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1.
Different Effects of Atorvastatin on Cardiometabolic Risk Factors in Young Women With and Without Hyperprolactinemia.
Krysiak, R, Szkróbka, W, Okopień, B
Journal of clinical pharmacology. 2019;(1):83-89
Abstract
Long-term prolactin excess is often accompanied by numerous metabolic complications. No previous study has compared the effect of statin therapy on circulating levels of cardiometabolic risk factors in patients with elevated and normal prolactin levels. The study population consisted of 3 age-, weight-, and lipid-matched groups of young women: 19 women with untreated hyperprolactinemia (group A), 20 normoprolactinemic women receiving bromocriptine treatment (because of previous hyperprolactinemia) (group B), and 20 untreated women with prolactin levels within the reference range (group C). Because of elevated total and low-density lipoprotein cholesterol levels, all women were then treated with atorvastatin (40 mg daily). Apart from measuring plasma lipids, glucose homeostasis markers, and hormone levels at the beginning of the study and 12 weeks later, we measured circulating levels of uric acid, high-sensitivity C-reactive protein, homocysteine, and fibrinogen. Despite similar baseline levels of plasma lipids, levels of uric acid, high-sensitivity C-reactive protein, homocysteine, and fibrinogen as well as the degree of insulin resistance were higher in group A than in the remaining 2 groups. Atorvastatin reduced total and low-density lipoprotein cholesterol levels in all study groups. However, only in normoprolactinemic women (groups B and C) did atorvastatin reduce circulating levels of nonlipid cardiometabolic risk factors, whereas only in group A did the drug slightly impair insulin sensitivity. The results of the study suggest that cardiometabolic effects of atorvastatin depend on the prolactin status of patients.
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Drug effect of atorvastatin on middle cerebral atherosclerotic stenosis and high resolution NMR diagnosis.
Chen, X, Wang, S, Lin, L, Li, Y, Zhang, H
Pakistan journal of pharmaceutical sciences. 2018;(3(Special)):1169-1173
Abstract
Atherosclerosis (AS) is a chronic inflammatory reaction with the pathological changes in the lipid deposition of arterial intima. The disorder of blood lipid metabolism is the main factor of the occurrence and development of AS, and the inflammatory reaction and autoimmune reaction also run through the development of AS. In this study, we compared the efficacy and safety of atorvastatin, simvastatin, pravastatin and rosuvastatin in the treatment of AS. At the same time, we used high resolution magnetic resonance imaging (MRI) to assess the changes in plaque area in the middle cerebral artery and the patch area before and after drug treatment. After 6 months of treatment, the number of intima-media thickness (IMT), plaque and plaque in each group were significantly lower than that before the same group. The results showed that statin treatment of AS could significantly reduce the level of blood lipids, but rosuvastatin and atorvastatin had better effects on anti inflammation and maintaining plaque stability and the drug safety was good.
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Effects of Atorvastatin on Serum High-Sensitive C-Reactive Protein and Total Cholesterol Levels in Asian Patients With Atrial Fibrillation.
Wang, J, Wang, AR, Zhang, MJ, Li, Y
American journal of therapeutics. 2017;(1):e20-e29
Abstract
Elevated serum levels of high-sensitive C-reactive protein (hs-CRP) and total cholesterol (TC) correlate with atherosclerotic vascular disease and increased frequency of vascular events. In this study, we investigated the effect of atorvastatin treatment on serum hs-CRP and TC levels, and the recurrence rate of atrial fibrillation (AF) in patients. Furthermore, a meta-analysis was performed to confirm the findings in this study. A total of 105 patients with AF were recruited to this study, including 55 patients with AF who were treated with amiodarone and atorvastatin (the treatment group) and 50 patients with AF who were treated with only amiodarone (the control group). Patients were treated for 12 months and followed up regularly for 1 year. Serum hs-CRP and TC levels in patients before and after treatment were recorded, and AF recurrence rate at 3, 6, and 12 months of treatment was obtained. Statistical analyses were performed with R 3.1.0 software and STATA 12.0 software. For patients in both treatment and control groups, serum hs-CRP and TC levels were high before the treatments began (both P < 0.05). However, after 12 months of treatment, serum hs-CRP and TC levels in the treatment group was dramatically reduced compared with the control group (hs-CRP: 3.63 ± 2.14 mg/L vs. 2.75 ± 1.89 mg/L, t = 2.24, P = 0.027; TC: 4.66 ± 1.13 mmol/L vs. 4.20 ± 1.06 mmol/L, t = 2.15, P = 0.034). After 12 months of treatment, the AF recurrence rate in the treatment group was significantly lower than the control group (16.4% vs. 34.0%; χ = 4.37; P = 0.037). In addition, 13 studies were selected for meta-analysis. Pooled results of the meta-analysis showed that serum hs-CRP and TC levels decreased significantly in the treatment group compared with the case group [hs-CRP: SMD = 0.95, 95% confidence interval (CI) = 0.62-1.29, and P < 0.001; TC: SMD = 1.39, 95% CI = 0.65-2.13, and P < 0.001]. Our study presents compelling evidence that atorvastatin is highly effective in reducing serum hs-CRP and TC levels and lowering the recurrence rate of AF.
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4.
Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner.
Theusch, E, Kim, K, Stevens, K, Smith, JD, Chen, YI, Rotter, JI, Nickerson, DA, Medina, MW
The pharmacogenomics journal. 2017;(3):222-229
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Abstract
Statins are widely prescribed to lower plasma low-density lipoprotein (LDL) cholesterol levels. They also modestly reduce plasma triglyceride (TG), an independent cardiovascular disease risk factor, in most people. The mechanism and inter-individual variability of TG statin response is poorly understood. We measured statin-induced gene expression changes in lymphoblastoid cell lines derived from 150 participants of a simvastatin clinical trial and identified 23 genes (false discovery rate, FDR=15%) with expression changes correlated with plasma TG response. The correlation of insulin-induced gene 1 (INSIG1) expression changes with TG response (rho=0.32, q=0.11) was driven by men (interaction P=0.0055). rs73161338 was associated with INSIG1 expression changes (P=5.4 × 10-5) and TG response in two statin clinical trials (P=0.0048), predominantly in men. A combined model including INSIG1 expression level and splicing changes accounted for 29.5% of plasma TG statin response variance in men (P=5.6 × 10-6). Our results suggest that INSIG1 variation may contribute to statin-induced changes in plasma TG in a sex-specific manner.
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COQ2 polymorphisms are not associated with increased risk of statin-induced myalgia/myopathy in the Czech population.
Hubacek, JA, Adamkova, V, Zlatohlavek, L, Steiner-Mrazova, L, Vrablik, M
Drug metabolism and personalized therapy. 2017;(4):177-182
Abstract
BACKGROUND The gene COQ2, encoding 4-hydroxybenzoate-polyprenyltransferase (coenzyme Q2), belongs to the candidates potentially influencing statin treatment tolerability. This enzyme is involved in the biosynthesis of coenzyme Q10 (CoQ10), in which depletion induced by statin treatment is implicated in the development of statin-associated muscle symptoms (SAMS). Thus, polymorphisms in the COQ2 gene might explain susceptibility to SAMS. METHODS Adult patients with SAMS (on low doses of atorvastatin and simvastatin)-induced myalgia/myopathy (n=278), patients on statins but without SAMS (n=293) and population (part of the post-MONICA [Multinational MONItoring of trends and determinants in CArdiovascular disease] study) controls (n=561) were genotyped (polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] assay) for rs6535454 and rs4693075 polymorphisms within the COQ2 gene loci. RESULTS Distribution of rs6535454 in patients with SAMS (GG=51.1%, GA=40.0%, AA=8.9%) did not significantly differ (p=0.33; respectively 0.32 for codominant models of the analysis) from that in the population controls (GG=48.1%, GA=45.0%, AA=6.9%) or the SAMS-unaffected patients (GG=49.8%, GA=40.3%, AA=9.7%). Similarly, neither rs4693075 was associated with SAMS (CC=36.8%, CG=48.2%, GG=15.0% in patients suffering SAMS vs. CC=36.6%, CG=47.5%, GG=15.9 in controls and CC=35.8%, CG=48.2%, GG=15.9% in symptom-free patients, p=0.94 and 0.95 for codominant models of the analysis). Also, the haplotype distributions were not significantly different between the groups analyzed. CONCLUSIONS The polymorphisms of the COQ2 gene do not associate with SAMS in the Czech patients treated with low doses of statins. This is another clue that the coenzyme Q10 pathway is not the most important for the development of SAMS.
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Saliva versus plasma bioequivalence of rusovastatin in humans: validation of class III drugs of the salivary excretion classification system.
Idkaidek, N, Arafat, T
Drugs in R&D. 2015;(1):79-83
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Abstract
Bioequivalence of rusovastatin in healthy human volunteers was done using saliva and plasma matrices in order to investigate the robustness of using saliva instead of plasma as a surrogate for bioequivalence of class III drugs according to the salivary excretion classification system (SECS). Saliva and plasma samples were collected for 72 h after oral administration of rusovastatin 40 mg to 12 healthy humans. Saliva and plasma pharmacokinetic parameters were calculated by non-compartmental analysis. Analysis of variance, 90 % confidence intervals, and intra-subject and inter-subject variability values of pharmacokinetic parameters were calculated using Kinetica program V5. Human effective intestinal permeability was also calculated by SimCYP program V13. Rusovastatin falls into class III (high permeability/low fraction unbound to plasma proteins) and hence was subjected to salivary excretion. A correlation coefficient of 0.99 between saliva and plasma concentrations, and a saliva/plasma concentration ratio of 0.175 were observed. The 90 % confidence limits of area under the curve (AUClast) and maximum concentration (C max) showed similar trends in both saliva and plasma. On the other hand, inter- and intra-subject variability values in saliva were higher than in plasma, leading to the need for a slightly higher number of subjects to be used in saliva studies. Non-invasive saliva sampling instead of the invasive plasma sampling method can be used as a surrogate for bioequivalence of SECS class III drugs when an adequate sample size is used.
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Rosuvastatin reduces ischemia-reperfusion injury in patients with acute coronary syndrome treated with percutaneous coronary intervention.
Jiang, F, Yang, J, Zhang, L, Li, R, Zhuo, L, Sun, L, Zhao, Q
Clinical cardiology. 2014;(9):530-5
Abstract
BACKGROUND Statins reduce the incidence of cardiovascular events after percutaneous coronary intervention (PCI), but no clinical studies have investigated the role of statins in ischemia-reperfusion injury after PCI. HYPOTHESIS Rosuvastatin could reduce ischemia-reperfusion injury in patients with acute coronary syndrome treated with PCI. OBJECTIVES We investigated the effects of rosuvastatin on ischemia-reperfusion injury in patients with acute coronary syndrome after PCI and evaluated short-term prognosis. METHODS Patients scheduled for emergent PCI were given either rosuvastatin for ≥6 months (10 mg/d, every night; n = 55) or no statins (control group; n = 65). Serum superoxide dismutase activity, malondialdehyde, brain natriuretic peptide (BNP), and high-sensitivity C-reactive protein (hs-CRP) were determined before and after PCI, as well as left ventricular ejection fraction and left ventricular end-diastolic volume. Major adverse cardiac events were observed at follow-ups for 6 months. RESULTS Superoxide dismutase activity in the rosuvastatin-treated group was higher than that of the control group; serum levels of malondialdehyde were lower. BNP and hs-CRP levels in the rosuvastatin-treated group were lower than that of the control group. Four weeks after PCI, the left ventricular ejection fraction in the treatment group was higher than that of the control group, and the left ventricular end-diastolic volume was lower. At the 6-month follow-up, there was no difference in major adverse cardiac events between the 2 groups. CONCLUSIONS Rosuvastatin before PCI reduced ischemia-reperfusion injury in patients with acute coronary syndrome, which suggests the importance of application of rosuvastatin before PCI for early intervention.
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Lovastatin for reduction of leptin in nondialysis patients with type 2 diabetic nephropathy.
Gholamin, S, Razavi, SM, Taghavi-Garmestani, SM, Ghorbanihaghjo, A, Rashtchizadeh, N, Safa, J, Vatankhah, AM, Azizi, T, Argani, H
Iranian journal of kidney diseases. 2014;(3):201-6
Abstract
INTRODUCTION Diabetic Nephropathy (DN) is one of the main complications of diabetes mellitus, mostly ending to end-stage renal disease. Leptin and C-reactive protein (CRP), as inflammatory markers implicated in the progression of DN, increase in diabetes mellitus, while transferrin and albumin, as members of anti-oxidant defense mechanism, are found to decline. MATERIALS AND METHODS In a controlled clinical trial, 65 patients with type 2 DN were assigned to receive lovastatin or placebo, for 3 months, to assess statins' impact on serum levels of leptin, CRP, transferrin, albumin, and lipid profile. RESULTS Serum levels of CRP (3.52 +/- 4.16 mg/dL to 2.84 +/- 3.06 mg/dL, P = .02), leptin (10.78 +/- 8.30 mg/dL to 7.80 +/- 5.41 mg/dL, P = .006), low-density lipoprotein cholesterol (116.16 +/- 46.54 mg/dL to 85.46 +/- 29.22 mg/dL, P = .001), and total cholesterol (199.00 +/- 43.33 mg/dL to 164.67 +/- 35.19 mg/dL, P = .001) were lowered after lovastatin therapy. Mean serum level of high-density lipoprotein cholesterol increased (40.00 mg/dL to 42.80 mg/dL, P = .005) after the treatment. Lovastatin had no significant effect on albumin and transferrin. Placebo did not change any of the parameters after 3 months. CONCLUSIONS The effect of statins on the inflammatory markers involved in the development of DN is a new approach to evidence supporting the pleiotropic effect of this drug group.
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Cascade plasma filtration during the first year after CABG in patients with hyperlipidemia refractory to statins.
Ezhov, MV, Il'ina, LN, Safarova, MS, Afanasieva, OI, Adamova, IY, Atanesyan, RV, Konovalov, GA, Akchurin, RS, Pokrovsky, SN
Atherosclerosis. Supplements. 2013;(1):101-5
Abstract
OBJECTIVE To evaluate the effect of a 12-month course of weekly lipid apheresis on vein graft patency after coronary artery bypass grafting (CABG) in patients with hyperlipidemia refractory to statins. METHODS In a 12-month prospective controlled clinical trial we enrolled 34 male patients (mean age 57 ± 8 years) who passed through successful CABG and low-density lipoprotein cholesterol (LDL-C) level >2.6 mmol/L prior to the operation despite statin treatment. Patients were allocated into 2 groups: active (n = 17, weekly apheresis by cascade plasma filtration (CPF) plus atorvastatin), and control (n = 17, atorvastatin alone). Graft patency was evaluated by multislice computed tomography at 3 months and by angiography at 12 months after an operation. RESULTS Both groups were comparable in clinical and biochemical characteristics. During each CPF procedure, LDL-C level decreased by 64 ± 9%, apoB - by 65 ± 8%, Lp(a) - by 52 ± 15%,; these changes were significant compared to baseline and the control group. Mean net difference in LDL-C level between apheresis and control groups was 1.1 ± 0.3 mmol/L. Vein graft patency at study end was 88.2% (45 of 51) in the apheresis group versus 72.7% (40 of 55) in the control group (p = 0.05). Use of apheresis was associated with decreased vein graft occlusions by 46%: relative risk 0.54; 95% confidence interval 0.27 to 1.02; p = 0.05. CONCLUSION Our data suggest that the use of lipoprotein apheresis with CPF results in a better vein graft patency during the first year after CABG in patients with hyperlipidemia refractory to statins.
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Simvastatin therapy decreases MMP-9 levels in obese women.
Andrade, VL, do Valle, IB, Sandrim, VC
Journal of clinical pharmacology. 2013;(10):1072-7
Abstract
Statins exert cholesterol-independent beneficial effects on multiple targets including the cardiovascular system, in addition to modulating matrix metalloproteinases (MMPs) expression. The purpose of this study was to assess the effects of simvastatin treatment in obese women without comorbidities. We recruited 33 obese women that received placebo or simvastatin at 20 mg/day for 45 days. Plasma MMP-9, MMP-2, TIMP-1, and TIMP-2 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Cardiovascular risk was assessed by the Framingham risk score and Castelli indexes I and II. Treatment with simvastatin significantly reduced MMP-9 levels and the MMP-9/TIMP-1 ratio (P < .05) when compared to the placebo group (P > .05). Conversely, we found no effect on MMP-2, TIMP-1, and TIMP-2 levels or on the MMP-2/TIMP-2 ratio (P > .05). The Framingham risk score and Castelli I and II indexes were significantly reduced in the simvastatin-treatment group (P < .05), while we found no effect on the placebo group. These findings may have clinical importance since simvastatin therapy reduced cardiovascular risk and MMP-9 levels in obese woman without comorbidities, indicating a potentially new therapeutic approach.