bluuebunny/crossref_metadata_2025_split huggingface dataset:
436-P: Comparison of the ASCVD and UK Prospective Diabetes Study Risk Engine with Carotid Intima Media Thickness and Brachial-Ankle Pulse Wave Velocity
Authors: HONG SANG MO , CHOI YUN MI , HONG EUN-GYOUNG 
Published: June 2019

Object: We explored and compare the efficacy of ACC-AHA-atherosclerotic cardiovascular disease (ASCVD) risk score and UK Prospective Diabetes Study (UKPDS) risk engine with the presence of subclinical carotid and peripheral atherosclerosis in patients with type 2 diabetes(T2DM) patients.
Methods: We studied 746 T2DM patients aged 20 years and older, who visited Hallym University Dongtan Sacred Heart Hospital from Noember 2012 to June 2014. Carotid atherosclerosis was defined as carotid intima-media thickness (IMT) &gt; 1mm or the presence of carotid artery plaque. Peripheral atherosclerosis was defined as over than 1750 cm/s of brachial-ankle pulse wave velocity (baPWV). Ten-year coronary heart disease (CHD) risk was determined using the ASCVD and UKPDS risk engine.
Results: The mean 10-year CHD risks of UKPDS and ASCVD were 13.9±13.0% and 12.7±13.3%, respectively. The prevalence of carotid atherosclerosis and peripheral atherosclerosis were 13.3% and 22.9%. The risk for carotid atherosclerosis and peripheral atherosclerosis increased 6.12 (95% CI 3.3-11.4) times and 10.0 (95% CI 5.9-17.1) times in high risk group (≥20% 10-year UKPDS risk) than low-risk group, respectively. The risk for carotid atherosclerosis and peripheral atherosclerosis increased 7.891 (95% CI 4.4-14.0) times and 15.6 (95% CI 9.2-26.2) times in high risk group (≥20% 10-year ASCVD-predicted coronary heart disease risk) than low-risk group, respectively. In multiple regression analysis with ASCVD and UKPDS risk for carotid atherosclerosis and peripheral atherosclerosis, only ASCVD risk were statically significant (all p&lt;0.001).
Conclusion: Carotid atherosclerosis and peripheral atherosclerosis were prevalent in patients with T2DM and positively correlate d with 10-year CHD risk. In comparison of ASCVD and UKPDS risk engine, ASCVD risk engine was more proper in patients with T2DM.

Disclosure
S. Hong: None. Y. Choi: None. E. Hong: None.
441-P: Chitotriosidase Activity Is Inversely Associated with Diastolic Blood Pressure and HbA1c but Not with Arterial Stiffness in Patients with Type 2 Diabetes without Complications
Authors: D'ONOFRIO LUCA , LUORDI CECILIA , MIGNOGNA CARMEN , CARLONE ANGELA , MORETTI CHIARA , TARTAGLIONE LIDA , MADDALONI ERNESTO , LETO GAETANO , MAZZAFERRO SANDRO , BUZZETTI RAFFAELLA 
Published: June 2019

Background and Aim: Chitotriosidase (Chit), a mammalian chitinases secreted by monocytes and epithelial cells, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. Aim of the study was to evaluate Chit activity as a precocious biomarker of arterial stiffness in T2D patients without overt vascular complications.
Methods: Arterial stiffness was measured by Cardio-Ankle Vascular Index (CAVI) in 174 T2D patients (mean±SD age=55±4 years, 103 men) without established diabetic complications. For this cross-sectional study, we measured Chit activity by electrochemiluminescent assay in the sera from the 41 patients with the lowest (L_CAVI) and the 42 patients with the highest (H_CAVI) CAVI values.
Results: Compared with L_CAVI, H_CAVI patients were older (57±4years vs. 52±4years, p&lt;0.01), had longer T2D duration (6±3years vs. 4±3years, p=0.02), higher diastolic blood pressure (DBP) (90±9 vs. 86±9mmHg, p=0.03), HbA1c (6,5±0,9% vs. 6,01±0,6%, p&lt;0.01) and fasting blood glucose (130±29 vs. 117±27 mg/dL, p=0,024) values, lower BMI (28,5±4,2 vs. 32,3±7,2 kg/m2, p=0.01) and glomerular filtration rate (91,3±11,2 vs. 96,1±10,0mL/min/1.73m2, p=0.04). Chit activity was similar in L_CAVI and H_CAVI groups (11,6±5,6 vs. 14,0±8,3 nmol/mL/h respectively). Although, Chit was inversely related to DBP (r=-0.22; p &lt;0.041) and HbA1c (r=-0.21; p=0.048) and directly related to albuminuria (r=0.22; p=0.04). No significant differences were found in systolic blood pressure, gender, lipid profile, calcium, urate, inflammatory markers between the two groups.
Conclusion: Arterial stiffness raises with age, metabolic control, DBP and impaired kidney function. Chit is also associated with DBP, metabolic control and kidney damage but did not result as a direct marker of arterial stiffness in T2D patients without established complications.

Disclosure
L. D'Onofrio: None. C. Luordi: None. C. Mignogna: None. A. Carlone: None. C. Moretti: None. L. Tartaglione: None. E. Maddaloni: Speaker's Bureau; Self; Merck & Co., Inc., Pikdare. G. Leto: None. S. Mazzaferro: None. R. Buzzetti: None.

Funding
Sapienza University of Rome (“Avvio alla ricerca 2016”)
443-P: Reduced Cardiorenal Function and In-Hospital Mortality in Patients with Type 2 Diabetes Mellitus and ST-Segment Elevation Myocardial Infarction
Authors: GENOVESE STEFANO , COSENTINO NICOLA , CAMPODONICO JENESS , DE METRIO MONICA , MOLTRASIO MARCO , RONDINELLI MAURIZIO , DE FERRARI GAETANO , MARENZI GIANCARLO 
Published: June 2019

Background: ST-segment elevation myocardial infarction (STEMI) patients with diabetes mellitus (DM) have higher in-hospital mortality than those without. Since cardiac and renal functions are the main variables associated with outcome in STEMI, we hypothesized that this prognostic disparity may depend on a higher rate of cardiac and renal dysfunction in DM patients.
Methods: We included 5,152 STEMI patients treated with primary angioplasty. Left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were evaluated at hospital admission. The primary endpoint was in-hospital mortality. A composite of in-hospital mortality, cardiogenic shock, and acute kidney injury was the secondary endpoint.
Results: Eight-hundred-seventy-nine (17%) patients had DM. The incidence of LVEF≤40% (30% vs. 22%; P&lt;0.001), eGFR≥60 ml/min/1.73m2 (27% vs. 18%; P&lt;0.001), or both (12% vs. 6%; P&lt;0.001) was higher in patients with DM. In-hospital mortality was higher in DM than in non-DM patients (6.1% vs. 3.5%; P=0.002) with an unadjusted OR of 1.81 (95% confidence interval [CI] 1.31-2.50; P=0.003). However, DM was no longer associated with an increased mortality risk after adjustment for cardiac and renal function (OR 1.03, 95% CI 0.68-1.56; P=0.89). A similar behavior was observed for the secondary endpoint, with an unadjusted OR for DM of 1.52 (95% CI 1.25-1.85; P&lt;0.001) and an OR after adjustment for cardiac and renal function of 1.07 (95% CI 0.85-1.36; P=0.53).
Conclusion: The study indicates that the increased in-hospital mortality and morbidity of DM patients with STEMI is driven by the underlying cardio-renal dysfunction, rather than to the mere presence of DM.

Disclosure
S. Genovese: Advisory Panel; Self; Novartis Pharmaceuticals Corporation, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Hikma Pharmaceuticals. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Takeda Pharmaceutical Company Limited. N. Cosentino: None. J. Campodonico: None. M. De Metrio: None. M. Moltrasio: None. M. Rondinelli: Consultant; Self; Sanofi. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Takeda Pharmaceutical Company Limited. G. De Ferrari: None. G. Marenzi: Speaker's Bureau; Self; Merck Sharp & Dohme Corp.

Funding
Centro Cardiologico Monzino
444-P: Evaluating Factors Associated with Cardiovascular and Cerebrovascular Complications of Type 2 Diabetes
Authors: PREWITT TODD G. , MANNER DAVID , DECLUE RICHARD W. , NAIR RADHIKA , BAJPAI SANJAY K. , WONG-JACOBSON SIEW HOONG , JUNEJA RATTAN , PENG XIAOMEI 
Published: June 2019

Our aim was to understand characteristics of patients with type 2 diabetes mellitus (T2DM) who develop macrovascular complications. This was a retrospective observational study using administrative claims from a large national health plan. We identified patients with T2DM between January 2010 and June 2012; date of the first claim for T2DM was set as the index date. Patients 18-89 years of age enrolled in a health plan for at least one year prior (baseline) and post-index, with at least one HbA1c value during pre-index, were identified. Patients were categorized into incident and prevalent cohorts of T2DM based on absence/presence of claims during the baseline period. Patients with cerebrovascular and cardiovascular complications (CV complications), as defined by the diabetes complications severity index, were evaluated. Descriptive analyses were used to evaluate characteristics of patients with and without CV complications. Landmark dynamic risk modeling was used to identify factors predicting CV complications for those with no history of CV complications during the baseline period. We identified 111,205 patients with T2DM; 61,101 (54.6%) had no history of CV complications at baseline. During the five years post-index, 13,059 (21.4%) and 31,472 (51.5%) had a cerebrovascular or cardiovascular complication, respectively. Proportions were slightly higher in the prevalent T2DM cohort, especially for cerebrovascular complications (22.3% vs. 20.2%, P&lt;0.001). For patients with no history of CV complications, landmark dynamic risk modeling identified smoking (HR 1.26), obesity/overweight (HR 1.14), hypertension (HR 1.27), dyslipidemia (HR 1.11) and peripheral vascular disease (HR 1.19) increased risk of CV complications (P&lt;0.001). Identifying modifiable variables that change over time, and the presence of chronic comorbidities, can aide development of specific interventions to evaluate and treat patients with T2DM, while addressing risk of CV complications.

Disclosure
T.G. Prewitt: None. D. Manner: Employee; Self; Eli Lilly and Company. R.W. DeClue: Employee; Self; Humana. R. Nair: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., GlaxoSmithKline plc. S.K. Bajpai: Employee; Self; Eli Lilly and Company. S. Wong-Jacobson: None. R. Juneja: Employee; Self; Eli Lilly and Company. X. Peng: None.

Funding
Eli Lilly and Company
452-P: Albumin/Creatinine Ratio and Pulse Wave Velocity Predicts Coronary Artery Disease and Renal Outcome in Type 2 Diabetic and Prediabetic Subjects
Authors: SANCHEZ RAMIRO A. , SANCHEZ MARIA J. , RAMIREZ AGUSTIN J. 
Published: June 2019

Introduction: Silent coronary heart disease is frequently undetected in type 2 diabetes mellitus (DM2) and prediabetes determined by glucose intolerance (GI). Pulse wave velocity (PWV) and albumin-creatinine ratio (ACR) have been considered markers of cardiovascular mortality, coronary heart disease and chronic renal failure.
Aims: To evaluate the incidence of coronary heart disease (CHD) and its relationship with urinary albumin-creatinine ratio, glomerular filtration rate (GFR) and PWV in type 2 DM with silent CHD.
Methods: We analyzed 92 individuals (44 male), 49 (60±7y) type 2 DM non-insulin dependents and 43 prediabetics (43±4y), with Grade I-II hypertension and no symptoms of CHD. All type 2 DM patients were under hypoglycemic treatment with an A1C hemoglobin between 5.5 and 6.5%. Every patient underwent a myocardial perfusion SPECT scan. In those subjects with ischemic patterns, a coronary angiography was performed. In addition, a PWV, glomerular filtration rate (CrCl), and ACR were evaluated. Statistics: mean±SEM, and ANOVA followed by Post Hoc analysis among groups.
Results: Silent CHD was found in 48.59% of DM2 and 25.58% of GI. DM2 and GI patients with CHD had higher ACR and PWV and reduced glomerular filtration rate (p&lt;0.05). DM2 and GI showed a negative relationship between GFR and ACR (p&lt;0.05). Type 2 diabetic and GI showed a negative relation between GFR and ACR or PWV when having GFR above 60 mil.min. Meanwhile, in type 2 Diabetics with CHD and GFR &lt; 60 ml.min a negative relationship with PWV was only, suggesting a cardiorenal interaction in type 2 diabetes.
Conclusions: Higher PWV, lower GFR and ACR predict the incidence of CHD in DM2. GI also represent a group of higher risk for coronary heart disease with the same predictors showed in DM2. PWV seems to represent a reliable marker.

Disclosure
R.A. Sanchez: None. M.J. Sanchez: None. A.J. Ramirez: None.
46-OR: A Novel Interaction between AT1 Receptor and Cytochrome-p450 Lipid Metabolites in Diabetic Retinopathy
Authors: AL-SHABRAWEY MOHAMED , IBRAHIM AHMED , TAWFIK AMANY M. , HENG WANG MONG HENG 
Published: June 2019

Nearly all patients with type 1 diabetes and 60% of those with type 2 diabetes develop diabetic retinopathy (DR). Thus, there is an urgent need to identify new therapeutic targets to prevent or at least to minimize microvascular dysfunction associated with DR. Activation of the renin-angiotensin system (RAS) contributes to breakdown of blood-retinal barrier (BRB) and neovascularization in DR. Clinical studies underscored RAS as a promising therapeutic target to treat DR. Although, blockade of RAS has reduced the incidence of DR in clinical studies, it did not reduce the progression of DR. Cytochrome-P450 metabolizes arachidonic acid to the pro-angiogenic and -permeability mediators, epoxyeicosatrienoic acids (EETs) which are metabolized by the soluble epoxide hydrolase (sEH) to inactive products. Our experiments demonstrated that:
1.) Angiotensin II (Ang II) increases retinal expression of sEH by 2.8 fold (2.84 ± 1.1 vs. 1 ± 0.08, P &lt; 0.05, n = 4), which is blunted by angiotensin receptor-1 (AT1) inhibition;
2.) both sEH blockade and knockout (KO), which accumulate EETs, enhance Ang II-induced BRB injury as shown by 1.58 fold increase in retinal albumin leakage (1.58 ± 0.4 vs. 1 ± 0.13, P &lt; 0.05, n = 4) and 2.8 fold (2.8 ± 1.7 vs. 1 ± 0.09, P &lt; 0.05, n = 4), respectively. These results were confirmed by fluorescein angiogram analysis;
3.) Administration of synthetic 11,12-EET enhances intravitreal Ang II-induced retinal albumin leakage by 2.2 fold (2.2 ± 0.5 vs. 1 ± 0.18, P &lt; 0.05, n = 4); and
4.) sEH KO potentiates diabetes (STZ)-induced retinal damage. This was associated with upregulation of retinal vascular endothelial growth factor (VEGF) and glucose transporter-1 (GLUT-1).
In conclusion, our data demonstrate that in DR, activation of retinal AT1 triggers a compensatory mechanism by increasing retinal sEH that decreases EETs production. Thus, the use of combined EETs blockade with AT1 blocker holds the promise, as a new therapeutic strategy to prevent or reduce DR.

Disclosure
M. Al-Shabrawey: None. A. Ibrahim: None. A.M. Tawfik: None. M.H. Wang: None.

Funding
American Heart Association (SE00144); National Institutes of Health (R01EY023315 to M.A-S.)
462-P: Diabetes Is Associated with Progression of Coronary Arterial Calcification in Patients New to Dialysis
Authors: ROY NEIL , YANG DANWEN , ROSAS SYLVIA 
Published: June 2019

Background and Objective: Coronary artery calcification is a risk marker of atherosclerosis. Recently, a large multicenter, prospective observational study showed the CAC density was inversely related to the occurrence of cardiac vascular events. The proposed hypothesis is that low density area is more prone to rupture due to large lipid core and a marker of plaque instability. However, high CAC density in 125 chronic hemodialysis patients was associated with increased mortality. Our aim was to determine CAC density in new dialysis patients, and the role of DM in the progression of CAC density.
Design, Setting, Participants, and Measurements: Ninety-eight initial dialysis patients were enrolled. CAC density was calculated by Agatson score divided by calcium volume score. CAC density progression was measured by the difference in score between CT/time. Sixty-seven study participants had repeat CAC measures at one year.
Results: The mean age of study participants was 50.1 ± 12.7 years. A third were women, and 64.7% were black. The baseline CAC density for DM group was 85.2 (interquartile range (IQR), 10.3-452) compared to 0(IQR, 0-90.3) for non-DM group was (P=0.01). Seventy percent of diabetes patients had progression of calcium density while forty one percent of nondiabetic patients had progression of calcium density score. (P=0.02). Hazard ratio for DM after adjust for age and smoke is 2.0 (1.05-72.6).
Conclusions: Our results indicate that DM is a risk factor for high calcium density of individuals new to dialysis patients and is a risk factor for progression of calcium density score. Increased calcium density in new dialysis patient is a risk factor for CAC progression, rather than a marker of plaque stabilization.

Disclosure
N. Roy: None. D. Yang: None. S. Rosas: Research Support; Self; Bayer US, Ironwood Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.
468-P: Nonalcoholic Steatohepatitis Is Associated with Diabetic Cardiomyopathy in Type 2 Diabetes
Authors: CHO DONG-HYEOK 
Published: June 2019

Background: Abnormalities in cardiac structure and function in type 2 diabetic patients may develop in the absence of ischemic heart disease. These abnormalities are attributed to diabetic cardiomyopathy. Impaired diastolic heart function has been observed in persons with nonalcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in type 2 diabetes.
Methods: We studied 92 patients with type 2 diabetes (51 men; mean age 62 ± 6 years) who had undergone liver ultrasonography and conventional Doppler echocardiography. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time (DT), using echocardiography.
Results: Fifty-four patients (58.7%) had NAFLD. On echocardiography, LVEF was within normal range in both groups, whereas LV mass index (P=0.035) and LA diameter (P=0.021) were significantly greater in the NAFLD patients. The systemic vascular resistance and arterial elasticity were not different. NAFLD patients had lower E/A ratio (P=0.014) and longer DT (P=0.042) than those without steatosis. When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (46.2%, 55.6%, 60.0%; none, simple steatosis, advanced fibrosis, respectively; P for trend = 0.025). In multivariate logistic regression, liver fibrosis was independently associated with diastolic dysfunction (OR=1.46, 95% CI=1.02-2.46, P=0.041) after adjusting for cardiometabolic risk factors.
Conclusions: Our data show that in patients with type 2 diabetes and NAFLD, liver fibrosis was associated with LV diastolic dysfunction and may be an independent risk factor for diastolic dysfunction.

Disclosure
D. Cho: None.
476-P: Pemafibrate, a PPAR Alpha Agonist, Attenuates Neointima Formation after Vascular Injury in Nondiabetic and Diabetic Mice
Authors: HORIKAWA TSUYOSHI , NOMIYAMA TAKASHI , TAKAHASHI HIROYUKI , KAWANAMI TAKAKO , HAMAGUCHI YURIKO , TANAKA TOMOKO , YANASE TOSHIHIKO 
Published: June 2019

Recently, the prevention of cardiovascular events has become one of most important purpose of diabetes care. We have previously reported that GLP-1 receptor agonist exendin-4 (BBRC 2011) and DPP-4 inhibitor linagliptin (Cardiovasc Diabetol 2014) attenuate neiontima formation after vascular injury. On the other hand, PPAR agonist is also reported its vascular protective effect. Then, we examined whether selective PPAR alpha agonist pemafibrate could attenuate neointima formation after vascular injury and vascular smooth muscle cell (VSMC) proliferation. We performed endothelial denudation injury in mice treated with high fat diet (HFD) or normal chow. Orally administered pemafibrate significantly attenuated neointima formation after vascular injury in both HFD and normal chow mice. Interestingly, pemafibrate increased serum FGF-21 concentration and decreased serum insulin concentration in HFD mice. In addition, body weight was slightly but significantly decreased by pemafibrate in HFD mice. In vitro experiments, pemafibrate attenuated VSMC proliferation in growth curve in a dose dependent manner, but not another PPAR alpha agonist bezafibrate. This suggested that the attenuation of VSMC proliferation by pemafibrate could be the drug effect, not class effect of PPAR alpha agonist. BrdU assay revealed that pemafibrate inhibited DNA synthesis in VSMC dose-dependently. In cell cycle distribution, G1 to S phase entry was significantly inhibited by pemafibrate in flow cytometry analysis. However, apoptosis was not induced by pemafibrate in VSMC in TUNEL assay. These data suggested that pemafibrate attenuates neiontima formation after vascular injury and VSMC proliferation inhibiting cell cycle progression.

Disclosure
T. Horikawa: None. T. Nomiyama: None. H. Takahashi: None. T. Kawanami: None. Y. Hamaguchi: None. T. Tanaka: None. T. Yanase: None.
480-P: Diabetes and Experimental Myocardial Infarction Synergize to Accelerate Atherosclerosis Destabilization
Authors: KRAMER FARAH , MARTINSON AMY M. , PAPAYANNOPOULOU THALIA , MURRY CHARLES E. , KANTER JENNY E. 
Published: June 2019

In addition to increasing the risk of an initial myocardial infarction (MI), diabetes increases the risk of a recurrent MI. Work by others suggests that an experimental MI can accelerate atherosclerosis via monocytosis. To test if diabetes and experimental myocardial infarction synergize to accelerate atherosclerosis, we induced atherosclerosis in Ldlr-/-; Gp+ mice, lethally irradiated them and transplanted with either wild type (WT) or LysM-Cre-mediated CD49D-deficient bone marrow. Following recovery, diabetes was induced using lymphocytic choriomeningitis virus, or saline was used as a control. The mice were subjected to ligation of the left anterior descending coronary artery to induce experimental MI or a sham surgery and then maintained for an additional 3 weeks. Diabetic (D) mice exhibited hyperglycemia and elevated plasma cholesterol and triglyceride levels compared to nondiabetic (ND) mice, but neither hematopoietic genotype or MI influenced that. All mice subjected to MI had significantly reduced left ventricular function. Neither diabetes nor MI resulted in monocytosis compared to ND sham mice. Despite not affecting total lesion size, the combination of diabetes and MI resulted in larger necrotic cores in the aortic sinus and in the brachiocephalic artery (9.8 ± 1% of total lesion in aortic sinus in ND sham, 11.9 ± 1% in ND MI, 15.4 ± 1% in D sham and 18.1 ± 2% in D MI, P&lt;0.001 comparing ND Sham to D MI, n=14-24, ANOVA). The expansion of the necrotic cores was dependent on monocyte recruitment, since mice with myeloid cells deficient in the adhesion molecule CD49D were protected from necrotic core expansion. Diabetes and MI also synergized to accelerate macrophage cell death (6.1 ± 3% of peritoneal macrophages were dead in ND sham, 6.1 ± 3% in ND MI, 11± 1% in D sham and 20 ± 3% in D MI, n=3-6, p&lt;0.05 ANOVA).
In summary, diabetes and experimental MI destabilize the atherosclerotic lesion, potentially explaining why patients with diabetes are at an increased risk of recurrent MI.

Disclosure
F. Kramer: None. A.M. Martinson: None. T. Papayannopoulou: None. C.E. Murry: Other Relationship; Self; Cytocardia. J.E. Kanter: None.

Funding
American Diabetes Association (1-16-IBS-153 to J.E.K.)