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Background Drug-induced liver injury is one of the most common adverse drug reactions, and atorvastatin is one of the widely used statin lipid-lowering drugs in clinical practice, which is susceptible to hepatic injury. Currently, there is limited research data on the clinical characteristics of liver injury induced by atorvastatin. Objective To investigate the clinical characteristics of liver injury induced by atorvastatin, so as to improve clinicians' understanding of liver injury induced by atorvastation. Methods The patients who were hospitalized and treated with atorvastatin in the First Affiliated Hospital of Guangxi Medical University from January 2012 to August 2022, developed liver injury and were evaluated as liver injury induced by atorvastation based on Roussel Uclaf Causality Assessment Method were selected, and analyzed on clinical characteristics. Results A total of 84 cases of liver injury induced by atorvastation were diagnosed by Causality Assessment Method. The patients with liver injury induced by atorvastation were more male (72.6%), with an average age of (60.2±11.5) years, and all of them were comorbid with the underlying diseases (100.0%) ; two cases (2.4%) reached moderate liver injury, and the cure or improvement rate after treatment reached 100.0%. According to the stage of the disease, the main manifestation was an acute course (100.0%) ; according to the damaged target cells, the mixed type was the most frequent (60.7%), followed by the cholestasis type (26.2%) and the hepatocyte type (11.9%). The statistical results showed that 78.6% of the patients with liver injury occurred within 3 months after taking atorvastation and predominantly in the 1st to 2nd week; and 81.0% of the patients developed liver injuryat 80 defined daily dose (DDD) of cumulative atorvastation. Conclusion Liver injury induced by atorvastation occurs mostly in male, middle-aged and elderly patients patients with underlying diseases, mostly have mild liver injury and good prognosis, and the clinical types were mostly mixed type and cholestasis type. Liver injury occurs mainly within 3 months and the occurrence of liver injury induced by atorvastation was dose-dependent.

Background: Statins are widely prescribed for the management of hyperlipidemia and the prevention of cardiovascular diseases. Atorvastatin and rosuvastatin are among the most commonly used statins, with varying impacts on lipid profiles, side effect profiles, patient adherence, and health-care costs. Understanding these differences within specific populations can inform more tailored and cost-effective treatment strategies. Aims and Objectives: This study aimed to evaluate the differences in side effect management, patient outcomes, and health-care costs between atorvastatin and rosuvastatin therapies in a cohort from Coimbatore, Tamil Nadu, India. Materials and Methods: An observational study was conducted with 100 patients at the Karpagam Faculty of Medical Sciences and Research, evenly split between atorvastatin (n=50) and rosuvastatin (n=50) groups. Data on demographic characteristics, side effects, low-density lipoprotein (LDL) cholesterol reduction, medication adherence, and health-care costs were collected and analyzed. Results: The cohort had an average age of 62 years, with a higher prevalence of males (57%). Socioeconomic analysis showed 30% from low-income, 50% from middle-income, and 20% from high-income backgrounds. Side effects were more common in the atorvastatin group (35%) compared to the rosuvastatin group (28%), with muscle pain and gastrointestinal issues being predominant. Rosuvastatin treatment resulted in higher adherence rates (90%) and more significant LDL cholesterol reduction but incurred higher annual health-care costs (INR 28,000) versus atorvastatin (INR 25,000) (P=0.04). Conclusion: Both statins effectively reduced LDL cholesterol; however, rosuvastatin demonstrated higher patient adherence but at an increased cost. These findings underscore the need for individualized statin therapy that considers both clinical outcomes and economic constraints, particularly in settings with limited health-care resources.

Triple negative breast cancer (TNBC) as the most aggressive molecular subtype of breast cancer is characterized by high cancer cell proliferation and poor patient prognosis. Abnormal lipid metabolism contributes to the malignant process of cancers. Study observed significantly enhanced cholesterol biosynthesis in TNBC. However, the mechanisms underlying the abnormal increase of cholesterol biosynthesis in TNBC are still unclear. Hence, we identified a member of the serine/threonine protein kinase family PKMYT1 as a key driver of cholesterol synthesis in TNBC cells. Aberrantly high-expressed PKMYT1 in TNBC was indicative of unfavorable prognostic outcomes. In addition, PKMYT1 promoted sterol regulatory element-binding protein 2 (SREBP2)-mediated expression of enzymes related to cholesterol biosynthesis through activating the TNF/ TNF receptor-associated factor 1 (TRAF1)/AKT pathway. Notably, downregulation of PKMYT1 significantly inhibited the feedback upregulation of statin-mediated cholesterol biosynthesis, whereas knockdown of PKMYT1 promoted the drug sensitivity of atorvastatin in TNBC cells. Overall, our study revealed a novel function of PKMYT1 in TNBC cholesterol biosynthesis, providing a new target for targeting tumor metabolic reprogramming in the cancer.

Objective: According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to thedeposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongatedglycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growthfactor-β (TGF-β) promotes the expression of genes linked to proteoglycan GAG chain elongation (CHSY1 and CHST11)via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is knownto exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research wasto ascertain the influence of atorvastatin on TGF-β-stimulated expression of CHST11 and CHSY1 and associatedsignaling pathways using an in vitro model.Materials and Methods: In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubatedwith atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate thephosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNAexpression of CHST11 and CHSY1.Results: Our research results indicated that atorvastatin inhibited TGF-β-stimulated CHSY1 and CHST11 mRNAexpression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakenedTGF-β-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-β-Smad2C pathway.Conclusion: These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulationof the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by whichatorvastatin exerts its pleiotropic effects against atherosclerosis.

Background: Hypercholesterolemia is a main driver of atherosclerosis. Cholesterol-containing lipoproteins induce endothelial dysfunction and macrophage activation. Foam cell formation results from the uptake of cholesterol-containing lipoproteins by macrophages, it is an essential step in the initiation and progression of atherosclerosis. Aims and Objectives: To evaluate the efficacy and safety of alternate day versus daily dosing of atorvastatin in patients with dyslipidemia. Materials and Methods: This open-label, prospective, observational study was conducted on dyslipidemic patients who came into the medicine Outpatient Department of Dhanalakshmi Srinivasan Medical College and Hospital, Tamil Nadu. Approval for the study was taken from the Institutional Ethical Committee. The duration of the study was 3 months. The efficacy of atorvastatin was checked by noting their blood lipid profile status. Results: Out of 100 patients included in the study 79 completed the study whereas 21 patients were lost in follow-up, 42 patients were analyzed in daily dose (Group A), and 37 patients in alternate dose (Group B) of atorvastatin (20 mg). There was no statistically significant difference based on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels both prior and post-treatment in both the groups. Adverse drug reactions (ADR) profile showed a statistically significant difference between both the groups after treatment by atorvastatin (P=0.0001), with more ADRs noted in a daily dosing group. Conclusion: The results of this study show that alternate dosing of atorvastatin was better tolerated than daily dosing hence physicians can consider choosing an alternate day therapy to reduce pill burden on patients.

Objective To investigate the change in intestinal flora and its association with liver CYP2E1 in mice with li-ver injury caused by high-intensity atorvastatin (ATO). Methods According to the treatment method, 40 C57BL/6 mice were divided into low-intensity ATO group (ATO-L group), medium-intensity ATO group (ATO-M group), high-intensity ATO group (ATO-H group), and control group (CON group), with 10 rats in each group. The mice in the ATO-L group, the ATO-M group, and the ATO-H group were given 1 mL normal saline containing ATO at doses of 10, 20, and 30 mg/kg, respectively, by gavage, and those in the CON group were given an equal volume of normal saline by gavage, for 4 consecutive weeks. HE staining and transmission electron microscopy were used to observe liver pathological state. Related methods were used to measure the se-rum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10, the activity of superoxide dismutase (SOD) in liver tissue, and the mRNA expression level of CYP2E1 in liver tissue. 16SrDNA sequencing was used to analyze the distribution of intestinal flora in fresh feces of mice, and a correlation analysis was conducted to investigate the correlation of the relative abundance of bacterial genera with significant diffe-rences with the mRNA expression level of CYP2E1 and SOD activity in liver tissue. Results HE staining and transmission electron microscopy showed varying degrees of liver injury in the ATO-M and ATO-H groups. There were significant differences in the serum levels of ALT, AST, IL-6, and TNF-α and SOD activity in liver tissue between groups (F=4.57-7.74,P

Abstract Purpose Hypocholesterolemic medications similar to atorvastatin are efficient in lowering blood lipid levels; however, compared to other medications in the statin family, their impact on bone metabolism is claimed to be insufficient. The impact of atorvastatin on bone regeneration in dental implantology in individuals with hyperlipidemia who received atorvastatin in the clinic is doubtful. Methods In the study, 16 male New Zealand rabbits of 6 months were used. All rabbits were fed a high-cholesterol diet for 8 weeks, and hyperlipidemia was created. It was confirmed that the total cholesterol level in rabbits was above 105 mg/dl. A critical-sized defect was created in the mandible. The defect was closed with xenograft and membrane. Oral 10 mg/kg atorvastatin was started in the experimental group, and no drug was administered in the control group. At 16th week, animals were sacrificed. For histomorphological examination, the new bone area, osteoclast, and osteoblast activities were evaluated. Results While new bone area (45,924 µm2, p

Introduction ATP-binding cassette transporter A1 (ABCA1) encoded by ABCA1 gene is one of the important protein involved in lipid metabolism. The effect of statin therapy on dyslipidemia varies among individuals and it may be due to different genetic polymorphism. The R219K polymorphism of ABCA1 gene is found to have a significant role in the response of statin.

Objective To investigate the influence of high-dose atorvastatin on bile acid metabolism in mice with liver injury and its mechanism. Methods A total of 40 specific pathogen-free male C57BL/6 mice were randomly divided into normal saline group (group A) and low-, middle-, and high-dose atorvastatin groups (groups B, C, and D, respectively), with 10 mice in each group. After 30 days of intragastric administration of normal saline and atorvastatin at a dose of 10, 20, and 30 mg/kg, respectively, orbital blood was collected from the mice in each group, and these groups were compared in terms of the serum levels of total bile acid (TBA), endotoxin (ET), aspartate aminotransferase (AST), and alanine aminotransferase (ALT); after liver tissue samples were collected, HE staining was performed to observe the pathological changes of liver tissue, and PCR was used to measure the mRNA expression levels of the bile acid metabolism-related genes farnesoid X receptor (FXR) and multidrug resis-tance-associated protein 2 (MRP2) in liver tissue. Results The mice in group D had slight swelling, sporadic inflammatory cell infiltration, and feather-like degeneration in liver tissue. Compared with the other groups, group D had significant increases in the serum levels of TBA, ET, AST, and ALT (P

Background: Matrix metalloproteinases (MMPs) play an important role in the pathophysiology of atherosclerosis. Reportedly, statins can decrease MMP activity in patients with atherosclerotic cardiovascular disease, but this effect has not been studied in healthy individuals. Methods: MMPs 2, 7, and 9 and several other parameters were measured before and after a four-week course of moderate-dose atorvastatin (20 mg/day) in 21 healthy individuals. Results: Atorvastatin treatment resulted in lower total cholesterol, LDL-cholesterol, non-HDL-cholesterol, and triglycerides (p < 0.001 for all), but higher levels of plasma enzymes AST, ALT, CK, and LDH (p < 0.05 for all). No effect of atorvastatin on plasma MMP median concentrations was recorded. Before treatment, moderate positive significant correlations were found between MMP-7 and age, blood lipids, and blood count-derived inflammatory markers. Pre-treatment MMP-7 was best predicted by the total cholesterol-to-HDL cholesterol ratio in a remnant cholesterol-weighted least squares regression model. After atorvastatin treatment, MMP-7 no longer correlated with these markers. Conclusions: While the effect of statins on plasma MMPs in atherosclerosis is controversial, short-term moderate-dose atorvastatin treatment does not seem to affect levels of MMPs 2, 7, and 9 in healthy individuals. However, an intriguing correlation between MMP-7 and atherosclerosis-related blood lipids and neutrophil-associated inflammatory biomarkers seems to be disrupted by atorvastatin independently of hsCRP, possibly via pleiotropic effects.

Key Clinical Message Statins can commonly cause myopathy. Most of the time, stopping the culprit drug should solve the problem. However, if the drug has been discontinued but muscle weakness continues to worsen, immune‐mediated myopathy should be taken into consideration.

Abstract Introduction Atorvastatin is regarded as the most frequently prescribed statin worldwide for dyslipidemia. However, clinical response and risk of adverse effects to statin therapy are associated with genetic variations. Numerous research linked statins pharmacokinetics (PK) variations to genetic polymorphisms in cytochromes P450 (CYPs) metabolic enzymes. Objective This article reviews the association between CYP3A4/5 genetic variations and response to atorvastatin therapy globally, which includes atorvastatin PK, and the risk for adverse reactions, with a hint to the Egyptians. Methods Up to March 30, 2022, electronic medical databases like PubMed, Web of Science, MEDLINE, and Egyptian Knowledge Bank (EKB) were searched. All articles that highlighted the relationship between CYP3A4/5 genetic polymorphisms and atorvastatin efficacy/safety profile were included in this review. Results Initially, 492 articles were retrieved after an exhaustive search. There were 24 articles included according to the inclusion criteria. Findings of association studies of CYP3A4/5 genetic polymorphisms with response to atorvastatin varied among different ethnicities. CYP3A4*1B was associated with better therapeutic outcomes after atorvastatin therapy in Chileans and vice versa in Americans. Caucasians with myalgia while using atorvastatin were at significant risk of suffering severe muscle damage if they were carriers of CYP3A5*3/*3. As far as we can report for the Egyptian population, the impact of CYP3A4/5 genetic variations on the response to atorvastatin therapy was understudied. Conclusion More pharmacogenetic studies amongst diverse populations worldwide, like the Egyptian population, are necessary to detect further atorvastatin-gene interactions. Graphical Abstract

Background: Hyperlipidemia can be defined as an increased concentration of lipids in the blood. Foxtail millet (FTM) is a nutrient-rich cereal containing several phytochemicals which have possible lipid-lowering and glucose-lowering abilities. Atorvastatin is an HMG Co-A Reductase Inhibitor commonly prescribed for Hyperlipidemia. Aims and Objectives: The aim of this study was to compare the hypolipidemic effect of FTM with that of Atorvastatin in Sprague–Dawley rats. Materials and Methods: Twelve 12 male Sprague–Dawley rats were segregated into Group-A and Group-B with six (6) rats in each group. The rats in both groups were fed high-fat diet for 21 days and for the next 21 days the 6 rats in Group-A were fed FTM in the form of pellets, the 6 rats in Group-B were administered Atorvastatin in a dose of 5 mg/kg. The body weight (BW) and lipid profiles of the rats were measured at three stages-day 0, day 21, and day 42. Results: FTM showed an 18.1% rise in high-density lipoprotein (HDL-C). It showed a fall in BW, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and very LDL (VLDL-C) which were 15.5%, 14.0%, 12.8%, 18.3%, and 16.0%, respectively. With Atorvastatin the rise in HDL-C was 13.4%. The fall in BW, TC, TG, LDL-C, and VLDL-C was 30.2%, 30.5%, 24.9%, 27.5%, and 34.4%, respectively. Conclusion: The present study results showed that FTM had a noticeable positive effect on the lipid profile and BW in Dyslipidemia in comparison to Atorvastatin.

Background Previous studies have shown that the rs1044925 single nucleotide polymorphism (SNP) of ACAT-1 gene is associated with the risk of coronary heart disease and ischemic stroke, and both are correlated to the level of blood lipid. Objective To observe the relationship between rs1044925 SNP of ACAT-1 gene and acute coronary syndrome (ACS) , and the relationship between rs1044925 SNP and the change of serum lipids level in response to atorvastatin treatment in patients with ACS. Methods 111 patients diagnosed with ACS and treated with percutaneous coronary intervention (PCI) in the Department of Geriatric Cardiovascular, People's Hospital of Guangxi Zhuang Autonomous from January 2016 to January 2018 were selected in ACS group (67 males and 44 females) . All patients were treated with atorvastatin 20 mg per night, Clopidogrel 75 mg, once a day (or tegranolol 90 mg, twice a day) , and Aspirin 100 mg, once a day. Atorvastatin 20 mg/night was routinely used after PCI. The control group consisted of 338 healthy people in the same time period (170 males and 168 females) . ACAT-1 rs1044925 SNP was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) . The baseline blood lipid levels of ACS group and control group were detected. The blood lipid parameters of the ACS group were measured after treatment of atorvastatin for one year averagely. Results There was no statistical difference in serum TC between the ACS group and the control group (P>0.05) , but there were statistical differences in the levels of TG, HDL-C, LDL-C, ApoAI, and ApoB (P0.05) . There was no statistical difference in the levels of TC, TG, HDL-C, LDL-C, ApoAI and ApoB among each genotype group of ACAT-1 rs1044925 SNP in the control group (P>0.05) . After atorstatin treatment, the serum TC, LDL-C, ApoAI, ApoB and lipoprotein (Lp) (α) levels in ACS patients were statistically different from baseline levels (P0.05) . There was no statistical difference in the baseline of Lp (α) level among genotypes (P>0.05) in ACS patients, but after 1 year of treatment, the Lp (α) level of each genotype was statistically different (P0.05) . There was statistical difference among the decrease in the levels of Lp (α) after atorvastatin treatment among different genotypes (P

Objective To explore the efficacy of atorvastatin combined with compound probiotics in the treatment of hyperlipidemia. Methods From January 2019 to December 2019, 33 patients with hyperlipidemia were recruited from the People‘s Hospital of Inner Mongolia Autonomous Region and were randomly divided into the test group（n=18） and the control group（n=15） using a randomized, double-blind, controlled trial design. The 20mg atorvastatin （once a day） plus compound probiotics（once a day, 2g each time） was given in test group, and the same dose of atorvastatin plus placebo was given in control group. The blood lipid level was measured once every 4 weeks for 12 weeks to compare the blood lipid levels at each time point between two groups. Results There were no significant differences in the baseline data between two groups (P＞0.05). There were no significant differences in the levels of TC, TG, LDL-C and other blood lipid levels related to the treatment effects between two groups(P＞0.05). At the different time points, there were statistical differences in the levels of TC, TG, LDL-C and other blood lipids(P

Abstract Background Zika virus (ZIKV), an arbovirus of global concern, has been associated with neurological complications including microcephaly in newborns and Guillain–Barré syndrome in adults. Like other flaviviruses, ZIKV depends on cholesterol to facilitate its replication; thus, cholesterol has been proposed as a therapeutic target to treat the infection using FDA-approved statins. Cholesterol is stored in intracellular lipid droplets (LD) in the form of cholesterol esters and can be regulated by autophagy. We hypothesize that the virus hijacks autophagy machinery as an early step to increase the formation of LD and viral replication, and that interference with this pathway will limit reproduction of virus. Methods We pretreated MDCK cells with atorvastatin or other inhibitors of autophagy prior to infection with ZIKV. We measured viral expression by qPCR for NS1 RNA and immunofluorescence for Zika E protein. Results Autophagy increases in virus-infected cells as early as 6 h post infection (hpi). In the presence of atorvastatin, LD are decreased, and cholesterol is reduced, targeting key steps in viral replication, resulting in suppression of replication of ZIKV is suppressed. Other both early- and late-acting autophagy inhibitors decrease both the number of LD and viral replication. Bafilomycin renders cholesterol is inaccessible to ZIKV. We also confirm previous reports of a bystander effect, in which neighboring uninfected cells have higher LD counts compared to infected cells. Conclusions We conclude that atorvastatin and inhibitors of autophagy lead to lower availability of LD, decreasing viral replication. We conclude that bafilomycin A1 inhibits viral expression by blocking cholesterol esterification to form LD. Video Abstract Graphical Abstract

Abstract Background Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (MSCs) pretreated with atorvastatin (ATV) (MSCATV-EV) have a superior cardiac repair effect on acute myocardial infarction (AMI). The mechanisms, however, have not been fully elucidated. This study aims to explore whether inflammation alleviation of infarct region via macrophage polarization plays a key role in the efficacy of MSCATV-EV. Methods MSCATV-EV or MSC-EV were intramyocardially injected 30 min after coronary ligation in AMI rats. Macrophage infiltration and polarization (day 3), cardiac function (days 0, 3, 7, 28), and infarct size (day 28) were measured. EV small RNA sequencing and bioinformatics analysis were conducted for differentially expressed miRNAs between MSCATV-EV and MSC-EV. Macrophages were isolated from rat bone marrow for molecular mechanism analysis. miRNA mimics or inhibitors were transfected into EVs or macrophages to analyze its effects on macrophage polarization and cardiac repair in vitro and in vivo. Results MSCATV-EV significantly reduced the amount of CD68+ total macrophages and increased CD206+ M2 macrophages of infarct zone on day 3 after AMI compared with MSC-EV group (P

Radiation therapy is one of the major subsets of cancer treatments. Normal tissue toxicity and tumor cell resistance are two main obstacles during radiotherapy treatments. Toxicity to healthy tissue limits the applied dose, resulting in inadequate tumor control. On the other hand, the resistances of cancer cells lead to increased doses of radiotherapy. Therefore, agents that can simultaneously reduce the toxicity of normal tissues and increase the sensitivity of tumor cells to radiotherapy could be a potential solution to increase the efficiency of radiotherapy during cancer treatment. Many studies have found that atorvastatin, as an HMG coenzyme A reductase (HMG-CoA) inhibitor, and protects normal tissue while sensitizing cancer cells to radiotherapy via various molecular mechanisms and signaling pathways. This review summarizes the evidence for radioprotective and radiosensitivity effects of atorvastatin in vitro and in vivo studies.

Background: Hyperlipidemia is an umbrella term for any of the genetic or acquired disorders that result in an elevated level of lipids circulating in the blood. These lipids can enter the walls of arteries and increase the risk of developing hardening of the arteries, which can lead to atherosclerosis, stroke, and heart attack. Objectives: The present study tries to investigate the impact of lipid-lowering drugs on lipid profile in patients with hyperlipidemia and to determine the best drug of choice in such patients. Materials and Methods: Sixty hyperlipidemia patients with the mean age of 45.52 ± 13.24 years admitted to a private clinic in Hilla city, Iraq, during a period extant from October 2022 to November 2022 were subjected to the present cross-sectional study. Patients were categorized according to the type of drug used and gender. Group 1 (G1) patients treated with rosuvastatin, group 2 (G2) patients treated with atorvastatin, group 3 (G3) patients treated with ezetimibe, and group 4 (G4) patients treated with combination of ezetimibe + simvastatin. Lipid profile was determined using enzymatic method. Results: The combination of ezetimibe + simvastatin has a better effect to lower the body mass index. Ezetimibe alone reduces total cholesterol (TC), whereas combination of ezetimibe + simvastatin was found to reduce TC, low-density lipoprotein cholesterol (LDL-C) and triacylglycerol (TG). Rosuvastatin raises the high-density lipoprotein cholesterol (HDL-C). Conclusions: The combination of ezetimibe and simvastatin gives a good result in reducing the level of TC in the body, and this leads to a better reduction of LDL-cholesterol than using atorvastatin alone.

Aim. To study the vasoprotective effects of atorvastatin depending on the achievement of the target level of low-density lipoprotein cholesterol (LDL-C) in patients with ST-segment elevation myocardial infarction (STEMI) within 48 weeks of follow-up. Materials and methods. Included were 112 STEMI patients who received atorvastatin 204080 mg. On days 79 from the onset of the disease, after 24 and 48 weeks, ultrasound examination of the carotid arteries with RF technology and applanation tonometry were performed, the lipid profile was determined. The patients were divided into groups: group 1 (n=41) of highly effective therapy (HET) who achieved the target LDL-C after 24 and 48 weeks; group 2 (n=29) in relatively effective therapy (RET) achieving target values at 24th or 48th week; group 3 (n=42) insufficiently effective therapy (IET) did not reach the target LDL-C. Results. When examining the carotid arteries in the HET group, the intima-media thickness (IMT) decreased by 10.713.1%, the b index by 14.926.3% after 2448 weeks. In the RET group, the IMT regression was 10.413.3%; b index 23.9% by the 48th week. In the IET group, the b index decreased by the 48th week by 14.3%. According to applanation tonometry in the HET group, the central pressure did not change. In the RET group, systolic pressure in the aorta increased by 1015.7% after 2448 weeks, pulse pressure by 33.9% by the end of observation. With IET, the increase was 8.66.8 and 19.825.9%, respectively. The odds ratio of developing endpoints in the RET group was 4.7 (95% CI 1.226.4; p=0.02), in the IET group 3.9 (95% CI 1.124.8; p=0.03) compared with HET. Conclusion. The most pronounced vasoprotective effect and a decrease in cardiovascular risk are associated with the achievement of the target LDL-C throughout the entire treatment period.

Background: Persistent immune activation and inflammation in HIV-infection are linked to excess cardiovascular risk and other non-communicable diseases. Periodic asymptomatic CMV-reactivity in HIV infected patients over a lifetime may contribute to non-AIDS defining morbidity. Despite undetectable levels of HIV and CMV, these patients continue to have increased levels of biomarkers and immune activations. Statin administration is thought to reduce subclinical atherosclerosis by decreasing LDL-C levels. It may also add beneficial effects against CMV infection. Methods: We are conducting a double-blind placebo-controlled trial in which patients are randomized to receive either atorvastatin or placebo with a ratio of 1:1. This trial aims to study the effect of atorvastatin in statin-naive virally-suppressed HIV-infected patients with stable ART and CMV seropositivity on carotid intima media thickness (CIMT), tool that evaluates subclinical atherosclerosis. The study recruits 80 patients at HIV integrated care unit of Cipto Mangunkusumo hospital. All eligible subjects have CIMT evaluation as primary outcome, along with flow mediated vasodilatation (FMD), liver fibrosis and steatosis evaluation, fasting lipid, neurocognitive test, community periodontal index (CPI), and residual immune activation as secondary outcomes in 48 weeks. Ethics and dissemination: This study has received an ethical approval from Health Research Ethics Commitee–Universitas Indonesia and Cipto Mangunkusumo Hospital. Before joining the study, all participants fill in an informed consent form. At the end of study analysis, the trial results will be published and disseminated in peer-reviewed journals. Discussion: The main purpose of our study is to evaluate the effect of atorvastatin administration on CIMT changes in statin naïve virally suppressed HIV-infected patients with stable ART and CMV seropositivity Registration: ClinicalTrials.gov ID NCT04101136; registered on 24 September 2019.

Key Clinical Message We report a case of biopsy‐proven cutaneous leukocytoclastic vasculitis developing 10 days after starting verapamil and atorvastatin in a patient with long‐standing Sjogren's syndrome. This highlights the need to monitor for this rare adverse effect.

Background: Statins may be protective against viral infection and have been suggested for the treatment of coronavirus disease 2019 (COVID-19). Objective: In this study, we aimed to evaluate the effect of atorvastatin on COVID-19 patients. Methods: Our study is a randomized double-blind controlled clinical trial that constitutes a population of COVID-19 patients admitted to Bu-Ali Sina Hospital in Qazvin, Iran, from May to August 2021. For the intervention and control groups, in addition to the national standard treatment, atorvastatin 40 mg tablet and placebo were daily administered for 7 days, respectively. A questionnaire including demographic characteristics, history of underlying diseases, vital signs, laboratory and imaging results, and outcome (alive, died) was completed on the first, third, and fifth days of hospitalization. Finally, the obtained data were analyzed by SPSS software, version 25. Findings: One hundred five patients with COVID-19 (62 females and 43 males, mean age 69 years) were studied. On days 3 and 5 after the intervention, no significant difference was observed between the groups in terms of vital signs, laboratory findings, hospitalization time, and need for intensive care unit hospitalization. However, 5.7% of patients in the atorvastatin group and 0% of patients in the control group died (P=0.243). Among the studied variables, C-reactive protein (P=0.227 vs P=0.002), blood urea nitrogen (P=0.055 vs P

Background and purpose: Benzo[a]pyrene (BaP) is an environmental pollutant that has genotoxic and carcinogenic effects. Atorvastatin (ATV), as a lipid-lowering drug, has antioxidant, anti-inflammatory and anti-apoptotic properties. This study investigated the effects of ATV on chronic liver and kidney damage induced by BaP. Materials and methods: In this experimental study, adult female rats were randomly divided into seven groups (n= 8 per group), including control group, olive oil group, ATV group (10 mg/kg), BaP groups (10 and 20 mg/kg), and ATV + BaP groups (10 and 20 mg). The drugs were administered by oral gavage for ten consecutive days. Histopathologic evaluation of the liver and kidney tissues was done one month after drug administration. Results: Histopathologic changes in both liver and kidney tissues such as inflammatory cell infiltration, plasma leakage, reduced acidophilia of hepatocytes, and renal tubular cells were seen in the groups receiving BaP. Findings showed that BaP at 20 mg/kg caused more serious harm than that at 10 mg/kg. ATV treatment protected structural changes in liver and kidney tissues. Conclusion: Current study showed that destructive effects of benzopyrene remain until one month after administration. The protective effects of atorvastatin against benzopyrene-induced hepatotoxicity were confirmed over time.

ABSTRACT Introduction COVID-19 is associated with endothelial activation and systemic inflammation; consequently, statins can be used in its treatment as they have anti-inflammatory, antithrombotic, and profibrinolytic properties and may interfere with COVID-19 viral entry into cells through disruption of cell membrane lipid rafts. Objective We performed a meta-analysis of randomized clinical trials that compared statin therapy to placebo or to standard care in adult patients hospitalized for COVID-19. Methods We searched the MEDLINE, EMBASE, and Cochrane Library databases for all-cause mortality, hospitalization duration, and admission to the intensive care unit. Results Of the 228 studies reviewed, four studies were included, with a total of 1,231 patients, of whom 610 (49.5%) were treated with statins. There was no significant difference in all-cause mortality (odds ratio [OR] 0.96; 95% confidence interval [95%CI]: 0.61-1.51; p=0.86; I2=13%), duration of hospitalization (mean difference [MD] 0.21; 95%CI: -1.74-2.16; p=0.83; I2=92%), intensive care unit admission (OR= 3.31; 95%CI: 0.13-87.1; p=0.47; I2=84%), need for mechanical ventilation (OR= 1.03; 95%CI: 0.36-2.94; p=0.95; I2=0%), or increase in liver enzyme levels (OR= 0.58; 95%CI: 0.27-1.25; p=0.16; I2=0%) between patients treated with or without statin therapy. Conclusion Our findings suggest that in adult patients hospitalized with COVID-19, statin therapy results in no difference in clinical outcomes when compared to outcomes by placebo or standard of care. Prospero database registration: (www.crd.york.ac.uk/prospero) under the number CRD42022338283.

Statement of the Problem: Molar teeth with furcation involvement are one of the most common problems in patients with periodontal disease. Regeneration methods are of the most controversial treatment strategies for these lesions. Purpose: The purpose of this study was to determine the effect of plasma rich in growth factors (PRGF) with 1.2% Atorvastatin (ATV) in the treatment of furcation involvement of mandibular molars. Materials and Method: The present randomized clinical trial was conducted on 15 patients with moderate periodontitis and class II furcation involvements; 24 defects were located in four groups of six, including debridement, ATV1.2%, PRGF, PRGF with ATV1.2%. The parameters of vertical probing depth (VPD), vertical clinical attachment level (VCAL), gingival index (GI), horizontal probing depth (HPD) and gingival recession (GR) were measured at baseline (T0), immediately before surgery (T1), 3 (T2), and 6 (T3) months after surgery. Moreover, the bone conditions were evaluated by digital subtraction radiography before and six months after surgery. Data were analyzed using SPSS23 software. Results: No significant difference in radiographic parameters was observed among the groups (p= 0.08). There was no significant difference in the mean levels of VPD, VCAL and HPD among the groups at different times (p

Background and objectives: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by the accumulation of large amounts of fat in the hepatocytes. Given that atorvastatin is effective for treatment of NAFLD, the present study investigated effects of high-fat/fructose diet (HFFD) with atorvastatin on liver enzymes and lipid profile in a NAFLD rat model. Methods: Thirty-two male Wistar rats were divided into four groups: 1) normal control, 2) HFFD control, 3) HFFD + atorvastatin, and 4) normal + atorvastatin. The groups received HFFD for 15 weeks to induce hepatosteatosis. Atorvastatin was administrated at the dose of 10 mg/kg/day. Lipid profile and liver enzymes were measured after eight weeks of intervention. Results: Triglyceride, cholesterol, gamma-glutamyl transferase, and aspartate transaminase were significantly reduced in the HFFD + atorvastatin group compared with the HFFD control group. In addition, cholesterol, high-density lipoprotein, alkaline phosphatase, and gamma-glutamyl transferase were significantly increased in the normal + atorvastatin group compared with the normal control group. Low-density lipoprotein increased significantly in the HFFD + atorvastatin group and the normal + atorvastatin group compared with other groups. There was a significant difference in the alanine transaminase levels between the groups taking atorvastatin. In fact, alanine transaminase level was lowest in the normal + atorvastatin group. Conclusion: Atorvastatin improves the lipid profile and fatty liver and controls liver enzymes. Therefore, it can be used with caution to improve the lipid profile and reduce the complications of NAFLD.

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors used worldwide to manage dyslipidaemia and thus limit the development of atherosclerotic disease and its complications. These atheroprotective drugs are now known to exert pleiotropic actions outside of their cholesterol-lowering activity, including altering immune cell function. Macrophages are phagocytic leukocytes that play critical functional roles in the pathogenesis of atherosclerosis and are directly targeted by statins. Early studies documented the anti-inflammatory effects of statins on macrophages, but emerging evidence suggests that these drugs can also enhance pro-inflammatory macrophage responses, creating an unresolved paradox. This review comprehensively examines the in vitro, in vivo, and clinical literature to document the statin-induced changes in macrophage polarization and immunomodulatory functions, explore the underlying mechanisms involved, and offer potential explanations for this paradox. A better understanding of the immunomodulatory actions of statins on macrophages should pave the way for the development of novel therapeutic approaches to manage atherosclerosis and other chronic diseases and conditions characterised by unresolved inflammation.

Abstract Leukocytoclastic vasculitis is an entity associated with drugs, infections, cryoglobulinemia, and connective tissue diseases but can also be idiopathic, systemic, or organ localized. Moreover, LCV associated with drugs is a rare disorder. When it is present usually has an elevation of anti‐neutrophil cytoplasmic antibody, most likely anti‐myeloperoxidase, which can be helpful to orient the diagnosis. We are presenting a 55‐year‐old female with a past medical history of diabetes mellitus (DM) and hyperlipidemia (HLD) who presented with a painful and pruritic rash localized in the abdomen and lower extremities that started 1 week after initiated atorvastatin for management of hyperlipidemia. This is the first case ever reported of leukocytoclastic vasculitis ANCA negative associated with atorvastatin, to our best knowledge.

Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra-muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality.

Introduction: Contrast-induced nephropathy (CIN) is associated with increased disability and death. Randomized clinical trial studies have shown that short-term treatment with statins prior to cardiac intervention was capable of reducing the incidence of CIN. Therefore, the aim of this study was to compare the incidence of CIN after primary PCI in patients receiving high-dose rosuvastatin and atorvastatin. Methods: This clinical trial was performed in Mazandaran Heart Center Hospital on patients referred to the emergency department who underwent primary PCI with a diagnosis of STEMI. Patients received 1 cc/kg/h normal saline from PCI for up to 12 hours. Patients with EF less than or equal to 35% received intravenous normal saline at half the usual dose. SPSS software version 24 was used for data analysis. P value less than 0.05 was considered to be statistically significant. Results: 206 patients were included in the study that the most underlying diseases of patients (79, 38.3%) were hypertension, followed by anemia (76, 36.9%) and diabetes mellitus (52, 25.2%). Among these, in the first criterion, 10 (8.1%) and 4 patients (4.8%) were in the atorvastatin and rosuvastatin groups, respectively, which did not have a statistically significant difference (P = 0.264). Examination of GFR subgroups also showed that GFR above 30 had significant differences between the two groups. Conclusion: The use of different statins has had similar results in the prevention of CIN in patients undergoing primary PCI. Rosuvastatin has no special advantage over atorvastatin, showing that the use of any of these drugs can be useful in patients requiring angiography.

Background and objectives: Programmed autophagy is a genetically and evolutionarily conserved process that destroys long-lived cellular proteins and organelles. This study aimed to investigate effects of continuous and interval exercise training with or without atorvastatin supplementation on Beclin1, LC3-I and LC3-П expression in old rats with type 2 diabetes. Methods: Sixty three male Wistar rats were divided into eight groups. Continuous exercise was performed at a speed of 15-29 m/min for 5-22 minutes. Interval exercise program consisted of six 2.5-minute sets that included a four-minute rest period between each set. The rats in the supplementation groups also received 20 mg/kg body weight atorvastatin daily via intraperitoneal injection. At the end of the training period, the expression of Beclin1, LC3-I and LC3-П in soleus muscle was measured by RT-PCR. One-way ANOVA was used for data analysis at statistical significance of 0.05. Results: The results showed that both exercise trainings with or without atorvastatin significantly reduced LC3I, LC3-II and Beclin1 compared with the diabetic control group (P0.05). Conclusion: The results indicate that continuous and interval exercise program alone and combined with atorvastatin supplementation could significantly reduce LC3-1, LC3-II and Beclin1 level in soleus muscle of old diabetic rats.

A number of studies have now been conducted confirming the relationship between arterial hypertension (AH) and nonalcoholic fatty liver disease (NAFLD). It has been proved that the presence of AH increases or provokes the development of NAFLD. A study of telmisartan effectiveness in combination with atorvastatin and ursodeoxycholic acid (UDCA) in patients with AH and NAFLD was carried out in this article. Material and methods. The study included 39 patients diagnosed with arterial hypertension in combination with NAFLD, who were treated with a combination of drugs: Telmisartan, Atorvastatin and UDCA for 12 weeks. The comparison group consisted of 33 patients with NAFLD who received basic NAFLD therapy without telmisartan and atorvastatin. The study analyzed the efficacy of the prescription of this combination on the clinical condition of patients with AH combined with NAFLD, their hemodynamic parameters, the levels of blood lipid spectrum, IL-6, leptin, adiponectin, and the dynamics of echocardiographic and ultrasonographic parameters. Results and discussion. It has been revealed, that application of telmisartan, atorvastatin and UZHK combination for 12 weeks significantly reduced BP levels to the target values, improved hemodynamic indexes, led to reduction of atherogenic components of blood lipid spectrum. And also prescription of this combination decreased IL-6 and leptin levels, increased adiponectin content, which contributed to improvement of the general state of patients, decrease in the severity of clinical and functional manifestations of NAFLD.

Background and Aim: Atorvastatin is one of the medicines used for the treatment of high blood cholesterol which recently has been shown to have antioxidant effects in the cell. The aim of this study was to evaluate the effect of atorvastatin on the growth and quality of immature mouse oocytes in vitro. Materials and Methods: 400 oocytes were prepared from ovaries of 40 NMRI mice and divided into two groups of control (culture medium) and atorvastatin (culture medium + 2 μM atorvastatin). Then oocyte qualitative parameters including zona pellucida thickness (ZP), Perivitelline space size (PVS) and oocyte diameter (OD) were determined using invert microscope and image-J software. Results: Quantitative parameters of zona pellucida thickness and oocyte diameter were increased in the atorvastatin group compared to those in the control group. In the evaluation of oocytes quality, the number of oocytes exhibiting +1 score in the atorvastatin and control groups were (70%) and (55.4%) respectively, which showed a significant difference between the two groups (P≤0.05). The numbers of polar bodies exhibiting +1 score in the atorvastatin and control groups were (36.18%) and (18.5%) respectively (P≤0.05). Conclusion: Use of atorvastatin had a significant effect on the growth and final quality of the immature oocytes in vitro and it can possibly be used to increase the efficiency of in vitro fertilization in the future.

Background and aims: The abnormal increase in blood cholesterol can cause many problems. Statins have a cholesterol-lowering effect, but they also have adverse effects. Garlic prevents the formation of cholesterol due to its antibiotic properties. This study aimed to investigate the comparative effect of garlic powder and atorvastatin on hypercholesterolemia-induced reproductive failure in female rats. Methods: In the present experimental study, 48 adult female Wistar rats were divided into eight groups (n=6), including control, atorvastatin (10 mg/kg/d; orally), atorvastatin (20 mg/kg/d; orally), garlic powder (100 mg/kg/d; orally), hypercholesterolemia (1.5 mg/kg/d of cholesterol; orally), hypercholesterolemia + atorvastatin (10 mg/kg/d), hypercholesterolemia + atorvastatin (20 mg/kg/d), and hypercholesterolemia + garlic powder. After 30 days, rats were euthanized and blood samples were obtained from their heart for serological assessments. The right ovary was transferred to 10% formalin for histological analyses, and the left ovary was transferred to a −80°C freezer for evaluation of oxidative stress markers. Data were statistically analyzed by ANOVA and Tukey’s test using SPSS version 24.0 (P

Background and purpose: Ascorbic acid is an important antioxidant and its depletion is a risk factor for periodontal diseases. This study aimed to evaluate the effect of 2% atorvastatin dentifrice and ascorbic acid on improving clinical periodontal parameters in patients with chronic periodontitis. Materials and methods: This clinical trial included 72 patients with moderate and severe chronic periodontitis attending periodontology department in Yazd Dental School, Iran. They were randomly divided into four groups (n=18 per group). Group 1 was the control group that used 0.2% fluoride dentifrice after Scaling and Root Planing (SRP). Group 2 used 0.2% flouride dentifrice + adjunctive use of atorvastatin 2% following SRP. Group 3 used 0.2% fluoride dentifrice and 250mg chewable ascorbic acid tablet after SRP. Group 4 used 0.2% fluoride dentifrice + adjunctive use of atorvastatin 2% and 250mg chewable ascorbic acid after SRP. Periodontal parameters including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and modified gingival index (MGI) were measured at baseline and one month after treatment. Data were analyzed in SPSS V17 applying Chi square, ANOVA, and Tukey test. Results: After one month, significant decreases were seen in CAL (P= 0.0001) and MGI (P= 0.029). In groups 2 and 4, the decrease in CAL was significantly higher than the control group (P= 0.0001) and in comparison between case groups there were significant differences between groups 3 and 4 (P= 0.0001). In group 3, significant decrease was seen in MGI compared to the control group (P

Abstract Background Momordica. charantia is popularly used as a medicinal herb in ethnomedicine for the management of cardiovascular diseases. In this study, we evaluated the beneficial effects of the ethanolic extract of M. charantia (Linn.) in experimentally induced cardiovascular disorders using cholesterol-fed Wistar rat. Methods Seventy-two experimental rats were randomly assigned into nine 9 groups of 8 rats each and treated as follows: Rats in group A (control) were given distilled water only; Rats in group B were given 30 mg/kg of cholesterol dissolved in coco-nut oil (cholesterol solution); Rats in group C were given cholesterol solution and 100 mg/kg Atorvastatin; Rats in group D were given 250 mg/kg of M. charantia and cholesterol solution; Rats in group E were given 500 mg/kg of M. charantia and cholesterol solution; Rats in group F were given 250 mg/kg. M. charantia; Rats in group G were given 500 mg/kg M. charantia; Rats in group H were given 1 ml of coconut oil; Rats in group I were given 100 mg/kg of Atorvastatin. Results Mean LDL-cholesterol was significantly (P

Background: Statins present a plethora of pleiotropic effects including anti-inflammatory and antimicrobial responses. A,α-difluorophenylacetamides, analogs of diclofenac, are potent pre-clinical anti-inflammatory non-steroidal drugs. Molecular hybridization based on the combination of pharmacophoric moieties has emerged as a strategy for the development of new candidates aiming to obtain multitarget ligands. Methods: Considering the anti-inflammatory activity of phenylacetamides and the potential microbicidal action of statins against obligate intracellular parasites, the objective of this work was to synthesize eight new hybrid compounds of α,α-difluorophenylacetamides with the moiety of statins and assess their phenotypic activity against in vitro models of Plasmodium falciparum and Trypanosoma cruzi infection besides exploring their genotoxicity safety profile. Results: None of the sodium salt compounds presented antiparasitic activity and two acetated compounds displayed mild anti-P. falciparum effect. Against T. cruzi, the acetate halogenated hybrids showed moderate effect against both parasite forms relevant for human infection. Despite the considerable trypanosomicidal activity, the brominated compound revealed a genotoxic profile impairing future in vivo testing. Conclusions: However, the chlorinated derivative was the most promising compound with chemical and biological profitable characteristics, without presenting genotoxicity in vitro, being eligible for further in vivo experiments.

Despite steady improvements in cardiovascular disease (CVD) prevention, a scarce proportion of patients achieve the recommended LDL-C goals, even under high-intensity lipid-lowering therapy (LLT). Our study aimed to evaluate the attainment rate of LDL-C targets recommended by the 2019 European guidelines, and to characterize potential factors associated with LDL-C goal achievement and change patterns in LLT. We conducted a retrospective, observational study on patients treated with high-intensity atorvastatin or rosuvastatin ± ezetimibe at cardiology and internal medicine clinics across Spain. It included 1570 evaluable patients (median age: 62 years; established CVD: 77.5% [myocardial infarction: 34.3%]; and 85.8% at very high cardiovascular risk). Rosuvastatin ± ezetimibe was the LLT in 52.2% of patients, and atorvastatin ± ezetimibe in 47.8%. LLT had been modified in 36.8% of patients (side effects: 10%), being the most common switch from atorvastatin- to rosuvastatin-based treatment (77.2%). The risk-based LDL-C goal attainment rate was 31.1%, with 78.2% high-risk and 71.7% very high-risk patients not achieving the recommended LDL-C targets. Established CVD and familial hypercholesterolemia were significantly associated with the non-achievement of LDL-C goals. Although having limitations, this study shows that the guideline-recommended LDL-C goal attainment rate is still suboptimal despite using high-intensity statin therapy in a real-world setting in Spain.

Background and purpose: Statins are among the most widely used drugs in treatment of cardiovascular diseases. Reducing the side effects of these drugs is of great importance in preventing treatment failure. The aim of this study was to investigate the role of rs4149056 polymorphism in statin-induced myopathy in patients with cardiovascular diseases in West of Mazandaran province, Iran. Materials and methods: A descriptive cross-sectional study was carried out in 161 patients taking atorvastatin who attended Cardiovascular Clinic in Ramsar Imam Sajjad Hospital and Tonekabon Shahid Rajaee Hospital, 2017-2018. All patients were given atorvastatin at 40 mg daily for 8 weeks and all lipid markers and CPK enzyme levels as a measure of myopathy were measured. Then, the patients received atorvastatin at 20 mg for 4 weeks and all lipid markers were measured again. PCR-ARMS method was used to determine the distribution of rs4149056 polymorphism. Results: According to findings, reducing the dose of atorvastatin caused significant differences in total cholesterol and LDL levels (P0.05). Drug dose change caused significant differences in levels of triglycerides in patients with TC genotype and HDL in patients with CC genotype (P

Objective: To determine the myopathy in patients with diabetes taking atorvastatin and look for the factors correlated with the presence of myopathy among these patients. Study Design: Cross sectional analytical study. Place and Duration of Study: Department of Medicine, Pak Emirates Military Hospital Rawalpindi from, Jul to Dec 2018. Methodology: A total of 166 patients of both genders with type 2 diabetes mellitus taking atorvastatin for at least three to twelve months were included. Blood samples were drawn and Creatinine kinase (CK) levels were determined by automated analysis by colorimetry. Myopathy was taken as muscle symptoms associated with elevations in Creatinine Kinase at least 10 times the upper limit of normal. Results: Mean age of patients was 51.530 ± 5.70 years with age range from 40-70 years with. Mean duration of diabetes was 6.174 ± 2.27 years, mean duration of taking atorvastatin 7.186 ± 2.17 months and mean creatinine kinase levels were 1760.325 ± 5111.71 IU/L. Males were 68.7% as compare to females 31.3%. Myopathy was seen in 8.4% patients. Long duration of Diabetes Mellitus and atorvastatin use was statistically significantly related with the presence of myopathy. Conclusion: Myopathy was found in a significant number of patients taking atorvastatin. High risk population in our study emerged out to be patients with long duration of Diabetes Mellitus and long use of atorvastatin.

Background and Aims: The present study aimed to compare the effects of three therapeutic methods (including herbal, atorvastatin, and exercise) on liver enzymes and lipid profiles in hypercholesterolemic rats. Materials and Methods: A number of 32 male Wistar rats were randomly assigned to four groups (n=8), including hypercholesterolemia (Hc) control group, anvil extract at a dose of 100 mg/kg, (Ext), exercise (E), and atorvastatin (AT) at a dose 10 mg/kg. Endurance training, anvil extract, and atorvastatin were performed three sessions per week for 8 weeks. Thereafter, liver biochemical tests, including alkaline phosphatase (ALT), aspartate aminotransferase (AST), and lipid profiles were performed using a biochemical autoanalyzer (Ra-2000 made in USA) and the kits provided by Pars Azmun company. The data were analyzed in SPSS software using analysis of variance (ANOVA) and Tukeychr('39')s test were used for data analysis. Results: The results of statistical analysis indicated that all variables (e.g., Alanine transaminase, Triglyceride, High-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL), except for ALT, AST, and cholesterol, were significant in all groups. The results of the statistical analysis demonstrated that triglycerides and VLDL significantly reduced in the atorvastatin and exercise groups, compared to the hypercholesterolemic control group. Furthermore, HDL had a significant increase in the exercise group, compared to the atorvastatin, extract, and control groups. In addition, LDL significantly decreased in the exercise group, compared to the atorvastatin group. Conclusion: The results of the current study pointed to the similar effects of medication and exercise on the improvement of some lipid profiles. Nonetheless, exercise is advantageous over the use of medicine and herbal extracts due to the positive effects of exercise on the reduction of blood lipids and the absence of any side effects.

Background: Preclinical evidence indicates that statins possess diverse antineoplastic effects in different types of tumors. However, clinical studies have yielded conflicting results regarding the potential of statins to either increase or decrease the risk of cancer. Our objective was to examine the relationship between the dose of a treatment and its impact on melanoma tumor growth and angiogenesis in an in vivo setting. Materials and Methods: Melanoma cells were injected into C57BL6 mice in four groups. They received 0, 1, 5, and 10 mg/kg of atorvastatin daily. Three others received the mentioned doses one week before the inoculation of melanoma animals. At the end of the third week, the animals were euthanized in a humane manner, and both blood samples and tumor specimens were collected for subsequent analysis. Results: The tumor size was 1.16 ± 0.25 cm3 in a group treated with therapeutic dose of atorvastatin and was significantly larger than that in the control group (0.42 ± 0.08 cm3). However, there were no significant differences between the two other doses and the control group (0.72 ± 0.22, 0.46 ± 0.08 cm3 in atorvastatin-treated groups with 5 and 10 mg/kg). The vascular density of the tumors was significantly increased in the lowest dose of the atorvastatin treatment group, similar to the results of tumor size (P < 0.05). Conclusion: Atorvastatin, at low therapeutic concentrations, has been observed to stimulate tumor growth and exhibit pro-angiogenic effects. Therefore, it is advised to exercise caution and recommend clinically relevant doses of statins to patients with cancer.

Background: Statins play a vital role in the management of high-risk patients with atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effect of two doses of 40 and 80 mg of atorvastatin on lipid profiles and inflammatory markers among patients with acute coronary syndrome (ACS). Materials and Methods: This single-blind, randomized clinical trial was conducted on 60 patients with ACS referred to Heshmatiyeh Hospital, Sabzevar, Iran. Eligible subjects were randomly assigned to either 80 mg/day (atorvastatin, 80 mg/day) or 40 mg/day intervention (atorvastatin, 40 mg/day) groups. Serum lipid profiles (low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglyceride [TG], and total cholesterol), an inflammatory marker (creatine phosphokinase [CPK]), and liver function biomarkers (alanine aminotransferase, aspartate aminotransferase) were assessed before starting treatment and 3 months later. Results: According to the paired t-test, there was a significant difference before and after intervention in each group regarding mean LDL and HDL values (P < 0.05). The result of the ANCOVA test revealed that the LDL and CPK was substantially lower in the 80 mg/day group as compared to the 40 mg/day group after 3-month intervention (62.45 ± 16.78 mg for 80 mg/day vs. 73.63 ± 20.00 for 40 mg/day P = 0.040 and 84.85 ± 6.53 IU/L for 80 mg/day vs. 120.70 ± 6.41 IU/L for 40 mg/day P = 0.001, respectively). Although the mean of HDL, TG, and cholesterol in the 80 mg/day group was lower than that of the 40 mg/day group after implementing the intervention, these differences were not statistically significant (P > 0.05). Conclusion: Findings suggest that increasing the dose of atorvastatin decreases the mean serum levels of LDL and CPK but has no effect on the mean serum HDL levels and liver function biomarkers.

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease that affects about 25% of the general population. No definitive treatment for NAFLD has been identified yet. The aim was to determine the effect of atorvastatin (ATO) and flaxseed on related indicators of NAFLD-induced fat/fructose-enriched diet (FFD). Materials and Methods: Forty male Wistar rats were divided into five groups. NAFLD groups received FFD and carbon tetrachloride (CCl4) to induce NAFLD. After intervention with ATO (10 mg/kg/day) and/or flaxseed (7.5 g/kg/day), liver enzymes and lipid profiles in serum were determined at eight week of interventions. Results: Triglycerides (TG) and cholesterol (CHO) in FFD + ATO, FFD + flaxseed, and FFD + ATO + flaxseed had a significant decrease and low-density lipoprotein (LDL) level and LDL/high-density lipoprotein (HDL) ratio showed a significant increase in the FFD + flaxseed compared to the FFD. The levels of aspartate transaminase (AST), alanine transaminase (ALT), and gamma-glutamyltransferase (GGT) were significantly reduced in the FFD + ATO, FFD + flaxseed, and the FFD + ATO + flaxseed. In addition, Alkaline phosphatase (ALP) levels were significantly different between normal and FFD. Fasting blood sugar (FBS) levels were significantly different in the FFD + flaxseed and the FFD + ATO + flaxseed compared to the FFD. Conclusion: ATO therapy along with flaxseed controls NAFLD-related indices and FBS. Therefore, it can be stated with caution that ATO and flaxseed can be used to improve lipid profile and reduce the complications of NAFLD.

Background: Acupuncture therapy has been widely used as an alternative therapy to treat multiple diseases, such as sequelae of stroke, pain, facial paralysis and so on. In recent years, few adverse events related to acupuncture treatment have been reported, among which hematoma, bleeding and dizziness are the main manifestations. However, to date, there have been no existing cases reported the association between acupuncture therapy and asymptomatic/pauci-symptomatic hyperCKemia. Case presentation: We report a patient who developed hyperCKemia during 5 sessions of acupuncture at different frequencies. After stopping acupuncture treatment for 1 month, follow-up showed a significant downward trend in serum creatine kinase (sCK). However, after that this patient started to get acupuncture treatment again in order to improve the sequelae of stroke. Meantime, the sCK rose again. Conclusion: HyperCKemia may associated with acupuncture therapy. All kinds of adverse events of acupuncture should be recorded comprehensively and objectively so as to improve the safety standard system of acupuncture therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate & compare the mean change in fasting serum total cholesterol and LDL-C levels from baseline, after 12 weeks of oral treatment with oral Rosuvastatin and with Atorvastatin in type 2 diabetic patients with primary hyperlipidemia. Study Design: Cross sectional comparative study. Place and Duration of Study: The present study was conducted in the Medicine Department, Pakistan Naval Ship, Shifa Hospital, Karachi, from Mar to Sep 2016. Methodology: The sample was collected by non- probability convenient sampling. The total of 114 DM type 2 patients were randomly divided into two equal groups. Group A was given Rosuvastatin whereas group B was given Atorvastatin orally daily for 12 weeks along with oral treatment for diabetes. After 12 weeks, Fasting Serum Total Cholesterol and Serum LDL-C were estimated, and noted as final levels. Results: There was greater reduction in terms of mean change in serum total cholesterol levels and low-density lipoprotein – cholesterol (LDL-C) levels with Rosuvastatin as compared to Atorvastatin in type 2 diabetic patients with hyperlipidemia. Conclusion: Rosuvastatin can significantly improve lipid profile as compared to Atorvastatin in type 2 diabetic patients with hyperlipidemia.

Background and Aim: Statins are among extensively used medications in diabetic patients. This study was designed to assess the outcome of atorvastatin pretreatment in renal ischemia- reperfusion in diabetic rats. Material and Methods: Wistar male rats (180-230 gr) were divided into 5 groups: normal control (CN), atorvastatin control (5 mg/kg) (CA), diabetic control (CD), diabetic group receiving atorvastatin 0.5 mg/kg (DA/a), diabetic group receiving atorvastatin 5 mg/kg (DA/b). Affter induction of type II diabetes by injection of nicotinamide and streptozotocin, the rats received daily atorvastatin or normal saline gavage for 2 months. Then, under anesthesia ischemia was induced for 45 min followed by reperfusion for 24 h. Blood and urine samples were collected for the measurement of lipid profile and renal function indices. Statistical analysis was performed by one-way analysis of variance and Tukey post-hoc test. Results: Total cholesterol and LDL were reduced in the group receiving atorvastatin (5 mg/kg) (P

Objective: The risk of cardiovascular disease increased in diabetic patients due to lipoprotein metabolism disorder and insulin resistance. There is different type of dyslipidemia in diabetic patient. The nicotinic acid (niacin) is categorized as vitamin B family and decreases low-density lipoproteins (LDL) and triglyceride (TG) level and increases high-density lipoproteins (HDL). The aim of this study was to compare the effect of niacin treatment with and without atorvastatin on lipid profile on diabetic patient. Materials and Methods: This study is cross over clinical trial on 30 diabetic patients (9 men, 21women) referred to diabetes research center of Yazd (IRAN). At initiation of study administered atorvastatin alone (20 mg/day) for 6 weeks (protocol A), and after 3 weeks washout period, started atorvastatin (20 mg/day) with niacin (50 mg/day) for 6 weeks (protocol B). Statistical analysis was accomplished by using SPSS for windows, version 11.50 and kappa and paired T-test. Results: Patients on protocol B had statistically significant more increase of HDL-C (P-value= 0.08) and decrease of TG than profile A (P-value= 0.024). Also, 2 hours post prandial blood sugar and HbA1c changes in two groups were not significant A (P-value= 0.226), B (P-value= 0.918). Patient in group B had statistically significant decrease in systolic blood pressure and diastolic blood pressure than group A (P-value= 0.010, P-value= 0.015). Conclusion: This study showed decrease of TG, LDL-C and total cholesterol and increase of HDL in both groups. There are significant changes in HDL-C and TG in group B that used niacin with atorvastatin than group A.

Objective: To observe the pharmacokinetic pattern of an innovator atorvastatin formulation, among Pakistani healthy volunteers. Study Design: Quasi-experimental design. Place and Duration of Study: It was conducted at research center of Army Medical College, from Dec 2011 to Aug 2012. Methodology: Twenty-four healthy male volunteers among Pakistani population participated in present study after approval by ethical committee. Each subject was given single dose of two oral tablet of atorvastatin each containing 40mg of atorvastatin after an overnight fast. Blood samples were collected at different time interval up to 48 hours. Atorvastatin was detected in human plasma using validated methodology involving use of highly sensitive HPLC technique. Acetonitrile and 0.05M sodium phosphate buffer were used for mobile phase and for internal standard progesterone was used. Pharmacokinetic indicators, including Cmax, Tmax, t1/2, AUC(0-t), and AUC(0-infinity), were calculated by using Computer program (APO, MWPHARM, and Ver. 3.60). Results: Pharmacokinetic parameters of 80 mg of tablet atorvastatin were observed in human plasma after oral administration of single oral dose. Drug was detected in plasma with mean peak concentration Cmax 23.97 μg/l and time to reach peak concentration Tmax 3.29 hours. Elimination half-life and elimination rate constant of atorvastatin was 6.11 ± 2.21 hours and 0.13 ± 0.06 l/hr respectively. Applying trapezoidal rule (t=48), for calculating AUC, it was to be found 175.24 ± 59.28 hr/μg/l for AUC0-48 and was 174.28 ± 60.50 hr/μg/l for AUC0–∞ MRT for atorvastatin was calculated as 8.81 ± 3.20 hours. Conclusion: Pharmacokinetic profile of branded.........