辛伐他汀与非诺贝特合用致横纹肌溶解症1例

1例76岁女性糖尿病患者,因高血脂联合使用辛伐他汀(40mg/晚)和非诺贝特(200mg/早),出现双侧腓肠肌压痛,CK值为10268 IU/L。停用两种降脂药后,给予补液和改善微循环等对症治疗,症状逐渐好转。     

辛伐他汀对大鼠急性心肌梗死后心室重塑的保护作用

目的:研究在心肌梗死后辛伐他汀对钙调神经磷酸酶(CaN)的表达以及心室重塑的影响.方法:将SD大鼠随机分为假手术组、单纯模型组和辛伐他汀组,每组10只.用SD大鼠建立急性心肌梗死模型以致心衰.8 wk后测定左室质量指数,B超检测左室形态结构,Western Blot检测心肌CaN蛋白表达.结果:①单纯模型组和辛伐他汀组心肌肥厚指数明显高于假手术组,辛伐他汀组心肌肥厚指数明显低于单纯模型组(P<0.05).②单纯模型组和辛伐他汀组心肌CaN蛋白表达水平高于假手术组(P<0.05),辛伐他汀组低于单纯模型组(P<0.05).结论:辛伐他汀可能参与干预CaN介导的心肌肥厚通路从而改善心脏功能.     

肠外与肠内营养药临床应用的现状分析

目的:了解临床营养药的应用的现状和问题。方法:通过对临床医生、专家的问卷调查和定性访谈,对肠外营养(Parenteral Nutrition,PN)与肠内营养(Enteral Nutrition,EN)药的临床应用现况及其问题,以及营养药合理应用的主要因素进行了描述性分析。结果:营养支持已经广泛应用于临床各科室诸多疾病,但注重EN使用的医师仅占25．8%;究其原因,83．9%的医生认为对EN的新概念和技术进展了解不够,其次主要原因是医保具体支付政策和医院运营经济政策的问题。结论:为了控制临床住院费用,促进临床营养治疗的合理开展,不仅要制定其临床应用指南,普及教育,还要在技术层面制定相应的具体支付政策;舍此,医疗费用的宏观控制不仅很难操作,更无从谈起其合理性和科学性。     

大剂量辛伐他汀强化治疗对缺血性脑血管患者脑血管储备能力的影响

目的探讨大剂量辛伐他汀强化治疗对缺血性脑血管患者脑血管储备能力的影响及安全性。方法将108例缺血性脑血管病患者随机分成观察组与对照组各54例,2组均在常规治疗的基础上口服辛伐他汀,观察组40mg/次,对照组20mg/d,2组均1次/d,疗程均为6个月。比较2组患者临床疗效、脑血管储备功能(CVR)及屏气指数(BHI)、药物不良反应、复发率及病死率。结果观察组CVR(35.19±5.24)、BHI(1.54±0.33)明显高于对照组;不良反应发生率为(31.48%)、复发率、病死率(5.77%、3.85%)明显低于对照组(P0.05、0.01)。结论大剂量辛伐他汀强化治疗能有效改善脑血管储备能力,降低复发率及病死率,但需严密监测药物不良反应。     

大鼠急性心肌梗死后心脏炎症细胞因子基因和蛋白表达及辛伐他汀干预研究

目的探讨辛伐他汀对急性心肌梗死(AMI)后大鼠心脏炎症细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)mRNA表达和蛋白质产生的影响。方法Wistar大鼠36只分3组:(1)假手术(Sham)组;(2)心肌梗死对照(MI-C)组;(3)辛伐他汀(MI-S)组。动物笼养4周取出心脏,沿乳头肌等分为二,一半用逆转录聚合酶链反应法测定心脏细胞因子mRNA表达,另一半用Western blot测定细胞因子蛋白质生成量。结果Sham组上述细胞因子均无明显表达,MI-C组TNF-α,IL-1β,IL-6和IL-10 mRNA和蛋白产生均显著高于Sham组;同MI-C组比较,MI-S组的TNF-α,IL-1β,IL-6 mRNA和蛋白生成均显著下降,而IL-10的mRNA和蛋白明显升高。结论辛伐他汀明显降低AMI后大鼠心脏的致炎症细胞因子,而升高炎症保护因子IL-10。     

Simvastatin Regulates Myocardial Cytokine Expression and Improves Ventricular Remodeling in Rats after Acute Myocardial Infarction

Purpose: Studies have showed that inflammatory cytokines were involved in the process of left ventricular (LV) remodeling after acute myocardial infarction (AMI), anti-inflammation treatment ameliorated LV remodeling and improved cardiac performance. Hydroxymethylglutary coenzyme A reductase inhibition (statins) could affect the expression of inflammatory cytokines. We hypothesized that statins have beneficial effects on early LV remodeling and cardiac performance in rats with AMI by modulating the production of inflammatory cytokines.Methods: Rats with AMI were treated with placebo or simvastatin (gastric gavage) for 4 weeks. The pro-inflammatory cytokines: tumor necrosis factor (TNF)-, interleukin (IL)-1, IL-6 and the anti-inflammatory cytokine: IL-10 excreted by cardiac myocytes was examined. Echocardiography, hemodynamics and collagen type I production were measured to evaluate LV remodeling and cardiac function.Results: The mRNA expression and protein production of TNF-, IL-1, IL-6 and IL-10 in AMI group were significantly elevated compared with sham rats. Simvastatin markedly attenuated the production of TNF-, IL-1, IL-6 and increased IL-10 levels in the noninfarcted and infarcted regions, reduced collagen deposition in the noninfarcted myocardium and improved left ventricular function. However simvastatin did not alter plasma lipids.Conclusions: Simvastatin ameliorates early LV remodeling and improve cardiac function after AMI. Simultaneously, it decreased pro-inflammatory and increased anti-inflammatory cytokines, which suggests, but does not prove, a causal relationship independent of plasma lipid-lowering effects.Jinying Zhang and Xiang Cheng contribute to the work equally.This study was supported by grants from National Natural Science Foundation of China (No. 30370574).     

The Effect of Aggressive Versus Conventional Lipid-lowering Therapy on Markers of Inflammatory and Oxidative Stress

Purpose Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention. It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins. We aimed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress. Materials and methods This was a multi-centre, double-blind, placebo-controlled trial. Patients with previous cardiovascular disease, who did not achieve low density lipoprotein (LDL) cholesterol levels <2.6 mmol/l on conventional statin therapy (simvastatin 40 mg) were randomized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks (aggressive treatment). Lipids, C-reactive protein, soluble cellular adhesion molecules, neopterin, von Willebrand Factor, and antibodies against oxidized LDL were measured at baseline and after 16 weeks. Results Lipid levels decreased significantly in the aggressive treatment group (LDL-C reduction 20.8%; P < 0.001), whereas a slight increase was observed in the conventional group (LDL-C increase 3.7%; P = 0.037). A significant reduction in antibodies against oxidized LDL was seen in the aggressive (13.4%; P < 0.001) and the conventional (26.8%; P < 0.001) group, but there was no difference between groups (P = 0.25). Furthermore, no significant differences in change in other biomarkers was observed between both groups. Conclusions This study does not support the hypothesis that a more profound reduction in inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy.     

Lipid-altering efficacy and safety of simvastatin 80 mg/day: long-term experience in a large group of patients with hypercholesterolemia. World Wide Expanded Dose Simvastatin Study Group

BACKGROUND: Elevated levels of low-density lipoprotein (LDL) cholesterol promote the development of atherosclerosis and coronary heart disease. HYPOTHESIS: Simvastatin 80 mg/day will be more effective than simvastatin 40 mg/day at reducing LDL cholesterol and will be well tolerated. METHODS: Two similar, randomized, multicenter, controlled, double-blind, parallel-group, 48-week studies were performed to evaluate the long-term lipid-altering efficacy and safety of simvastatin 80 mg/day in patients with hypercholesterolemia. One study conducted in the US enrolled patients meeting the National Cholesterol Education Program (NCEP) LDL cholesterol criteria for pharmacologic treatment. In the other multinational study, patients with LDL cholesterol levels > or = 4.2 mmol/l were enrolled. At 20 centers in the US and 19 countries world-wide, 1,105 hypercholesterolemic patients, while on a lipid-lowering diet, were randomly assigned at a ratio of 2:3 to receive simvastatin 40 mg (n = 436) or 80 mg (n = 669) once daily for 24 weeks. Those patients completing an initial 24-week base study were enrolled in a 24-week blinded extension. Patients who had started on the 80 mg dose in the base study continued on the same dose in the extension, while those who had started on the 40 mg dose were rerandomized at a 1:1 ratio to simvastatin 40 or 80 mg in the extension. RESULTS: There was a significant advantage in the LDL cholesterol-lowering effect of the 80 mg dose compared with that of the 40 mg dose, which was maintained over the 48 weeks of treatment. The mean percentage reductions (95% confidence intervals) from baseline in LDL cholesterol for the 40 and 80 mg groups were 41% (42, 39) and 47% (48, 46), respectively, for the 24-week base study, and 41% (43, 39) and 46% (47, 45), respectively, after 48 weeks of treatment (p < 0.001 between groups). Larger reductions in total cholesterol and triglycerides were also observed with the 80 mg dose compared with the 40 mg dose at Weeks 24 and 48. Both doses were well tolerated, with close to 95% of patients enrolled completing the entire 48 weeks of treatment. Myopathy (muscle symptoms plus creatine kinase increase > 10 fold upper limit of normal) and clinically significant hepatic transaminase increases (> 3 times the upper limit of normal) occurred infrequently with both doses. There was no significant difference between the groups in the number of patients with such increases, although there were more cases for both with the 80 mg dose. CONCLUSIONS: Compared with the 40 mg dose, simvastatin 80 mg produced greater reductions in LDL cholesterol, total cholesterol, and triglycerides. Both doses were well tolerated.     

Effects of simvastatin,an HMG-CoA reductase inhibitor,in patients with hypertriglyceridemia

BACKGROUND: Patients with elevated levels of serum triglycerides (TG) often have other associated lipid abnormalities (e.g., low levels of high-density lipoprotein cholesterol [HDL-C]) and are at increased risk of developing coronary heart disease. Although the therapeutic benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in hypercholesterolemic patients have been well established, less is known about the effects of statins in patient populations with hypertriglyceridemia. HYPOTHESIS: The purpose of this study was to evaluate the lipoprotein-altering efficacy of simvastatin in hypertriglyceridemic patients. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. In all, 195 patients with fasting serum triglyceride levels between 300 and 900 mg/dl received once daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks. RESULTS: Compared with placebo, simvastatin treatment across all doses resulted in significant reductions (p < 0.05 - < 0.001) in serum levels of triglycerides (-20 to -31% decrease) and TG-rich lipoprotein particles. Significant (p < 0.001) reductions were also seen in low-density lipoprotein cholesterol (-25 to -35%) and non-HDL-C (-26 to -40%). Levels of HDL-C were increased (7-11%) in the simvastatin groups compared with placebo (p < 0.05 - < 0.001). CONCLUSION: The results of this study demonstrate the beneficial effects of simvastatin in patients with hypertriglyceridemia.     

辛伐他汀对不稳定型心绞痛患者血清sCD40L水平的影响

目的：探讨辛伐他汀对不稳定型心绞痛患者血清中可溶性CD40L（sCD40L）水平的影响。方法：48例ACS患者随机分为2组：A组（安慰剂组）,B组（辛伐他汀组）。采用间接免疫荧光流式细胞术和酶联免疫吸附法（ELISA）及常规酶法分别测定2组患者用药前与用药2、4和6周后血清sCD40L含量及总胆固醇（TC）水平。结果：B组患者服药2、4及6周后血清sCD40L含量明显低于A组（P〈0.05,P〈0.01,P〈0.01）。B组患者服药2、4及6周后血清sCD40L含量呈逐渐下降趋势,同用药前相比均有显著性差异（P〈0.05,P〈0.01,P〈0.01）。B组患者服药2、4及6周后血浆TC含量与用药前相比均有统计学意义（P〈0.05,P〈0.01,P〈0.01）。B组患者血清sCD40L水平的降低与血浆TC含量的降低无明显相关性（P〉0.05）。结论：他汀类药物能明显降低不稳定型心绞痛患者体内sCD40L的水平,对减轻炎症反应、稳定斑块有一定作用。