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Clinical and Applied... 2024Ticagrelor is an antiplatelet drug, and its use increases the risk of bleeding. Coronary artery disease is significantly influenced by the widespread occurrence of...
PURPOSE
Ticagrelor is an antiplatelet drug, and its use increases the risk of bleeding. Coronary artery disease is significantly influenced by the widespread occurrence of diabetes mellitus. In order to decrease the incidence of clinical adverse events, a novel bleeding and thrombosis score is developed in this research.
METHODS
We conducted a retrospective analysis of patient data from two medical centers who were diagnosed with diabetes mellitus and treated with ticagrelor. We gathered information on every patient from the electronic database of the hospital and follow-up. The collected data were statistically analyzed to obtain risk factors for bleeding and ischemic events.
RESULTS
A total of 851 patients with diabetes mellitus who have been administered ticagrelor are included in our investigation. A total of 76 patients have bleeding events and 80 patients have ischemic events. The analysis of multiple variables indicates that characteristics like the age of >65, having a previous occurrence of bleeding, experiencing anemia, using aspirin, and taking atorvastatin are linked to a higher likelihood of bleeding. Additionally, the age of >65, smoking, having a history of blood clots, and having a BMI ≥ 30 are found to increase the risk of ischemia.
CONCLUSION
The AB score established in this study was better than the HAS-BLED score,and the same is true for the ABST score to the CHADS-VASc score. This new risk assessment model can potentially detect patients who are at high risk for bleeding and ischemic events. For high-risk patients, the dose of ticagrelor can be adjusted appropriately or the medication can be adjusted.(2023-09-11, ChiCTR2300075627).
Topics: Humans; Ticagrelor; Female; Male; Hemorrhage; Aged; Retrospective Studies; Middle Aged; Diabetes Mellitus; Platelet Aggregation Inhibitors; Risk Factors; Ischemia; Thrombosis
PubMed: 38780348
DOI: 10.1177/10760296241254107 -
Journal of Physiological Investigation Mar 2024Arteriosclerosis (AS) is a chronic inflammatory disease and Buyang Huanwu decoction (BHD) has been identified as an anti-atherosclerosis effect, and the study is aimed...
Arteriosclerosis (AS) is a chronic inflammatory disease and Buyang Huanwu decoction (BHD) has been identified as an anti-atherosclerosis effect, and the study is aimed to investigate the underlying mechanism. The E4 allele of Apolipoprotein E (ApoE) is associated with both metabolic dysfunction and an enhanced pro-inflammatory response, ApoE-knockout (ApoE-/-) mice were fed with a high-fat diet to establish an arteriosclerosis model and treated with BHD or atorvastatin (as a positive control). The atherosclerotic plaque in each mouse was evaluated using Oil red O Staining. Elisa kits were used to evaluate blood lipid, interleukin-6 (IL-6), IL-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), IL-4, IL-10, and tumor growth factor beta (TGF-β) contents, while Western blot was applicated to measure inducible nitric oxide synthase (iNOS), arginase I (Arg-1) expression. Meanwhile, pyruvate kinase M2 (PKM2), hypoxia-inducible factor-1 alpha (HIF-1α) and its target genes glucose transporter type 1 (GLUT1), lactate dehydrogenase A (LDHA), and 3-phosphoinositide-dependent kinase 1 (PDK1), as well as IL-6, IL-1β, TNF-α, IL-4, IL-10, and TGF-β were evaluated by the quantitative reverse transcription-polymerase chain reaction. BHD treatment significantly reduced body weight and arteriosclerosis plaque area and blood lipid levels including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Meanwhile, BHD demonstrated a significant suppression of M1 polarization, by decreased secretion of iNOS and pro-inflammatory factors (IL-6, IL-1β, and TNF-α) in ApoE-/- mice. The present study also revealed that BHD promotes the activation of M2 polarization, characterized by the expression of Arg-1 and anti-inflammatory factors (IL-4 and IL-10). In addition, PKM2/HIF-1α signaling was improved by M1/M2 macrophages polarization induced by BHD. The downstream target genes (GLUT1, LDHA, and PDK1) expression was significantly increased in high fat feeding ApoE-/- mice, and those of which were recused by BHD and Atorvastatin. These results suggested that M1/M2 macrophages polarization produce the inflammatory response against AS progress after BHD exposure.
Topics: Animals; Drugs, Chinese Herbal; Mice; Atherosclerosis; Macrophages; Male; Apolipoproteins E; Disease Models, Animal; Mice, Knockout, ApoE; Mice, Knockout; Mice, Inbred C57BL; Cytokines
PubMed: 38780292
DOI: 10.4103/ejpi.EJPI-D-23-00040 -
Immunity, Inflammation and Disease May 2024Kawasaki disease (KD) is an autoimmune disease with cardiovascular disease as its main complication, mainly affecting children under 5 years old. KD treatment has made...
BACKGROUND
Kawasaki disease (KD) is an autoimmune disease with cardiovascular disease as its main complication, mainly affecting children under 5 years old. KD treatment has made tremendous progress in recent years, but intravenous immunoglobulin (IVIG) resistance remains a major dilemma. Bibliometric analysis had not been used previously to summarize and analyze publications related to IVIG resistance in KD. This study aimed to provide an overview of the knowledge framework and research hotspots in this field through bibliometrics, and provide references for future basic and clinical research.
METHODS
Through bibliometric analysis of relevant literature published on the Web of Science Core Collection (WoSCC) database between 1997 and 2023, we investigated the cooccurrence and collaboration relationships among countries, institutions, journals, and authors and summarized key research topics and hotspots.
RESULTS
Following screening, a total of 364 publications were downloaded, comprising 328 articles and 36 reviews. The number of articles on IVIG resistance increased year on year and the top three most productive countries were China, Japan, and the United States. Frontiers in Pediatrics had the most published articles, and the Journal of Pediatrics had the most citations. IVIG resistance had been studied by 1889 authors, of whom Kuo Ho Chang had published the most papers.
CONCLUSION
Research in the field was focused on risk factors, therapy (atorvastatin, tumor necrosis factor-alpha inhibitors), pathogenesis (gene expression), and similar diseases (multisystem inflammatory syndrome in children, MIS-C). "Treatment," "risk factor," and "prediction" were important keywords, providing a valuable reference for scholars studying this field. We suggest that, in the future, more active international collaborations are carried out to study the pathogenesis of IVIG insensitivity, using high-throughput sequencing technology. We also recommend that machine learning techniques are applied to explore the predictive variables of IVIG resistance.
Topics: Humans; Bibliometrics; Drug Resistance; Immunoglobulins, Intravenous; Mucocutaneous Lymph Node Syndrome
PubMed: 38775687
DOI: 10.1002/iid3.1277 -
Frontiers in Pharmacology 2024The purpose of this study is to identify the relationship between coenzyme Q 10 (CoQ10)-related gene polymorphisms and statin-related myotoxicity (SRM).
INTRODUCTION
The purpose of this study is to identify the relationship between coenzyme Q 10 (CoQ10)-related gene polymorphisms and statin-related myotoxicity (SRM).
METHODS
We retrospectively analyzed prospectively collected samples from February to May 2021. To investigate the association between CoQ10-related genetic factors and SRM, we selected 37 single nucleotide polymorphisms from five genes (, and ). The odds ratio (OR) and adjusted OR with 95% confidence intervals (CI) were calculated for univariate and multivariable logistic regression analyses, respectively.
RESULTS
A total of 688 stroke patients were included in the analysis, including 56 SRM cases. In the multivariable analysis, two models were constructed using demographic factors only in model I, and demographic and genetic factors in model II. Compared to other statins, atorvastatin decreased the SRM risk whereas ezetimibe use increased the SRM risk in model I and model II. Patients with rs4693075 G allele, rs11548336 TT genotype, and rs10849757 A allele had a 2.9-fold (95% CI: 1.6-5.3), 1.9-fold (95% CI: 1.1-3.5), and 3.3-fold (95% CI: 1.5-8.3) higher risk of SRM, respectively.
CONCLUSION
This study could be utilized to develop a personalized medicine strategy in patients treated with statins.
PubMed: 38774208
DOI: 10.3389/fphar.2024.1358567 -
BMC Gastroenterology May 2024Many old people have at least one chronic disease. As a result, multiple drugs should be used. Gastrointestinal complications may occur because of the harmful effects of...
BACKGROUND
Many old people have at least one chronic disease. As a result, multiple drugs should be used. Gastrointestinal complications may occur because of the harmful effects of these chronic drugs on the stomach. The study aimed to assess the prevalence of upper gastrointestinal complications in patients taking chronic medications, the severity of these symptoms, and whether they take any gastro-protective drugs or not.
METHODOLOGY
This was a cross-sectional study through face-to-face questionnaires from internal outpatient clinics at a specialized hospital. Patients with chronic diseases who were taking at least one chronic medication were included in the study. Data Collection Form was used to gather information. The Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) was used to evaluate the severity of the upper gastrointestinal symptoms. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 21.
RESULTS
A total of 400 patients with chronic diseases and using multiple medications were included. Among them, 53.8% were females and 56% were married, 58.5% were unemployed, 70% were not smokers, the mean age was 54.7 ± 17.5 years. The most common comorbid diseases among the patients were diabetes, hypertension, and arthritis, with percentages of 44.3%, 38%, and 27.3%, respectively. The mean number of chronic medications used was 3.36 ± 1.6 with a range of 1 to 9. The most commonly used was aspirin with a percentage of 50%, followed by atorvastatin, bisoprolol, and insulin with percentages of 29.5%, 25%, and 20.3%, respectively. Among the 400 participants, 362 (90.5%) suffered from upper gastrointestinal side effects like indigestion (65.8%), heartburn (78.3%), nausea (48.8%), and regurgitation (52.0%). Based on SF-LDQ scoring, of the 400 respondents, 235(58.8%), 109(27.3%) and 18(4.5%) suffered from mild, moderate and severe dyspepsia, respectively. A high percentage 325 (81.3%) of participants were prescribed gastro-protective medications. Proton pump inhibitors were the most prescribed group in 209 (52.3%) patients. Dyspepsia was significantly associated with older age (p-value = 0.001), being educated (p-value = 0.031), not being single (p-value < 0.001), having health insurance (p-value = 0.021), being a smoker (p-value = 0.003), and using ≥ 5 medications (p-value < 0.001).
CONCLUSION
Upper gastrointestinal complications among patients with chronic diseases were very common. Fortunately, the symptoms were mild in most cases. The risk increased with age and using a higher number of medications. It is important to review patients' medications and avoid overuse of them, in addition to use gastro-protective agents when needed.
Topics: Humans; Female; Male; Cross-Sectional Studies; Middle Aged; Prevalence; Chronic Disease; Gastrointestinal Diseases; Aged; Adult; Severity of Illness Index; Comorbidity; Arabs; Dyspepsia; Surveys and Questionnaires; Polypharmacy
PubMed: 38773426
DOI: 10.1186/s12876-024-03267-y -
Advances in Therapy Jul 2024Fixed-dose combinations (FDCs) of angiotensin II receptor blockers, calcium channel blockers, and statins are conventional therapeutic interventions prescribed for... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Pharmacokinetic Comparison of a Fixed-Dose Combination of Candesartan Cilexetil/Amlodipine/Atorvastatin Versus Co-administration of Individual Formulations in Healthy Participants.
INTRODUCTION
Fixed-dose combinations (FDCs) of angiotensin II receptor blockers, calcium channel blockers, and statins are conventional therapeutic interventions prescribed for cardiovascular diseases. This study aimed at drawing a comparison between the pharmacokinetics and safety of an FDC and the corresponding individual formulations in healthy subjects.
METHODS
A randomized, open-label, single-dose, three-sequence, three-period, partially repeated crossover study was conducted with a cohort of healthy volunteers. A 14-day washout period was maintained between each of the three periods. In this study, candesartan cilexetil, amlodipine, and atorvastatin was administered orally as FDCs of 16/10/40 mg in study 1 and 16/5/20 mg in study 2. The maximum plasma concentration (C) and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC) of candesartan, amlodipine, and atorvastatin were estimated as the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the FDC to individual formulations. If the within-subject coefficient of variation (CV) of C was greater than 0.3, the bioequivalence (BE) range calculated using the reference-scaled average bioequivalence was used to assess whether the 90% CI was within the BE range.
RESULTS
The GMRs (90% CIs) for the AUC for candesartan and amlodipine were 0.9612 (0.9158-1.0089)/0.9965 (0.9550-1.0397) and 1.0033 (0.9800-1.0271)/1.0067 (0.9798-1.0344), and the GMRs (90% CIs) for C were 0.9600 (0.8953-1.0294)/0.9851 (0.9368-1.0359) and 1.0198 (0.9950-1.0453)/1.0003 (0.9694-1.0321) in studies 1 and 2, respectively. The extended BE ranges calculated from the CV of the C of atorvastatin were 0.7814-1.2797 and 0.7415-1.3485, respectively. The GMRs (90% CIs) for the AUC of atorvastatin were 1.0532 (1.0082-1.1003)/1.0252 (0.9841-1.0680), and the GMRs (90% CIs) for C were 1.0630 (0.9418-1.1997)/0.9888 (0.8792-1.1120) in studies 1 and 2, respectively.
CONCLUSION
The C and AUC values of candesartan cilexetil/amlodipine/atorvastatin 16/10/40 mg and 16/5/20 mg, respectively, were within the BE ranges. There were no clinically significant differences in safety between the two formulations.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, study 1: NCT04478097; study 2: NCT04627207.
Topics: Humans; Biphenyl Compounds; Amlodipine; Benzimidazoles; Tetrazoles; Male; Cross-Over Studies; Adult; Drug Combinations; Female; Atorvastatin; Young Adult; Area Under Curve; Middle Aged; Angiotensin II Type 1 Receptor Blockers; Calcium Channel Blockers; Therapeutic Equivalency; Antihypertensive Agents; Heptanoic Acids; Healthy Volunteers
PubMed: 38771476
DOI: 10.1007/s12325-024-02869-y -
Heliyon May 2024Statins are widely used to reduce the risk of cardiovascular disease (CVD). Patients with end-stage renal disease (ESRD) on hemodialysis have significantly increased...
BACKGROUND
Statins are widely used to reduce the risk of cardiovascular disease (CVD). Patients with end-stage renal disease (ESRD) on hemodialysis have significantly increased risk of developing CVD. Statin treatment in these patients however did not show a statistically significant benefit in large trials on a patient cohort level.
METHODS
We generated gene expression profiles for statins to investigate the impact on cellular programs in human renal proximal tubular cells and mesangial cells in-vitro. We subsequently selected biomarkers from key statin-affected molecular pathways and assessed these biomarkers in plasma samples from the AURORA cohort, a double-blind, randomized, multi-center study of patients on hemodialysis or hemofiltration that have been treated with rosuvastatin. Patient clusters (phenotypes) were created based on the identified biomarkers using Latent Class Model clustering and the associations with outcome for the generated phenotypes were assessed using Cox proportional hazards regression models. The multivariable models were adjusted for clinical and biological covariates based on previously published data in AURORA.
RESULTS
The impact of statin treatment on mesangial cells was larger as compared with tubular cells with a large overlap of differentially expressed genes identified for atorvastatin and rosuvastatin indicating a predominant drug class effect. Affected molecular pathways included TGFB-, TNF-, and MAPK-signaling and focal adhesion among others. Four patient clusters were identified based on the baseline plasma concentrations of the eight biomarkers. Phenotype 1 was characterized by low to medium levels of the hepatocyte growth factor (HGF) and high levels of interleukin 6 (IL6) or matrix metalloproteinase 2 (MMP2) and it was significantly associated with outcome showing increased risk of developing major adverse cardiovascular events (MACE) or cardiovascular death. Phenotype 2 had high HGF but low Fas cell surface death receptor (FAS) levels and it was associated with significantly better outcome at 1 year.
CONCLUSIONS
In this translational study, we identified patient subgroups based on mechanistic markers of statin therapy that are associated with disease outcome in patients on hemodialysis.
PubMed: 38765135
DOI: 10.1016/j.heliyon.2024.e30709 -
Diabetes & Metabolism Journal May 2024It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study...
Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.
BACKGROUND
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
METHODS
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
RESULTS
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events.
CONCLUSION
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
PubMed: 38763510
DOI: 10.4093/dmj.2023.0077 -
Respiratory Research May 2024Obesity is associated with airway hyperresponsiveness and lung fibrosis, which may reduce the effectiveness of standard asthma treatment in individuals suffering from...
BACKGROUND
Obesity is associated with airway hyperresponsiveness and lung fibrosis, which may reduce the effectiveness of standard asthma treatment in individuals suffering from both conditions. Statins and proprotein convertase subtilisin/kexin-9 inhibitors not only reduce serum cholesterol, free fatty acids but also diminish renin-angiotensin system activity and exhibit anti-inflammatory effects. These mechanisms may play a role in mitigating lung pathologies associated with obesity.
METHODS
Male C57BL/6 mice were induced to develop obesity through high-fat diet for 16 weeks. Conditional TGF-β1 transgenic mice were fed a normal diet. These mice were given either atorvastatin or proprotein convertase subtilisin/kexin-9 inhibitor (alirocumab), and the impact on airway hyperresponsiveness and lung pathologies was assessed.
RESULTS
High-fat diet-induced obesity enhanced airway hyperresponsiveness, lung fibrosis, macrophages in bronchoalveolar lavage fluid, and pro-inflammatory mediators in the lung. These lipid-lowering agents attenuated airway hyperresponsiveness, macrophages in BALF, lung fibrosis, serum leptin, free fatty acids, TGF-β1, IL-1β, IL-6, and IL-17a in the lung. Furthermore, the increased RAS, NLRP3 inflammasome, and cholecystokinin in lung tissue of obese mice were reduced with statin or alirocumab. These agents also suppressed the pro-inflammatory immune responses and lung fibrosis in TGF-β1 over-expressed transgenic mice with normal diet.
CONCLUSIONS
Lipid-lowering treatment has the potential to alleviate obesity-induced airway hyperresponsiveness and lung fibrosis by inhibiting the NLRP3 inflammasome, RAS and cholecystokinin activity.
Topics: Animals; Male; Mice, Inbred C57BL; Diet, High-Fat; Obesity; Mice; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pulmonary Fibrosis; Mice, Transgenic; PCSK9 Inhibitors; Atorvastatin; Mice, Obese; Proprotein Convertase 9; Antibodies, Monoclonal; Bronchial Hyperreactivity; Antibodies, Monoclonal, Humanized
PubMed: 38762465
DOI: 10.1186/s12931-024-02842-x -
Cureus Apr 2024Introduction The vast pleiotropic effect of statins has intrigued many researchers to select them as potential candidates against bacterial infections. The role of...
Introduction The vast pleiotropic effect of statins has intrigued many researchers to select them as potential candidates against bacterial infections. The role of statins against bacterial pathogens remains debatable. This study was undertaken to evaluate and compare the antibacterial effect of commonly available statins against the most frequently isolated bacterial pathogens causing respiratory tract infections in our tertiary care hospital using sputum as a sample. Materials and methods The study was conducted in the Microbiology Laboratory of our hospital. Drugs including atorvastatin, rosuvastatin, and simvastatin were purchased in pure form from Sigma Aldrich. Dimethylsulfoxide (DMSO) was used as a solvent for all three drugs. The positive controls used were gentamycin and amoxicillin for Gram-negative and Gram-positive bacteria, respectively. Data regarding all the culture and sensitivity results of sputum samples of patients admitted to the Respiratory Intensive Care Unit over the past 12 months were analyzed. The most common bacterial pathogens and isolated from sputum specimens were taken for our study. The antibacterial effect of statins was studied using two methods: the agar cup diffusion method and the broth dilution method. The zone of inhibition and minimum inhibitory concentration of the drugs were calculated and analyzed. Statistical analysis was performed using GraphPad Prism software version 10.2.0. A one-way ANOVA test was used to determine if there was any statistical difference between the different statins and antibiotic groups. An unpaired t-test was used to determine the statistical difference between the statins. Results and discussion For the agar cup diffusion method, our results displayed a lack of antibacterial activity of all three statins atorvastatin, rosuvastatin, and simvastatin against all three bacterial strains and after overnight incubation by agar cup method at concentrations of 3.125 μg/ml, 6.25 μg/ml, 12.5 μg/ml, 25 μg/ml and 50 μg/ml, respectively. The zone of inhibition observed was less than 4 mm (resistant) for all the serial dilutions of atorvastatin, rosuvastatin, and simvastatin. For the broth dilution method, the ANOVA test showed amoxicillin and gentamicin to have high statistically significant microbial growth inhibitory activity (p-value < 0.005) compared to atorvastatin and rosuvastatin. Statistically, though atorvastatin showed significant antimicrobial activity compared to normal saline and rosuvastatin, this was not considered clinically significant as the antimicrobial activity shown by atorvastatin was very negligible compared to the controls used and did not correspond to the serial dilutions of the drug. Conclusion Atorvastatin, rosuvastatin, and simvastatin lacked antibacterial activity against all three bacterial strains isolated from sputum specimens: and . Hence, the use of statins as an antimicrobial drug for respiratory tract infections has limited applications.
PubMed: 38741867
DOI: 10.7759/cureus.58108