoing Orthotropic Liver Transplantation.
Authors: Dangl Michael , Grant Jelani , Vincent Louis T , Ebner Bertrand , Maning Jennifer , Olorunfemi Odunayo P , Olarte Neal , Sancassani Rhea , Colombo Rosario A
Published: May 2021

Introduction:
Pre-orthotropic liver transplant (OLT) cardiac risk assessment commonly focuses on evaluation of coronary artery disease (CAD). However, the effect of atrial fibrillation (AF) on post-OLT outcomes is less well known. In this study, we sought to evaluate the prevalence and effect of pre-transplant AF on 30-day post-operative outcomes in patients undergoing OLT.

Methods:
The National Inpatient Sample Database was queried from 2011 to 2017 for relevant ICD-9 and -10 procedural and diagnostic codes. Baseline characteristics and in-hospital outcomes were compared in patients who underwent OLT with AF and those without.

Results:
Among 45,357 patients who underwent OLT, 35.8 % were women. The prevalence of AF prior to transplant was 2,932 (6.5%) with a trend towards increasing prevalence between 2011 and 2017 with an annual change rate of 4.19%, see Figure 1. Compared to the non-AF cohort, the AF group was older (59.9±7.9 vs 51.2±16.9 years old, p<0.001), with a higher prevalence of diabetes mellitus (DM), CAD, chronic kidney disease, heart failure (HF), anemia, and thrombocytopenia (p<0.001 for all). In-hospital 30-day mortality (5.8% vs. 3.6%, p<0.001), intra-operative cardiac arrest (8.1% vs. 1.7%, p<0.001), post-operative ventricular tachycardia (7.5% vs. 2.6%, p<0.001) and acute kidney injury (64.2% vs. 49.3%, p<0.001) were higher in the AF group when compared to those without. Using a multivariate logistic regression model to adjust for confounding factors, AF was still predictive of an increased odds of in-hospital 30-day mortality (OR: 1.92; 95% CI [1.61-2.30], p<0.001).

Conclusion:
In patients undergoing OLT, pre-transplant AF is increasing in prevalence and appears to be associated with worse in-hospital outcomes and 30-day mortality. This effect may be driven in part by a higher prevalence of concurrent cardiovascular disease and associated risk factors in patients with AF. Greater emphasis should be placed on AF in the preoperative cardiovascular risk stratification of patients undergoing OLT.
Abstract P026: Cardiovascular Risk Factors, Lifestyle And Social Determinants: Results From A Population-based Cross-sectional Study In Brazil (laparc Study)
Authors: de Souza Mello Tomás , Marinho Beatriz D , Azevedo Rafael B , Antequera Lucas , Velasco Pedro Julio , Moura Carlos , Mourão Maria , Simão Ramon , Almeida Mateus , Pecly Inah , Muxfeldt Elizabeth
Published: May 2021

Objective:
To evaluate the relationship between the main cardiovascular (CV) risk factors and socioeconomic indicators in a population of young adults provided by a Primary Healthcare Center in a large urban area of Brazil.

Methods:
Cross-sectional population study that included adults aged between 20- and 50-years old provided by a Primary Healthcare Center in Rio de Janeiro, Brazil. Demographic data (gender and age), socioeconomic data (education level, occupation, employment), CV risk factors (smoking, sedentary lifestyle, obesity, hypertension, diabetes, dyslipidemia) were recorded. The metabolic profile was evaluated through laboratory tests. Those who studied up to high school were considered poorly educated.

Results:
A total of 604 individuals were enrolled [39% male, mean age: 38.8 ± 8,9 years]. The median of schooling was 12 years. In addition, 288 individuals had high schooling, of which 44.5% were male. A total of 130 individuals did not study or work. Women with low education had a higher risk of smoking, hypertension, and obesity, with no difference regarding labor or study activities. Otherwise, men with low education had higher risk of sedentary lifestyle and hypertension. Among men, not working or studying increased the risk of smoking and hypertension.

Conclusions:
We found an inverse association between socioeconomic status and the prevalence of CV risk factors. Women are more affected by low schooling, while men are more affected by their working occupation. The study suggests that socioeconomic factors influence the CV risk, affecting men and women differently, pointing to the need for public policies to reverse this situation.
Abstract P027: Individualized Protein Based Cardiovascular Risk Stratification: Impact On Patient And Physician Decision Making In Patients With Real World Cardiovascular Disease
Authors: Erben Austin , Housholder Sandra , Gill Rosalynn , Williams Stephen A , Trujillo Nelson P
Published: May 2021

There is a growing population of patients with established cardiovascular disease and residual cardiovascular risk. Identification of patients who would benefit most from more advanced risk reduction strategies would be ideal.

Hypothesis:
Identification of secondary risk of MACE may change both physician recommendations and patient choices regarding goal directed therapy (GDT).

Methods:
Retrospective review of 244 patients with established CAD with traditional assessment of secondary cardiovascular risk and SomaScan proteomic risk assessment followed over 3 years. Patients were evaluated for GDT and standard measurements were made at baseline. SomaScan protein risk score was obtained. Patients received advice regarding risk and offered GDT with established secondary prevention goals. Willingness to change, physician recommendations to change therapy and therapy changes were recorded. Patients were followed over three years.

Results:
244 patients were included in the cohort; 186 males (76%), 58 females (24%). Mean age of 66, range 32-84. Diagnosis of coronary artery disease was made based on imaging in 121 patients (49%) and clinical events including CABG, MI, PCI in 123 patients (51%). Secondary cardiovascular risk of MACE by SomaScan was assessed in 5 predefined risk classes. There were 70 patients in class I (0-9.9%), 116 patients in Class II (10-19.9%), 41 patients in Class III (20-29.9%), 12 patients in Class IV (30-59%) and I patient in Class V (60-100%). GDT was already present in 143 patients including statin therapy, ACE inhibition and daily aspirin. In the cohort, 101 patients were sub-optimally treated. After reviewing results of SomaScan results, 20 patients initiated GDT, 52 patients intensified GDT. This included addition of second lipid lowering agent, initiation of PCSK-9 inhibitors, ACE-inhibition and intense lifestyle management. Overall, 30% of the overall cohort had a change in therapy: 39 patients were advised to alter therapy and did not, 17 patients would not begin goal directed therapy, 22 patients would not intensify management to meet accepted goals. Two deaths occurred during the study period. There were 14 episodes of MACE.

Conclusions:
In this population of patients with established cardiovascular disease only 58% were on guideline-based therapy. Use of SomaScan results in conjunction with standard assessment allowed an additional 30% of patients to change therapy with initiation of GDT and intensification of GDT to meet current guidelines.
Abstract P028: Increased Cardiometabolic Risk And Autonomic Function Alterations In Normal Weight Obesity
Authors: Duque Alice P , Barbosa Isadora M , Lins Alessandra S , de Jesus Fernando G , Araújo Christiane F , Nogueira Ilana d , Carvalho Ana Carolina d , Huguenin Grazielle V , De Lorenzo Andrea R , Mediano Mauro , Junior Luiz Fernando R
Published: May 2021

Introduction:
Normal weight obesity (NWO) is defined by the presence of normal body mass index (BMI) with high body fat percentage. In this setting, high body fat seems to affect even non-obese individuals, predicting cardiovascular risk.

Hypothesis:
High body fat percentage, in eutrophic individuals, affects anthropometry, hemodynamic, autonomic function and cardiometabolic risk.

Methods:
This cross-sectional study recruited workers of a public hospital from 2018 to 2020. Inclusion criteria: age ≥ 18 yr.; BMI: 18.5 to 24.9 Kg/m
2
. Exclusion criteria: pregnancy/lactating women; BMI < 18.5 Kg/m
2
or ≥ 25 Kg/m
2
. High body fat percentage was categorized, by sex and age, as: 20 to 39 years, >19.9% and >32.9%; 40 to 59 years, >21.9% and >33.9%; and 60 to 79 years, >24.9% and >35.9% for men and women, respectively. Blood assays: fasting glucose, lipid profile and C reactive protein; anthropometry: neck, waist and hip circumferences; bioimpedance: visceral fat area and body fat percentage; hemodynamic parameters: blood pressure and double product; autonomic function: orthostatic test (30:15 ratio), orthostatic hypotension test and heart rate variability (HRV): high and low frequency and sympathovagal index; cardiometabolic risk: body shape index, atherogenic dyslipidemia, atherogenic index, atherogenic index of plasma and Framingham score. Statistical analysis: Mann-Whitney and chi-squared test. P<0.05. Ethics: according to Helsinki declaration, revised in 2013.

Results:
A total of 52 from 241 volunteers were eutrophic: 23 were NWO, that exhibited higher visceral fat area, anthropometric measures, blood pressure and double product; and worse lipid profile, HRV frequency domain and cardiometabolic risk parameters compared to the 29 with normal body fat percentage
(table 1)
.

Conclusions:
NWO individuals have metabolic, hemodynamic, anthropometric and autonomic alterations that, associated with new indexes related to atherogenesis, confirm the early cardiometabolic risk of this profile.
Abstract P031: Endothelial Microparticles In Pediatric Obesity
Authors: Jang Subin , Palzer Elise F , Rudser Kyle D , Fox Claudia K , Hebbel Robert P , Dengel Donald R , Milbauer Liming , Kelly Aaron S , Ryder Justin R
Published: May 2021

Introduction:
Endothelial activation represents one of the earliest signs of the atherosclerotic process. Microparticles (MPs) in plasma, particularly endothelial MPs (EMPs) are reproducible biomarkers of endothelial dysfunction with a simple blood draw. The goal of this study was to examine the association of obesity with MPs, EMPs (CD31+/CD41– and/or CD 144+/CD31–), and activated EMPs (CD106+).

Hypothesis:
We hypothesized that higher body mass index (BMI), body fat percent (BF%), and visceral adipose tissue (VAT) would be associated with higher levels of MPs, EMPs, and activated EMPs.

Methods:
This was a cross-sectional study of 280 children and adolescents ages 8-18 years old. Whole venous blood was collected and processed for platelet free-plasma (PFP) collection less than 3 hours after being drawn. PFP samples were prepared using serial centrifugations and then frozen as 100 μl aliquots at -80
°
C. MPs were measured using flow cytometry with size ranging from 0.3 to 1.0 μm. EMPs were defined as MP with CD31+/CD41– and/or CD 144+/CD31–. Active EMP was identified as EMP with CD 106+. BF% and VAT were measured using dual X-ray absorptiometry. Linear (total MPs and EMPs) and logistic (activated EMPs) regression models were used to examine the associations with adiposity group, BF%, and VAT, adjusting for Tanner stage, sex, and race.

Results:
The mean age of the cohort was 12.7 years, consisting of 147 females and BMI distribution: 112 normal-weight, 77 overweight/obesity, 91 severe obesity. Youth with overweight/obesity and severe obesity had higher numbers of total MPs (28,690 per μL PFP/g [-2,315, 59,695], p=0.07 and 52,744 per μL PFP/g [22,163, 83,324], p<0.001, respectively) and total EMPs (350 per μL PFP/g [81, 618], p=0.011 and 278 per μL PFP/g [13, 543], p=0.040, respectively) compared to peers with normal weight. In the entire cohort, higher BF% was associated with higher MPs (1,646 per μL PFP per percent [509, 2,783], p=0.005) and EMPs (11 per μL PFP per percent [2, 21], p=0.023), and higher VAT was associated with higher MPs (34 per μL PFP/g [11, 57], p=0.004) but not EMPs. Logistic regression analysis showed higher odds of active EMPs (odds ratio, 1.72 [1.0, 2.97], p=0.0502) in those with a BMI >85
th
percentile compared to youth with a BMI <85
th
percentile. In the entire cohort, BF% (odds ratio, 1.02 [1.00, 1.04], p=0.108) and VAT (odds ratio, 1.00 [1.00, 1.00], p=0.472) were not significantly associated with active EMPs.

Conclusions:
Higher levels of endothelial cell damage and activation were associated with obesity and excess adiposity in youth. The potential role of MPs and EMPs as useful biomarkers of cardiovascular disease risk merits further study.
Abstract P035: Early Neurodevelopment Related Variables And Cardiovascular Health: Findings From The Multidimensional Assessment Of Preschoolers Study
Authors: Reges Orna , Yang Xiaoyun , Krefman Amy , Wakschlag Lauren , Flynn Rachel , MacNeill Leigha , Davis Matthew , Marino Bradley S , Labarthe Darwin R , Van Horn Linda , Hou Lifang , Lloyd-Jones Donald M , Allen Norrina B
Published: May 2021

Background:
Cardiovascular health (CVH) declines with age starting in early childhood. Neurodevelopmental health (NDH) measures, such as executive function, in early childhood have been associated with subsequent behavioral and lifestyle outcomes; however, little is known about the association of NDH measures in early life with CVH during childhood.

Objective:
To assess the association of preschool NDH with CVH in later childhood/early adolescence.

Methods:
Among participants from the Multidimensional Assessment of Preschoolers Study (MAPS), we defined 3 neurodevelopment domains at baseline (ages 3-7 years): executive functioning, developmental functioning, and emotion and behavior regulation (each as a z-score of its component surveys and direct assessment). At the tween follow-up wave (ages 9-14 years), MAPS participants completed a CVH examination including assessment of physical activity, diet, blood pressure, and BMI defined as favorable vs unfavorable CVH metrics according to AHA recommendations. Multivariate logistic regression models were used to assess the association of each NDH domain with favorable/unfavorable CVH metrics at follow up. Models were adjusted for age, race, gender, and poverty.

Results:
We included 229 SES-diverse children (46.2% boys; 52% living in poverty at baseline; mean baseline age 4.7 yr; mean follow-up age: 11.3 yr). At follow-up, there were 179 (78.2%) children with favorable CVH and 50 (21.8%) children with unfavorable CVH. Better performance on all 3 NDH domains at baseline was demonstrated among children with favorable CVH at follow-up compared to those with unfavorable CVH, with mean z-score of 0.04 among those with favorable CVH compared to -0.15 among those with unfavorable CVH for executive functioning (p<0.001), 0.02 compared to -0.07 for developmental functioning (p=0.004), and 0.02 compared to -0.06 for emotion and behavior regulation (p=0.027). After adjustment, associations between executive functioning, developmental functioning, and emotion/behavior regulation and favorable CVH were attenuated to non-significance {OR (95% CI): 1.21 (0.80-1.81), 1.03 (0.64-1.67), 1.08 (0.73-1.59), respectively}.

Conclusions:
These findings suggest a possible association between neurodevelopmental domains and CVH, although findings were not significant after adjustment. The heterogeneity of the sample may have obscured effects and the moderating role of the environment may elucidate explanatory pathways. More research with larger sample sizes is needed to better understand the impact of early-life NDH with adolescent CVH.
Abstract P039: No Beneficial Associations Between Dairy Products And Kidney Function After Myocardial Infarction
Authors: van Westing Anniek C , Cruijsen Esther , Geleijnse Johanna M
Published: May 2021

Introduction:
Population-based studies showed beneficial associations between (low-fat) dairy products and kidney function. Kidney function declines with age, which is accelerated after myocardial infarction (MI). Little is known about dairy consumption and kidney function in MI patients.

Hypothesis:
Dairy intake may slow down kidney function decline after MI.

Methods:
We analysed 2,247 Dutch post-MI patients (60-80 years, 81% men) from the Alpha Omega Cohort. Dietary intakes, including types of dairy, were assessed at baseline (2002-2006) using a validated 203-item food frequency questionnaire. Glomerular filtration rate was estimated at baseline and after ~40 months, using the Chronic Kidney Disease (CKD) Epidemiology Collaboration equations for serum cystatin C alone (eGFR
cysC
, in ml/min per 1.73m
2
). Associations between dairy intake and annual eGFR
cysC
change were obtained using multivariable linear regression models, adjusting for age, sex, lifestyle and dietary factors. Betas (β), with 95% confidence intervals (95% CI), represent additional eGFR
cysC
changes on top of annual decline, per increment in dairy intake.

Results:
At baseline, 22% was obese, 18% had diabetes and 15% had CKD (eGFR
cysC
<60). Median dairy intakes were 70 g/day for milk (62% consumed low-fat milk), 41 g/day for yogurt and 17 g/day for hard cheeses. The mean ± SD eGFR
cysC
at baseline was 82 ± 19, which on average declined by 3.42 ± 11.04, corresponding to an annual decline of 0.99 ± 3.21. Total milk consumption was not associated with annual eGFR
cysC
change in the multivariable model (β: 0.01 per 100 g/day, 95% CI: -0.08;0.10; Figure 1). Associations for hard cheeses (per 10 g/day) and yogurt (per 25 g/day) with eGFR
cysC
decline were also weak and non-significant. Sensitivity analyses in non-diabetic (n=1,843) or non-CKD patients (n=1,910) yielded similar results (Figure 1).

Conclusions:
Milk, hard cheeses and yogurt consumption were not associated with eGFR
cysC
decline in Dutch post-MI patients.
Abstract P047: US Asian Indians Dying With Atherosclerosis Are More Likely To Have Concurrent Diabetes Mellitus
Authors: Nair Deepak R , Chauhan Abhyuday , Vaidya Dhananjay
Published: May 2021

Background:
Asian Indians (AI) in the US are known to have a high prevalence of atherosclerotic diseases and diabetes mellitus (DM). However, it is not known if these two cluster as causes of death in AI compared to the rest of US population.

Methods:
Using 2017 Multiple Cause-of-Death Data from the National Centre for Health Statistics, we included deaths at age ≥ 45 years among US residents where AI vs not-AI could be ascertained (n = 7940 AI; n = 2.6 million not-AI). DM (ICD-10 range: E10-E14) and any atherosclerosis (either of: ischemic heart disease, ischemic stroke, atherosclerosis; ICD-10 range: I20-I25, I69, I70, respectively) as contributing causes of death were identified in AI and not-AI. We calculated dichotomous tetrachoric correlation (Rho) between DM and atherosclerosis as co-occurring contributing causes. To examine whether this association differed by age decade and sex, we calculated the difference in fraction of deaths with DM in those with atherosclerosis versus those without atherosclerosis as a co-occurring cause of death.

Results:
There were 114,210 atherosclerosis deaths and 24,331 DM deaths in 2017 in the sample. DM and atherosclerosis as contributing causes correlated more strongly in AI (Rho = 0.36, p < 0.001) as compared to not-AI (Rho = 0.31, p < 0.001; difference between groups, p < 0.001). The excess fraction of deaths due to DM when atherosclerosis also contributed vs when atherosclerosis did not contribute was higher in AI men of all ages and in most ages for AI women, except for a group where AI death numbers were smaller (Figure).

Conclusion:
Our findings highlight the increased burden of co-occurring DM and atherosclerotic disease together contributing as causes of death in AI compared to not-AI in the US. Public health strategies targeted to AI should focus on prevention and clinical treatment of both conditions jointly, in both men and women, especially during young adulthood and middle age.
Abstract P052: Less Appendicular Lean Mass Adjusted For Body Mass Index Is Associated With Higher Incident Diabetes In Middle-aged Adults In The CARDIA Study
Authors: Haines Melanie S , Leong Aaron , Porneala Bianca , Zhong Victor W , Lewis Cora E , Schreiner Pamela J , Miller Karen K , Meigs James B , Carnethon Mercedes R
Published: May 2021

Although less muscle mass is associated with greater diabetes prevalence in cross-sectional studies, prospective data in middle-aged Black and White adults are lacking. Middle age is a critical window as accelerated muscle loss is yet to occur, and preventing diabetes reduces lifelong morbidity and mortality. We hypothesized that lower appendicular lean mass adjusted for body mass index (ALM/BMI) is associated with higher incident diabetes in middle-aged Black and White adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study. ALM/BMI was measured by dual x-ray energy absorptiometry (DXA) in 2005-06 among middle-aged US men (n=855) and women (n=1045) in CARDIA. Incident diabetes occurred if any of the following were met in 2010-11 or 2015-16 among persons without diabetes in 2005-06: fasting glucose ≥7 mmol/L (126 mg/dL), 2-hour glucose ≥11.1 mmol/L (200 mg/dL) on a 75-gram glucose tolerance test, HbA
1C
≥48 mmol/mol (6.5%), or use of glucose-lowering medications. We used logistic regression models with sex stratification given sex differences in ALM. In men, mean age was 45.0 ± 3.5 y, BMI 28.0 ± 4.3 kg/m
2
, and ALM/BMI 1.07 ± 0.14 m
2
. In women, mean age was 45.2 ± 3.6 years, BMI 28.4 ± 6.4 kg/m
2
, and ALM/BMI 0.73 ± 0.12 m
2
. Diabetes developed in 70 men (8.2%) and 72 women (6.9%). For each standard deviation increase in ALM/BMI (m
2
), the risk of diabetes decreased by 22% in men and 29% in women (Table 1). After adjusting for age, race, smoking, education, physical activity, and waist circumference, the association of ALM/BMI with diabetes incidence was no longer significant. Associations were similar between race-ethnic groups. In conclusion, less relative skeletal muscle mass is associated with a greater risk of developing diabetes in middle-aged men and women over 10 years, which is largely explained by the relationship of ALM/BMI to other metabolic risk factors. Low skeletal muscle mass in middle age is a marker for greater diabetes risk and may be a target for preventative interventions.
Abstract P054: Duration Of Diabetes, Glucose Excursions, Glycemic Control, And Low Heart Rate Variability: The Atherosclerosis Risk In Communities (aric) Study
Authors: Rooney Mary R , Echouffo Tcheugui Justin B , Norby Faye L , Soliman Elsayed Z , Chen Lin Y , Selvin Elizabeth
Published: May 2021

Introduction:
Individuals with diabetes often have low heart rate variability (HRV)—a marker of autonomic dysfunction. How diabetes duration, glucose excursions, and poor glycemic control relate to HRV is not well characterized.

Objectives:
To evaluate the associations of diabetes status, duration of diabetes, and biomarkers of glucose excursions (1,5-anhydroglucitol [1,5-AG]—a measure of glycosuria) and glycemic control with HRV.

Methods:
We conducted a cross-sectional analysis of ARIC Study participants who underwent a 2-minute electrocardiogram at visit 4 (1996-98). We considered root mean square of successive differences in normal-to-normal R-R intervals (rMSSD, measure of parasympathetic activity), standard deviation of normal-to-normal R-R intervals (SDNN, total variability), low frequency (LF, primarily sympathetic activity), high frequency (HF, reflects parasympathetic activity), and LF/HF ratio (sympathetic-parasympathetic balance) as HRV indices. In persons with diabetes, we compared geometric means of HRV indices by diabetes duration (<5 years vs ≥5 years), 1,5-AG (<6 μg/mL vs ≥6 μg/mL), and glucose control (estimated A1C <8% vs ≥8%). We obtained p-values from linear regressions adjusted for age and sex.

Results:
Among 10169 participants (mean age 63, 57% female, 22% black), participants with diabetes had significantly lower rMSSD, SDNN, LF, HF, and LF/HF ratio compared to those without diabetes (
Table
). Among the 1667 participants with diabetes, longer duration of diabetes, low 1,5-AG, and poor glycemic control were associated with lower rMSSD, SDNN, LF, and HF. No statistically significant associations were found for diabetes duration, 1,5-AG, glycemic control with LF/HF ratio.

Discussion:
Our results demonstrate that longer duration of diabetes, glucose excursions, and poor glycemic control are associated with some measures of low HRV. This study underscores that cardiac autonomic neuropathy is a common but overlooked complication of long-standing and/or poorly managed diabetes.
Abstract P060: Plasma Osteocalcin And Incident Diabetes Mellitus: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Misialek Jeffrey R , Stremke Elizabeth R , Selvin Elizabeth , Sedaghat Sanaz , Pankow James S , Lutsey Pamela L
Published: May 2021

Introduction:
Diabetes is a major risk factor for cardiovascular disease. Osteocalcin is a vitamin K-dependent, bone-derived hormone that functions as an endocrine regulator of energy metabolism, male fertility, and cognition. Early studies of endocrine effects of osteocalcin have shown that genomic deletion of osteocalcin in mice resulted in a diabetic phenotype (i.e. glucose intolerance, and insulin resistance). However, results from clinical studies have shown mixed associations between blood levels of osteocalcin and risk of incident type 2 diabetes mellitus.

Hypothesis:
Lower values of plasma osteocalcin would be associated with an increased risk of diabetes.

Methods:
A total of 11,557 ARIC participants without diabetes at baseline were followed from ARIC visit 3 (1993-1995) through 2018. Diabetes cases were identified through self-report on annual and semi-annual follow-up phone calls. Plasma osteocalcin data was measured using an aptamer-based proteomic profiling platform (SomaLogic). We used Cox regression to evaluate the association of quintiles of plasma osteocalcin and incident diabetes. The primary model adjusted for age, sex, and race-center.

Results:
Participants were age 60 ± 5.6 years at visit 3, 56% identified as female, 21% identified as Black. There were 3,031 incident diabetes cases over a median follow-up of 17.9 years. Mean ± SD was 10.053 ± 0.775. When comparing the highest quintile of plasma osteocalcin (values 10.42 to 14.66) to the lowest quintile (values 9.03 to 9.52), there was no association with incident diabetes (HRs [95% CIs]: 0.92 [0.81, 1.02]). There was also no significant trend across the quintiles (p = 0.19). Results were similar when adjusting for additional potential confounders, and when limiting the follow-up time to 10 years.

Conclusions:
These data do not support the hypothesis that total plasma osteocalcin, as measured by Somalogic proteomic panel, is a biomarker associated with diabetes risk. It is possible that total plasma or serum osteocalcin and/or other isoforms of osteocalcin protein (i.e. gamma carboxylated or uncarboxylated osteocalcin) measured via other validated methodologies may be linked to diabetes.
Abstract P061: Dairy Consumption, Dairy Fat Biomarkers And Type 2 Diabetes Risk After Myocardial Infarction
Authors: Jacobo Cejudo Maria G. , Cruijsen Esther , Heuser Christiane , Soedamah-Muthu Sabita S. , Voortman Trudy , Geleijnse Johanna M. (Marianne)
Published: May 2021

Introduction:
Dairy consumption, especially yogurt, and circulating biomarkers of dairy fat (odd chain fatty acids, OCFAs), have been associated with a lower risk of type 2 diabetes (T2D) in population-based studies. Whether these associations are also present in post-myocardial infarction (MI) patients is unknown.

Hypothesis:
We hypothesized that dairy consumption and circulating OCFAs (pentadecanoic [15:0] plus heptadecanoic acid [17:0]) may be inversely associated with incident T2D after MI.

Methods:
We included 3347 Dutch post-MI patients from the Alpha Omega Cohort, who were initially free of T2D. At baseline (2002-2006), dairy consumption was estimated with a 203-item food frequency questionnaire and plasma OCFAs were measured in cholesteryl esters using gas chromatography. Incident T2D was ascertained through self-reported physician diagnosis and medication use. Multivariable Cox models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CI) for incident T2D and dairy types and OCFAs (per 1 standard deviation (SD) increment).

Results:
At baseline, patients were on average 68.9 years old (± 5.5 SD), 80% were men and 87% used statins (2684 and 2908 of 3347 patients respectively). During a median follow-up time of 40 months (10,550 person-years), 181 patients developed T2D. Almost all patients consumed dairy (3300 of 3347), with a median intake of 273 g/d for total dairy. After multivariable adjustment, dairy and its subtypes consumption was not associated with T2D incidence, with HRs ranging from 1.01 to 1.07 per 1-SD increment (all p> 0.05). When analysed in categories (highest vs lowest intake), HRs (95% CI) were 1.05 (0.73-1.52) for milk and 1.08 (0.77-1.51) for yoghurt intake. In line with these findings, no significant association was found for circulating OCFAs 0.97 (0.83-1.12)(
Figure 1
).

Conclusion:
Dairy consumption, based on self-report and plasma biomarkers, was neutrally associated with T2D incidence in a population of Dutch post-MI patients with a relatively high habitual dairy intake.
Abstract P062: Trends And Disparities In Diabetes Among Adults In The United States, 1999-2018
Authors: Liu Junxiu , Yi Stella S , Russo Rienna , Mayer Victoria , Li Yan
Published: May 2021

Introduction:
Diabetes (DM) increases cardiovascular disease morbidity and mortality and the risk of severe complications/death among patients with COVID-19. We aimed to estimate the trends of DM over time among adults in the US.

Hypothesis:
We anticipated an increase in DM and persistent disparities by racial/ethnic and socioecnomic subgroups from 1999 to 2018.

Methods:
Data were from a nationally representative sample of US adults (≥20 years; NHANES 1999-2018). Diagnosed DM was defined as a self-reported previous diagnosis of DM by a physician or any other health professionals (other than during pregnancy). Undiagnosed DM was defined as elevated levels of fasting plasma glucose (FPG≥126 mg/dL) or HbA1c (≥6.5%). Total DM included those who had either diagnosed or undiagnosed diabetes. Prediabetes was defined as no DM but a HbA1c level of 5.7% - 6.4% or an FPG level of 100 mg/dL-125 mg/dL. All estimates were age-standardized to the 2010 US census population for age groups 20-44, 45-64, and 65+ years. All analyses accounted for the complex survey design. Logistic regressions were conducted to calculate a P-value for trend.

Results:
Our sample included 53,533 US adults. From 1999 to 2018, the age-adjusted prevalence of total DM increased significantly from 9.05% (95% CI, 7.80%-10.2%) to 13.9% (95% CI, 12.5%-15.4%) and the prevalence of prediabetes increased from 22.5% (20%-25.2%) to 40.2% (37.4%-43.1%) (P-trends<0.001). The rate of increase in prevalence was higher among Mexican Americans but lower among non-Hispanic black individuals compared to non-Hispanic white individuals (all P-trends<0.01, P-interaction=0.003). Trends in total DM by education and income levels were similar to the overall trend but disparities persisted between low- and high-socioeconomic groups (all P-trends<0.001, P-interaction>0.05) (
Figure 1
).

Conclusions:
The prevalence of DM increased significantly from 1999 to 2018 among US adults. There are substantial and persistent disparities between racial/ethnic and socioeconomic subgroups.