Effect of sacubitril valsartan on cardiac function and endothelial function in patients with chronic heart failure with reduced ejection fraction.

OBJECTIVE: The aim of the present study was to observe the effect of sacubitril valsartan on cardiac function and vascular endothelial function in patients with chronic heart failure with reduced ejection fraction (HFrEF). METHODS: A total of 80 patients with HFrEF were randomly divided into an observation group and a control group, with 40 patients in each group. Sacubitril valsartan was added to the conventional treatment in the observation group, and perindopril was added to the conventional treatment in the control group. Both groups were treated continuously for 12 weeks. The left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), flow-mediated vasodilatory function (FMD) of the brachial artery, and levels of plasma Ang II, endothelin 1 (ET-1), and calcitonin gene-related peptide (CGRP), together with the serum nitric oxide (NO) and NO synthase (NOS) were compared before and after treatment in the groups. RESULTS: Before the treatment, the levels of LVEF, LVEDD, FMD, Ang II, ET-1, CGRP, NO, and NOS in the observation group were not significantly different from those in the control group (P > 0.05). However, the levels of LVEF, FMD, CGRP, NO, and NOS in both groups were significantly higher after the treatment than those before the treatment (P < 0.05) and significantly higher in the observation group than those in the control group. The difference was statistically significant (P < 0.05). Meanwhile, the levels of LVEDD, Ang II, and ET-1 in both groups decreased significantly after the treatment (P < 0.05) and were significantly lower in the observation group than those in the control group. The difference was statistically significant (P < 0.05). CONCLUSION: Sacubitril valsartan might improve endothelial function while increasing cardiac function in HFrEF patients.

Effects of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use on cancer therapy-related cardiac dysfunction: a meta-analysis of randomized controlled trials.

Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) may attenuate cancer therapy-related cardiac dysfunction (CTRCD). However, results of the previous studies were not consistent. We performed a meta-analysis to evaluate the influence of ACEI/ARB on CTRCD. Randomized controlled trials (RCTs) were obtained by searching of PubMed, Embase, and Cochrane's Library databases. A random-effect model was used to pool the results. Nine RCTs with 1095 cancer patients that underwent chemotherapy with anthracycline and/or trastuzumab were included. Using of ACEI/ARB significantly preserved left ventricular ejection fraction (LVEF, weighed mean difference = 4.24%, p = 0.002) compared with controls. Subgroup analyses showed that the benefits of ACEI/ARB on LVEF following chemotherapy were consistent and independent of study characteristics including study design, sample size, cancer type, chemotherapy protocols, preventative medications of ACEI or ARB, methods for LVEF measurement, and follow-up durations. The benefits on LVEF following chemotherapy were more remarkable in studies using ACEI and followed ≤ 12 months (p for subgroup difference = 0.04 and 0.02). Use of ACEI/ARB did not significantly reduce the risk of cardiotoxicity events (risk ratio [RR] = 0.63, p = 0.22) but increased the risk of hypotension in these patients (RR = 3.94, p = 0.008). These results indicated that using of ACEI/ARB may moderately attenuate CTRCD following chemotherapy with anthracycline and/or trastuzumab. Large-scale RCTs are needed to evaluate whether the benefits of ACEI/ARB on LVEF are clinically relevant.

N-terminal pro-B-type natriuretic peptide and outcomes in type B aortic dissection in China: a retrospective multicentre study.

OBJECTIVES: N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is an unfavourable factor responsible for poor outcomes in the cardiovascular diseases. Nevertheless, the prognostic role of NT-pro-BNP in type B aortic dissection (TBAD) remains unclear. The aim of the current study was to investigate the relationship between NT-pro-BNP levels and in-hospital and long-term adverse prognosis in patients with TBAD. DESIGN: A retrospective multicentre study. SETTING: Liutie Central Hospital, Nanfang Hospital and Huiyang Hospital in China. PARTICIPANTS: A total of 657 consecutive patients with TBAD were enrolled in the study. NT-pro-BNP was measured at admission and included patients were divided into three groups according to the tertiles of NT-pro-BNP (pg/mL): <95 (n=220), 95-312 (n=218) and >312 (n=219). PRIMARY AND SECONDARY OUTCOME MEASURES: Long-term mortality and in-hospital major adverse clinical events. RESULTS: Overall, in-hospital death occurred in 27 patients (4.1%), which was significantly higher in upper tertiles of NT-pro-BNP (0.5% vs 4.1% vs 7.8%, p<0.001). The incident of in-hospital major adverse clinical events increased along with higher NT-pro-BNP (1.4% vs 11.5% vs 15.5%, p<0.001). NT-pro-BNP >210 pg/mL had 81.5% sensitivity and 58.6% specificity for predicting in-hospital death (area under the curve= 0.774, 95% CI 0.692 to 0.855; p<0.001). After a median of 3.1 years of follow-up, 97 (14.8%) patients died. The Kaplan-Meier analysis indicated that the long-term cumulative mortality was higher in patients with NT-pro-BNP >210 pg/mL compared with patients with NT-pro-BNP ≤210 pg/mL (log-rank=26.92, p<0.001). In multivariable Cox survival modelling, NT-pro-BNP >210 pg/mL was independently associated with long-term death (adjusted HR 2.47, 95% CI 1.45 to 4.22, p=0.001). CONCLUSIONS: NT-pro-BNP resulted as an independent predictor of adverse prognosis in patients with TBAD, thus could be used as a potential risk-stratification tool.

Prognostic value of hyperuricemia in patients with acute coronary syndrome: A meta-analysis.

BACKGROUND: The prognostic significance of elevated circulating uric acid level in patients with acute coronary syndrome (ACS) is conflicting. This meta-analysis aimed to assess the prognostic value of hyperuricemia in patients with ACS. METHODS: A comprehensive literature search was performed in Pubmed, Embase, VIP, CNKI and WanFang databases up to 16 June 2018. All observational studies that investigated the prognostic value of hyperuricemia in ACS patients were selected. Outcome of interests was major adverse cardiovascular events (MACEs), all-cause mortality or cardiovascular mortality. RESULTS: A total of nine studies enrolling 8776 ACS patients were included and analysed. ACS patients with hyperuricemia had an increased risk of MACEs (risk ratio [RR]: 1.86; 95% confidence intervals [CI]: 1.47-2.35), all-cause mortality (RR 1.86; 95% CI: 1.49-2.32) and cardiovascular mortality (RR: 1.74; 95% CI: 1.36-2.22) after adjustment for the conventional risk factors. Stratified analysis showed that the prognostic significance of hyperuricemia was consistently observed in each subgroups. CONCLUSIONS: This meta-analysis suggests that hyperuricemia independently predicts MACEs and death in ACS patients. Determination of uric acid level has potential to improve risk stratification of adverse outcomes in ACS patients.

2,3,5,4'­Tetrahydroxystilbene­2­O­ß­D­glucoside inhibits septic serum­induced inflammatory injury via interfering with the ROS­MAPK­NF­κB signaling pathway in pulmonary aortic endothelial cells.

Sepsis is characterized by injury to the microvasculature and the microvascular endothelial cells, leading to barrier dysfunction. However, the specific role of injury in septic endothelial barrier dysfunction remains to be elucidated. In the present study, it was hypothesized that endothelial cell inflammatory injury is likely required for barrier dysfunction under septic conditions in vitro. 2,3,5,4'­Tetrahydroxystilbene­2­O­ß­D­glucoside (TSG), a compound extracted from Chinese herbs, is able to inhibit the inflammatory injury of septic­serum in endothelial cells. In the present study, cell viability was assayed by CCK­8 method; mRNA and protein expression was identified by RT­qPCR, western blot or Elisa, respectively and the production of reactive oxygen species was observed by a fluorescence microscope. The present study indicated that septic serum significantly decreased the cell viability of pulmonary aortic endothelial cells (PAECs) following co­cultivation for 6 h, which occurred in a time­dependent manner. TSG notably increased the viability of PAECs in a time­ and concentration­dependent manner. Further investigations revealed that septic serum increased the secretion of interleukin (IL)­1ß, IL­6 and C­reactive protein in PAECs, whereas pretreatment with TSG significantly decreased the secretion of these inflammatory factors. These data indicated that septic serum increased inflammatory injury to the PAECs, and TSG decreased this injury via the reactive oxygen species­mitogen­activated protein kinase­nuclear factor­κB signaling pathway.

Blood pH in coronary artery microthrombosis of rats.

OBJECTIVE: To study the mechanism and significance of pH change in the coronary artery microthrombosis of rats. METHODS: After the sodium laurate-induced model of coronary artery microthrombosis of rats was constructed, the vascular endothelial cells were separated and then cultured in the mediums with different pH values for 24 h. Enzyme linked immunosorbent assay was used to detect the content of von Willebrand factor (vWF) in the medium; while the real-time PCR and western blot assay were used to detect the expression of fibrinogen-like protein 2 (FGL2) at the mRNA and protein level. The comprehensive evaluation was performed to discuss the effect of pH change on the coronary artery microthrombosis of rats. RESULTS: The expression level of vWF detected by enzyme linked immunosorbent assay was 336.67 ± 24.95, 311.33 ± 14.98, 359.67 ± 39.63, 354.67 ± 49.01 and 332.00 ± 33.42 (pg/mL) respectively; while the expression of vWF in the model group was 570.00 ± 57.94, 524.67 ± 57.94, 437.00 ± 95.38, 415.33 ± 44.38 and 444.67 ± 74.31 respectively. Being cultured under the different pH values, the relative expression level of FGL2 mRNA in the model group was 7.93 ± 0.93, 6.70 ± 0.70, 5.03 ± 0.32, 5.13 ± 0.40 and 5.57 ± 0.83 respectively. CONCLUSIONS: The coronary artery microthrombosis of rats can cause the high expression and secretion of vWF. Meanwhile, FGL2 is also up-regulated in the thrombosis and such up-regulation is more significant in the condition with low pH, which indicates that the low pH condition may be one of factors that contribute to the cardiovascular diseases.

Apoptosis and calcification of vascular endothelial cell under hyperhomocysteinemia.

In recent years, it is found that increase in Hcy level in blood can directly or indirectly cause vascular endothelial cell injury and induce vascular calcification. However, the mechanism of vascular endothelial cell injury and vascular calcification has not been studied thoroughly. This paper carried out experiment for research aiming at discussing the effect and action mechanism of Hhcy on endothelial cells and vascular calcification. Firstly, human umbilical vein endothelial cells (HUVECs) were cultured and then intervened by Hcy of different concentrations (0, 0.01, 0.1, 1.0, 3.0, 5.0 mmol/L) and at different action time (3, 6, 12, 24 h). Then apoptosis rate and reactive oxygen were detected by flow cytometry. At the same time, the model for the culture of rat vascular calcification was set up and induced into Hhcy so as to detect the total plasma Hcy level and judge vascular calcification degree. The results showed that with the increase in Hcy concentration and extension of action period, the apoptosis rate and generation of reactive oxygen of HUVECs all significantly increased, and the differences were all statistically significant (P < 0.01). In animal calcification model, mass of black particle deposition was seen after Von Kossa staining of rat vessels in calcification group. Compared with the control group, the vascular calcium content, alkaline phosphatase activity and osteocalcin content in calcification group all increased (P < 0.01). The content of plasma lipid conjugated olefine from highest to lowest wasas follows: calcification plus homoetheionin, homoetheionin, and calcification group. There was no significant difference between the calcification group and control group. All these findings suggested that Hcy could induce the apoptosis of endothelial cells and its effect degree depended on its concentration and action period; Hhcy could promote the calcification of blood vessels, and its mechanism might relate with the strengthening of lipid peroxidation. The above results leave great benefits on clinical prevention works.