Short- and long-term effects of lovastatin and pravastatin alone and in combination with cholestyramine on serum lipids,lipoproteins and apolipoproteins in primary hypercholesterolaemia

Summary The effects of the HMG CoA reductase inhibitors lovastatin and pravastatin on serum lipids, lipoproteins and apolipoproteins have been studied in 35 patients with primary hypercholesterolaemia.LDL cholesterol was lowered to the same extent by both agents compared on a mg basis of each drug per day. HDL cholesterol was increased by lovastatin but not by pravastatin. The reduction in serum triglycerides, VLDL triglycerides and VLDL cholesterol was more pronounced after lovastatin than pravastatin. After 1 year the effect of combined treatment with 40 mg pravastatin and 8 g cholestyramine on the reduction in LDL cholesterol (–39%) in 13 patients was comparable to that of 80 mg lovastatin plus 8 g cholestyramine (–40%) in 12 patients with identical baseline values.Differences were also found in the effects of the combination therapy with the two drugs on HDL cholesterol, serum triglycerides, VLDL triglycerides, VLDL cholesterol, and apolipoproteins.     

冠状动脉粥样硬化与血脂代谢紊乱的因素分析

目的:探讨血脂代谢紊乱与冠状动脉粥样硬化之间的关系。方法:收集我院心内科住院前1个月内未服用降脂药且行冠状动脉造影患者共407例,冠状动脉狭窄≥50%者为冠心病组,无狭窄者为非冠心病组。冠心病组根据管腔受累内径、主要血管受累支数、病变损害程度进行评分。取患者空腹12h静脉血送检,将有无冠心病和冠脉病变程度、范围、积分与各项血脂指标进行相关分析。结果:冠心病组三酰甘油(TG)、载脂蛋白B(apoB)、脂蛋白a[LP(a)]致动脉硬化指数[log(TG/HDL-C)]、非高密度脂蛋白(NHDL)、脂蛋白a/高密度脂蛋白胆固醇[LP(a)/HDL-C]高于非冠心病组(P<0.05或P<0.01),血浆HDL-C、载脂蛋白A(1apoA1)低于非冠心病组(均P<0.05)。冠状动脉病变程度、范围、病变血管积分与患者的血浆LP(a)、NHDL、log(TG/HDL-C)、LP(a)/HDL-C比值呈正相关,与HDL-C呈负相关。对与病变血管积分相关的血脂指标与病变血管积分进行线性回归分析,与NHDL、log(TG/HDL-C)相比,LP(a)/HDL-C比值的增加,对病变积分影响最大。结论:血浆NHDL、log(TG/...     

西藏高原地区血脂水平和海拔关系的研究

目的:调查我国西藏高原地区居民的血脂水平是否与海拔相关。方法:选取西藏昌都地区的成年健康体检者407例,依受试者居住地海拔不同分为10组,调查各组三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的水平及异常率,比较不同海拔地区血脂水平及血脂异常率的差异。结果:TC和LDL-C水平及HDL-C的异常率在各组间差异有统计学意义(P<0.05),TG和HDL-C的水平及高TG、高TC、高LDL-C比率差异无统计学意义(P>0.05)。TG、TC、HDL-C和LDL-C的水平与海拔未见相关。结论:西藏高原地区血脂水平与海拔无相关性。     

Long-term effect of pindolol on lipids and lipoproteins in men with newly diagnosed hypertension

Summary This is the first long-term study of pindolol in a population-based sample of men with newly diagnosed hypertension.Eighty-two patients, with a diastolic pressure of 100 mm Hg or more, were identified after screening 6000 men. Many patients were overweight. 82 population controls, matched by sex, age and body mass index, were also recruited. Fourty-eight per cent of the patients and 25% of the controls had a family history of hypertension.Serum triglyceride and urate values were higher in patients than controls at the baseline investigation. Seventy-four patients were followed for 1 year. The dose of pindolol averaged 7.7 mg once daily after 1 year.The diastolic blood pressure was reduced by 13.4 mm Hg. The target pressure of 95 mm Hg or less was achieved in 89% of the patients. The HDL-cholesterol concentration was normal and did not change, whereas the LDL-cholesterol concentration decreased by 0.15 mmol · l^–1 during treatment. The total triglyceride values increased transiently up to 6 months, but no significant increase was seen after one year.It is concluded that pindolol had no adverse effect on serum cholesterol and its HDL- and LDL-fractions during 1 year of treatment.     

Comparative effects of simvastatin and cholestyramine in treatment of patients with hypercholesterolaemia

Summary The efficacy and safety of 20 mg simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) and of 16 g cholestyramine daily in the treatment of 34 hypercholesterolaemic patients have been compared after dietary treatment and stratified randomization. The effect of combined treatment with the two drugs was studied in 5 patients with severe hypercholesterolaemia.After 6 weeks of treatment the simvastatin group showed a significantly greater (p<0.05) decrease in the mean total plasma cholesterol concentration from 7.88 to 5.48 mmol/l than in the cholestyramine group in whom there was a fall from 7.82 to 6.73 mmol/l. Simvastatin decreased the mean plasma LDL cholesterol concentration from 6.07 to 3.76 mml/l and cholestyramine decreased it from 6.16 to 4.46 mmol/l. Simvastatin also reduced the mean plasma total triglycerides by 24%, VLDL triglycerides by 20% and VLDL cholesterol by 36%, while cholestyramine led to increases in these parameters by 64%, 85% and 63%, respectively. Mean plasma HDL cholesterol concentration and the subfractions HDL₂ and HDL₃ cholesterol were significantly increased by simvastatin. Simvastatin and cholestyramine reduced the mean plasma apolipoprotein B concentration by 28% and 13%, respectively.The mean plasma apolipoprotein A–I concentration was significantly higher only on simvastatin treatment.Simvastatin did not cause any subjective or objective side effects, while cholestyramine caused gastrointestinal problems in 31% of patients. Small increases in serum alanine aminotransferase (S-ALT) activity were seen with both drugs. Cholestyramine significantly raised the serum alkaline phosphatase (S-ALP) although to a level still within the normal range.It is concluded that 20 mg simvastatin was more effective than 16 g cholestyramine in the treatment of hypercholesterolaemia. Simvastatin was also better tolerated and it is more convenient for patients to take.     

壳聚糖对低密度脂蛋白和脂蛋白(a)代谢的影响

目的　研究壳聚糖对低密度脂蛋白和脂蛋白 (a)代谢的影响。方法　壳聚糖经剌猬腋下静脉注入 ,2min后给予12 5I标记低密度脂蛋白、12 5I标记脂蛋白 (a)、12 5I标记去唾液酸低密度脂蛋白或12 5I标记去唾液酸脂蛋白 (a) ,1h后处死动物 ,测定血、肝、肾、脾、胆汁和肾上腺中的放射性含量。结果　实验发现肝对去唾液酸低密度脂蛋白和去唾液酸脂蛋白 (a)摄入均增加 ,但去唾液酸低密度脂蛋白被肝重新利用释放入血 ,而去唾液酸脂蛋白 (a)被大部分排出体外。由于肾和肾上腺亦能增加对去唾液酸低密度脂蛋白的摄取 ,因此不排除低密度脂蛋白受体参与去唾液酸低密度脂蛋白代谢 ,但去唾液酸脂蛋白 (a)和一部分去唾液酸低密度脂蛋白可能经去唾液酸脂蛋白相关受体代谢。壳聚糖能使肝和肾上腺对低密度脂蛋白的摄入增加 ,同时使血中低密度脂蛋白浓度降低 ,脾细胞对低密度脂蛋白的摄取也明显降低。结论　实验提示壳聚糖可能通过激活低密度脂蛋白受体起到降脂作用。     

Effect of ezetimibe monotherapy on the concentration of lipoprotein subfractions in patients with primary dyslipidaemia

ABSTRACT

Background: Recent studies suggest that the distribution of lipoprotein subfractions is an independent predictor of vascular events. Therefore, we evaluated the effect of ezetimibe (a selective cholesterol transport inhibitor) on the concentrations of lipoprotein subfractions in patients with primary dyslipidaemia.

Materials and methods: Patients (n = 50) with primary dyslipidaemias were recruited. The concentrations of the individual lipoprotein subfractions were measured using the Lipoprint system at baseline and after 16 weeks of treatment.

Results: Ezetimibe reduced total, low-density lipoprotein cholesterol (LDL?C) and non-high-density lipoprotein cholesterol (HDL?C) values as well as apolipoprotein B concentrations. Subfractionation of apolipoprotein B-containing lipoproteins showed that the reduction in LDL?C values was due to a fall in the concentrations of all LDL subfractions. However, a more pronounced trend towards a decrease in the concen­trations of dense LDL subfractions was observed. Patients with triglyceride values >1.7?mmol/L had significantly greater reductions in the concentrations of small, dense LDL particles compared with those with normal triglyceride levels (49 vs. 19%, respectively; p < 0.05). Ezetimibe decreased the concentrations of HDL?C mainly due to a fall in the concentration of dense HDL subfractions.

Conclusion: Ezetimibe can favourably affect the distribution of LDL subfractions, especially in patients with elevated triglyceride values. Further studies are needed to clarify the significance of the ezetimibe-induced reduction in the concentrations of dense HDL particles.     

Efficacy and safety of high dose fluvastatin in patients with familial hypercholesterolaemia

Summary The efficacy and safety of the HMG CoA reductase inhibitor fluvastatin have been evaluated in a double blind study in 52 patients with familial hypercholesterolaemia. A standard AHA Phase II lipid lowering diet was prescribed throughout the study. After 6 weeks of a single blind dosage stabilisation period, in which patients received fluvastatin 40 mg qPM, patients were randomly allocated to one of two double blind treatment groups: group A (n=24) received fluvastatin 20 mg b. d. for 12 weeks and fluvastatin 20 mg AM + 40 mg PM for an additional 12 weeks; Group B (n=28) received fluvastatin 40 mg qPM during the entire study. Safety and tolerability were evaluated by the analysis of biochemical and haematological parameters, and ophthalmological and physical examinations. Efficacy was analysed by the determination of plasma lipids, lipoproteins and apoproteins.Fluvastatin 40 mg/d was associated with up to a 27.4% decrease in LDL-C and a 9.6% increase in HDL-C concentrations. Increasing the dose of fluvastatin from 20 mg b. d. to 60 mg per day in Group A was associated with a 7.1% decrease in LDL-C, a 12.1% increase of HDL-C and a 12.8% decrease in the LDL-C/HDL-C ratio. In comparison with Group B (40 mg qPM) LDL-C, HDL-C and the LDL-C/HDL-C ratio in Group A (60 mg) differed by –8.9%, 6.6% and –12%, respectively. During treatment with 40 mg qPM, one patient developed an asymptomatic but notable elevation of CK to 1823 U/l (normal range 0–100 U/l) that was caused by strenuous exercise. No other notable biochemical or haematological abnormalities were recorded.It is concluded that in patients with heterozygous FH the increase of fluvastatin from 40 to 60 mg/d provided an additional significant effect on plasma LDL-C and HDL-C levels and in the LDL-C/HDL-C ratio, without producing any deleterious effect.     

铬(Ⅲ)配合物治疗高脂蛋白血症95例

本文报道用铬(Ⅲ)配合物治疗各型高脂蛋白血症95例的临床疗效。采用自身单盲前后对照观察,先服安慰剂1.5mo,继服本药5mg bid 1.5mo。血清总胆固醇增高者42例,治疗后平均下降0.7mmol/1,总有效率65％。甘油三酯增高者89例,平均下降1.4 mmol/1,总有效率74％。治疗后各项血脂水平改变与服安慰剂后相比有非常显著性差异(P<0.01)。治前同时血糖增高者,亦有明显下降,平均下降0.74 mmol/1。血液流变学指标亦有不同程度的改善。治疗中未发现有毒副反应。本药为一种治疗脂质及糖代谢紊乱的有效药物,值得进一步研究。     

Effect of simvastatin on plasma lipids,apolipoproteins and lipoprotein particles in patients with primary hypercholesterolaemia

Summary The effect of treatment with simvastatin, a new HMG-CoA reductase inhibitor, has been investigated in 27 patients with primary hypercholesterolaemia.It produced a significant decrease of cholesterol and phospholipids in plasma, LDL and apolipoprotein B-containing lipoproteins. Plasma apolipoproteins B, C-III and E were also significantly lowered. The concentration of lipoprotein particles recognized by monoclonal antibodies (BL₃, BL₅ and BL₇), associated with atherosclerotic disease, was also lowered by the treatment.Lipoproteins LpA-II:A-I were not changed, while LpA-I, which has been suggested to be the protective fraction of the apo A-I-containing lipoproteins, was slightly and inconsistently increased.     

Long-term safety,tolerability and efficacy of combination therapy with aliskiren and amlodipine in patients with hypertension

ABSTRACT

Background: The National Institute for Health and Clinical Excellence (NICE) has been widely recognised as setting an international standard for high-quality health technology assessments (HTAs) including economic evaluation.

Scope: A previous critical analysis of NICE Technology Appraisal No. 98 (TA98), evaluating methylphenidate, dexamphetamine and atomoxetine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, revealed a number of issues, which must cast doubt on the robustness of the NICE approach when addressing a complex clinical decision problem. The exploration of potential underlying problems will be followed by a discussion of lessons for international healthcare policy-makers, and is intended to be an invitation to further debate and inquiry, not a presentation of definitive conclusions.

Symptoms: Pertaining to the technology assessment report, potential problems were identified relating to an unnecessarily narrow scope, data search and selection strategy, the distinction between efficacy and effectiveness, data synthesis across studies and clinical effect measures, and limitations of the economic model. The appraisal process moderated the asserted ‘clear conclusions’ of the assessment but could not compensate for some of its gaps.

Conclusions: It is suggested that key issues contributing to these problems may have included a separation of clinical and economic perspectives, a highly standardised reference case analysis that was followed schematically, the absence of an effective system for quality assurance of technology assessments, and transparency deficits of the economic evaluation. Further considerations for international policy-makers looking at NICE as a potential role model for HTAs are discussed, such as institutional context, the objectives of collectively financed healthcare and related value judgments, the reliance on QALYs as a universal and comprehensive measure of health benefits, the appropriate perspective for analysis, and process-related implications.     

Influence of hydrochlorothiazide on the plasma levels of triglycerides,total cholesterol and HDL-cholesterol in patients with essential hypertension

Summary

The influence of hydrochlorothiazide (HCT) treatment on the plasma levels of triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL-cholesterol) was studied in lo patients with essential hypertension. After a placebo period of 4 weeks, 50?mg HCT twice daily was given for a period of 9 months, followed by a second placebo period of 4 weeks. Triglycerides, total cholesterol and HDL-cholesterol were determined at the end of both placebo periods and after 1, 3, 6 and 9 months of HCT. For the whole group, there were no significant changes in triglycerides or HDL-cholesterol, whereas total cholesterol significantly increased during HCT. In 6 patients, plasma triglycerides were higher during HCT as compared to both placebo periods. In only 4 patients did HDL-cholesterol increase during HCT. Changes in triglycerides, total cholesterol and HDL-cholesterol were not related and no correlation was found with changes in blood pressure, body weight or serum potassium. In conclusion, this study confirms a possible adverse effect of diuretic treatment on plasma lipids, which should be considered when determining therapeutic regimens for hypertension.     

Lack of primary effect of sulphonylurea (glipizide) on plasma lipoproteins and insulin action in former Type 2 diabetics with attenuated insulin secretion

Summary A double-blind, placebo-controlled investigation has been made into the effects of 8 weeks of glipizide treatment in diabetics previously classified as Type 2 but with subsequent attenuation of insulin secretion and thence maintained on exogenous insulin.Although all patients were exposed to therapeutic plasma concentrations of glipizide, fasting blood glucose, haemoglobin A₁ and plasma lipoproteins (HDL, LDL, total cholesterol and triglycerides) did not show any consistent improvement following this treatment.It appears unlikely that SU (glipizide) has any primary effect on insulin action or on plasma lipoproteins. Its primary action is to augment insulin release and availability, so, its use should be restricted to Type 2 diabetics who retain insulin secretion.     

Decreased biliary excretion of tributylmethyl ammonium in cholestyramine pretreated rats due to reduced formation of ion-pair complexes with hepatic bile salts

The hypothesis that higher molecular weight (MW) quaternary ammoniums (QAs) form lipophilic ion-pair complexes with bile salts in the liver, and are subsequently excreted into bile via a canalicular transporter, P-gp, was re-examined in the present study for its validity. The biliary excretion of tributylmethyl ammonium (TBuMA), a QA with a MW of 200, in bile salt-depleted rats was determined. Depletion was induced by a daily oral administration of a resin, cholestyramine, at a dose of 0.5 g/kg for 2 consecutive weeks, which decreased the concentration of total bile salts in the liver by 38%. When TBuMA was administered intravenously (12 micromol/kg) to these rats, the plasma level, area under the plasma concentration-time curve (AUC), systemic clearance (CL) and volume of distribution (V(ss)) of the compound remained unchanged, whereas bile flow (23.03 vs 16.94 microl/min, p<0.05) and biliary clearance (CL(bile), 12.75 vs 5.34 ml/min/kg, p<0.01) were decreased significantly. These results implied the biliary clearance of TBuMA in rats with bile salt depletion was significantly decreased as a result of decreased ion-pair complexation of TBuMA. The above results are consistent with our hypothesis and the existence of a MW threshold (i.e. 200+/-50 for rats) for the biliary excretion of QAs.     

Effects of pravastatin on plasma and urinary mevalonate concentrations in subjects with familial hypercholesterolaemia: a comparison of morning and evening administration

In order to determine whether there is a difference in the effect of the hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin on cholesterol synthesis between the morning and the evening, we studied the 24-h profile of mevalonate in plasma and urine in 11 subjects with heterozygous familial hypercholesterolaemia. In study 1, eight subjects with familial hypercholesterolaemia took pravastatin (20 mg) once in the morning, and another 20-mg dose in the evening after a 1-week wash-out period. In study 2, five subjects with familial hypercholesterolaemia took pravastatin (20 mg per day) in the morning on 3 consecutive days and on 3 days in the evening after a 1 day wash-out. Plasma mevalonate concentrations were reduced at 9 h and 5 h after pravastatin administration in the morning and the evening, respectively. Urinary mevalonate excretion was significantly reduced at 4–8 h after pravastatin administration in the morning (51 vs 19 nmol · h^–1) and at 4–16 h after pravastatin administration in the evening (56 vs 27 nmol · h^–1). Daily urinary mevalonate excretion was equally and significantly reduced by pravastatin in the morning or evening. In conclusion, we found that morning and evening administration of pravastatin caused equal reductions in plasma and urinary mevalonate concentrations.     

Anti-inflammatory and hypolipemic effects in vitro of simvastatin comparing to epicatechin in patients with type-2 hypercholesterolemia

Objective

The study involved 25 patients with type-2 hypercholesterolemia (mean age 49.3 ± 11.3). The control group consisted of 28 healthy individuals (mean age 50.7 ± 7.2).

Methods

The cholesterol concentrations in plasma membranes of erythrocytes were measured by means of Liebermann-Burchard reagent. The membrane lipid peroxidation in whole erythrocytes was determined. The membrane fluidity was estimated by spin labelled method.

Results

The in vitro study shows that the cholesterol concentration in membranes incubated with simvastatin and epicatechin decreases; in healthy donors there are no changes. Simvastatin does not lead to changes in the lipid peroxidation in the in vitro data. Epicatechin decreases the level of membrane lipid peroxidation in patients with hypercholesterolemia and in healthy donors. Simvastatin and epicatechin cause an increase in the fluidity of plasma membranes of erythrocytes.

Conclusions

Simvastatin causes the decrease in cholesterol concentration in erythrocytes membranes not only in the in vivo but also the in vitro experiments. Flavonoids have antioxidant properties in vitro. Simvastatin influences the lipid peroxidation only in vivo, not in vitro systems. This observation is an additional contribution to the statins’ pleiotropic effect.     

Mixed treatment comparison of efficacy and tolerability of biologic agents in patients with rheumatoid arthritis

Abstract

Objective:

To determine the comparative efficacy and tolerability of abatacept and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and inadequate response to conventional disease modifying anti-rheumatic drugs (DMARDs).     

贝派地酸在血脂异常和他汀类药物不耐受患者中的应用进展

血浆低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)升高是公认的动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease,ACSVD)的危险因素之一.目前用于治疗高LDL-C血症的主要药物为他汀类药物,其他可选药物包括...     

The efficacy and tolerability of atenolol,nifedipine, and their combination in the management of hypertension

Summary In this randomized, double-blind, crossover study we investigated the haemodynamic effects of a beta-blocker (atenolol 50 mg) and a calcium antagonist (nifedipine SR 20 mg) given either separately or in combination in three groups of hypertensive patients. Each treatment was administered twice daily.The fixed combination given twice daily for four weeks produced reductions in blood pressure which lasted for at least 12 h after administration of the last dose. The control of blood pressure by the combination was superior to that achieved by its individual components.Adverse effects normally associated with nifedipine were less frequent when it was given with atenolol. Compliance with treatment was good, but best when the drugs were given together rather than separately.A fixed combination of atenolol and nifedipine may prove useful in treating hypertensive patients inadequately controlled on beta-blocker therapy alone.     

Antitumor efficacy of liposome-encapsulated NVP-BEZ 235 in combination with irreversible electroporation

Irreversible electroporation (IRE) is an emerging minimally invasive tumor ablation technique that delivers short pulses of strong electric fields and kills cancer cells by disrupting their cell membranes with the electric pulses. However, clinical studies report that more than 10% of local tumor recurrences occur at the original ablated site. NVP BEZ-235 (BEZ) is a dual PI3K/mTOR inhibitor that has substantial anticancer effects. However, the clinical trials of BEZ was not satisfactory because of its low bioavailability and high toxicity, which stemmed from the use of oral administration of high doses over a long period of time. In this research, we prepared a liposomal formulation of BEZ (L-BEZ) for intratumoral injection and studied its antitumor efficacy alone and in combination with IRE. We hypothesized that IRE could release BEZ from the liposomes and that the combination could decrease tumor viability. Our results show that IRE released BEZ from its liposomal encapsulation. The combination of L-BEZ and IRE killed more Hep3B tumor cells in vitro than did L-BEZ or IRE alone and also inhibited cancer cell proliferation in nude mice bearing Hep3B xenografts. Combination of chemotherapeutic agent loaded nanoparticles could enhance the antitumor efficacy of IRE.