BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properti...BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properties,potentially offering antiepileptic effects.AIM To evaluate the anticonvulsant effects of rosuvastatin in animal models of epilepsy.METHODS Ninety-six albino mice were divided into 16 groups.In the maximal electroshock seizure(MES)model,eight groups received intraperitoneal vehicle,carbama-zepine,rosuvastatin,or a combination.Outcomes measured included seizure protection[tonic hind limb extension(THLE)],duration of THLE,seizure duration,and mortality.In the pentylenetetrazol(PTZ)model,eight groups were pretreated with vehicle,valproate,rosuvastatin,or a combination,with outcomes measured as seizure latency,seizure duration,and mortality.RESULTS In the MES model,rosuvastatin exhibited protection against THLE in a small percentage of mice.Rosuvastatin shortens the duration of THLE in a dose-dependent manner.However,none of these were statistically significant com-pared to the control group.The combination of rosuvastatin 10 mg/kg with carbamazepine 4 mg/kg resulted in a significant reduction in seizure duration compared to the control group,better than carbamazepine alone at 4 mg/kg and 6 mg/kg.In the PTZ model,rosuvastatin alone showed no significant effects on latency,duration of seizure,or mortality.However,rosuvastatin 10 mg/kg combined with valproate 100 mg/kg significantly delayed the onset of seizures,seizure duration and mortality percentage,better than valproate alone at 100 mg/kg.CONCLUSION Rosuvastatin enhanced the anticonvulsant effects of carbamazepine and valproate.Further studies are required to explore the antiepileptic potential of rosuvastatin at various doses,durations,dosage forms,routes and models.展开更多
Obesity associated dyslipidemia and its negative effects on the heart and blood vessels have emerged as a major healthcare challenge around the globe. The use of statins, potent inhibitors of hydroxyl-methyl glutaryl ...Obesity associated dyslipidemia and its negative effects on the heart and blood vessels have emerged as a major healthcare challenge around the globe. The use of statins, potent inhibitors of hydroxyl-methyl glutaryl (HMG) Co-A reductase, a rate-limiting enzyme in cholesterol biosynthesis, has significantly reduced the rates of cardiovascular and general mortality in patients with coronary artery disease. How statins lower plasma cholesterol levels presents a mechanistic conundrum since persistent exposure to these drugs in vitro or in vivo is known to induce overexpression of the HMG Co-A reductase gene and protein. In an attempt to solve this mechanistic puzzle, Schonewille et al, studied detailed metabolic parameters of cholesterol synthesis, inter-organ flux and excretion in mice treated with 3 common statins, rosuvastatin, atorvastatin or lovastatin, each with its unique pharmacokinetics. From the measurements of the rates of heavy water (D<sub>2</sub>O) and [<sup>13</sup>C]-acetate incorporation into lipids, the authors calculated the rates of whole body and organ-specific cholesterol synthesis in control and statin-treated mice. These analyses revealed dramatic enhancement in the rates of hepatic cholesterol biosynthesis in statin-treated mice that concomitantly elicited lower levels of cholesterol in their plasma. The authors have provided strong evidence to indicate that statin treatment in mice led to induction of compensatory metabolic pathways that apparently mitigated an excessive accumulation of cholesterol in the body. It was noted however that changes in cholesterol metabolism induced by 3 statins were not identical. While sustained delivery of all 3 statins led to enhanced rates of biliary excretion of cholesterol and its fecal elimination, only atorvastatin treated mice elicited enhanced trans-intestinal cholesterol excretion. Thus, blockade of HMGCR by statins in mice was associated with profound metabolic adaptations that reset their cholesterol homeostasis. The findings of Schonewille et al, deserve to be corroborated and extended in patients in order to more effectively utilize these important cholesterol-lowering drugs in the clinic.展开更多
Background Coronary artery calcification(CAC),a hallmark of atherosclerosis,paradoxically associates with reduced cardiovascular risk under statin therapy despite accelerated calcification progression,prompting this s...Background Coronary artery calcification(CAC),a hallmark of atherosclerosis,paradoxically associates with reduced cardiovascular risk under statin therapy despite accelerated calcification progression,prompting this study to explore CAC metrics as potential mediators between statin use and major adverse cardiovascular events(MACE).Methods Clinical data of 246 hospitalized patients who underwent coronary computed tomography angiography(CCTA)at Guangdong Provincial People's Hospital from January 2023 to June 2023 were retrospectively analyzed.Linear regression was used to evaluate the relationship between statin use and CAC parameters.Multivariable Poisson regression models were applied to explore the associations of statin use and CAC parameters with MACE risk.A mediation analysis was performed to assess the role of CAC parameters in the statin-MACE relationship.Results Statin use was independently associated with increased calcification score(β=0.648,P<0.001),CAC volume(β=0.623,P<0.001),and calcified plaque proportion(β=0.606,P=0.002).Multivariable Poisson regression indicated that statin use significantly reduced MACE risk[incidence rate ratio(IRR):0.33,P=0.018],whereas calcification score(IRR:2.63,P=0.026)and CACvolume(IRR:2.66,P=0.044)were associated with elevated MACE risk;Calcified plaque proportion showed no significant association.Mediation analysis revealed that calcification score(β=0.035,P=0.021)and CAC volume(β=0.023,P=0.018)exerted masking effects,while calcified plaque proportion had no mediating role.Conclusions Calcification score and CACvolume demonstrated limited masking effects in the association between statin use and MACE.展开更多
BACKGROUND The pleiotropic effects of statins,including anti-inflammatory and immunomodulatory actions,have prompted investigation into their perioperative role in colorectal cancer(CRC)surgery.However,findings remain...BACKGROUND The pleiotropic effects of statins,including anti-inflammatory and immunomodulatory actions,have prompted investigation into their perioperative role in colorectal cancer(CRC)surgery.However,findings remain inconsistent due to heterogeneity in study designs,statin regimens,and outcome definitions.This reviews current observational evidence,emphasizing the duration of statin therapy and its association with postoperative outcomes.AIM To evaluate the association between statin therapy and postoperative outcomes in patients undergoing CRC surgery.METHODS A systematic literature search was conducted using PubMed and Google Scholar through March 2025.Five cohort studies evaluating statin use in CRC surgery were included.Primary outcomes assessed included anastomotic leak,surgical site infection,and 30-day and 90-day mortality.Data on statin duration and confounders such as comorbidities and surgical variables were also extracted.RESULTS Three studies investigated the rates of anastomotic leaks in patients who used statins compared to those who did not.Two of the studies found no significant difference,while one noted a marginally higher leak rate among statin users.Diabetes,smoking habits,and operative time were found to be common confounding factors.Conversely,the use of statins was consistently linked to a decrease in 30-day mortality in propensity-matched groups,although findings regarding 90-day mortality were variable.CONCLUSION Statin therapy may confer short-term survival benefits in CRC surgical patients,potentially via anti-inflammatory or cytoprotective mechanisms.While evidence regarding anastomotic leaks remains inconclusive,trends suggest improved postoperative outcomes.These findings are constrained by methodological heterogeneity,underscoring the need for prospective,randomized studies to confirm benefits and identify optimal patient subgroups.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma(HCC).Recent clinical evidence indica...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma(HCC).Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics.However,it is still unclear if these drugs can lower the specific risk of HCC among patients with MASLD.AIM To investigate the impact of statin use on the risk of HCC development in patients with MASLD.METHODS A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with MASLD.The difference in HCC risk between statin users and non-users was calculated among MASLD patients.We also evaluated the risk difference between lipophilic versus hydrophilic statins and the effect of cumulative dose on HCC risk reduction.RESULTS A total of four studies consisting of 291684 patients were included.MASLD patients on statin therapy had a 60%lower pooled risk of developing HCC compared to the non-statin group[relative risk(RR)=0.40,95%CI:0.31-0.53,I2=16.5%].Patients taking lipophilic statins had a reduced risk of HCC(RR=0.42,95%CI:0.28-0.64),whereas those on hydrophilic statins had not shown the risk reduction(RR=0.57,95%CI:0.27-1.20).The higher(>600)cumulative defined daily doses(cDDD)had a 70%reduced risk of HCC(RR=0.30,95%CI:0.21-0.43).There was a 29%(RR=0.71,95%CI:0.55-0.91)and 43%(RR=0.57,95%CI:0.40-0.82)decreased risk in patients receiving 300-599 cDDD and 30-299 cDDD,respectively.CONCLUSION Statin use lowers the risk of HCC in patients with MASLD.The higher cDDD and lipophilicity of statins correlate with the HCC risk reduction.展开更多
In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause e...In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition;in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer’s disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin, on bone and osteometabolic diseases. However, statins in high doses cause inflammation in bone defects and inhibit osteoblastic differentiation, negatively contributing to bone repair. Thus, different types of studies with different concentrations of statins have been studied to positively or negatively correlate this drug with bone regeneration. In this review we will address the positive, negative or neutral effects of statins in relation to bone defects providing a comprehensive understanding of their application. Finally, we will discuss a variety of statin-based drugs and the ideal dose through a theoretical basis with preclinical, clinical and laboratory work in order to promote the repair of bone defects.展开更多
Recent data suggest that, in addition to improving dyslipidemia, statin may reduce the risk of infections and infection-related complications. The aim of this study is to make a review of the literature about the effe...Recent data suggest that, in addition to improving dyslipidemia, statin may reduce the risk of infections and infection-related complications. The aim of this study is to make a review of the literature about the effects of statins on clinically relevant outcomes of patients admitted to the hospital and having an infection and/or sepsis, principally in terms of intensive care unit admissions and related death.展开更多
We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuv...We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.展开更多
Acute pancreatitis （AP） secondary to drugs is uncommon, with an incidence ranging from 0.3% to 2.0% of AP cases. Drug-induced AP due to statins is rare, and only 12 cases have thus far been reported. In this case re...Acute pancreatitis （AP） secondary to drugs is uncommon, with an incidence ranging from 0.3% to 2.0% of AP cases. Drug-induced AP due to statins is rare, and only 12 cases have thus far been reported. In this case report, we report a case of a 50-year-old female on pravastatin therapy for 3 d prior to developing symptoms of AP. The common etiological factors for AP were all excluded. The patient was admitted to the intensive care unit secondary to respiratory distress, though she subsequently improved and was discharged 14 d after admission. Although the incidence of drug-induced AP is low, clinicians should have a high index of suspicion for it in patients with AP due to an unknown etiology. Clinicians should be aware of the association of statins with AR If a patient taking a statin develops abdominal pain, clinicians should consider the diagnosis of AP and conduct the appropriate laboratory and diagnostic evaluation if indicated.展开更多
In manuscript named "Statin use and risk of diabetes mellitus" by Chogtu et al, authors defined that pravastatin 40 mg/dL reduced the risk of diabetes by 30% in West of Scotland Coronary Prevention study. In...In manuscript named "Statin use and risk of diabetes mellitus" by Chogtu et al, authors defined that pravastatin 40 mg/dL reduced the risk of diabetes by 30% in West of Scotland Coronary Prevention study. In fact, pravastatin 40 mg/d L reduced coronary heart disease risk approximately 30% in mentioned study.展开更多
BACKGROUND Statins have an important and well-established role in the prevention of atherosclerotic cardiovascular disease(ASCVD).However,several studies have reported widespread underuse of statins in various practic...BACKGROUND Statins have an important and well-established role in the prevention of atherosclerotic cardiovascular disease(ASCVD).However,several studies have reported widespread underuse of statins in various practice settings and populations.Review of relevant literature reveals opportunities for improvement in the implementation of guideline-directed statin therapy(GDST).AIM To examine the impact of cardiologist intervention on the use of GDST in the ambulatory setting.METHODS Patients with at least one encounter at the adult Internal Medicine Clinic(IMC)and/or Cardiology Clinic(CC),who had an available serum cholesterol test performed,were evaluated.The 2 comparison groups were defined as:(1)Patients only seen by IMC;and(2)Patients seen by both IMC and CC.Patients were excluded if variables needed for calculation of ASCVD risk scores were lacking,and if demographic information lacked guideline-directed treatment recommendations.Data were analyzed using student t-tests or χ^2,as appropriate.Analysis of Variance was used to compare rates of adherence to GDST.RESULTS A total of 268 patients met the inclusion criteria for this study;211 in the IMC group and 57 in the IMC-CC group.Overall,56%of patients were female,mean age 56 years(±10.65,SD),22%Black or African American,56%Hispanic/Latino,14%had clinical ASCVD,13%current smokers,66%diabetic and 63%hypertensive.Statin use was observed in 55%(n=147/268)of the entire patient cohort.In the IMC-CC group,73.6%(n=42/57)of patients were prescribed statin therapy compared to 50.7%(n=107/211)of patients in the IMC group(P=0.002).In terms of appropriate statin use based on guidelines,there was no statistical difference between groups[IMC-CC group 61.4%(n=35/57)vs IMC group,55.5%(n=117/211),P=0.421].Patients in the IMC-CC group were older,had more cardiac risk factors and had higher proportions of non-white patients compared to the IMC group(P<0.02,all).CONCLUSION Although overall use of GDST was suboptimal,there was no statistical difference in appropriate statin use based on guidelines between groups managed by general internists alone or co-managed with a cardiologist.These findings highlight the need to design and implement strategies to improve adherence rates to GDST across all specialties.展开更多
Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, are considered as one of the most important drugs and the drug of choice for reducing an abnormal cholesterol level. Statins are nor...Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, are considered as one of the most important drugs and the drug of choice for reducing an abnormal cholesterol level. Statins are normally used to decrease the risk of coronary heart disease (CHD), but they tend to be associated with liver adverse effects. The objective of this prospective study was to investigate the effect of atorvastatin therapy on the liver function in patients with CHD. Study comprised of 66 newly diagnosed CHD patients who were selected from UNRWA clinics in the Gaza Strip. The patients were clinically examined and treated with atorvastatin (10 - 40 mg/day). A questionnaire was used to collect the data concerning patient’s characteristics. Total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), liver enzymes tests such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total and direct blood bilirubin were measured before starting treatment and after 3 and 6 months of treatment. The results showed a significant increase in the mean values of ALT, AST, total bilirubin and direct bilirubin levels after 3 months then decreased after the next 3 months, but they were higher than the baseline with insignificant association.展开更多
Osteoprotegerin (OPG) is a protein produced by many cell types that has the remarkable property of inhibiting bone loss. It does this by binding to the key bone resorptive cytokine, receptor activator of NF-kB ligand ...Osteoprotegerin (OPG) is a protein produced by many cell types that has the remarkable property of inhibiting bone loss. It does this by binding to the key bone resorptive cytokine, receptor activator of NF-kB ligand (RANKL). This cytokine is produced mainly by osteoblastic cells and is instrumental in osteoclast differentiation. If the ratio of RANKL:OPG increases, bone resorption increases and results in bone loss in diseases such osteoporosis, rheumatoid arthritis and hypercalcaemia of malignancy. Hence, if drugs can be found that increase OPG, this will decrease the activity of osteoclasts and therefore bone resorption. Statins are cholesterol lowering drugs that have recently been shown to increase bone formation in rodents. It was hypothesised from this finding that this could be due to an increase in OPG production. If these commonly prescribed drugs could be used to prevent bone loss or to increase bone formation then this may prove a useful means of reducing fracture risk in patients. Treating Saos-2 osteoblast-like cells in vitro with mevastatin increased OPG production and secretion through the mevalonate pathway. A failure of geranylgeranylation of Rho and/or farnesylation of Ras proteins leads to an increase in PI-3K activation then AKT activation leading to several different signaling pathways such as MAPK’s and NF-kB. NF-kB and p38MAPK inhibitors prevented the statin stimulation of OPG but not the decrease in cell number, suggesting that statins regulate OPG secretion via PI-3K, p38MAPK and NF-kB.展开更多
The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used in the primary and secondary prevention of cardiovascular diseases to lower serum cholesterol levels. As type 2 diabetes mellitus ...The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used in the primary and secondary prevention of cardiovascular diseases to lower serum cholesterol levels. As type 2 diabetes mellitus is accompanied by dyslipidemia, statins have a major role in preventing the long term complications in diabetes and are recommended for diabetics with normal low density lipoprotein levels as well. In 2012, United States Food and Drug Administration released changes to statin safety label to include that statins have been found to increase glycosylated haemoglobin and fasting serum glucose levels. Many studies done on patients with cardiovascular risk factors have shown that statins have diabetogenic potential and the effect varies as per the dosage and type used. The various mechanisms for this effect have been proposed and one of them is downregulation of glucose transporters by the statins. The recommendations by the investigators are that though statins can have diabetogenic risk, they have more long term benefits which can outweigh the risk. In elderly patients and those with metabolic syndrome, as the risk of diabetes increase, the statins should be used cautiously. Other than a subset of population with risk for diabetes; statins still have long term survival benefits in most of the patients.展开更多
文摘BACKGROUND Epilepsy impacts millions of people,with many not responding to existing treatments.Some evidence links neuroinflammatory processes to epilepsy.Statins exhibit anti-inflammatory and neuroprotective properties,potentially offering antiepileptic effects.AIM To evaluate the anticonvulsant effects of rosuvastatin in animal models of epilepsy.METHODS Ninety-six albino mice were divided into 16 groups.In the maximal electroshock seizure(MES)model,eight groups received intraperitoneal vehicle,carbama-zepine,rosuvastatin,or a combination.Outcomes measured included seizure protection[tonic hind limb extension(THLE)],duration of THLE,seizure duration,and mortality.In the pentylenetetrazol(PTZ)model,eight groups were pretreated with vehicle,valproate,rosuvastatin,or a combination,with outcomes measured as seizure latency,seizure duration,and mortality.RESULTS In the MES model,rosuvastatin exhibited protection against THLE in a small percentage of mice.Rosuvastatin shortens the duration of THLE in a dose-dependent manner.However,none of these were statistically significant com-pared to the control group.The combination of rosuvastatin 10 mg/kg with carbamazepine 4 mg/kg resulted in a significant reduction in seizure duration compared to the control group,better than carbamazepine alone at 4 mg/kg and 6 mg/kg.In the PTZ model,rosuvastatin alone showed no significant effects on latency,duration of seizure,or mortality.However,rosuvastatin 10 mg/kg combined with valproate 100 mg/kg significantly delayed the onset of seizures,seizure duration and mortality percentage,better than valproate alone at 100 mg/kg.CONCLUSION Rosuvastatin enhanced the anticonvulsant effects of carbamazepine and valproate.Further studies are required to explore the antiepileptic potential of rosuvastatin at various doses,durations,dosage forms,routes and models.
文摘Obesity associated dyslipidemia and its negative effects on the heart and blood vessels have emerged as a major healthcare challenge around the globe. The use of statins, potent inhibitors of hydroxyl-methyl glutaryl (HMG) Co-A reductase, a rate-limiting enzyme in cholesterol biosynthesis, has significantly reduced the rates of cardiovascular and general mortality in patients with coronary artery disease. How statins lower plasma cholesterol levels presents a mechanistic conundrum since persistent exposure to these drugs in vitro or in vivo is known to induce overexpression of the HMG Co-A reductase gene and protein. In an attempt to solve this mechanistic puzzle, Schonewille et al, studied detailed metabolic parameters of cholesterol synthesis, inter-organ flux and excretion in mice treated with 3 common statins, rosuvastatin, atorvastatin or lovastatin, each with its unique pharmacokinetics. From the measurements of the rates of heavy water (D<sub>2</sub>O) and [<sup>13</sup>C]-acetate incorporation into lipids, the authors calculated the rates of whole body and organ-specific cholesterol synthesis in control and statin-treated mice. These analyses revealed dramatic enhancement in the rates of hepatic cholesterol biosynthesis in statin-treated mice that concomitantly elicited lower levels of cholesterol in their plasma. The authors have provided strong evidence to indicate that statin treatment in mice led to induction of compensatory metabolic pathways that apparently mitigated an excessive accumulation of cholesterol in the body. It was noted however that changes in cholesterol metabolism induced by 3 statins were not identical. While sustained delivery of all 3 statins led to enhanced rates of biliary excretion of cholesterol and its fecal elimination, only atorvastatin treated mice elicited enhanced trans-intestinal cholesterol excretion. Thus, blockade of HMGCR by statins in mice was associated with profound metabolic adaptations that reset their cholesterol homeostasis. The findings of Schonewille et al, deserve to be corroborated and extended in patients in order to more effectively utilize these important cholesterol-lowering drugs in the clinic.
文摘Background Coronary artery calcification(CAC),a hallmark of atherosclerosis,paradoxically associates with reduced cardiovascular risk under statin therapy despite accelerated calcification progression,prompting this study to explore CAC metrics as potential mediators between statin use and major adverse cardiovascular events(MACE).Methods Clinical data of 246 hospitalized patients who underwent coronary computed tomography angiography(CCTA)at Guangdong Provincial People's Hospital from January 2023 to June 2023 were retrospectively analyzed.Linear regression was used to evaluate the relationship between statin use and CAC parameters.Multivariable Poisson regression models were applied to explore the associations of statin use and CAC parameters with MACE risk.A mediation analysis was performed to assess the role of CAC parameters in the statin-MACE relationship.Results Statin use was independently associated with increased calcification score(β=0.648,P<0.001),CAC volume(β=0.623,P<0.001),and calcified plaque proportion(β=0.606,P=0.002).Multivariable Poisson regression indicated that statin use significantly reduced MACE risk[incidence rate ratio(IRR):0.33,P=0.018],whereas calcification score(IRR:2.63,P=0.026)and CACvolume(IRR:2.66,P=0.044)were associated with elevated MACE risk;Calcified plaque proportion showed no significant association.Mediation analysis revealed that calcification score(β=0.035,P=0.021)and CAC volume(β=0.023,P=0.018)exerted masking effects,while calcified plaque proportion had no mediating role.Conclusions Calcification score and CACvolume demonstrated limited masking effects in the association between statin use and MACE.
文摘BACKGROUND The pleiotropic effects of statins,including anti-inflammatory and immunomodulatory actions,have prompted investigation into their perioperative role in colorectal cancer(CRC)surgery.However,findings remain inconsistent due to heterogeneity in study designs,statin regimens,and outcome definitions.This reviews current observational evidence,emphasizing the duration of statin therapy and its association with postoperative outcomes.AIM To evaluate the association between statin therapy and postoperative outcomes in patients undergoing CRC surgery.METHODS A systematic literature search was conducted using PubMed and Google Scholar through March 2025.Five cohort studies evaluating statin use in CRC surgery were included.Primary outcomes assessed included anastomotic leak,surgical site infection,and 30-day and 90-day mortality.Data on statin duration and confounders such as comorbidities and surgical variables were also extracted.RESULTS Three studies investigated the rates of anastomotic leaks in patients who used statins compared to those who did not.Two of the studies found no significant difference,while one noted a marginally higher leak rate among statin users.Diabetes,smoking habits,and operative time were found to be common confounding factors.Conversely,the use of statins was consistently linked to a decrease in 30-day mortality in propensity-matched groups,although findings regarding 90-day mortality were variable.CONCLUSION Statin therapy may confer short-term survival benefits in CRC surgical patients,potentially via anti-inflammatory or cytoprotective mechanisms.While evidence regarding anastomotic leaks remains inconclusive,trends suggest improved postoperative outcomes.These findings are constrained by methodological heterogeneity,underscoring the need for prospective,randomized studies to confirm benefits and identify optimal patient subgroups.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma(HCC).Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics.However,it is still unclear if these drugs can lower the specific risk of HCC among patients with MASLD.AIM To investigate the impact of statin use on the risk of HCC development in patients with MASLD.METHODS A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with MASLD.The difference in HCC risk between statin users and non-users was calculated among MASLD patients.We also evaluated the risk difference between lipophilic versus hydrophilic statins and the effect of cumulative dose on HCC risk reduction.RESULTS A total of four studies consisting of 291684 patients were included.MASLD patients on statin therapy had a 60%lower pooled risk of developing HCC compared to the non-statin group[relative risk(RR)=0.40,95%CI:0.31-0.53,I2=16.5%].Patients taking lipophilic statins had a reduced risk of HCC(RR=0.42,95%CI:0.28-0.64),whereas those on hydrophilic statins had not shown the risk reduction(RR=0.57,95%CI:0.27-1.20).The higher(>600)cumulative defined daily doses(cDDD)had a 70%reduced risk of HCC(RR=0.30,95%CI:0.21-0.43).There was a 29%(RR=0.71,95%CI:0.55-0.91)and 43%(RR=0.57,95%CI:0.40-0.82)decreased risk in patients receiving 300-599 cDDD and 30-299 cDDD,respectively.CONCLUSION Statin use lowers the risk of HCC in patients with MASLD.The higher cDDD and lipophilicity of statins correlate with the HCC risk reduction.
文摘In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition;in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer’s disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin, on bone and osteometabolic diseases. However, statins in high doses cause inflammation in bone defects and inhibit osteoblastic differentiation, negatively contributing to bone repair. Thus, different types of studies with different concentrations of statins have been studied to positively or negatively correlate this drug with bone regeneration. In this review we will address the positive, negative or neutral effects of statins in relation to bone defects providing a comprehensive understanding of their application. Finally, we will discuss a variety of statin-based drugs and the ideal dose through a theoretical basis with preclinical, clinical and laboratory work in order to promote the repair of bone defects.
文摘Recent data suggest that, in addition to improving dyslipidemia, statin may reduce the risk of infections and infection-related complications. The aim of this study is to make a review of the literature about the effects of statins on clinically relevant outcomes of patients admitted to the hospital and having an infection and/or sepsis, principally in terms of intensive care unit admissions and related death.
文摘We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.
文摘Acute pancreatitis （AP） secondary to drugs is uncommon, with an incidence ranging from 0.3% to 2.0% of AP cases. Drug-induced AP due to statins is rare, and only 12 cases have thus far been reported. In this case report, we report a case of a 50-year-old female on pravastatin therapy for 3 d prior to developing symptoms of AP. The common etiological factors for AP were all excluded. The patient was admitted to the intensive care unit secondary to respiratory distress, though she subsequently improved and was discharged 14 d after admission. Although the incidence of drug-induced AP is low, clinicians should have a high index of suspicion for it in patients with AP due to an unknown etiology. Clinicians should be aware of the association of statins with AR If a patient taking a statin develops abdominal pain, clinicians should consider the diagnosis of AP and conduct the appropriate laboratory and diagnostic evaluation if indicated.
文摘In manuscript named "Statin use and risk of diabetes mellitus" by Chogtu et al, authors defined that pravastatin 40 mg/dL reduced the risk of diabetes by 30% in West of Scotland Coronary Prevention study. In fact, pravastatin 40 mg/d L reduced coronary heart disease risk approximately 30% in mentioned study.
文摘BACKGROUND Statins have an important and well-established role in the prevention of atherosclerotic cardiovascular disease(ASCVD).However,several studies have reported widespread underuse of statins in various practice settings and populations.Review of relevant literature reveals opportunities for improvement in the implementation of guideline-directed statin therapy(GDST).AIM To examine the impact of cardiologist intervention on the use of GDST in the ambulatory setting.METHODS Patients with at least one encounter at the adult Internal Medicine Clinic(IMC)and/or Cardiology Clinic(CC),who had an available serum cholesterol test performed,were evaluated.The 2 comparison groups were defined as:(1)Patients only seen by IMC;and(2)Patients seen by both IMC and CC.Patients were excluded if variables needed for calculation of ASCVD risk scores were lacking,and if demographic information lacked guideline-directed treatment recommendations.Data were analyzed using student t-tests or χ^2,as appropriate.Analysis of Variance was used to compare rates of adherence to GDST.RESULTS A total of 268 patients met the inclusion criteria for this study;211 in the IMC group and 57 in the IMC-CC group.Overall,56%of patients were female,mean age 56 years(±10.65,SD),22%Black or African American,56%Hispanic/Latino,14%had clinical ASCVD,13%current smokers,66%diabetic and 63%hypertensive.Statin use was observed in 55%(n=147/268)of the entire patient cohort.In the IMC-CC group,73.6%(n=42/57)of patients were prescribed statin therapy compared to 50.7%(n=107/211)of patients in the IMC group(P=0.002).In terms of appropriate statin use based on guidelines,there was no statistical difference between groups[IMC-CC group 61.4%(n=35/57)vs IMC group,55.5%(n=117/211),P=0.421].Patients in the IMC-CC group were older,had more cardiac risk factors and had higher proportions of non-white patients compared to the IMC group(P<0.02,all).CONCLUSION Although overall use of GDST was suboptimal,there was no statistical difference in appropriate statin use based on guidelines between groups managed by general internists alone or co-managed with a cardiologist.These findings highlight the need to design and implement strategies to improve adherence rates to GDST across all specialties.
文摘Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, are considered as one of the most important drugs and the drug of choice for reducing an abnormal cholesterol level. Statins are normally used to decrease the risk of coronary heart disease (CHD), but they tend to be associated with liver adverse effects. The objective of this prospective study was to investigate the effect of atorvastatin therapy on the liver function in patients with CHD. Study comprised of 66 newly diagnosed CHD patients who were selected from UNRWA clinics in the Gaza Strip. The patients were clinically examined and treated with atorvastatin (10 - 40 mg/day). A questionnaire was used to collect the data concerning patient’s characteristics. Total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), liver enzymes tests such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total and direct blood bilirubin were measured before starting treatment and after 3 and 6 months of treatment. The results showed a significant increase in the mean values of ALT, AST, total bilirubin and direct bilirubin levels after 3 months then decreased after the next 3 months, but they were higher than the baseline with insignificant association.
文摘Osteoprotegerin (OPG) is a protein produced by many cell types that has the remarkable property of inhibiting bone loss. It does this by binding to the key bone resorptive cytokine, receptor activator of NF-kB ligand (RANKL). This cytokine is produced mainly by osteoblastic cells and is instrumental in osteoclast differentiation. If the ratio of RANKL:OPG increases, bone resorption increases and results in bone loss in diseases such osteoporosis, rheumatoid arthritis and hypercalcaemia of malignancy. Hence, if drugs can be found that increase OPG, this will decrease the activity of osteoclasts and therefore bone resorption. Statins are cholesterol lowering drugs that have recently been shown to increase bone formation in rodents. It was hypothesised from this finding that this could be due to an increase in OPG production. If these commonly prescribed drugs could be used to prevent bone loss or to increase bone formation then this may prove a useful means of reducing fracture risk in patients. Treating Saos-2 osteoblast-like cells in vitro with mevastatin increased OPG production and secretion through the mevalonate pathway. A failure of geranylgeranylation of Rho and/or farnesylation of Ras proteins leads to an increase in PI-3K activation then AKT activation leading to several different signaling pathways such as MAPK’s and NF-kB. NF-kB and p38MAPK inhibitors prevented the statin stimulation of OPG but not the decrease in cell number, suggesting that statins regulate OPG secretion via PI-3K, p38MAPK and NF-kB.
文摘The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used in the primary and secondary prevention of cardiovascular diseases to lower serum cholesterol levels. As type 2 diabetes mellitus is accompanied by dyslipidemia, statins have a major role in preventing the long term complications in diabetes and are recommended for diabetics with normal low density lipoprotein levels as well. In 2012, United States Food and Drug Administration released changes to statin safety label to include that statins have been found to increase glycosylated haemoglobin and fasting serum glucose levels. Many studies done on patients with cardiovascular risk factors have shown that statins have diabetogenic potential and the effect varies as per the dosage and type used. The various mechanisms for this effect have been proposed and one of them is downregulation of glucose transporters by the statins. The recommendations by the investigators are that though statins can have diabetogenic risk, they have more long term benefits which can outweigh the risk. In elderly patients and those with metabolic syndrome, as the risk of diabetes increase, the statins should be used cautiously. Other than a subset of population with risk for diabetes; statins still have long term survival benefits in most of the patients.
