辛伐他丁对支架新生内膜的作用

目的观察他丁类调脂药物对支架再狭窄和支架内新生内膜的影响.方法对单支冠脉病变行支架植入术的患者随机接受或不接受调脂药物的治疗,10月后复查冠脉造影和血管内超声检查.结果 65位患者随机接受辛伐他丁10mg治疗.辛伐他丁组患者在接受降脂治疗后血清总胆固醇降低15%,低密度脂蛋白胆固醇下降了26%,高密度脂蛋白胆固醇增加12%.辛伐他丁组和对照组支架再狭窄率无差异(分别为30.3%和37.5%,P>0.05).定量冠脉造影结果两组比较,两组参考段血管直径、支架最小管腔直径以及直径狭窄率均无明显差异.血管内超声发现辛伐他丁组参考段血管内膜腔截面积、最小血管内膜腔截面积以及最小支架截面积均无显著性差异.新生内膜截面积两组比较对照组大于辛伐他丁组,但无统计学意义.结论辛伐他丁长期治疗能够有效降低血中致动脉粥样硬化的脂蛋白.但10 mg/日的辛伐他丁对支架的再狭窄率以及支架内膜增生无明显影响.     

普伐他丁与维生素E联合应用对家兔动脉粥样硬化内皮功能不全的影响

目的研究普伐他丁与维生素E联合应用对家兔动脉粥样硬化动脉内皮依赖舒张反应的影响。方法34只新西兰家兔分为正常对照组、胆固醇喂养组、普伐他丁组及联合治疗组,饲养12周。取一段靠近升主动脉起始部的动脉做常规病理切片,一段近端腹主动脉做血管功能测定,观察其对不同浓度乙酰胆碱及硝普钠的舒张反应。结果普伐他丁显著降低血浆总胆固醇水平,抑制动脉粥样硬化的形成并改善动脉受损的内皮依赖舒张反应,而联合应用普伐他丁与维生素E比单一普伐他丁效果更为明显,乙酰胆碱引起的腹主动脉平均最大舒张百分数4组分别为(62.3±2.5)%、(3.7±3.2)%、(40.8±10.2)%、(52.6±4.5)%,组间差异有显著性(P＜0.01)。结论联合应用普伐他丁与维生素E对动脉粥样硬化时受损的内皮功能的改善作用更强,应用于临床可能有重要价值。     

L-精氨酸对高脂血症家兔主动脉和冠状动脉粥样硬化斑块面积的影响

选择健康雄性新西兰白兔144只（体重2．0～2．2kg），分为空白对照组、硝笨吡啶组、消心痛组、L-精氨酸组和高胆固醇组。预防性给药90天，治疗性给药是在预防性给药的基础上停喂胆固醇，其余处理因素不变，再观察90天。结果发现喂养1、1．5和2g／kgL-精氨酸均能减少高胆固醇血症所诱导的主动脉和冠状动脉粥样硬化斑块面积，硝笨吡啶组和消心痛组的病变重于L-精氨酸用药组，但比高胆固醇组轻。L-精氨酸（1g／kg）抗家兔动脉粥样硬化的效果优于硝苯吡啶（1．44mg／kg）及消心痛（2．88mg／kg）。以上结果表明，L-精氨酸有显著的抗实验性家兔动脉粥样硬化的作用，硝苯吡啶和消心痛也有类似作用，但效果不及L-精氨酸。     

替格瑞洛对经CYP3A4途径代谢的他汀治疗急性冠脉综合征的影响

【】 目的 观察对CYP3A4酶有抑制作用的替格瑞洛联合经CYP3A4酶代谢的阿托伐他汀治疗急性冠脉综合征(acute coronary syndrome,ACS)患者的短期内的安全性及对降脂作用的影响。方法 连续入选2016年1月至2016年6月北京安贞医院急诊科收治的ACS患者共244例,随机分为阿托伐他汀 替格瑞洛组(以下简称为替格瑞洛组)和阿托伐他汀 氯吡格雷组(以下简称为氯吡格雷组)。收集入院24小时内和院外一个月内胆固醇(CHOL)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酸激酶(CK)及血清肌酐(Scr)水平,同时计算LDL-C达标率。结果 替格瑞洛组在肝功能损害、肌肉毒性及肾功能损害的发生率上均高于氯吡格雷组(2.8%比0.7%,1.9%比0.7%,4.47%比3.04%),但差异均未达到统计学意义,P值均大于0.05。在LDL-C达标率上,替格瑞洛组为53.3%,明显高于氯吡格雷组的38.0% (P=0.017,P<0.05)。两组在降低CHOL、TG水平上,替格瑞洛组要略优于氯吡格雷组(18.09%比17.93%,6.23%比2.58%),但差异没有统计学意义,P>0.05。结论 在急性冠脉综合征患者治疗中,短期内替格瑞洛对经肝酶CYP3A4代谢的阿托伐他汀的安全性影响较小,整体安全性较好,且在相同剂量的阿托伐他汀治疗下,替格瑞洛联合阿托伐他汀在LDL-C达标率上更有优势。     

普罗布考联合阿托伐他汀对冠心病患者氧化型低密度脂蛋白及其抗体的影响

目的比较冠心病患者使用普罗布考联合阿托伐他汀与单用阿托伐他汀对氧化型低密度脂蛋白及其抗体的影响。方法将48例冠心病患者随机分为单药治疗组(阿托伐他汀20 mg/d)和联合治疗组(普罗布考1g/d+阿托伐他汀20 mg/d),分别测量两组患者服药前和服药1个月后氧化型低密度脂蛋白、氧化型低密度脂蛋白抗体和血脂水平。结果两组患者治疗后血清低密度脂蛋白、氧化型低密度脂蛋白、总胆固醇和甘油三酯水平较治疗前明显降低(P<0.01);单药治疗组氧化型低密度脂蛋白抗体水平无明显变化;联合治疗组氧化型低密度脂蛋白抗体水平明显降低(P<0.01),且低密度脂蛋白、氧化型低密度脂蛋白、总胆固醇的降低幅度大于单药治疗组(P<0.05)。结论普罗布考联合阿托伐他汀与单用阿托伐他汀均能降低冠心病患者血清氧化型低密度脂蛋白水平,但联合治疗组比单药治疗组降低更明显。单用阿托伐他汀对氧化型低密度脂蛋白抗体无明显影响,但联合普罗布考可明显降低氧化型低密度脂蛋白抗体水平。     

高低密度脂蛋白胆固醇对血小板免疫活化的影响及氟伐他汀的干预作用

目的 观察高低密度脂蛋白胆固醇对体内及体外血小板膜PAC-1和CD40L表达的影响及氟伐他汀的干预作用并探讨可能的机制.方法 以低密度脂蛋白胆固醇正常的健康对象为对照,通过流式细胞仪检测高低密度脂蛋白胆固醇患者服用氟伐他汀前后血小板膜PAC-1和CD40L表达阳性率变化;高低密度脂蛋白胆固醇血浆体外孵育健康血小板及低密度脂蛋白胆固醇直接孵育血小板并用氟伐他汀干预,流式细胞仪、RT-PCR及Westen blotting法检测血小板膜PAC-1和CD40L表达阳性率及血小板总CD40L mRNA及蛋白含量.结果 高低密度脂蛋白胆固醇患者PAC-1和CD40L表达较对照组显著升高(9.47%±1.96%比5.73%±1.20%、3.04%±0.62%比1.87%±0.49%,P均<0.01),服用氟伐他汀一个月后随低密度脂蛋白胆固醇浓度降低,血小板膜PAC-1和CD40L表达阳性率均有不同程度降低(7.29%±1.35%比 9.47%±1.96%、2.17%±0.53%比3.04%±0.62%,P均<0.01);体外高低密度脂蛋白胆固醇血浆较低密度脂蛋白胆固醇正常血浆更能促进血小板膜PAC-1和CD40L的表达(10.47%±1.39%比6.39%±1.23%、3.19%±0.73%比1.87%±0.47%,P均<0.01),氟伐他汀在体外未能显著抑制血小板膜PAC-1和CD40L表达(10.39%±1.41%比10.47%±1.39%、3.21%±0.69%比3.19%±0.73%,P均>0.05);单纯高低密度脂蛋白胆固醇在体外亦不能显著增加血小板膜PAC-1和CD40L的表达(3.99%±1.74%比3.87%±1.63%、0.83%±0.46%比0.77%±0.44%,P均>0.05),而高低密度脂蛋白胆固醇+ADP组血小板膜PAC-1、CD40L表达阳性率较ADP组显著增高(17.73%±2.09%比11.31%±2.12%、4.17%±0.71%比2.91%±0.69%,P<0.05),氟伐他汀的体外作用不显著;低密度脂蛋白胆固醇对血小板总CD40L mRNA和蛋白表达无明显影响,但高低密度脂蛋白胆固醇能够显著促进ADP活化血小板CD40L蛋白表达(1.63±0.19比1.40±0.21,P<0.05),氟伐他汀体外不能抑制这一作用.结论 高低密度脂蛋白胆固醇在体内体外均能够促进血小板膜PAC-1和CD40L的表达,氟伐他汀在体内能抑制这一作用;低密度脂蛋白胆固醇本身不能够活化血小板免疫功能,但能够促进活化血小板,氟伐他汀体外无抑制血小板免疫活化的作用.     

氟伐他汀对高脂饮食兔动脉粥样硬化发生早期干预作用

目的　观察氟伐他汀对高脂饮食兔动脉粥样硬化发生的早期干预作用。方法　健康纯种新西兰白兔40只 ,随机等分为实验组 (高脂饮食 +氟伐他汀10mg·kg-1·d-1)和对照组 (高脂饮食 )。分别于实验前及实验第 2、4、6、8周每组随机抽取 4只 ,兔耳中动脉抽血测血脂水平 ,气栓法处死测定主动脉内斑块面积占内膜总面积的比例。结果　实验组和对照组两组实验前的总胆固醇、低密度脂蛋白胆固醇及主动脉斑块面积占内膜总面积的比例均无差异 ,虽然随着时间的推移 ,两组的总胆固醇、低密度脂蛋白胆固醇及主动脉斑块面积占内膜总面积的比例均上升 ,但从实验第 2周以后的总胆固醇、低密度脂蛋白胆固醇及主动脉斑块面积占内膜总面积的比例治疗组均低于对照组 (P均小于 0 .0 5 )。结论　氟伐他汀能早期干预高脂饮食兔动脉粥样硬化的发生、发展     

硝苯吡啶对高脂血症家兔和患者脂质代谢的影响

本文观察了硝苯吡啶(Nif)对实验性高脂血症、动脉粥样硬化家兔脂质代谢的影响。结果表明,Nif对喂饲胆固醇(Ch)家兔有显著降低血浆总胆固醇、甘油三酯、低密度脂蛋白Ch、载脂蛋白B,升高血浆高密度脂蛋白Ch(HDL-Ch)及其亚类HDL_2-Ch,减少主动脉组织Ch、epoB沉积和粥样病变面积的作用。并观察了37例高血压病伴高脂血症患者,其口服Nif治疗后其血脂变化与动物实验结果一致。Nif影响脂质代谢的机制可能与Nif能加强低密度脂蛋白(LDL)受体途径处理LDL有关。     

钙通道拮抗剂对老年高血压病骨质代谢的影响

分组观察硝苯吡啶钙拮抗剂对老年高血压病骨质密度的影响。随机选择长期口服硝苯吡啶的老年男性高血压病病人 30例 ,作为观察组 ,正常老年男性 35例 ,作为对照组。分别测定治疗前后血清钙磷浓度、碱性磷酸酶浓度及骨质密度。长期口服硝苯吡啶的老年男性高血压病病人血清钙磷浓度、碱性磷酸酶及骨质密度与正常老年男性比较 ,无显著性差异 (P >0 0 5)。长期口服硝苯吡啶对老年男性高血压病病人骨质密度无明显影响     

普罗布考与阿托伐他汀合用对急性冠状动脉综合征的调脂及抗氧化作用

目的 观察普罗布考与阿托伐他汀联合治疗对急性冠状动脉综合征患者血脂、血清氧化型低密度脂蛋白水平及对氧磷酶1活性的影响.方法 38例急性冠状动脉综合征患者随机分为对照组(n=20,阿托伐他汀10mg/d)和治疗组(n=18,阿托伐他汀10 mg/d+普罗布考1 000 mg/d),随访4周.两组在治疗前后分别测定血清总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯、血清氧化型低密度脂蛋白水平及对氧磷酶1活性.结果 治疗4周后,对照组低密度脂蛋白胆固醇降低15.4%、高密度脂蛋白胆固醇上升13.7%(P<0.05),血清总胆固醇、甘油三酯略有下降但未达到统计学意义(P>0.05);治疗组血清总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯分别下降28.1%、28.5%、14.2%(P<0.01)和23.3%(P<0.05);与对照组相比,治疗组血清总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇下降更为明显(P<0.01).治疗后,两组血清氧化型低密度脂蛋白水平均明显降低,对氧磷酶1活性均明显升高(P<0.01);而治疗组血清氧化型低密度脂蛋白水平和对氧磷酶1活性的变化比对照组更为明显(P<0.01).治疗前的血清氧化型低密度脂蛋白水平、对氧磷酶活性及两者治疗后的变化值与血脂各指标之间均无相关关系(P>0.05),而对氧磷酶活性与血清氧化型低密度脂蛋白水平呈显著负相关(r=-0.669,P<0.01).结论 阿托伐他汀与普罗布考合用具有协同降胆固醇作用和抗氧化作用,但普罗布考降高密度脂蛋白胆固醇的作用不能被阿托伐他汀抵消.     

Antioxidant Effects of Lovastatin and Vitamin E on Experimental Atherosclerosis in Rabbits

The effects of the administration of vitamin E (10 mg/day) plus lovastatin (2 mg/day; group A, n = 10), lovastatin alone (2 mg/day; group B, n = 10), and placebo (group C, n = 10) were compared over 24 weeks in a randomized, single-blind controlled trial. All groups of rabbits received a trans fatty acid (TFA)–rich diet (5–10 g/day) for 36 weeks. Treatment with vitamin E plus lovastatin (group A) and lovastatin (group B) started after 12 week of administration of TFA-rich diet was associated with a significant but similar decline in serum cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides in both groups at 36 weeks. Lipid peroxides and diene conjugates showed a significant decline in association with a significant increase in the plasma level of vitamin E in group A rabbits at 36 weeks. However, the lovastatin group B showed a lesser but significant decrease in lipid peroxides and diene conjugates at 36 weeks, indicating that lovastatin may have antioxidant activity. In control group C, the increase in blood lipids and oxidative stress at 36 weeks was much greater than the decrease in groups A and B. After experimental lipid peroxidation at 24 weeks in all of the rabbits, 2 of 10 group B and 3 of 10 group C rabbits died due to coronary thrombosis; there were no deaths in group A. Thus antioxidant therapy with vitamin E can provide protection against death due to free radical stress. Aortic lipids and sudanophilia indicating athorosclorosis were significantly lower in groups A and B than in group C. The atherosclerotic coronary plaque sizes were significantly smaller in group A (18.5 ± 3.6 μm) than in groups B (41.6 ± 4.2 μm) and C (85 ± 6.7 μm). Aortic plaque sizes were also smaller in group A than in group B and C. It is possible that antioxidant therapy with vitamin E, as an adjunct to lipid lowering with lovastatin, can provide additional benefit in the inhibition of oxidative stress and atherosclerosis. The antioxidant activity of lovastatin has not been reported, to our knowledge. This revised version was published online in July 2006 with corrections to the Cover Date.     

人血高密度脂蛋白注射液对高胆固醇饲料所致新西兰白兔动脉粥样硬化病变的作用及与洛伐他汀的比较

目的研究人血高密度脂蛋白(HDL)注射液对喂高胆固醇饲料家兔主动脉粥样指纹病变的影响.方法实验家兔给与1%胆固醇饲料8周.在此期间,HDL组每只家兔每周静脉注射50 mg人血HDL;洛伐他汀组每只家兔每天皮下注射10mg洛伐他汀;安慰剂组每只家兔每天静脉注射20mL生理盐水.人血HDL注射液由清华紫光古汉生物制药集团有限公司生产并提供.结果在试验期间,各组实验动物喂高胆固醇饲料后血脂水平均有升高.第八周后,实验动物主动脉内膜表面富脂粥样病变面积比分别为安慰剂组32.6%±21.7%(x±s,下同);HDL组9.16%±7.87%;洛伐他汀组20.8%±13.1%.血清总胆固醇水平分别为安慰剂组10.0±2.30g/L;HDL组2.92±1.41g/L;洛伐他汀组3.74±1.73g/L.血清HDL胆固醇水平分别为安慰剂组0.43±0.12g/LHDL组 0.62±0.23g/L;洛伐他汀组0.23±0.14g/L.HDL组血管壁胆固醇含量比安慰剂组和洛伐他汀组都明显降低,说明人血HDL具有比洛伐他汀更有效的抗动脉粥样硬化病变作用.结论人血HDL能够有效地抑制喂胆固醇饲料家兔主动脉粥样病变的作用,并能够调节血脂,减少动脉壁脂质沉积.     

Aortic enzymes and lactate in high altitude-raised and cholesterol-fed rabbits

Fourteen male rabbits born at elevation 4000 ft (first experimental series) were transferred at age of 2 months to elevation 12470 ft and raised there for 18 weeks. Half of the animals remained on a commercial rabbit chow (group H) while the other half was on the same diet supplemented with cholesterol (group C). Eight male rabbits raised at sea level served as controls (group S). Intima-media homogenates from the thoracic aortas were assayed for lactate dehydrogenase (LDH), malate dehydrogenase (MDH), lipoamide dehydrogenase, pyruvate kinase (PK), phosphofructokinase (PFK) and the lysosomal hydrolases beta-glucuronidase and N-acetyl-beta-glucosaminidase (NAGA). Aortic lactate and glucose were also measured. Thirty-two male rabbits (second experimental series) were subdivided into 4 groups. Rabbits were fed a cholesterol-supplemented diet not only at high altitude (8 rabbits matching group C) but also 8 animals raised at sea level. The degree of atherosclerosis in the aortas of these 4 groups was assessed by measuring the aortic cholesterol contents. Plasma cholesterol was also determined. In the aortas of the rabbits of group H the activity of PK was significantly elevated, and the activity of the lysosomal hydrolases significantly decreased compared with aortas of group S rabbits. There was no difference in the other enzyme activities or in the aortic glucose and lactate content of these groups. Cholesterol feeding of the animals of group C resulted in a significantly increased activity of the lysosomal hydrolases as well as of LDH and PK. The lipid analyses (second experimental series) revealed a trend to a lower concentration of aortic cholesterol in the high altitude than in the sea level animals, both fed a cholesterol diet, in spite of the higher plasma cholesterol concentrations in the high altitude animals. The low aortic lysosomal hydrolase activities in the high altitude rabbits are in accord with their comparatively lower susceptibility to experimental atherosclerosis. This metabolic feature may be due to a lower degree of exposure of these aortas to injurious factors, such as infections or lower blood pressure. The elevated activity of PK without increased lactate content in group H animals seems to parallel the well-known general adaptation of the organism to high altitude hypoxia, and does not indicate a metabolic switch toward anaerobic glycolysis.     

Lovastatin preserves renal function in experimental diabetes

Although hyperlipidemia has been associated with the progression of glomerulosclerosis, little attention has been directed toward the use of lipid-lowering agents in altering diabetic nephropathy. We tested the hypothesis that lovastatin and the combination of lovastatin and enalapril would preserve renal function in streptozotocin-induced diabetic Wistar rats. Five groups of animals were studied: group 1, nondiabetic (n = 10); group 2, diabetic, insulin only (n = 12); group 3, lovastatin, (15 mg/kg/day, n = 13); group 4, enalapril, (50 mg/L drinking water, n = 10) and group 5, lovastatin plus enalapril, (n = 14). After 8 weeks of treatment, glomerular filtration rate (GFR, insulin clearance) was measured in anesthetized animals. The diabetic group was characterized by a GFR of 0.18 +/- 0.03 ml/min/g of kidney weight (gKW), a blood glucose level of 441 +/- 36 mg/dL, plasma cholesterol and triglyceride levels of 64 +/- 6.0 and 103 +/- 26.0 mg/dL. Lovastatin preserved GFR, 0.52 +/- 0.06 ml/min/gKW compared with the diabetic control subjects (P < 0.05). Enalapril also maintained GFR (0.42 +/- 0.06 ml/min/gKW, P < 0.05). In the lovastatin plus enalapril group, GFR (0.62 +/- 0.05 ml/min/gKW) was greater than in the enalapril group (P < 0.05), but was not different from the lovastatin group. Plasma lipid levels were not altered in any of the groups. Assessment of the kidneys by histology after treatment showed that the mesangial matrix injury score was better in the lovastatin, enalapril, and lovastatin plus enalapril groups compared with the diabetic group (P < 0.05). Lovastatin, enalapril, and lovastatin plus enalapril abrogated the decline in GFR and glomerular injury in diabetic rats. Lovastatin's direct renal protective effect seems to be independent of its lipid-lowering properties.     

Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit

Seventy-two rabbits were separated into groups to receive no drug, subcutaneous verapamil, metoprolol, hydralazine, metoprolol and hydralazine, or oral verapamil in 1 of 3 doses daily for 10 weeks. They also received a high-cholesterol diet and had serum triglyceride, cholesterol, and verapamil levels measured twice during the study. Blood pressure (BP), heart rate and weight were measured every 10 days. Approximately 60% of the rabbits given verapamil had detectable levels of the drug in their serum. This group had significantly less severe atherosclerosis in their aortas at the time they were killed, even though they had significantly higher cholesterol levels than the other groups. This group also did not have different BP than the other groups (except for the subcutaneous verapamil group). Thus, protection from atherosclerosis by verapamil in the cholesterol-fed rabbit is not the result of lowering of BP.     

氨氯地平抗兔动脉粥样硬化的实验研究

目的　观察氨氯地平的抗动脉粥样硬化 (AS)效应并探讨其机制。方法　将 32只大耳白兔随机分为 :对照组、模型组、硝苯地平治疗组、氨氯地平治疗组 ,每组 8只兔分别给予普通饲料、高脂饲料、高脂饲料 +硝苯地平、高脂饲料 +氨氯地平喂养 6 0d ,试验前、中、后测定血浆和红细胞的脂质、脂质过氧化物、红细胞膜流动性 (M Flu)、血浆内皮素 (ET)、全血血小板活化因子 (PAF)以及血小板聚集率 (PAR)水平 ,实验后取心脏、主动脉、肝脏作组织生化和病理学检查。结果　氨氯地平与硝苯地平作用类似 ,可降低血中ET、PAF水平 ,升高高密度脂蛋白胆固醇 (HDL C)水平 ,减少肝脏、主动脉以及红细胞膜胆固醇含量 ,抑制血液和组织的脂质过氧化损伤 ,保护血管内皮细胞和红细胞的功能 ,调整血管平滑肌细胞的表型并抑制其增殖 ,降低血小板聚集活性。结论　氨氯地平和硝苯地平具有显著的抗动脉粥样硬化作用。     

Treating patients with documented atherosclerosis to national cholesterol education program-recommended low-density-lipoprotein cholesterol goals with atorvastatin,fluvastatin, lovastatin and simvastatin

Objectives. This study compared the efficacy and safety of atorvastatin, fluvastatin, lovastatin, and simvastatin in patients with documented atherosclerosis treated to U.S. National Cholesterol Education Program (NCEP) recommended low-density-lipoprotein (LDL) cholesterol concentration (≤100 mg/dl [2.59 mmol/liter]).Background. For patients with advanced atherosclerosis, NCEP recommends lipid-lowering drug therapy if LDL cholesterol remains ≥130 mg/dl (3.36 mmol/liter).Methods. A total of 318 men or women with documented atherosclerosis and LDL cholesterol ≥130 mg/dl (3.36 mmol/liter) and ≤250 mg/dl (6.5 mmol/liter), and triglycerides ≤400 mg/dl (4.5 mmol/liter) participated in this 54-week, multicenter, open-label, randomized, parallel-group, active-controlled, treat-to-target study. Patients were titrated at 12-week intervals until the LDL cholesterol goal was reached. Number of patients reaching target LDL cholesterol levels and dose to reach target were evaluated.Results. At the starting doses, atorvastatin 10 mg produced significantly greater decreases (p < 0.05) in plasma LDL cholesterol than the other treatments. Subsequently, the percentage of patients reaching goal at the starting dose was 32% for atorvastatin, 1% for fluvastatin, 10% for lovastatin and 22% for simvastatin. Atorvastatin-treated patients required a lower median dose than other treatments. Median doses at week 54 with the last available visit carried forward were atorvastatin 20 mg/day, fluvastatin 40 mg/day + colestipol 20 g/day, lovastatin 80 mg/day, simvastatin 40 mg/day.Conclusions. A significantly greater number (p < 0.05) of patients with confirmed atherosclerosis treated with atorvastatin reached the target LDL cholesterol concentration at the starting dose than patients treated with fluvastatin or lovastatin, and significantly fewer (p < 0.05) patients treated with atorvastatin required combination therapy with colestipol to achieve target LDL cholesterol concentrations than all other statins tested.     

Hypertension and atherosclerosis in cholesterol-fed rabbits. II. One-kidney, one clip Goldblatt hypertension treated with nifedipine

Eight groups of New Zealand white rabbits were used to study the effects of moderate chronic one-kidney, one clip hypertension (HT) and long-term nifedipine therapy on atherogenesis. Four groups were fed a normal diet (ND) over an 8-month study period; two groups, one of which was given nifedipine, remained normotensive (NT) throughout the study. Of the two HT groups, one remained hypertensive for 7 months; the blood pressure of the other group was normalized after 2 months with nifedipine. The other four groups of animals were similarly constructed except that they were fed a 0.1% cholesterol diet (CD). The results showed that: although scattered fibromuscular vascular lesions were present in the aortas of normal-diet, HT animals no atheroma was observed; neither moderate chronic HT nor abrupt, short-term HT exacerbated atherogenesis in the CD-animals; nifedipine therapy had no suppressive effect on either fibromuscular lesions or atherogenesis; nifedipine therapy reduced the aorta weight of the normotensive ND and CD groups; the aortic triglyceride content of both dietary groups was reduced by nifedipine; cholesterol content was unaffected; left ventricular hypertrophy was evident only in HT-untreated groups; and only the weight of the left ventricle of the ND-NT-treated group was significantly reduced, but the mitochondria volume per unit volume of left ventricle myocardial cells was reduced only in the NT-CD group treated with nifedipine. It is concluded that an antihypertensive dosage of nifedipine administered to animals with atherosclerosis does not suppress subsequent atherogenesis.     

Nifedipine suppressed atherosclerosis in cholesterol-fed rabbits but not in Watanabe heritable hyperlipidemic rabbits

We studied the effects of nifedipine, a calcium antagonist, on atherosclerosis in cholesterol-fed rabbits and Watanabe heritable hyperlipidemic rabbits (WHHL rabbits). Japanese White rabbits were fed 120g of 2% cholesterol rabbit chow daily, and WHHL rabbits were fed standard rabbit chow. In each experiment, the rabbits were divided into two groups. Twenty milligrams of nifedipine was given orally twice a day to the nifedipine group, and the control group was given a placebo in the same way. The rabbits were sacrificed at the end of the 12th week in the case of cholesterol-fed rabbits, and the 20th week in the case of WHHL rabbits. Among the cholesterol-fed rabbits, the percentage of aortic intimal surface area covered by atherosclerotic lesions (AS%) was 25.9 +/- 7.6% (mean +/- S.D.) in the nifedipine group (n = 7), and 55.6 +/- 22.8% in the placebo group (n = 8) (p less than 0.01). The cholesterol content of thoracic and abdominal aorta in the nifedipine group was lower than those in the placebo group (p less than 0.05). Among the WHHL rabbits, the AS% was 33.4 +/- 14.1% in the nifedipine group (n = 5), and 27.0 +/- 11.7% in the placebo group (n =6) (n.s.). The aortic cholesterol and calcium contents also showed no significant differences between the two groups. We concluded that nifedipine suppressed atherosclerosis in cholesterol-fed rabbits but not in WHHL rabbits. The different responses suggest that the effect of nifedipine could be mediated by low density lipoprotein receptors or that the early exposure to hyperlipidemic serum from birth might affect cell functions of WHHL rabbits.