Effects of atorvastatin and pravastatin on malondialdehyde-modified LDL in hypercholesterolemic patients.

The aim of the present study was to compare the effects of atorvastatin and pravastatin on lipid parameters and the concentration of malondialdehyde-modified low-density lipoprotein (MDA-LDL) in hypercholesterolemic patients. A total of 17 patients (10 men, 7 women; mean age, 68+/-9 years) who were indicated for drug therapy based on the National Cholesterol Education Program II underwent an 8-week regimen of atorvastatin (10 mg/day) or pravastatin (10 mg/day) with a 4-week washout period between drugs. After an overnight fast, lipid parameters and MDA-LDL concentration were measured before and after the 8-week treatment with each drug. Both atorvastatin and pravastatin produced significant reductions in low-density lipoprotein (LDL) cholesterol and MDA-LDL concentrations, with a significant increase in high-density lipoprotein cholesterol concentration. The percent reductions in LDL cholesterol and MDA-LDL concentration were significantly greater with atorvastatin than pravastatin (46 +/-6% vs 24+/-10%, p<0.0001, and 44+/-10% vs 14+/-13%, p<0.0001, respectively). The ratios of percent reductions in MDA-LDL concentrations and percent reductions in LDL cholesterol concentrations were significantly greater for atorvastatin than pravastatin (0.96+/-0.19 vs 0.59+/-0.55, p<0.0001). In conclusion, atorvastatin reduced serum concentrations of LDL cholesterol and MDA-LDL to a greater degree than pravastatin, indicating that atorvastatin not only has stronger lipid-lowering effects, but also stronger antioxidative effects than pravastatin.     

Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure

BACKGROUND: Heart failure has been associated with impaired endothelial function, increased inflammatory process and elevated oxidative stress status. Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and/or advanced atherosclerosis. AIM: To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and vascular cells adhesion molecule (sVCAM-1) in patients with ischemic heart failure. METHODS: Thirty-eight male patients with ischemic cardiomyopathy were randomly divided into three groups and received either atorvastatin 10 mg/day (n = 14), a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day (n = 12), or no statin or antioxidant treatment (n=12, controls) for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration, respectively. RESULTS: RH% was significantly improved in both the atorvastatin-treated (p < 0.01) and atorvastatin plus vitamin E groups (p < 0.05), but the increase was significantly higher in the atorvastatin-treated group (p < 0.05). Serum levels of IL-6, TNF-alpha and sVCAM-1 were decreased in the atorvastatin-treated group (p < 0.05 for all), but remained unaffected in the other two groups (p = NS for all). CONCLUSIONS: Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure, an effect partly depressed by vitamin E.     

阿托伐他汀对急性心肌梗死患者内皮功能和斑块稳定性的影响

目的:观察阿托伐他汀对急性心肌梗死(AMI)患者血清高敏C反应蛋白(hsCRP)、内皮素1(ET1)、心肌肌酸激酶同工酶(CKMB)的影响,探讨阿托伐他汀在斑块稳定性和炎症反应中的作用。方法:选取AMI患者59例,按发病前是否因心绞痛、降脂服用过阿托伐他汀分为治疗组[27例,服阿托伐他汀(20mg,qd)2周以上]与对照组(32例,未服阿托伐他汀)。采用放射免疫法、酶联免疫吸附法检测2组患者血清hsCRP、ET1、CKMB水平。结果:治疗组血浆hsCRP、ET1、CKMB水平低于对照组,差异有统计学意义(P<0.05)。结论:阿托伐他汀可抑制炎症反应,改善内皮功能,稳定粥样斑块,缩小心肌梗死范围。     

Effect of atorvastatin on endothelial function in patients with familial hypercholesterolemia

AIM: To study the influence of treatment with HMG-CoA reductase inhibitor atorvastatin on endothelial function in patients with familial hypercholesterolemia type IIa. MATERIALS AND METHODS: Sixteen patients (5m/11w, 51-/+3 years) with familial hypercholesterolemia were studied before and after 3 months of therapy with atorvastatin 20 mg/day. EDRF release test (D.Celermajer, 1992) was used to assess flow-mediated endothelium-dependent vasodilatation (FMD) of the brachial artery in response to reactive hyperemia. Plasma nitrite/nitrate (NOx) levels were measured as an indirect index of nitric oxide (NO) production in vivo using HPLC. RESULTS: Atorvastatin treatment resulted in a 32% reduction in total serum cholesterol (CH), 41% reduction in low density lipoprotein (LDL) CH, 16% reduction in triglycerides and a 21% increase in high density lipoprotein CH. Flow mediated dilatation (FMD) was impaired at baseline (5.8-/+0.9%) and significantly improved up to 9.5-/+0.9% after 3 month atorvastatin therapy (p<0.002). Change in FMD inversely correlated with baseline FMD (r = -0.58, p<0.05). There was no significant correlation between FMD and neither total serum CH nor LDL CH levels at baseline. During atorvastatin therapy significant reduction of plasma NOx levels occurred from 53.4-/+5.1 mcmol/l at baseline (range 42.6-86.2 mcmol/l) to 35.5-/+5.1 mcmol/l (18.4-46.0 mcmol/l) after treatment (p<0.02, n=7). CONCLUSION: In patients with familial hypercholesterolemia atorvastatin produced beneficial effect on endothelial function (increase in flow-mediated dilatation, decrease in NOx).     

Effects of atorvastatin on in-stent stenosis in normo- and hypercholesterolemic rabbits

BACKGROUND: In-stent stenosis is characterized by a prolonged proliferation and inflammatory reactions around the stent struts. Potentially the antiproliferative and lipid-lowering effects of atorvastatin can synergistically limit neointima formation after stenting. METHODS: Palmaz-Schatz stents were placed in the iliac arteries of white New Zealand rabbits. One half of the animals was fed an 0.5% hypercholesterolemic diet, the other half was normocholesterolemic. Both groups received either atorvastatin (3 mg/kg bodyweight) daily or placebo (n=10 each in the four groups). After 28 days the segments were excised. RESULTS: Injury scores as a result of vessel trauma induced by stent-overstretch injury differed significantly between the four groups (median 1.0-1.9) and the stent-induced injury outweighed the beneficial effects of statin therapy on neointima formation by far. Smooth-muscle-cell proliferation was significantly increased in both hypercholesterolemic groups. Intimal and medial proliferation as well as inflammatory infiltrates around the stent strut were reduced by 20-40% in animals that received statin therapy although the injury score in both statin groups was 19 and 60% higher than in control animals. CONCLUSION: Thus, the data of this study indicate that smooth muscle cell proliferation and inflammation in stented vessels can be reduced by atorvastatin both in hypercholesterolemic rabbits and in animals with normal lipid levels.     

Effects of simvastatin and pravastatin on gonadal function in male hypercholesterolemic patients

Inhibition of cholesterol biosynthesis by hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors could, in theory, adversely affect male gonadal function because cholesterol is a precursor of steroid hormones. The objective of this randomized double-blind trial was to compare the effects of simvastatin, pravastatin, and placebo on gonadal testosterone production and spermatogenesis. After a 6-week placebo and lipid-lowering diet run-in period, 159 male patients aged 21 to 55 years with type IIa or IIb hypercholesterolemia, low-density lipoprotein (LDL) cholesterol between 145 and 240 mg/dL, and normal basal levels of testosterone were randomly assigned to treatment with simvastatin 20 mg (n = 40), simvastatin 40 mg (n = 41), pravastatin 40 mg (n = 39), or placebo (n = 39) once daily. After 24 weeks of treatment, mean total cholesterol levels were decreased 24% to 27% and mean LDL cholesterol was decreased 30% to 34% in the 3 active-treatment groups (P < .001 for all comparisons to placebo). At 24 weeks, there were no statistically significant differences between the placebo group and any of the active-treatment groups for the change from baseline in testosterone, human chorionic gonadotropin (hCG)stimulated testosterone, free testosterone index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), or sex hormone-binding globulin (SHBG). Moreover, there were no statistically significant differences at week 12 or week 24 for the change from baseline in sperm concentration, ejaculate volume, or sperm motility for any active treatment relative to placebo. Both simvastatin and pravastatin were well tolerated. In summary, we found no evidence for clinically meaningful effects of simvastatin or pravastatin on gonadal testosterone production, testosterone reserve, or multiple parameters of semen quality.     

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。     

早期阿托伐他汀联合普罗布考治疗对急性冠状动脉综合征患者血管内皮功能的影响

目的 观察阿托伐他汀联合普罗布考早期治疗对急性冠状动脉综合征(ACS)患者血管内皮功能的影响.方法 30例ACS患者在入院24 h内随机分到他汀组(阿托伐他汀20 mg/d,n=15)与联合治疗组(阿托伐他汀20 mg/d和普罗布考500 mg/d,n=15).治疗前、治疗1周和4周后分别检测患者血清血脂与高敏C反应蛋白(hs-CRP)水平,并应用高频超声测肱动脉血流介导的内皮依赖血管舒张功能(FMD)和由硝酸甘油诱导的内皮非依赖血管舒张功能(NMD).结果 经治疗1和4周后,两组血清总胆固醇、低密度脂蛋白胆固醇(LDL-C)和hs-CRP水平均低于治疗前,联合治疗组血清总胆蚓醇水平下降较他汀组更明显(P<0.05).治疗1周后,FMD均明显高于治疗前(他汀组:3.75%±0.78%比1.09%±0.44%;联合治疗组:3.67%±0.36%比1.24%±0.37%;均P<0.01),两组比较差异无统计学意义.联合治疗组4周后FMD明显高于1周后(6.85%±0.64%比3.67%±0.36%,P<0.01);他汀组则无显著变化(P=0.954).两组NMD在治疗4周后均明显高于治疗前(P<0.01),但两组比较差异无统计学意义.相关分析显示,FMD和NMD的改善与血脂或hs-CRP水平的变化无显著相关.结论 提示早期阿托伐他汀联合普罗布考治疗较单用阿托伐他汀能更明显地改善ACS患者的血管内皮功能.     

Antioxidant vitamin C improves endothelial function in obstructive sleep apnea

RATIONALE: Obstructive sleep apnea (OSA) is associated with oxidative stress, endothelial dysfunction, and increased cardiovascular morbidity and mortality. OBJECTIVE: We tested the hypothesis that endothelial dysfunction in patients with OSA is linked to oxidative stress. METHODS: In the present study, we measured flow-mediated dilation (FMD) of the brachial artery by ultrasound in 10 otherwise healthy, untreated patients with OSA and 10 age-and sex-matched control subjects without sleep-disordered breathing before and after intravenous injection of the antioxidant vitamin C. The investigator performing the FMD measurements was blinded to the status of the patients. RESULTS: When compared with control subjects, baseline FMD was significantly reduced in the patients with OSA. After intravenous injection of 0.5 g vitamin C, vasoreactivity remained unchanged in the control subjects. In the patients with OSA, ascorbate led to an increase in FMD to a level comparable to that observed in the control group. CONCLUSION: The reduced endothelial-dependent vasodilation in untreated patients with OSA acutely improves by the free radical scavenger vitamin C. These results are in favor of oxidative stress being responsible for the endothelial dysfunction in OSA. Antioxidant strategies should be explored for the treatment of OSA-related cardiovascular disease.     

The effects of atorvastatin on coronary endothelial function in patients with recent myocardial infarction

BACKGROUND: Endothelial dysfunction is a key early event in atherosclerosis that occurs in acute coronary syndrome. It was reported that atorvastatin improves the endothelial function of skeletal muscle vessels, but the effect on the coronary artery is unknown. HYPOTHESIS: The purpose of this study is to determine the effects of atorvastatin on coronary endothelial function in humans. METHODS: Non-infarct-related coronary arteries of 48 patients with acute myocardial infarction who had undergone successful percutaneous transluminal coronary angioplasty were examined. Three groups were studied: hyperlipidemia with use of atorvastatin (Group 1, n=17), hyperlipidemia without statin use (Group 2, n=18), and normal cholesterol level controls (Group 3, n=13). Statin treatment was started at discharge. Acetylcholine (Ach) was infused into the coronary artery and the diameter was assessed by quantitative angiography at baseline and after 6 months. RESULTS: Acetylcholine given in doses of 1, 3, 10, and 30 mg/min increased the coronary artery diameter change in a dose-dependent manner. In the initial study, patients in the three groups had similar responses to Ach. The mean diameter change after 6 months was significantly improved in Group 1 compared with Groups 2 and 3 (-11 +/- 3% vs. -20 +/- 7% and -21 +/- 6%, respectively; p < 0.01 in each case). Multivariate regression analysis showed that atorvastatin (p < 0.01) was the significant determinant for improvement of endothelial function. CONCLUSIONS: These findings suggest that atorvastatin improves endothelial function of the coronary artery in patients with myocardial infarction.     

Noninvasive assessment of the effect of atorvastatin on coronary microvasculature and endothelial function in patients with dyslipidemia

INTRODUCTION AND OBJECTIVES: The effect of statins has been monitored mainly in peripheral arteries. It is now possible to study coronary microcirculation by analyzing coronary reserve with transthoracic echocardiography. The aim of this study was to use this noninvasive technique to evaluate the effect of atorvastatin on peripheral endothelial function and on the coronary microvasculature in patients with dyslipidemia. PATIENTS AND METHOD: We included 21 patients with dyslipidemia but no clinical antecedents of atherosclerosis. Mean (SD) age was 64.9 (11) years, and women made up 61.9% of the group. All patients were treated with 20 mg atorvastatin during 3 months. Lipid profile, carotid intima-media thickness, endothelium-dependent vasodilation and coronary flow reserve were determined at baseline and at the end of treatment. All studies were performed with echocardiographic techniques. RESULTS: Together with improvements in the lipid profile, we found a 43% increase in endothelium-dependent vasodilation (4.3 [4.4] to 6.2 [3.8]; P=.07) and a 25% increase in coronary flow reserve (2.5 [0.6] vs 3.1 [0.8]; P=.002). The increase in endothelium-dependent vasodilatation correlated with age (r=-0.60; P=.004), intima-media thickness (r=-0.47; P=.029), low-density lipoprotein level before treatment (r=-0.43; P=.05), and baseline endothelium-dependent vasodilatation (r=-0.63; P=.002). The increase in coronary flow reserve correlated with low-density lipoprotein level after treatment (r=-0.51; P=.04). CONCLUSIONS: Short-term treatment with atorvastatin improved the lipid profile, coronary microvascular function and endothelium-dependent vasodilation in the peripheral circulation. The noninvasive assessment of coronary reserve is feasible with transthoracic echocardiography.     

Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men.

BACKGROUND: The regulatory function of the endothelium is altered in hypercholesterolemia, and the subsequent endothelial dysfunction plays a central role in the development of atherosclerosis. OBJECTIVE: To determine whether endothelial function in hypercholesterolemic patients is affected by replacing a saturated fat-enriched diet with a low-fat, low-saturated fat diet (the U.S. National Cholesterol Education Program stage 1 [NCEP-1] diet) or a diet rich in monounsaturated fat (such as that common in Mediterranean countries). DESIGN: Intervention dietary study with a baseline phase and two randomized crossover dietary periods. SETTING: Hospital Universitario Reina Sofía, Córdoba, Spain. PATIENTS: 22 hypercholesterolemic men. INTERVENTION: Patients followed a diet high in saturated fat, then were assigned in a crossover design to the NCEP-1 diet or a Mediterranean diet. Each dietary period lasted 28 days. MEASUREMENTS: Plasma P-selectin levels, lipid concentrations, and endothelial function. RESULTS: Compared with the saturated fat diet, flow-mediated dilatation increased during the Mediterranean diet but not during the NCEP-1 diet. In addition, levels of plasma cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and P-selectin decreased during the NCEP-1 and Mediterranean diets. CONCLUSION: In hypercholesterolemic men, diets low in fat (especially saturated fat) and diets rich in monounsaturated fats improve endothelial function.     

维生素E与维生素C联合治疗对糖耐量受损患者糖代谢的影响

目的　观察维生素C与维生素E联合治疗对糖耐量受损 (IGT)患者糖代谢的影响。　方法　以口服葡萄糖耐量试验 (OGTT)筛查IGT患者 15 9例 ,随机分成治疗组和对照组 ,治疗组予口服维生素C 5 0 0mg/d及维生素E 2 0 0mg/d ,6个月 ;对照组不进行任何治疗。分别于治疗前后检测血糖 (PG)及胰岛素 (Ins) ,用稳态模型评价胰岛素抵抗指数 (HOMA IR)及胰岛细胞分泌功能指数(HOMA β)。 　结果　治疗组FPG、Ins及HOMA IR较试验前及对照组均明显下降 ,HOMA β无明显变化。对照组试验前后各项指标无明显变化。试验结束时 ,对照组有 3例转为糖尿病 (DM ) ,占3 8% ,治疗组无DM发生。经 χ2 检验两组DM的发生率差异无显著意义 (χ2 =3 8,P >0 0 5 )。　结论　维生素C与维生素E联合应用可以改善IGT患者的糖代谢 ,减轻其IR。     

超量阿托伐他汀对不稳定型心绞痛患者血管内皮功能的影响

目的：探讨短期大剂量阿托伐他汀对不稳定型心绞痛（UAP）患者早期血管内皮功能改善的疗效。方法：72例UAP Ⅲ级患者被分为大剂量组和常规量组，于人院后给予口服不同剂量的阿托伐他汀2周，分别测定治疗前后的血脂（TC、TG、LDL—C、HDL—C）、反应性充血引起的肱动脉舒张内径变化率（ΔD％）。并于2周内观察各组发生心脏意外事件的情况。结果：大剂量组服药2周后血脂TC、TG、LDL-C水平显著下降（P〈0．05），肱动脉AD％明显增高（P〈0．01），心脏意外事件发生率为62．86％，常规量组血脂指标均无明显变化，心脏意外事件发生率为83．78％，较之大剂量组显著增加（P〈0．05）。结论：对于不稳定型心绞痛Ⅲ级患者短期大剂量阿托伐他汀治疗可改善血管内皮功能、降低心脏意外事件发生率，改善预后。     

Effects of rosuvastatin on endothelial function of patients after PCI

目的 观察瑞舒伐他汀对冠状动脉(简称冠脉)支架术后患者内皮功能的影响.方法 将108例冠脉支架术患者随机分为治疗组(62例)和对照组(46例),两组患者均给予氯吡格雷、阿司匹林、消心痛等常规药物治疗,治疗组在此基础上,加用瑞舒伐他汀10 mg,1次/晚,总疗程为6个月;用酶联免疫吸附试验(ELISA)测定两组患者术前、术后1天、术后1、3、6个月外周血清中内皮型一氧化氮合酶(eNOS)、血管内皮素-1(ET-1)含量.结果 (1)两组患者术前和术后1天血清ET-1水平比较差异无统计学意义(P＞0.05),治疗组术后1、3、6个月与对照组比较,血清ET-1水平显著降低(P＜0.01);(2)两组患者术前和术后1天血清eNOS水平比较差异无统计学意义(P＞0.05),治疗组术后1、3、6个月与对照组比较,血清eNOS水平明显升高(P＜0.01).结论 瑞舒伐他汀对ET-1和eNOS具有很好的调控作用,可以减轻冠脉支架植入术对内皮的损伤,更好地保护血管内皮.