bluuebunny/crossref_metadata_2025_split huggingface dataset:
P679Long-term cardiovascular outcomes after percutaneous coronary interventions in patients with acute coronary syndrome and cancer
Authors: Ma Y , Cheng Y J , Ohene B E , Yang L X , Zhou Y J 
Published: October 2019

Abstract

Background
Over time, the use of PCI increased and mortality decreased comparably in patients with ACS and cancers. Although the adverse cardiac effect of cancer has been widely reported, we know less on whether lung cancer confers worse clinical outcomes in patients with established ACS, particularly those undergoing PCI.

Methods
All cancer patients who were admitted in the hospital with ACS as initial diagnosis and underwent PCI from January 2006 to December 2016 were enrolled, and were divided into 2 groups according to their malignancy types: lung cancer and others. Population data was collected and clinical follow-up was performed by either telephone contact or office visit. Survival was graphically represented using Kaplan-Meier curves. Differences in survival rates were compared using the log-rank test. Analysis was performed with SPSS statistical software, version 22.0 for Windows. See Figure 1.

Results
16,062 patients suffered from various cancers and 55,401 patients underwent PCI. After cross referencing the two patient lists, 337 patients were enrolled who underwent cancer prior to ACS, and 15.1% (n=51) had a medical history of lung cancer. See Figure 2 and 3. Male gender was more prevalent in the lung cancer group than other cancers group (84.3% vs 60.5%, P=0.01). There was no significant difference between lung cancer and other cancers group in the presence of traditional cardiovascular risk factors, such as hypertension, hyperlipidemia, obesity, diabetes mellitus, history of smoking, history of drinking and the family history of coronary artery disease (P>0.05 for all). Among all coronary complex lesions, calcified lesions was more prevalent in lung cancer group (21.6% vs 11.5%, P=0.04), although there was no significant difference between two groups in left main lesions, bifurcation lesions and CTO lesions (P>0.05 for all). For anticancer therapy, patients with lung cancer received more radiotherapy (29.4% vs 13.6%, P=0.01) and chemotherapy (37.3% vs 25.5%, P=0.08). Follow-up was available for 289 of the 337 patients (85.8%). See table 1. The incidence of cardiovascular death (5.9% vs 1.0%, P=0.02) was higher in the lung cancer group. As shown the Kaplan-Meier curves in Figure 1, the survival rate free from all-cause death (log rank P=0.034, Figure 4A) and cardiovascular death (log rank P=0.013, Figure 4B) was significantly lower in lung cancer group than in other cancers group during the follow-up.
Figures and Table

Conclusions
Lung cancer has a non-negligible prevalence in patients with ACS undergoing PCI, with significantly worse long-term cardiovascular outcomes. The results of our study reinforce the importance of understanding to patients who need closer follow-up, careful evaluation, and intervention.
P684Long-term outcomes in patients with cancer undergoing percutaneous coronary intervention: analysis from a Japan multicenter registry
Authors: Endo A , Sawano M , Ikemura N , Takei M , Suzuki K , Hasegawa T , Takahashi T , Nakagawa S , Fukuda K , Kohsaka S 
Published: October 2019

Abstract

Background
Cancer and cardiovascular disease (CVD) is the most common cause of death in developed countries, and substantial overlap exist in their medical care. However, the detailed and updated information on outcome of cancer patients with cardiovascular disease (CVD), particularly in clinically significant coronary artery disease (CAD) remain unknown.

Purpose
We sought to describe the prevalence and long-term outcomes of cancer patients undergoing percutaneous coronary intervention (PCI), which has become a coronerstone in the management of CVD.

Methods
Patient data extracted from a regional prospectiveprocedure-based multicenter registry for PCI was analyzed. A total of 4,455 patients who underwent PCI at 15 hospitals within metropolitan Tokyo from September 2008 to 2012 were followed for 2 years. “Active” cancer patient was defined as having a history of cancer not cured or in remission. We analyzed in acute and stable presentation.The occurrence of clinical outcomes was assessed via Kaplan-Meier survival curve, and Cox-regression hazard model to adjust for known clinical predictors.

Results
Within the studied patients, 173 (3.9%) had a concomitant “active” cancer at the time of intervention. There was a significant difference between the patients with and without active cancer in each situation. In stable presentation, cancer group were older, lower BMI, frequently had silent ischemia, COPD and cerebrovascular/peripheral disease, and less often had dyslipidemia compared with non-cancer group. In acute presentation, cancer group were older, frequently had COPD, CKD, peripheral disease and history of HF compared with non-cancer group. The prescription rate of RAAS inhibitor was lower in the cancer group than in the non-cancer group in acute presentation. Notably, in both acute and stable presentation, these patients had significantly higher risk of all-cause mortality (HR 8.01: 95%, p<0.001 and HR5.53: 95%, p<0.001, respectively), and they were also at higher risk of major cardo- and cerebrovascular events (MACCE; HR2.38, p<0.001, HR2.33, p=0.001), when referenced to non-cancer patients after 2 year of follow-up.

Conclusion
Cancer patient was present in 3.9% of all PCI patients and was strongly associated with both non-cardiac and cardiac adverse events.
P688Cardiac dysfunction as a predictor of hepatic sinusoidal obstruction syndrome after hematopoietic cell transplantation
Authors: Park H , Kim M , Jeong H K , Kim H Y , Kim K H , Cho J Y , Yoon H J , Park J C 
Published: October 2019

Abstract

Background
Hepatic sinusoidal obstruction syndrome (HSOS) is a well-known fatal complication of hematopoietic cell transplantation (HCT), but the impact of cardiac abnormalities on the occurrence of HSOS has been poorly evaluated. Therefore, the authors investigated whether the structural changes or dysfunction of the heart before HCT is associated with the future occurrence of HSOS.

Methods
A total of 92 patients who underwent HCT were divided into 2 groups; HSOS group (n=11, 6 males, 53.8±15.9 years) vs no HSOS group (n=81, 51 males, 48.6±14.7 years). According to the modified Seattle criteria, HSOS was defined as otherwise unexplained occurrence of 2 or more of the following events within 20 days of HCT; serum total bilirubin >2 mg/dL, hepatomegaly or right upper quadrant pain, sudden weight gain due to fluid accumulation (>2% of baseline body weight). Echocardiography examinations were performed 1 month before HCT, and echocardiographic findings were compared between the groups.

Results
HSOS was developed in 11 patients (12.0%). HSOS group had significantly larger left ventricular end-diastolic volume index (LVEDVI) (65.2±4.9 vs 53.2±6.9 ml/m2, p<0.001) and relatively worse systolic function than no HSOS group (LV ejection fraction: 56.4±3.4 vs 65.1±5.9%, p<0.001, LV global longitudinal strain: −17.9±1.4 vs −20.1±2.0%, p=0.001). LV diastolic functional parameters were also significantly worse in HSOS group than in no HSOS group (E/E' ratio: 11.3±1.8 vs 9.1±2.0, p=0.002, left atrial global longitudinal strain: 27.7±3.3 vs 34.9±5.9%, p<0.001). However, left atrial volume index was not different between the groups (30.8±2.8 vs 29.0±3.3 ml/m2, p=0.078). By receiver operation characteristic curve analysis, among significantly different variables, LVEDVI was the most powerful predictor for HSOS, and the optimal cutoff value was 59.25 mL/m2. (81.8% sensitivity and 77.8% specificity, AUC 0.909).
Predictor of HSOS: ROC analysis

Conclusions
The present study demonstrated that structural changes or dysfunction of the heart are more prevalent in patients with HSOS after HCT and larger LVEDVI, among them, can be a useful predictor of upcoming HSOS. Routine echocardiographic study before HCT would be useful to identify high risk group for HSOS, and the development of HSOS should be carefully monitored in HCT patients with cardiac structural changes or dysfunction on echocardiography.
P709Improvement in endothelial function and arterial elastic properties facilitates response to cardiac resynchronization therapy
Authors: Karamichalakis N D , Ikonomidis I , Parissis J , Simitsis P , Xydonas S , Letsas K , Manolatos D , Efremidis M , Sideris A , Filippatos G 
Published: October 2019

Abstract

Background
Cardiac resynchronization therapy (CRT) is a well-established therapy in heart failure (HF) patients with prolonged QRS. In HF patients, reduced nitric oxide availability and increased oxidative stress promote endothelial dysfunction (ED) and arterial stiffness.

Purpose
To investigate the pathophysiologic changes in endothelium and arterial elastic properties in CRT patients and their correlation to therapy.

Methods
We studied 32 HF patients before and 3 months after CRT implantation. In each visit we performed a 12-lead ECG and assessed markers of endothelial function. Specifically, we examined flow-mediated dilatation of the brachial artery (FMD), carotid to femoral pulse wave velocity (cfPWV), as well as the layer of endothelial glycocalyx using the Perfused Boundary Region (PBR) of the sublingual microvessel range: 5–25 microns. We also evaluated left ventricle ejection fraction (LVEF), left ventricle (LV) global longitudinal strain (GLS) and arterial elastance (Ea) to ventricular elastance (Ees) ratio (Ea/Ees) by echocardiography.

Results
32 HF CRT patients, at age 65.5 (±10.9) years, with reduced LVEF (baseline LVEF: 27±7%, LVESV: 151±42 ml, GLS: 6.47±2.89%) were followed-up for a median of 115 days (IQR: 36). During follow up, all markers of ED demonstrated significant change: FMD was increased by 4.37±3.34% (p<0.001), cfPWV and PBR 5–25 were reduced by 1.10±1.56 (p=0.003) and 0.13±0.25 microns (p=0.028) respectively. LVEF was significantly increased (mean change: 7.50±4.77%) and LVESV was significantly reduced (mean change: −26.91±17.20 ml). 16 of 32 patients were responders (LVESV change ≥15% compared to baseline). Among the changes of the examined markers during follow-up, response to CRT correlated with the change of FMD (OR: 3.10, 95% CI: 1.47–15.51, p=0.039) and change of Ea/Ees (OR: 0.000, 95% CI: 0.000–0.061, p=0,0239).
Effect of change in measurements during follow-up on response to CRT Measurement OR (95% CI) Main effect p-value FMD change 3.100 (1.470–15.513) 0.0397 cfPWV change 0.669 (0.295–1.354) 0.0622 PBR 5–25 change 1.773 (0.008–455.458) 0.828 Ea/Ees change 0.000 (0.000–0.061) 0.0239

Conclusion
Improvement in endothelial function and arterial elastic properties evaluated by FMD and Ea/Ees respectively are related with effective CRT.
P723A novel CD147 inhibitor SP-8356 attenuates plaque progression and stabilizes vulnerable plaque in ApoE-deficient mice
Authors: Pahk K , Joung C , Song H Y , Kim S , Kim W 
Published: October 2019

Abstract

Aim
Plaque vulnerability is the crucial pathophysiological feature in atherosclerosis-related cardiovascular event such as myocardial infarction and stroke. CD147 has been suggested to play key roles in plaque vulnerability through interacting with cyclophilin A (CypA) and resultant activation of matrix metalloproteinase-9 (MMP-9). Here we report that the novel synthetic CD147 inhibitor SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one) inhibits CD147/MMP-9 pathways and reduces plaque progression and stabilizes plaque vulnerability.

Methods
Advanced atherosclerotic plaque was induced in apolipoprotein E-deficient (ApoE KO) mice by partial ligation of the right carotid artery coupled with an atherogenic diet. SP-8356 (50 mg/kg) was orally given daily for 3 weeks. Histomolecular analysis was carried out on harvested carotid arteries.

Results
Surface plasmon resonance assay showed the specific binding of SP-8356 with CD147. SP-8356 inhibited CypA-CD147 interaction and MMP-9 activation. In ApoE KO mice model, SP-8356 inhibited plaque formation, reduced the number of macrophages, increased the number of vascular smooth muscle cells, increased the fibrous cap thickness, and increased the collagen type I contents in fibrous cap. SP-8356 also reduced the apoptotic cells in the plaque lesion.

Conclusions
Owing to its improvement of plaque stability and inhibitory effect on plaque development, SP-8356 could be a potential therapeutic drug candidate for atherosclerosis and related clinical manifestations.
P733Cholesterol uptake triggers macrophage proliferation in the plaque
Authors: Hilgendorf I , Haerdtner C , Kornemann J , Krebs K , Dufner B , Hoppe N , Stachon P , Wolf D , Zirlik A , Princen H , Bode C 
Published: October 2019

Abstract

Background
Guidelines recommend cholesterol lowering for primary and secondary prevention of cardiovascular disease. While lipid lowering has been reported to induce plaque regression, the underlying mechanisms have remained speculative.

Purpose
We hypothesize that lipid uptake triggers local macrophage proliferation in the plaque, and conversely, statin treatment inhibits local macrophage proliferation leading to plaque regression.

Methods
Mixed bone marrow chimeras were generated in LDLR−/− mice reconstituted with wild type and scavenger receptor deficient or cholesterol exporter deficient bone marrow cells to study cell autonomous effects on macrophage proliferation. APOE*3-Leiden.huCETP mice with established atherosclerosis were randomized to three groups: Continued cholesterol diet, cholesterol diet supplemented with 0.01% atorvastatin, and cholesterol free diet for 4 weeks to study mechanisms of plaque regression.

Results
Proliferation of scavenger receptor A and CD36 deficient macrophages with impaired lipid uptake was reduced by 30–50% in the plaque, while ABCA1/ABCG1 exporter deficiency resulted in cholesterol overloading and apoptosis. Oral atorvastatin treatment decreased total plasma cholesterol levels by 50% to the same extend as cholesterol free diet feeding in APOE*3-Leiden.huCETP. Cholesterol lowering resulted in a 50% reduction in local macrophage proliferation and plaque regression with reduced macrophage and lipid contents and increased collagen. GFP bone marrow reconstitution of APOE*3-Leiden.huCETP mice in which the aortas were shielded from irradiation showed infiltrating monocytes to contribute only 11% to the plaque macrophage pool during plaque progression, thereby underscoring the relevance of targeting macrophage proliferation for plaque regression. Finally, rates of macrophage proliferation in human carotid artery plaques correlated with serum LDL-cholesterol levels, in line with our experimental studies.

Conclusion
Foam cell formation in atherosclerotic plaques triggers their proliferation. Targeting macrophage proliferation leads to plaque regression.
P734Research on the mechamism of renal sympathetic denervation in the treatment of insulin resistance
Authors: Xu M , Lu C 
Published: October 2019

Abstract

Background
Insulin resistance is the main pathogenesis of type 2 diabetes. In order to better control the blood glucose of diabetic patients, the key is to improve the insulin sensitivity. With the in-depth study on the mechanism of insulin resistance, sympathetic nerve is an important part of it, but the specific mechanism is not clear.

Objective
This experiment aims to observe the effects of RDN on insulin resistance and skeletal muscle mitochondrial function in spontaneous diabetes ZDF rats.

Methods
6 SPF healthy male ZDF (fa/+) rats were selected as control group, 12 healthy males ZDF (fa/fa) rats were randomly divided into sham group and RDN group. In the sham group and RDN group, the rats were treated with sham operation or bilateral renal sympathetic denervation respectively. Insulin sensitivity was tested in all rats with Hyperinsulinemic-euglycemic clamp test 2 weeks after RDN. The skeletal muscle ATPsyn, COXIV, UCP3 and SOD2 were tested by Western-blot method.

Results
The result showed that 2 weeks after RDN, the blood glucose level of the RDN group decreased significantly (P=0.000) when compared with the sham group. The glucose infusion rate (GIR) in sham and RDN group decreased significantly when compared with the control group (P=0.000). After RDN, the GIR in RDN group increased significantly. ATPsyn, COXIV which were the key enzyme of oxidative metabolism in skeletal muscle mitochondria decreased significantly in the sham and RDN group when compared with control group (P=0.001). However, parameters improved dramatically after RDN (P=0.001).
Table 1. Comparision of Baseline in each group 2 weeks after RDN Control (n=6) Sham (n=6) RDN (n=6) Pa Pb Pc Weight (g) 311.1±8.5 410.8±10.7 377.9±15.3 0.000 0.001 0.002 BBG (mmol/L) 5.97±0.16 21.42±1.45 7.91±0.54 0.000 0.001 0.000 BISN (ng/mL) 100.67±4.18 162.17±3.13 134.67±2.50 0.000 0.001 0.001 TG (mmol/L) 2.71±0.28 6.90±0.24 4.88±0.23 0.000 0.001 0.002 TC (mmol/L) 2.38±0.17 6.98±0.15 5.40±0.09 0.000 0.000 0.000 HDL-C (mmol/L) 7.92±0.44 2.95±0.22 5.35±0.19 0.000 0.000 0.000 LDL-C (mmol/L) 3.72±0.37 4.12±0.17 3.98±0.17 0.001 0.000 0.000 aCompared with Control Group and Sham Group. bCompared with RDN Group and Sham Group. cCompared with Sham Group and RDN Group.
Relative results

Conclusion
Our results showed that RDN improved the insulin sensitivity in diabetes rats. The mechanism may be related to the decrease of oxidative stress and function improvement in skeletal muscle mitochondrial by RDN.
P736Histone marks induced by the methyltransferase SETD7 modulate angiogenic response in diabetes
Authors: Mohammed S A , Costantino S , Akhmedov A , Ambrosini S , Karsay G , Brown P , Luscher T F , Paneni F 
Published: October 2019

Abstract

Introduction
Despite advances in revascularization strategies, type 2 diabetic (T2D) patients with peripheral artery disease (PAD) continue to have a high risk of limb amputation. Hence, strategies that promote vascularization can be considered as a novel therapeutic option in T2D patients with PAD. Epigenetic modifications of histones and DNA have emerged as key modulators of gene expression. Mono-methylation of histone 3 at lysine 4 (H3K4m1) – a specific epigenetic signature induced by the methyltransferase SETD7 – favours a chromatin conformation enabling the transcription of genes involved in inflammation and oxidative stress.

Purpose
To investigate whether SETD7 modulates angiogenesis in experimental diabetes.

Methods
Human aortic endothelial cells (HAECs) were cultured in growth factor-free medium and exposed either to normal glucose (NG, 5 mM) or high glucose (HG, 25 mM) for 48 hours. SETD7 protein and H3K4me1 levels were investigated by Western blot and chromatin immunoprecipitation (ChIP). Knockdown of SETD7 was achieved by small interfering RNA (siRNA). Pharmacological blockade of SETD7 was performed by using the highly selective inhibitor (R)-PFI-2, while its inactive enantiomer, (S)-PFI-2, was used as a control. Scratch and tube formation assays were performed to investigate the impact of SETD7 on angiogenic properties of HAECs. RNA sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) were employed to unveil putative genes regulated by SETD7 in HG-treated HAECs. SETD7 expression was also investigated in muscular specimens isolated from type 2 diabetic (db/db) mice and non-diabetic mice undergoing hindlimb ischemia for 21 days.

Results
HG exposure in HAECs led to a time-dependent increase of both SETD7 gene and protein expression, as compared to NG. SETD7 upregulation in HG-treated HAECs was associated with an increase of H3K4me1 levels as well as with impaired endothelial cell migration and tube formation. Of interest, both gene silencing and pharmacological blockade of SETD7 rescued hyperglycemia-induced impairment of angiogenic properties in HAECs. RNA-seq in HG-treated HAECs with and without SETD7 depletion unveiled an array of differentially expressed genes, which were mainly involved in blood vessel growth and angiogenic response, as assessed by IPA analysis. Among dysregulated genes, ChIP assays showed that SETD7-dependent chromatin changes enabled the transcription of Semaphorin 3G (SEMA-3G), a negative regulator of endothelial cell migration. Indeed, gene silencing of SETD7 blunted SEMA-3G expression in HAECs exposed to HG. Consistent with our in vitro observations, SETD7 was upregulated in adductor muscle specimens from db/db mice undergoing hindlimb ischemia as compared to non-diabetic animals.

Conclusions
Pharmacological blockade of SETD7 by (R)-PFI-2 may represent a potential therapeutic approach to boost post-ischemic vascularization in T2D patients with PAD.
P742Effects of platelet microparticles on the formation and stability of atherosclerotic plaque in ApoE knockout mice
Authors: Wang Z , Pan L , Chen L , Hu H 
Published: October 2019

Abstract

Background
After activation by different factors, platelets can release a large number of platelet microparticles (PMPs), and continue to play a more durable and extensive role in promoting inflammation and thrombosis. Previous studies by our group have shown that PMPs can promote endothelial cell migration and lumen formation in vitro, and promote the release of inflammatory factors from monocytes. However, it is unclear whether PMPs can promote angiogenesis in the plaque and promote vascular wall inflammation and further lead to plaque instability.

Purpose
To investigate the effect of platelet microparticles (PMPs) from C57BL/6 mice on promoting atherosclerotic plaque formation and plaque stability in ApoE−/− mice.

Methods
Forty male apolipoprotein E knockout (ApoE−/−) mice, aged 8 weeks and fed for 4 weeks with high-fat diet, were randomly divided into four groups (n=10 in each group)according to the table of random digit. The mice were respectively injected with PBS (PBS group), PMPs-free supernatants (SUP group), low-dose PMPs (LDP group) and high-dose PMPs (HDP group) once a week through tail vein injection for 8 weeks. At the end of the experiment, the mice were euthanized and the blood samples were collected to detect blood routine, blood lipids, liver and kidney function and inflammatory factors including CRP, IL-1β, TNF-α; The aorta and brachiocephalic trunk were sampled to detect the atherosclerotic plaque formation. Oil Red O staining, H&E staining, Masson staining and immunohistochemistry (CD68, MMP-9, α-SMA) were used to examine the stability of the atherosclerotic plaque in each group.

Results
There were no significant differences in body weight, blood routine (WBC, RBC, PLT, HGB), blood lipids (TG, TCH, LDL, HDL), liver (ALT, AST)and kidney function (UN, Cr)in each group. The levels of serum CRP, IL-1β and TNF-α in LDP group and HDP group were significantly higher than those in PBS group and SUP group (P<0.05). The total area of aortic atherosclerotic plaques in LDP group and HDP group were significantly greater than those in PBS group and SUP group (P<0.05). Compared with the PBS group, the lipid cores of the plaques in the other three groups were significantly increased (P<0.05). The content of collagen and the amount of smooth muscle cells in the plaques were significantly lower in HDP group than in PBS group (P<0.05), while macrophages increased significantly in HDP group (P<0.05).

Conclusion
PMPs promote the formation of atherosclerotic plaques in high-fat-fed ApoE−/− mice, as well as macrophage infiltration and inflammation in the plaques, reduce the content of collagen and the amount of smooth muscle cells, thus decreasing the stability of plaques.