Effects of atorvastatin and atorvastatin withdrawal on soluble CD40L and adipocytokines in patients with hypercholesterolaemia

OBJECTIVE: Beyond lipid lowering, statins have pleiotropic effects with favourable benefits against atherogenesis.Withdrawal of statin therapy has been demonstrated to abrogate vascular protective activity and even increase the incidence of thrombotic vascular events.The purpose of this study is to investigate the serial changes of soluble CD40 ligand (sCD40L) and two adipocytokines, adiponectin and resistin, after short-term atorvastatin therapy and withdrawal in patients with hypercholesterolaemia. METHODS AND RESULTS: Thirty-two patients with hypercholesterolaemia received atorvastatin 10 mg/day for 3 months. Serum lipid profiles, and levels of sCD40L, adiponectin and resistin, were assessed before and immediately after 3 months' statin therapy. Serum levels of sCD40L and adiponectin were also measured on the 3 consecutive days after statin withdrawal.After 3 months' statin therapy, levels of sCD40L (1.93 +/- 1.13 vs. 1.30 +/- 0.97 ng/mL), total cholesterol and low-density lipoprotein cholesterol (LDL-C) were all reduced significantly (p < 0.05). However, sCD40L level tended to increase towards baseline on the first and second days after statin withdrawal, but was not significantly elevated until the third day after withdrawal (1.89 +/- 1.28 vs. 1.30 +/- 0.97 ng/mL, p < 0.05).Total cholesterol and LDL-C levels did not increase during the 3 days of statin withdrawal. No significant changes of adiponectin and resistin levels were shown after statin therapy. CONCLUSIONS: These results indicate that the effect of statin on sCD40L level was abrogated after therapy withdrawal, and was independent of serum cholesterol level. Statin therapy did not significantly alter levels of adiponectin and resistin.     

Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus

This study evaluated the effects of rosiglitazone therapy on lipids and the efficacy and safety of rosiglitazone in combination with atorvastatin in patients with type 2 diabetes mellitus. Three-hundred thirty-two patients entered an 8-week, open-label, run-in treatment phase with rosiglitazone 8 mg/day, and 243 were randomized to a 16-week, double-blinded period of continued rosiglitazone plus placebo, atorvastatin 10 mg/day, or atorvastatin 20 mg/day. With rosiglitazone alone, a modest increase in low-density lipoprotein (LDL) cholesterol (9%), a shift in LDL phenotype from dense to large buoyant subfractions (52% of patients), and an increase in total high-density lipoprotein (HDL) cholesterol levels (6%), predominantly in HDL(2) levels (13%), occurred from week 0 to week 8. When atorvastatin was added, there was a further increase in HDL(3) (5%) and expected significant reductions (p <0.0001) in LDL cholesterol (-39%), apolipoprotein B (-35%), and triglyceride levels (-27%). Glycemic control achieved with rosiglitazone alone was not adversely affected by add-on atorvastatin. The combination was well tolerated compared with placebo. To conclude, in addition to the beneficial effects of rosiglitazone on glycemic control, rosiglitazone and atorvastatin in combination achieved 2 goals: the reduction of LDL cholesterol to <100 mg/dl and the removal of small dense LDL in patients with type 2 diabetes mellitus.     

调脂治疗对急性脑梗死患者血清炎性因子水平的影响

目的探讨阿托伐他汀调脂治疗对急性脑梗死患者血清炎性因子水平的影响。方法选择急性脑梗死患者120例,根据颈动脉超声检查结果分为稳定斑块组60例和易损斑块组60例,2组又随机各选30例分别服用阿托伐他汀10mg/晚(小剂量)和阿托伐他汀40 mg/晚(大剂量)治疗。所有患者治疗前和治疗后2周,检测血脂及血清高敏C反应蛋白(hs-CRP)、可溶性细胞间黏附因子1(sICAM-1)、可溶性血管细胞黏附分子1(sVCAM-1)和可溶性CD40配体(sCD40L)及基质金属蛋白酶3(MMP-3)。结果治疗前,易损斑块组sCD40L、sVCAM-1和MMP-3水平明显高于稳定斑块组(P<0.05,P<0.01)。治疗后2周,2组大剂量治疗患者血清LDL-C、hs-CRP、sICAM-1、sVCAM-1、sCD40L和MMP-3水平明显低于小剂量治疗患者(P<0.01)。结论大剂量阿托伐他汀调脂治疗,能降低患者血清炎性因子的水平,具有抑制炎症和稳定斑块作用。     

Comparison of the effects of combination atorvastatin (40 mg) + ezetimibe (10 mg) versus atorvastatin (40 mg) alone on secretory phospholipase A2 activity in patients with stable coronary artery disease or coronary artery disease equivalent

Secretory phospholipase A2 (sPLA2) is an enzyme that plays an important role in the pathogenesis of atherosclerosis and of adverse cardiovascular events. It is currently the target of emerging therapeutic agents. Our study was designed to investigate the effect of aggressive lowering of low-density lipoprotein (LDL) cholesterol with ezetimibe and atorvastatin on sPLA2 activity. We randomized 100 patients with stable coronary artery disease (CAD) or CAD equivalent (diabetes, stroke, or peripheral vascular disease) to receive ezetimibe 10 mg/day in association with atorvastatin 40 mg/day (combination therapy group) versus atorvastatin 40 mg/day and placebo (monotherapy group). Patients on statin therapy before inclusion were allowed to enter the study as long as the potency of the statin was lower than atorvastatin 40 mg/day. Lipid profile, high-sensitivity C-reactive protein (hs-CRP), and sPLA activity were measured at baseline and after 8 weeks of therapy. The decrease in LDL cholesterol was more significant in the combination therapy group, but the decrease in hs-CRP was similar. sPLA2 activity significantly decreased in the ezetimibe/atorvastatin group from 29 U/ml (interquartile range 23 to 35) to 26 U/ml (23 to 29, p = 0.001) but remained similar in the placebo/atorvastatin group (23 U/ml, 19 to 32, vs 22 U/ml, 19 to 28, p = NS). In a multivariate stepwise linear regression model, change in sPLA2 correlated with change in hs-CRP (p <0.001), baseline LDL cholesterol level (p = 0.001), body mass index (p = 0.003), diabetes mellitus (p = 0.04) and combination therapy with ezetimibe/atorvastatin (p = 0.05). In conclusion, this study demonstrates that coadministration of ezetimibe and atorvastatin decreases sPLA2 activity.     

Combination therapy with rosiglitazone and glibenclamide compared with upward titration of glibenclamide alone in patients with type 2 diabetes mellitus

AIM: To compare the efficacy of combination therapy using rosiglitazone (8 mg per day) and glibenclamide (7.5 mg per day) with upward titration of glibenclamide as monotherapy (maximum dose=15 mg per day) in reducing HbA(1c) levels over 26 weeks in patients with type 2 diabetes mellitus (T2DM). METHODS: Three hundred and forty patients with T2DM inadequately controlled (FPG > or =7.0 and < or =15.0 mmol/l) on glibenclamide 7.5 mg per day were randomised to either additional treatment with rosiglitazone 8 mg per day or up-titration of the glibenclamide dose (maximum dose=15 mg per day). RESULTS: After 26 weeks, treatment with rosiglitazone combination reduced HbA(1c) by 0.81% (P<0.0001) and FPG by 2.4 mmol/l (P<0.0001) compared with glibenclamide monotherapy. HOMA-S and HOMA-B increased by 12 and 28%, respectively (P<0.0001 for both) with combination compared with glibenclamide monotherapy. With rosiglitazone combination and glibenclamide monotherapy, total cholesterol: HDL ratio reduced by 5 and 13%, triglycerides reduced by 6 and 2%, and FFAs reduced by 15 and 8%, respectively. Both treatments were well tolerated and had predictable safety profiles. CONCLUSION: For patients inadequately controlled on glibenclamide, addition of rosiglitazone provides significantly improved glycaemic control compared with uptitration of glibenclamide. This may be preferable to continued monotherapy with higher doses of glibenclamide.     

芪参益气滴丸对冠状动脉介入术后炎症因子及心脏不良事件的影响

目的 观察芪参益气滴丸对急性冠脉综合征（ACS）患者经皮冠状动脉介入术（PCI）后炎症因子及主要不良心脏事件（MACE,包括复发心绞痛、急性心肌梗死、严重心律失常、心力衰竭、冠心病死亡）影响.方法纳入60例行PCI的ACS患者,随机分为常规治疗组（n=30）和芪参益气滴丸联合常规治疗组（芪参组,n=30）,采用酶联反应吸附法（ELISA法）比较两组术后24h和术后6个月血清高敏C反应蛋白（hs-CRP）、可溶性CD40配体（sCD40L）及基质金属蛋白酶-9（MMP-9）水平变化,并比较两组6个月MACE事件发生率.结果术后24h两组血清hs-CRP、sCD40L和MMP-9水平均无统计学差异（P＞0.05）;6个月后,两组hs-CRP、sCD40L和MMP-9水平分别是3.18±0.71mg/l、5.86±2.01 ng/dl和240.56±60.6 ng/dl.与对照组相比,芪参组血清hs-CRP、sCD40L及MMP-9均明显降低,差异有统计学意义（P＜0.05）,随访6个月,芪参组MACE发生率较对照组更低（13.33% vs.26.67%,P＜0.05）,且差异有统计学意义.结论 芪参益气滴丸可降低介入术后炎症因子hs-CRP、SCD40L和MMP-9的水平,同时降低MACE近期发生率.     

不同调脂方案对冠心病患者基质金属蛋白酶的影响

目的 比较冠状动脉狭窄50%～70%的冠心病人群中,40 mg阿托伐他汀与10 mg阿托伐他汀和10 mg依折麦布联合治疗的调脂作用和安伞性.探讨单用他汀治疗和联合治疗对基质金属蛋白酶(MMP)的影响.方法 选取冠状动脉狭窄50%～70%的冠心病患者42例(不置入支架),分为较大剂量阿托伐他汀(40 mg)组(单用他汀组)19例和小剂量阿托伐他汀(10 mg)联合依折麦布(10 mg)组(联合治疗组)23例.在服药前,用药4周,用药12周分别测定总胆同醇(1℃),甘油三酯,低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇,肝功能,肾功能,肌酸激酶,基质金属蛋白酶_2(MMP-2),基质金属蛋白酶-9(MMP-9),基质金属蛋白酶组织抑制因子-1(TIMP-1).结果 (1)单用他汀组和联合治疗组均在4周就可以明显降低患者的TC,LDL-C.12周时单用他汀组的LDL-C是(1.94±0.49)mmol/L,较前下降37.82%,联合治疗组的LDL-C是(1.92±0.54)mmol/L,较前下降38.26%,两组之间差异无统计学意义.(2)单用他汀组和联合治疗组的患者肝功能,肾功能,肌酸激酶在用药后无明显升高.(3)单用他汀组的MMP-2,MMP-9在12周时均较基线有明显降低,TiMP-1有明显升高.结论 (1)单用他汀治疗和联合治疗降脂疗效无差异.(2)两种治疗都没有引起患者肝、肾功能异常和肌酶异常.(3)40 mg阿托伐他汀治疗明显降低患者MMP-2、MMP-9,升高TIMP-1.     

吡格列酮和阿托伐他汀联合应用对经皮冠状动脉介入治疗后的抗炎作用

目的观察吡格列酮和阿托伐他汀联合应用对冠心病合并2型糖尿病PCI术后患者抗炎症作用的影响。方法选择冠心病合并2型糖尿病行PCI的患者116例,随机分为观察组56例,接受吡格列酮15 mg/d和常规治疗;对照组60例仅接受常规治疗。术后随访12周。分别于治疗前、治疗4、12周后检测血脂、高敏C反应蛋白(hs-CRP)、TNF-α、基质金属蛋白酶9(MMP-9)及颈动脉内膜中层厚度(IMT)变化。结果 2组患者治疗后4、12周hs-CRP、MMP-9、TNF-α明显下降(P<0.05,P<0.01);与对照组比较,观察组治疗后12周hs-CRP、MMP-9、TNF-α明显下降(P<0.05);与治疗前比较,2组患者治疗后4周(除TG外)、12周TC、LDL-C明显下降(P<0.05,P<0.01)。2组患者治疗后12周时HDL-C明显升高,TG明显下降(P<0.01)。结论冠心病合并2型糖尿病患者吡格列酮和阿托伐他汀联合应用能有效降低炎性因子水平。     

强化他汀治疗对择期PCI患者冠脉无复流及血浆APN与炎性因子的影响

目的:观察强化他汀治疗对择期经皮冠状动脉介入治疗（PCI）患者术中出现无复流风险及其血浆脂联素（APN）、血清高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、炎性因子高敏C反应蛋白(hs-CRP)的影响。方法:70例择期PCI患者随机分为强化他汀组（强化组,n=35）及常规他汀组（常规组,n=35）,强化组阿托伐他汀每日80 mg,2 d术前进行预处理,2 d后每日40 mg,服1月,常规组术前每日20 mg, 2 d,术后长期服用。分别检测术前及术后1月、3月hs-CRP、HDL-C、LDL-C、APN;观察术中无复流的发生率;主要终点是30 d内的主要不良心脏事件(MACE;死亡,心肌梗死或计划外的血管重建)。结果:两组均未出现MACE,均无明显不良反应。1月后两组APN、HDL-C均有上升,强化组APN:（8±4）mg/L,常规组:（6±3）mg/L;强化组上升明显（P<0.05）。两组hs-CRP、LDL-C均有下降,强化组hs-CRP:（3.2±2.1）mg/L,常规组:（4.5±2.3）mg/L;强化组显著性下降（P<0.05）;术前与术后比较差异有统计学意义(P<0.05)。强化组术中无复流3例,常规组5例,两组差异未达到统计学意义。结论:强化他汀治疗能够降低择期PCI患者血浆炎性因子水平,升高血浆APN水平。     

不同剂量阿托伐他汀对2型糖尿病患者体内炎症的影响

目的:探讨阿托伐他汀防治2型糖尿病并发动脉粥样硬化患者的可能机制。方法:用胶乳免疫增强比浊法测定2型糖尿病患者外周血中高敏C-反应蛋白(hs-CRP)水平、用酶联免疫吸附双抗体夹心法测定2型糖尿病患者外周血中白细胞介素6(IL-6)的水平,并观察不同剂量阿托伐他汀对它们的影响。结果:阿托伐他汀能显著降低2型糖尿病患者外周血中hs-CRP、IL-6的水平(P<0.05),增大剂量效果更显著(P<0.05),同时对肝功能及血肌酸磷酸激酶(CK)影响不大。结论:阿托伐他汀对2型糖尿病患者炎症有抗炎作用,且在一定范围内随着剂量的增加而加强,其抗炎作用可能是防治糖尿病并发动脉粥样硬化的机制之一。     

Enhanced levels of soluble CD40 ligand and C-reactive protein in a total of 312 patients with metabolic syndrome

The metabolic syndrome (MS) is associated with a systemic inflammatory response that plays an important pathogenetic role in atherothrombotic disease. Increasing evidence indicates that CD40-CD40 ligand interactions constitute an important mediator for vascular inflammation. The purpose of this study was to assess whether high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) levels were increased in patients with MS. During the study period from January 2004 to August 2004, 312 patients with MS and 98 control subjects were included. Anthropometric measurements, blood pressure assessment, electrocardiography, and blood measurements including fasting blood glucose, postprandial blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, glycated hemoglobin, white blood cell (WBC), platelets, hs-CRP, and sCD40L were performed. Patients with MS were divided into 3 groups based upon their glucose tolerance (group 1, normal glucose tolerance; group 2, prediabetic group; and group 3, diabetes mellitus). Patients with MS showed a significant increase of WBC, hs-CRP, and sCD40L levels compared with control subjects. The levels of both hs-CRP and sCD40L were positively correlated with body mass index (BMI). High-sensitivity CRP levels were also positively correlated with waist circumferences, fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, and negatively correlated with high-density lipoprotein cholesterol. In patients with MS, both hs-CRP and sCD40L levels were positively correlated with WBC count. We found a positive correlation between sCD40L and platelets. Among the subgroups of patients with MS, the mean levels of WBC, hs-CRP, and sCD40L did not show any significant differences. In conclusion, elevated levels of WBC, hs-CRP, and sCD40L in MS patients provide further insight into the relationship between MS and inflammation. In our study, positive correlations between BMI and both hs-CRP and sCD40L levels suggest that BMI is an important determinant of a chronic inflammatory state in patients with MS. Moreover, this study reports significantly increased levels of WBC, hs-CRP, and sCD40L not only in diabetic subjects with MS but also in prediabetic subjects and nondiabetic subjects with MS compared with control subjects. Our data suggest that MS patients have proinflammatory state independent of their glucose tolerance status. In our study, the positive correlation between the levels of sCD40L and platelets in patients with MS supports previous reports indicating that sCD40L are derived predominantly from platelets.     

阿托伐他汀对急性冠状动脉综合征病人疗效观察

目的研究不同剂量的阿托伐他汀对急性冠状动脉综合征病人血脂、基质金属蛋白酶(matrixmetalloproteinases,MMP)、高敏C反应蛋白C(highsensitivity-Creactiveprotein,hs-CRP)水平和生活质量的影响。方法选取我院急性冠状动脉综合征病人51例,随机分为小剂量治疗组28例,口服阿托伐他汀10mg,每日1次,共30d;大剂量治疗组23例,口服阿托伐他汀80mg,每日1次,共30d,治疗前和治疗30d时测定血脂、MMP-1、MMP-9、金属蛋白酶组织抑制物和hs-CRP,并进行活动平板检查。病人每周接受门诊或电话随访。结果30d后,两治疗组血脂水平、血清MMP-1、MMP-9、hs-CRP水平均降低,两组下降程度差异有统计学意义。胸痛发作次数减少,硝酸甘油用量减少和运动平板运动持续时间增加,两组相比差异有统计学意义(P<0.05)。结论阿托伐他汀治疗可减少急性冠状动脉综合征病人斑块基质成分降解和炎症反应,改善病人生活质量,大剂量阿托伐他汀应用获益更多。     

早期调脂干预对急性心肌梗死患者炎症因子的影响

目的观察早期较大剂量阿托伐他汀治疗急性心肌梗死(AMI)3d后患者血清可溶性CD40L(sCD40L)、P-选择素及可溶性血管粘附分子水平的变化,以探讨早期调脂干预对AMI斑块稳定、抑制炎症反应的作用。方法选取43例AMI患者随机分为常规治疗组(无服用任何调脂药物,21例)和阿托伐他汀组(立普妥20mg,qd,22例),测定治疗前后sCD40L、P-选择素、可溶性细胞间粘附分子-1(sICAM-1)和可溶性血管细胞间粘附分子-1(sV-CAM-1)的水平。结果两组治疗前后血脂水平变化无显著性差异。阿托伐他汀组治疗后血清sCD40L、P-选择素、sICAM-1分别下降35％、41％、30％,明显低于治疗前水平(P<0.05),sVCAM-1稍下降,但无统计学意义;在常规治疗组治疗前后上述指标均无明显变化。在阿托伐他汀组sCD40L、P-选择素、sICAM-1的降低与总胆固醇(TC)(分别为r=0.08,P=0.56;r=0.16,P=0.34;r=0.12,P=0.41),低密度脂蛋白胆固醇(LDL-C)(分别为r=0.09,P=0.88;r=0.11,P=0.46;r=0.18,P=0.77)的下降百分数之间无相关关系。结论在AMI的早期使用阿托伐他汀治疗3d,可明显降低血清炎症因子水平,可能有利于动脉粥样硬化斑块的稳定。     

罗格列酮对兔动脉粥样硬化MMP-2、TIMP-2表达的影响

目的:通过比较罗格列酮和辛伐他汀对兔动脉粥样硬化基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制因子-2(TIMP-2)表达的影响,探讨罗格列酮抗动脉粥样硬化的作用机制。方法:将36只雄性新西兰兔随机分为对照组、模型组、辛伐他汀组和罗格列酮组;采用皮下注射同型半胱氨酸硫内酯及高脂饲养的方法建立兔动脉粥样硬化模型。检测血清氧化低密度脂蛋白(ox-LDL)、sCD40L水平和主动脉粥样硬化组织中MMP-2和TIMP-2的表达。结果:与对照组相比,其他3组MMP-2蛋白表达显著升高,而TIMP-2蛋白表达显著降低;与模型组比较,辛伐他汀和罗格列酮组MMP-2表达显著降低,TIMP-2表达显著增加,血清ox-LDL、sCD40L水平显著降低。辛伐他汀组和罗格列酮组比较,差异无统计学意义。结论:罗格列酮可通过下调兔主动脉粥样硬化组织中MMP-2、上调TIMP-2的表达,降低血清ox-LDL和sCD40L水平,减轻大动脉内膜的炎性反应,发挥抗动脉粥样硬化的作用。     

Serial changes in circulating concentrations of soluble CD40 ligand and C-reactive protein in patients with unstable angina undergoing coronary stenting.

BACKGROUND: This study tested the hypothesis that serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) significantly reflect serial changes in patients with unstable angina, and thus the serum concentrations of these inflammatory biomarkers may be good candidates for predicting late restenosis after coronary stenting. METHODS AND RESULTS: The circulating concentrations of sCD40L and hs-CRP were prospectively measured (both pre-procedure, and on days 21, 90, and 180 after the procedure) in 77 consecutive patients with unstable angina undergoing coronary stenting. These inflammatory mediators were also evaluated in 30 healthy volunteers. The serum concentrations of sCD40L and hs-CRP were significantly higher pre-procedure in study patients than in normal control subjects (all p values < 0.0001). These inflammatory markers then declined to a substantially lower concentration by day 21 (all p values < 0.05). Circulating concentrations of hs-CRP in each patient then differed little from each other afterwards. However, the sCD40L concentration was once again raised significantly on days 90 and 180 as compared to day 21 (both p values < 0.05). This study found no significant link between raised circulating concentrations of sCD40L and hs-CRP and late restenosis. CONCLUSIONS: Circulating concentrations of sCD40L and hs-CRP were significantly increased in unstable angina patients pre-procedure and declined substantially thereafter. However, the circulating concentrations of these 2 inflammatory mediators were not useful in predicting late restenosis following coronary stenting.     

The effects of rosiglitazone and metformin on the plasma concentrations of resistin in patients with type 2 diabetes mellitus

Resistin is a protein secreted from adipose tissue that is thought to play a role in insulin sensitivity. We examined the effects of rosiglitazone and metformin on the plasma resistin levels in individuals with type 2 diabetes mellitus. Patients with type 2 diabetes mellitus who showed poor glycemic control with glimepiride (4 mg/d) were randomized to rosiglitazone (4 mg/d) and metformin (500 mg bid) treatment groups. All subjects continued glimepiride treatment as well. The plasma concentrations of resistin were measured at baseline and at 6 months of treatment for both groups. The anthropometric parameters, fasting plasma glucose, HbA1c, total cholesterol, triglyceride, high-density lipoprotein cholesterol, free fatty acids, and adiponectin concentrations were also measured. After 6 months of treatment, the reduction in plasma glucose levels was similar between the 2 groups. There were no significant changes in the lipid profiles of either group during the study period. The plasma resistin levels decreased in the rosiglitazone group (2.49 +/- 1.93 vs 1.95 +/- 1.59 ng/ml; P < .05) but increased in the metformin group (2.61 +/- 1.69 vs 5.13 +/- 2.81 ng/ml; P < .05). The plasma adiponectin concentrations were increased in the rosiglitazone group (2.91 +/- 1.46 vs 4.23 +/- 1.77 microg/ml; P < .05) but were unchanged in the metformin group. In summary, rosiglitazone treatment decreased the plasma resistin levels whereas metformin treatment increased them in patients with type 2 diabetes mellitus showing poor glycemic control with sulfonylurea therapy. These results suggest that the observed changes in plasma resistin levels are not the consequences of improved insulin resistance, nor are they consequences of glycemic control. Considering the potential role of resistin in insulin resistance, decrease in resistin levels may contribute to improving insulin action with rosiglitazone treatment.     

Spotlight on Rosiglitazone in the Management of Type 2 Diabetes Mellitus

Rosiglitazone, a thiazolidinedione with a different side chain from those of troglitazone and pioglitazone, reduces plasma glucose levels and glucose production and increases glucose clearance in patients with type 2 diabetes mellitus. Insulin sensitivity, pancreatic beta-cell function and surrogate markers of cardiovascular risk factors are significantly improved by rosiglitazone. Double-blind trials of 8 to 26 weeks of rosiglitazone 4 or 8 mg/day monotherapy indicate significant decreases in fasting plasma glucose (-2 to -3 mmol/L with 8 mg/day) and glycosylated hemoglobin levels [HbA(1c); -0.6 to -0.7% (-0.8 to -1.1% in drug-naive patients) with 8 mg/day]. Significant decreases in hyperglycemic markers occurred when rosiglitazone was combined with metformin (HbA(1c) -0.8 to -1.0%), a sulfonylurea (-1.4%) or insulin (-1.2%) for 26 weeks versus little change with active comparator monotherapy. Efficacy was maintained in trials of < or =2 years, and was also apparent in various ethnic subgroups, elderly patients and both obese and nonobese patients. Rosiglitazone is currently not indicated in combination with injected insulin. It should be administered in conjunction with diet and exercise regimens. Rosiglitazone is generally well tolerated. Despite rare individual reports of liver function abnormalities in rosiglitazone recipients, the incidence of these in clinical trials (< or =2 years' duration) was similar to that in placebo and active comparator groups. Fluid retention associated with rosiglitazone may be the cause of the increased incidence of anemia in clinical trials, and also means that patients should be monitored for signs of heart failure during therapy. Although bodyweight is increased overall with rosiglitazone therapy, increases are in subcutaneous, not visceral, fat; hepatic fat is decreased. The pharmacokinetic profile of rosiglitazone is not substantially altered by age or renal impairment, nor are there important drug interactions. Rosiglitazone is not indicated in patients with active liver disease or increased liver enzymes. Conclusions: Oral rosiglitazone 4 or 8 mg/day provides significant antihyperglycemic efficacy and is generally well tolerated, both as monotherapy and in combination with other antihyperglycemic agents, in patients with type 2 diabetes mellitus who do not have active liver disease. Long-term data are required before conclusions can be drawn about the clinical significance of positive changes to surrogate markers of cardiovascular disease risk and improvements to pancreatic beta-cell function. Rosiglitazone significantly improves insulin sensitivity and, as such, is a welcome addition to the treatment options for patients with type 2 diabetes mellitus.     

Anti-inflammatory effects of atorvastatin: modulation by the T-786C polymorphism in the endothelial nitric oxide synthase gene

Statins produce cholesterol-independent, anti-inflammatory effects, which result at least in part from increased endothelial nitric oxide production. These effects may be modulated by polymorphisms in the endothelial nitric oxide synthase (eNOS) gene. Here, we examined whether the T-786C polymorphism of eNOS gene affects the concentrations of markers of atherosclerosis and inflammation (sCD40L, sVCAM-1, sICAM-1, sP-selectin, MCP-1, high sensitivity (hs)-CRP, MMP-2, MMP-9, and TIMP-1). We also studied whether atorvastatin-induced anti-inflammatory effects are modulated by this polymorphism. Healthy male volunteers (N=200), Caucasians, non-smokers, were genotyped for the T-786C polymorphism by restriction fragment length polymorphism. Subjects with TT or CC genotype received placebo for 14 days followed by 14 days of treatment with atorvastatin, 10mg/day p.o. The concentrations of inflammatory markers were measured with ELISA kits or by gelatin zymography. Serum cholesterol and LDL-cholesterol were significantly reduced after atorvastatin treatment in both genotype groups (P<0.05). No significant differences between genotype groups were found in the concentrations of the inflammatory markers after placebo. However, atorvastatin significantly reduced the concentrations of sCD40L, sVCAM-1, sP-selectin and MMP-9 in subjects with CC (but not TT) genotype (P<0.05). While atorvastatin decreased hs-CRP levels in both genotype groups (P<0.05), no significant effects were found on the concentrations of sICAM-1, MCP-1, pro-MMP-9, pro-MMP-2 and TIMP-1. These results suggest no effects for the T-786C polymorphism on the concentrations of inflammatory markers. However, this polymorphism modulates the anti-inflammatory effects of atorvastatin. These findings may be relevant for the primary prevention of cardiovascular events in subjects with CC genotype, who may be at increased cardiovascular risk and could benefit from treatment with statins.     

阿托伐他汀对老年2型糖尿病患者颈动脉硬化的影响

目的探讨阿托伐他汀对老年2型糖尿病患者颈动脉硬化的影响。方法选择100例合并颈动脉硬化的老年2型糖尿病患者,随机分为对照组50例(仅控制血糖)和联合组50例(在控制血糖基础上,口服阿托伐他汀20mg/晚),疗程为12个月。测定治疗前后颈动脉硬化相关指标、血脂及高敏C反应蛋白(hs-CRP)。结果两组患者治疗前颈动脉内膜中层厚度(IMT)、斑块检出率、斑块Crouse积分及颈动脉内径无显著差异;与治疗前比较,对照组治疗12个月后颈动脉IMT、斑块检出率及Crouse积分明显增加(P<0.05),颈动脉内径、血脂及hs-CRP水平无明显变化;联合组治疗12个月后颈动脉IMT、斑块检出率、Crouse积分明显降低,颈动脉内径明显增加(P<0.05),治疗6个月、12个月后血清LDL-C、TG、TC、hs-CRP明显降低,HDL-C明显升高(P<0.05)。IMT、Crouse积分均与LDL-C、TG、TC、hs-CRP呈正相关,与HDL-C呈负相关(P<0.05)。结论在控制血糖的同时,联合应用阿托伐他汀,对延缓老年2型糖尿病患者颈动脉硬化进展有一定影响。     

不同剂量阿托伐他汀对经皮冠状动脉介入治疗术后基质金属蛋白酶-9和高敏C反应蛋白的影响

目的 探讨不同剂量阿托伐他汀对直接经皮冠状动脉介入治疗术（PCI）后基质金属蛋白酶-9 （MMP-9）和高敏C反应蛋白（hs-CRP）的影响.方法 96例接受直接PCI的急性心肌梗死（AMI）患者随机分为大剂量组和标准剂量组,两组各48例,于术前分别给予阿托伐他汀钙片40 mg和20 mg口服,术后两组分别继续每日睡前口服40 mg和20 mg持续1周,1周后均同为20 mg睡前口服.于术前及术后24小时、72小时、1周和1个月测定血清MMP-9、hs-CRP水平.结果 两组hs-CRP、MMP-9水平PCI术后24小时均升高（P＜0.01）,术后72小时逐渐下降,术后l周低于术前（P ＜0.01）;40 mg剂量组下降更显著.结论 AMI患者PCI术后使用大剂量阿托伐他汀不良反应无明显增加,可明显降低hs-CRP、MMP-9水平,减少炎症反应,保护血管内皮功能,预防支架内血栓形成.