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Current Health Sciences Journal 2024Atorvastatin is an HMG-CoA reductase inhibitor that is prescribed to prevent adverse cardiovascular events by reducing blood total cholesterol (Chol) and LDL-Chol. Here...
Atorvastatin is an HMG-CoA reductase inhibitor that is prescribed to prevent adverse cardiovascular events by reducing blood total cholesterol (Chol) and LDL-Chol. Here we report a case related to an unusual response of HDL-Chol upon the administration of atorvastatin following an acute myocardial infarction. While atorvastatin substantially reduced LDL and triglycerides (TAG) of the patient as desired, it also lowered the HDL significantly, and in a dose-dependent manner. It is widely known that statins have several major side effects, but a significant suppression on HDL has been rarely reported so far. In addition, atorvastatin is deemed the likely cause for unintentional weight loss of this subject.
PubMed: 38846474
DOI: 10.12865/CHSJ.50.01.19 -
Respiratory Medicine Case Reports 2024There is no approved drug treatment for autoimmune pulmonary alveolar proteinosis (APAP), although traditionally requires complex treatments such as whole lung lavage...
There is no approved drug treatment for autoimmune pulmonary alveolar proteinosis (APAP), although traditionally requires complex treatments such as whole lung lavage (WLL). We herein report on a 67-year-old man diagnosed with APAP. Treatment with atorvastatin (5 mg daily) resulted in significant improvement in symptoms, lung function, and computed tomography findings, with enhanced oxygenation, although serum anti-GM-CSF antibody levels remained elevated. This case suggests that the remission observed in this case could potentially be attributed to a direct effect of atorvastatin within the pulmonary alveoli. Statins may be considered as one of the treatment options for APAP.
PubMed: 38845787
DOI: 10.1016/j.rmcr.2024.102042 -
World Journal of Cardiology May 2024Lipid treatment practices and levels in post-acute myocardial infarction (AMI) patients, which are crucial for secondary prevention.
BACKGROUND
Lipid treatment practices and levels in post-acute myocardial infarction (AMI) patients, which are crucial for secondary prevention.
AIM
To evaluate the lipid treatment practices and lipid levels in post-myocardial infarction (MI) patients at a tertiary care hospital in Pakistan.
METHODS
In this cross-sectional study, we analyzed patients who had experienced their first AMI event in the past 3 years. We assessed fasting and non-fasting lipid profiles, reviewed statin therapy prescriptions, and examined patient compliance. The recommended dose was defined as rosuvastatin ≥ 20 mg or atorvastatin ≥ 40 mg, with target total cholesterol levels set at < 160 mg/dL and target low-density lipoprotein cholesterol (LDL-C) at < 55 mg/dL.
RESULTS
Among 195 patients, 71.3% were male, and the mean age was 57.1 ± 10.2 years. The median duration since AMI was 36 (interquartile range: 10-48) months and 60% were diagnosed with ST-segment elevation MI. Only 13.8% of patients were advised to undergo lipid profile testing after AMI, 88.7% of patients were on the recommended statin therapy, and 91.8% of patients were compliant with statin therapy. Only 11.5% had LDL-C within the target range and 71.7% had total cholesterol within the target range. Hospital admission in the past 12 months was reported by 14.4%, and the re-admission rate was significantly higher among non-compliant patients (37.5% 5.6%). Subsequent AMI event rate was also significantly higher among non-compliant patients (43.8% 11.7%).
CONCLUSION
Our study highlights that while most post-AMI patients received the recommended minimum statin therapy dose, the inadequate practice of lipid assessment may compromise therapy optimization and raise the risk of subsequent events.
PubMed: 38817645
DOI: 10.4330/wjc.v16.i5.282 -
JAMA Neurology May 2024Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic...
IMPORTANCE
Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis.
OBJECTIVE
To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis.
DESIGN, SETTING, AND PARTICIPANTS
The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed.
INTERVENTIONS
Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90).
MAIN OUTCOMES AND MEASURES
The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome.
RESULTS
A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively.
CONCLUSIONS AND RELEVANCE
Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03635749.
PubMed: 38805216
DOI: 10.1001/jamaneurol.2024.1433 -
Journal of Geriatric Cardiology : JGC Apr 2024Chronic renal failure (CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF...
BACKGROUND
Chronic renal failure (CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia (VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process.
METHODS
A total of 48 rats were randomly divided into sham operation group (Sham group), CRF group, CRF + atorvastatin group (CRF + statin group), and CRF + etanercept group (CRF + rhTNFR-Fc group). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43 (GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay.
RESULTS
Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay, immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fc group.
CONCLUSIONS
In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.
PubMed: 38800544
DOI: 10.26599/1671-5411.2024.04.007 -
Atherosclerosis May 2024Activation of vascular smooth muscle cell inflammation is recognised as an important early driver of vascular disease. We have previously identified the let-7 miRNA...
BACKGROUND AND AIMS
Activation of vascular smooth muscle cell inflammation is recognised as an important early driver of vascular disease. We have previously identified the let-7 miRNA family as important regulators of inflammation in in vitro and in vivo models of atherosclerosis. Here we investigated a dual statin/let-7d-5p miRNA combination therapy approach to target human aortic SMC (HAoSMC) activation and inflammation.
METHODS
In vitro studies using primary HAoSMCs were performed to investigate the effects of let-7d-5p miRNA overexpression and inhibition. HAoSMCs were treated with combinations of the inflammatory cytokine tumor necrosis factor-α (TNF-α), and atorvastatin or lovastatin. HAoSMC Bulk RNA-seq transcriptomics of HAoSMCs revealed downstream regulatory networks modulated by let-7d-5p miRNA overexpression and statins. Proteome profiler cytokine array, Western blotting and quantitative PCR analyses were performed on HAoSMCs to validate key findings.
RESULTS
Let-7d-5p overexpression significantly attenuated TNF-α-induced upregulation of IL-6, ICAM1, VCAM1, CCL2, CD68, MYOCD gene expression in HAoSMCs (p<0.05). Statins (atorvastatin, lovastatin) significantly attenuated inflammatory gene expression and upregulated Let-7d levels in HAoSMCs (p<0.05). Bulk RNA-seq analysis of a dual Let-7d-5p overexpression/statin therapy in HAoSMCs revealed that let-7d-5p activation and statins converge on key inflammatory pathways (IL-6, IL-1β, TNF-α, IFN-γ). Let-7d-5p overexpression led to reduced expression of the ox-LDL receptor OLR1, and this was associated with lower ox-LDL uptake in HAoSMCs. In silico analysis of smooth muscle cell phenotypic switching shows that overexpression of let-7d-5p in HAoSMCs maintains a contractile phenotype.
CONCLUSIONS
Targeting the Let-7 network alongside statins can modulate HAoSMC activation and attenuate key inflammatory pathway signals.
PubMed: 38796407
DOI: 10.1016/j.atherosclerosis.2024.117573 -
International Journal of Molecular... May 2024The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing...
The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing enzymes. Customizing statin therapy, including treatment with atorvastatin, may improve clinical outcomes. Currently, there is a lack of guidelines allowing the prediction of the therapeutic efficacy of lipid-lowering statin therapy. This study aimed to determine the effects of clinically significant gene variants of on atorvastatin therapy in patients with acute coronary syndromes. In total, 92 patients with a confirmed diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) were sequenced for target regions within the gene on the Illumina Miniseq system. The CYP2C19 poor metabolizer phenotype (carriers of , , and alleles) was detected in 29% of patients. These patients had significantly lower responses to treatment with atorvastatin than patients with the normal metabolizer phenotype. CYP2C19-metabolizing phenotype, patient age, and smoking increased the odds of undertreatment in patients (∆LDL-C (mmol/L) < 1). These results revealed that the CYP2C19 phenotype may significantly impact atorvastatin therapy personalization in patients requiring LDL lipid-lowering therapy.
Topics: Humans; Cytochrome P-450 CYP2C19; Atorvastatin; Female; Male; Acute Coronary Syndrome; Middle Aged; Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Alleles
PubMed: 38791422
DOI: 10.3390/ijms25105385 -
Medicine May 2024Hyperlipidemia is a common feature of chronic diseases. The aim of this work was designed to assess the role of probiotics (Lactobacillus casei Zhang, Bifidobactetium... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hyperlipidemia is a common feature of chronic diseases. The aim of this work was designed to assess the role of probiotics (Lactobacillus casei Zhang, Bifidobactetium animalis subsp. lactis V9, and Lactobacillus plantarum P-8) in the treatment of hyperlipidemia.
METHODS
Thirty three patients with hyperlipidemia were randomly divided into a probiotic group (n = 18) and a control group (n = 15). The probiotic group was administered probiotics (2 g once daily) and atorvastatin 20 mg (once daily), and the control group was administered a placebo (2 g once daily) and atorvastatin 20 mg (once daily). Serum and fecal samples were gathered for subsequent analyses.
RESULTS
Time had a significant effect on the total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) levels in the probiotic and control groups (P < .05). The gut microbial abundance in the probiotic group was markedly higher than that in the control group following 3-month probiotic treatment (P < .05). At the phylum level, probiotics exerted no notable effects on the relative abundance of Firmicutes, Bacteroidetes, and Actinobacteria but elevated that of Tenericutes and reduced Proteobacteria. At the genus level, probiotics increased the relative abundance of Bifidobacterium, Lactobacillus, and Akkermansia, and decreased that of Escherichia, Eggerthella, and Sutterella relative to the control group in months 1, 2, and 3 (P < .05).
CONCLUSIONS
Probiotics optimize the gut microbiota structure and decrease the amount of harmful bacteria in patients with hyperlipidemia. Probiotics can influence the composition of gut microorganisms and increase their diversity and abundance in vivo. It is recommended to use probiotics combined with atorvastatin to treat patients with hyperlipidemia.
Topics: Humans; Atorvastatin; Probiotics; Hyperlipidemias; Double-Blind Method; Male; Female; Middle Aged; Gastrointestinal Microbiome; Adult; Treatment Outcome; Triglycerides; Cholesterol, LDL; Anticholesteremic Agents; Lactobacillus plantarum; Feces; Aged; Combined Modality Therapy
PubMed: 38788020
DOI: 10.1097/MD.0000000000037883 -
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