Serum lipids and lipoproteins in ischaemic heart disease following withdrawal of long-term metroprolol treatment

Summary In 39 patients who had been treated with metoprolol 100–200 mg daily or placebo for three years after acute myocardial infarction, serum lipids and lipoproteins were studied while the patients were on treatment as well as after its withdrawal. Withdrawal was performed over 1 week. Treatment had to be reinstituted in 6 patients (1 ex placebo and 5 ex metoprolol) because of aggravated symptoms.During the entire study period total cholesterol was significantly higher in the metoprolol withdrawal group and LDL cholesterol tended to be higher. HDL cholesterol in both groups increased significantly during the initial 28-day period following withdrawal of treatment. In both groups VLDL triglycerides tended to decrease during the first 28 day without treatment. Other lipoprotein fractions in both groups were unchanged.Overall, in patients who tolerated the ending of 3 years of treatment with metoprolol after myocardial infarction, there was no significant effect on lipoprotein fractions as compared to a placebo group.     

Lipoprotein lipids and apoproteins during beta-blocker administration: Comparison of penbutolol and atenolol

Summary Serum lipoprotein lipid and apoprotein concentrations were determined in 21 hypertensive men during administration of two beta-blockers, penbutolol or atenolol, for 6 months preceded by a 4 week placebo period. Post-heparin plasma lipoprotein lipase and hepatic lipase activities were also measured.There was a trend to an increase of triglyceride and VLDL triglyceride concentrations during penbutolol administration, but the changes were not significant. Penbutolol also increased the total cholesterol by 11% at 3 months (mainly due to increase of VLDL cholesterol), but this effect diminished at 6 months.Atenolol did not cause any significant change in the total cholesterol but increased HDL cholesterol by 7% at 1 month, the change being due to rise of the HDL₃. The HDL₃ accounted also for a significant decrease of HDL cholesterol seen in the men receiving penbutolol at 6 months. HDL₂ cholesterol as well as the LDL/HDL₂ cholesterol ratio remained unchanged in both groups.Neither drug consistently influenced the post-heparin plasma lipase activities or the serum apoprotein A or B concentrations.In contrast to an earlier study the results suggest that the clinically most important HDL subfraction, the HDL₂, remains unaffected during treatment with beta-blockers.     

Effect of metoprolol and pindolol monotherapy on plasma lipid- and lipoprotein-cholesterol levels (including the HDL subclasses) in mild hypertensive males and females.

Forty-five patients with mild hypertension were treated for 2 months with either metoprolol or pindolol in a randomized, blind, crossover study. The effects of metoprolol (100-300 mg/day) and pindolol (5-15 mg/day) on triglyceride (TG), cholesterol (C), high-density lipoprotein cholesterol (HDL-C), and HDL subfraction (HDL2-C and HDL3-C) levels were compared in males and females separately. Pindolol and metoprolol significantly elevated (10% above baseline level) the plasma TG level in both males and females. After metoprolol treatment, the HDL-C level remained unchanged in both sexes; however, a shift was found between HDL2-C and HDL3-C:HDL2-C decreased and a concomitant elevation in HDL3-C was observed. Pindolol significantly decreased total C, HDL-C, and HDL2-C levels in males. A similar trend (although the changes were not significant) was found in females. The results demonstrate the role of beta blockers in the inhibition of TG-rich lipoprotein elimination. These findings suggest that during long-term administration of metoprolol and pindolol, risks and benefits from beta-blocker therapy must be carefully considered. Continuous monitoring of lipid profiles is suggested during this treatment in order to avoid the potential worsening effect of beta blockers on risk factors of ischemic heart disease.     

Blood lipid effects of antihypertensive therapy: a double-blind comparison of the effects of methyldopa and propranolol

Thirty-two middle-aged men with essential hypertension completed a double-blind randomly allocated comparison of the effects of methyldopa versus propranolol on blood lipid levels. After a four-week period on a placebo for each drug, subjects were titrated for the next six weeks with either methyldopa from 500 to 2000 mg/day or propranolol from 80 to 320 mg/day plus a placebo for the other drug until supine diastolic blood pressure was below 90 mm Hg or the ceiling dose was reached. Subjects were then maintained on the achieved drug dose for an additional six weeks and finally switched back to a placebo for each drug for four more weeks. Blood lipid levels were measured twice during each study period and the values averaged and compared. Neither drug significantly affected levels of total plasma cholesterol. However, both drugs reduced high-density lipoprotein (HDL) cholesterol levels about 10 per cent and increased the total cholesterol to HDL cholesterol ratio. In addition, propranolol significantly increased plasma triglyceride levels (28.3 per cent). The changes in lipid levels were not dose related. Whether or not these blood lipid changes persist and their possible clinical implication during prolonged therapy remain to be elucidated.     

Effects of gemfibrozil and other fibric acid derivatives on blood lipids and lipoproteins

Fibric acid derivatives (FADs) are a class of drugs that have been shown to reduce the production of very low-density lipoprotein (VLDL) while enhancing VLDL clearance due to the stimulation of lipoprotein lipase activity. The drugs can reduce plasma triglyceride levels while raising high-density lipoprotein (HDL) cholesterol levels. Their effects on low-density lipoprotein (LDL) cholesterol levels are less marked and more variable. There is evidence that oral gemfibrozil (Lopid, Parke-Davis, Morris Plains, NJ) can reduce the risk of serious coronary events, specifically in those patients who had elevations of both LDL cholesterol levels and total plasma triglyceride levels with lower HDL cholesterol levels. Newer FADs (bezafibrate, ciprofibrate, fenofibrate) have been shown to have greater efficacy in reducing LDL cholesterol than gemfibrozil but, in general, these drugs are not as effective as the other primary drugs used to lower LDL levels. The FADs are also used to treat adult patients with very high levels of triglycerides who have pancreatitis and whose disease cannot be managed with dietary therapy. The FADs are well tolerated, with dyspepsia and abdominal pain the most common adverse effects. A small risk of cholelithiasis exists with these drugs, and caution should be used when combining these drugs with HMG-CoA reductase inhibitors because the combination increases the incidence of hyperlipidemic myositis and rhabdomyolysis.     

某些药物对大鼠血浆和肝脏脂蛋白脂酶活性及血浆胆固醇的影响

Lipoprotein lipase (LPL) is one of the most important factors in lipoprotein metabolism. The plasma and liver LPL activities (indicaded by fatty acid release), the ratio of LPL activity to total lipase activity and theoplasma cholesterol levels in rats treated with drugs were determined so as to study the relationship between LPL and lipoprotein metabolism.Plasma LPL activity is negatively related to the total cholesterol and high density lipoprotein cholesterol levels. As the liver LPL activity, increased, the plasma LPL activity also increased. When rats were treated with insulin, phenytoin or Radix Polygonum multiflorum, the plasma and liver LPL activities and the ratio of LPL activity to total lipase activity increased, whereas the plasma total cholesterol and high density lipoprotein cholesterol levels decreased. No significant effect of phenytoin on the total cholesterol level was observed, When large doses of phenytoin were used, the plasma very low density lipoprotein and low density lipoprotein cholesterol level increased and the ratio of high density lipoprotein cholesterol to total cholesterol decreased.     

某些药物对大鼠血浆和肝脏脂蛋白脂酶活性及血浆胆固醇的影响

高浓度极低密度脂蛋白(VLDL)和高浓度低密度脂蛋白(LDL)血症是冠心病的易患因子,脂蛋白脂酶(LPL)可使VLDL转化为LDL,故LPL可能促进动脉粥样斑块的形成。但LPL又可促进高密度脂蛋白(HDL)的生成,而HDL是防止动脉粥样硬化斑块形成的有利因子,故又认为LPL可能有利于防止斑块的生成。由此可见LPL对动脉粥样硬化的影响具有两面性,LPL在脂蛋白代谢中的作用非常复杂。     

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

The influence of hydrochlorothiazide (HCT) treatment on the plasma levels of triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL-cholesterol) was studied in 10 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.     

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.     

Comparison of the effects of nicardipine and metoprolol on lipid and glycidic metabolism in hypertensive subjects.

Various aspects of carbohydrate and lipid metabolism have been studied in two groups of patients with mild hypertension before and after six months of treatment with either nicardipine (n = 10) or metoprolol (n = 10). A significant reduction of the arterial blood pressure was seen with both treatment regimens. Circulating plasma glucose, insulin, C peptide and triglyceride concentrations were measured at hourly intervals from 08 h 00 to 17 h 00, in patients on an isocaloric diet (35 kcalth/kg/die). Plasma glucose concentrations were unchanged and insulin and C peptide concentrations were higher in association with metoprolol treatment. In contrast, nicardipine-treated patients had similar plasma insulin, but lower plasma glucose, C peptide and triglyceride concentrations after treatment. The changes in day-long plasma glucose and insulin-stimulated glucose uptake had increased in association with metoprolol treatment and decreased following nicardipine. Finally plasma cholesterol concentrations did not change following metoprolol therapy, whereas plasma high density lipoprotein cholesterol increased in association with nicardipine treatment. The data seem to indicate that the negative effect of nicardipine on secretion of insulin is balanced by an improvement in glucose uptake.     

Beta-blocker effects on plasma lipids during prolonged treatment of hypertensive patients with hypercholesterolemia

The aim of this study was to compare the effects of long-term monotherapy with four different beta-blockers on plasma lipids in hypercholesterolemic hypertensive patients. We studied 152 subjects with essential hypertension [diastolic blood pressure (DBP) >90 mm Hg], total cholesterol (TC) >240 and <330 mg/dl, and triglycerides (TGs) <300 mg/dl. After a 4-week washout period with placebo, patients were randomized to receive propranolol, 160 mg/day (n = 37), atenolol, 100 mg/day (n = 38), bisoprolol, 10 mg/day (n = 39), or celiprolol, 400 mg/day (n = 38), for 18 months. No cholesterol-reducing drug was allowed. Blood samples for evaluation of TC, low-density lipoprotein cholesterol (LDL-C), HDL cholesterol (HDL-C), and TGs were taken before and after the placebo period and subsequently every 6 months. No beta-blocker worsened TC or LDL-C. Nonselective propranolol caused the most pronounced changes in HDL-C and TGs. Beta1-Selective atenolol produced the same qualitative effects, but to a lesser extent. The more beta1-selective bisoprolol did not affect HDL-C and TGs. Celiprolol significantly improved the lipid profile by significantly decreasing TC, LDL-C, and TGs, and increasing HDL-C. These findings suggest that in hypercholesterolemic hypertensive patients, (a) beta1-selective beta-blockers are likely to adversely affect plasma lipids to a lesser extent than nonselective ones; and (b) celiprolol is able to improve the lipid pattern, which could be because of its peculiar ancillary properties.     

Effects of bezafibrate and gemfibrozil on serum lipoproteins in primary hypercholesterolemia

29 patients with primary hypercholesterolemia were treated for 8 weeks each with either bezafibrate (200 mg t.i.d.) or gemfibrozil (600 mg b.i.d.) in a randomized cross-over trial. Compared to placebo bezafibrate was significantly more effective on low density lipoprotein (LDL)-cholesterol (-28% versus -18%) and the LDL/high density lipoprotein (HDL) ratio (-34% versus -24%) by exploratory statistics. There was also a trend for a more marked reduction of bezafibrate on total cholesterol and apoliproprotein B as well as more pronounced increase in HDL-cholesterol and apolipoprotein A-I. The triglyceride reduction tended to be more extensive with gemfibrozil. Complicance to both drugs was good. No side-effects were observed. The results are considered important with respect to the potential of bezafibrate in reducing the risk of cardiovascular disease.     

Increased platelet adhesion and aggregation in hypertensive patients: effect of atenolol.

Fourteen patients with established hypertension followed a double-blind crossover-styled trial to study the effects of 100 mg/day atenolol compared to placebo. Atenolol was found to be an effective antihypertensive agent, reducing both systolic and diastolic blood pressure. Hypertensive patients appear to have increased in vitro platelet adhesion and aggregation. Atenolol significantly reduced platelet adhesion, but had little effect on aggregation. This may be important in contributing towards the now-recognised cardio-protective effect of the beta-adrenoceptor blocking agents. Blood chemistry and haematological parameters were unchanged; but whereas plasma cholesterol and plasma triglyceride levels remained normal, there was a significant fall in plasma high-density lipoprotein cholesterol levels. Side effects were very few.     

Changes in the lipoprotein profile during antihypertensive therapy

Abstract: In the Oslo study serum lipids have been studied during treatment with some of the most frequently used antihypertensive drugs. Hydrochlorothiazide induced no significant changes. However, those patients with the most marked increase in uric acid showed an increase of serum ti iglycerides. Total cholesterol was unchanged in these men. The β-adrenoceptorblocking drugs propranolol, aterolol and oxprenolol caused a reduction of HDL cholesterol and an increase of total triglycerides. Tolal cholesterol remained unchanged. Pindolol induced no significant lipoprotein changes. Prazosin reduced total cholesterol and total triglycerides. HDL. cholesterol remained unchanged. LDL + VLDL cholesterol was reduced.     

The effects of antihypertensive drugs on serum lipids and lipoproteins. II. Non-diuretic drugs

This review examines the effects of various antihypertensive drugs on blood lipids, lipoproteins, and apolipoproteins. A large number of studies have documented the elevation of total cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, and very-low density lipoprotein (VLDL) cholesterol with many thiazide-type diuretic drugs, albeit mainly in short term studies. When added to thiazide diuretics, both beta 1-selective and non-selective beta-blocking drugs elevate total triglycerides and VLDL triglycerides, lower high density lipoprotein (HDL) cholesterol and raise the ratio of total cholesterol to HDL cholesterol ratio. Most non-selective beta-blockers have similar effects when used as monotherapy, but the beta 1-selective agents appear not to affect HDL cholesterol in monotherapy. Prazosin appears free of adverse lipid effects and has improved lipid-lipoprotein concentrations in many studies. Preliminary data on several other drugs also suggest a favourable lipid profile and additional study is warranted - among these are guanabenz, clonidine, pindolol, labetalol, indapamide, and guanfacine. Elevations in serum triglycerides are often ignored on various counts, but triglycerides have been found to be a strong risk factor in European studies and in women over the age of 50 years in the Framingham study. Despite the unfavourable short term effects of diuretics, the theoretical risk of the lipid-lipoprotein changes remains unclear because HDL cholesterol and the total cholesterol to HDL cholesterol ratio are often unchanged. For this and other reasons, a long term trial comparing thiazide-type diuretics with drugs with the most favourable lipid-lipoprotein profile is needed. Until this is accomplished, in most settings diuretic-based regimens are still preferred initially since they are of proven, if limited, efficacy against the cardiovascular complications of hypertension.     

Effects of vitamin E on cholesterol levels of hypercholesterolemic patients receiving statins.

PURPOSE: The effects of vitamin E supplementation on the cholesterol levels of hypercholesterolemic patients receiving statin therapy were studied. METHODS: In this prospective, single-blind, placebo-controlled, randomized trial, patients who were currently taking either lovastatin or simvastatin for a primary diagnosis of hypercholesterolemia were given placebo for two weeks and then randomized to receive a supplement of either 400 IU of vitamin E or matching placebo after dinner for eight weeks, followed by a two-week washout period. RESULTS: Vitamin E supplementation increased plasma alpha-tocopherol concentrations approximately 1.6-fold and increased excretion of its urinary metabolite 4-fold significantly from week 2 to week 6 (p < 0.001 for both comparisons). During the eight-week supplementation period, no statistically significant differences in any lipoprotein cholesterol fraction were detected between groups; however, a 6% decrease in high-density-lipoprotein (HDL) cholesterol was detected within the vitamin E group from week 2 to week 6 (p < 0.05), but the decrease was not sufficient to change the cardiac risk ratio. Neither cytochrome P-450 isoenzyme (CYP) 3A (as measured by hydroxylation of urinary cortisol) nor cholesteryl ester transfer protein (CETP) activity was significantly altered during the study. CONCLUSION: Vitamin E supplementation did not affect total or low-density-lipoprotein cholesterol levels in hypercholesterolemic patients receiving lovastatin or simvastatin. A small but significant decrease in HDL cholesterol levels was observed in the group that received vitamin E supplementation during the supplementation period, but this decrease was no longer significantly different from the placebo group's levels two weeks postsupplementation. The decrease in HDL cholesterol levels did not appear to be related to either CYP3A or CETP.     

Gemfibrozil in hyperlipidaemic patients with peripheral arterial disease: some undiscovered actions

The effects of gemfibrozil were assessed in 27 hyperlipidaemic patients with stable peripheral arterial occlusive disease. Gemfibrozil (600 mg twice daily) was administered for 12 weeks after 2 weeks of placebo medication, thus enabling patients to act as their own controls. Serum cholesterol levels were reduced by a mean of 11.3%, triglycerides by 42.3% and low density lipoprotein cholesterol by 19.9%. Small but significant increases in HDL3 and apolipoprotein A-II also occurred. New findings included significant reductions in plasma lipid peroxides and Factor VIIc levels and a mean increase of 19% in antithrombin III concentrations. Furthermore, plasma fibrinogen levels increased by a mean of 17.6%, a potentially adverse effect of gemfibrozil that has not been previously reported.     

Effects of Panax ginseng extract on lipid metabolism in humans.

The purpose of this study was to examine the effects of Panax ginseng extract (PGE) on lipid metabolism in humans by measuring cholesterol, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). Serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and plasma MDA levels were decreased by administration of PGE for 8 weeks (6g per day), however, high density lipoprotein (HDL) was increased. Those results suggest that hypolipidemic effect of PGE is associated with a decrease in TC, TG, LDL, MDA levels and an increase in HDL. These findings support scientific claims that ginseng has the hypolipidemic potential. Administration of PGE increased SOD and CAT activities while decreased MDA level indicating that antioxidant potential of PGE might induce hypolipidemic effect as one of action mechanism.     

Plasma lipid profiles and antihypertensive agents: effects of lisinopril, enalapril, nitrendipine, hydralazine, and hydrochlorothiazide

Previous studies have documented potentially adverse effects of diuretics and beta-blocking agents on plasma lipid profiles. This study was designed to establish the effects on lipid profiles of the angiotensin-converting enzyme inhibitors lisinopril and enalapril, alone and in combination with hydrochlorothiazide (HCTZ), the calcium-channel blocker nitrendipine, HCTZ, and hydralazine. After a two-week, single-blind, placebo phase, 77 patients with essential hypertension were given active agent as monotherapy in a double-blind fashion for 8-20 weeks. The dose of each agent was titrated to achieve diastolic blood pressure less than 90 mm Hg. At the end of placebo and treatment phases, plasma was analyzed for triglycerides, total cholesterol, and high-(HDL), and low-density lipoprotein (LDL) cholesterol. Overall, few changes in lipid contents were noted. Total cholesterol decreased during therapy with hydralazine but increased in patients receiving the combination of lisinopril and HCTZ. HDL cholesterol was depressed in those taking HCTZ alone and in combination with lisinopril. LDL cholesterol was lowered during therapy with hydralazine but was otherwise unaffected by all other agents. None of the agents evaluated significantly affected triglyceride concentrations. Thus, monotherapy with lisinopril, enalapril, and nitrendipine do not affect plasma lipid concentrations. Hydralazine lowers total and LDL cholesterol. If these findings are confirmed in trials with larger numbers of patients, these effects on lipid profiles may influence choice of agent in the therapy of essential hypertension.     

CNS-related subjective symptoms during treatment with beta 1-adrenoceptor antagonists (atenolol, metoprolol): two double-blind placebo controlled studies.

1. Whilst a number of studies have investigated whether metoprolol and atenolol, the most widely used beta 1-adrenoceptor antagonists, differ with regard to CNS-related subjective symptoms, few placebo-controlled studies using standardised questionnaires have been performed. 2. In the present report, the findings of two randomised, double-blind, cross-over studies in healthy volunteers are presented. The subjects were treated with placebo and atenolol (100 mg once daily) (Study 1) and metoprolol (100 mg once daily) and placebo (Study 2). 3. Subjective experiences were evaluated using a standardised instrument, the Minor Symptoms Evaluation-profile (MSE-profile), which was filled in 4, 8 and 24 h after intake of the tablets. A Type A questionnaire was also completed by the subjects. 4. At 4 h both metoprolol and atenolol were found to affect negatively vitality and contentment, but these effects had declined after 8 h. A significant adverse effect on sleep was shown for atenolol compared with placebo, while no negative effect was observed for metoprolol. No significant differences were found in relation to Type A behaviour and beta-adrenoceptor blockade. The number of subjects with Type A personality was, however, low. 5. The results of the studies indicate that the subjective symptoms of the beta 1-adrenoceptor blockers are mild, and that the effects appear consistently with the recognised pharmacokinetic profiles of the two drugs.