Effects of long-term treatment with metoprolol and hydrochlorothiazide on plasma lipids and lipoproteins

Abstract. In order to evaluate the effects of one-year antihypertensive treatment on plasma lipids and lipoproteins, 65 patients whose diastolic blood pressure was in the range 95-120 mmHg were randomly allocated to groups that received either hydrochlorothiazide or metoprolol, or both drugs when the response to one of them was insufficient to control blood pressure. Blood pressure was effectively reduced in all groups. Patients on hydrochlorothiazide showed a significant increase (P < 0.01) in low-density lipoprotein cholesterol (LDL-C) after 3 months of treatment. A significant increase in triglycerides was observed after 6 and 12 months, together with a decrease in high-density lipoprotein cholesterol (HDL-C) after 12 months (P < 0.05) of treatment in patients on metoprolol. In patients treated with both hydrochlorothiazide and metoprolol, total cholesterol increased after 3 (P < 0.001) and 6 months (P < 0.05), triglycerides increased after 6 (P < 0.01) and 12 months (P< 0.01), and LDL-C increased after 3 (P< 0.05), 6 (P < 0.001) and 12 months (P < 0.01) of treatment, respectively. In 61% of the patients, three or more lipid parameters were affected during the study period. We conclude that long-term antihypertensive treatment with hydrochlorothiazide, metoprolol, and particularly with both drugs, can induce lipid effects that deserve recognition, because in some cases these might counteract the possible benefit of a reduction in blood pressure on the prevention of coronary heart disease.     

Effects of rosuvastatin on lipids, lipoproteins and apolipoproteins in the dyslipidaemia of diabetes.

AIMS: To compare the effects of rosuvastatin and atorvastatin 10 and 20 mg on plasma lipid and lipoprotein profiles in patients with Type 2 diabetes mellitus and triglycerides < or = 6.0 mmol/l. METHODS: A double-blind, randomized, multicentre study to assess the effect of rosuvastatin and atorvastatin, at 10 mg/day for 8 weeks followed by 20 mg/day for a further 8 weeks, on low-density lipoprotein cholesterol (LDL-C), together with a range of secondary lipid and lipoprotein end points. RESULTS: Rosuvastatin reduced mean LDL-C levels from baseline over 16 weeks by 57.4%, while atorvastatin reduced mean LDL-C levels by 46.0% over the same period. The difference in LDL-C reduction between treatments was statistically significant (P < 0.001). Rosuvastatin also produced statistically significantly greater mean reductions from baseline in levels of total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B and lipid ratios. More patients achieved European LDL-C (< 2.5 mmol/l) and total cholesterol (< 4.5 mmol/l) goals with rosuvastatin than with atorvastatin. Rosuvastatin was associated with a significantly (P < 0.049) greater mean percentage increase in glycated haemoglobin (HbA(1c)) from baseline compared with atorvastatin; however, patients in both treatment groups maintained good glycaemic control. Both rosuvastatin and atorvastatin were well tolerated. CONCLUSIONS: Greater reductions in LDL-C were achieved with rosuvastatin compared with equal doses of atorvastatin, enabling more patients with Type 2 diabetes to achieve European LDL-C goals.     

Luminal loss and restenosis after coronary angioplasty. The role of lipoproteins and lipids.

AIMS: Lipoproteins and lipids, especially lipoprotein(a), have been studied as risk factors for restenosis after coronary angioplasty with conflicting results. We investigated the association between serum levels of lipoprotein(a) apolipoprotein A-1, apolipoprotein B-100, total-cholesterol, high density lipoprotein-cholesterol, triglycerides, and coronary luminal loss and restenosis after angioplasty.METHODS: The lipoproteins and lipids were measured in 305 consecutive patients who underwent successful angioplasty and reangiography 20+/-3 weeks after angioplasty. Single-vessel dilatation was performed in 251 patients. Luminal loss was defined as minimal luminal diameter post-angioplasty minus minimal luminal diameter at follow-up, divided by the interpolated reference diameter of the vessel. Restenosis was defined according to three dichotomous categorical criteria: (1) >50% diameter stenosis at follow-up (2) loss of >50% of the gain achieved by angioplasty, (3) the need for target vessel revascularization.RESULTS: There was no significant association between the serum levels of lipoproteins and lipids and luminal loss. Univariate analysis did not show any significant difference in the serum levels of any of the lipoproteins and lipids between the restenosis and no-restenosis groups. Multivariate analysis revealed that only the angiographic variables (luminal gain and post-angioplasty minimal luminal diameter) were associated with luminal loss and restenosis after angioplasty.CONCLUSION: Lipoproteins and lipids were neither associated with luminal loss nor independent risk factors for restenosis after angioplasty.     

阿托伐他汀对ApoE基因敲除小鼠血清白细胞三烯浓度及动脉粥样硬化斑块的影响

目的研究阿托伐他汀对ApoE（-/-）动脉硬化模型小鼠血清白细胞三烯浓度的影响,探讨阿托伐他汀的抗动脉硬化机制。方法将ApoE（-/-）小鼠分为对照组（n=12）、动脉硬化模型组（n=12）、阿托伐他汀干预组（n=12）。检测3组ApoE（-/-）小鼠血清的白细胞三烯B4和白细胞三烯D4浓度、测量主动脉斑块校正面积并进行比较。结果对照组主动脉未见动脉硬化病变;动脉硬化模型组建模成功,见不稳定斑块;阿托伐他汀干预组较动脉硬化模型组动脉硬化病变显著减轻,斑块校正面积显著下降,差异有统计学意义（13.24%±3.08%vs.29.08%±6.46%,P〈0.001）。动脉硬化模型组的血清白细胞三烯B4、白细胞三烯D4浓度显著高于对照组,差异有统计学意义[（34.79±4.47）ng.mL-1vs.（12.07±2.35）ng.mL-1,P〈0.001;（2 862.48±48.77）n.L-1vs.（2 357.10±53.57）ng.L-1,P〈0.001）]。阿托伐他汀干预组血清白细胞三烯B4、白细胞三烯D4浓度显著低于动脉硬化模型组,差异有统计学意义[（20.93±2.19）ng.mL-1vs.（34.79±4.47）ng.mL-1,P〈0.001;（2 592.06±22.45）ng.L-1vs.（2 862.48±48.77）ng.L-1,P〈0.001）]。结论阿托伐他汀可能通过降低血清白细胞三烯B4和白细胞三烯D4浓度,减轻炎症反应,稳定斑块,发挥抗动脉硬化作用。     

阿托伐他汀对血脂异常兔血清和脂肪细胞分泌肿瘤坏死因子-α的影响

目的观察阿托伐他汀干预对血脂异常兔血清及脂肪细胞分泌肿瘤坏死因子-α(TNF-α)的影响,并探讨其可能机制。方法10只新西兰大白兔给予高胆固醇饮食饲养8周后,随机分为高胆固醇组和阿托伐他汀组,每组5只。另选普通饮食12周兔5只作为对照组。12周末,取腹股沟皮下脂肪组织行脂肪细胞培养,酶联免疫吸附法检测血清及脂肪细胞培养液中TNF-α水平。半定量逆转录聚合酶链反应测定脂肪细胞TNF-αmRNA的表达。结果阿托伐他汀干预4周能明显降低血脂异常兔血清总胆固醇、低密度脂蛋白胆固醇、TNF-α水平和脂肪细胞TNF-αmRNA表达量(P<0.05)。阿托伐他汀呈剂量依赖性降低脂肪细胞TNF-α表达和分泌。结论阿托伐他汀降低血脂异常兔血清TNF-α水平,其机制可能与其调脂及抑制脂肪细胞TNF-α的分泌有关。     

雌-孕激素替代治疗对绝经后妇女血脂和脂蛋白代谢的长期作用

目的　观察雌 孕激素替代治疗 (HRT)对绝经后妇女血脂和脂蛋白代谢的长期作用。方法　 193例健康绝经后妇女分为A组 (高胆固醇血症组 ) 6 3例、B组 (无高胆固醇血症组 ) 6 0例和C组 (对照组 ) 70例 ,A、B组均给予倍美力 (天然结合型雌激素 ) 0 .6 2 5mg d +安宫黄体酮 2mg d治疗 ,连续 3年监测血清性激素、血脂及脂蛋白水平。结果A组总胆固醇 (TC) ,低密度脂蛋白胆固醇 (LDL C)水平分别下降 12 .1% (P <0 .0 1)、15 .7% (P <0 .0 1) ,B组LDL C下降 4 .5 % (P <0 .0 5 ) ,A、B组高密度脂蛋白胆固醇 (HDL C)水平均明显升高 ,分别为 15 .1% (P <0 .0 1)、2 5 .8% (P <0 .0 1) ,均在第 3个月就出现明显改变 ,并在服药期间可保持疗效 ,对照组则变化不明显。B组TC有下降趋势 ,各组甘油三酯 (TG)均有增高趋势 ,但差异均无显著性意义。A、B组血清 17 β雌二醇 (17 βE2 )和孕酮于第 3个月显著升高 ,血清卵泡刺激素、黄体生成素水平则于第 6个月明显下降 ,并在服药期间可保持疗效 ,而对照组变化不明显。结论　绝经后妇女HRT能改善血清TC、TG、LDL水平 ,并在服药期间可保持疗效 ,对具有高胆固醇血症者效果更佳     

Double-blind placebo-controlled study of the effects of bezafibrate on blood lipids, lipoproteins, and fibrinogen in hyperlipidaemic type 1 diabetes mellitus

The effects of bezafibrate 400 mg day-1 or placebo administered for 3 months, were compared in 36 patients with stable Type 1 diabetes and hypercholesterolaemia and/or hypertriglyceridaemia. Baseline characteristics of the 17 bezafibrate- and 19 placebo-treated patients were comparable in most respects with the exception of concentrations of fasting serum triglycerides and blood glucose which were lower (NS) and plasma fibrinogen which were higher (p less than 0.05), in those later treated with bezafibrate. Serum cholesterol concentrations decreased after 3 months bezafibrate treatment (from 7.1(0.2) (SE) to 6.3 (0.3) mmol l-1, p less than 0.05), predominantly due to a reduction in low density lipoprotein (LDL) cholesterol (from 4.8(0.3) to 4.2(0.3) mmol l-1, p less than 0.05). Over the same period bezafibrate reduced serum triglycerides from 1.78 (95% Cl 1.23-2.57) to 1.26(1.02-2.09) mmol l-1 (p less than 0.05), and plasma fibrinogen from 4.1(0.2) to 2.9(0.2) g l-1, p less than 0.001. Serum apolipoprotein B and apolipoprotein (a) showed no statistically significant changes. Overall there was no change in high density lipoprotein (HDL) cholesterol. However, in patients who were initially hypertriglyceridaemic there was significant increase in the cholesterol content of HDL and the HDL2-cholesterol subfraction (both p less than 0.05). After 3 months treatment with bezafibrate, fasting blood glucose levels were reduced from 8.5(1.1) to 6.4(0.7) mmol l-1, p less than 0.05, without any change in glycosylated haemoglobin (9.2(0.4) to 9.1(0.5)%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-density lipoproteins induce the polar secretion of PAI-1 by endothelial cells in culture

Patients with hypercholesterolemia and with coronary atherosclerosis have increased plasma levels of plasminogen activator inhibitor (PAI)-1. PAI-1 and low-density lipoproteins (LDL) are also present in the walls of atherosclerotic vessels, where they participate in the development and remodeling of the atherosclerotic plaques. We investigated the influence of LDL on the apical (luminal) and basolateral (subendothelial) secretion of PAI-1 by human umbilical vein endothelial cells in a two-compartment cell-culture model. Confluent cells were incubated with LDL either in the apical compartment or in the basal compartment. Cells incubated with culture medium served as controls. A significantly higher concentration of PAI-1 was found in both the apical (P = 0.025) and the basal compartment (P = 0.025) if cells were incubated with LDL on the basolateral side. In contrast, incubation of the cells with LDL apically resulted in an increased PAI-1 concentration only in the apical compartment (P = 0.028) and not in the basal compartment. Our findings indicate that the LDL particles that reach the subendothelial space can induce an increased release of PAI-1 by endothelial cells into the vessel lumen and also contribute to the release of PAI-1 into the subendothelial space and thus to the process of atherosclerotic plaque remodeling.     

阿托伐他汀治疗混合型高脂血症的疗效和安全性

目的　评估红惠医药发展公司生产的阿托伐他汀 (Atorvastatin)治疗高脂血症 ,特别是混合型高脂血症的疗效和安全性。方法　试验组 (阿托伐他汀 10mg d) 5 2例和对照组 (舒降之 10mg d) 5 3例 ,进行随机单盲平行对照试验 ,观察两组降脂疗效和不良反应发生情况。结果　经过 8周治疗 ,阿托伐他汀组TC、LDL C、TG和 (TC HDL C) HDL C分别下降 30 % ,40 % ,30 %和 36 % (P <0 .0 1) ,HDL C虽有升高 (5 % ) ,但差异无显著性意义 (P >0 .0 5 )。组间比较 ,阿托伐他汀降LDL C和TG作用明显优于辛伐他汀 (P <0 .0 5 ) ,降TC作用则两组相似。两组不良反应均很轻微和少见。结论　阿托伐他汀 10mg d治疗混合型高脂血症可以明显降低TC、LDL C ,TG和 (TC HDL C) HDL C ;阿托伐他汀降低LDL C和TG的作用大于同剂量辛伐他汀 ;阿托伐他汀的不良反应轻微 ,耐受性好。     

The effects of chlorpropamide and insulin on serum lipids,lipoproteins and fractional triglyceride removal

Summary The effects of chlorpropamide on serum lipids, lipoproteins and fractional triglyceride removal have been studied over 12 months on 10 maturity onset diabetics not controlled on diet alone. Similar studies were carried out in 6 maturity onset diabetics who had failed to respond to sulphonylureas and 6 new insulin requiring diabetics. In the chlorpropamide treated patients there was an initial fall in serum and VLDL triglyceride but this effect was lost at 12 months. There was no change in fractional triglyceride removal. At 12 months there was a fall in LDL and a rise in HDL cholesterol. An initial improvement in glucose tolerance and insulin secretion was maintained at 12 months.In the insulin treated group the initial fall in serum and VLDL triglyceride was maintained at 12 months and was accompanied by an increase in fractional triglyceride removal. There was also a fall in LDL and a rise in HDL cholesterol at 12 months.The failure of chlorpropamide to maintain the reduction in serum and VLDL triglyceride could be of importance in the genesis of coronary heart disease in maturity onset diabetics. The fall in LDL and rise in HDL cholesterol found both with chlorpropamide and insulin might be beneficial.     

A comparison between nicotinic acid and acipimox in hypertriglyceridaemia--effects on serum lipids, lipoproteins, glucose tolerance and tolerability

Serum and lipoprotein lipid levels, oral glucose tolerance and side-effects were compared in an open cross-over study of 31 non-diabetic patients with hypertriglyceridaemia (type II B and IV) before and after 6 weeks of treatment with nicotinic acid (3 g daily) and acipimox (0.75 g daily), a new nicotinic acid-like drug, respectively. Acipimox was about equally potent in reducing serum and VLDL lipid levels and in increasing HDL cholesterol levels. Acipimox had no significant negative effects on glucose metabolism measured by an oral glucose tolerance test compared with nicotinic acid, which decreased the late glucose tolerance as well as the area under the glucose curve (P less than 0.05 for the difference between the two treatments). The incidence and severity of flush or any other recorded side-effects was higher after nicotinic acid treatment than after acipimox. In addition, no effects on laboratory parameters such as liver enzymes and uric acid were seen after treatment with acipimox. The results of this study demonstrate that acipimox is a satisfactory alternative to nicotinic acid in patients with hypertriglyceridaemia.     

阿托伐他汀对高血压病血vWF及BNP影响的近期疗效观察

目的探讨不同剂量阿托伐他汀治疗对血管内皮功能及脑钠肽（BNP）水平的影响。方法在我院确诊的150例高血压病同时具有高脂血症患者随机分成A、B、C三组,分别接受10、20、40mg／d阿托伐他汀治疗4周。比较3组血脂水平、血管内皮功能相关指标血管性假性血友病因子（vWF）及BNP水平。结果与治疗前比较,不同剂量阿托伐他汀治疗组vWF及BNP水平均明显下降,C组明显低于A、B组（P〈0．01）,3组不良反应相似。结论阿托伐他汀降脂治疗可改善高血压病患者的内皮功能,40mg阿托伐他汀作用比较明显。     

血脂与冠状动脉病变关系的探讨

目的　探讨血脂水平与冠状动脉病变的关系。方法　 2 2 8例进行过选择性冠状动脉造影的住院冠心病病人按冠状动脉狭窄程度积分为正常组、单支组、双支组、三支组四组。测定和比较血脂各项指标 TC、TG、HDL、L DL、apo A1 、apo B1 0 0 、L p(a)。结果　 L p(a)、HDL、apo A1 / apo B1 0 0 在各组之间存在着差异。L p(a)随着冠状动脉病变程度加重而增高 ,apo A1 / apo B1 0 0 随着冠状动脉病变程度加重而减少。 HDL与冠状动脉积分呈负相关 ,L p(a)与冠状动脉积分呈正相关。结论　 HDL和 L p(a)对预测冠状动脉病变有重要意义     

参七脉心通胶囊对颈动脉硬化患者血清NO及ET的影响

目的观察参七脉心通胶囊对颈动脉硬化并高脂血症患者的血脂、血清一氧化氮（NO）、血浆内皮素（ET）水平的影响,进一步探讨参七脉心通胶囊抗动脉粥样硬化的机制。方法将70例高脂血症并颈动脉硬化患者随机分为参七脉心通胶囊中药组（中药组）及阿托伐他汀西药组（西药组）,每组35例,分别给予参七脉心通胶囊及阿托伐他汀口服治疗12周。于清晨空腹抽取服药前、服药后及停药2周后的静脉血,检测血总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、NO、ET水平。结果治疗12周后两组患者TC、TG、LDL及ET明显降低,血清NO及HDL水平明显升高,与治疗前相比显差异有统计学意义（P〈0.01）,其中西药组优于治疗组（P〈0.05）;停药2周后西药组所有患者TC、TG和LDL水平较治疗后升高,NO水平明显降低,与服药前无明显差异（P＞0.05）;而ET水平则明显回升,甚至高于服药前水平（P〈0.05）。在中药组却未出现这种趋势。结论参七脉心通胶囊对高脂血症并颈动脉硬化患者的血管内皮功能有明显保护作用,从而防治动脉硬化的进一步发展。     

普罗布考联合阿托伐他汀和阿司匹林治疗颈动脉粥样硬化的疗效

目的观察普罗布考、阿托伐他汀、阿司匹林联合应用（PAS疗法）对颈动脉粥样硬化症的疗效。方法入选73例经B超证实有颈动脉粥样硬化斑块的患者,随机分为PAS组和AS组,随访6个月。其中PAS组37例,给予普罗布考0．375g×2次／d、阿托伐他汀10mg／d、阿司匹林100mg／d;AS组36例,给予阿托伐他汀10mg／d、阿司匹林100mg／d。观察治疗前后患者的血脂水平、血清氧化型低密度脂蛋白（OX-LDL）及血清C反应蛋白（CRP）水平,超声检测治疗前后颈动脉内-中膜厚度（IMT）及斑块厚度。结果治疗前PAS组及AS组血脂、OX-LDLCRP、IMT及斑块厚度基线水平差异无统计学意义（P〉O．05）。治疗后PAS组及AS组以上指标均降低,差异有统计学意义（P〈0．05）;除TG和HDL-C外,PAS组较AS组降低更明显,差异有统计学意义（P〈0．05）。结论普罗布考联合阿托伐他汀和阿司匹林治疗在降低血脂的同时,可降低患者的ox-LDL及CRP水平,疗效较单纯阿托伐他汀和阿司匹林治疗明显,同时也可改善患者的IMT及斑块总积分;稳定颈动脉粥样硬化斑块需长期干预治疗及随访观察。     

Effect of exercise training and diet modification on serum lipids and lipoproteins in coronary artery disease patients treated with thiazides

The effects of chronic exercise training and diet modification on serum lipids and lipoproteins were measured in 17 hypertensive males and 41 normotensive males with documented coronary artery disease (CAD). Exercise consisted of aerobic activities which were performed at approximately 75-85% of the symptom-limited maximum heart rate for 30-40 minutes, three times weekly for 3 months. Each participant's diet was also controlled, the recommended daily intake of fat and cholesterol was no more than 40 g/day and 200 mg/day, respectively. Significant increases in estimated VO2max and total cholesterol/high density lipoprotein (HDL) and a significant decrease in serum triglycerides were documented after training. Significant differences in serum cholesterol and triglycerides between the nondiuretic and diuretic patients were also noted. No significant changes were found in low density lipoprotein (LDL), HDL, or body weight. Vigorous aerobic training and diet modification can favorably modify the deleterious effects of diuretic medications on serum triglycerides and total cholesterol/HDL in patients with documented CAD.     

Effects of serum and lipoproteins on steroidogenesis in cultured bovine luteal cells

The effects of serum and lipoproteins on the function of bovine luteal cells in tissue culture were examined. Corpora lutea from regularly cycling dairy cows were dissociated with collagenase and cultured in Ham's F-12 medium with or without serum. The serum-free medium was supplemented with insulin, transferrin and hydrocortisone. Addition of LH to the serum-containing medium did not increase progesterone (P4) production. When the luteal cells were cultured in serum-free medium. LH produced a dose-dependent increase (P less than 0.001) in P4 production during the first 24 h of culture. The responsiveness of the cells to LH then gradually declined, and remained low until days 9-11 of culture, at which time the cells regained their ability to respond to LH. The luteal cells were responsive to dibutyryl cAMP in both serum-containing and serum-free medium. Serum lipoproteins (low and high density) were able to produce a 150-260% increase in progesterone production by the luteal cells cultured in serum-free medium. The results indicate that the presence of serum in the cell culture medium inhibits the responsiveness of luteal cells to LH at a step prior to the increase in cellular cAMP, and that serum lipoproteins can be used to increase progesterone production by cultured bovine luteal cells.