Mediating Effect of the NLR on the Relationship Between HbA1c and Left Atrial Stiffness in Overweight Patients With Hypertension.

BACKGROUND: We aimed to investigate the association between hemoglobin A1c (HbA1c) and left atrial (LA) stiffness in patients with hypertension and to explore the mediating effect of the neutrophil/lymphocyte ratio (NLR) on this association. METHODS: Essential hypertensive patients (n = 292) aged 18-83 years were enrolled and divided into two groups based on the LA stiffness index (LASI): Group I (LASI ≤ 0.32, n = 146) and Group II (LASI > 0.32, n = 146). The LASI was defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to LA reservoir strain. Multivariate linear regression analysis was performed to determine the independent predictors of the LASI. RESULTS: Age, BMI, SBP, HbA1c, CRP, and NLR were significantly greater in Group II than in Group I (P < 0.05). Additionally, Group II had a greater LA volume index (LAVI), left ventricular mass index (LVMI), and early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') and lower LA reservoir, conduit, and booster pump strains than Group I (P < 0.001). Univariate and multivariate linear regression models revealed that age, SBP, HbA1c, and the NLR were independently associated with the LASI. Further mediation analysis was performed to determine the mediating effect of the NLR on the association between HbA1c and the LASI and revealed that the NLR had a mediating role only in overweight hypertensive patients, and the proportion of the mediating effect was 21.9%. CONCLUSIONS: The NLR was independently correlated with the LASI and played a mediating role in the relationship between HbA1c and the LASI in overweight hypertensive patients.

Rutaecarpine Inhibits Doxorubicin-Induced Oxidative Stress and Apoptosis by Activating AKT Signaling Pathway.

Patients with cancer who receive doxorubicin (DOX) treatment can experience cardiac dysfunction, which can finally develop into heart failure. Oxidative stress is considered the most important mechanism for DOX-mediated cardiotoxicity. Rutaecarpine (Rut), a quinazolinocarboline alkaloid extracted from Evodia rutaecarpa was shown to have a protective effect on cardiac disease. The purpose of this study is to investigate the role of Rut in DOX-induced cardiotoxicity and explore the underlying mechanism. Intravenous injection of DOX (5 mg/kg, once a week) in mice for 4 weeks was used to establish the cardiotoxic model. Echocardiography and pathological staining analysis were used to detect the changes in structure and function in the heart. Western blot and real-time PCR analysis were used to detect the molecular changes. In this study, we found that DOX time-dependently decreased cardiac function with few systemic side effects. Rut inhibited DOX-induced cardiac fibrosis, reduction in heart size, and decrease in heart function. DOX-induced reduction in superoxide dismutase (SOD) and glutathione (GSH), enhancement of malondialdehyde (MDA) was inhibited by Rut administration. Meanwhile, Rut inhibited DOX-induced apoptosis in the heart. Importantly, we further found that Rut activated AKT or nuclear factor erythroid 2-related factor 2 (Nrf-2) which further upregulated the antioxidant enzymes such as heme oxygenase-1 (HO-1) and GSH cysteine ligase modulatory subunit (GCLM) expression. AKT inhibitor (AKTi) partially inhibited Nrf-2, HO-1, and GCLM expression and abolished the protective role of Rut in DOX-induced cardiotoxicity. In conclusion, this study identified Rut as a potential therapeutic agent for treating DOX-induced cardiotoxicity by activating AKT.

The protective effects of renin-angiotensin system componts on vascular calcification.

Renin-angiotensin system (RAS) has important roles in cardiovascular disease. Angiotensin II (Ang II) and angiotensin-(1-7) (Ang-(1-7)) are major effector peptides of RAS. However, the roles of Ang II type 2 receptor (AT2R) need to be further explored and the roles of Ang-(1-7) are still not very clear on vascular calcification (VC). Therefore, we hypothesized they have effects on preventing VC in vivo and in vitro. VC model is established by inorganic phosphate (IP) cultured with vascular smooth muscle cells (VSMC) for in vitro study and by 5/6 nephrectomy in mice for in vivo study. Increased calcified nodules by Alizarin Red S staining and mRNA expressions of bone morphogenetic protein-2 (BMP-2) and osteocalcin (OCN) by reverse transcription polymerase chain reaction in calcified WT VSMC were significantly inhibited in calcified AT2R overexpression (SmAT2) VSMC or after Ang-(1-7) treatment. After 5/6 nephrectomy, the ratio of positive and total area by Alizarin Red S and von Kossa staining and mRNA expressions of BMP-2 and OCN were significantly increased in ApoE/AT2R knockout mice compared with apolipoprotein E knockout mice, and which were significantly inhibited with Ang-(1-7) administration. Both AT2R and Ang-(1-7) have the effects on preventing VC induced by IP, at least in part through inhibiting BMP-2, OCN expressions, and in which Ang-(1-7) had protective roles mainly through Mas receptor rather than AT2R.

2019 Chinese Hypertension League guidelines on home blood pressure monitoring.

In China, automated blood pressure monitors have been readily available for home use. Home blood pressure monitoring has been indispensable in the management of hypertension. There is therefore a need to establish guidelines for home blood pressure monitoring on the basis of the 2012 consensus document. In this guidelines document, the committee put forward recommendations on the selection and calibration of blood pressure measuring devices, the frequency (times) and duration (days) of blood pressure measurement, and the diagnostic threshold of home blood pressure.

Ascending aortic distensibility and target organ damage in primary hypertension without diabetes.

To investigate the relationship between ascending aortic distensibility (AAD) and hypertensive target organ damage (TOD) and its potential value in prediction. One hundred and sixty seven primary hypertension inpatients who underwent coronary CTA examination were enrolled into our study. Retrospective ECG-triggering scanning mode were applied and the images were reconstructed every 5% phase in the entire R-R interval. Maximum and minimum ascending aortic areas as well as the AAD value were calculated on the interested slice. AAD (P < 0.001) and brachial-ankle pulse wave velocity (baPWV, P < 0.05) were changed significantly as the deterioration of TOD. Multivariate logistic regression analysis between TOD and its possible influence factors indicated that AAD was the only independent risk factor for the presence and severity of TOD. One standard deviation decrease on AAD would increase the risk of TOD significantly: TOD1 (odds ratio 0.45, P < 0.05), TOD2 (odds ratio 0.23, P < 0.05), and TOD3 (odds ratio 0.01, P < 0.05). The odds ratio of TOD in the third tertile group was found 5.47 times higher than that in the second tertile group, and the second tertile group TOD odds ratio was 6.4 times higher than that in the first tertile group. Decline of AAD can be taken as the independent predict factor for TOD in primary hypertension patients, superior to baPWV method and other conventional predictors. Without additional contrast media consumption and radiation dose, AAD derived from coronary CTA may provide early detection for hypertensive TOD.

Ascending Aortic Elasticity and Related Risk Factors Study on Prehypertension Patients.

BACKGROUND: A new feature of coronary computed tomography angiography (CTA) is to estimate ascending aortic elasticity without additional cost, but its applicable benefit for prehypertension patients is still unclear. The aim of this study is to discuss the characteristic of ascending aortic elasticity for specific prehypertension patients and its risk factors. METHODS: Coronary CTA examinations of 398 participants were performed using a 128 slicer CT scanner. The differences of 3 ascending aortic elasticity related indices, including aortic distensibility (AD), aortic compliance (AC), and aortic stiffness (ASI), and anatomical measurements were analyzed among the normal, prehypertension, and primary hypertension groups. RESULTS: No difference was found for normalized minimum cross-sectional diameter and area for the ascending aorta between prehypertension and normal groups. AD, AC, and ASI were significantly different in 3 groups. Between prehypertension and normal groups, AD and AC were found much smaller but no difference were found for ASI; while between prehypertension and hypertension groups, significant differences were found in AD and ASI, and AC was found to a lesser extent. Risk factor study for prehypertension patients indicated that age and systolic pressure were the independent risk factors for AD decline. CONCLUSION: As a byproduct, coronary CTA can provide multiple aortic elasticity related indices for the prehypertension patients, without additional contrast media consumption and radiation dose. It is proofed that the early detection of ascending aortic elasticity index changes, especially for AD are essential for identifying the high-risk individuals in the prehypertension populations. CLINICAL TRIALS REGISTRATION: Our public trials registry number ChiCTR-RIC-15007482.

Protective effect of thymoquinone improves cardiovascular function, and attenuates oxidative stress, inflammation and apoptosis by mediating the PI3K/Akt pathway in diabetic rats.

Thymoquinone is the main active monomer extracted from black cumin and has anti­inflammatory, antioxidant and anti­apoptotic functions. However, the protective effects of thymoquinone on cardiovascular function in diabetes remain to be fully elucidated. The present study aimed to investigate the molecular mechanisms underling the beneficial effects of thymoquinone on the cardiovascular function in streptozotocin­induced diabetes mellitus (DM) rats. Supplement thymoquinone may recover the insulin levels and body weight, inhibit blood glucose levels and reduce the heart rate in DM­induced rats. The results indicated that the heart, liver and lung to body weight ratios, in addition to the blood pressure levels, were similar for each experimental group. Treatment with thymoquinone significantly reduced oxidative stress damage, inhibited the increased endothelial nitric oxide synthase protein expression and suppressed the elevation of cyclooxygenase­2 levels in DM­induced rats. In addition, thymoquinone significantly suppressed the promotion of tumor necrosis factor­α and interleukin­6 levels in the DM­induced rats. Furthermore, administration of thymoquinone significantly reduced caspase­3 activity and the promotion of phosphorylated­protein kinase B (Akt) protein expression levels in DM­induced rats. These results suggest that the protective effect of thymoquinone improves cardiovascular function and attenuates oxidative stress, inflammation and apoptosis by mediating the phosphatidylinositol 3­kinase/Akt pathway in DM­induced rats.

Use of Dual-Source Computed Tomography to Evaluate Renal Cortical Perfusion in Patients With Essential Hypertension Without Diabetes: Preliminary Results.

OBJECTIVES: To assess renal cortical perfusion parameter changes using computed tomography (CT) renal perfusion examination in patients with essential hypertension (EH), especially those with EH-related target organ damage (TOD), and to correlate renal perfusion parameters with clinical and laboratory data. METHODS: Consecutive patients with EH (without exclusion criteria) and healthy controls underwent 128-slice dual-source CT perfusion imaging. Quantitative perfusion analysis of renal cortex parameters [blood flow (BF), blood volume, time to peak, and mean transit time] was performed. RESULTS: Ninety-one participants (60 patients with EH, 31 healthy controls) underwent renal perfusion CT imaging, and 84 participants (92.3%) were eligible for perfusion analysis. The BF values were lower in patients with EH than that in controls. Blood flow was correlated with age (P < 0.01), duration of hypertension (P < 0.01), estimated glomerular filtration rate (eGFR; P < 0.01), pulse pressure (P < 0.05), and body mass index (BMI; P < 0.05). Duration of hypertension, eGFR, and BMI were independently associated with BF. No parameter differed between control subjects and those with EH but not. Blood flow was lower in patients with TOD than in control subjects (P < 0.01), but no other parameter differed. Blood flow was lower (P < 0.01) and mean transit time and time to peak were higher (P < 0.05) in the TOD than that in the non-TOD group. CONCLUSIONS: Essential hypertension, especially EH-related TOD, alters renal cortical perfusion parameters, especially BF. Four-dimensional spiral CT renal perfusion examination showed that duration of hypertension, eGFR, and BMI were independently associated with decreased BF.

Identification of genes related to the early stage of Angiotensin II-induced acute renal injury by microarray and integrated gene network analysis.

BACKGROUND/AIMS: Angiotensin II (Ang II) mediated signaling plays a key role in the development of chronic kidney damage that contributes to renal fibrosis. However, the gene expression changes regulated by Ang II in the early stage of acute renal injury remain unclear. METHODS: C57BL/6 wild-type (WT) mice were injected with Ang II (1500 ng/kg/min) for 1, 3 and 7 days. A time series analysis of microarrays was performed to evaluate Ang II-induced differentially gene expression in the kidneys. The data of gene expression in the kidney was further dissected by ANOVA analysis, gene expression profiles, gene network construction and quantitative real-time RT-PCR. Ang II-induced renal inflammation and fibrosis in mice were confirmed by pathological examination. RESULTS: Our microarray data showed that a total of 1,511 differentially expressed genes were identified in the kidneys at 1, 3 and 7 days after Ang II infusion. These genes function in multiple biological processes, including response to stimuli, immune response, cell adhesion, metabolic process, kidney development, regulation of blood pressure, and ion transport, which may play critical roles in the pathobiology of Ang II-induced acute renal injury at the early stage. Furthermore, among these genes, 20 genes were further selected for final investigation. The dynamic gene network analysis demonstrated that fatty acid binding protein 1 (Fabp1) localized in the core of the network. CONCLUSIONS: Our data suggests that genes involved in lipid metabolic process, especially Fabp1, may play a central role in the development of Ang II-induced acute renal injury at the early stage.

Myocardial dysfunction in early diabetes patients with microalbuminuria: a 2-dimensional speckle tracking strain study.

The aim of this study was to assess myocardial dysfunction in primary diabetes patients with microalbuminuria by 2-dimensional speckle tracking strain. Sixty-two patients with diabetes with or without hypertension and 37 matched hypertension controls were consecutively recruited from January 2011 to 2013. Routine physical examinations, laboratory tests, and echocardiography were performed in all patients. Subjects enrolled were divided into three groups according to history and urine albumin/creatinine ratio (ACR): group I: patients with only hypertension and normoalbuminuria (ACR < 30 mg/g), group II: patients with both hypertension and diabetes and normoalbuminuria (ACR < 30 mg/g), and group III: patients with both hypertension and diabetes and microalbuminuria (ACR 30-300 mg/g). Echocardiographic images of three cardiac cycles were acquired for off-line analysis using the GE EchoPAC software. Indices of cardiac function, including longitudinal, radial and circumferential strains, torsion, and left ventricular ejection fraction (LVEF) were assessed. Statistical analysis was performed using SPSS 13.0. Finally, 56 subjects and 32 controls were included in the analyses. There was no significant difference in age, gender, heart rate, BMI, and LVEF among groups, except for the blood pressure, ACR, and HbA1c. E wave, A wave, EDT, E m, and E/E m in group III were different with those in group I. Mean longitudinal strain (mSL), average SL of six segments in 4-chamber apical view (SL4) decreased obviously. The peak circumferential strain decreased in group III, while the torsion was compensatively increased. ACR was negatively related to mSL, SL4, E/E m, and positively related to torsion. We deduced that ACR maybe a predictor for myocardial damage in primary diabetes.

[Advanced oxidation protein products promote expression of stromal-cell derived factor-1alpha of ECV304 cells through ERK signal pathway].

OBJECTIVE: To explore the effects of advanced oxidation protein products (AOPP) on expressions of stromal cell-derived factor-1alpha (SDF-1alpha) in ECV304 cells and the signal pathway that mediated the effects. METHODS: AOPP-BSA was made from bovine serum albumin (BSA) and sodium hypochlorite. After treated with AOPP-BSA of different concentrations (50, 100, 200 micromol/L), the expressions of SDF-1alpha mRNA in ECV304 cells were measured by reverse transcription-polymerase chain reaction (RT-PCR) and the expressions of SDF-1alpha protein and the levels of phosphorylated extracellular signal-regulated kinase (ERK) in ECV304 cells were analyzed by Western blot. In inhibition test, U0126, the special inhibitor of ERK of different concentrations (0.1, 1, 10 rmol/L) were added into ECV304 cells culture media for 1 hour, then the cells were treated with AOPP-BSA for 24 hours, at last the protein levels in supernatant were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: AOPP-BSA obviously promoted the expressions of SDF-1alpha mRNA and increased the levels of SDF-1beta protein of ECV304 cells in dose-dependent manner (all P < 0.01), after 15 minutes treated with 200 micromol/L AOPP-BSA, the levels of phosphorylated ERK of ECV304 cells increased significantly (P < 0.01). When the ERK pathway was blocked by U0126, the promoting effects of AOPP-BSA on expressions of SDF-la protein in ECV304 cells were significantly inhibited in dose-dependent manner (P < 0.05). CONCLUSION: AOPP induced the expression of SDF-la of ECV304 cells, ERK signal pathway is an important pathway that mediated the effects.

[Comparison on efficacy and safety between domestic levosimendan versus dobutamine for patients with acute decompensated heart failure].

OBJECTIVE: To compare the efficacy and safety of domestic levosimendan versus dobutamine for patients with acute decompensated heart failure (ADHF). METHODS: ADHF patients from 8 medical centers were recruited in this multicenter, blind, positive-controlled, randomized study and received 24 h intravenous levosimendan (n = 114) or dobutamine (n = 114) therapy. SWAN-GANZ catheter was performed in patients with pulmonary capillary wedge pressure (PCWP) ≥ 15 mm Hg (1 mm Hg = 0.133 kPa) and cardiac index (CI) ≤ 2.5 L·min(-1)×m(-2) (n = 39 each). RESULTS: Compared with baseline level, LVEF increased [(31.56 ± 9.69)% vs. (28.44 ± 7.08)%, P < 0.01] at 24 h in both groups. LVEF increase at 24 h was similar between two groups [(3.11 ± 6.90)% vs. (3.00 ± 6.63)%, P > 0.05]. The PCWP decrease at 24 h was significantly greater in levosimendan group than in dobutamine group [(-8.90 ± 7.14) mm Hg vs. (-5.64 ± 6.83) mm Hg, P = 0.04]. Decrease in NT-proBNP at 3 days was also more significant in levosimendan group than in dobutamine group [the percentage change compared to baseline: (-22.36 ± 38.98)% vs. (-8.56 ± 42.42)%, P < 0.01]. Dyspnea improvement at 24 h was more significant in levosimendan group than in dobutamine group. The incidences of adverse reactions and events were similar between two groups. CONCLUSION: LVEF improvement is similar between dobutamine and domestic levosimendan while greater decreases in PCWP and NT-proBNP are achieved with domestic levosimendan in patients with ADHF.

[Clinical observation on isolated electroacupuncture for treatment of peripheral facial paralysis].

OBJECTIVE: To study on therapeutic effect of isolated electroacupuncture on peripheral facial paralysis. METHODS: One hundred cases were randomly divided into an observation group of 60 cases and a control group of 40 cases. The observation group were treated by isolated electroacupuncture and the control group by normal electroacupuncture. Jiache (ST 6), Yangbai (GB 14), Dicang (ST 4), Xiaguan (ST 7), Fengchi (GB 20) and Hegu (LI 4) were selected and same drugs were administrated in the two groups. Then their therapeutic effects were observed. RESULTS: Forty-five cases were cured, 11 cases were markedly effective and 4 cases improved with an effective rate of 100.0% in the observation group, and corresponding figures were 26, 2 and 10 cases, and 95.0% in the control group, the observation group being better than the control group (P < 0.01). CONCLUSION: Isolated electroacupuncture has a significant therapeutic effect on facial paralysis, being better than that of normal electroacupuncture.