A time-series analysis of short-term ambient ozone exposure and hospitalizations from acute myocardial infarction in Henan, China.

Epidemiological studies in recent years have identified an association between exposure to air pollutants and acute myocardial infarction (AMI); however, the association between short-term ozone (O3) exposure and AMI hospitalization remains unclear, particularly in developing countries. Therefore, this study collected information on 24,489 AMI patients, including daily air pollutant and meteorological data in Henan, China, between 2016 and 2021. A distributed lagged nonlinear model combined with a Poisson regression model was used to estimate the nonlinear lagged effect of O3 on AMI hospitalizations. We also quantified the effects of O3 on the number of AMI hospitalizations, hospitalization days, and hospitalization costs. The results showed that single- and dual-pollution models of O3 at lag0, lag1, and lag (01-07) were risk factors for AMI hospitalizations, with the most significant effect at lag03 (RR = 1.132, 95% CI:1.083-1.182). Further studies showed that males, younger people (15-64 years), warm seasons, and long sunshine duration were more susceptible to O3. Hospitalizations attributable to O3 during the study period accounted for 11.66% of the total hospitalizations, corresponding to 2856 patients, 33,492 hospital days, and 90 million RMB. Maintaining O3 at 10-130 µg/m3 can prevent hundreds of AMI hospitalizations and save millions of RMB per year in Henan, China. In conclusion, we found that short-term exposure to O3 was significantly associated with an increased risk of hospitalization for AMI in Henan, China, and that further reductions in ambient O3 levels may have substantial health and economic benefits for patients and local healthcare facilities.

Antihypertensive effect of telmisartan versus perindopril in hypertensive patients.

OBJECTIVE: We performed this meta-analysis determining the antihypertensive effect of telmisartan versus perindopril in patients with essential hypertension. BACKGROUND: The comparison of antihypertensive effects between telmisartan and perindopril were controversial. METHODS: Pubmed, Web of Science, and Cochrane Central were searched for all published studies. RESULTS: The antihypertensive effects were assessed in 753 patients included in 7 trials with a mean follow-up of 20 ± 16 weeks. There was no significant difference between telmisartan and perindopril in reduction of systolic blood pressure (SBP, weighted mean differences (WMD) 0.02 (95% confidence interval (CI), ‒2.78, 2.81) mm Hg, p > 0.05). The reduction of diastolic BP (DBP) treated with telmisartan was greater than perindopril in these patients (WMD ‒2.05 (95% CI, ‒2.60, ‒1.49) mm Hg, p < 0.001). Considering the effects of different doses on BP reduction, a sub-analysis was performed. The reduction of DBP treated with 40 mg/day telmisartan was greater than 4‒5 mg/day perindopril (WMD ‒2.18 (95% CI, ‒2.83, ‒1.53) mm Hg, p 0.05). CONCLUSION: The reduction of DBP is greater treated with telmisartan than perindopril in patients with essential hypertension (Tab. 2, Fig. 4, Ref. 34). Text in PDF www.elis.sk Keywords: essential hypertension, blood pressure, telmisartan, perindopril, meta-analysis.

Intravascular Renal Denervation Reduces Ambulatory and Office Blood Pressure in Patients with Essential Hypertension: A Meta-Analysis of Randomized Sham-Controlled Trials.

BACKGROUND: This meta-analysis was designed to evaluate the antihypertensive efficacy of intravascular renal denervation (RDN) in patients with essential hypertension, especially to determine the magnitude of blood pressure (BP) reduction with RDN therapy using second-generation catheters. METHODS: PubMed was searched to identify randomized sham-controlled trials from inception through August 2021. The endpoints were changes in 24-h ambulatory BP or office BP. This meta-analysis was performed by calculating the weighted mean difference (WMD) with 95% confidence interval (CI) using the random-effects model when the I2 index was <50%. A fixed-effects model was used when the I2 index was ≥50%. RESULTS: A total of 1,297 patients were included in 8 randomized, sham-controlled trials in this meta-analysis. Intravascular RDN reduced 24-h ambulatory systolic BP (SBP) -3.02 (WMD, 95% CI: -4.95, -1.10, p < 0.01) and diastolic BP (DBP) -1.66 (WMD, 95% CI: -2.44, -0.88, p < 0.001) mm Hg, respectively. In the studies using first-generation catheters, the WMDs of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham control were -2.67 (95% CI: -5.08, -0.27; p < 0.05; I2 = 0%, p = 0.53) and -0.82 (95% CI: -2.19, 0.56; p > 0.05; I2 = 0%, p = 0.64) mm Hg. In the studies using second-generation catheters, the WMDs of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham control were -3.14 (95% CI: -5.94, -0.33, p < 0.05; I2 = 71%, p = 0.008) and -2.06 (95% CI: -3.02, -1.11, p < 0.001; I2 = 50%, p = 0.09) mm Hg. Intravascular RDN using second-generation catheters reduced office SBP -6.30 (WMD, 95% CI: -7.67, -4.93, p < 0.001; I2 = 43%, p = 0.14) and DBP -3.88 (WMD, 95% CI: -4.44, -3.33, p < 0.001; I2 = 42%, p = 0.14) mm Hg, respectively. CONCLUSIONS: Intravascular RDN using second-generation catheters reduces ambulatory and office BP in patients with essential hypertension. The selection of appropriate hypertensive patients may be the major challenge for the performance of intravascular RDN in routine clinical practice.

Long-term changes in ischemic burden after chronic total occlusion percutaneous coronary intervention: a retrospective observational study.

OBJECTIVE: There is uncertainty of the benefit of percutaneous coronary intervention (PCI) for chronic coronary total occlusion (CTO). The study aimed to investigate potential long-term changes in ischemic burden in patients with CTO after PCI. METHODS: Patients who underwent CTO PCI with available records of 15O-H2O positron emission tomography within 3 months prior to and at least 6 months after successful CTO PCI were retrospectively included. Data on perfusion defect size, hyperemic myocardial blood flow (MBF), and coronary flow reserve (CFR) within the CTO area before and after CTO PCI were extracted and compared for evaluating ischemic burden. The comparisons were also performed after stratifying by baseline perfusion defect sizes. RESULTS: A total of 74 eligible patients were included with an average age of 62.0±7.5 years. Significant decrease in perfusion defect size (3 (2-4) versus 1 (0-2) segments, P<0.001) and significant increase in hyperemic MBF (1.32±0.39 versus 2.27±0.52 mL/min/g, P<0.001) and CFR (1.72±0.47 versus 2.73±0.73, P<0.001) were observed after CTO PCI when compared to that at baseline. When stratifying by baseline perfusion defect size, no significant differences were observed between groups in changes of hyperemic MBF (P=0.301) and CFR (P=0.850), but patients with larger perfusion defect size exhibited greater reduction in perfusion defect size (P<0.001). CONCLUSIONS: CTO PCI relieved ischemic burden for at least 6 months, and patients with larger baseline perfusion defect size might benefit more from CTO PCI in terms of ischemic burden.

Yixintongmai Inhibits Proliferation and Migration and Promotes Apoptosis of Vascular Smooth Muscle Cells Cultured with High Glucose.

OBJECTIVE: This study was designed to evaluate the effects of yixintongmai on proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) cultured with high glucose. METHODS: VSMCs of the thoracic aorta from 5- to 8-week-old male Sprague-Dawley rats were cultured with normal (4.5 mM) or high (25 mM) glucose, respectively. The concentration of yixintongmai powder at 360 µg/ml was chosen according to pre-experimental results. RESULTS: Yixintongmai inhibited the proliferation of VSMCs (CCK-8 assay: 0.75 ± 0.04 versus 0.98 ± 0.09 OD, P < 0.001; cell counting: 37533 ± 1861 versus 56009 ± 3779 cells/well, P < 0.001) and the expression of proliferating cell nuclear antigen (0.74 ± 0.08 fold, P < 0.001) as compared with high glucose (HG). Yixintongmai inhibited the migration of VSMCs (transwell assay: 146 ± 16 versus 265 ± 62 cells; P < 0.001), scratch wound assay (0.17 ± 0.01 fold, P < 0.001), and the expression of matrix metalloproteinases-9 (0.87 ± 0.03 fold, P < 0.001) as compared with HG. Yixintongmai decreased mitochondrial membrane potentials (0.36 ± 0.12 fold, P < 0.001) and promoted early (2.11 ± 0.20 fold, P < 0.01) and late (2.11 ± 0.28 fold, P < 0.01) apoptosis of VSMCs as compared with HG. Yixintongmai inhibited the expression of B-cell lymphoma 2 (0.83 ± 0.07 fold, P < 0.01) and stimulated the activity of cleaved-capase-3/caspase-3 (2.00 ± 0.12 fold, P < 0.05) as compared with HG. Yixintongmai inhibited reactive oxygen species generation (0.46 ± 0.03 fold, P < 0.01) and the expression of NADPH oxidase-1 (0.84 ± 0.04 fold, P < 0.001), nuclear factor-kappa B (NF-κB) p65 (0.71 ± 0.07 fold, P < 0.001), phosphorylated NF-κB p65 (0.39 ± 0.02 fold, P < 0.0001), and inhibited nuclear translocation of NF-κB p65 (0.87 ± 0.03 fold, P < 0.001) in VSMCs as compared with HG. CONCLUSIONS: Yixintongmai inhibits the proliferation and migration and promotes the apoptosis of VSMCs cultured with HG, which suggests the potential anti-atherosclerotic effects of this traditional Chinese medicine.

Puerarin protects cardiomyocytes from ischemia-reperfusion injury by upregulating LncRNA ANRIL and inhibiting autophagy.

This study analyzed the roles of puerarin and LncRNA ANRIL in myocardial ischemia-reperfusion injury. Hypoxia/reperfusion (H/R) model was established with H9C2 cells. Effects of puerarin of gradient concentrations on cardiomyocytes at different time points of hypoxia and reoxygenation were detected by quantitative real-time polymerase chain reaction (qRT-PCR), cell counting kit-8 (CCK-8), and microscope observation. Effects of puerarin on cardiomyocyte viability, ANRIL expression, contents of lactate dehydrogenase (LDH) and malondialdehyde (MDA), apoptosis, and expressions of autophagy-related genes after H/R injury were determined by CCK-8, quantitative real-time polymerase chain reaction (qRT-PCR), ELISA, flow cytometry, and Western blot, respectively. After cell transfection, the effects of overexpressed and knockdown of ANRIL on cardiomyocytes and H/R-injured cardiomyocytes were examined by rescue experiments. The ischemia-reperfusion (I/R)-injured rat model was established to examine the protective effect of puerarin in vivo. Prolonged hypoxia downregulated ANRIL expression in cardiomyocytes and reduced cardiomyocyte viability. Prolonged reoxygenation increased apoptosis. Both cardiomyocyte viability and ANRIL expression showed a dose-dependent relationship with puerarin. Puerarin reversed the effects of H/R injury on cardiomyocyte viability, ANRIL expression, contents of LDH and MDA, apoptosis, and expressions of autophagy-related genes. Overexpression and knockdown of ANRIL regulated the functions of cardiomyocytes and the expressions of autophagy-related genes. Puerarin reversed the effects of knockdown of ANRIL on H/R-injured cells. The results of In vivo experiments confirmed that puerarin protected myocardial tissues by up-regulating ANRIL and inhibiting autophagy.

Chronotherapy of Hypertension with Angiotensin Receptor Blockers-A Meta-Analysis of Blood Pressure Measured by Ambulatory Blood Pressure Monitoring in Randomized Trials.

BACKGROUND: We performed this meta-analysis evaluating the efficacy of chronotherapy of hypertension with angiotensin receptor blockers (ARBs). METHODS: We searched Pubmed, Web of Science, and Cochrane for all published randomized trials that compare antihypertensive effects of ARBs between bedtime dosing and awakening dosing. Blood pressure (BP) was measured by ambulatory BP monitoring in patients with mild or moderate essential hypertension. RESULTS: The effects of ARBs on BP were assessed in 805 essential hypertensive patients included in 8 trials with a follow-up of 12 ± 3 weeks. The sleep-time systolic and diastolic BP (SBP, DBP) with bedtime dosing greatly decreased as compared with awakening dosing (weighted mean differences [WMD] for SBP WMD -5.23 [95% confidence intervals (CI), -7.27, -3.20] mm Hg, p < 0.001; WMD for DBP -2.94 [95% CI, -4.52, -1.36] mm Hg, p < 0.001). The reduction of daytime SBP (WMD 0.98 [95% CI, -0.20, 2.17] mm Hg, p = 0.10), DBP (WMD 0.11 [95% CI, -0.68, 0.89] mm Hg, p = 0.79), 24 hour SBP (WMD -0.75 [95% CI, -1.93, 0.42] mm Hg, p = 0.21) and DBP (WMD -0. 77 [95% CI, -1.55 0.01] mm Hg, p = 0.05) with bedtime dosing was similar with awakening dosing. CONCLUSIONS: Bedtime dosing with ARBs is more effective in lowering sleep-time BP than awakening dosing in patients with essential hypertension, suggesting a utilization of chronotherapy of hypertension with ARBs to reduce sleep-time high BP. Larger multi-ethnic studies are needed to investigate the efficacy of chronotherapy of hypertension.

Fluorescent Magnetic Iron Oxide NanoparticleEncapsulated Protein Hydrogel Against Doxorubicin-Associated Cardiotoxicity and for Enhanced Cardiomyocyte Survival.

Doxorubicin (DOX) is a widely used and effective anticancer drug. However, it shows high cardiotoxicity in several patients. The exact biological mechanisms of DOX-induced cardiotoxicity remain unclear. In the present study, we developed and assessed novel injectable hydrogel matrices combined with nanoparticles and secretome biomolecules to reduce DOXinduced cytotoxicity in human stem cell-derived cardiomyocytes. A Fe2O3 nanoparticle-loaded biocompatible silk sericin nanocomposite form was fabricated and used as an injectable carrier for secretome for in vivo cardiomyocyte metabolism. The formulated hydrogels carrying secretome were analyzed in vitro for proliferation, migration, and tube formation of human stem cell-derived cardiomyocytes. Biological analyses revealed that the secretome-encapsulated florescent Fe3O2 Silk sericin (Sec@MSS) hydrogel markedly reduced calcein-PI dual staining in cardiomyocytes, revealing significantly induced apoptosis. Furthermore, we evaluated the mitochondrial membrane potential for DOX and Sec@MSS hydrogel, and demonstrated apoptosis of the cardiomyocytes in the DOX-alone and Sec@MSS groups. However, the cardiotoxicity of Sec@MSS sericin was much lower than that in the DOX group, and was further evaluated via VEGFR and TUNEL analyses. The results indicate that Sec@MSS hydrogel might serve as an effective treatment agent in cardiac diseases in the future.

Prognostic indicators of new onset atrial fibrillation in patients with acute coronary syndrome.

BACKGROUND: This study aims to estimate prognostic indicators of new onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS) through 3 to 5 years of follow-up. HYPOTHESIS: For patients with ACS, some prognostic indicators can be used to predict new onset AF. METHODS: The Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) program was launched in 2014 by a collaborative initiative of the American Heart Association and Chinese Society of Cardiology. We enrolled 866 patients with ACS in a telephone follow-up program. We inquired about each patient's general health and invited each patient to our hospital for further consultation. We also performed ambulatory electrocardiography and other relevant examinations. RESULTS: A total of 743 ACS patients were included in the study. After 3 to 5 years, 50 (0.67%) patients developed AF. In multivariable Cox models adjusting for AF risk factors in ACS patients, we found that NT-proBNP [hazard ratio (HR) 2.625, 1.654-4.166, P < .05], creatine kinase-MB (CK-MB) (HR 4.279, 1.887-9.703, P < .05), and left ventricular ejection fraction (LVEF) (HR 0.01, 0.001-0.352, P < .05) were significantly associated with AF receiver operating characteristic (ROC) curves were used to determine a cutoff level for AF screening. NT-proBNP using a cutoff of 1705 ng/L resulted in a sensitivity of 58% and a specificity of 89.8%. CK-MB using a cutoff of 142.5 ng/L resulted in a sensitivity of 73.3% and a specificity of 58.3%. CONCLUSION: For patients with ACS, NT-proBNP, CK-MB, and LVEF have a considerable prognostic value for predicting whether AF would be detected during follow-up.

Liraglutide reduces systolic blood pressure in patients with type 2 diabetes mellitus: A meta-analysis of randomized trials.

The antidiabetic effect of liraglutide in patients with type 2 diabetes mellitus has been explored in several trials. We performed this meta-analysis determining the effects of liraglutide on blood pressure in these patients. Three electronic databases (Pubmed, Web of Science, and Cochrane Central) were searched for all published articles evaluating the effects of liraglutide on blood pressure in subjects with type 2 diabetes mellitus. Total 968 patients were included in 10 randomized, double-blind, placebo-controlled trials with a follow-up of 16 ± 9 weeks. Liraglutide 1.8 mg/day reduced systolic blood pressure (weighted mean differences -5.39 (95% confidence interval, -7.26, -3.51) mm Hg, p < .001) and body weight (weighted mean differences -2.07 (95% confidence interval, -2.62, -1.51) kg, p < .001) in patients with type 2 diabetes mellitus. There was no significant difference for changes of diastolic blood pressure between liraglutide 1.8 mg/day and placebo in these patients (weighted mean differences -0.53 (95% confidence interval, -1.96, 0.89) mm Hg, p > .05). The increases of heart rate were greater than placebo in patients treated with liraglutide 1.8 mg/day (weighted mean differences 6.03 (95% confidence interval, 4.78, 7.29) kg, p < .001). There was no significant correlation between reduction of systolic blood pressure and weight loss in patients treated with liraglutide 1.8 mg/day (p = .24). In conclusion, liraglutide reduces systolic blood pressure and body weight in patients with type 2 diabetes mellitus. These data suggest the beneficial effects of liraglutide on cardiovascular protection and may improve prognosis in these patients.

Acute glycemic variability on admission predicts the prognosis in hospitalized patients with coronary artery disease: a meta-analysis.

PURPOSE: Increased glycemic variability has been related with poor prognosis in patients with coronary artery disease (CAD). However, whether diabetic status or subtype of CAD could affect the association remains unknown. We performed a meta-analysis to systematically evaluate the association between the mean amplitude of glycemic excursions (MAGE) on continuous glucose monitoring and the incidence of major adverse cardiovascular events (MACEs) in CAD patients. METHODS: Relevant prospective cohort studies were identified through search of PubMed, Embase, WanFang, and CNKI databases. A random-effect model was used to pool the results. Subgroup analyses were performed to evaluate the influences of the predefined study characteristics on the outcome. RESULTS: Eleven cohort studies with 2666 hospitalized patients with acute coronary syndrome (ACS) or stable CAD for percutaneous coronary intervention were included. Pooled results showed that higher MAGE at admission was associated with higher incidence of MACEs during follow-up (adjusted relative risk [RR]: 1.84, p < 0.001; I2 = 12%). Stratified analyses showed that the association between higher MAGE and higher risk of MACEs in CAD patients were consistent in patients with or without diabetes, and in those with ACS or stable CAD (p for subgroup difference both >0.05). Significant publication bias was detected (p = 0.041). Trim-and-fill analysis retrieved three studies to generate symmetrical funnel plots. Meta-analysis that incorporated these studies showed similar results (RR: 1.80, p < 0.001). CONCLUSIONS: Increased glycemic variability may be associated with poor prognosis in CAD patients regardless of the diabetic status and the subtype of CAD.

SERP1 prevents hypoxia-reoxygenation-induced H9c2 apoptosis through activating JAK2/STAT3 pathway-dependent attenuation of endoplasmic reticulum stress.

The endoplasmic reticulum (ER) stress plays an important role in myocardial ischemia/reperfusion (MI/R) injury. SERP1, the stress-associated endoplasmic reticulum protein 1, is involved in regulating ER stress response. However, whether it associates with MI/R injury is not identified. Here, we show that SERP1 is induced in the mouse heart after MI/R injury as well as in H9c2 cells under hypoxia/reoxygenation (H/R) treatment. Additionally, SERP1 overexpression reduces H/R-induced H9c2 apoptosis. Moreover, SERP1 overexpression suppresses H/R-induced ER stress and activates JAK2/STAT3 pathway. Furthermore, JAK2/STAT3 pathway inhibition by the specific inhibitor JSI-124 minimizes the suppressive effect of SERP1 overexpression on H/R-induced ER stress and H9c2 apoptosis. Together, these results uncover the protection of SERP1 against H/R-induced H9c2 apoptosis and further relate it to JAK2/STAT3 pathway-dependent attenuation of ER stress. This study suggests SERP1 as a potential regulator invovled in the pathophysiology of MI/R injury.

A Meta-analysis of antihypertensive effect of telmisartan versus candesartan in patients with essential hypertension.

OBJECTIVE: The comparison of antihypertensive effects between telmisartan and candesartan in patients with essential hypertension has been investigated in several small studies. The results were not consistent. We performed this meta-analysis determining the antihypertensive effect of telmisartan versus candesartan in these patients. METHODS: We searched Pubmed, Web of Science, and Cochrane Central for all published studies comparing the antihypertensive effects between telmisartan and candesartan in patients with essential hypertension. RESULTS: The antihypertensive effects were assessed in 302 patients included in 4 trials with a mean follow-up of 10 ± 4 weeks. There were no significant differences between telmisartan and candesartan in reduction of systolic blood pressure (SBP) and diastolic BP (DBP) in patients with essential hypertension (weighted mean differences (WMD) for SBP 1.98 mm Hg (95% confidence interval (CI), -0.53, 4.49), p > 0.05; WMD for DBP 0.26 mm Hg (95% CI, -1.65, 2.16), p > 0.05), respectively. In a sub-analysis including 2 randomized studies, there was not a significant difference for the reduction of SBP (WMD 0.90 (95% CI, -2.88, 4.68) mm Hg, p > 0.05) or DBP (WMD -0.80 (95% CI, -3.40, 1.81) mm Hg, p > 0.05) treated with telmisartan or candesartan. CONCLUSIONS: This meta-analysis provides the evidence that the antihypertensive effects of telmisartan and candesartan are similar on SBP and DBP reduction in patients with essential hypertension, suggesting that strict designed randomized controlled trial would be helpful to compare antihypertensive effects of angiotensin II receptor blockers (ARBs) and improve the choice of ARBs in antihypertensive therapy.

Effects of ANRIL polymorphisms on the likelihood of coronary artery disease: A meta-analysis.

BACKGROUND: Whether antisense noncoding RNA in the INK4 locus (ANRIL) polymorphisms are associated with the likelihood of coronary artery disease (CAD) remains controversial. Therefore, we performed this study to explore correlation between ANRIL polymorphisms and CAD. METHODS: Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios and 95% confidence intervals were calculated. RESULTS: Nineteen studies were enrolled for analyses. Pooled overall analyses showed that rs1333040 (dominant model: P < 0.0001; recessive model: P < 0.0001; allele model: P < 0.0001), rs1333049 (dominant model: P = 0.02; allele model: P = 0.02) and rs2383207 (additive model: P = 0.004; allele model: P = 0.03) polymorphisms were significantly associated with the likelihood of CAD. Further subgroup analyses revealed that rs1333040, rs1333049, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms were all significantly correlated with the likelihood of CAD in East Asians. Additionally, rs2383206, rs10757274, and rs10757278 polymorphisms were also significantly correlated with the likelihood of CAD in Caucasians and West Asians. CONCLUSIONS: Our findings indicated that rs1333040, rs1333049, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms may serve as genetic biomarkers of CAD in East Asians. Moreover, rs2383206, rs10757274, and rs10757278 polymorphisms may also serve as genetic biomarkers of CAD in Caucasians and West Asians.

Empagliflozin reduces blood pressure and uric acid in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

The antidiabetic effect of empagliflozin in patients with type 2 diabetes mellitus has been explored in several trials. We performed this meta-analysis determining the effects of empagliflozin on blood pressure, uric acid, estimated glomerular filtration rate, blood lipids, blood glucose, and body weight in patients with type 2 diabetes mellitus. We searched three electronic databases (Pubmed, Web of Science, and Cochrane Central) for all published articles evaluating the effects of empagliflozin on blood glucose or blood pressure in subjects with type 2 diabetes mellitus. Total 5781 patients were included in 12 randomized controlled trials with a follow-up of 28 ± 22 weeks. Empagliflozin 10 or 25 mg reduced systolic and diastolic blood pressure, uric acid, hemoglobin A1c, fasting plasma glucose, and body weight in patients with type 2 diabetes mellitus (all p < 0.001). There were no differences for changes of estimated glomerular filtration rate between empagliflozin 10 or 25 mg and placebo in these patients (all p > 0.05). In conclusion, empagliflozin reduces systolic and diastolic blood pressure, uric acid, hemoglobin A1c, fasting plasma glucose, and body weight. These data suggest the beneficial effects of empagliflozin on these cardiovascular risk factors in patients with type 2 diabetes mellitus.

Antihypertensive effect of azilsartan versus olmesartan in patients with essential hypertension: a meta-analysis.

OBJECTIVE: The comparison of antihypertensive effects between azilsartan and olmesartan in patients with essential hypertension has been investigated in several studies. The results were not consistent. We performed this meta-analysis determining the antihypertensive effect of azilsartan versus olmesartan in patients with essential hypertension. METHODS: Pubmed, Web of Science, and Cochrane Central were searched for all published randomized studies comparing the antihypertensive effects between azilsartan and olmesartan in patients with essential hypertension. RESULTS: The antihypertensive effects were assessed in 1402 patients included in five trials. The reduction of office systolic blood pressure treated with azilsartan was greater than olmesartan (weighted mean differences (WMD) - 2.15 (95% confidence interval (CI), - 3.78, - 0.53) mm Hg, p < 0.01). There was no significant difference in reduction of office diastolic blood pressure between azilsartan and olmesartan (WMD - 0.99 (95% CI, - 2.06, 0.08) mm Hg, p > 0.05). The reduction of office systolic blood pressure treated with azilsartan was greater than olmesartan at same dose for both drugs (WMD - 2.24 (95% CI, - 4.03, - 0.44) mm Hg, p < 0.05), whereas there was no significant difference in reduction of office diastolic blood pressure between azilsartan and olmesartan (WMD - 0.55 (95% CI, - 1.76, 0.66) mm Hg, p > 0.05). CONCLUSIONS: This meta-analysis provides the evidence that the reduction of office systolic blood pressure treated with azilsartan was greater than olmesartan in patients with essential hypertension. These findings suggest the importance of strict designed randomized controlled trials in determining antihypertensive effects of angiotensin II receptor blockers in clinical practice.

Effect of vitamin D on ventricular remodelling in heart failure: a meta-analysis of randomised controlled trials.

OBJECTIVES: The level of vitamin D is considered to be associated with the development and progression of heart failure (HF). However, it is still unclear whether supplementation of vitamin D could improve ventricular remodelling in patients with HF. This study aimed to systematically evaluate the influence and safety of additional vitamin D supplementation on ventricular remodelling in patients with HF. DESIGN: This study is a meta-analysis of randomised controlled trials (RCTs). SETTING: The PubMed, EMBASE, CNKI, Cochrane library, Web of Science databases and grey literature were searched for RCTs regarding the effect of vitamin D on ventricular remodelling in patients with HF (from database creation to October 2017). RevMan V.5.3 software was employed for data analysis. PARTICIPANTS: Seven RCTs with a total of 465 patients, including 235 cases in the vitamin D group and 230 cases in the control group, were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF) and the incidence of adverse reactions. RESULTS: Compared with the control group, a decrease in the LVEDD (mean difference (MD)=-2.31 mm, 95% CI -4.15 to -0.47, p=0.01) and an increase in the LVEF (MD=4.18%, 95% CI 0.36 to 7.99, p=0.03) were observed in the vitamin D group. Subgroup analysis also revealed a reduced LVEDD in adults (>18 years) and adolescents (<18 years) of the vitamin D group relative to that in those of the control group. High-dose vitamin D (>4000 IU/day) was more effective at reducing the LVEDD than low-dose vitamin D (<4000 IU/day). Moreover, vitamin D supplementation was more effective at reducing the LVEDD and increasing the LVEF in patients with reduced ejection fraction than in patients without reduced ejection fraction. CONCLUSION: Vitamin D supplementation inhibits ventricular remodelling and improves cardiac function in patients with HF. TRIAL REGISTRATION NUMBER: CRD42017073893.

Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization.

Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure. During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension. Here, using Fasudil carried liposomes, we specifically inhibited the ROCK-II expression in Kupffer cells and blood monocytes. Through this macrophage/monocyte specific treatment of Fasudil, we successfully protected the liver from IRI by shifting Kupffer cells/monocytes from M1/classical to M2/patrolling phenotype in the liver and peripheral blood. Our finding provides novel insights into the macrophage/monocyte-specific drug delivery and the treatment of liver IRI.

Effect of ticagrelor versus prasugrel on platelet reactivity: a meta-analysis.

BACKGROUND AND OBJECTIVE: Whether ticagrelor is superior to prasugrel in inhibiting platelet reactivity (PR) has remained unclear, possibly because different test methods have been used to determine this. Therefore, using a different test method, we performed a meta-analysis comparing the effects of ticagrelor and prasugrel on PR. METHODS AND RESULTS: PubMed, Embase, Web of Science, and Google Scholar were searched - without language restrictions (last updated on 26 February 2017) - for randomized trials comparing the effects of prasugrel with those of ticagrelor in patients with coronary artery disease. Selected studies were chosen for pooled analysis according to the inclusion and exclusion criteria. Data are presented as mean difference (MD) and 95% confidence interval. For the loading dose, using the VerifyNow-P2Y12 (VN) test, the PR was similar for both the prasugrel and ticagrelor groups [MD=10.80 (-9.81-31.40), P=0.30]. Using the vasodilatorstimulated phosphoprotein test, the PR was also similar for both the ticagrelor and prasugrel groups [MD=-2.87 (-6.35-0.60), P=0.10]. For the maintenance dose, using the VN test, the PR was lower in the ticagrelor group than in the prasugrel group [MD=-43.37 (-60.53 to -26.21), P<0.01]. Finally, using the vasodilator-stimulated phosphoprotein test, the PR was lower in the ticagrelor group than in the prasugrel group [MD=-9.23 (-15.82 to -2.64), P<0.01]. CONCLUSION: There was no difference between ticagrelor and prasugrel in terms of PR under the loading dose, but ticagrelor had a lower degree of PR under the maintenance dose. The results were not affected by the different PR test methods.

Predictive value of cystatin C in people with suspected or established coronary artery disease: A meta-analysis.

BACKGROUND AND AIMS: Circulating cystatin C has been recognized as an independent predictor of cardiovascular and all-cause mortality in the general population. We aimed to evaluate the prognostic value of baseline circulating cystatin C levels in people with suspected or established coronary artery disease (CAD) by conducting a meta-analysis. METHODS: We searched Pubmed and Embase databases up to October 2016 for prospective observational studies investigating the predictive value of elevated circulating cystatin C levels in people with suspected or established CAD. Adverse vascular outcomes included all-cause mortality, cardiovascular mortality, or total adverse vascular events consisting of death, myocardial infarction, revascularization, stroke, and heart failure. RESULTS: Ten studies involving participants with known or suspected CAD were included in this meta-analysis. When comparing the highest with the lowest cystatin C levels, the pooled hazard ratio (HR) was 2.27 (95% confidence interval [CI] 1.86-2.78) for all-cause mortality, 2.24 (95% CI 1.69-2.97) for cardiovascular mortality, and 1.87 (95% CI 1.57-2.24) for total adverse vascular events, respectively. Subgroup analysis results showed that this association was not influenced by follow-up duration, region, or CAD type. CONCLUSIONS: Elevated circulating cystatin C is independently associated with adverse vascular outcomes in people with suspected or established CAD in terms of all-cause mortality, cardiovascular mortality, and total adverse vascular events. This increased risk is probably independent of creatinine/estimated glomerular filtration rate.