阿托伐他汀对不伴有高胆固醇血症的慢性心衰患者的血管内皮功能的影响

目的：研究短期使用阿托伐他汀对不伴有高胆固醇血症的慢性充血性心力衰竭（CHF）患者内皮依赖性血管舒张功能的影响。方法：共52名CHF患者在不改变患者长期使用的抗心衰药物的基础上给予阿托伐他汀（40mg／d）或者安慰剂,为期6周,试验前后对受试者进行血管内皮功能、血管神经激素水平及超声心动图的检测。结果：与安慰剂组相比．阿托伐他汀组治疗后肱动脉内径明显扩张（P〈0．01）;含服硝酸甘油后肱动脉内径也明显扩张（P〈0．05）;②与安慰剂组比较,阿托伐他汀组C型尿钠肽,内皮素1水平明显下降。血一氧化氮和降钙素基因相关肽水平明显上升（P〈0．01）;③较之安慰剂组,阿托伐他汀组左室收缩末内径明显缩小,左室舒张末内径、左室射血分数及心输出量等明显增加（P〈0．01）。结论：不伴有高胆固醇血症的慢性心衰患者加用阿托伐他汀能更有效改善患者血管内皮舒张功能、血管神经激素水平及心功能。     

高胆固醇血症对兔胰岛β细胞的影响及阿托伐他汀的干预作用

目的 研究高胆固醇血症对兔胰岛β细胞的影响及阿托伐他汀的干预作用.方法 24只新西兰白兔随机分为正常对照组、高胆固醇组及阿托伐他汀组.饲喂6周后,测空腹血脂、血糖、胰岛素浓度;行口服葡萄糖耐量试验(OGTT);取胰腺组织用免疫组织化学法观察胰岛形态;实时荧光定量PCR检测胰腺胰岛素原mRNA的表达;分光光度法测定丙二醛(MDA)、还原型谷胱甘肽(GSH)含量.结果 高胆固醇组糖负荷后30、60 min血糖值、葡萄糖曲线下面积及胰岛素抵抗指数(HOMA-IR)升高,胰岛素敏感指数(ISI)、β细胞功能指数(HBCI/IR)降低;β细胞增生肥大,胰岛素阳性表达明显增多;胰岛素原mRNA表达上调;MDA吸光度值明显增高,GSH则降低.与高胆固醇组比较,阿托伐他汀组β细胞增生有所改善;MDA吸光度值降低,GSH则升高;胰岛素原mRNA表达、OG-TT、HOMA-IR、HBCI/IR、ISI无显著差异.结论 高胆固醇通过诱导胰腺氧化-抗氧化失衡导致胰岛β细胞形态与功能受损,阿托伐他汀减轻了胰岛细胞的氧化应激,但并未改善高胆固醇诱发的糖代谢紊乱.     

阿托伐他汀治疗老年高胆固醇血症患者对胰岛素抵抗的影响

一、对象与方法　　 1.对象 :2 0 0 1年 11月至 2 0 0 2年 1月我院二内科住院的老年患者 36例 ,男 2 8例 ,女 8例 ,年龄 6 0～ 75岁 ,平均6 4 8岁。其中高胆固醇血症〔总胆固醇 (ＴＣ)≥ 5 7ｍｍｏｌ/Ｌ〕患者 13例 ,混合型高脂血症〔ＴＣ≥ 5 7ｍｍｏｌ/Ｌ、甘油三酯 (ＴＧ)≥ 1 7ｍｍｏｌ/Ｌ〕患者 2 3例 ,排除冠心病、高血压、甲状腺疾病、糖尿病、慢性胰腺炎、肝肾疾病 ,所有患者治疗前2个月均未进行降脂治疗。　　 0 2 .观察方法 :本组对象试验前均于早晨空腹 (禁食 12ｈ以上 )采静脉血化验 ,包括ＴＣ、ＴＧ、低密度脂蛋白胆固醇(Ｌ…     

阿托伐他汀对高胆固醇血症患者AT1表达的影响

目的 通过观察高胆固醇血症患者血管紧张素Ⅱ(AngⅡ)1型受体(AT1)表达的变化及阿托伐他汀对其表达变化的影响,探讨肾素-血管紧张素系统(RAS)在动脉粥样硬化(AS)发生的作用及他汀多效性作用的机制.方法 在该院健康查体中心随机选取健康对照者40例和高胆固醇血症患者60例,分别为对照组和高脂组;高脂组予以阿托伐他汀20 mg/d,睡前口服,共12 w.对照组、高脂组他汀治疗前及治疗后,肘静脉取血,分离血清、血浆并提取血小板.放射免疫分析法检测血浆的AngⅡ水平,RT-PCR和Western印迹方法分别检测血小板AT1的mRNA和蛋白质表达水平.结果 ①高脂组治疗前的血浆AngⅡ水平较对照组明显升高[(92.13±22.27)pg/ml vs(50.85±12.15)pg/ml](P＜0.01),治疗后的血浆AngⅡ水平较治疗前明显降低[(78.57±18.33)pg/ml vs(92.13±22.27)pg/ml](P＜0.05).②高脂组治疗前血小板的AT1 mRNA和蛋白质表达较对照组明显升高[0.93±0.22 vs 0.25±0.06(P＜0.01)和1.35±0.32 vs 0.42±0.10(P＜0.01)],治疗后血小板的AT1 mRNA和蛋白质表达较治疗前明显降低[(0.52±0.13 vs 0.93±0.22(P＜0.01)和0.72±0.16 vs 1.35±0.32(P＜0.01)].③高脂组治疗前AngⅡ与AT1表达的相关分析显示,AT1表达与血浆的AngⅡ呈显著正相关(r=0.607,P＜0.01).结论 阿托伐他汀下调高胆固醇血症患者血小板AT1表达的增高.     

阿托伐他汀对代谢综合征患者踝臂指数和C反应蛋白的影响

基础研究和临床研究显示,血清C反应蛋白（CRP）是重要的致动脉粥样硬化的炎症因子。踝臂指数（ABI）是诊断外周动脉病准确、简便,无创的方法,而他汀类药物可改善外周动脉病（PAD）。本文旨在观察阿托伐他汀短期治疗对代谢综合征（Ms）患者ABI和CRP的影响。     

阿托伐他汀对急性冠脉综合征患者血浆TF的影响

目的观察阿托伐他汀对急性冠脉综合征患者组织因子(TF)表达的影响。方法将2011年3月—2012年3月100例急性冠脉综合征患者随机分为两组,对照组48例予常规治疗,治疗组52例在常规治疗的基础上加用阿托伐他汀,比较两组间TF水平变化。结果治疗组总有效率为90.4%,显著高于对照组的62.5%(P<0.05)。治疗组治疗后TF水平低于对照组,差异有统计学意义(P<0.05)。结论阿托伐他汀除了可调节血脂外,还可降低急性冠脉综合征患者血浆TF表达,从而减少急性冠脉事件发生。     

阿托伐他汀对高胆固醇血症患者载脂蛋白A1和B的影响

血脂的异常是心血管的主要危险因素 ,近年来研究表明载脂蛋白A1 (apoA1 )和载脂蛋白B(apoB)与冠状动脉粥样硬化性心脏病密切相关。本文旨在观察阿托伐他汀对原发性高胆固醇血症患者apoA1 和apoB的作用。1　对象与方法63例经高脂血症膳食控制方案〔1〕及 4周进行饮食控制的导入期之后 ,血清总胆固醇 (TC)≥ 5 .98mmol/L的原发性高胆固醇血症患者入选。曾使用调脂药物者需先经过 2周清洗期。其中男32例 ,女 31例 ,年龄 ( 5 5 .42± 1 0 .48)岁。根据治疗前基础apoB值将患者分为apoB升高组 ( 4 2例 )和apoB正常组 ( 2 1例 )。患者每晚顿服…     

阿托伐他汀对高胆固醇血症兔主动脉环氧合酶2的影响

目的检测环氧合酶2在高胆固醇血症兔主动脉粥样硬化中的表达,探讨阿托伐他汀对环氧合酶2表达的影响及其意义。方法选取健康雄性新西兰兔24只,随机分为正常饮食组(n=8)和高胆固醇饮食组(n=16),喂养8周后,将后者随机分为高胆固醇血症组(n=8)和阿托伐他汀组[2.5 mg/(kg.d),n=8],继续喂养6周后,取各组兔主动脉,行动脉粥样硬化病变面积测定,采用逆转录聚合酶链反应检测主动脉环氧合酶2 mRNA的表达,酶联免疫吸附法测定血清白细胞介素6水平,免疫组织化学法测定主动脉粥样硬化斑块中环氧合酶2和基质金属蛋白酶9的表达。结果高胆固醇饮食兔经阿托伐他汀干预6周后,动脉粥样硬化斑块面积较高胆固醇血症组显著缩小(43.0%±12.5%比83.0%±11.6%,P<0.05)。高胆固醇饮食兔主动脉环氧合酶2 mRNA表达较正常饮食兔明显增强(1.03±0.09比0.09±0.01,P<0.05),阿托伐他汀干预后明显下降(0.57±0.10,P<0.05),且主动脉环氧合酶2 mRNA表达与斑块面积和血清白细胞介素6水平均呈正相关(r分别为0.803和0.795,P均<0.05)。高胆固醇血症组14周时主动脉粥样硬化斑块中环氧合酶2蛋白表达明显增强,而阿托伐他汀组显著性降低(62.4%±8.5%比34.3%±8.8%,P<0.05),且环氧合酶2蛋白表达与基质金属蛋白酶9的蛋白表达呈正相关(r=0.887,P<0.05)。结论环氧合酶2在动脉粥样硬化的发生和发展中可能起重要的促进作用,阿托伐他汀可能通过降低高胆固醇血症兔主动脉及其粥样斑块中环氧合酶2的表达,抑制基质金属蛋白酶9和白细胞介素6的分泌,从而发挥降脂以外的抗炎症作用。     

阿托伐他汀治疗单纯收缩期高血压伴高胆固醇血症临床观察

随着现代生活节奏的加快和生活水平的提高,人群中高血压发病率逐渐增加,而由于人均寿命的延长,单纯收缩期高血压(ISH)更加多见[1].对单纯收缩期高血压治疗,我院联合使用阿托伐他汀取得了较满意的疗效,现报告如下.     

阿托伐他汀对高血压合并急性冠脉综合征患者血脂及hs-CRP的影响

目的探究阿托伐他汀对高血压合并急性冠脉综合征患者血脂及hs-CRP水平的影响。方法从2016年1月-2018年1月在我院就诊的高血压合并急性冠脉综合征患者中选取68例进行研究,以随机抽签法将其分成两组,每组各34例,两组均采用相同的降压治疗方案,在此基础上,对照组采用辛伐他汀治疗,观察组采用阿托伐他汀治疗,比较两组治疗前后血脂指标及hs-CRP水平。结果治疗后,观察组的TC、TG、LDL-C、hs-CRP水平显著低于对照组,且HDL-C值明显高于对照组(P<0.05)。结论阿托伐他汀能够有效改善高血压合并急性冠脉综合征患者的血脂水平,并可减轻炎症反应,对于稳定动脉粥样硬化斑块、改善预后具有积极意义。     

Effect of atorvastatin (10 mg/day) on glucose metabolism in patients with the metabolic syndrome

Large interventional studies have shown that statins may reduce the incidence of type 2 diabetes mellitus. However, it is uncertain whether short-term statin therapy can affect insulin sensitivity in patients with the metabolic syndrome. We evaluated the effect of atorvastatin (10 mg/day) in 10 insulin-resistant subjects (age 40 +/- 12 years, body mass index 33.6 +/- 5.2 kg/m(2), triglycerides 2.84 +/- 1.99 mmol/L [249 +/- 175 mg/dl], glucose 6.06 +/- 0.67 mmol/L [109 +/- 12 mg/dl)] using the homeostasis model assessment (HOMA) index (parameter of insulin resistance derived from fasting glucose and fasting insulin concentrations; 5.7 +/- 2.6) in a randomized placebo-controlled, double-blind, crossover study. Subjects were randomized to receive placebo or atorvastatin, each given for 6 weeks separated by a 6-week wash-out period. At the beginning and end of each treatment phase, the patients underwent an oral glucose tolerance test, a 72-hour continuous glucose measurement, and a detailed lipid determination, including a standardized fat tolerance test. Compared with placebo, atorvastatin resulted in a significant (p = 0.05) reduction in the HOMA index (-21%), fasting C-peptides (-18%), glucose (area under the curve during the oral glucose tolerance test, -7%), and a borderline (p = 0.08) reduction of insulin (-18%). The parameters derived from the continuous 72-hour glucose monitoring did not change. A significant reduction also occurred in the total and low-density lipoprotein cholesterol concentrations, although the fasting and postprandial triglyceride concentrations did not change significantly. However, we found a significant correlation between atorvastatin-induced changes in the HOMA and baseline HOMA and between the atorvastatin-induced changes in triglycerides and insulin concentrations. The free-fatty acid, interleukin-6, and high sensitivity C-reactive protein concentrations did not change. Our data indicated that in insulin-resistant, nondiabetic subjects, 6 weeks of atorvastatin (10 mg/day) resulted in significant improvement in insulin sensitivity.     

Comparison of effects of pitavastatin and atorvastatin on glucose metabolism in type 2 diabetic patients with hypercholesterolemia

Aims/Introduction

The distinct effects of different statins on glycemic control have not been fully evaluated. In this open‐label, prospective, cross‐over clinical trial, we compared the effects of pitavastatin and atorvastatin on glycemic control in type 2 diabetic patients with hypercholesterolemia.

Materials and Methods

A total of 28 Japanese type 2 diabetics with hypercholesterolemia treated with rosuvastatin (2.5 mg/day) for at least 8 weeks were recruited to this quasi‐randomized cross‐over study. At study entry, the patients assigned to sequence 1 received pitavastatin (2 mg/day) for 12 weeks in period 1 and atorvastatin (10 mg/day) for another 12 weeks in period 2, whereas patients assigned to sequence 2 received atorvastatin (10 mg/day) for 12 weeks in period 1 and pitavastatin (2 mg/day) for another 12 weeks in period 2. Blood samples were collected at three visits (baseline, after 12 and 24 weeks).

Results

Lipid control was similar in both statins. The difference in glycated hemoglobin between pitavastatin and atorvastatin treatments was −0.18 (95% confidence interval −0.34 to −0.02; P = 0.03). Compared with atorvastatin, pitavastatin treatment significantly lowered the levels of glycoalbumin, fasting glucose and homeostasis model assessment of insulin resistance.

Conclusions

Our results showed that treatment with pitavastatin had a more favorable outcome on glycemic control in patients with type 2 diabetes compared with atorvastatin. This trial was registered with UMIN (no. 000003554).     

Impaired glucose metabolism in hypertensive patients with/without the metabolic syndrome

BackgroundIn hypertension clinics, screening patients for the metabolic syndrome (MetS) is common practice, while performing the cumbersome oral glucose tolerance test (OGTT) is not. How large is the underestimation of diabetes and prediabetes that ensues is unknown.MethodsWe recruited N = 1397 patients with essential arterial hypertension who underwent a 75-g OGTT and were classified as normally glucotolerant (NGT) or having impaired glucose metabolism (IGM), and as affected or not by MetS (ATPIII criteria). The agreement between the OGTT and the ATPIII criteria in attributing a high cardiovascular risk was estimated by matching the categories of MetS and no-MetS with NGT and IGM.Resultsn = 677/1397 patients (48%) satisfied criteria for MetS, while n = 757/1397 (54%) had an IGM. MetS and IGM were both present in n = 512/1397 patients (36.6%), and both absent in n = 475/1397 (34%). Further n = 410/1397 patients (29%) were discordant for the two conditions: n = 165/410 (40%) had the MetS but were NGT, and n = 245/410 (60%) had IGM but no MetS. Among IGM patients, n = 168/757 (22%; of which 45 had no MetS) received a new diagnosis of diabetes based on OGTT criteria. Among all discordant patients, those with IGM and no MetS were more commonly males (p < 0.001), and had older age (p < 0.001) and lower body mass index (p < 0.05).ConclusionsAmong patients with hypertension, the estimate of the prevalence of diabetes and prediabetes, hence of the global cardiovascular risk, can be seriously flawed unless an OGTT is performed. Our results support a wider use of the OGTT in the management of hypertension.     

罗格列酮对非糖尿病代谢综合征患者糖脂代谢、胰岛素抵抗及炎症指标的影响

157名伴有低HDL-C和代谢综合征（MS）的非糖尿病患者随机分为两组,分别给予马来酸罗格列酮4mg或8mg／d治疗12周之后,两组FPG、2hPG、HbA1C、Fins、HOMA—IR、TG、hsC—RP、纤维蛋白原（FIB）和WBC均下降,HDL-C升高（P均＜0．05）,8mg组变化尤著;两组TC和LDL-C均无明显变化（P〉0．05）。对伴有低HDL—C和MS的非糖尿病患者予罗格列酮治疗能有效改善血糖和血脂,减轻IR和炎症状态。     

Effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance

ObjectiveTo determine the potential effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance and probe into the possible mechanisms.Research design and methodsTwenty-two subjects were treated with pioglitazone 30 mg/day for 4 months. At baseline and after treatment, each subject underwent an IVGTT. The acute insulin response (AIRg), the glucose disappearance rates (coefficients K) and the ratio of Δinsulin/Δglucose (ΔI/ΔG) were calculated according to IVGTT results. Hyperglycemic clamp study was conducted to determine the second-phase insulin response, insulin sensitivity index (ISI) and glucose infusion rate (GIR). Euglycemic–hyperinsulinemic clamp study was made to measure the glucose disposal rate (GDR). Plasma glucose, free fatty acids (FFAs), serum insulin and proinsulin levels were measured.ResultsAIRg unchanged (P = 0.25) after treatment, whereas the values of coefficients K (P < 0.01) and ΔI/ΔG increased (P < 0.05). The second-phase insulin response and GIR were both demonstrated marked increments (P < 0.01 and P < 0.01, respectively). Pioglitazone therapy also resulted in improvement of ISI value (P < 0.05). And the increment of GDR during the euglycemic–hyperinsulinemic clamp was also significant (P < 0.01). Furthermore, a decrease in fasting proinsulin level was observed (P < 0.001). And plasma glucose, FFAs and serum insulin levels all declined. The increase of ΔI₁/ΔG₁ was positively correlated with the improvement of GDR (r = 0.536, P = 0.089). And a positive relationship was observed between the change in the second-phase insulin response and change in K value (r = 0.682, P = 0.021).ConclusionsShort-term pioglitazone therapy improved beta-cell dysfunction, the mechanism might involve the attenuation of insulin resistance.     

Effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance

OBJECTIVE: To determine the potential effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance and probe into the possible mechanisms. RESEARCH DESIGN AND METHODS: Twenty-two subjects were treated with pioglitazone 30 mg/day for 4 months. At baseline and after treatment, each subject underwent an IVGTT. The acute insulin response (AIRg), the glucose disappearance rates (coefficients K) and the ratio of Deltainsulin/Deltaglucose (DeltaI/DeltaG) were calculated according to IVGTT results. Hyperglycemic clamp study was conducted to determine the second-phase insulin response, insulin sensitivity index (ISI) and glucose infusion rate (GIR). Euglycemic-hyperinsulinemic clamp study was made to measure the glucose disposal rate (GDR). Plasma glucose, free fatty acids (FFAs), serum insulin and proinsulin levels were measured. RESULTS: AIRg unchanged (P = 0.25) after treatment, whereas the values of coefficients K (P < 0.01) and DeltaI/DeltaG increased (P < 0.05). The second-phase insulin response and GIR were both demonstrated marked increments (P < 0.01 and P < 0.01, respectively). Pioglitazone therapy also resulted in improvement of ISI value (P < 0.05). And the increment of GDR during the euglycemic-hyperinsulinemic clamp was also significant (P < 0.01). Furthermore, a decrease in fasting proinsulin level was observed (P < 0.001). And plasma glucose, FFAs and serum insulin levels all declined. The increase of DeltaI1/DeltaG1 was positively correlated with the improvement of GDR (r = 0.536, P = 0.089). And a positive relationship was observed between the change in the second-phase insulin response and change in K value (r = 0.682, P = 0.021). CONCLUSIONS: Short-term pioglitazone therapy improved beta-cell dysfunction, the mechanism might involve the attenuation of insulin resistance.     

Effects of atorvastatin on ventricular late potentials and repolarization dispersion in patients with hypercholesterolemia

Emerging evidence suggests that statins have a favorable impact on the reduction of arrhythmia events and sudden cardiac death in patients with structural heart disease. We aimed to investigate the possibly and directly favorable effects of statins on ventricular late potentials, QT dispersion, and transmural dispersion of repolarization attained by analyzing clinical electrocardiography (ECG) risk stratification parameters in patients with hypercholesterolemia without structural heart disease. In total, 82 patients (45 females; mean age, 62 +/- 10 years) with hypercholesterolemia were enrolled in this prospective study to examine the effects of statin therapy (atorvastatin 10 mg/day for 3 months) on ECG risk stratification parameters. Surface 12-lead ECG and signal-average ECG (SAECG) were recorded before and after statin treatment. The SAECG parameters, QT dispersion, Bazett-corrected QT (QTc) dispersion, T wave peak-to-end interval (Tpe), and percentage of Tpe/QT interval were calculated and compared before and after statin therapy. Twelve-lead ambulatory 24-hour ECGs were recorded in 12 patients. The results demonstrated that after statin therapy for 3 months, serum levels of total cholesterol and low-density lipoprotein cholesterol were significantly reduced (both p values < 0.001). However, neither significant changes of each SAECG parameter nor the frequency of late potentials were demonstrated after atorvastatin therapy. In addition, no significant changes in QT dispersion, QTc dispersion, Tpe, or Tpe/QT were found. However, 24-hour ambulatory ECG revealed a flattening effect of circadian variation of QTc dispersion after atorvastatin therapy. In conclusion, the favorable antiarrhythmia effect of atorvastatin (10 mg/day) therapy cannot be directly reflected by analyzing these noninvasive ECG risk stratification parameters in low-risk patients with hypercholesterolemia.     

The effects of pitavastatin on glucose metabolism in patients with type 2 diabetes with hypercholesterolemia

BackgroundAlthough there have been several reports that statins cause insulin resistance that leads to the occurrence of type 2 diabetes in Caucasians, there has been no Japanese prospective studies investigating the effects of statins on the glucose metabolism system.Materials and methodsOur subjects were 86 Japanese patients with type 2 diabetes with hypercholesterolemia. Pitavastatin 2 mg/day was administered for 12 months and the lipid-related values, glucose metabolism values, and the presence/absence of side effects were investigated.ResultsNone of these factors was found to differ between before and after administration of pitavastatin in overall analysis of all subjects. In subgroup analysis, fasting blood glucose showed a decrease in the BMI ≥ 25 group and there was a significant difference between the BMI < 25 and BMI ≥ 25 groups (P-values: 0.021 and 0.0036). Although HbA1c showed an increase both in the group switched to pitavastatin and the BMI < 25 group (P-values: 0.035 and 0.033) and HOMA-β showed a decrease in the BMI < 25 group (P-values: 0.044), there were no significant differences in changes between each divided group and their counterparts.ConclusionIn the Japanese obese group with BMI ≥ 25, pitavastatin elicited a significant decrease in fasting blood glucose. It is not clear whether or not this is due to improved insulin resistance as a direct effect of pitavastatin, but in contrast to findings in Caucasians pitavastatin does not worsen insulin resistance in Japanese patients with type 2 diabetes complicated by hypercholesterolemia.