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Aim: The effect of long-term high-intensity statin therapy on coronary atherosclerosis among patients with acute ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this study was to quantify the impact of high-intensity statin therapy on plaque burden, composition, and phenotype in non-infarct-related arteries of STEMI patients undergoing primary percutaneous coronary intervention (PCI)., Methods and Results: Between September 2009 and January 2011, 103 STEMI patients underwent intravascular ultrasonography (IVUS) and radiofrequency ultrasonography (RF-IVUS) of the two non-infarct-related epicardial coronary arteries (non-IRA) after successful primary PCI. Patients were treated with high-intensity rosuvastatin (40 mg/day) throughout 13 months and serial intracoronary imaging with the analysis of matched segments was available for 82 patients with 146 non-IRA. The primary IVUS end-point was the change in per cent atheroma volume (PAV). After 13 months, low-density lipoprotein cholesterol (LDL-C) had decreased from a median of 3.29 to 1.89 mmol/L (P < 0.001), and high-density lipoprotein cholesterol (HDL-C) levels had increased from 1.10 to 1.20 mmol/L (P < 0.001). PAV of the non-IRA decreased by -0.9% (95% CI: -1.56 to -0.25, P = 0.007). Patients with regression in at least one non-IRA were more common (74%) than those without (26%). Per cent necrotic core remained unchanged (-0.05%, 95% CI: -1.05 to 0.96%, P = 0.93) as did the number of RF-IVUS defined thin cap fibroatheromas (124 vs. 116, P = 0.15)., Conclusion: High-intensity rosuvastatin therapy over 13 months is associated with regression of coronary atherosclerosis in non-infarct-related arteries without changes in RF-IVUS defined necrotic core or plaque phenotype among STEMI patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Dyslipidemia management situation in Chinese patients with high risk and very high risk has been demonstrated very low, despite the wide use of statins. The effects and safety of the combined treatment of ezetimibe (EZ) and statins in Chinese patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (T2DM) remain unknown., Methods: Chinese Patients with ACS and T2DM were divided into the statins group (n=40) and the combination group of EZ and statins (n=44). In order to evaluate the clinical effects on lipids-lowering, systemic inflammation response and clinical safety, the follow-up of all patients was carried out at day 7th and 30th after treatment., Results: The level of low-density lipoprotein cholesterol (LDL-C) in combination group and statins group was 1.87±0.42 and 2.18±0.58 mmol/L at day 7th, 1.51±0.29 and 1.94±0.49 mmol/L at day 30th, respectively. The control rates of LDL-C level in the combination group and the statins group were 77% and 45% at day 30(th), respectively. There was no significant improvement on high-density lipoprotein cholesterol (HDL-C) level during follow-up. The triglyceride (TG) levels were significantly reduced in both groups, while no obvious difference was observed between two groups. No significant difference on serum high-sensitivity C-reactive protein (hs-CRP) level between two groups was observed. Moreover, we did not observe any significant correlation between serum lipids levels and serum hs-CRP level during follow-up. The liver dysfunction and muscle related side effects (MRSE), creatine kinase (CK) and myopathy were not observed in both groups., Conclusion: Our study demonstrated that it is feasible to initiate combination therapy during acute phase for Chinese patients with ACS and T2DM, which can bring more significant effect on LDL-C-lowering and improve the control rate of LDL-C level with good safety.

Background: Contrast-induced nephropathy (CIN) is an important cause of acute renal failure. We observe the effect of rosuvastatin on preventing CIN in diabetic rats in current study., Methods: Diabetic rats were then divided into five groups: 1 diabetic rats (D), 2 diabetic rats + contrast media (DCM), 3 diabetic rats + rosuvastatin (DR), 4 diabetic rats + contrast media + rosuvastatin (DRCM), 5 non-diabetic rat control (NDCM). Contrast-induced nephropathy was induced by intravenous injection a single dose of indomethacin (10 mg/kg), double doses of N-nitro-L-arginine methyl ester (10 mg/kg) and a single dose of high-osmolar contrast medium meglumine amidotrizoate (6 ml/kg). DR and DRCM group rats were treated with rosuvastatin (10 mg/kg/day) by gavage for 5 days. At the end of treatment, the experimental groups were sacrificed, and their renal tissues were investigated histopathologically beside assessments of functional activities, nitric oxide metabolites, and oxidative stress and apoptic markers., Results: After 6 days, serum creatinine and urine microprotein were increased, and creatinine clearance, kidney nitrite were decreased in DCM rats compared with NDCM, D, DR and DRCM groups. Histopathology scores in group DCM were increased compared with groups NDCM, D and DR, but lower in group DRCM than in group DCM (p < 0.01). Kidney thiobarbituric acid-reacting substances (TBARS), serum malondialdehyde (MDA), and serum protein carbonyl content (PCC) were increased, and serum thiol was decreased in the DCM group compared with groups NDCM, D and DR; however, these results were reversed in group DRCM compared with group DCM. Both expression of IL-6, TNF-α and the percentage of apoptotic cells were increased in group DCM than in groups NDCM, D and DR, but they were decreased in group DRCM than in group DCM. The expression of phospho-p38, cleaved capase-3, and the Bax/Bcl-2 ratio, were increased in group DCM than in groups NDCM, D and DR, but were decreased in group DRCM than in group DCM., Conclusions: Our study demonstrated that rosuvastatin treatment attenuated both inflammatory processes and apoptosis and inhibited oxidative stress and the p38 MAPK pathway in a diabetic rat model in the setting of CIN.

Background: Co-administration of statin with imatinib is thought to result in greater improvement in pulmonary arterial hypertension (PAH) than imatinib treatment alone, and hence may allow greater effectiveness of imatinib therapy at lower doses., Methods: The effects of imanitib at dose of 20 and 50mg/kg bw given together with rosuvastatin or simvastatin were investigated with respect to right ventricle pressure (RVP), arterial blood pressure and right ventricle hypertrophy (RVH) in experimental monocrotaline (MCT)-induced pulmonary hypertension. Fourteen days after MCT injection, male rats were treated orally for another 14 days with imatinib, statin or a combination of the two., Results: Concurrent administration of statin (lipophilic simvastatin, hydrophilic rosuvastatin) and higher dose imatinib reversed the MCT-induced increase in RVP more than each drug alone and decreased RV hypertrophy (RV/LV+S ratio), significantly. The increased RVP and RV hypertrophy was found to be reversed when a lower dose of imatinib was co-administered with rosuvastatin or simvastatin., Conclusions: Statins may intensify the beneficial effects of imatinib in PAH, which may be due to the additional influence of statin on the decrease of platelet-derived growth factor (PDGF)-induced effects. These properties allow the dose of imatinib used in PAH treatment to be reduced and thereby might improve its safety profile., (Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Aim: To determine the lipid lowering effectiveness, cost effectiveness, and safety of rosuvastatin compared with pitavastatin in dyslipidemic patients with concurrent renal disorders., Methods: This single-center, prospective, open-label, randomized, 12-month study evaluated rosuvastatin (2.5 mg) and pitavastatin (1 or 2 mg) in 134 dyslipidemic patients with concurrent chronic kidney disease (CKD; rosuvastatin group, n=68; pitavastatin group, n=66). Lipid parameters [i.e., low density lipoprotein cholesterol (LDL-C), etc.], renal function parameters [i.e., estimated glomerular filtration rate (eGFR), etc.], glycated hemoglobin (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured at enrollment (baseline), month 6, and month 12., Results: The mean daily dose of rosuvastatin and pitavastatin was 2.5 mg and 1.4 mg, respectively. All lipid parameters were significantly more improved in the rosuvastatin group. eGFR improved from baseline in the rosuvastatin group (p ＜ 0.0001) and showed no tendency to worsen in the pitavastatin group (p=0.2232). In multiple regression analysis (n=134), it was significantly associated with a percent change in total cholesterol (β=0.2296; p=0.0112), smoking (β=0.1927; p=0.0224), and HbA1c (β=-0.1606; p=0.0585). Hs-CRP was significantly improved in both groups. An analysis eliminating the influence of antidiabetic medication showed a significant difference between groups in the change of HbA1c at month 6 from baseline (p=0.0016). No subjects in either group had new onset of diabetes mellitus. The cost of statin medication required to reduce LDL-C by 10 mg/dL was significantly lower for 2.5 mg of rosuvastatin (p=0.0116)., Conclusions: Rosuvastatin 2.5 mg had superior lipid lowering and cost effectiveness in dyslipidemic patients with concurrent CKD.(UMIN ID: UMIN000005812).

Background: There is well-known inter-individual variability in the cholesterol-lowering effect of statins. However, inter-individual variability in response to rosuvastatin treatment in subjects with hypercholesterolemia has not been clearly established. This study aimed to evaluate the associations of CYP2C9 genetic polymorphism with the efficacy and safety of rosuvastatin in Chinese patients with hyperlipidemia., Methods: A total of 218 patients with hyperlipidemia were selected and treated with 10 mg rosuvastatin per day for 12 weeks. Blood samples were collected prior to the treatment and after 4, 8, and 12 weeks of treatment. Clinical biochemistry analyses for serum lipid profiles were performed. Genotyping for CYP2C9 polymorphisms was performed using allele-specific real-time PCR., Results: 197 out of 218 patients featured a wild-type CYP2C9*1/*1 genotype, and 21 patients featured a CYP2C9*1/*3 or CYP2C9*3/*3 mutation genotype. No patients with CYP2C9*2 alleles were identified. Sixteen patients discontinued the medication due to adverse effects. No serious adverse events (i.e., hepatotoxicity or myolysis) were observed. After the 12 weeks of treatment, we observed significant reductions in total cholesterol (TC), triglycerides and low-density lipoprotein (LDL) levels compared to baseline (p < 0.05). Patients with the mutant genotype showed a higher TC-lowering and LDL-lowing effect compared to those with wild-type genotypes (TC: 45.05% vs. 38.96%, p = 0.041; LDL: 44.97% vs. 39.28%, p = 0.029). The frequency of adverse drug reactions in the studied patients did not differ by CYP2C9 genotypes (p > 0.05)., Conclusions: This study suggests that the CYP2C9 polymorphism may be involved in the lipid-lowering efficacy of rosuvastatin in patients with hyperlipidemia.

Objective: To evaluate the effects of ezetimibe/simvastatin (EZE/SIMV) and rosuvastatin (ROSUV) on oxidative stress (OS) markers in patients with diabetic polyneuropathy (DPN)., Methods: We performed a randomized, double-blind, placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus (T2DM) and DPN, as evaluated by composite scores and nerve conduction studies (NCS). Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo, EZE/SIMV 10/20 mg, or ROSUV 20 mg for 16 weeks. All patients were assessed before and after treatment: primary outcomes were lipid peroxidation (LPO), and nitric oxide (NO) surrogate levels in plasma; secondary outcomes included NCS, neuropathic symptom scores, and metabolic parameters. Data were expressed as mean ± SD or SEM, frequencies, and percentages; we used nonparametric analysis., Results: LPO levels were reduced in both statin arms after 16 weeks of treatment (p < 0.05 versus baseline), without changes in the placebo group. NO levels were not significantly affected by statin treatment, although a trend towards significance concerning increased NO levels was noted in both statin arms. No significant changes were observed for the NCS or composite scores., Discussion: EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy. This trial is registered with NCT02129231.

Recently, we derived "humanized" spontaneously hypertensive rats (SHR-CRP) in which transgenic expression of human CRP induces inflammation, oxidative stress, several features of metabolic syndrome and target organ injury. In addition, we found that rosuvastatin treatment of SHR-CRP transgenic rats can protect against pro-inflammatory effects of human CRP and also reduce cardiac inflammation and oxidative damage. In the current study, we tested the effects of rosuvastatin (5 mg/kg) on kidney injury in SHR-CRP males versus untreated SHR-CRP and SHR controls. All rats were fed a high sucrose diet. In SHR-CRP transgenic rats, treatment with rosuvastatin for 10 weeks, compared to untreated transgenic rats and SHR controls, was associated with significantly reduced systemic inflammation which was accompanied with activation of antioxidative enzymes in the kidney, lower renal fat accumulation, and with amelioration of histopathological changes in the kidney. These findings provide evidence that, in the presence of high CRP levels, rosuvastatin exhibits significant anti-inflammatory, anti-oxidative, and renoprotective effects.

Background: Anaemia has been linked with mortality in HIV infection. The mechanism of anaemia in the era of contemporary antiretroviral therapy is not understood. The aim of this study was to describe the association between anaemia and markers of immune activation and inflammation in a cohort of HIV-infected adults on stable antiretroviral therapy., Methods: We performed a cross-sectional study of HIV-infected adults on antiretroviral therapy with HIV-1 RNA<1,000 copies/ml. Soluble and cellular markers of inflammation and immune activation were measured. Relationships between haemoglobin levels, anaemia (haemoglobin <13 g/dl for men and <12 g/dl for women) and mild anaemia (haemoglobin <14 g/dl for men and <13 g/dl for women) and these markers were explored using multivariable linear regression., Results: Among the 147 participants, median age was 46 years, 78% were men, 68% were African American and 29% were Caucasian. Median body mass index (BMI) was 26.7 kg/m(2), nadir and current CD4(+) T-cell counts were 179 and 613 cells/mm(3), respectively, and 78% had HIV-1 RNA<50 copies/ml (range 20-600 copies/ml). Median (IQR) haemoglobin was 14.3 (13.1-15.1) g/dl; 14% were anaemic and 33% had at least mild anaemia. In multivariable analyses, mild anaemia was independently associated with female sex, older age, shorter duration of antiretroviral therapy, lower white blood cell count, higher platelet count, higher sCD14 and a greater number of CD14(dim)CD16(+) cells or 'patrolling' monocytes, which remained significant after further adjusting for race and BMI., Conclusions: Having haemoglobin <14 g/dl for men and <13 g/dl for women was independently associated with monocyte activation (sCD14 and CD14(dim)CD16(+) cells) in HIV-infected adults on stable antiretroviral therapy.

Introduction: The prevalence of chronic kidney disease (CKD), a risk factor for cardiovascular disease (CVD), is increasing worldwide. Statin treatment, the cornerstone of prevention or treatment of CVD, might have beneficial effects on urine protein excretion and renal function as determined by the glomerular filtration rate, whereas it might protect from acute kidney injury (AKI), mainly due to contrast-induced AKI. These beneficial effects on CKD may not be drug class effects; specific statins at specific doses may help prevent CKD deterioration and reduce CVD risk. We analysed all statin studies that had renal and CVD endpoints as main outcome measures. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched up to February 2015., Areas Covered: We consider the effects of statins on microalbuminuria, proteinuria, glomerular filtration rate, AKI associated with angiography or percutaneous coronary intervention and on CVD event rates in patients with CKD., Expert Opinion: Current evidence points towards the need to prescribe high-potency statins in patients with CKD, before a major decline in kidney function occurs. This may reduce CVD risk and delay the progress of CKD. Administration of either atorvastatin or rosuvastatin can prevent contrast-induced AKI before angiography or percutaneous coronary intervention. The combination of simvastatin + ezetimibe may decrease vascular events in patients with advanced CKD.

Background: Non-adherence is a major obstacle with long-term daily statin therapy., Objective: This retrospective study reviewed the medical records of patients with hyperlipidemia during an 8-year period in a private internal medicine practice. Periodic dosing was negotiated following several patients' refusal of statin therapy because of muscle aches or cost., Methods: The clinical impetus was patient adherence to statin therapy. Treatment was initiated by dispensing rosuvastatin or atorvastatin in a stepwise patient-directed approach (from two times/week to three times/week to every other day, up to five times/week). The primary endpoint was to assess the concentration of low-density lipoprotein cholesterol (LDL-C) and the total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio with patient-directed dosing intervals. The secondary endpoint was a head-to-head comparison of atorvastatin and rosuvastatin to evaluate the mean decrease in the LDL-C and TC/HDL-C ratio., Results: Chart review identified 46 patients who had been treated. Two patients with persistent myalgia terminated treatment before 12 weeks. Among the remaining 44 patients, 20 received doses of rosuvastatin from 15 to 100 mg per week, and 24 received atorvastatin from 20 to 140 mg per week. There was a significant decrease from pre-treatment in the mean TC/HDL-C ratio of 1.72 (31.1%, P < 0.0001) and mean LDL-C of 43.3 mg/dL (30.2%, P < 0.0001). An independent samples t-test showed a non-significant reduction of the mean TC/HDL-C ratio and LDL-C with rosuvastatin versus atorvastatin., Conclusion: Periodic dosing of rosuvastatin or atorvastatin using a gradual, patient-directed, stepwise approach guided by cholesterol levels is an effective method of lipid lowering and carried a favorable 95.6% adherence rate.

Background: Fat embolism syndrome is a life-threatening condition with treatment centering on the provision of excellent supportive care and early fracture fixation. No pharmacologic intervention has yet shown any clear benefit. We used high-dose rosuvastatin specifically for its anti-inflammatory effects to treat a patient with severe fat embolism syndrome. We also suggest that magnetic resonance imaging and transcranial Doppler studies are helpful in establishing the diagnosis and for monitoring the patient's course., Patient: A 17-year-old boy developed severe cerebral fat embolism syndrome with multifocal strokes after sustaining bilateral femur fractures., Results: In spite of profound and prolonged neurological impairment, our patient experienced dramatic recovery by the time he was discharged from inpatient rehabilitation several weeks after his initial injury. Magnetic resonance imaging revealed the classic "starfield" pattern of infarcts on diffusion-weighted sequences early in the illness. Additionally, serial transcranial Doppler studies demonstrated dramatically elevated microembolic events that resolved completely during the course of treatment., Conclusion: We feel that the acute administration of high-dose rosuvastatin early in the development of our patient's illness may have contributed to his ultimate recovery. Therapeutic guidelines cannot be extrapolated from a single patient, but our experience suggests that statin therapy could be potentially beneficial for individuals with severe fat embolism syndrome, and this approach deserves further clinical evaluation. Additionally, the diagnosis and monitoring of cerebral involvement in fat embolism syndrome is facilitated by both magnetic resonance imaging and transcranial Doppler studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: The aim of the current study was to determine the efficacy of the 4 most commonly prescribed statins (rosuvastatin, atorvastatin, pravastatin, and simvastatin) for managing dyslipidemia among diabetic patients with and without metabolic syndrome (MetS)., Material and Methods: This was a cohort observational population-based study conducted at Hamad Medical Hospital and Primary Health Care Centre. The participants were 1542 consecutive diabetes patients who were diagnosed with dyslipidemia and were prescribed any of the indicated statins. Sociodemographic and clinical characteristics were taken from medical records, and lipid profile at baseline and 2 years after the initiation of statin therapy were retrieved from electronic medical records database (EMR-viewer). Reduction in different lipid profile after 2 years of therapy was compared among different types of statins between patients with and without MetS., Results: Out of total 1542 subjects, 562(36.4%) were diagnosed with MetS using the criteria of International Diabetes Federation. Among those with MetS, 125 were prescribed with atorvastatin, 162 pravastatin, 177 rosuvastatin, and 98 simvastatin. Among those without MetS, 365 used atorvastatin, 172 pravastatin, 345 rosuvastatin, and 98 simvastatin therapies. Among patients with MetS, rosuvastatin therapy resulted in significantly higher low-density lipoprotein cholesterol and total cholesterol reduction (23%, P = .006; and 20.3%, P = .015, respectively) as compared with other statins. Similarly, significantly higher percentage of patients receiving rosuvastatin therapy were successful in achieving the target of total cholesterol <4 mmol/L and triglycerides <1.7 mmol/L after 2 years (38.4%, P = .012; and 67.2%, P = .010, respectively) as compared with other therapies. In contrast, among patients without MetS, rosuvastatin therapy resulted in highest percentage drop in total cholesterol (20.1%; P = .016) than other statin therapies., Conclusion: The present study confirmed that rosuvastatin therapy in commonly prescribed doses is the most effective statin for low-density lipoprotein cholesterol goal achievement and for improving the lipid profile in hypercholesterolemic diabetic patients with and without MetS., (© The Author(s) 2014.)