Effect of ezetimibe/simvastatin compared with atorvastatin on lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia

Aim: To evaluate the effects of the usual starting and next higher doses of ezetimibe/simvastatin and atorvastatin on the cholesterol content of lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia. Methods: This post hoc analysis compared the effects of treatment with ezetimibe/simvastatin 10/20 mg vs. atorvastatin 10 and 20 mg/day and ezetimibe/simvastatin 10/40 mg/day vs. atorvastatin 40 mg/day on the cholesterol content of lipoprotein subclasses in the modified intent‐to‐treat (mITT) population (n = 1013) and in subgroups of patients with triglyceride (TG) levels <200 mg/dl (n = 600) and ≥200 mg/dl (2.6 mmol/l) (n = 413). Results: Ezetimibe/simvastatin significantly reduced low‐density lipoprotein cholesterol (LDL‐C) subclasses LDL₁‐C, LDL₂‐C and LDL₃‐C; real LDL‐C (LDL‐C^r); intermediate‐density lipoprotein cholesterol (IDL‐C), IDL₁‐C, IDL₂‐C; very low‐density lipoprotein cholesterol (VLDL‐C), VLDL₃‐C; and remnant‐like lipoprotein cholesterol (RLP‐C) from baseline more than atorvastatin at all dose comparisons (p < 0.01) in the mITT population. Significant improvements were also observed in high‐density lipoprotein cholesterol (HDL‐C) subclass HDL₃‐C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL_{1 + 2}‐C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL₄‐C and LDL‐C subclass patterns (A, B and I) were comparable for both treatments. Generally, similar results were observed for patients with TG levels <200 and ≥200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL₂‐C, slightly smaller decreases in all IDL subclasses and greater decreases in all VLDL‐C subclasses than those with lower TG levels. Frequency of pattern B was also reduced more in patients with higher TGs for both treatments. Conclusions: Ezetimibe/simvastatin reduced the cholesterol content of most lipoprotein subclasses from baseline with generally similar efficacy in patients with low and high TGs. Despite the different mechanism of action of ezetimibe, the response to ezetimibe/simvastatin and atorvastatin treatment related to these lipoprotein subclasses was generally consistent with the overall effects of these therapies on the major lipid/lipoprotein classes. The clinical significance of these results awaits further study.     

Simvastatin increases osteoblasts and osteogenic proteins in ovariectomized rats

Background  Previous reports have indicated that statins could prevent bone loss in ovariectomized (OVX) rats and increase the expressions of osteogenic genes in cultured osteoblasts. In this study, we hypothesized that simvastatin might increase osteoblast number and protein expressions of osteogenic markers localized in bones in concomitance with the prevention of bone loss in OVX rats.
Materials and methods  Fifty-four 3-month-old OVX and sham-operated (SHAM) female Sprague–Dawley rats were used. Simvastatin (10–20 mg kg⁻¹ day⁻¹) was administrated orally for 6 weeks. Trabecular volume, osteoblast number and osteogenic proteins including BMP2, collagen type I and osteocalcin on bone sections obtained from lumbar vertebral body, distal femur and proximal tibia were measured.
Results  The results showed that SHAM rats had significantly less trabecular bone volume and osteoblast number than that of OVX rats 6 weeks after operation. Oral simvastatin treatment (10–20 mg kg⁻¹ day⁻¹) increased bone volume and osteoblast number in the distal femurs, proximal tibiae and vertebrae of OVX rats. Furthermore, the osteoblastic cells with immuno-stained BMP2, collagen type I and osteocalcin in vertebral bones were significantly increased by simvastatin treatment (20 mg kg⁻¹ day⁻¹) in OVX rats.
Conclusions  This study demonstrates that simvastatin enhances the production of osteogenic proteins in bone and this effect may contribute to the prevention of bone loss in OVX rats.     

瑞舒伐他汀治疗老年人下肢动脉粥样硬化的效果评价

目的:观察瑞舒伐他汀治疗老年人下肢动脉粥样硬化的临床效果,为他汀类药物在抗老年人下肢动脉样硬化中的应用提供临床依据。方法:选取下肢动脉粥样硬化疾病患者90例(年龄≥60岁),随机分为辛伐他汀组和瑞舒伐他汀组(每组各45例),在其基础疾病常规治疗的同时分别给予辛伐他汀40 mg和瑞舒伐他汀10 mg治疗。于治疗开始时和32周结束时分别测定2组患者总胆固醇(TC)、低密度脂蛋白(LDL-C)和超敏C反应蛋白(hs-CRP)等生化指标,同时对2组患者下肢动脉内膜厚度、硬化强度、斑块和动脉狭窄程度进行评分比较。结果:治疗32周时,2组患者TC、LDL-C和hs-CRP水平较治疗前下降(P<0.05),治疗32周时瑞舒伐他汀组患者TC、LDL-C和hs-CRP水平均低于辛伐他汀组(P<0.05)。治疗32周时,与用药前比较,2组患者下肢动脉内膜厚度、斑块和狭窄评分均较治疗前下降(P<0.05);且瑞舒伐他汀组患者内膜厚度、斑块和狭窄评分均低于辛伐他汀组(P<0.05);硬化强度评分治疗前后比较差异无统计学意义(P>0.05)。结论:他汀类药物均可降脂并抗下肢动脉硬化,且瑞舒伐他汀降脂及抗动脉硬化作用优于辛伐他汀。     

辛伐他丁减少Connexin43表达和兔粥样硬化斑块形成

目的:证明辛伐他丁可以通过减少缝隙连接蛋白43(Connexin43, Cx43)的表达影响粥样斑块的形成及稳定性. 方法:高脂饲料喂养建立粥样硬化模型,治疗组给予辛伐他丁口服,活体内的Cx43和巨嗜细胞检测使用免疫组织化学方法,培养平滑肌细胞的Cx43检测使用免疫印记方法,Cx43的半定量使用计算机图像处理. 结果:药物干预的培养细胞和模型治疗组中Cx43的表达均明显减少,斑块的组成中,炎症细胞减少50%,胶原纤维平滑肌细胞含量增加. 结论: Cx43介导的细胞间通讯在粥样硬化形成中起重要作用,同时辛伐他丁减少Cx43的表达可以增加斑块的稳定性,Cx43成为动脉粥样硬化治疗中一个新的治疗靶点.     

急性冠状动脉综合征患者早期辛伐他汀干预对血脂和高敏C反应蛋白的影响

目的观察急性冠状动脉综合征(ACS)患者早期辛伐他汀治疗对血清高敏C反应蛋白(hs-CRP)和血脂水平的影响,探讨他汀类药物在ACS早期干预中的作用.方法选择住院的ACS患者80例,采用随机、单盲、对照方法将ACS患者分为对照组(n=38,每日口服安慰剂)和辛伐他汀治疗组(n=42, 辛伐他汀20 mg/d,发病48 h内开始服用),两组其他治疗相同;观察4周,于治疗前后分别检测患者血清hs-CRP及血脂的浓度.hs-CRP浓度采用酶联免疫吸附法测定,血脂采用酶法.结果治疗4周后,辛伐他汀组与对照组相比,患者血清hs-CRP和总胆固醇(TC)、甘油三酯(TG)及低密度脂蛋白胆固醇(LDL-C)浓度显著降低(P均<0.01),而对照组治疗前后差异无显著性(均为P>0.05).结论 ACS患者早期辛伐他汀治疗可明显改善血脂,降低hs-CRP水平.辛伐他汀具有减少炎症反应和稳定斑块的作用.     

辛伐他汀对稳定型心绞痛患者QT间期离散度的影响

目的：探讨辛伐他汀对稳定型心绞痛患者QT间期离散度（QTd）的影响。方法：60例稳定型心绞痛患者采用随机、单盲的方法分为辛伐他汀组和对照组（未服用他汀类药物）。观察6个月后所有稳定型心绞痛患者治疗前后QTd、心率校正的QT间期离散度（QTcd）、QT间期最大值（QTmax）、QT间期最小值（QTmim）的变化。结果：两组稳定型心绞痛患者治疗后QTmax和QTd、QTcd均较治疗前有明显减少（P〈0．05）,辛伐他汀组减少尤其明显,两组间比较差异有显著性（P〈0．05）。结论：稳定型心绞痛患者存在显著QTd增加,辛伐他汀可显著降低稳定型心绞痛患者QTd,从而降低心律失常的发生。     

辛伐他汀和胰岛素样生长因子-Ⅰ对人肺成纤维细胞增殖的影响

目的研究辛伐他汀和胰岛素样生长因子-Ⅰ（IGF-Ⅰ）共同对人肺成纤维细胞（HFL-1）增殖的影响。方法培养人肺成纤维细胞,采用MTT法检测在辛伐他汀和IGF-Ⅰ单独／共同作用下对人肺成纤维细胞增殖的影响。结果辛伐他汀和IGF-Ⅰ共同作用于人肺成纤维细胞时,IGF-Ⅰ的促细胞增殖作用受到抑制。结论辛伐他汀可抑制IGF-Ⅰ对人肺成纤维细胞的促增殖作用。     

氯沙坦钾联合辛伐他汀对糖尿病肾病患者尿足细胞排泄的影响

 目的 观察氯沙坦钾联合辛伐他汀对糖尿病肾病患者尿足细胞排泄的影响.方法 选择30例采用胰岛素控制血糖的2型糖尿病合并高胆固醇血症患者,按照患者自愿原则分成两组,其中A组(15例)给予氯沙坦钾100 mg/d +饮食控制血脂;B组(15例)给予氯沙坦钾100 mg/d +辛伐他汀20 mg/d +饮食控制.15例健康志愿者作为对照组.经6周洗脱期后,再随访观察3个月,然后采用间接免疫荧光镜检法检测治疗前后患者单克隆抗体 podocalyxin标记的尿足细胞水平.结果 A组脱落2例,B组脱落1例.与对照组相比,A、B两组尿足细胞水平均较高.经过洗脱期之后,A、B两组胆固醇、血糖、血压均能控制在要求范围.经过治疗后,尿足细胞水平较治疗前有所下降,且治疗后B组尿足细胞水平要明显低于A组.结论 糖尿病肾病尿足细胞的变化可作为判断病情活动的标志之一,氯沙坦钾和辛伐他汀联合治疗在降低糖尿病肾病患者血压、血脂的同时,也可显著减少尿足细胞的排泄,改善糖尿病肾病的预后.     

低分子肝素钙联合辛伐他汀治疗不稳定型心绞痛疗效观察

目的观察采用低分子肝素钙联合辛伐他汀治疗不稳定型心绞痛(UA)的治疗效果。方法观察组除常规用药外,加用低分子肝素钙5 000 u,每12 h皮下注射1次,连用7~10 d,辛伐他汀20 mg,每晚顿服1次,连服8周。对照组除常规用药外,另加普通肝素100 mg加50 g.L-1葡萄糖溶液500 mL维持静脉滴注,维持激活全血凝固时间于正常值的1.5~2倍,连用7~10 d。检测2组治疗前后总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C),并评定疗效。结果观察组总有效率(92%)明显高于对照组(76%)(P<0.05)。2组治疗前TC、TG、LDL-C、HDL-C比较均无显著性差异(P>0.05);对照组治疗前后TC、TG、LDL-C、HDL-C比较均无显著性差异(P>0.05);观察组治疗后HDL-C明显升高,TC、LDL-C、TG均下降,与治疗前比较均有显著性差异(P<0.05),与对照组治疗后比较均有显著性差异(P<0.05)。结论采用低分子肝素钙联合辛伐他汀治疗UA效果明显,安全可靠。     

Statin use and risk of breast cancer

BACKGROUND: Findings that statins inhibited the proliferation of breast cancer cells in vitro and in rodents have raised interest in whether the use of statins might decrease a woman's risk of developing breast cancer. We analyzed data from a population-based case-control study to evaluate the association between the use of statins and breast cancer risk. METHODS: Cases of incident invasive breast cancer in women 50 years of age or older and diagnosed from 1995-2001 were identified from population-based cancer registries in Wisconsin, Massachusetts, and New Hampshire. Controls were randomly selected, within each state, from lists of licensed drivers and Medicare beneficiaries. Information on the use of statins and other breast cancer risk factors was ascertained from structured telephone interviews. RESULTS: Overall, breast cancer cases were not more likely than controls to have ever used statins. Ever use of lipophilic statins as a group (simvastatin, lovastatin, and fluvastatin) and ever use of the hydrophilic statin pravastatin were also not associated with breast cancer risk. Ever use of fluvastatin was associated with a decreased risk of breast cancer (odds ratio [OR], 0.5; 95% confidence interval, 0.3-0.8) but the magnitude of the ORs did not vary across categories of duration of use. CONCLUSIONS: The use of statins overall was not associated with breast cancer risk.