血脂康对高脂饮食家兔血管内皮细胞功能的保护作用

目的探讨血脂康对高胆固醇饮食家兔血管内皮细胞功能的保护作用。方法健康纯种新西兰白兔３０只，随机分层分组法分为对照组（普通饲料），高脂组（普通饲料＋１５％胆固醇），治疗组（普通饲料＋１５％胆固醇＋血脂康０８ｇ·ｋｇ－１·ｄ－１），在实验不同阶段，观察各组家兔血清脂质、一氧化氮及血浆内皮素、前列环素、血栓素含量及血管内皮细胞病理形态学改变。结果实验前各组血清总胆固醇（ＴＣ）、甘油三酯（ＴＧ）、低密度脂蛋白胆固醇（ＬＤＬＣ）、血浆内皮素（ＥＴ）１、血清一氧化氮（ＮＯ）、血浆血栓素（ＴＸ）Ｂ２及６酮前列腺素（ＰＧ）Ｆ１α等无明显差异。实验１２周，高脂组、血脂康治疗组血清ＴＣ、ＴＧ、ＬＤＬＣ及血浆ＥＴ１、ＴＸＢ２及ＴＸＢ２／６酮ＰＧＦ１α比值明显高于对照组，但治疗组明显低于高脂组（Ｐ值均＜０．０５）；血浆ＮＯ低于对照组（Ｐ＜０．０５），但治疗组高于高脂组（Ｐ＜０．０５）。病理结果显示：血脂康治疗组主动脉、冠状动脉粥样硬化病变及血管内皮细胞损伤明显轻于高脂组。结论血脂康具有明显的调整脂质代谢及保护血管内皮细胞功能的作用。     

阻断肾内肾素-血管紧张素系统对转化生长因子β1mRNA及细胞外基质表达的作用

目的探讨苯那普利延缓肾脏疾病进展的可能作用机制。方法采用实验性肾小球硬化模型,治疗组给苯那普利（４ｍｇ·ｋｇ－１·ｄ－１）。用比色法和放免法分别测定肾内血管紧张素转换酶（ＡＣＥ）活性和血管紧张素Ⅱ（ＡｎｇⅡ）含量,免疫组化检测肾组织转化生长因子β１（ＴＧＦβ１）和细胞外基质（ＥＣＭ）,原位杂交观察ＴＧＦβ１ｍＲＮＡ表达。结果治疗组肾内ＡＣＥ活性和ＡｎｇⅡ与非治疗组比较,受到明显抑制（Ｐ＜０．０１）。治疗组肾小球和肾小管区ＴＧＦβ１ｍＲＮＡ表达量显著低于非治疗组（Ｐ＜００１）。同时,ＥＣＭ在肾小球内沉积也较非治疗组显著减少（Ｐ＜０．０１）。结论苯那普利通过阻断肾内肾素血管紧张素系统,在下调ＴＧＦβ１表达和ＥＣＭ积聚中起重要作用。     

原发性高血压患者尿α1-微球蛋白、转铁蛋白的变化及非洛地平对其的影响

目的：研究原发性高血压（ＥＨ）患者尿蛋白的排泄情况及非洛地平对其的影响。　　方法：测定３０ 例正常人（正常对照组）及６０ 例ＥＨ患者（ＥＨ组,其中包括轻度ＥＨ组３２例、中度ＥＨ组２８例）用药前后的尿α１－微球蛋白、转铁蛋白及血清肌酐。　　结果：①轻度ＥＨ组尿α１ －微球蛋白、转铁蛋白明显高于对照组（Ｐ＜ ０．０１）,中度ＥＨ组尿α１－微球蛋白、转铁蛋白明显高于轻度ＥＨ组和正常对照组（Ｐ＜ ０．０１;Ｐ＜ ０．００１）,且与病程有关。②血清肌酐在中度ＥＨ组明显高于正常对照组（Ｐ＜ ０．０５）,轻度ＥＨ组较正常对照组无明显升高（Ｐ＞ ０．０５）。③非洛地平治疗后,轻度、中度ＥＨ组尿α１ －微球蛋白、转铁蛋白较治疗前明显降低（Ｐ＜ ０．０１;Ｐ＜ ０．００１）,轻度ＥＨ组血清肌酐较治疗前无明显降低（Ｐ＞ ０．０５）,而在中度ＥＨ组血清肌酐较治疗前明显下降（Ｐ＜ ０．０５）。　　结论：尿α１ －微球蛋白、转铁蛋白较血清肌酐能更早的识别高血压肾脏损害,非洛地平降压的同时能预防或延缓肾脏损害的发生、发展。     

补体膜攻击复合物和CD59在不同免疫病理类型IgA肾病发病机理中的作用

为进一步阐明导致不同免疫病理类型ＩｇＡ肾病（ＩｇＡＮ）患者预后不同的机理，应用ＰＡＰ四层法对２８例肾小球单纯ＩｇＡ沉积（单纯ＩｇＡ组）及３２例ＩｇＧ、ＩｇＡ、ＩｇＭ共同沉积（ＧＡＭ组）ＩｇＡＮ患者肾组织膜攻击复合物（ＭＡＣ）和ＣＤ５９的分布情况，结合其肾小球内沉积的补体成分以及病理改变和临床特点进行了分析，结果表明：单纯ＩｇＡ组临床表现、病理改变轻，ＧＡＭ组临床表现、病理改变重。ＧＡＭ组肾组织经典途径补体成分Ｃｌｑ、Ｃ４沉积（均为Ｐ＜０．０１），肾小球系膜区及毛细血管袢ＭＡＣ沉积（分别为Ｐ＜０．０５、Ｐ＜０．０１），肾小球硬化＞２５％（Ｐ＜０．０５）和中重度小管间质病变的发生率（Ｐ＜０．０５），均较单纯ＩｇＡ组明显增多，且ＧＡＭ组皮质区域间质面积较单纯ＩｇＡ组明显增宽（Ｐ＜０．０１）。尽管ＣＤ５９在两组中分布无统计学差异，但若按肾小球ＣＤ５９分布强度将患者分为Ａ组（＋）和Ｂ组（２＋），结果发现ＣＤ５９Ａ组肾小球硬化＞２５％（Ｐ＜０．０５），中重度小管间质病变的发生率明显增多（Ｐ＜０．０１），皮质区域间质面积明显增宽（Ｐ＜０．０１）。在硬化的肾小球内ＭＡＣ分布多而ＣＤ５９分布少     

血脂康对实验性家兔动脉粥样硬化形成及其脂质过氧化损伤的影响

目的：探讨血脂康对实验性家兔动脉粥样硬化（ＡＳ）的形成及其脂质过氧化损伤的影响。方法：将纯种新西兰白兔采用随机分层分组法分为３组，即对照组、高脂组和治疗组。以高胆固醇饮食建立家兔动脉粥样硬化模型观察各组家兔血脂、血浆过氧化脂质、超氧化物歧化酶及主动脉、冠状动脉的病理改变。结果：血脂康能明显降低高胆固醇饮食家兔血清胆固醇、甘油三酯、低密度脂蛋白胆固醇含量（Ｐ＜０．０５），轻度增加血清高密度脂蛋白胆固醇含量（Ｐ＞０．０５），明显地抑制血浆过氧化脂质的形成（Ｐ＜０．０５）及超氧化物歧化酶含量的降低（Ｐ＜０．０５）；抑制肝脏、肾脏过氧化脂质的形成及超氧化物歧化酶含量的降低（Ｐ＜０．０５）。治疗组主动脉硬化斑块面积与动脉总面积比值明显降低，泡沫细胞层数明显减少，主动脉及冠状动脉病变明显减轻。结论：血脂康具有明显的调整血脂、抑制高胆固醇饮食家兔动脉粥样硬化形成及其脂质过氧化损伤的作用     

大黄治疗大鼠系膜增殖性肾炎的实验研究

为了解中药大黄对系膜增殖性肾炎的治疗效果，用计算机图像分析及ＥＬＩＳＡ法观察了大黄对抗Ｔｈｙ－１肾炎大鼠系膜区细胞外基质的影响，并检测了肾小球培养上清中的白细胞介素－１（ＩＬ－１）活性。结果表明，大黄不仅减少了肾炎大鼠基质的堆积，还能降低肾小球培养上清中的纤维连接蛋白（ＦＮ）浓度和ＩＬ－１活性。肾小球ＦＮ浓度在未治疗组非常显著地高于对照组与大黄组（Ｐ＜０．０１），其中大黄组又显著低于对照组（Ｐ＜０．０５）。肾小球ＩＬ－１活性未治疗组显著高于大黄组，而大黄组又显著高于正常对照组（Ｐ＜０．０５）。大黄能改善系膜增殖性肾炎大鼠系膜区基质的堆积，其作用可能与其抑制肾小球分泌ＩＬ－１有关。     

大黄对糖尿病大鼠肾小球形态改变的影响及定量分析

用先进的图像分析系统，观察了中药大黄提取物Ⅰ号对链脲菌素（ＳＴＺ）所致糖尿病肾病大鼠模型肾小球形态学的影响，结果提示，在病程第三天糖尿病组大鼠肾小球干均体积较大黄提取物Ⅰ号治疗组大鼠明显增大（Ｐ＜０．０１）；病程的第三、七和第１４天糖尿病组大鼠肾小球系膜区平均面积较治疗组扩大，有统计学差异（分别为Ｐ＜０．０１．Ｐ＜０．０１和Ｐ＜０．００１）．本研究在实验性大鼠的体内进一步证实大黄提取物Ⅰ号抑制肾脏肥大的作用。     

鱼翅海参营养液抗衰老和降血脂作用的实验研究

用剂量分别为０．００、１．３３、６．６７ｍｌ／ｋｇ·ｄ－１，鱼翅海参营养液饲养大鼠５ｗ。结果表明：低剂量与高剂量组大鼠肝脏、心肌组织中ＬＰＯ比对照组分别降低３９．１％（Ｐ＜０．０５）、５４．３％（肝ＬＰＯ）（Ｐ＜０．０１）和４．５％（Ｐ＞０．０５），２８．５％（心ＬＰＯ）（Ｐ＜０．０５）；两实验组均明显提高外周血Ｔ淋巴细胞的转化率（Ｐ＜０．０５）；血清总胆固醇、低密度脂蛋白胆固醇、动脉粥样硬化指数高剂量组均明显低于对照组（Ｐ＜０．０１）；两实验组主动脉胆固醇及主动脉斑块面积均显著低于对照组（Ｐ＜０．０５）．提示鱼翅海参营养液具有较好的抗氧化、降血脂和提高机体免疫功能的作用。     

心钠素两种不同受体mRNA在阿霉素诱导的肾病综合征大鼠肾脏的表达

目的：在阿霉素诱导的肾病综合征大鼠动物模型探讨肾病水肿发病机理。方法：观察阿霉素诱导的肾病综合征大鼠模型扩容利尿反应及心钠素（ＡＮＰ）两种受体的表达。结果：肾病大鼠对扩容利尿的反应较正常对照组明显下降（Ｐ＜０．０１）。虽然两组大鼠在扩容时血浆心钠素上升幅度相似，但其尿中ＡＮＰ第二信使ｃＧＭＰ的排泄（ＵｃＧＭＰＶ）在肾病组比正常对照组明显下降（５．８５±２．６～３１．４±７．５ｖｓ６．０２±３．０～９８．４５±１６．８ｐｍｏｌ／ｍｉｎ，Ｐ＜０．０１）。Ｎｏｒｔｈｅｒｎ杂交显示，两组大鼠肾脏ＡＮＰ－Ａ受体ｍＲＮＡ表达相似，但肾病组大鼠肾脏ＡＮＰ－Ｃ受体ｍＲＮＡ表达较正常对照组明显升高（Ａ×ａｒｅａ１ｖｓ０．３２，Ｐ＜０．０１）。结论：肾病综合征水钠潴留可能与其肾脏ＡＮＰ－Ｃ受体高表达有关。     

低分子肝素对糖尿病大鼠肾脏病变的影响

目的研究低分子肝素对糖尿病大鼠肾脏病变的保护作用及其机制。方法观察低分子肝素对肾小球功能、形态及肾小球基底膜超微结构的影响。结果（１）在病程不同时期（４、８、１２、１６周）治疗组尿白蛋白明显低于非治疗组（Ｐ＜０．０５）；（２）１６周时，光镜及电镜下治疗组肾小球系膜增生、基底膜增厚和足突融合等病变较非治疗组明显减轻，而两组血糖、肾小球平均截面积、肾小球平均体积、肾小球滤过率及血压无明显差异（Ｐ＞０．０５）。结论低分子肝素对糖尿病大鼠的肾脏病变具有一定防治作用，其机制可能不是通过改善血糖及血液动力学实现的。     

Pravastatin Has Cholesterol-Lowering Independent Effects on the Artery Wall of Atherosclerotic Monkeys

Objectives. This study examined the direct effects of pravastatin on the artery wall of atherosclerotic monkeys after dietary lipid lowering.Background. Clinical trials suggest that hepatic hydroxymethylglutaryl coenzyme A reductase inhibitors may reduce the risk of coronary heart disease out of proportion to their effect on angiographically assessed lumen stenosis.Methods. Thirty-two cynomolgus monkeys were fed an atherogenic diet for 2 years (progression phase) and then fed a lipid-lowering diet either containing (n = 14) or not containing (n = 18) pravastatin in the diet for an additional 2 years (treatment phase). As designed, total plasma cholesterol and high density lipoprotein concentrations did not differ between groups at the beginning of or during the treatment phase of the experiment (p > 0.05).Results. Quantitative angiography revealed that coronary arteries of the pravastatin-treated monkeys dilated 10 ± 3%, whereas those from untreated control monkeys constricted −2 ± 2% in response to acetylcholine (p < 0.05). There were no treatment effects on plaque size of coronary arteries measured at the end of the treatment phase of the study (0.110 ± 0.048 mm²[untreated] vs. 0.125 ± 0.051 mm²[pravastatin]; p > 0.05) or on the amount of reduction in plaque size in common iliac arteries during the treatment phase of the study (48 ± 5% [untreated] vs. 45 ± 6% [pravastatin]; p > 0.05). However, histochemical analysis of the atherosclerotic lesions indicated that the arteries from pravastatin-treated monkeys had significantly fewer macrophages in the intima and media, less calcification and less neovascularization in the intima (p < 0.05).Conclusions. We conclude that compared with control monkeys, the arteries of pravastatin-treated monkeys had better dilator function and plaque characteristics more consistent with plaque stability than those of monkeys not receiving pravastatin. These beneficial arterial effects of pravastatin occurred independently of plasma lipoprotein concentrations and despite similar changes in plaque size between the groups.     

Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study

This multicenter, double-blind, placebo-controlled, dose-response study was conducted in patients with primary hypercholesterolemia to examine the effects of pravastatin, a selective inhibitor of HMG-CoA reductase, on plasma lipids and lipoproteins. A total of 306 patients on cholesterol-lowering diets received twice daily doses of 5 mg, 10 mg, 20 mg pravastatin, or placebo for 12 weeks. Marked reductions in low density lipoprotein (LDL) cholesterol and total cholesterol were observed after 1 week of treatment; maximum lipid-lowering effects occurred at 4 weeks and were sustained for the duration of the trial. At week 12, pravastatin treatment resulted in dose-dependent mean reductions from baseline in LDL cholesterol of 17.5%, 22.9%, and 30.8% for the 3 doses tested (P less than or equal to 0001 compared with baseline and placebo). The reduction in LDL cholesterol was log-linear with respect to dose; each doubling of dose reduced LDL cholesterol an additional 6.5%. Dose-dependent reductions in total cholesterol from 12.9% to 23.3% also occurred (P less than or equal to 0.001). Triglycerides decreased by as 15.4% (P less than or equal to 0.001) and high-density lipoprotein (HDL) cholesterol increased approximately 7% (P less than or equal to 0.01), but these effects were not dose-dependent. No patient receiving pravastatin was discontinued during the 12-week trial. Transient episodes of rash and headache occurred. Slight increases in mean serum levels of ASAT and ALAT occurred, and 2% of both placebo- and pravastatin-treated patients reported myalgia although there was no clinically significant elevation of creatine kinase. These data indicate that pravastatin favorably affects all lipid parameters and is well tolerated.     

Pravastatin sodium, an inhibitor of HMG-CoA reductase, decreases HDL cholesterol by transfer of cholesteryl ester from HDL to VLDL in Japanese white rabbits

In a recent paper, we reported that pravastatin sodium (pravastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme. A reductase, decreases the concentrations of low density lipoprotein (LDL) cholesterol through an LDL receptor pathway in Japanese White (JW) rabbits, whereas this agent lowers high density lipoprotein (HDL) cholesterol in a manner correlated with a reduction of very low density lipoprotein (VLDL) cholesterol secretion from the liver. In the present study, we administered pravastatin to JW rabbits at 30 mg/kg for 14 days and examined further the mechanisms for the reduction of HDL cholesterol. A striking finding was that the 4-day administration of pravastatin at 30 mg/kg selectively decreased the concentration of HDL cholesterol. Since 4-day administration of pravastatin to JW rabbits did not change the concentrations of hepatic LDL receptor proteins, these receptors were not likely to be involved in the reduction of HDL cholesterol. Another important finding was that pravastatin suppressed VLDL cholesteryl ester (CE) secretion from the liver, but not that of other VLDL lipids and VLDL proteins, indicating that the CE-poor VLDL particles were secreted by the consecutive administration of pravastatin. There were, however, no differences in the levels of VLDL cholesterol between the control and pravastatin-treated groups over the experimental period of 14 days. These observations raised the possibility that the reduction of HDL cholesterol in the pravastatin-treated group was due to the transfer of CE molecules from HDL particles to these CE-poor VLDL particles. Molecular species analysis supported this notion that the VLDL-CE in the pravastatin-treated group was rich in cholesteryl linoleate, indicating that the CE in this group mainly originated from HDL, whereas the VLDL-CE in the control group was rich in cholesteryl oleate, indicating that the CE in this group originated from the liver. The present study suggests that pravastatin lowers HDL cholesterol by transferring CE from these lipoproteins to VLDL in JW rabbits.     

Renoprotective effect of pravastatin in salt-loaded Dahl salt-sensitive rats.

The pathophysiological features of nephrosclerosis may be analogous to those of atherosclerosis, which is intimately related to lipid metabolism. Thus, we examined whether a lipid-lowering agent, pravastatin, would ameliorate renal damage in hypertensive model animals. Salt-loaded Dahl salt-sensitive (S) rats were given pravastatin (2 mg/ml in drinking water) for 5 weeks. Pravastatin decreased systolic blood pressure. Although pravastatin did not influence the serum total, high-density, or low-density lipoprotein cholesterol, serum triglycerides were decreased. Pravastatin decreased urinary protein excretion and ameliorated histopathological damage in salt-loaded Dahl S rats. Increased urinary excretion of 8-iso-prostagaldin F2alpha and 8-hydroxy-2'-deoxyguanosine and renal superoxide overproduction and decreased reduced glutathione in the renal parenchyma were ameliorated with pravastatin in Dahl S rats fed a high salt diet. Therefore, pravastatin inhibited the progression of renal injury in salt-loaded Dahl S rats, through its antioxidant as well as its depressor effects.     

Pravastatin affects blood pressure and vascular reactivity

Summary To investigate the effect of endogenous cholesterol synthesis on blood pressure and vascular response, a HMG CoA reductase inhibitor, pravastatin (1 or 10mg/kg per day) was administered orally for 2 or 4 weeks to spontaneously hypertensive rats (SHR/lzm) and normotensive Wistar-Kyoto (WKY/lzm) rats. Blood pressure was significantly increased in the pravastatin-treated groups of both strains, occurring in WKY after a longer treatment period than in SHR. The thoracic aortas from SHR and WKY were pretreated with pravastatin (10^–4M). The vascular response to norepinephrine in terms of both contractility and sensitivity, was increased in the pravastatin-treated SHR aorta but not in the WKY aorta. The increased response was not observed in the presence of mevalonate. Acetylcholine-induced vascular relaxation in the aortas from both strains was not affected by pravastatin pretreatment. These results suggest that the vascular response to norepinephrine may be affected by the intracellular cholesterol synthesis pathway.     

Risk factors for the progression of diabetic nephropathy: role of hyperlipidaemia and its correction

Hypertension, proteinuria and hyperlipidaemia are major factors implicated in the progression of chronic renal failure towards uraemia. All of these factors are frequently more pronounced in diabetic nephropathy. We evaluated the rate of progression of renal insufficiency in 12 patients with diabetic nephropathy (DN group) and 18 patients with non-diabetic chronic nephropathy (CN group) during a 2-year period. All patients had high blood pressure on angiotensin-converting enzyme (ACE) inhibitor therapy, hypercholesterolaemia and proteinuria in the non-nephrotic range. Basal glomerular filtration rate (GFR) had an overlapping range in the two groups. The rate of GFR decline during the 2-year period was similar for the DN and CN groups (0.23 vs 0.21 ml/min per month) and correlated with the mean values of low-density lipoprotein (LDL)-cholesterol for both groups (DNr=0.569, CNr=0.511,P<0.05). After 1 year of ACE inhibitor therapy we randomly allocated a subset of patients in each group (6 DN and 9 CN) to receive HMG-CoA-reductase inhibitor (simvastatin or pravastatin 10 mg/day). We observed a decrease in total (–21%) and LDL-cholesterol (–32%) and triglycerides (–11%) and an increase in high-density lipoprotein (HDL)-cholesterol (+8%). The rate of GFR decline was lower in the statin-treated group compared with the previous period (DN–0.21 vs –0.25 ml/min per month; CN –0.18 vs –0.22 ml/min per month). Our data support the hypothesis that associated risk factors rather than diabetes per se are responsible for the rate of progression of renal failure in DN and that the correction of lipid abnormalities may play a key role in slowing the rate of renal function decline.     

Are Canadian guidelines for cholesterol lowering in high-risk patients optimal?

Recent Canadian lipid guidelines recommend that all high-risk patients receive medication to reduce low density lipoprotein cholesterol (LDL-C) below 2.5 mmol/L. The recently published Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) studies compared strategies of cholesterol lowering with atorvastatin 80 mg versus pravastatin 40 mg. Atorvastatin halted the progression of atherosclerosis (whereas atherosclerosis progressed in the patients receiving pravastatin), and resulted in a 16% reduction in the primary composite end point (all-cause death, myocardial infarction, unstable angina, revascularization and stroke) compared with the pravastatin-treated group. In the PROVE IT trial, LDL-C was reduced by atorvastatin to 1.6 mmol/L and by pravastatin to 2.46 mmol/L. Although lower LDL-C levels are one explanation for the improved outcomes with atorvastatin, pleiotropic differences of the two statins, such as their effects on inflammation and coagulation, cannot be excluded. Until trials are completed that compare outcomes from LDL-C lowering to different targets with the same statin, it is premature to recommend changes to the current Canadian guidelines. However, future recommendations may suggest much lower LDL-C targets than those currently recommended.     

Renoprotective effects of telmisartan on renal injury in obese Zucker rats

The purpose of the present study was to investigate the renoprotective effect of telmisartan, an angiotensin II receptor antagonist, on the early stages of diabetic nephropathy in obese Zucker rats, which is a type 2-related diabetes mellitus model. Telmisartan 1, 3 or 10?mg/kg/day was orally administered to 7-week-old rats that demonstrated glucose tolerance without albuminuria or proteinuria, for 24 consecutive weeks (Experiment A). In another experiment (Experiment B), oral administration of telmisartan 10?mg/kg/day was initiated at the age of 16?weeks after the rats demonstrated marked proteinuria, and continued for 24?weeks. Telmisartan inhibited the increase in proteinuria and albuminuria in a dose-dependent manner, and the inhibition for all telmisartan groups was statistically significant by the completion of administration (Experiment A). Telmisartan also displayed similar inhibitory effects on proteinuria and albuminuria in Experiment B. Histologically, telmisartan [3 and 10?mg/kg/day] was associated with a significant decrease in the progression of glomerulosclerosis, and significantly improved interstitial cell infiltration, interstitial fibrosis and dilation and atrophy of renal tubules. Furthermore, telmisartan treatment was associated with a tendency towards normalized plasma lipids (total cholesterol and triglyceride). Our results suggest that telmisartan has a definite renoprotective effect against renal injury in type II diabetic nephropathy.     

Effect of withdrawal of pravastatin therapy on C-reactive protein and low-density lipoprotein cholesterol

In addition to lowering cholesterol, statins effectively lower C-reactive protein (CRP) levels. The effects of withdrawal from long-term statin therapy on CRP are unknown. This study examined the effect of withdrawal from 4 years of statin treatment on CRP. We prospectively evaluated the effects of withdrawal from pravastatin (40 mg) treatment on CRP levels in 566 subjects who participated in a randomized, placebo-controlled trial. Median (interquartile range) CRP levels before randomization were 1.29 mg/L (0.63 to 2.73) and mean low-density lipoprotein (LDL) cholesterol was 4.06 +/- 0.92 mmol/L. Four years after randomization, placebo-treated patients (n = 266) had a nonsignificant 9% increase in CRP, whereas there was a 12% decrease (p = 0.001) in the pravastatin-treated patients (n = 300). LDL cholesterol only decreased in pravastatin-treated patients (-27%; p <0.001). Withdrawal from pravastatin led to a significant increase in both CRP and LDL cholesterol to approximately pretreatment levels (p <0.05 and <0.001, respectively). Changes in CRP after withdrawal from pravastatin could not be predicted by the change in LDL cholesterol. The difference between the pravastatin and placebo groups in terms of change in CRP by withdrawal was consistent and persisted in analysis corrected for body mass index, smoking status, blood pressure, and baseline levels of total cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, or triglycerides. In conclusion, withdrawal from pravastatin treatment resulted in an increase in CRP to approximately baseline levels, which is not related to the increase in LDL cholesterol.     

Pravastatin vs gemfibrozil in the treatment of primary hypercholesterolemia. The Italian Multicenter Pravastatin Study I

This study compared the efficacy and safety of pravastatin and gemfibrozil in the treatment of primary hypercholesterolemia. Three hundred eighty-five outpatients from 13 lipid clinics in Italy participated in this randomized double-blind study. Patients were assigned to receive either 40 mg once daily of pravastatin or 600 mg of gemfibrozil twice daily after an initial diet lead-in period. After 24 weeks, mean reductions from baseline values of plasma total and low-density lipoprotein cholesterol were, respectively, 23% and 30% with pravastatin and 14% and 17% with gemfibrozil. Significant lipid-lowering effects were noted within 4 weeks. Apolipoprotein B decrease was 21% with pravastatin and 13% with gemfibrozil. A statistically significant increase of high-density lipoprotein cholesterol of 5% was achieved with pravastatin compared with a 13% increase for gemfibrozil. Serum triglyceride values decreased 5% with pravastatin and 37% with gemfibrozil. Familial and polygenic hypercholesterolemic patients were also examined separately. Pravastatin effectiveness in reducing low-density lipoprotein cholesterol was greater by 6% in polygenic than in familial hypercholesterolemic patients. Treatment for 25 patients (eight treated with pravastatin and 17 treated with gemfibrozil) was discontinued during the study. The incidence of clinical symptoms and laboratory alterations was low for both treatment groups. Pravastatin and gemfibrozil were well tolerated, but pravastatin was significantly more effective in reducing total and low-density lipoprotein cholesterol levels in primary (either familial or polygenic) hypercholesterolemias than gemfibrozil.