Effect of melatonin on serum lipids in patients with hypercholesterolemia: a pilot study.

BACKGROUND: Indirect evidence suggests that melatonin may lower serum cholesterol. We undertook a pilot study to assess the effect of melatonin on serum lipids in patients with hypercholesterolemia. METHODS: Patients with a low-density lipoprotein (LDL) level greater than 160 mg/dL despite a 3-month trial of a low-fat diet were enrolled. Patients were randomized in a single-blind, cross-over fashion to receive placebo, 0.3 mg melatonin, or 3 mg melatonin at bedtime for 6 weeks. Serum lipids (total cholesterol, triglycerides, high-density lipoprotein, LDL) were obtained at baseline and after each treatment arm. The means of the lipid components were compared between placebo and each active treatment arm. Statistical analysis was performed using repeated-measures analysis of variance. RESULTS: Twenty-one patients were enrolled in the study. Five patients dropped out of the study, two because of side effects to melatonin and three because of protocol violations. There was no statistically significant difference in lipid components between placebo and both melatonin doses. There was a trend toward a decreased total cholesterol and LDL with the 3-mg dosage. Three patients had significant decreases in LDL on 3 mg melatonin. CONCLUSION: At the dosage studied, melatonin had no uniform effect on serum lipids in patients with hypercholesterolemia.     

Effect of combining viscous fibre with lovastatin on serum lipids in normal human subjects

OBJECTIVES: Soluble fibre supplements are recommended to reduce the levels of low-density lipoprotein cholesterol (LDL-C). Limited information exists on the interaction between fibre and hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). The purpose of the present study was to evaluate the per se effect of psyllium (10 g/day) and lovastatin (20 mg/day) alone and in combination on serum lipids in normal human volunteers. METHODS: In a 4-week open label, randomised, parallel study, subjects were randomised to receive 20 mg of lovastatin, 10 g of psyllium or 20 mg of lovastatin plus 10 g of psyllium in evening daily. Levels of total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), TC/LDL-C ratio, LDL-C/HDL-C ratio and triglycerides were determined after 1, 2, 3 and 4 weeks of treatment. RESULTS: The study group comprised 36 adult, male subjects. All treatments were well tolerated, and after 4 weeks the mean LDL-C, TC and TG levels in the group receiving 20 mg of lovastatin plus 10 g of psyllium fell by 30.88%, 26.88% and 26.21% from baseline, compared with 24.78%, 19.55% and 32.88% in the group receiving 20 mg of lovastatin and 3.58%, 2.90% and 10.95% in the group receiving 10 g of psyllium respectively. Although additive effect was observed in the group receiving combination compared with group receiving lovastatin, the observed difference was not statistically significant. No significant changes from baseline in HDL-C levels occurred. CONCLUSIONS: Psyllium soluble fibre should be considered as a safe and well-tolerated dietary supplement option to enhance cholesterol lowering.     

Effect of cyclosporin A on serum lipids in primary biliary cirrhosis patients

Hyperlipidemia is a common complication of PBC. Ten patients with serologically and histologically defined PBC were randomized to receive either oral cyclosporin A (CyA) or placebo for one year. Fasting blood samples were obtained from subjects at the beginning, and following one year of treatment, for plasma lipids, apolipoproteins AI (apo AI) and B (apo B), and lecithin-cholesterol acyltransferase (LCAT) activity. On entry to the study there were no significant differences between groups for serum concentrations of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), free cholesterol (FC), total phospholipids (TPL), apo AI, apo B and LCAT activity. Compared to normal laboratory values, baseline TC was elevated in 5/10, LDL-C in 5/10, TPL in 6/10, while LCAT activity was decreased in 8/10 patients. The percent change after one year for CyA group vs the placebo group are as follows: total cholesterol, -22 vs -8%; LDL cholesterol -33 vs -25%; free cholesterol, -39 vs -14%; total phospholipids, -46 vs -23%; and LCAT activity, +/- 236 vs +/- 43%. The decrease in TC, LDL-C, FC, TPL with increase in LCAT activity suggests that CyA administration is associated with improvement in the lipid abnormalities of PBC.     

Regression of tendon xanthomas in patients with familial hypercholesterolemia treated with lovastatin

Plasma concentrations of total and low-density lipoprotein cholesterol are increased twofold to threefold in patients with heterozygous familial hypercholesterolemia. This sustained increase leads to accelerated rates of cholesterol deposition in the coronary arteries and to the development of tendon xanthomas. To assess whether hypolipidemic therapy with lovastatin, alone and in combination therapy with colestipol hydrochloride or nicotinic acid, results in regression of lipid deposits in the tendons of these patients, we have measured Achilles tendon diameters by xeroradiography before and after treatment. In 20 patients treated for a mean of 43 months (during which time plasma cholesterol concentrations decreased from 430 to 247 mg/dL), the diameter of both the left and right Achilles tendons measured at three different locations decreased by 0.55 to 1.5 mm. Larger reductions were seen in the tendons of seven of these patients who were treated for a mean of 64 months and whose mean concentrations of cholesterol fell from 488 to 279 mg/dL. We conclude that effective long-term hypolipidemic therapy leads to diminution in the size of Achilles tendon xanthomas in patients with heterozygous familial hypercholesterolemia and that such therapy is associated with mobilization of tissue stores of cholesterol in these patients.     

Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia

3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitors are widely used to decrease plasma cholesterol levels in patients with heterozygous familial hypercholesterolemia (FH) who are at increased risk of premature coronary artery disease. Tissue-culture and animal studies have indicated that administration of HMG CoA reductase inhibitors (eg, lovastatin, simvastatin, etc) induces a compensatory increase in the activity of HMG CoA reductase, both by increasing its synthesis and decreasing catabolism. To determine in human subjects whether cessation of therapy with this class of drugs leads to induction of HMG CoA reductase activity and above-normal rates of cholesterol biosynthesis, we measured urinary concentrations of mevalonic acid (an indicator of cholesterol biosynthesis) after the cessation of therapy with lovastatin and simvastatin (80 mg/day) in patients with heterozygous FH. Plasma concentrations of LDL increased promptly on discontinuation of reductase inhibitor therapy but did not increase above pretreatment levels at any point after drug discontinuation. Similarly, the 24-hour urinary excretion of mevalonic acid was reduced during treatment with lovastatin or simvastatin and increased promptly on discontinuation of drug but did not increase to levels exceeding those found at baseline when the patients were receiving dietary therapy only. We conclude that cessation of treatment with HMG CoA reductase inhibitors in patients with FH does not result in a rebound increase in cholesterol biosynthesis and that no rebound overshoot occurs in plasma concentrations of low-density-lipoprotein cholesterol.     

Low-dose effect of simvastatin (MK-733) on serum lipids, lipoproteins, and apolipoproteins in patients with hypercholesterolemia

The effects of simvastatin (MK-733), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum lipids, lipoproteins, and apolipoproteins were investigated in 29 patients (12 men, 17 women, aged 37 to 73) with moderate to severe hypercholesterolemia. It was given in doses of 2.5 mg/day for four months and 5 mg/day for the succeeding four months. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein (apo) B decreased by 18% (263 +/- 7 mg/dl to 216 +/- 7 mg/dl, P less than 0.01), 24% (180 +/- 7 mg/dl to 136 +/- 7 mg/dl, P less than 0.01), and 21% (133 +/- 4 mg/dl to 104 +/- 3 mg/dl, P less than 0.01), respectively, four months after treatment. Similar reductions (17%, 24%, and 23%, respectively, P less than 0.01) were observed at eight months. A significant reduction in triglyceride (TG) was observed (173 +/- 15 mg/dl to 136 +/- 11 mg/dl at eight months, P less than 0.01), as was a significant increase in serum high-density lipoprotein cholesterol (HDL-C) (48 +/- 2 mg/dl to 52 +/- 2 mg/dl at eight months, P less than 0.01). However, apo AI and apo AII remained unchanged. Atherogenic indices of (TC--HDL-C)/ HDL-C, LDL-C/HDL-C, and apo B/Apo AI ratios were significantly (P less than 0.01) reduced after treatment. No significant changes were observed in lipoprotein lipase, hepatic TG lipase, and lecithin: cholesterol acyltransferase (LCAT) activities. Simvastatin was well tolerated and no critical side effects were noted in the eight-month study period. These data indicate that simvastatin, even at a low dose of 2.5 to 5 mg daily, causes consistent reductions in serum TC, LDL-C, apo B, and TG, and a rise in HDL-C and antiatherogenic lipoproteins.     

Effect of lovastatin on lipoprotein fluidity in patients with hypercholesterolaemia.

Lovastatin was administered to six hypercholesterolaemic patients (mean plasma cholesterol 450 mg dl-1). Plasma lipoproteins (VLDL, LDL, and HDL) were separated before and following 7 and 12 weeks treatment with lovastatin. Fluidity was quantified by fluorescence polarization measurements using 1,6-diphenyl 1,3,5 hexatriene (DPH) as the fluorescent probe. Lovastatin treatment resulted in a significant reduction of total plasma cholesterol, LDL cholesterol and VLDL cholesterol (-41%, -44%, -68%, respectively). Fluidity measurements showed significant (p < 0.01) increase in LDL fluidity by 11% and 21% after 7 and 12 weeks of lovastatin treatment, whereas, VLDL fluidity was increased by 27% after 12 weeks of therapy. HDL fluidity was not altered. These alterations in the fluidity of the atherogenic lipoproteins (LDL and VLDL) in hypercholesterolaemic patients may prove to be of significance in reducing the risk of atherosclerosis.     

Effects of lovastatin and gemfibrozil on high-density lipoprotein subfraction density and composition in patients with familial hypercholesterolemia.

The effects of gemfibrozil and lovastatin treatment on composition and hydrated density distribution of high-density lipoprotein (HDL) were studied in 21 patients with heterozygous familial hypercholesterolemia with the use of HDL density gradient ultracentrifugation. At baseline the patients with familial hypercholesterolemia had a markedly reduced or missing HDL2 subfraction and their HDL3 was more dense with reduced content of cholesteryl ester and increased content of triglyceride compared with HDL of control subjects with normal lipid values. Gemfibrozil and lovastatin caused primarily similar alterations in HDL components in HDL2 and HDL3 subfractions. Both agents increased apolipoprotein AI and apolipoprotein AII concentrations significantly in HDL2, whereas the apolipoprotein changes in HDL3 were relatively smaller. The difference between the effects of these two agents was related to the HDL lipid composition. Gemfibrozil increased the cholesterol concentrations of HDL2 and HDL3 (p less than 0.05 for both), and lovastatin caused significant increases in HDL2 (p less than 0.05) and HDL3 phospholipids (p less than 0.01). The observed similarity of qualitative alterations in HDL subfractions produced by these two agents in patients with familial hypercholesterolemia differs from those reported in other types of hyperlipidemia and is probably a consequence of the basic abnormalities in HDL that are characteristic of familial hypercholesterolemia.     

银屑病患者血脂水平分析

目的研究银屑病患者脂代谢紊乱情况,分析不同类型银屑病患者血脂变化特点。方法将332例银屑病患者按临床表现分为脓疱型、寻常型及红皮病型,比较各组间的血脂水平。结果与对照组比较,银屑病组总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(ApoA1)水平较低,差异有统计学意义(P0.05),脂蛋白[Lp(a)]水平较高,差异有统计学意义(P0.05);脓疱型银屑病型与寻常型、红皮病型相比,血清TC、HDL-C、LDL-C及ApoA1均较低,差异有统计学意义(P0.05)。结论银屑病患者体内存在脂代谢紊乱,且其紊乱严重情况可能与疾病类型有关。     

芎芍胶囊对颈动脉粥样硬化患者血脂和同型半胱氨酸水平的影响

[目的]探讨芎芍胶囊对颈动脉粥样硬化患者之血脂、同型半胱氨酸的水平的影响。[方法]依据病例选择标准及中国中西医结合学会活血化瘀专业委员会制定的血瘀证诊断标准。选择我院40例患者，随机分为两组：芎芍组、普罗布考对照组各20例。治疗前后分别测试：TC、TG、HDL-C、LDL-C、VLDL-C及apoA1、apoB，HCy浓度。[结果]两组患者治疗后TC、TG、LDL-C均较治疗前明显降低，组间比较无明显差异。芎芍胶囊组治疗后TC／HDL-C明显降低（P〈0．05），普罗布考组无明显改变。芎芍胶囊组治疗后ApoB、ApoB／ApoA1明显降低（P〈0．01），普罗布考组仅见ApoB降低（P〈0．05）。芎芍胶囊治疗后血浆HCy有所下降，但无统计学意义（P〉0．05），普罗布考组HCy无明显变化（P〉0．05）。[结论]芎芍胶囊可明显降低AS患者的TC、TG、LDL-C及载脂蛋白ApoB、ApoB／ApoA水平，但对HCy降低不显著，说明芎芍胶囊对AS斑块的消减作用、改善AS患者血管重构作用等与HCy水平无关，可能与降低血脂、升高CGRP水平及抑制血小板聚集、改善内皮细胞功能等有关。     

辛伐他汀对高胆固醇血症患者动脉弹性的影响

目的探讨辛伐他汀对高胆固醇血症患者动脉弹性的影响。方法采用动脉弹性功能测定仪检测52例高胆固醇血症患者使用辛伐他汀前和使用4周后大动脉弹性（C1）、小动脉弹性（C2）和血浆总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）。结果用药4周后，TC和LDL-C均较用药前明显下降（均为P〈0．01），C1和C2较用药前明显升高（均为P〈0．01）。结论辛伐他汀可明显降低高胆固醇血症患者TC和LDL-C，同时显著改善动脉弹性。     

Association between ischemia-modified albumin,lipids and inflammation biomarkers in patients with hypercholesterolemia

ObjectivesThe aim of this study was to evaluate the association between ischemia-modified albumin (IMA), lipids and inflammation biomarkers in patients with hypercholesterolemia, and the possible involvement of IMA in atheromatous plaque development and oxidative stress.Design and methodsGlucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, oxidized LDL (ox-LDL), ox-LDL autoantibodies, high-sensitivity C reactive protein (hs-CRP), and IMA were measured in 37 subjects with hypercholesterolemia and 37 controls.ResultsTotal cholesterol, LDL cholesterol, triglycerides, ox-LDL, ox-LDL autoantibodies, hs-CRP, and IMA were higher in the hypercholesterolemia group, and HDL cholesterol levels were lower in this group. We observed significant correlations between IMA and total cholesterol, LDL cholesterol, ox-LDL antibodies, and hs-CRP levels. Significant correlations were also observed between hs-CRP and total cholesterol, HDL cholesterol, LDL cholesterol, ox-LDL, ox-LDL autoantibodies, and triglycerides.ConclusionsHypercholesterolemia is associated with an increase in inflammatory and oxidative stress biomarkers, and it also reduces the capacity of albumin to bind cobalt owing to ischemia, resulting in an increased IMA. IMA formation appears to be associated with oxidative stress and atheromatous plaque development.     

Peroxidation of serum lipids in patients with breast cancer

Parameters of chemiluminescence of lipid peroxidation (LP), induced by hydrogen peroxide in the blood serum of oncology patients (n = 60), were examined in the process of their combined therapy. During the dynamic observations, complete correlations were found between the peculiarities of manifestations and of the clinical course of the tumor process, the level of free-radical LP and the antioxidants of blood serum. A comprehensive assessment of all mentioned indices can be used to monitor the efficiency of a conducted therapy.     

Cardiovascular effects of acute hypercholesterolemia in rabbits. Reversal with lovastatin treatment.

Hypercholesterolemia was induced in New Zealand white rabbits by feeding them a 0.5% cholesterol-enriched rabbit chow for 2 wk. Half of the cholesterol-fed rabbits were given lovastatin, a potent inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate limiting enzyme in cholesterol biosynthesis, and the other half were given its vehicle (i.e., DMSO). At the end of 2 wk, the rabbits underwent experimental myocardial ischemia or a sham ischemia procedure. Ischemic animals fed the cholesterol-enriched diet for 2 wk experienced much greater cardiac damage than ischemic rabbits fed the control diet, despite the absence of any atherosclerosis. Lovastatin was shown to protect the ischemic rabbit myocardium by three different indices of ischemic damage: (a) maintenance of creatine kinase (CK) activity in the ischemic myocardium; (b) reduced loss of free amino-nitrogen containing compounds from the ischemic myocardium; and (c) blunting the rise of plasma CK activity. These effects were not due to differences in myocardial oxygen demand between the groups. Arteries isolated from animals fed the cholesterol-enriched diet developed defects in endothelium-dependent relaxation in both large vessels as well as coronary resistance vessels. Acute hypercholesterolemia increases the severity of myocardial ischemia while at the same time impairing endothelium-dependent relaxation. These deleterious changes can be significantly attenuated by treatment with lovastatin.     

Niacin-ER and lovastatin treatment of hypercholesterolemia and mixed dyslipidemia

OBJECTIVE: To review the currently available information on the once-daily combination of niacin extended-release (ER)/lovastatin in the treatment of patients with hypercholesterolemia and mixed dyslipidemia at high risk for cardiovascular events. DATA SOURCES: MEDLINE (1966-July 2002) was searched for primary and review articles. Data from the manufacturer were also included. STUDY SELECTION/DATA EXTRACTION: All articles and product labeling deemed relevant to the combination of niacin and statins (i.e., lovastatin) were included for review. English-language studies selected for inclusion were limited to those with human subjects. DATA SYNTHESIS: The Food and Drug Administration approved a new fixed-dose combination of niacin-ER/lovastatin, which is administered once daily. The efficacy and safety of the combined agent have been proven to be similar to either component used alone or in combination for management of hyperlipidemia and mixed dyslipidemia. CONCLUSIONS: Elevated low-density lipoprotein cholesterol (LDL-C) is independently associated with a higher risk for cardiovascular events. Lowering of elevated LDL-C concentrations with statin monotherapy may be insufficient in patients at high risk for cardiovascular events. In fact, consideration of elevated triglycerides (TGs) and/or low concentrations of high-density lipoprotein cholesterol (HDL-C) in patients with elevated LDL-C places them at greater risk. The addition of niacin may enhance or improve the lipid profile of those who require a further decrease of TGs and/or increase of HDL-C even after stable statin therapy. Niacin-ER offers efficacy similar to that of immediate-release niacin, but minimal myopathy and hepatotoxicity (compared with sustained-release niacin). Although no clinical outcomes are available, current evidence shows that the combination product offers adequate lowering of LDL-C and TGs and increasing HDL-C. The data suggest that therapy with the niacin-ER and lovastatin combination product is safe and does not increase the incidence of adverse effects.