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- Volume 22, Issue 4, 2024
Current Vascular Pharmacology - Volume 22, Issue 4, 2024
Volume 22, Issue 4, 2024
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Endocrine Disorders and Peripheral Arterial Disease - A Series of Reviews Cushing Syndrome-Cortisol Excess
Cushing syndrome (CS), characterised by endogenous or exogenous glucocorticoid hormone excess, is associated with several systemic complications, including impaired glucose metabolism, which often becomes clinically manifest as diabetes mellitus (DM). In addition, CS can harm the arterial wall because of hyperglycaemia, dyslipidaemia, hepatic steatosis, and central obesity. These metabolic disorders promote atherosclerosis by synthesising adipokines, leptin, and proinflammatory cytokines. Lower limb arterial complications in CS are common and significantly impact morbidity and mortality. Furthermore, CS, in combination with DM, is likely to cause more diffuse vascular disease that predominantly affects distal arterial beds. In conclusion, CS promotes atherosclerosis, including peripheral artery disease, by causing functional and morphological deterioration of the arterial vessel wall and increasing the presence of classical risk factors of atherosclerosis.
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Efficacy and Safety of Bempedoic Acid in Patients with High Cardiovascular Risk: An Update
Authors: Ozge T. Caklili, Manfredi Rizzo and Mustafa CesurStatins play a significant role in the prevention of cardiovascular (CV) diseases (CVDs); however, non-adherence with statin treatment or statin intolerance (mainly attributed to muscleassociated side effects) is not uncommon. New agents such as bempedoic acid (BA) can provide more treatment options. BA is administered orally, once daily, at a dose of 180 mg in current clinical practice. It can decrease circulating low-density lipoprotein cholesterol (LDL-C) levels by nearly 30% as monotherapy or by 20% as an add-on to statins. CV outcome studies have shown that BA decreases major adverse CV event risk in patients with established CVD or high CV risk by 13%. When patients with high CV risk were analyzed alone, the risk reduction was 30%. Its side effects include a rise in serum uric acid levels and liver enzyme activity, whereas it does not increase diabetes risk as statins do. BA can be used as adjunctive therapy to statins in patients at high CV risk in whom lipid targets cannot be achieved or as an alternative to statins in patients with statin intolerance.
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Roles of MDA-LDL/OX-LDL/LOX-1 and TNF-α/TLR4/NF-ΚB Signaling Pathways in Myocardial Damage by Implantations of Cardiac Pacemakers in Elderly Patients
Authors: Xia Li, Wenhang Zhou, Dianxuan Guo, Youdong Hu, Hualan Zhou and Ying ChenIntroduction: Permanent pacemakers are an established treatment for sick sinus syndrome and high-grade atrioventricular block. Permanent cardiac pacemaker implantations may damage the myocardium. Objective: This study evaluated markers of myocardial injury, oxidative stress and inflammation in elderly patients with permanent pacemaker implantations. Methods: Various markers were measured at 1, 2, 3 and 4 months after permanent pacemaker implantations in elderly patients. Results: The levels of high-sensitivity troponin T (hsTnT), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), malondialdehyde-modified low-density lipoprotein (MDA-LDL), oxidized low-density lipoprotein (OX-LDL), tumour necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-ΚB) were increased in 2-month group compared with control and 1- month groups (P<0.001), and were further increased at 4-month group compared with 2- and 3- month groups after pacemaker implantations (P<0.001). Patients with dual-chamber pacemakers had higher levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-ΚB than patients with single chamber pacemakers (P<0.001). Patients who underwent the pacemakers with the active fixation leads had raised levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-ΚB compared patients with pacemakers using the passive fixation leads (P<0.001). Myocardial blood flows in 3-month and 4-month groups were lower than 1-month and 2-month groups (P<0.001). Conclusion: Levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-ΚB were elevated in elderly patients with permanent pacemaker implantations and the activations of oxidative stress and pro-inflammatory signalling pathways may be associated with myocardial damages and ischemia after pacemaker implantations in elderly patients.
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Sedation with Ketamine-Propofol in Patients Undergoing Transcatheter Aortic Valve Implantation: A Comparative Retrospective Study on General Anesthesia
Authors: Nurdan Yilmaz, Yasar G. Gul and Murat UgurlucanBackground: Transcatheter aortic valve implantation (TAVI) is used for patients with severe aortic stenosis who are at high risk for surgery. Since these patients are elderly and have comorbidities, their management is of great importance. Objectives: This retrospective study compares two anesthesia techniques during TAVI: sedation (ketamine and propofol) and general anesthesia. Methods: Patients with severe aortic stenosis undergoing TAVI during 2021 in our hospital were retrospectively screened. Demographic data, comorbidities, anesthesia management, complications, and mortality of the patients were obtained from the records. Results: There were 137 patients treated with TAVI; 74 (54%) patients had sedation and 63 (46%) had general anesthesia. When the anesthesia management was evaluated, no significant difference in mortality was observed between the patients who received general anesthesia and sedation. After univariate and multivariate logistic regression analyses were performed to investigate factors having an impact on mortality, anemia (only in univariate analysis) in the whole study population was a statistically significant risk factor for mortality in patients undergoing TAVI (p<0.014). Conclusion: There was no significant difference in mortality in terms of anesthesia management. Anemia was a risk factor for mortality (only in univariate analysis) in the whole study population. We concluded that conscious sedation with ketamine and propofol is effective and safe for TAVI procedures compared to general anesthesia.
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Identification of Critical Genes Differentiating Stable and Unstable Atherosclerotic Plaques: A Bioinformatic and Computational Analysis
Background: Identification of biomarkers to distinguish between stable and unstable plaque formation would be very useful to predict plaque vulnerability. Methods: We downloaded microarray profiles of gene set enrichment (GSE) accession numbers including GSE71226 and GSE20680 (group A: containing healthy vs stable plaque samples) and GSE62646 and GSE34822 (group B: containing stable vs unstable plaque samples) from Gene expression omnibus (GEO) database. Differentially expressed genes were compared in both data sets of each group. Results: Ten and 12 key genes were screened in groups A and B, respectively. Gene Ontology (GO) enrichment was applied by the plugin “BiNGO” (Biological networks gene ontology tool) of the Cytoscape. The key genes were mostly enriched in the biological process of positive regulation of the cellular process. The protein-protein interaction and co-expression network were analyzed by the STRING (search tool for the retrieval of interacting genes/proteins) and GeneMANIA (gene multiple association network integration algorithm) plugin of Cytoscape, respectively, which showed that Epidermal growth factor (EGF), Heparin-binding EGF like growth factor (HBEGF), and Matrix metalloproteinase 9 (MMP9) were at the core of the network. Further validation of key genes using two datasets showed that Phosphodiesterase 5A (PDE5A) and Protein S (PROS1) were decreased in unstable plaques, while Suppressor of cytokine signaling (SOCS3), HBEGF, and Leukocyte immunoglobulin-like receptor B4 (LILRB4) were increased. Conclusion: The present study used several datasets to identify key genes associated with stable and unstable atherosclerotic plaque.
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Cardiovascular Protection of Aspirin in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis
Authors: Ting Chen, Yunlei Deng and Rong GongPurpose: To evaluate aspirin's cardiovascular (CV) protective effect in chronic kidney disease (CKD) patients. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science (up to December 2022) for randomized controlled trials (RCTs) and observational studies comparing aspirin with placebo in CKD patients for the prevention of CV disease (CVD). Efficacy outcomes included CVD, heart failure, myocardial infarction, stroke, CV and all-cause mortality; safety outcomes included major bleeding, minor bleeding, and renal events. Results: Six RCTs and 6 observational studies, including 35,640 participants, met the inclusion criteria and reported relevant CV outcomes, with a mean follow-up of 46.83 months. The pooled data showed aspirin had no significant preventive effect on CVD events (RR=1.03; 95% CI, 0.84-1.27). However, CV mortality was significantly reduced in the aspirin group (RR=0.74; 95% CI, 0.58-0.95). Furthermore, aspirin use did not increase the risk of major bleeding and renal events but significantly increased minor bleeding events (RR=2.11; 95% CI, 1.30-3.44). Renal events were significantly increased after sensitivity analysis (RR=1.10; 95% CI, 1.04-1.16). Conclusion: Aspirin did not prevent CV events, with a significantly increased risk of minor bleeding and renal events. Besides, aspirin use had no statistically significant reduction in the risk of all-cause mortality but had a statistically significant reduction in the risk of CV mortality.
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Statins and Venous Thromboembolic Disease - Where are we Now?
Authors: Pavel Poredoš, Debabrata Mukherjee and Aleš BlincClassical risk factors for atherosclerosis also play a role in the pathogenesis of venous thromboembolism (VTE). Low-density lipoprotein cholesterol has prothrombotic and endothelium- deteriorating effects which are not limited to the arterial system. The association between hypercholesterolemia and VTE has been established, but the benefits of statins in the prevention of VTE assessed by observation studies seemed equivocal. The large, randomized trial Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) recorded the occurrence of VTE as a protocol-specified endpoint and reported a reduced incidence of VTE among subjects taking 20 mg of rosuvastatin daily vs placebo (hazard ratio 0.57; 95% confidence interval 0.37-0.86; p=0.007). Similar results were confirmed by meta-analyses of observation studies and randomized trials. Recently, a Mendelian randomization study that took the presence of gene variants coding for less efficient hydroxymethyl-glutaryl coenzyme A reductase activity as a proxy for statin treatment, confirmed a small, but significant negative association between the score of selected genetic polymorphisms and the incidence of VTE. However, since the protective effects of statins are limited, they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment.
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Volumes & issues
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Volume 22 (2024)
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Volume 21 (2023)
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Volume 20 (2022)
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Volume 19 (2021)
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Volume 18 (2020)
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Volume 17 (2019)
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Volume 16 (2018)
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Volume 15 (2017)
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Volume 14 (2016)
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Volume 13 (2015)
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Volume 12 (2014)
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Volume 11 (2013)
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Volume 10 (2012)
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Volume 9 (2011)
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Volume 8 (2010)
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Volume 7 (2009)
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Volume 6 (2008)
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Volume 5 (2007)
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Volume 4 (2006)
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Volume 3 (2005)
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Volume 2 (2004)
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Volume 1 (2003)