bluuebunny/crossref_metadata_2025_split huggingface dataset:
P732Maternal high-fat diet promotes the expansion of abdominal aortic aneurysm in adult offspring by enhancing osteoclast-like macrophage differentiation
Authors: Saburi M , Yamada H , Wada N , Motoyama S , Sugimoto T , Kubota H , Miyawaki D , Wakana N , Matoba S 
Published: October 2019

Abstract

Background and objective
Maternal high-fat diet (HFD) has been shown to modulate vascular function and remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) formation.

Methods and results
Eight-week-old female wild-type mice (C57BL/6) were fed a HFD or normal diet (ND) one week prior to mating and received during pregnancy and lactation. In eight-week-old offspring of both genders, AAA was induced with the application of 0.5M calcium chloride (CaCl2) on the infrarenal aorta. Male offspring of HFD-fed dams (O-HFD) showed a significant increase in maximum outer diameter of AAA at 1, 4 and 8 weeks after surgery compared with offspring of ND-fed dams (O-ND) (P<0.05). The lengths of outer circumference assessed by histological analysis were increased in O-HFD (P<0.05). Likewise, female O-HFD showed a greater length of outer circumference than female O-ND (P<0.05). While the number of F4/80-positive cells at 1 wk after surgery was comparable between the male O-HFD and O-ND, the percentage of MMP-9/F4/80 double-positive cells was significantly increased in male O-HFD. Consistently, fluorescent image of abdominal aorta taken by IVIS at 1 wk after surgery revealed a 2-fold increase in MMP activity (P<0.01). Intriguingly, F4/80-positive cells in male O-HFD showed a 2.5-fold increase in co-staining with tartrate-resistant acid phosphate (TRAP), typical marker of osteoclast-like macrophages which abundantly secrete proteases than classically activated macrophages (M1), while the percentage of TNF-α/F4/80 double-positive cells was comparable between the 2 groups. Pharmacological inhibition of osteoclastogenesis by zoledronic acid (ZA) (100μg/kg) completely abolished the exaggerated AAA development in male O-HFD to a similar extent of that in male O-ND, while AAA development in male O-ND mice did not change even after ZA treatment. Furthermore, in vitro TNF-α-induced osteoclast differentiation of bone marrow-derived macrophages (BMDMs) showed a significantly higher number of TRAP-positive cells, accompanied by increased calcitonin receptor mRNA expression. Western blotting analysis showed that protein expression level of NFATc1, master regulator of osteoclastogenesis, was significantly higher in BMDM of O-HFD than O-ND.

Conclusion
Our findings demonstrate that maternal HFD accelerates CaCl2-induced AAA expansion, accompanied by the exaggerated accumulation of osteoclast-like macrophages and augmented activity of MMPs. Inhibition of macrophages skewing toward osteoclast-like cells could be a potential therapeutic target for preventing AAA development.
P737Endothelial ERK2/thromboxane receptor pathway induces endothelial dysfunction, insulin resistance and steatohepatosis through superoxide with high fat high sucrose diet
Authors: Sato A , Satoh Y , Endo S , Kimura T , Osaki A , Horii S , Ito K , Kagami K , Namba T , Adachi T 
Published: October 2019

Abstract

Introduction
Metabolic syndrome (MetS) is well known as the risk of cardiovascular diseases associated with endothelial dysfunction and induces steatohepatosis. Insulin resistance is a major character of MetS, which affects intracellular signaling pathways and endothelial function. Extracellular signal-regulated kinase (ERK) is a major component of insulin signal and many of vasoactive peptides, which were released in MetS, can activate it in endothelium. However, the role of endothelial ERK in nitric oxide (NO) bioactivity in MetS in in vivo has been unknown.

Purpose
The aim of this study is to clarify the role of endothelial ERK2 on NO bioactivity in mice model of MetS.

Methods and results
We created endothelial specific ERK2 knock out mice (EE2KO) crossing Tie2-Cre mice and ERK2 flox mice and fed them with normal or high-fat/high-sucrose diet (HFHSD) for 24 weeks. Serum glucose and insulin levels and HOMA-IR were lowered in EE2KO with HFHSD without changing body weight. In wild type mice (WT) with HFHSD, nonalcoholic fatty liver disease (NAFLD) activity score, fibrosis score and serum ALT level were increased, all of which were blunted in EE2KO. EE2KO with HFHSD lowered systolic blood pressure (WT: 123.7±5.83 mmHg, EE2KO: 101.4±3.66 mmHg, P<0.01, N=8) without changing heart rate, which was increased to the same levels with L-NAME, an endothelial NO synthase inhibitor, in both groups. Serum NO levels measured with serum nitrite/nitrate concentrations were increased in EE2KO with HFHSD (WT: 23.10±3.74 μmol/l, EE2KO: 41.71±6.73 μmol/l, P<0.05, N=12). Endothelial function was assessed with the isometric tension measurement of aortic rings with acetylcholine (ACh). ACh-induced relaxation was improved in EE2KO with HFHSD. Superoxide production of aorta from EE2KO was lowered than WT with HFHSD in dihydroethidium (DHE) staining. S18886, an antagonist of the thromboxane A2-prostanoid (TP) receptor, decreased superoxide production of aorta in DHE staining resulting in improving endothelial function in the isometric tension measurement of aortic rings. Oral administrations of S18886 decreased systolic blood pressure, serum fasting glucose and insulin levels, and surprisingly improved steatohepatosis by decreasing NAFLD activity score and fibrosis score.
Relaxation of aortic rings with ACh

Conclusions
Endothelial ERK2/TP receptor pathway increases superoxide production and decreased NO bioactivity, resulting in deteriorating endothelial function, insulin resistance and steatohepatosis, which were improved by antagonist of the TP receptor in mice model of MetS. The present study indicates that ERK2/TP pathway could be a therapeutic target for complications of MetS.
P750Role of circulating endothelial cells post-heart transplantation
Authors: Rywik T , Braniewska A , Kowalik I , Firczuk M , Kozar-Kaminska K , Wojciechowska A , Kasprzyk-Pawelec A , Sobieszczanska-Malek M , Leszek P , Rozentryt P , Zielinski T 
Published: October 2019

Abstract

Background
The role of endothelial progenitor cells (EPC) in heart transplantation (HT) is not well defined. Thus, the aim of this study was to evaluate prospectively the dynamic changes of circulating EPC levels in relation to post-HT rejection risk.

Methods
There were 27 HT recipients who had EPC from peripheral blood quantified during 6 months follow-up after HT. Patients were monitored regularly, by right ventricular endomyocardial biopsy assessment, for cellular rejection (ACR) defined as grade ≥2 or an antibody-mediated rejection (AMR) characterized by histopathological changes recorded as AMR1H. The primary end-point was acute rejection, either AMR or ACR.

Results
ACR and AMR were observed in 7 (25.9%) and 6 (22.2%) subjects respectively. EPC levels, after logarithmic transformation, immediately post-HT were alike regardless of ACR status, however patients with lower EPC were at risk of AMR at 1 month (Table 1). On the other hand patients with a significant reduction of EPC at 1 month post-HT compared with HT were less likely to have either ACR or AMR (p=0.0003). During longer post-HT observation (12 months) patients had similar EPC levels regardless of the rejection events. Dynamic changes in EPC levels are presented in figure. Nonetheless, greater changes in EPC expressed by coefficient of variation were associated with the risk of either AMR or ACR compared to the participants without rejection (mean [lower–upper quartile]) 15 [13–18] vs 8 [5–13]; p=0.02) and (22 [14–26] vs 8 [5–13]; p=0.01) respectively.
EPC by rejection – 1st month following HT ACR (+) AMR (+) ACR (−) and AMR (−) p^ p p N=3 (mean± SD) N=4 (mean± SD) N=20 (mean± SD) ACR (+) vs ACR (−) and AMR (−) AMR (+) vs ACR (−) and AMR (−) EPC log HT 5.14±1.55 3.81±1.01 5.30±0.88 0.0325 0.97 0.025 EPC log M1 4.97±0.59 3.69±1.33 4.15±1.29 0.4160 0.55 0.78 Delta EPC log M1-HT -0.17±1.98* −0.12±1.30* −1.15±1.18# 0.2195 0.44 0.32 ACR – acute cellular rejection; AMR or – acute antibody-mediated rejection; EPC log – endothelial progenitor cells after logarithmic transformation; HT – within 24 hours post-transplantation; M1 – at 1-month post-transplantation; Delta EPC log M1-HT – difference in EPC log between M1 and HT. #p=0.0003 for the difference between M1 vs HT; *p=ns for the difference between M1 vs HT; ^pP – for the difference among the groups.
Changes in EPC level post-HT

Conclusions
Early reduction of EPC levels was predictive of a lower risk of ACR or AMR. Greater dynamic changes of EPC during 6 months of observation were associated with a higher risk of rejection suggesting an important role of EPC in the pathological processes post-HT. Thus our findings suggest significant role of EPC post-HT with respect to rejection status.

Acknowledgement/Funding
Intramural research grant from the Institute of Cardiology
P757Methamphetamine-associated cardiomyopathy: a case-controlled study of clinical characteristics, management and outcomes
Authors: Wang T K M , Kueh A , Gabriel R , Sutton T , Lund M , Kerr A , Looi J L 
Published: October 2019

Abstract

Background
Methamphetamine-associated cardiomyopathy (MAC) is an increasingly diagnosed condition with poor prognosis, and there remains paucity of literature including how MAC differs from other cardiomyopathies. We compared the characteristics and outcomes MAC patients with non-ischaemic cardiomyopathy controls at our centre.

Methods
Clinical profile, management and outcomes were prospectively assessed in consecutive patients with MAC at our hospital from 2006–2018. They were compared with randomly chosen controls with non-ischaemic dilated cardiomyopathy of similar age-group (20–65 year).

Results
Both groups had 62 patients followed for 3.0±2.9 years. MAC patients were younger, with higher proportion of Maori ethnicity, unemployment and cardiogenic shock during index admission and lower proportion of Pacific ethnicity, cardiovascular risk factors and atrial fibrillation. MAC patients also had higher peak NT-proBNP, lower ejection fraction, and lower attendance rate to outpatient appointments. There was no index admission mortality in both groups. MAC had higher mortality and trend to higher heart failure re-admissions rates during follow-up (Figure 1). Amongst MAC patients, baseline left ventricular end diastolic diameter and failure of improvement in right ventricular systolic function by one category during follow-up were independent predictors of mortality, while failure of improvement of left ventricular ejection fraction by one category predicted heart failure readmission.
Figure 1

Conclusions
MAC patients were younger but sicker on presentation, with higher mortality and trend towards higher heart failure readmission rates during medium-term follow-up than controls. Adherence to therapy and attendance to appointments may improve cardiac systolic function over time to reduce adverse clinical endpoints.
P768Cardiopulmonary exercise testing for assessing frailty status in stable elderly patients with heart failure
Authors: Hirashiki A , Kawashima K , Nomoto K , Kokubo M , Shimizu A , Arai H 
Published: October 2019

Abstract

Introduction
Frailty is a syndrome associated with aging that produces subclinical dysfunction across multiple organ systems and leads to increased risk of mortality. The Kihon Checklist (KCL) was developed by the Japanese Ministry of Health, Labor and Welfare to identify older persons in need of care; it is a reliable tool for predicting general frailty in older adults. There is little information about the relationship between frailty status and exercise capacity.

Purpose
To investigate whether cardiopulmonary exercise testing (CPX) parameters are associated with frailty in stable elderly patients with heart failure (HF).

Methods
Ninety-two stable elderly patients with HF were evaluated by using CPX and the total KCL (t-KCL). A t-KCL score of 0–3 was classified as robust, 4–7 as pre-frail, and ≥8 as frail. Diagnostic performance (DP) -plot analysis was used to assess the utility of CPX parameters to distinguish between the presence and absence of frailty.

Results
Mean age, left ventricular ejection fraction, plasma brain natriuretic peptide, peak work rate (WR), peak VO2, and t-KCL score were 81.7 years, 57.8%, 182 pg/mL, 49.6 W, 13.2 mL/kg/min, and 10.7, respectively. t-KCL score was significantly correlated with peak VO2 (r=−0.53, p<0.001) and peak WR (r=−0.63, p<0.001). In the patients with frailty (n=63), peak WR was significantly lower than that in patients without frailty (n=29; 40.8 and 71.0 W, respectively, p<0.001). Multivariate analysis revealed that peak WR was the only significant independent predictor of frailty (β=−0.111, p<0.001). In the DP-plot analysis, a cut-off value for peak WR of 51.9 W was the best predictor of frailty (accuracy; 0.706, Figure).
Cut-off value for peak WR

Conclusions
Frailty status was significantly associated with peak WR in stable elderly patients with HF. CPX may be useful for assessing frailty status in stable elderly patients with HF.
P788Discharge echocardiographic parameters of RV and LV function but not of changes in cardiac unloading are related to 12-month prognosis during hospitalization for acute decompensated heart failure
Authors: Monney P , Barras N , Tzimas G , Abdurashidova T , Regamey J , Yerly P , Hugli O , Hullin R 
Published: October 2019

Abstract

Introduction
Acute decompensated heart failure (ADHF) is associated with a high mortality and rehospitalization rate. The aim of this study was to assess whether echocardiographic markers of systolic and diastolic function, and their changes under treatment during hospitalization for ADHF, would predict 12-months mortality.

Methods
Adult patients admitted to our emergency department for ADHF between June 2015 and January 2018 were included if a complete transthoracic echocardiography (TTE) could be obtained within 12 hours of admission. TTE was repeated upon discharge. Baseline clinical and echocardiographic characteristics were collected on admission and at discharge, and outcome at 12 months was obtained by telephone interview. All parameters are given as median [interquartile range].

Results
A total of 221 patients were identified but 45 excluded because of in-hospital death (n=8), early transfer to another hospital (n=31) or refusal to perform discharge TTE (n=6), leaving 176 patients for final analysis. Age was 83 [74–87] years, 95 (54%) were men and 89 (51%) were in sinus rhythm. Baseline TTE was performed within 6.6h [4.1–11.9] of admission and median duration of hospital stay was 13 days [9–19]. Admission ejection fraction (EF) was 45% [37–54] (29% HFrEF, 37% HFmrEF, 34% HFpEF). Between admission and discharge, significant changes were observed for global longitudinal LV strain (−10.3 [−7.2 to 15.1] to −11.8% [−8.1 to 15.0], p=0.017), mitral E velocity (100 [80–124] to 96 cm/s [74–117], p=0.001), E/e' ratio (16 [12–20] to 15 [11–19], p=0.003, RV basal diameter (41 [36–45] to 41mm [34–44], p=0.007), tricuspid regurgitation gradient (41 [34–52] to 35 mmHg [28–44], p=0.0001 and vena cava diameter (22 [19–26] to 19 mm [15–23],. Deaths occurred in 35 (20%) at 12 months follow-up. In our multivariable model, none of the changes in TTE parameters was predictive of mortality. Age (OR 1.09, p0.01), LVEF (OR 0.95, p0.02) and TAPSE (OR 0.86, p0.01) measured at discharge, but not LV or RV strain, were identified as independent predictors of 12-months mortality (see figure).
Survival according to LVEF and TAPSE

Conclusion
Several changes in TTE parameters were observed during hospitalization for ADHF, reflecting effective cardiac unloading with diuretic treatment. However, none of these changes appears to have prognostic significance. LVEF and TAPSE at discharge were identified as the only independent echocardiographic predictors of 12-months mortality, in addition to age.

Acknowledgement/Funding
Swiss Heart Foundation
P794Long-term prognostic value of the combination of AHEAD score and wasting syndrome in patients admitted for acute decompensated heart failure with reduced or preserved LV ejection fraction
Authors: Yamada T , Morita T , Furukawa Y , Tamaki S , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Abe M , Yamamoto K , Kayama K , Kawahira M , Tanabe K , Fukunami M 
Published: October 2019

Abstract

Background
Comorbidities are associated with poor clinical outcome in heart failure patients (pts). AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score has been related to clinical outcomes in acute decompensated heart failure (ADHF) pts. On the other hand, heart failure is one of a number of disorders associated with the development of wasting syndrome. Previous studies have reported reduced mortality rates in heart failure patients with increased body mass index (BMI), so-called, obesity paradox. We sought to investigate the prognostic value of the combination of AHEAD score and the cachectic state in ADHF pts, relating to reduced or preserved LVEF (HFrEF or HFpEF).

Methods and results
We studied 303 pts admitted for ADHF and discharged with survival (HFrEF (LVEF <50%); n=163, HFpEF (LVEF ≥50%; n=140). We evaluated AHEAD score (range 0–5, atrial fibrillation, hemoglobin <13 mg/dL for men and 12 mg/dL for women, age >70 years, creatinine >130 μmol/L, and diabetes mellitus) and wasting syndrome was defined as BMI <20 kg/m2 and serum albumin level (Alb) <3.2 g/dl at the discharge. During a follow-up period of 5.1±4.2 years, 121 pts died. At multivariate Cox analysis, AHEAD score and wasting syndrome was significantly and independently associated with the total mortality, in pts with not only HFrEF but also HFpEF. Pts with both high AHEAD score (≥3: AUC 0.625 [0.542–0.709] in HFrEF and ≥3: AUC 0.611 [0514–0.708] in HFpEF, by ROC curve analysis) and wasting syndrome had a higher risk of mortality than those with either and none of them in HFrEF (71% vs 51% vs 40%, p<0.0001, respectively) and HFpEF (78% vs 33% vs 24%, p<0.0001, respectively).

Conclusion
The combination of AHEAD score and wasting syndrome would be useful for stratifying patients at risk for the mortality in ADHF pts, regardless of HFrEF or HFpEF.
P797Association of office and ambulatory blood pressure with mortality and cardiovascular endpoints
Authors: Yang W.-Y , Melgarejo J D , Thijs L , Zhang Z.-Y , Wei F.-F , Hansen T W , Asayama K , Staessen J A 
Published: October 2019

Abstract

Background
Blood pressure (BP) is the strongest modifiable risk factor predicting death and cardiovascular complications. However, which BP index has greater clinical relevance is not established.

Purpose
To compare associations of adverse health outcomes with commonly used BP indexes.

Methods
Longitudinal population-based cohort study of 11,135 adults recruited in Europe, Asia and South America with baseline observations collected from 1985 until 2010 and last follow-up year ranging from 2006 to 2016. Multivariable-adjusted analyses addressed the associations of primary endpoints (total mortality and composite CV endpoints) and secondary endpoints (CV mortality, cardiac and coronary endpoints and stroke) with conventional BP, automated office BP and ambulatory BP indexes. Model performance was assessed by the integrated discrimination improvement (IDI) and change in the area under the curve (ΔAUC).

Results
The study included 49.3% women. Median age was 54.7 years. Over 13.8 years (median), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a cardiovascular endpoint. Both endpoints were related to all single systolic BP (SBP) indexes (P<0.001). In models that included both 24-h and nighttime SBP, the HRs for total mortality and the cardiovascular endpoint in relation to 24-h SBP were 0.98 (95% confidence interval, 0.92–1.06) and 1.17 (1.08–1.28) and HRs associated with nighttime SBP were 1.18 (1.11–1.27) and 1.12 (1.04–1.21), respectively. Otherwise, depending on the SBP index combined with 24-h or nighttime SBP, HRs for both endpoints associated with 24-h or nighttime SBP retained significance (P≤0.004), ranging from 1.12 (1.07–1.17) to 1.56 (1.41–1.74). In models that included either 24-h or nighttime SBP, HRs associated with other SBP indexes weakened, lost significance or reversed. IDI and ΔAUC for adding 24-h or nighttime SBP to other SBP indexes were consistently greater than unity except for combining 24-h and nighttime SBP. These findings were consistent for secondary endpoints, for systolic and diastolic BP, and in sensitivity analyses performed to evaluate the influence of antihypertensive drug treatment at baseline, various definitions of day and night, and the contribution of different cohorts to the overall results.

Conclusions
Associations of outcomes were strongest for 24-h and nighttime ambulatory BP, which outperformed all other BP indexes in predicting 10-year absolute risk and which should therefore be prioritised in clinical practice.

Acknowledgement/Funding
The European Union, the European Research Council, the European Research Area Net for Cardiovascular Diseases, et al.
P829The impact of APOC3 and APOE gene polymorphisms on response to statin therapy in acute myocardial infarction
Authors: Teterina M , Geraskin A , Potapov P , Babaeva L , Pisaryuk A , Goreva L , Balatskiy A , Meray I , Kobalava Z 
Published: October 2019

Abstract

Background and aim
Many genetic studies have been reported about the association between APOE, APOC3 gene polymorphisms and response to statin therapy in myocardial infarction, but results remain controversial. The aim of this study was to investigate the association between SNP rs7412 (APOE), rs2854117 (APOC3), rs2854116 (APOC3) and lipid-lowering effect of atorvastatin and rosuvastatin in patients with myocardial infarction.

Methods
Polymorphism of genes APOE (rs7412), APOC3 (rs2854117 and rs2854116) was determened. Lipid profile was determined on admission and after 1 year of treatment.

Results
78 patients with myocardial infarction treated with maximal tolerated dose of atorvastatin or rosuvastatin were included. More pronounced reduction of lipid levels was associated with of T allele of rs7412 (APOE), p<0,05. ANOVA demonstrated greater low-density lipoprotein and total cholesterol decrease in patients with combination of genes CT/TT (rs7412, APOE) and CC (rs2854117, APOC3) genotypes, CT/TT (rs7412, APOE) and CT (rs2854116, APOC3) genotypes.

Conclusion
The genetic variants of APOC3 and APOE are useful markers and can be use to predict response to lipid-lowering therapy with statin in myocardial infarction.