早期他汀类药物治疗对急性心肌梗死患者的益处

目的:探讨早期他汀类药物治疗对急性心肌梗死患者带来的益处。方法:571例急性心肌梗死患者分为他汀类药物治疗组和非他汀类药物治疗组,观察两组患者CK和CK-MB的峰值变化、发生充血性心力衰竭的风险和院内死亡率的变化情况。结果:他汀类药物治疗组院内死亡率、CK和CK-MB的峰值降低,进展为CHF的风险降低。结论:对急性心肌梗死患者在一般治疗的基础上早期应用他汀类药物治疗可获得很大的益处,且安全、可靠。     

辛伐他汀对动脉粥样硬化斑块内巨噬细胞MMP-3表达的影响

目的:观察辛伐他汀对动脉粥样硬化斑块内巨噬细胞MMP-3表达的影响.方法:在新西兰大白兔动脉粥样硬化模型基础上,分离、培养动脉粥样硬化斑块内巨噬细胞,应用免疫组化、RT-PCR及Western Blotting等方法观察辛伐他汀对巨噬细胞MMP-3表达的影响.结果:辛伐他汀能够明显抑制斑块内巨噬细胞MMP-3的表达,但对MMP-3 mRNA的表达无明显影响.结论:辛伐他汀具有独立于其系统性降脂作用之外的稳定动脉粥样硬化斑块的作用,此抑制作用可能不在基因转录水平,而是影响其后转录过程.     

他汀类药物致不良反应文献分析

目的:探讨临床一线降脂药他汀类药物致不良反应的一般规律及特点,为临床合理用药提供参考。方法:对2000年～2005年国内报道的使用他汀类药物致不良反应19例进行分类统计、分析。结果:不良反应临床表现以肌肉毒性反应常见,其次为肝脏毒性反应以及其它不良反应(神经系统反应、关节肿痛、过敏等)。结论:应严格掌握用药指征、规范用药剂量及联合用药,密切观察患者临床表现及生化指标监测结果,确保其用药安全,减少不良反应的发生。     

不同剂量他汀类药物对冠心病并发高脂血症患者的血脂及血管内皮功能的影响

①目的探讨不同剂量他汀类药物对冠心病并发高脂血症患者的血脂及血管内皮功能的影响。②方法选择冠心病并发高脂血症患者200例，随机分为4组，分别服用辛伐他汀10mg、20mg；阿托伐他汀10mg、20mg，4周后分别检测血脂水平、血管内皮功能的变化。③结果辛伐他汀、阿托伐他汀治疗4周后，可有效降低冠心病并发高脂血症患者的TC、TG、LDL-c水平，并改善血管内皮功能（NO升高，ET水平降低），差异具有显著性，在同种药物中20mg组优于10mg组，差异显著（P〈0．05）。④结论阿托伐他汀、辛伐他汀通过有效降低冠心病并发高脂血症患者的TC、TG、LDL—c水平，改善血管内皮功能，而且与剂量有关。     

Short-term reduction in bone markers with high-dose simvastatin

The effect of statins on bone mass and fracture rates is uncertain. Therefore, we investigated whether statin therapy acutely altered bone turnover as measured by changes in bone serum markers (bone-specific alkaline phosphatase, osteocalcin, and type I collagen N-telopeptide cross-links). Fasting blood samples were obtained from 55 (M/F 39/16) healthy nonsmoking adults (mean ± standard deviation: age, 50.4±7.5 years; body mass index, 27.8±4.9 kg/m²) with low-density lipoprotein cholesterol concentrations between 3.38–4.90 mmol/l. Subjects were randomized to four possible 8-week treatment regimens: placebo (n =14), pravastatin 40 mg/daily (n =12), simvastatin 20 mg/daily (n =14) or simvastatin 80 mg/daily (n =15). High-dose simvastatin (80 mg/daily) produced a significant reduction in bone-specific alkaline phosphatase as compared with other treatment regimens (p =0.009). However, there were no changes in urinary N-telopeptide cross-links, a sensitive marker of bone resorption. Short-term use of high-dose simvastatin lowers the level of the serum bone marker bone-specific alkaline phosphatase, which suggests the possibility of reduced bone turnover.     

Atorvastatin reduces thrombin generation after percutaneous coronary intervention independent of soluble tissue factor

INTRODUCTION: Statins were previously shown to suppress cellular tissue factor (TF) in vitro. Here, we investigated the effect of atorvastatin on the TF-pathway and thrombin generation after coronary angioplasty and stenting in vivo. MATERIALS AND METHODS: A cohort of 30 patients with coronary artery disease (CAD) was randomised to treatment with either none (n=10), 10 mg (n=10) or 80 mg (n=10) atorvastatin per day for the postinterventional period of 6 months starting the day before percutaneous coronary intervention (PCI). Fasting blood samples were collected on admission and after 6 weeks and 6 months of statin therapy to determine sTF, free tissue factor pathway inhibitor (TFPI) and prothrombin fragment F1.2 by immunoassay. RESULTS: Soluble TF (sTF) significantly correlated with thrombin generation as measured by prothrombin fragment F1.2 at baseline. This correlation was lost 6 weeks and 6 months after initiation of statin therapy. In vivo, F1.2 was significantly lowered after 6 months of statin therapy by both, low dose (0 vs. 10 mg: 1.3+/-0.3 vs. 0.7+/-0.2 ng/ml; P<0.05) and high dose (0 vs. 80 mg: 1.2+/-0.3 vs. 0.6+/-0.2 ng/ml; P=0.01) atorvastatin compared to control. However, sTF and free TFPI did not change significantly with atorvastatin therapy when compared to baseline or control. CONCLUSIONS: Our results demonstrate reduced in vivo generation of thrombin six months after percutaneous coronary intervention and statin therapy independent of sTF and free TFPI.     

Statins and survival outcomes in patients with metastatic renal cell carcinoma

BackgroundA growing body of evidence has demonstrated the anti-neoplastic activity of statins. The objective of this study was to investigate the effect of statin use on survival in patients with metastatic renal cell carcinoma (mRCC) treated in the modern therapy era.Patients and methodsWe conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Statistical analyses were performed using Cox regression and the Kaplan–Meier method.ResultsWe identified 4736 patients treated with sunitinib (n = 1059), sorafenib (n = 772), axitinib (n = 896), temsirolimus (n = 457), temsirolimus + interferon (IFN)-α (n = 208), bevacizumab + temsirolimus (n = 393), bevacizumab + IFN-α (n = 391) or IFN-α (n = 560), of whom 511 were statin users. Overall, statin users demonstrated an improved overall survival (OS) compared to non-users (25.6 versus 18.9 months, adjusted hazard ratio [aHR] 0.801, 95% confidence interval [CI] 0.659–0.972, p = 0.025). When stratified by therapy type, a benefit in OS was demonstrated in statin users compared to non-users in individuals receiving therapy targeting vascular endothelial growth factor (28.4 versus 22.2 months, aHR 0.749, 95% CI 0.584–0.961, p = 0.023) or mammalian target of rapamycin (18.6 versus 14.0 months, aHR 0.657, 95% CI 0.445–0.972, p = 0.035) but not in those receiving IFN-α (15.6 versus 14.8 months, aHR 1.292, 95% CI 0.703–2.275, p = 0.410). Adverse events were similar between users and non-users.ConclusionsWe demonstrate that statin use may be associated with improved survival in patients with mRCC treated in the targeted therapy era. Statins could represent an adjunct therapy for patients with mRCC; however, this is hypothesis generating and requires prospective evaluation.     

eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity

Purpose  Statins have pleiotropic effects, including endothelial nitric oxide synthase (eNOS) upregulation and increased nitric oxide formation, which can be modulated by a genetic polymorphism in the promoter region of the eNOS gene (T-786C). Here, we report our investigation of whether this polymorphism modulates the effects of atorvastatin on the fluidity of erythrocyte membranes. Methods  We genotyped 200 healthy subjects (males, 18–60 years of age) and then randomly selected 15 of these with the TT genotype and 15 with the CC genotype to receive placebo or atorvastatin (10 mg/day oral administration) for 14 days. Cell membrane fluidity was evaluated by electron paramagnetic resonance (EPR) and spin-labeling method. The EPR spectra were registered on a VARIAN-E4 spectrometer. Thiobarbituric acid-reactive species (TBA-RS) and plasma membrane cholesterol were determined in the erythrocytes. Results  Atorvastatin reduced membrane fluidity in CC subjects (P < 0.05) but not in those with the TT genotype (P > 0.05). While no significant differences were found in plasma membrane cholesterol concentrations, higher TBA-RS concentrations were found in the CC subjects than in the TT subjects (P < 0.05). Conclusions  These findings suggest that a short treatment with atorvastatin is disadvantageous to subjects with the CC genotype for the T-786C polymorphism compared to those with TT genotype, at least in terms of the hemorheological properties of erythrocytes.