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Cardiac injury is the main dose-limiting factor for doxorubicin (Dox) use as an anticancer agent. The cardiotoxicity of Dox is linked to a number of complex mechanisms, including oxidative stress, mitochondrial damage, intracellular calcium dysregulation, and apoptosis/necrosis. This study investigates several aspects of Dox-induced cardiotoxicity. We investigated the effects of pre-treatment with rosuvastatin and telmisartan, which were used in different doses alone or combination, on the acute cardiotoxicity induced by Dox. The results of this study showed that Dox induced significant pathological changes in the cardiomyocytes. Adverse effects were observed on several biomarkers related to cardiac damage like cardiac troponin I (cTnI) and lactate dehydrogenase (LDH), oxidative stress like malondialdehyde (MDA), an inflammatory process like interleukin-17 (IL-17) with important histopathological changes. We illusterate the cardio-protective contribution of the two pharmacological agents against the acute cardiotoxic effects of Dox. This is manifested by the significant improvement in the biomarker levels and the associated histological damage. This study points out the beneficial use of both rosuvastatin and telmisartan alone or in combination as a clinical option for decreasing the acute toxicity of Dox on cardiomyocytes., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Control of hyperlipidemia is believed to reduce major cardiovascular events such as cardiovascular death, myocardial infarction, nonfatal stroke, hospitalization for unstable angina, and coronary revascularization. The benefits of monotherapy with Bempedoic acid (BA) as a hypolipidemic agent given after induction of myocardial infarction (MI) in reducing the risk of acute MI worth being investigated, therefore this study was designed to investigate the effectiveness of Bempedoic acid on reducing cardiovascular risk factors in rats with induced hyperlipidemia and myocardial infarction compared to Rosuvastatin. Male albino rats (n=40) were divided into five equal groups, each with eight rats, the first group served as a negative control group, the second group (diet-induced hyperlipidemia and Isoprenaline induced myocardial infarction) served as a positive control group, the third group (diet-induced hyperlipidemia and Isoprenaline induced myocardial infarction) received daily oral administration of Rosuvastatin for 12 weeks, the fourth group (diet-induced hyperlipidemia, DIH) received Bempedoic acid for 4 weeks as prophylaxis and then myocardial infarction was induced and Bempedoic acid administration was continued for the remaining 8 weeks, and the fifth group (diet-induced hyperlipidemia and Isoprenaline induced myocardial infarction) received a daily oral administration of Bempedoic acid for 12 weeks as a treatment. After 12 weeks, blood samples were withdrawn by cardiac puncture for measuring and evaluating lipid profiles and other parameters. Bempedoic acid and Rosuvastatin significantly reduce mean serum levels of lipid profiles; Total cholesterol, LDL and triglyceride, increase HDL and reduce cardiac enzyme levels as compared with the positive control group. The findings from this study suggested that Bempedoic acid as monotherapy either as a therapy or as prophylaxis was effective in reducing lipid parameters, LDL, Tch, and TG and cardiac enzymes creatine kinase-MB (CK-MB) and serum level of cardiac troponin-I (cTn-I) compared with the positive control group and was not superior to Rosuvastatin in these parameters but taking BA as prophylaxis could prevent the morbidity with cardiovascular events as it was effective in reducing the above parameters by greater percentages than BA and Rosuvastatin therapy.. Both drugs showed similar profiles in blood pressure and heart rate measurements.

Curcumin nicotinate (Curtn) is a synthesized ester derivative of curcumin and niacin. Our previous study has shown that Curtn lowers serum low-density lipoprotein cholesterol (LDL-C) levels in apoE -/- mice and promotes LDL-C uptake into HepG2 cells in vitro. The present study was to test the hypothesis that Curtn decreases serum LDL-C levels through decreased expression of pro-protein convertase subtilisin/kexin type 9 (PCSK9) and subsequent increase in LDL receptor expression. Male Wistar rats on high-fat diet (HFD) were treated with Curtn or rosuvastatin. Curtn or rosuvastatin treatment significantly decreased serum levels of total cholesterol (TC) and LDL-C in rats on HFD with increased liver LDL receptor expression. LDL-C-lowering effect of Curtn was not observed in LDL receptor deficient (LDLR -/- ) mice on HFD, while rosuvastatin still decreased serum lipid levels in LDLR -/- mice, indicating that the reduction of serum LDL-C levels by Curtn treatment was LDL receptor-dependent. Curtn treatment also significantly decreased the protein expression of PCSK9 in Wistar rats and LDLR -/- mice. In HepG2 cells with overexpression of human PCSK9, Curtn treatment significantly increased LDL-C uptakes into hepatocytes, and increased LDL receptor distribution on cell surface in association with decreased PCSK9 protein expression. RNAi-LDLR significantly attenuated the effect of Curtn on LDLR distribution on cell surface. These data indicates that Curtn would decrease serum LDL-C level at least partially through inhibition of PCSK9 expression, and subsequent increase in LDL receptor expression and distribution in hepatocytes, serving as a potential novel compound to treat hyperlipidemia., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Torasemide is a loop diuretic with a molecule that is chemically similar to the sulphonamides described as eosinophilic granulomatosis with polyangiitis (EGPA) triggering drugs. The presented case is probably the first description of torasemide-induced vascular purpura in the course of EGPA. Any diagnosis of vasculitis should be followed by an identification of drugs that may aggravate the disease. A 74-year-old patient was admitted to the Department of Dermatology with purpura-like skin lesions on the upper, and lower extremities, including the buttocks. The lesions had appeared around the ankles 7 days before admission to the hospital and then started to progress upwards. The patient complained on lower limb paresthesia and pain. Other comorbidities included bronchial asthma, chronic sinusitis, ischemic heart disease, mild aortic stenosis, arterial hypertension, and degenerative thoracic spine disease. The woman had previously undergone nasal polypectomy twice. She was on a constant regimen of oral rosuvastatin 5 mg per day, spironolactone 50 mg per day, metoprolol 150 mg per day, inhaled formoterol 12 μg per day, and ipratropium bromide 20 μg per day. Ten days prior to admission, she was commenced on torasemide at a dose of 50 mg per day prescribed by a general practitioner due to high blood pressure. Doppler ultrasound upon admission to the hospital excluded deep venal thrombosis. The laboratory tests revealed leukocytosis (17.1 thousand per mm3) with eosinophilia (38.6%), elevated plasma level of C-reactive protein (119 mg per L) and D-dimers (2657 ng per mm3). Indirect immunofluorescent test identified a low titer (1:80) of antinuclear antibodies, but elevated (1:160) antineutrophil cytoplasmic antibodies (ANCA) in the patient's serum. Immunoblot found them to be aimed against myeloperoxidase (pANCA). A chest X-ray showed increased vascular lung markings, while high-resolution computed tomography revealed peribronchial glass-ground opacities. Microscopic evaluation of skin biopsy taken from the lower limbs showed perivascular infiltrates consisting of eosinophils and neutrophils, fragments of neutrophil nuclei, and fibrinous necrosis of small vessels. Electromyography performed in the lower limbs because of their weakness highlighted a loss of response from both sural nerves, as well as slowed conduction velocity of the right tibial nerve and in both common peroneal nerves. Both clinical characteristics of skin lesions and histopathology suggested a diagnosis of EGPA, which was later confirmed by a consultant in rheumatology. The patient was commenced on prednisone at a dose of 0.5 mg per kg of body weight daily and mycophenolate mofetil at a daily dose of 2 g. The antihypertensive therapy was modified, and torasemide was replaced by spironolactone 25 mg per day. The treatment resulted in a gradual regression of skin lesions within a few weeks. The first report of EGPA dates back to 1951. Its authors were Jacob Churg and Lotte Strauss. They described a case series of 13 patients who had severe asthma, fever, peripheral blood eosinophilia, and granulomatous vasculitis in microscopic evaluation of the skin. Three histopathological criteria were then proposed, and Churg-Strauss syndrome was recognized when eosinophilic infiltrates in the tissues, necrotizing inflammation of small and medium vessels, and the presence of extravascular granulomas were observed together in a patient (1). Only 17.4% of patients met all three histopathological criteria, and the diagnosis of the disease was frequently delayed despite of its overt clinical picture (2). In 1984, Lanham et al. proposed new diagnostic criteria which included the presence of bronchial asthma, eosinophilia in a peripheral blood smear >1.5 thousand per mm3, and signs of vasculitis involving at least two organs other than the lungs (3). Lanham's criteria could also delay the recognition of the syndrome before involvement of internal organs, and the American College of Rheumatology therefore established classification criteria in 1990. These included the presence of bronchial asthma, migratory infiltrates in the lungs as assessed by radiographs, the presence of abnormalities in the paranasal sinuses (polyps, allergic rhinitis, chronic inflammation), mono- or polyneuropathy, peripheral blood eosinophilia (>10% of leukocytes must be eosinophils), and extravascular eosinophilic infiltrates in a histopathological examination. Patients who met 4 out of 6 criteria were classified as having Churg-Strauss syndrome (4). The term EGPA was recommended to define patients with Churg-Strauss syndrome in 2012 (5). EGPA is a condition with low incidence (0.11-2.66 cases per million) and morbidity. It usually occurs in the fifth decade of life (6,7), although 65 cases reports of EGPA in people under 18 years of age could be found in the PubMed and Ovid Medline Database at the end of 2020 (8). The etiopathogenesis of the disease has not been fully explained so far. Approximately 40-60% of patients are positive to pANCA (9), but the role of these antibodies in the pathogenesis of EGPA remains unclear. They are suspected to mediate binding of the Fc receptor to MPO exposed on the surface of neutrophils. Subsequently, this may active neutrophils and contribute to a damage of the vascular endothelium (9,10). Glomerulonephritis, neuropathy, and vasculitis are more common in patients with EGPA who have detectable pANCA when compared with seronegative patients. There are at least several drugs which potentially may EGPA. The strongest association with the occurrence of EGPA was found with the use of leukotriene receptor antagonists (montelukast, zafirlukast, pranlukast), although they are commonly used in the treatment of asthma, which is paradoxically one of the complications of the syndrome (13). Although no relationship has been demonstrated so far between the occurrence of EGPA and the intake of drugs from the groups used by the presented patient, a clear time relationship can be observed between the commencement of torasemide and the onset of symptoms in our patient. To date, only three cases of leukocytoclastic vasculitis have been reported after the administration of torasemide. Both of them developed cutaneous symptoms of the disease within 24 hours of the administration of torasemide in patients with no previous history of drug hypersensitivity, but they disappeared quickly within 8-15 days after drug discontinuation (14,15). The chemical structure of torasemide is similar to the molecule of sulfonamides which were previously found to be a triggering factors for EGPA (12). This drug belongs to the group of loop diuretics classified as sulfonamide derivatives. A comparison of the chemical structure of torasemide and sulphanilamide molecules is presented in Figure 1. The clear time relationship between starting the administration of torasemide and the occurrence of purpura-like lesions suggests that it was an aggravating factor for EGPA in our patient. A coexistence of several disorders (asthma, nasal polyps, symptoms of peripheral neuropathy) in our patient suggest EGPA could have developed in her years before oral intake of torasemide. The sudden onset of skin symptoms shows torasemide to be possible inducing factor for the development of vascular purpura in patients suffering from EGPA but without previous cutaneous involvement.

Background: Natural killer (NK) cells are dichotomously involved in chronic hepatitis B (CHB) infection as principal members of innate immunity. An effective treatment should enhance the antiviral potentials of NK cells and not their immunomodulatory roles. TIM-3 (T-cell immunoglobulin and mucin-containing domain) is a molecule with an essential role in controlling immune tolerance. TIM-3 demonstrated the highest expression among NK cells of patients with chronic liver disorders. Statins have been reported to attenuate the levels of TIM-3 on NK cells., Objectives: To investigate the frequencies of NK cells, NKT cells, and TIM-3+ population in patients with CHB upon rosuvastatin (RSV) intervention., Methods: Thirty confirmed patients with CHB were randomly assigned into two groups of 15 (receiving 20 mg of RSV or placebo per day) for 12 weeks. We evaluated the percentages of TIM-3+ cells by staining the peripheral blood mononuclear cells (PBMCs) with CD3, CD16, and CD56 markers using flow cytometry., Results: Our findings indicated that RSV administration could increase CD3- CD56+ NK cells (P>0.05) and CD3+ CD16+ CD56+ NKT cells (P<0.05). RSV intervention could reduce the percentages of TIM-3+ cells among NK cells (P<0.01) and NKT cells (P> 0.05) of patients with CHB compared with the placebo group., Conclusions: The increased population of NK and NKT cells and the effective reduction of TIM-3+ cells among patients with CHB delineated that rosuvastatin could be proposed as an appropriate modulator of innate immune response (regarding NK and NKT cells) in favor of enhancing their antiviral activities.

Background: Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles., Methods: Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions., Results: Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size., Conclusions: The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374., Competing Interests: I confirm that this does not alter our adherence to PLOS ONE policies on sharing data and materials. The study design, data collection, statistical analysis, or publications were not influenced by the sponsors and are the exclusive responsibility of the investigators.

Soluble epidermal growth factor receptor (sEGFR) levels are elevated in patients with type 2 diabetes mellitus (T2DM) and positively correlate with blood glucose and cholesterol levels. However, how cholesterol-lowering treatment in patients with T2DM affects the sEGFR level is unknown. Therefore, we investigated the change of serum sEGFR after cholesterol-lowering treatment in type 2 diabetic patients with hypercholesterolemia. This study is a non-randomized, prospective observational study. A total of 115 patients were treated in either the rosuvastatin monotherapy group (R group, 5 mg/day, n = 59) or the rosuvastatin/ezetimibe combination therapy group (RE group, 5 mg/10 mg/day, n = 56) for 12 weeks. We measured serum levels of lipids and sEGFR using an ELISA kit before and after 12 weeks of treatment in each group. The low-density lipoprotein cholesterol (LDL-C) level was significantly reduced (from 130.27 ± 27.09 to 76.24 ± 26.82 mg/dL; P < .001) after 12 weeks of treatment and more so in the RE group than in the R group (from 131.68 ± 28.72 to 87.13 ± 27.04 mg/dL, P < .001 in the R group; from 128.78 ± 25.58 to 64.75 ± 21.52 mg/dL, P < .001 in the RE group; R vs RE group, P < .001). The sEGFR level was significantly decreased after 12 weeks of treatment (from 50.34 ± 13.31 to 45.75 ± 11.54 ng/mL; P = .007). The RE group only showed a significant reduction in the sEGFR level after treatment (from 50.94 ± 12.10 to 44.80 ± 11.36 ng/mL; P = .007). Moreover, the sEGFR level was significantly reduced only when the LDL-C level was significantly reduced (from 50.46 ± 10.66 to 46.24 ± 11.86 ng/mL; P = .043). The serum sEGFR level was significantly reduced by cholesterol-lowering treatment with rosuvastatin alone or rosuvastatin/ezetimibe. We suggested that sEGFR may play a significant role in insulin resistance (IR) and inflammation, which are central pathophysiological mechanisms. We confirmed the possibility of using sEGFR as a biomarker to predict a good response to lipid-lowering treatment in type 2 diabetes patients with hypercholesterolemia., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes spinal inflammation and fusion. Although the cause of AS is unknown, genetic factors (e.g., HLA-B27) and environmental factors (e.g., sex, age, and infection) increase the risk of AS. Current treatments for AS are to improve symptoms and suppress disease progression. There is no way to completely cure it. High blood cholesterol and lipid levels aggravate the symptoms of autoimmune diseases. We applied hyperlipidemia drugs ezetimibe and rosuvastatin to AS mice and to PBMCs from AS patients. Ezetimibe and rosuvastatin was administered for 11 weeks to AS model mice on the SKG background. Then, the tissues and cells of mice were performed using flow cytometry, computed tomography, immunohistochemistry, and immunofluorescence. Also, the normal mouse splenocytes were cultured in Th17 differentiation conditions for in vitro analysis such as flow cytometry, ELISA and RNA sequencing. The 10 AS patients' PBMCs were treated with ezetimibe and rosuvastatin. The patients' PBMC were analyzed by flow cytometry and ELISA for investigation of immune cell type modification. Ezetimibe caused substantial inhibition for AS. The present study showed that ezetimibe inhibits Th17 cell function, thereby slowing the progression of AS. It is well known that statins are more effective in reducing blood lipid concentrations than ezetimibe, however, our results that ezetimibe had a better anti-inflammatory effect than rosuvastatin in AS. This data suggests that ezetimibe has an independent anti-inflammatory effect independent of blood lipid reduction. To investigate whether ezetimibe has its anti-inflammatory effect through which signaling pathway, various in vitro experiments and RNA sequencing have proceeded. Here, this study suggests that ezetimibe can be an effective treatment for AS patients by inhibiting Th17 differentiation-related genes such as IL-23R and IL-1R. Thus, this study suggests that ezetimibe has therapeutic potential for AS through inhibition of Th17 differentiation and the production of pro-inflammatory cytokines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moon, Lee, Na, Lee, Cho, Choi, Park and Cho.)

High-density lipoproteins (HDL) undergo adverse remodeling and loss of function in the presence of comorbidities. We assessed the potential of lipid-lowering approaches (diet and rosuvastatin) to rescue hypercholesterolemia-induced HDL dysfunction. Hypercholesterolemia was induced in 32 pigs for 10 days. Then, they randomly received one of the 30-day interventions: (I) hypercholesterolemic (HC) diet; (II) HC diet + rosuvastatin; (III) normocholesterolemic (NC) diet; (IV) NC diet + rosuvastatin. We determined cholesterol efflux capacity (CEC), antioxidant potential, HDL particle number, HDL apolipoprotein content, LDL oxidation, and lipid levels. Hypercholesterolemia time-dependently impaired HDL function (−62% CEC, −11% antioxidant index (AOI); p < 0.01), increased HDL particles numbers 2.8-fold (p < 0.0001), reduced HDL-bound APOM (−23%; p < 0.0001), and increased LDL oxidation 1.7-fold (p < 0.0001). These parameters remained unchanged in animals on HC diet alone up to day 40, while AOI deteriorated up to day 25 (−30%). The switch to NC diet reversed HDL dysfunction, restored apolipoprotein M content and particle numbers, and normalized cholesterol levels at day 40. Rosuvastatin improved HDL, AOI, and apolipoprotein M content. Apolipoprotein A-I and apolipoprotein C-III remained unchanged. Lowering LDL-C levels with a low-fat diet rescues HDL CEC and antioxidant potential, while the addition of rosuvastatin enhances HDL antioxidant capacity in a pig model of hypercholesterolemia. Both strategies restore HDL-bound apolipoprotein M content.

Our aim in this study was to develop a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the measurement of atorvastatin, rosuvastatin and their major metabolites, and furthermore to evaluate patients' adherence to statin therapy and to investigate the effect of statin therapy on various hematological and biochemical parameters. A simple protein precipitation was performed for the extraction of analytes and the extracted samples were injected directly. The levels of drugs and their metabolites were measured by the validated method in a total of 210 patients diagnosed with unstable angina pectoris (USAP), ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). Various biochemical and hematological parameters were measured. The linearity ranges for atorvastatin and rosuvastatin were 1.22-2,500 and 0.97-2000 ng/ml, respectively. The inter-assay coefficient of variation for all analytes was ≤ 6%. In patients diagnosed with USAP, STEMI and NSTEMI, treatment compliance rates were 22.1, 23.5 and 41.2% for atorvastatin and 36.1, 40.2 and 67.1% for rosuvastatin, respectively. An economical, simple and reliable measurement method has been developed. Our findings support the poor patient compliance with statin therapy in the included population. It was observed that 6 months of statin treatment caused slight changes in biochemical and hematological parameters., (© 2022 John Wiley & Sons Ltd.)

Background: This study compared the efficacy of two statin treatments (simvastatin vs rosuvastatin) in achieving the combined goal of low-density lipoprotein cholesterol (LDL-C) <2.6 mmol/L and non-high-density lipoprotein cholesterol (non-HDL-C) <3.4 mmol/L in patients with type 2 diabetes and dyslipidemia., Methods: After a 5-week run-in, 89 patients with type 2 diabetes having fasting triglyceride (TG) levels of 1.7 to 5.7 mmol/L or non-HDL-C levels of 3.4 to 5.2 mmol/L were randomized to receive simvastatin 20 mg daily for 4 weeks followed by 40 mg for 8 weeks or rosuvastatin 10 mg for 4 weeks followed by 20 mg for 8 weeks. The primary end-point was the percentage of patients achieving the combined goal at week 12., Results: Although significant between-group differences were observed in changes in LDL-C and non-HDL-C levels, both study treatments were sufficiently intensive for a 40% to 55% LDL-C reduction. At the end of the study, the two groups had similar percentages of patients who achieved the combined lipid goal (84% vs 89%, p = 0.66). All patients who attained the combined lipid goal also met the apolipoprotein B (Apo-B) target of <0.9 g/L. No between-group differences were noted in changes in HDL-C and TG levels at week 12. The patients tolerated both treatments well., Conclusion: In our study, ≈85% of patients with type 2 diabetes and dyslipidemia could achieve the combined lipid goal with statin monotherapy. The two statin treatments could sufficiently control diabetic dyslipidemia (NCT00506961)., Competing Interests: Conflicts of interest: Dr. Wayne H.-H. Sheu, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Background: Trimethylamine N-oxide (TMAO)-related metabolites are associated with the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) and are known to disrupt lipid metabolism. The aims of this study were to evaluate the associations between TMAO-related metabolites and blood lipids and determine how lowering the lipid profile via rosuvastatin therapy influences TMAO-related metabolites., Methods: A total of 112 patients with suspected ASCVD were enrolled in this study. The levels of plasma TMAO-related metabolites, including TMAO, choline, carnitine, betaine, and γ-butyrobetaine (GBB), were analyzed by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) before and after rosuvastatin therapy in all patients. Statistical methods were used to detect the associations between TMAO-related metabolites and blood lipids and determine how rosuvastatin therapy alters the levels of these metabolites., Results: A significant positive correlation was found between TMAO and triglycerides (TG) (r = 0.303, P < 0.05). Furthermore, significant negative correlations were found between TMAO and high-density lipoprotein cholesterol (HDL-c) and between betaine and low-density lipoprotein cholesterol (LDL-c) (r = - 0.405 and - 0.308, respectively, both P < 0.01). Compared to baseline, significantly lower TMAO levels and higher carnitine, betaine and GBB levels were observed after rosuvastatin therapy, while the lipids decreased significantly (P < 0.05). The significant correlation between TMAO and TG or between betaine and LDL-c disappeared after rosuvastatin therapy (r = 0.050 and - 0.172, respectively, both P > 0.05). However, a significantly positive association between carnitine and TC and a negative association between carnitine and LDL-c or between betaine and TG were found after adjustment for sex, age, body mass index (BMI) and lipids (P < 0.05)., Conclusions: This study suggests that TMAO-related metabolites are significantly associated with blood lipids, although some of them are changed postrosuvastatin therapy. Lower TMAO and higher TMAO precursors were observed after rosuvastatin therapy compared to baseline. This study indicates that elevated TMAO precursors after rosuvastatin therapy and their potential impact on ASCVD should be considered in the clinic., (© 2022. The Author(s).)

Cardiovascular disease is one of the leading causes of death around the world with various efforts being made to reduce risk in patients through preventive measures. One major method for prevention has been managing cholesterol, particularly low-density lipoprotein to decrease atherosclerotic plaque burden, potentially decreasing future cardiac complications. Statins have been the gold standard therapy for hypercholesterolemia treatment due to their ease of dosing, limited drug interactions, and favorable safety profile. Unfortunately, statin therapy alone is not always effective enough to adequately control a patient's elevated lipid levels and combination therapy may be warranted. Ezetimibe is commonly added to regimens to help augment cholesterol lowering by inhibiting the absorption of cholesterol. The recent approval of a combination tablet of high-intensity rosuvastatin and ezetimibe has introduced a potentially more beneficial option for cholesterol management in addition to the only available combination of moderate intensity simvastatin and ezetimibe. We aimed to identify potential beneficial effects of ezetimibe by comparing its use in combination with high-intensity rosuvastatin compared to a statin therapy alone or in combination with moderate intensity simvastatin through a literature review. The current evidence indicated that combination therapy outperformed statin monotherapy in reduction of low-density lipoprotein cholesterol and patients were more likely to achieve their target low-density lipoprotein cholesterol goal level. This suggests rosuvastatin/ezetimibe combination holds a potential place in therapy for patients requiring a more aggressive reduction in cholesterol to help prevent atherosclerotic disease., Competing Interests: Dr Qing Ma reports grants from Gilead Science CO-US-380-5529, outside the submitted work. The author reports no conflicts of interest in this work., (© 2022 Chilbert et al.)

Background: Inflammation has been considered as a possible mechanism for the initiation and recurrence of venous thromboembolism (VTE). Statins have anti-inflammatory and potential immune-modulatory effects, but their effect on plasmad-dimer levels is controversial., Hypothesis: In this study, we aimed to evaluate the impact of rosuvastatin on D-dimer and other inflammatory serum markers in VTE patients., Methods: We conducted a prospective, randomized study on 228 patients with VTE. Control group received conventional treatment (warfarin or rivaroxaban), whereas rosuvastatin-intervention group received rosuvastatin 10 mg daily, in addition to their conventional treatment for 3 months. Serum markers were extracted from both groups at the baseline and 3 months after the beginning of treatment., Results: After 3 months, in patients of the intervention group, there was a statistically significant decrease in levels ofd-dimer and mean platelet volume (MPV) but no significant change in neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio., Conclusions: Our results showed that a 3-month treatment with 10 mg rosuvastatin daily can significantly decrease the plasma levels ofd-dimer and MPV, which would support a potential role of statins to reduce activated systemic inflammation among VTE patients. Such effects can be used to reduce the rate of recurrent VTE in these patients., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Postmenopausal hormone-related cognitive decline has gained an immense interest to explore the underlying mechanisms and potential therapies. The current work aimed to study the possible beneficial effect of rosuvastatin (ROS) on the cognitive decline induced by ovariectomy in rats. Four groups were used as follows: control group, control + rosuvastatin, ovariectomy, and ovariectomy + rosuvastatin. After sham operation or ovariectomy, rats were given saline or oral dosages of ROS (2 mg/kg) every day for 30 days. The cognitive functions were assessed using the Morris water maze paradigm, Y-maze test, and new object recognition test. After rat killing, TLR4, caspase-8, and NLRP mRNA expression and protein levels of ASC, AIM2, caspase-1, NLRP1, and PKR were measured in hippocampus. This was complemented by the estimation of tissue content of NF-κΒ, IL-1β, and IL-18 and serum lipid profile quantification. Rosuvastatin showed a promising potential for halting the cognitive impairments induced by estrogen decline through interfering with the TLR4/NF-κΒ/NLRP1/3 axis and inflammasomes activation and the subsequent pyroptosis. This was complemented by the amendment in the deranged lipid profile. Rosuvastatin may exert a beneficial role in attenuating the inflammatory and apoptotic signaling mechanisms associated with postmenopausal cognitive decline. Further investigations are needed to unveil the relationship between deranged plasma lipids and cognitive function., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group ( P <0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups ( P <0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P <0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm 3 vs. 75.76 (48.20, 115.64) mm 3 , P >0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P >0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm 3 vs. 72.49 (51.91, 199.59) mm 3 , P <0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P <0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm 3 ) and (12.71% (8.39%, 24.41%)) at 24 months (both P <0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups( P >0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months ( P >0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.

Background: Acute ischemic stroke (AIS) is a fatal and disabling disease. Given the unsatisfactory results by current treatment strategies, optimizing the treatment of AIS is still an urgent problem to be solved., Objective: To determine the therapeutic efficacy of rosuvastatin (ROS) combined with thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) on senile AIS patients and analyze its effects on serum inflammatory responses and neurological function., Methods: A retrospective study was conducted on 150 senile AIS patients who visited the Longmen County People's Hospital between January 2019 and June 2021. Of them, 100 cases treated by ROS combined with rt-PA intravenous thrombolytic therapy (ivTT) were set as the observation group and the rest 50 cases receiving rt-PA alone were included in the control group. Intergroup comparisons were conducted with respect to the following parameters: neurological function (National Institutes of Health Stroke Scale, NIHSS; Scandinavian Stroke Scale, SSS), serum neuron-specific enolase (NSE) and high-sensitivity C-reactive protein (hs-CRP), therapeutic efficacy, incidence of adverse reactions, and patient satisfaction., Results: The observation group had lower NIHSS and SSS scores and serum NSE and hs-CRP than the control group. In addition, the observation group was found with a higher overall response rate, higher patient satisfaction, and fewer adverse reactions., Conclusion: ROS combined with rt-PA ivTT can better enhance the therapeutic efficacy of elderly patients with AIS, improve their neurological function, and reduce serum inflammatory responses., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Jianzhong Zhu et al.)

What Is Known and Objectives: Although the apixaban Food and Drug Administration (FDA) package insert recommends dose reduction in patients administered dual strong inhibitors of p-glycoprotein (P-gp) and cytochrome P-450 (CYP) 3A4, there are limited published data regarding potential drug-drug interactions between apixaban (Eliquis) and common p-glycoprotein (P-gp) and CYP3A4 inhibitors co-administered with statins. The aim of this study was to investigate the degree of elevation relative to apixaban serum peak and trough concentration after the co-administration of amiodarone, diltiazem and statins (atorvastatin, rosuvastatin and simvastatin)., Methods: Patients prescribed apixaban 5mg twice daily for at least one week were identified from the anticoagulation clinic database and contacted for potential enrolment. A total of 117 volunteers were enrolled with eight excluded due to discontinued use, resulting in 109 volunteers (44 females and 65 males delineated into age groups 40-64 and ≥65 years old) completing the observational study. Fifty-five volunteers were administered apixaban without the P-gp inhibitors amiodarone or diltiazem, with or without statins (atorvastatin, rosuvastatin and simvastatin). Fifty-four volunteers were administered apixaban with either amiodarone or diltiazem, with or without statins (atorvastatin, rosuvastatin or simvastatin). Peak and trough concentrations were assessed for each patient utilizing an apixaban anti-Xa assay., Results: Of the combinations studied, the mean apixaban trough concentration upon co-administration of amiodarone without a statin was elevated compared to apixaban alone (experimental 156.83 +/- 79.59 ng/ml vs. control 104.09 +/- 44.56 ng/ml; p = 0.04). The co-administration of diltiazem and rosuvastatin, and the administration of amiodarone without a statin led to greater than 1.5-fold increase in apixaban concentrations (peak experimental 315.19 +/- 157.53 ng/ml vs control 207.6 +/- 83.38 ng/ml; p = 0.08 and trough experimental 182.03 +/- 95.93 ng/ml vs control 112.32 +/- 37.78 ng/ml; p = 0.17) suggesting the need to assess dose adjustment for patients per the FDA package insert. In addition, the aggregated mean peak (p = 0.0056) and trough (p = 0.0089) elevation of CYP3A4 experimental groups (atorvastatin and simvastatin) co-administered apixaban and diltiazem were statistically significant compared with the aggregated non-CYP3A4 control groups (no statin and rosuvastatin)., What Is New and Conclusion: Herein, we report novel data regarding peak and trough apixaban concentrations after concomitant administration of P-gp and CYP3A4 inhibitors (amiodarone or diltiazem) co-administered with statins (atorvastatin, rosuvastatin or simvastatin). Providers should consider utilizing the apixaban anti-Xa assay or comparative heparin anti-Xa assay to determine if patients require dose reduction to decrease adverse events in high-risk patients prescribed apixaban and concomitant p-glycoprotein and CYP3A4 inhibitors amiodarone or diltiazem with and without a CYP3A4 or non-3A4 statin., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd.)

Mutations in the LDL receptor gene LDLR cause familial hypercholesterolemia (FH); however, the pharmacogenomics of specific LDLR mutations remains poorly understood. The goals of this study were to identify the genetic cause of a three-generation Chinese family affected with autosomal dominant FH, and to investigate the response of FH patients in the family to statin and evolocumab. Whole exome sequencing of the FH family with four patients and six unaffected members identified a heterozygous splicing mutation (c.1187-2A>G) in LDLR. The mutation co-segregated with FH in the family, providing strong genetic evidence to support its pathogenicity. The proband was a 48-year-old male FH patient who had an acute myocardial infarction (MI) and ventricular fibrillation (VF), and showed LDL-C of 5.23 mmol/L. A combination of life style modifications on food and exercise and treatment with rosuvastatin reduced his LDL-C to 2.05-2.80 mmol/L. Addition of ezetimibe did not improve rosuvastatin therapy, but addition of evolocumab further reduced LDL-C by 70% to 0.7 mmol/L at the first time and by 67% to 1.31 mmol/L at the second time. Rosuvastatin also reduced LDL-C for proband's father and sister by 40% and 43-63%, respectively. Lovastatin alone or addition to rosuvastatin treatment did not have any effect on LDL-C for the proband and his son. Both patients carry ApoE 3/4 genotype and SLCO1B1 rs4149056 TT genotype. These results suggest that combined treatment with rosuvastatin (but not lovastatin or ezetimibe) and evolocumab can control LDL-C to meet the LDL-C treatment goal for patients with LDLR splicing mutation c.1187-2A>G., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Post-thrombotic syndrome (PTS) is one of the most frequent complications of venous thromboembolism (VTE) leading to considerable morbidity and cost. Apart from appropriate anticoagulation, there is no drug or medical intervention that helps to prevent PTS. We conducted a multicenter randomized controlled trial to determine whether rosuvastatin can prevent PTS., Methods: 312 patients receiving standard anticoagulation for a newly diagnosed VTE were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days (n = 155) or no rosuvastatin (n = 157). At the last study visit (Day 180 ± 21), an independent observer who was blinded to study treatment performed a PTS assessment using the Villalta scale. The primary clinical outcome of the trial was mean Villalta score at Day 180. We also explored the presence of PTS as defined by Villalta score > 4 at Day 180. Patients mean age was 46.7 ± 10.8 years, 55.8% were female., Results: At Day 180, the Villalta score was 3.5 ± 0.3 in the rosuvastatin arm vs. 3.3 ± 0.3 in the control arm (p = 0.59), and presence of PTS (Villalta >4) was 29.7% in the rosuvastatin arm vs. 25.5% in the control arm (p = 0.41). Secondary analyses showed no difference between trial arms for presence of severe PTS at Day 180 (2.0% vs. 2.7%, p = 1) and for changes in Villalta score between baseline and Day 180 (-3.7 ± 4.4 vs. -4.0 ± 5.0, p = 0.59)., Conclusion: This randomized controlled pilot trial did not demonstrate efficacy of rosuvastatin to reduce Villalta score. Further studies with longer duration of exposure to rosuvastatin are needed., Trial Registration: ClinicalTrials.gov, number NCT02679664., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The study aimed to observe the effect of rosuvastatin on myocardial apoptosis in hypertensive rats through the silent information regulator 1 (SIRT1)/nuclear factor-κB (NF-κB) signaling pathway. The spontaneously hypertensive rat (SHR) model was established, and the rats were randomly divided into the SHR group, Rosuvastatin group and Control group. The blood pressure, creatine kinase (CK) and other myocardial indexes in each group were detected, the cardiac function indexes of rats were determined using magnetic resonance imaging (MRI) and echocardiography (ECG), and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in myocardial tissues were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the apoptosis level of myocardial tissues was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Finally, the expression levels of the SIRT1/NF-κB signaling pathway and apoptosis genes and proteins in myocardial tissues in each group were detected via quantitative polymerase chain reaction (qPCR) and Western blotting. In the SHR group, the blood pressure, the levels of serum creatinine (CR) and CK were increased (p<0.05). In the SHR group, both fractional shortening (FS%) and ejection fraction (EF%) were obviously lower than those in the control group (p<0.05), while both left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) were higher than those in the control group (p<0.05), and the levels of TNF-α, IL-6 and myeloperoxidase (MPO) were increased (p<0.05). The number of apoptotic cells in myocardial tissues in the SHR group was larger than that in the other two groups (p<0.05). In the SHR group, the expression levels of Caspase3 and NF-κB were remarkably higher than those in the Rosuvastatin group (p<0.05), while the expression levels of Bcl-2 and SIRT1 were remarkably lower than those in the Rosuvastatin group (p<0.05). Rosuvastatin can inhibit myocardial apoptosis in hypertensive rats through up-regulating SIRT1 and down-regulating NF-κB.

Background: The present study was aimed to evaluate the efficacy of 1.2% Atorvastatin (ATV) with 1.2% Rosuvastatin (RSV) as local drug delivery for treatment of Chronic Periodontitis (CP)., Materials and Methods: Forty patients were equally divided into two groups. Group A underwent scaling and root debridement and 1.2% ATV gel (1.2 mg/0.1 mL) was placed, whereas group B received scaling and root debridement and RSV (1.2 mg/0.1 ml) was placed., Results: The results showed that both the groups had improvement in all the recorded parameters, and the results obtained were statistically significant. When comparison was made between the groups, no significant difference was obtained between atorvastatin and rosuvastatin at baseline in all recorded parameters. However, after 6 months significant improvement was recorded in CAL (Clinical attachment level) and PD (Probing depth). The plaque index (PI) and gingival index (GI) score however showed improvement, but it did not attain the level of significance., Conclusion: The present study showed improvement in clinical parameters with the use of ATV and RSV gel when used in combination with scaling and root planing (SRP) in CP patients. Patients with RSV gel showed up significantly better than the ones in which ATV gel was placed., Competing Interests: None

Background and Purpose: Proprotein convertase subtilisin-kexin type 9(PCSK9) monoclonal antibody (Mab; Evolocumab) has been reported to inhibit low-density lipoprotein cholesterol (LDL-C) and Lipoprotein(a) [LP(a)] in coronary heart diseases (CHD) patients in America, Europe and Japan. However, little is known about the effect of Evolocumab in Chinese population. This retrospective study in Chinese CHD patients compared the efficacy without or with Evolocumab therapy added to the conventional treatment with a statin (Rosuvastatin) and a gut cholesterol absorption inhibitor (Ezetimibe)., Methods: CHD patients from our hospital were divided into three therapeutic groups, A) the statin monotherapy group (10 mg Rosuvastatin every night); B) the statin/cholesterol absorption inhibitor group (10 mg Rosuvastatin and 10 mg Ezetimibe daily); and C) the triple therapy with PCSK9 Mab group (10 mg Rosuvastatin daily, 10 mg Ezetimibe daily, and 140 mg Evolocumab once 2 weeks). The plasma lipid data were collected at 0, 4, 12, and 24 Week(s). The Graphpad Prism 7 program was used to perform all the statistical analysis., Results: Out of 103 patients 91 were eligible for further evaluation with 31 in group A, 31 in group B, and 29 in group C. The plasma LDL-C levels were reduced only by 33.82% in the Rosuvastatin monotherapy group, 52.13% in the Rosuvastatin/Ezetimibe group, and 73.59% in the Evolocumab/Rosuvastatin/Ezetimibe group (P < 0.0001) at 24 weeks compared to the prior therapy levels. Neither the statin therapy alone (5.95%; P = 0.6), nor the double therapy (5.27%; P = 0.7) affected LP(a) levels. In contrast, addition of Evolocumab to the double therapy significantly decreased LP(a) level by 37.2% (P < 0.0001)., Conclusion: Addition of Evolocumab to the standard double therapy in Chinese CHD patients improved the efficacy in LDL-C reduction when compared to Rosuvastatin alone or in Rosuvastatin/Ezetimibe double therapy. Furthermore, the addition of Evolocumab lowered LP(a) level in Chinese CHD patients., (Copyright © 2021. Published by Elsevier B.V.)

Background: Benign esophageal strictures result from caustic or radiation injury or surgical procedures. Statins have anti-inflammatory and anti-fibrotic activities. We examined the role of rosuvastatin in preventing benign esophageal fibrosis and stricture formation in a rabbit model., Methods: Twenty-six rabbits were assigned to control and rosuvastatin groups. The rabbits in the rosuvastatin group were administered rosuvastatin 5 mg/day, 2 weeks prior to the esophageal stricture phase. Esophageal strictures were established by applying 4% sodium hydroxide solution to the middle esophagus. Esophagography was performed to evaluate the degree of esophageal stenosis, and histopathologic assessment of esophageal tissue damage was performed with hematoxylin-eosin and Masson staining. The expressions of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) were examined by immunohistochemistry., Results: The incidence of strictures was significantly lower in the rosuvastatin group. Esophagography demonstrated mild stenosis in the narrowest inner esophageal diameter in the rosuvastatin group than in the control group, and Masson staining demonstrated significantly less collagen deposition in the rosuvastatin group. In addition, immunohistochemistry results showed that the expressions of TGF-β1, CTGF, and α-SMA significantly reduced in the rosuvastatin group., Conclusions: The present study demonstrated that rosuvastatin prevents benign esophageal stricture formation. This effect may be exerted through the anti-fibrotic activity of rosuvastatin, which may be exerted by the inhibition of CTGF and α-SMA production induced by TGF-β1., (© 2021. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Venous thromboembolism (VTE) is a frequent cardiovascular disease with severe complications, including recurrence and death. There is a great need for alternative prophylactic treatment options as anticoagulation is accompanied by increased bleeding risk. Statins are reported to reduce the risk of incident and recurrent VTE, but the mechanisms are elusive. Procoagulant phospholipids (PPL), and phosphatidylserine in particular, are crucial for efficient coagulation activation, but no studies have investigated the effect of statin treatment on plasma PPL activity., Objectives: To investigate the impact of rosuvastatin treatment on plasma PPL activity and levels of extracellular vesicles (EVs)., Patients/methods: Patients with a history of VTE (≥18 years) allowed to stop anticoagulant treatment were randomized to either 20 mg/day of rosuvastatin treatment or no treatment for 28 days in the Statins Reduce Thrombophilia (NCT01613794) trial. Plasma samples were collected at baseline and study end. PPL activity was measured in samples from 245 participants using a factor Xa-dependent clotting assay and EV levels by flow cytometry., Results: Rosuvastatin treatment yielded an overall 22% (95% confidence interval [CI] -38.2 to -5.8) reduction in PPL activity, and 37% (95% CI -62.9 to -11.2) reduction in PPL activity in participants with a history of pulmonary embolism. The effect of rosuvastatin on plasma PPL activity was not explained by changes in total cholesterol nor change in levels of total- or platelet-derived EVs., Conclusions: Rosuvastatin treatment caused a substantial decrease in plasma PPL activity, suggesting that a PPL-dependent attenuation of coagulation activation may contribute to a reduced VTE risk following statin treatment., (© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background and Objectives: Nephroprotective effect of statins is still controversial. The aim of this study was to investigate the possible hemin-like nephroprotective effect of rosuvastatin (RSV) in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: DN was induced in rats via a single dose of 50 mg/kg STZ i.p., with or without RSV (10 mg/kg orally) for 30 days. To investigate hemin-like effect of RSV on renal heme oxygenase-1 (HO-1), RSV was administered in the presence or absence of an inhibitor of HO-1; zinc protoporphyrin-XI (ZnPP), in a dose of 50 µmol/kg i.p. Results: Induction of diabetes with STZ caused, as expected, significant hyperglycemia, as well as deteriorated kidney function, lipid profile and histopathological architecture. The DN group also showed renal oxidative stress, indicated by decreased superoxide dismutase, catalase, and reduced glutathione, with increased malondialdehyde, myeloperoxidase and nitric oxide. Renal expression of inflammatory marker TNF-α, and pro-apoptotic marker caspase 3, were also increased in the DN group. Administration of RSV in DN rats did not improve glucose level but succeeded in recovering kidney function and normal structure as well as improving the lipid profile. RSV also improved renal oxidative, inflammatory, and apoptotic statuses. Interestingly, the administration of RSV increased renal expression and activity of HO-1 compared to the untreated DN group. Co-administration of ZnPP blocked the effect of RSV on HO-1 and deteriorated all RSV favorable effects. Conclusions: RSV can protect against DN, at least in part, via increasing renal HO-1 expression and/or activity, which seems to be upstream to RSV antioxidant, anti-inflammatory, and anti-apoptotic effects.

Objective: The protein encoded by mitogen-inducible gene 6 (MIG6) plays an essential role in the regulation of cholesterol homeostasis and bile acid synthesis in mice. However, the physiological functions of MIG6 remain poorly understood in humans. Therefore, we aimed to evaluate the relationship between the serum MIG6 concentration and low-density lipoprotein (LDL)-cholesterol in patients undergoing cholesterol-lowering treatment., Methods: We performed a non-randomized, prospective controlled trial. In total, 63 patients with type 2 diabetes and hypercholesterolemia were treated using either rosuvastatin monotherapy or rosuvastatin/ezetimibe combination therapy for 12 weeks. We then compared their serum lipid and MIG6 concentrations before and after treatment., Results: The serum LDL-cholesterol concentration of the participants significantly decreased and the concentration of MIG6 significantly increased during treatment. In addition, higher pre-treatment serum concentrations of MIG6 were associated with larger reductions in LDL-cholesterol, regardless of the therapeutic agent used., Conclusions: Serum MIG6 concentration significantly increases alongside the reduction in LDL-cholesterol achieved using cholesterol-lowering therapies in patients with diabetes and hypercholesterolemia. This is the first study to provide evidence that MIG6 may be involved in human cholesterol metabolism. CRIS registration number : KCT0003477. https://cris.nih.go.kr.

Regarding the drug interactions between sacubitril/valsartan and statins, we identified 3 reports of rhabdomyolysis with high-potency statins. However, it remains unknown whether the combined use of these medications could lead to additive or synergistic effects on rhabdomyolysis. This study aims to assess the disproportionality in reporting rhabdomyolysis for these medications when used alone or in combination. Case reports from the United States Food and Drug Administration's Adverse Event Reporting System from 1991 to Q4/2020 were used. Queries extracted reports based on exposure to statins alone, sacubitril/valsartan alone, and statin+sacubitril/valsartan each. Proportional reporting ratios (PRR) and 95% confidence intervals (CIs) were calculated, where a lower limit of the 95% CI (Lower 95% CI) value of ≥2.0 was interpreted as a safety signal. Lower 95% CIs for statins other than rosuvastatin alone demonstrated no potential safety signals for rhabdomyolysis, death, or the control event. The PRRs and 95% CI for rhabdomyolysis were 2.39 (2.01 to 2.84) with rosuvastatin alone and 2.06 (2.01 to 2.12) for sacubitril/valsartan alone. For atorvastatin+sacubitril/valsartan, the PRR and 95% CI were 0.95 (0.64 to 1.40). Statin+sacubitril/valsartan was not associated with a safety signal. However, rosuvastatin alone and sacubitril/valsartan alone were associated with rhabdomyolysis., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The objective of this study was to investigate the effects of Clostridium butyricum capsules combined with rosuvastatin on the intestinal flora, lipid metabolism, liver function and inflammation in patients with nonalcoholic fatty liver disease (NAFLD). For this purpose, a total of 96 patients with NAFLD were selected as research subjects and randomly divided into a control group (n=48) and an observation group (n=48). The Control group was treated with rosuvastatin, based on which observation group received Clostridium butyricum capsule treatment. The efficacy in the two groups of patients was compared, and the intestinal flora, lipid metabolism, liver function and inflammation were observed. Results showed that the efficacy in the observation group was significantly better than that in the control group (p<0.05). After treatment, the content of Eubacterium rectale in the observation group was lower than that in the control group, while the content of Bacteroides thetaiotaomicron and Bifidobacteria was notably higher than that in the control group (p<0.05). Moreover, the observation group had remarkably lower levels of total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), procollagen III peptide (PIIIP), collagen-IV (C-IV), hyaluronicacid (HA) and laminin (LN) as well as lower levels of tumor necrosis factor-alpha (TNF-α), catabolite activator protein (CAP) and interleukin-6 (IL-6) in serum than the control group (p<0.05). It was concluded that Clostridium butyricum capsules combined with rosuvastatin can effectively improve intestinal flora imbalance, reduce blood lipid levels, and alleviate liver fibrosis and liver function damage in the treatment of NAFLD, so it is of therapeutic value.

Introduction: Dyslipidemia-hypertension proves to be a major risk factor for cardiovascular diseases. In order to achieve better adherence and cost-effectiveness than free equivalent combination therapies, a fixed-dose combination therapy with telmisartan (TEL), rosuvastatin calcium (ROS) and amlodipine besylate (AML) is required in this type of patients., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Statins have shown anti-inflammatory pleiotropic effects in subjects with/at risk of cardiovascular disease. The aim of this study was to evaluate the inflammatory/immunomodulatory properties of rosuvastatin in subjects at low-to-moderate cardiovascular risk. Data was collected from patients' records, physical examination and blood sampling. Subjects were assigned to rosuvastatin 20 mg per day. Rosuvastatin significantly decreased C-reactive protein ( p = 0.045), and increased vascular endothelial growth factor ( p = 0.004) and epidermal growth factor ( p = 0.009). A multivariate analysis identified total cholesterol ( p = 0.027) and vascular endothelial growth factor ( p = 0.011) to be independently associated with rosuvastatin treatment. Given beneficial/harmful role of growth factors, vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), in cardiovascular disease, one would suggest the need for routine monitoring of growth factor levels, especially in patients on long-term statin therapy., (© 2022 Ana Vavlukis., published by Sciendo.)

Objective: To investigate the correlation between changes in serum RBP4, hs-CRP, and IL-27 levels and rosuvastatin in the treatment of coronary heart disease (CHD)., Methods: One hundred and twenty patients with CHD admitted in our hospital were selected as the research object, including 60 patients with acute coronary syndrome as the ACS group, and 60 patients with stable angina as the SA group. Another 60 patients without CHD who were examined in our hospital at the same time were included in the non-CHD group. The patients with CHD were further divided into the control group (CG) ( n  = 42, with routine treatment) and the study group (SG) ( n  = 78, with routine treatment and rosuvastatin) to measure serum RBP4, hs-CRP, and IL-27 levels and analyze the correlation between each index and rosuvastatin in the treatment of CHD., Results: After retrospective analysis, no significant difference was found among the ACS group, the SA group, and the non-CHD group ( P  > 0.05). As for serum RBP4, hs-CRP, and IL-27 levels, ACS group > SA group > non-CHD group, with obvious differences among groups ( P  < 0.05). After Spearman correlation analysis, a positive correlation was observed between Gensini score and serum RBP4, hs-CRP, and IL-27 levels in patients with CHD ( P  < 0.05). After treatment, serum RBP4, hs-CRP, and IL-27 levels were gradually reduced. At 4 weeks after treatment, serum RBP4, hs-CRP, and IL-27 levels of the CG and the SG were decreased conspicuously, and compared with the control, each index of the SG was obviously lower ( P  < 0.05)., Conclusion: Serum RBP4, hs-CRP, and IL-27 play an important role in the occurrence and development of CHD, with a positive correlation to the Gensini score, which can indicate the severity of cardiovascular disease to a certain extent. Meanwhile, rosuvastatin can remarkably reduce serum RBP4, hs-CRP, and IL-27 levels, which is of significance for prognosis., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Yali Wang et al.)

Some studies have suggested the antihypertensive effects of statins, a class of lipid-lowering agents, particularly in patients with hypertension. However, the evidence for the role of statins in blood pressure (BP) lowering is controversial, and no meta-analysis of rosuvastatin therapy has been conducted to assess its BP-lowering effects. Therefore, the aim of this meta-analysis of randomized controlled trials (RCTs) was to investigate the effects of rosuvastatin on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with hypertension. We systematically searched the electronic databases MEDLINE, EMBASE, and Cochrane Library to identify RCTs in which patients were assigned to groups of rosuvastatin plus antihypertensive agents vs. antihypertensive agents. The three authors independently selected the studies, extracted data, and assessed methodological quality. We included five RCTs in this meta-analysis with 288 patients treated with rosuvastatin and 219 patients without rosuvastatin. The mean DBP in the rosuvastatin group was significantly lower than that in the non-rosuvastatin group by -2.12 mmHg (95% confidence interval (CI) -3.72 to -0.52; Pfixed-effects model = 0.009; I2 = 0%, Pheterogeneity = 0.97). Rosuvastatin treatment also lowered the mean SBP compared with the non-rosuvastatin treatment by -2.27 mmHg, but not significantly (95% CI - 4.75 to 0.25; Pfixed-effects model = 0.08; I2 = 0%, Pheterogeneity = 0.82). In this study, we reviewed the antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia. We demonstrated a modest significant reduction of DBP and a trend toward a lowered SBP in patients with hypertension with rosuvastatin therapy. Rosuvastatin could be beneficial to control hypertension and, consequently, contribute toward reducing the risk of cardiovascular events in patients with hypertension and dyslipidemia., Competing Interests: The authors have declared that no competing interests exist.

Background: To determine the effect of genetic polymorphism of drug transporters on the efficacy of treatment with Rosuvastatin, Atorvastatin and Simvastatin in patients with hyperlipidemia., Methods: The study consists of 180 patients, aged 40-75 years, with hyperlipidemia. All patients were divided into two equal groups: patients with different SLCO1B1 (521CC, 521CT and 521TT) and MDR1 (3435CC, 3435TC and 3435TT) genotypes. Each group was divided into rosuvastatin-treated, atorvastatin-treated and simvastatin-treated subgroups. The lipid-lowering effect of statins was assessed by tracing changes in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels., Results: The use of statins over a 4-month period led to substantial reductions in TC and LDL-C levels. The hypolipidemic effect of studied agents was seen in both groups. However, it was less pronounced in patients with 521CC genotype. No statistically significantly differences were found between carriers of 3435TT, 3435CT and 3435CC genotypes., Conclusions: The lipid-lowering efficacy of rosuvastatin was higher compared to other two statins. Patients with SLCO1B1 521CC genotype are more likely to encounter a decrease in the hypolipidemic effect of statins. Such a risk should be considered when treating this category of patients. MDR1 polymorphism had no significant effect on statin efficacy., (© 2021. The Author(s).)

Omecamtiv mecarbil (OM) is a novel cardiac myosin activator in development for the treatment of heart failure. In vitro, OM is an inhibitor of BCRP. Rosuvastatin, a BCRP substrate, is one of the most commonly prescribed medications in patients with heart failure. The potential for a pharmacokinetic (PK) drug-drug interaction (DDI) was investigated, specifically to determine whether a single 50 mg dose of OM would impact the PKs of a single 10 mg dose of rosuvastatin in an open-label study in 14 healthy subjects. The ratios of the geometric least-square means (90% confidence intervals [CIs]) of rosuvastatin co-administered with OM compared to rosuvastatin alone were 127.1% (90% CI 113.8-141.9), 132.8% (90% CI 120.7-146.1), and 154.2% (90% CI 132.8-179.1) for area under the plasma-concentration time curve from time zero to infinity (AUC inf ), area under the plasma-concentration time curve from time zero to time of last quantifiable concentration (AUC last ), and maximum observed plasma concentration (C max ), respectively. Whereas the DDI study with rosuvastatin was conducted with the co-administration of a single dose of OM, in the clinical setting, patients receive OM at doses of 25, 37.5, or 50 mg twice daily (b.i.d.). Hence, to extrapolate the results of the DDI study to a clinically relevant scenario of continuous b.i.d. dosing with OM, physiologically-based pharmacokinetic (PBPK) modeling was performed to explore the potential of BCRP inhibition following continuous b.i.d. dosing of OM at the highest 50 mg dose. Modeling results indicated that following 50 mg b.i.d. dosing of OM, the predicted ratios of the geometric means (90% CIs) for rosuvastatin AUC inf and C max were 1.18 (90% CI 1.16-1.20) and 2.04 (90% CI 1.99-2.10), respectively. Therefore, these results suggest that OM, following multiple dose administration, is a weak inhibitor of BCRP substrates and is in accordance with that observed in the single dose OM DDI clinical study., (© 2021 Amgen Inc. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

We report a 13-year-old female with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome, panhypopituitarism, dyslipidemia, type 2 diabetes mellitus, and nonalcoholic fatty liver disease, who developed rhabdomyolysis and acute kidney injury, two weeks after switching from lovastatin to rosuvastatin. She had been on lovastatin for eight years without any adverse effects., Competing Interests: Declaration of Competing Interest All the authors have no con-flicts of interest to disclose., (Copyright © 2021 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Rosuvastatin therapy might have an effect on the inflammatory and coagulation biomarkers. However, the evidence about the effect of rosuvastatin therapy on the high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer levels among people living with human immunodeficiency virus (PLHIV) is still unclear. Therefore, this study investigated the relational effect of rosuvastatin therapy on serum/plasma hsCRP, IL-6 and D-dimer levels in PLHIV. The literature search was done from Embase, PubMed, and Web of Science databases. The review and meta-analysis included studies written in English language up to January 4, 2020. Random effects model was used to evaluate the pooled standard mean difference with 95% confidence interval. A meta-analysis was performed using nine articles with 392 PLHIV. The result revealed that the plasma/serum levels of IL-6 were significantly reduced after the intervention. However, hsCRP and D-dimer levels showed no significant difference ( p  > .05) between before and after the intervention. The subgroup analysis showed that there was significant association between PLHIV ages <45 years and cohort studies with IL-6 levels. The current CD4 + counts ≥350 cells/mm 3 correlated with hsCRP as well as IL-6. Similarly, nadir CD4 + counts ≥200 cells/mm 3 and duration of HIV diagnosis <10 years also showed significant association with IL-6 and D-dimer levels. It was also indicated that participants who were under antiretroviral drug for <7 years were significantly associated with hsCRP levels. This study established that IL-6 levels were significantly reduced after the intervention while hsCRP and D-dimer levels showed no significant difference between before and after the intervention.

Background: Intense statin therapy was found to impair testosterone production in men. Metformin administered to subjects with hypergonadotropic hypogonadism decreased gonadotropin production. The current study was aimed at investigating whether metformin treatment modulates the impact of high-dose rosuvastatin therapy on hypothalamic-pituitary-testicular axis activity in men., Methods: The study included 43 very high cardiovascular risk men with late-onset hypogonadism, 20 of whom had been treated with metformin (1.7-3 g daily) for at least 6 months. In all subjects, unsuccessful initial statin treatment was replaced with rosuvastatin (20-40 mg daily). Plasma lipid levels, glucose homeostasis markers, as well as circulating levels of gonadotropins, testosterone, bioavailable testosterone, dehydroepiandrosterone-sulfate, prolactin, estradiol and creatinine were measured at the beginning of the study and 4 months later in 28 individuals in whom rosuvastatin reduced LDL cholesterol levels to below 70 mg/dL., Results: There were no differences between treatment-induced changes in plasma lipids. In both study groups, rosuvastatin reduced total and bioavailable testosterone levels. However, only in metformin-naïve men, rosuvastatin increased LH and FSH levels and slightly impaired insulin sensitivity. The impact on gonadotropin concentrations correlated with treatment-induced decrease in testosterone levels. There were no significant differences between baseline and posttreatment values of dehydroepiandrosterone-sulfate, prolactin, estradiol and the glomerular filtration rate., Conclusion: The obtained results suggest that metformin prevents the compensatory increase in gonadotrope function induced by intense statin therapy., (© 2021. The Author(s).)

A 76-year-old woman with unstable angina underwent coronary stent implantation. At the same time, rosuvastatin therapy was started. However, she experienced repeated in-stent restenosis (ISR). Treatment with a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor along with rosuvastatin (5 mg/day) reduced plasma low-density lipoprotein cholesterol to 10 mg/dL, but failed to prevent further ISR. Eventually, an increase in the rosuvastatin dose to the permitted maximum of 20 mg/day succeeded in preventing further in-stent restenosis. Rather than using PCSK9 inhibitors, intensive statin treatment, using the maximum dose of statins, should be prioritized for the secondary prevention of coronary artery disease.

Liver ischemia and reperfusion could cause serious damage to liver tissues. Abnormal liver function could induce serious damage and threaten human health. Evidence emerged to suggest that rosuvastatin could relieve cerebral ischemia-reperfusion injury and alleviate the disease related to vessels by activating the expression of PPARγ. However, whether rosuvastatin could relieve the liver ischemia reperfusion injury by enhancing the expression of PPARγ is unclear. For the strictness of experimental findings, we established both the rat models and the cell model of liver ischemia reperfusion injury by respectively treating rats and cells with rosuvastatin. PPARγ inhibitor was also used for the stimulation of these cells and rats. Reactive oxygen species (ROS) levels, apoptosis and related protein levels were determined with ROS staining, ROS staining and western blotting for the detection of injury induced by oxygen-glucose deprivation and re-oxygenation (OGD/R). Pretreatment of rosuvastatin promoted the expression of PPARγ in liver tissues and MIHA cells. It also inhibited the ischemia reperfusion and OGD/R induced production of ROS while promoted the release of SOD in liver tissues and MIHA cells. Furthermore, rosuvastatin also alleviated the ischemia reperfusion -induced apoptosis of liver tissues and OGD/R-induced MIHA cells apoptosis. However, application of PPARγ inhibitor abolished the restorative effects of rosuvastatin on the apoptosis and oxidative stress on liver tissues and MIHA cells. Rosuvastatin prevented the liver ischemia reperfusion injury of rats by activating PPARγ., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although statins reduce cardiovascular morbidity and mortality, only about one-half of eligible patients receive treatment. Safe and appropriate consumer access to statins could have a significant positive public health impact., Objectives: This study compares the concordance between a participant and clinician assessment of eligibility for statin therapy using a technology-assisted approach., Methods: A total of 500 participants, 83 with limited literacy, completed an at-home Web-based application to assess appropriateness for treatment with rosuvastatin 5 mg. The Web application is designed to assess eligibility for a moderate-intensity statin based on current guidelines and deny access to individuals with contraindications to rosuvastatin. Subsequently, participants visited a research site where clinicians, blinded to the information the participant entered, performed an independent Web application assessment. The Web application is programmed for 1 of 3 rosuvastatin treatment outcomes: "OK to use," "not right for you," or "ask a doctor." The primary endpoint was the percent of participants whose self-selected eligibility for nonprescription rosuvastatin was concordant with clinician assessment., Results: For the primary endpoint, participant selection for statin therapy was concordant with clinician selection in 481 (96.2%) of 500 participants (95% confidence interval: 94.1%-97.7%), of whom 23 (4.6%) were deemed appropriate and 458 (91.6%) were deemed inappropriate for treatment. Discordance was due to incorrect self-selection ("OK to use") in 3 cases, incorrect rejection ("not right for you") in 14 cases and an incorrect "ask a doctor" outcome in 2 cases., Conclusions: The use of a technology-assisted approach to consumer self-selection for statin therapy resulted in participant self-selection that showed substantial agreement with clinician selection., Competing Interests: Funding Support and Author Disclosures This work was funded by AstraZeneca Pharmaceuticals. The sponsor was centrally involved in the study design and reviewed the manuscript, but the final decisions on content were made by the lead author after consultation with the other academic coauthors (Dr Nissen). Dr Nissen reports that the Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from AbbVie, AstraZeneca, Amgen, Eli Lilly, Esperion, Medtronic, MyoKardia, Novartis, Pfizer, and Silence Therapeutics—he is involved in these clinical trials, but receives no personal remuneration for his participation; and has served as a consultant for many pharmaceutical companies but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction. Dr Hutchinson and Ms Morris are employees of AstraZeneca. Dr Wang has received research grants to the Duke Clinical Research Institute from Abbott, AstraZeneca, Bristol Myers Squibb, Boston Scientific, CryoLife, Chiesi, Merck, Portola, and Regeneron; and has received consulting honoraria from AstraZeneca, Bristol Myers Squibb, CryoLife, and Novartis. Dr Ballantyne has received grants to his institution from Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, and the American Heart Association; and has served as a consultant for Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Esperion, Genentech, Gilead, Matinas BioPharma Inc., New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Sanofi-Synthelabo. Ms Travis, Dr Miller, and Ms Hynson are employees of Concentrics Research. Dr Ridker has reported that during the course of this project he received unrelated investigator-initiated research grant support from Novartis, Kowa, Amarin, Pfizer, and the National Heart, Lung, and Blood Institute; and has served as a consultant to Corvidia, Novartis, Flame, Agepha, Inflazome, AstraZeneca, Janssen, Civi Biopharm, SOCAR, Novo Nordisk, Uptton, Omeicos, and Boehringer Ingelheim. Ms Wolski has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been demonstrated to produce significantly greater reduction in LDL cholesterol levels and cardiovascular events than standard statin therapy. However, evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited., Methods: In this open-label randomized study, eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard care. Optical coherence tomography (OCT) assessments for target lesions were obtained at baseline and at 36 weeks of follow-up., Results: LDL cholesterol levels were significantly decreased in both the alirocumab and standard care arms, whereas the absolute reduction in LDL cholesterol was significantly greater in patients treated with alirocumab (1.72 ± 0.51 vs. 0.96 ± 0.59, P < 0.0001). Compared with standard care, the addition of alirocumab to statins was associated with significantly greater increases in minimum fibrous cap thickness (18.0 [10.8-29.2] μm vs 13.2 [7.4-18.6] μm; P = 0.029), greater increases in minimum lumen area (0.20[0.10-0.33] mm 2 vs 0.13 [0.12-0.24] mm 2 ; P = 0.006) and a greater diminution in maximum lipid arc (15.1̊ [7.8-24.5] vs. 8.4̊ [2.0-10.5]; P = 0.008)., Conclusions: The addition of alirocumab to statins can not only provide additional LDL cholesterol lowering effects but also have a potential role in promoting a more stable plaque phenotype., Trial Registration: ClinicalTrials.gov Identifier: NCT04851769 . Registered 2 Mar 2019., (© 2021. The Author(s).)

Background: Little is known of the acute effects of ezetimibe in patients with acute coronary syndrome (ACS) undergoing PCI. We investigated whether ezetimibe improves inflammation and vascular endothelial function in patients with ACS undergoing PCI., Methods: We randomized 171 patients with ACS undergoing PCI to receive ezetimibe 10 mg/day plus rosuvastatin 20 mg/day (combination group, n  = 81) versus rosuvastatin 20 mg/day (rosuvastatin group, n  = 90). Lipid profile, type II secretory phospholipase A2 (sPLA2-IIa), interleukin-1 β (IL-1 β ), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were measured at baseline and after 7 days. Three months after PCI, clinical outcomes were examined., Result: The levels of sPLA2-IIa and IL-1 β reduced significantly in both groups, but more when ezetimibe and rosuvastatin were coadministered (sPLA2-IIa: 6.16 ± 2.67 vs. 7.42 ± 3.53 ng/ml, p =0.01; IL-1 β : 37.39 ± 26.25 vs. 48.98 ± 32.26 pg/ml, p =0.01). A significant rise of VCAM-1 and ICAM-1 was observed on day 7 after PCI in the both groups, but was less in the combination group (VCAM-1: 918.28 ± 235.31 vs. 988.54 ± 194.41 ng/ml, p =0.03; ICAM-1: 213.01 ± 100.15 vs. 246.88 ± 105.71 ng/ml, p =0.03). Patients in the combination versus rosuvastatin group appeared to suffer from less major adverse events. Periprocedural therapy of ezetimibe improves rosuvastatin effects on proinflammatory responses and endothelial function associated with ACS patients undergoing PCI. This trial is registered with https://clinicaltrials.gov/ct2/show/ChiCTR-IPR-17012219 (Chinese Clinical Trial Registry, http://www.chictr.org.cn on 02/08/2017)., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Changqing Sun et al.)

Autoimmune phenomena and clinically apparent autoimmune diseases, including autoimmune hepatitis, are increasingly been reported not only after natural infection with the SARS-CoV-2 virus, but also after vaccination against it. We report the case of a 63-year old man without a history of autoimmunity or SARS-CoV-2 natural infection who experienced acute severe autoimmune-like hepatitis seven days after the first dose of the mRNA-1273 SARS-CoV-2 vaccine. Liver histology showed inflammatory portal infiltrate with interface hepatitis, lobular and centrilobular inflammation with centrilobular necrosis, in absence of fibrosis and steatosis. Serum immunoglobulin G was slightly elevated. Autoimmune liver serology showed an indirect immunofluorescence pattern on triple rodent tissue compatible with anti-mitochondrial antibody (AMA), but, unexpectedly, this pattern was not mirrored by positivity for primary biliary cholangitis (PBC)-specific molecular tests, indicating that this antibody is different from classical AMA. Anti-nuclear antibody (ANA) was also positive with a rim-like indirect immunofluorescence pattern on liver and HEp2 cell substrates, similar to PBC-specific ANA; however, anti-gp210 and a large panel of molecular-based assays for nuclear antigens were negative, suggesting a unique ANA in our patient. He carries the HLA DRB1*11:01 allele, which is protective against PBC. Response to prednisone treatment was satisfactory. The clinical significance of these novel specificities needs to be further evaluated in this emerging condition., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: We investigated whether the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy in patients requiring cholesterol-lowering therapy., Methods: This was a multicenter randomized, double-blind study to investigate the safety and efficacy of a fixed-dose combination of rosuvastatin 2.5 mg and ezetimibe 10 mg (R2.5+E10) compared to those of ezetimibe 10 mg monotherapy (E10), rosuvastatin 2.5 mg (R2.5), and rosuvastatin 5 mg monotherapy (R5) in patients with hypercholesterolemia. A total of 348 patients at 15 centers in Korea were screened, and 279 patients were randomized to different groups in the study. Clinical and laboratory examinations were performed at baseline and 4 and 8 weeks after intervention. The primary endpoint was the percentage change of low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up., Findings: Baseline characteristics were similar among the four groups. There were significant changes in lipid profiles at the 8-week follow-up. A greater decrease in the LDL cholesterol levels (primary endpoint) were found in the R2.5+E10 group (-45.7±18.6%) than in the E10 group (-16.7±14.7%, p<0.0001), R2.5 group (-32.6±15.1%, p<0.0001), and R5 group (-38.9±13.9%, p=0.0003). Similar outcomes were observed regarding the decrease in total cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B protein. In addition, changes in the triglyceride and HDL levels in the R2.5+E10 group were significantly different compared with those in the E10 group; however, the changes were similar to those in the other treatment groups. In patients with low and moderate risk, all patients achieved the target LDL cholesterol levels in the R2.5+E10 group (100%) compared to 13.0% in the E10 group, 47.6% in the R2.5 group, and 65.2% in the R5 group. Adverse effects were rare and similar in the four groups., Implications: Fixed-dose combination of low-intensity rosuvastatin and ezetimibe was more effective in lowering LDL cholesterol and achieving LDL cholesterol goals than moderate-intensity rosuvastatin monotherapy. These findings suggest that the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy for cholesterol management, particularly in patients with low and moderate risk. ClinicalTrials.gov identifier: NCT04652349., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Statins may help prevent cardiovascular disease (CVD) in people with human immunodeficiency virus (PWH) with chronic inflammation owing to their pleotropic lipid-lowering and anti-inflammatory properties., Methods: The impact of 48 weeks of rosuvastatin therapy on inflammation and immune activation in a double-blind, placebo-controlled trial in PWH at moderate cardiovascular disease risk was assessed., Results: Rosuvastatin did not alter plasma levels of interleukin 6, soluble tumor necrosis factor receptor type 2, CXCL10, soluble CD14, or soluble vascular cellular adhesion molecule 1 (P ≥ .1 for all). Proportions of CD16+ monocyte subsets were increased in PWH receiving rosuvastatin., Conclusions: The potential benefits of statin use in PWH with normal lipid levels requires further clinical outcome research., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

For cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low-density lipoprotein cholesterol targets, but their effects on other lipids are less reported. This study was designed to examine lipid changes in subjects with ST-segment elevation myocardial infarction (STEMI) after two highly effective lipid-lowering therapies. Twenty patients with STEMI were randomized to be treated with rosuvastatin 20 mg QD or simvastatin 40 mg combined with ezetimibe 10 mg QD for 30 days. Fasting blood samples were collected on the first day (D1) and after 30 days (D30). Lipidomic analysis was performed using the Lipidyzer platform. Similar classic lipid profile was obtained in both groups of lipid-lowering therapies. However, differences with the lipidomic analysis were observed between D30 and D1 for most of the analyzed classes. Differences were noted with lipid-lowering therapies for lipids such as FA, LPC, PC, PE, CE, Cer, and SM, notably in patients treated with rosuvastatin. Correlation studies between classic lipid profiles and lipidomic results showed different information. These findings seem relevant, due to the involvement of these lipid classes in crucial mechanisms of atherosclerosis, and may account for residual cardiovascular risk.Randomized clinical trial: ClinicalTrials.gov, NCT02428374, registered on 28/09/2014., (© 2021. The Author(s).)