High-dose Atorvastatin Research Articles

Effects of high dose atorvastatin on nerve function and expression of NF-kappa B and IL-6 in patients with acute cerebral infarction

Objective To study the effect of high-dose atorvastatin on nerve function and the levels of nuclear transcription factor-κB (NF-κB) and interleukin-6 (IL-6) in patients with acute cerebral infarction. Methods The clinical data of 72 patients with acute cerebral infarction treated by atorvastatin in our hospital from February 2017 to August 2018 were analyzed retrospectively, who were divided into routine dose group (36 cases) and high dose group (36 cases). NF-κB, IL-6 and NIH Stroke Scale (NIHSS) score were compared between the two groups. Results Before treatment, there were no statistically significant differences in the levels of NF-κB and IL-6 and NIHSS score between the two groups (P>0.05); after 14 days of treatment, the levels of NF-κB and IL-6 in the high dose group were (0.54±0.13) ng/L, (115.32±16.97) ng/L, which were lower than those of the normal dose group [(0.69±0.12) ng/L, (131.12±18.95) ng/L], with statistically significant differences (P<0.05). On the 7th, 14th, and 21st day after treatment, the NIHSS score in the high-dose group were (9.19±3.15), (8.51±2.03), and (5.78±1.39), respectively, which were lower than those in the conventional dose group [(14.75±3.44), (14.53±3.16), (13.14±3.05)], with statistically significant differences (P<0.05). Conclusion High dose of atorvastatin can effectively relieve inflammatory reaction and improve neurological function in patients with acute cerebral infarction. Key words: Acute cerebral infarction; Atorvastatin; High dose; Neurological function; Nuclear transcription factor-κB (NF-κB); Interleukin-6 (IL-6)

Prophylactic atorvastatin prior to intra-arterial administration of iodinated contrast media for prevention of contrast-induced acute kidney injury: A meta-analysis of randomized trial data .

The efficacy of high-dose atorvastatin pretreatment in reducing the incidence of contrast-induced nephropathy in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) has been examined in some randomized studies. However, the results across the trials remain controversial. This study sought to perform a meta-analysis to evaluate the effect of high-dose atorvastatin in the prevention of contrast-induced nephropathy (CIN) while undergoing CAG or PCI. Comprehensive literature searches for randomized controlled trials (RCTs) comparing high-dose atorvastatin vs. low-dose statin or placebo pretreatment for prevention of contrast-induced acute kidney injury in patients undergoing CAG were performed using PubMed, Embase, and the Cochrane library updated to June 2017. The primary outcome was the incidence of CIN. A total of 11 RCTs were included in this analysis. The high-dose atorvastatin treatment can significantly reduce the incidence of CIN (OR 0.46, 95% CI 0.35-0.62, p<0.00001). The benefit was consistent in comparison with the low-dose group (OR 0.41, 95% CI 0.25-0.66, p=0.0003) and the placebo group (OR 0.50, 95% CI 0.26-0.98, p=0.04). Our study demonstrates that high-dose statin pretreatment shows a benefit specifically in reducing the incidence of contrast-induced acute kidney injury in patients undergoing CAG, especially compared with low-dose statin pretreatment.

46. GCA: Diagnosed with a heavy heart

IntroductionGiant cell arteritis (GCA) represents a common cause of uncertainty for physicians. GCA can present as an indolent or aggressive process with a wide spectrum of symptoms and signs. The key to diagnosis is good clinical acumen and awareness of both common and rare associated conditions. Here we describe a rare and atypical presentation of a patient with GCA and chest pain.Case descriptionAn 83-year old male was admitted to the medical take with 3 hours of crushing chest pain associated with diaphoresis and nausea. He had been started on 60mg prednisolone by his GP 3 days preceding this for suspected GCA (scalp tenderness, jaw claudication, polymyalgia). Past medical history included: hypertension, recent strokes (bilateral cerebellar infarcts 3 months prior), previous DVTs and COPD. Examination revealed no abnormalities. Admission ECGs showed sinus rhythm with fixed T-wave inversion in aVL and V3. Chest radiograph was normal. Bloods tests revealed mildly raised inflammatory markers (CRP, ESR 24) and a dynamic troponin (324 – 1241 – 1431 ng/L). He was diagnosed with a non-ST elevation myocardial infarction (NSTEMI) and was referred to Cardiology for an angiogram. He was started on dual antiplatelets and high dose atorvastatin. On review by Rheumatology, his recent history of bilateral posterior circulation strokes was investigated further. Multi-level bilateral vertebral artery stenosis was seen on CT angiogram at the regional hyper-acute stroke unit and diagnosed as atheromatous in origin due to: a negative right-sided temporal artery biopsy, no GCA symptoms and modest inflammatory markers (CRP in the 30s and ESR in the 20s). Due to the onset of clear and acute GCA symptoms a left-sided temporal artery biopsy and PET scan was scheduled. Prednisolone was reduced to 40mg OD due to concern over its atherogenicity during a suspected NSTEMI. Coronary angiogram went on to show clear arteries and a subsequent cardiac MRI confirmed acute myocarditis. The left temporal artery biopsy revealed chronic inflammation with scattered giant cells. The patient was diagnosed with: GCA, extra-cranial vasculitis and myocarditis. He was treated with intravenous methylprednisolone, a weaning course of prednisolone and started on methotrexate (15mg weekly). The patient’s chest pain settled soon after admission and his troponin and inflammatory markers fell with prednisolone. DiscussionGCA seldom presents with myocarditis and can lead to significant morbidity and mortality. This remains an important differential in a patient with clear GCA features and chest pain. This case report adds to the growing body of evidence that myocarditis is a recognised feature of GCA. A literature review revealed 8 articles and a total of 9 patients with GCA who presented with or developed myocarditis.The initial diagnosis of an NSTEMI was reasonable in this case and the most probable cause of the patient’s symptoms, signs and blood results at the time. To this end, starting dual anti-platelets was justified. His prednisolone was reduced to 40mg due to concerns over accelerated atherosclerosis with high dose glucocorticoids in an already high-risk male with smoking history, hypertension and a stroke history. In retrospect, this was an unnecessary step, but arguably reasonable when weighing the risks and benefits of one treatment against a simultaneous acute illness (NSTEMI).Each subsequent investigation helped to diagnose and exclude certain conditions: the angiogram was necessary to exclude an acute coronary syndrome; cardiac MRI then went on to provide evidence of myocarditis; temporal artery biopsy confirmed GCA and a PET scan excluded any significant large vessel involvement. Interestingly, the first right-sided temporal artery biopsy 3 months prior was negative but the second left-sided biopsy was diagnostic. The BSR states that “contralateral biopsy is usually unnecessary”; however, a few studies have found discordant results when carrying out simultaneous bilateral biopsies with an increased diagnostic yield (Boyev et al., 1999; Breuer et al., 2009 and Durling et al., 2014), suggesting bilateral temporal artery biopsies could lead to less treatment delays and more accurate diagnoses.Key learning pointsMyocarditis is a recognised complication of giant cell arteritis.The key to diagnosis here was a thorough history and an open mind with regards to his background, particularly the bilateral strokes. Investigations initially did not support GCA-associated myocarditis. But the preceding typical GCA symptoms and recent strokes raised the suspicion of a more systemic vasculitis.Working off others’ diagnosis can be misleading. The very recent bilateral posterior circulation strokes and vertebral artery abnormalities were overlooked on admission due to being thoroughly worked up and disregarded as vasculitic by a tertiary stroke centre.Conflicts of interestThe authors have declared no conflicts of interest.

25. Use of rituximab in refractory primary antiphospholipid syndrome with pulmonary and cerebral manifestations

25. Use of rituximab in refractory primary antiphospholipid syndrome with pulmonary and cerebral manifestations

High dose of Atorvastatin versus Rosuvastatin as Preventive Strategies for Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention

High dose of Atorvastatin versus Rosuvastatin as Preventive Strategies for Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention

The comparative effects of high dose atorvastatin and proprotein convertase subtilisin/kexin type 9 inhibitor on the mitochondria of oxidative muscle fibers in obese-insulin resistant female rats

The present study aimed to compare the effects of high dose atorvastatin and a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on the mitochondrial function in oxidative muscle fibers in obese female rats. Female Wistar rats were fed with either a normal diet (ND: n = 12) or a high-fat diet (HFD: n = 36) for a total of 15 weeks. At week 13, ND-fed rats received a vehicle, and HFD-fed rats were divided to three groups to receive either a vehicle, 40 mg/kg/day of atorvastatin, or 4 mg/kg/day of PCSK9 inhibitor (SBC-115076) for 3 weeks. Soleus muscles were investigated to assess mitochondrial ROS, membrane potential, swelling, mitochondrial-related protein expression, and level of malondialdehyde (MDA). The results showed that HFD-fed rats with vehicle developed obese-insulin resistance and dyslipidemia. Both atorvastatin and PCSK9 inhibitor reduced obesity and dyslipidemia, as well as improved insulin sensitivity in HFD-fed rats. However, the efficacy of PCSK9 inhibitor to increase weight loss and reduce dyslipidemia in HFD-fed rats was greater than those of atorvastatin. An increase in MDA level, ratio of p-Drp1ser616/total Drp1 protein, CPT1 protein, mitochondrial ROS, and membrane depolarization in the soleus muscle were observed in HFD-fed rats with vehicle. PCSK9 inhibitor enabled the restoration of all these parameters to normal levels. However, atorvastatin facilitated restoration of some parameters, including MDA level, p-Drp1ser616/total Drp1 ratio, and CPT1 protein expression. These findings suggest that PCSK9 inhibitor is superior to atorvastatin in instigating weight loss, cholesterol reduction, and attenuation of mitochondrial oxidative stress in oxidative muscle fibers of obese female rats.

Comparative studies on the effects of different doses of atorvastatin combined with aspirin on inflammatory cytokines and carotid plaques in patients with ischemic cerebrovascular disease

Objective: To make comparative studies on the effects of different doses of atorvastatin combined with aspirin on inflammatory cytokines, blood lipids, blood glucose, other biochemical indexes and carotid plaques in patients with ischemic cerebrovascular disease (ICVD) and carotid plaques.Method: One hundred and twenty patients with ICVD and carotid plaques admitted by Renmin Hospital, Hubei University of Medicine Hospital from December 2016 to December 2017 were selected and randomly divided into experimental group and control group, 60 cases in each group. Patients in the control group was asked to orally take standard dose of atorvastatin (20 mg/d) combined with aspirin enteric-coated tablets (100 mg/d). Patients in the experimental group was asked to orally take high-dose atorvastatin (40 mg/d) combined with the same amount of aspirin enteric-coated tablets. Patients in two groups were treated for 6 months averagely. The levels of inflammatory factors, changes in blood biochemical parameters and carotid plaque degrees of patients in two groups before and after treatment were inspected and compared.Results: The levels of serum high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF-a), interleukin-6 (IL-6) and homocysteine (Hcy) in patients of the experimental group after treatment were higher than those in the control group, difference with statistical significance (p < .05). The total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) in patients of the experimental group after treatment were lower than those in the control group and before treatment. The high-density lipoprotein cholesterol (HDL-C) was higher than that of the control group and before treatment, the levels of fasting blood glucose (FBS) and glycosylated hemoglobin (HbAIc) in patients of the experimental group significantly increased compared to those before treatment, difference with statistical significance (p < .05). There was no significant change in the control group. The carotid intima-media thickness (IMT) and plaque area in patients of the experimental group were lower than those in the control group and before treatment, difference with statistical significance (p < .05).Conclusion: High-dose atorvastatin combined with aspirin for treatment of patients with ICVD can effectively reduce inflammatory inflammatory cytokine levels in serum and reduce IMT and carotid plaque area. With more obvious effect than lower dose of atorvastatin combined with aspirin, it is easy to cause blood glucose abnormality. So, it is necessary to pay attention to monitoring blood sugar during medication period.

Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System.

To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI). Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg-1·d-1, respectively) groups, atorvastatin (ATV) group (7.2 g·kg-1·d-1), chloroquine (CQ) group (10 g·kg-1·d-1), and highdose TXL + CQ group. After pharmacological administration for 7 days, rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion. Blood was taken for cardiac troponin I (cTnI) detection and hearts were harvested for infarct staining and apoptosis detection. The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting. Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL. TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.

1947-P: Comparative Effects of PCSK9 Inhibitor and High-Dose Atorvastatin on Mitochondria of Red Muscle Fibers in Obese Female Rats

Obesity and dyslipidemia cause mitochondrial dysfunction of skeletal muscle. Low dose atorvastatin impairs mitochondrial function of white muscle fibers but does not damage that of red muscle fibers. However, the effects of PCSK9 inhibitors and high dose atorvastatin on mitochondrial function of red muscle fibers have not been identified. Twenty-four female rats (180-200 g) were divided into 2 groups. Six rats were fed with normal diet (ND) and 18 rats were fed with high-fat diet (HFD) for 15 weeks. At week 12, ND-fed rats were treated with vehicle (NDV), while HFD-fed rats were equally subdivided and treated with either vehicle (HFV), 4 mg/kg/day of PCSK9 inhibitor (HFP), or 40 mg/kg/day of atorvastatin (HFA) for another 3 weeks. HFV rats developed obesity and dyslipidemia, as indicated by increased weight, visceral fat, and total cholesterol. Treatment with atorvastatin and PCSK9 inhibitor improved obesity and dyslipidemia. Increased lipid peroxidation (MDA), mitochondrial fission (pDrp1/Drp1), mitochondrial ROS production, and mitochondrial membrane depolarization were found in soleus muscle of HFV rats. Treatment with atorvastatin and PCSK9 inhibitor similarly improved lipid peroxidation and mitochondrial fission. However, only PCSK9 inhibitor improved mitochondrial ROS production and mitochondrial membrane depolarization. Our findings suggest that obesity increases lipid peroxidation, mitochondrial fission, mitochondrial ROS production, and mitochondrial membrane depolarization in red muscle fibers. PCSK9 inhibitor attenuates those deleterious effects of obesity. High dose atorvastatin improves lipid peroxidation and mitochondrial fission, but does not attenuate obesity-induced mitochondrial ROS production and mitochondrial membrane depolarization in red muscle fibers. The results imply that high dose atorvastatin causes adverse effects on red muscle fibers despite its benefit on the improvement of obesity and dyslipidemia. Disclosure C. Thonusin: None. S. Palee: None. B. Arunsak: None. P. Amput: None. W. Pratchayasakul: None. N. Chattipakorn: None. S.C. Chattipakorn: None. Funding Thailand Research Fund

Could Short-Term Perioperative High-Dose Atorvastatin Offer Antiarrhythmic and Cardio-Protective Effects in Rheumatic Valve Replacement Surgery?

To evaluate the role of prophylactic high-dose atorvastatin for prevention of postoperative atrial fibrillation (POAF), inflammatory response attenuation, and myocardial protection after valve replacement cardiac surgery. Randomized controlled trial. Assiut University Hospitals. Sixty-four adult patients undergoing cardiac valve replacement surgery. The participants were equally divided into 2 groups. Group S received 80 mg of atorvastatin (oral tablets), 12 and 2 hours preoperatively, and on the 2nd, 3rd, 4th, and 5th postoperative days. Control group C received placebo at the same time periods. The incidence of POAF, postoperative white blood cell count, serum C-reactive protein, interleukin 6, and troponin I. Group S patients showed a lower incidence of POAF compared with the placebo group (p = 0.031). The white blood cell count showed significant reductions in group S compared with group C on the second, third, fourth, and fifth postoperative days. The C-reactive protein level showed significant reductions on the third, fourth, and fifth postoperative days in group S compared with group C (p = 0.001, 0.001, and 0.001, respectively). The serum level of interleukin 6 showed a significant reduction on the fifth postoperative day in group S compared with group C (p = 0.001). There was no significant difference between the 2 groups regarding the troponin I level and inotropic score. Prophylactic use of high dose atorvastatin can decrease the incidence of POAF and attenuate the inflammatory process in adult patients undergoing isolated rheumatic cardiac valve replacement surgery.

Complementary low-density lipoprotein-cholesterol lowering and pharmacokinetics of adding bempedoic acid (ETC-1002) to high-dose atorvastatin background therapy in hypercholesterolemic patients: A randomized placebo-controlled trial

Bempedoic acid is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia. The aim of the study was to assess the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of bempedoic acid added to stable high-intensity atorvastatin background therapy and multiple-dose plasma pharmacokinetics of atorvastatin alone and combined with steady-state bempedoic acid. This was a phase 2 study in patients with hypercholesterolemia (NCT02659397). Patients received once-daily open-label atorvastatin 80mg for 4weeks then were randomized 2:1 at baseline to receive double-blind bempedoic acid 180mg (n=45) or placebo (n=23) plus open-label atorvastatin 80mg for 4weeks. Efficacy was assessed 4weeks after randomization. Atorvastatin and metabolites' steady-state levels were analyzed before first dosing with bempedoic acid and after 2weeks of treatment. The 4-week stabilization phase with 80mg atorvastatin resulted in approximately 40% lowering of LDL-C values from screening. The placebo-adjusted least squares mean lowering of LDL-C from baseline to Day 29 with bempedoic acid was 22% (P=.003). Placebo-adjusted reductions from baseline with bempedoic acid also were significant for total cholesterol (-10%; P=.014), non-high-density lipoprotein cholesterol (-13%; P=.015), apolipoprotein B (-15%; P=.004), and high-sensitivity C-reactive protein (-44%; P=.002). Point estimates of bempedoic acid effects on steady-state atorvastatin and ortho-hydroxy atorvastatin area under the curve were <30% and not clinically meaningful. Bempedoic acid 180mg added to stable high-dose atorvastatin therapy effectively lowers LDL-C in patients with hypercholesterolemia without causing clinically important increases in atorvastatin exposure.

Statins in Ischemic Stroke Prevention: What Have We Learned in the Post-SPARCL (The Stroke Prevention by Aggressive Reduction in Cholesterol Levels) Decade?

We describe the current status of lipid-lowering therapies for ischemic stroke prevention. The SPARCL trial published in 2006 has been a landmark study in vascular neurology. The trial demonstrated that high-dose atorvastatin prevents recurrent stroke, and led the AHA/ASA to recommend statin therapy for patients with stroke or TIA of atherosclerotic origin. Recently, the J-STARS study demonstrated that therapy with low-dose pravastatin reduced atherothrombotic infarction incidence among patients with prior ischemic stroke. Besides, several trials have shown improved stroke outcomes with non-statin lipid-lowering medications: IMPROVE-IT with ezetimibe on top of simvastatin and PCSK9 inhibitors-FOURIER with evocolumab and ODYSSEY-OUTCOMES with alirocumab-on top of statin therapy. LDL-cholesterol remains the primary lipid treatment target for reduction of stroke risk. Randomized trials have shown that each reduction of 40mg/dL in the level of LDL-cholesterol reduces the stroke risk by approximately one quarter, and further, reductions in LDL-cholesterol levels have shown to produce additional reductions in stroke risk. Currently, we have evidence of benefit for adding non-statin lipid-modifying therapies to statins to reduce stroke risk. Surely, these novel strategies to reduce residual lipidic risk will provide future benefits on stroke prevention.

Atorvastatin Improves Doxorubicin-Induced Cardiac Dysfunction by Modulating Hsp70, Akt, and MAPK Signaling Pathways.

Atorvastatin is a lipid-regulating drug that is commonly used in clinical practice and can stabilize plaques. Increasing evidence shows that statins have anti-heart failure (HF) effects, but their specific mechanism is not clear. The purpose of this study was to investigate the cardioprotective effects of atorvastatin on HF in rats and its mechanism. Continuous intraperitoneal injection of 2.5 mg/kg/w doxorubicin for 6 weeks, with a cumulative dose of 15 mg/kg, was used to induce a rat model of HF. Then, the rats were treated with low-dose atorvastatin, high-dose atorvastatin, or saline for 4 weeks. In the DOX-treated groups, echocardiography showed decreases in left ventricular ejection fraction and fractional shortening and increases in left ventricular end-diastolic diameter and left ventricular posterior wall thickness compared with those in the control group, and increased levels of brain natriuretic peptide and Hsp70 were also found in the doxorubicin-treated groups. Compared with saline intervention, atorvastatin ameliorated left ventricular ejection fraction, fractional shortening, left ventricular end-diastolic diameter, and left ventricular posterior wall thickness (a significant difference was observed only in the high-dose group) and reduced serum brain natriuretic peptide. Hematoxylin and eosin staining showed that atorvastatin ameliorated myocardial injury. The improvement in cardiac function induced by atorvastatin was accompanied by increased Hsp70 expression, decreased p-ERK and p-JNK expression, and a reduction in myocardial fibrosis shown by Masson staining. In addition, atorvastatin had a protective effect on the myocardial apoptosis signaling pathway, with increased p-Akt expression and downregulated cleaved caspase-3 expression, and the reduction in myocardial apoptosis was confirmed by a TUNEL assay. Therefore, our experiments demonstrated that atorvastatin may protect cardiac function by modulating Hsp70, p-Akt, p-ERK, and p-JNK signaling to reduce myocardial fibrosis and myocardial apoptosis.

Effect of loading dose of atorvastatin therapy prior to percutaneous coronary intervention in patients with acute coronary syndrome: a meta-analysis of six randomized controlled trials.

PurposeThe study sought to summarize the evidence of pre-procedural atorvastatin therapy to improve the prognosis of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).Patients and methodsWe searched PubMed and Embase from inception to July 2018 for randomized controlled trials that compared loading dose atorvastatin pretreatment with no or low dose for the prevention of cardiovascular events. The primary end points were all-cause mortality and myocardial infarction (MI) at 30 days. The secondary end point was 30-day major adverse cardiovascular events (MACE), a composite of all-cause mortality, MI, and revascularization.ResultsSix trials with 4,991 individuals were included in our meta-analysis. High-dose atorvastatin preloading before PCI was associated with a 27% relative reduction in MI (OR: 0.73, 95% CI, 0.56–0.94, P=0.015). All-cause mortality was nonsignificantly reduced by early treatment with high-potency atorvastatin (OR: 0.94, 95% CI, 0.69–1.30, P=0.725). There was a 20% reduction in MACE in the group of patients treated with statin loading prior to PCI (OR: 0.80, 95% CI, 0.66–0.97, P=0.026). When stratified according to the diagnosis of ACS, the results of MACE were only significant for those ST-elevation myocardial infarction patients undergoing PCI (OR: 0.67, 95% CI, 0.48–0.94, P=0.022) and were not noted in the group of non-ST elevation ACS patients (OR: 0.65, 95% CI, 0.35–1.22, P=0.179).ConclusionHigh-dose atorvastatin pretreatment leads to a significant reduction in MI and MACE at 30 days in ACS patients undergoing PCI, especially in ST-segment elevation MI.

Rho Kinase Inhibition Blunts Lesion Development and Hemorrhage in Murine Models of Aggressive Pdcd10/Ccm3 Disease.

Background and Purpose- Previously, murine models Krit1 +/- Msh2 -/- and Ccm2 +/- Trp53 -/- showed a reduction or no effect on cerebral cavernous malformation (CCM) burden and favorable effects on lesional hemorrhage by the robust Rock (Rho-associated protein kinase) inhibitor fasudil and by simvastatin (a weak pleiotropic inhibitor of Rock). Herein, we concurrently investigated treatment of the more aggressive Pdcd10/Ccm3 model with fasudil, simvastatin, and higher dose atorvastatin to determined effectiveness of Rock inhibition. Methods- The murine models, Pdcd10 +/- Trp53 -/- and Pdcd10 +/- Msh2 -/-, were contemporaneously treated from weaning to 5 months of age with fasudil (100 mg/kg per day in drinking water, n=9), simvastatin (40 mg/kg per day in chow, n=11), atorvastatin (80 mg/kg per day in chow, n=10), or with placebo (n=16). We assessed CCM volume in mouse brains by microcomputed tomography. Lesion burden was calculated as lesion volume normalized to total brain volume. We analyzed chronic hemorrhage in CCM lesions by quantitative intensity of Perls staining in brain sections. Results- The Pdcd10 +/- Trp53 -/- /Msh2 -/- models showed a mean CCM lesion burden per mouse reduction from 0.0091 in placebos to 0.0042 ( P=0.027) by fasudil, and to 0.0047 ( P=0.025) by atorvastatin treatment, but was not changed significantly by simvastatin. Hemorrhage intensity per brain was commensurately decreased by Rock inhibition. Conclusions- These results support the exploration of proof of concept effect of high-dose atorvastatin on human CCM disease for potential therapeutic testing.

Preoperative atorvastatin reduces bleeding and blood transfusions in patients undergoing elective isolated aortic valve replacement.

Minimization of bleeding to reduce the use of blood products is of utmost importance in cardiac surgery. Statins are known for their pleiotropic effects beyond lipid-lowering properties, and the use of atorvastatin preoperatively is associated with reduced risk of bleeding and blood product use after coronary surgery. However, no studies have investigated if this beneficial effect also extends to aortic valve surgery. In this retrospective cohort study, 1145 consecutive patients undergoing elective primary isolated aortic valve replacement meeting the inclusion and exclusion criteria were selected from January 2009 to December 2017 (547 in the atorvastatin group, 598 in the control group). Postoperative bleeding, blood product use, and complications were monitored during hospitalization. Postoperative bleeding was significantly lower in the atorvastatin group compared with the controls in the first 12 h after surgery (372 ± 137 vs 561 ± 219 ml; P = 0.001) and considering overall bleeding (678 ± 387 vs 981 ± 345 ml, P = 0.001). A total of 32.3% of controls and 26.3% of atorvastatin users received packed red blood cells (P = 0.027), and major surgical complications were similar between the groups. Postoperative length of stay was shorter in the atorvastatin group with an average reduction of 1 day of hospitalization (6.0 ± 1.4 vs 6.9 ± 2.1 days; P = 0.001). Postoperative bleeding among the atorvastatin-treated patients was significantly greater in those taking lower doses compared to those taking higher doses of atorvastatin with a 20% between-group difference (P = 0.001). Preoperative treatment with atorvastatin might reduce postoperative bleeding and transfusion of packed red blood cells in patients undergoing elective isolated aortic valve replacement. This result might translate into faster recovery after surgery and reduced hospitalization costs.

Effects of high dose atorvastatin before elective percutaneous coronary intervention on highly sensitive troponin T and one year major cardiovascular events; a randomized clinical trial

IntroductionSome studies have demonstrated that post-PCI elevated cardiac enzymes are associated with worse outcomes. In this study, we aimed to determine if high-dose treatment with atorvastatin before planned elective PCI reduces PMI or MACE at 1-year median follow-up. Material and methodsEligible participants were randomly allocated to group A (80 mg atorvastatin 12 h and 40 mg 2 h before PCI) and group B (40 mg atorvastatin daily). Blood samples were obtained before and at 24 h after PCI to measure hsTnT. All patients were followed regarding MACE (combination of death, re-hospitalizations for ACS, and unplanned coronary revascularization) during one year after PCI. Results207 patients randomly assigned to Group A (n = 97) or group B (n = 110). The rate of PMI was lower in group A (5.2%) compared to group B (10.9%); despite near to 50% lower rate of PMI in group A, binary logistic regression showed no significant association between atorvastatin recapture and PMI. The occurrence of MACE in 97 patients of group A was 11 (11.3%), higher than 11 (10%) cases of 110 patients in group B. Cox proportional hazards regression model shows no significant difference in MACE of study groups. ConclusionPretreatment of patients with stable angina who were planned to undergo an elective PCI with 120 mg of atorvastatin before the procedure confer them the same benefit in terms of PMI and MACE as 40 mg routine daily dosage of this statin does.

Is Vitamin D level elevated in patients on statin treatment?

Context: Statins are effective agents on both primary and secondary prevention in patients who are at high risk of cardiovascular disease, and the number of patients taking statins has significantly raised recently. Aims: The aim of this study was to evaluate the association between Vitamin D levels and statin usage, statin type, dose, and duration. Settings and Design: We enrolled 210 control and 174 patients who were taking statins, and whose Vitamin D levels were checked in the past 3 months. 25-hydroxy Vitamin D levels were analyzed by immunoassay. Subgroup analysis was done firstly according to statin types and other lipid-lowering agents, namely fenofibrate. Subjects and Methods: Statin dosage's effect on Vitamin D levels were analyzed in patients taking low-dose (10–20 mg/day) and high-dose (40–80 mg/day) atorvastatin. Patients were divided into three groups according to statin usage duration (short term: >1 month, less than a year, medium-term: 1–5 years, long term: >5 years). Statistical Analysis Used: Kolmogorov–Smirnov, Kruskal–Wallis, Bonferroni Dunn's multiple comparisons, Spearman rank tests were used. Results: About 71.26% of the patient group was using atorvastatin, 13.21% rosuvastatin, 4.59% pitavastatin, and 10.91% were on fenofibrate treatment. Vitamin D levels were statistically different among statin subtypes (P

Comparative effects of atorvastatin 80 mg and rosuvastatin 40 mg on the levels of serum endocan, chemerin, and galectin-3 in patients with acute myocardial infarction.

Objective:Endocan, chemerin, and galectin-3 are discrete biomarkers associated with cardiovascular diseases and acting through different pathophysiological pathways. The aim of this study is to investigate and compare the effects of high doses of atorvastatin and rosuvastatin on serum endocan, chemerin, and galectin-3 levels in patients with acute myocardial infarction (AMI).Methods:Sixty-three patients with AMI were randomized to receive atorvastatin (80 mg/day) or rosuvastatin (40 mg/day) after percutaneous revascularization. Serum levels of endocan, chemerin, and galectin-3 were evaluated at baseline and after 4-week therapy.Results:Endocan levels were not decreased statistically significantly with atorvastatin 80 mg, but rosuvastatin 40 mg markedly decreased the levels of endocan according to baseline [from 110.27 (86.03–143.69) pg/mL to 99.22 (78.30–122.87) pg/mL with atorvastatin 80 mg and from 110.73 (77.28–165.22) pg/mL to 93.40 (70.48–115.13) pg/mL with rosuvastatin 40 mg, p=0.242 for atorvastatin 80 mg and p=0.014 for rosuvastatin 40 mg]. Chemerin levels significantly decreased in both groups according to baseline [from 264.90 (196.00–525.95) ng/mL to 135.00 (105.95–225.65) ng/mL with atorvastatin 80 mg and from 309.95 (168.87–701.27) ng/mL to 121.25 (86.60–212.65) ng/mL with rosuvastatin 40 mg, p<0.001, respectively, for both groups]. Galectin-3 levels did not change markedly with atorvastatin 80 mg, but they decreased with rosuvastatin 40 mg [from 17.00 (13.10–22.25) ng/mL to 19.30 (15.25–23.45) ng/mL with atorvastatin 80 mg, p=0.721, and from 18.25 (12.82–23.82) ng/mL to 16.60 (10.60–20.15) ng/mL with rosuvastatin 40 mg, p=0.074]. There were no significant between-group differences in terms of absolute and percentage changes of endocan, chemerin, and galectin-3 at 4 weeks.Conclusion:We reported that both statins similarly decreased the endocan levels, whereas rosuvastatin seems to have more prominent effects on the reduction of the chemerin and galectin-3 levels in patients with AMI.

Efficacy Evaluation of High-Dose Atorvastatin Pretreatment in Patients with Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials.

BackgroundIt is unclear whether high-dose atorvastatin pretreatment benefits acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). To clarify this issue, we performed a meta-analysis of the published literature.Material/MethodsRandomized controlled trials (RCTs) assessing high-dose atorvastatin pretreatment in ACS patients undergoing PCI were enrolled. Short-term major adverse cardiac events (MACEs), changes in serum high-sensitivity C-reactive protein (hs-CRP), peak creatine kinase-myocardial band (CK-MB) level, and thrombolysis in myocardial infarction (TIMI) grade 3 flow after PCI were studied as clinical outcomes.ResultsSeventeen RCTs including 10 072 patients were retrieved. High-dose atorvastatin showed greater benefits in reducing the incidence of short-term MACEs (OR 0.72; 95% CI: 0.56 to 0.94; P=0.01) and hs-CRP level (SMD −1.59; 95% CI: −2.38 to −0.80; P<0.0001) among ACS patients after PCI. No significant difference was found between the 2 groups in terms of peak CK-MB (SMD −0.34; 95% CI: −0.79 to 0.10; P=0.13) or final TIMI flow grade 3 (OR 1.31; 95% CI: 0.73 to 2.36; P=0.36) after PCI. High-dose atorvastatin therapy also was not associated with alanine aminotransferase (ALT) elevation (OR 1.95; 95% CI: 0.95 to 4.03; P=0.07).ConclusionsThe results of this meta-analysis suggest that high-dose atorvastatin pretreatment reduces the incidence of short-term MACEs and hs-CRP level without increasing drug-induced hepatotoxicity in ACS patients after PCI.