Gemfibrozil therapy in primary type II hyperlipoproteinemia: effects on lipids, lipoproteins and apolipoproteins

Gemfibrozil lowers triglycerides, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol. It also promotes a significant increase of high density lipoprotein (HDL) cholesterol. It has been established that normalization of apolipoproteins is an important protective factor against atherosclerosis. The present report examines the effectiveness of 12 months of gemfibrozil treatment on plasma lipids and apolipoproteins in types IIa (VLDL 18 +/- 2 mg cholesterol/dL) and IIb (VLDL 58 +/- 7 mg cholesterol/dL) hypercholesterolemic patients. Gemfibrozil lowered plasma triglycerides, VLDL cholesterol and apolipoprotein B (apoB), increased HDL cholesterol and apoAI levels in both groups, and induced a very substantial reduction in LDL cholesterol in type IIa patients only. Even though HDL particles were enriched in cholesterol, indicating improvement in the reverse cholesterol transport and lower risk of atherosclerosis in both groups, it is important to note that production of cholesterol-poor LDL particles and reduction in LDL cholesterol and the LDL/HDL cholesterol ratio were observed only in the normotriglyceride group (type IIa). Due to the initially elevated concentration of plasma triglycerides and VLDL in type IIb patients and the increased catabolism of VLDL to LDL during gemfibrozil therapy, this drug has a more efficient regulating effect on LDL particles in type IIa compared with type IIb hyperlipidemia.     

Comparison between the effects of nafarelin and danazol on serum lipids and lipoproteins in patients with endometriosis

The effects of nafarelin (400 micrograms daily; 12 patients) and danazol (600 mg daily; 6 patients) on serum lipoproteins, high density lipoprotein (HDL) subfractions, and apoproteins-A-I and -A-II were studied. Lipoproteins were fractionated by sequential flotation from samples taken before and after 1, 3, and 6 months of treatment as well as 3 months after cessation of medication. Serum concentrations of estradiol, total and free testosterone, androstenedione, and sex hormone-binding globulin were also determined. On nafarelin treatment, serum total HDL and HDL2 cholesterol concentrations increased slightly, but total and low density lipoprotein (LDL) cholesterol levels were unchanged. There was no effect on apoproteins-A-I and -A-II or on total and very low density lipoprotein (VLDL) triglyceride concentrations. During treatment with danazol, the serum levels of total HDL and HDL2 cholesterol showed profound decrease, as did all the components of HDL2, including apoprotein-A-I. Concomitantly, the total mass of LDL was increased by 25%, accounted for by parallel rises in all of the components of LDL. Total and VLDL triglyceride concentrations decreased inconsistently. Both treatments resulted in hypoestrogenism of the same degree. The steep drop in the serum sex hormone-binding globulin level reflected the androgenic effect of danazol, whereas during nafarelin treatment, serum concentrations of testosterone and androstenedione were reduced. This difference in androgenic milieu may well explain the differences in the lipid profiles. We conclude that, regarding lipid effects, nafarelin is a more favorable treatment for endometriosis than is danazol.     

A comparison between lovastatin and gemfibrozil in the treatment of primary hypercholesterolemia.

A randomized, multicenter, double-blind, prospective, 18-week comparison of lovastatin with gemfibrozil was performed to compare their efficacy and tolerability in adults with types IIa and IIb primary hypercholesterolemia. Sixty men and 44 women aged 24 to 78 years participated in the trial. Each treatment group of 52 patients was closely matched by the randomization procedure. All participants met national cholesterol education program guidelines for evaluation and treatment. In all, 94 (90%) completed the 18 weeks of study. After 18 weeks of diet-plus-active treatment, lovastatin decreased serum total cholesterol and low-density lipoprotein (LDL) cholesterol significantly better than gemfibrozil (adjusted mean decreases were 63 vs 35 mg/dl for total cholesterol and 67 vs 28 mg/dl for LDL; p = 0.0001). Gemfibrozil was more effective than lovastatin in increasing high-density lipoprotein (HDL) cholesterol (8 vs 5 mg/dl adjusted mean HDL cholesterol increases; p = 0.0086) after 18 weeks. No significant differences in the adjusted mean ratio of total to HDL cholesterol were noted, but the lovastatin group had a significantly greater adjusted mean reduction in the ratio of LDL to HDL cholesterol (1.8 vs 1.3; p = 0.0013). The gemfibrozil group achieved significantly greater reductions in very low density lipoprotein (VLDL) cholesterol and triglycerides compared with the lovastatin group (adjusted mean decreases were 14 vs 1 mg/dl for VLDL cholesterol and 71 vs 15 mg/dl for triglycerides). After 18 weeks of lovastatin therapy, 49% of patients achieved goal LDL cholesterol, whereas only 9% of those who took gemfibrozil achieved this goal (p = 0.0001).     

Accelerated turnover of very low density lipoprotein triglycerides in chronic alcohol users. A possible mechanism for the up-regulation of high density lipoprotein by ethanol

The concentration of high density lipoproteins (HDL) is related to the catabolism of triglyceride-rich lipoproteins. In order to elucidate the mechanisms by which alcohol increases plasma HDL levels we measured the turnover kinetics of very low density lipoprotein (VLDL) triglycerides in 10 alcoholic men without liver disease and in nonalcoholic control men matched for age, weight and plasma VLDL triglyceride level. The study was repeated in the alcoholics after a 2-week abstinence period. The alcoholic men had elevated HDL cholesterol but reduced low density lipoprotein (LDL) cholesterol as compared to the controls. The fractional catabolic rate and the total turnover (production) rate of VLDL triglycerides were both significantly increased (P less than 0.05) in the alcoholic men before abstinence. After withdrawal of alcohol both the synthetic rate and the catabolic rate of VLDL triglycerides returned to normal and the HDL (HDL2 and HDL3) cholesterol fell. The per cent decrease in HDL2 cholesterol during abstinence was positively correlated to the respective fall of VLDL triglyceride fractional catabolic rate (r = +0.51). The results suggest that the absence of hypertriglyceridemia and the elevated levels of HDL in regular alcohol users may be partly based on increased metabolic clearance of VLDL particles and on subsequent accelerated transfer of the VLDL surface components to HDL.     

Micronized fenofibrate normalizes the enhanced lipidemic response to a fat load in patients with type 2 diabetes and optimal glucose control

This study evaluated the postprandial (PP) response to an oral fat load in 28 male patients with type 2 diabetes (mean HbA1c of 5.1%), all receiving metformin and performing physical exercise, compared with healthy subjects. The effects of micronized fenofibrate (200 mg once daily) on triglycerides (TG) and retinyl palmitate (RP) responses, lipoprotein mass concentrations, post-heparin lipase activities and coagulation factors were investigated after a 16-week double-blind, placebo-controlled period. Higher and delayed TG response after the oral fat load (P<0.001) corresponding to increases in both intestinally and endogenous TG-rich lipoproteins and lower lipoprotein lipase (LPL) activity 30 and 60 min post-heparin injection (P<0.05) were observed in the patients as compared with controls. Fasting PAI-1 activity, 6 h PP Factor VII and PAI-1 activities were higher in patients (P=0.036, P=0.032 and P=0.017, respectively). After fenofibrate treatment, TG and RP responses and peak LPL activity were no more significantly different from controls at baseline. Compared with placebo, fasting TG-rich lipoproteins and HDL(3) mass concentrations were significantly lower and higher, respectively; PP chylomicrons and very low density lipoprotein (VLDL) mass concentrations were lower; fasting and PP fibrinogen levels were significantly reduced after fenofibrate treatment. Diabetes control was unchanged throughout the study. Fenofibrate normalized the abnormal PP response and improved the fasting lipoprotein abnormalities in patients with type 2 diabetes and optimal glucose control.     

Adverse effects of obesity on lipid and lipoprotein levels in insulin-dependent and non-insulin-dependent diabetes

We studied the association of obesity with lipid and lipoprotein concentrations in 92 patients (49 men, 43 women) with insulin-dependent diabetes (IDDM), in 305 patients (152 men, 153 women) with non-insulin-dependent diabetes (NIDDM), and in 122 nondiabetic control subjects (65 men, 57 women). Obesity (body mass index, BMI) was associated with abnormal lipid and lipoprotein levels only in the presence of diabetes, and lipid and lipoprotein changes were substantially more abnormal in patients with NIDDM than in patients with IDDM. In men and women with NIDDM, obesity was associated with low high-density lipoprotein (HDL) and HDL2 cholesterol and high total, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) triglyceride concentrations. In men with IDDM, obesity was related only to low HDL and HDL2 cholesterol and in women with IDDM to low HDL3 cholesterol. BMI and diabetes status had a statistically significant interaction (analysis of variance) with respect to HDL and HDL2 cholesterol and total and VLDL triglycerides, indicating that the effects of obesity on lipids and lipoproteins were more severe in patients with diabetes than in nondiabetic subjects. In conclusion, obesity and diabetes status have an unfavorable interaction that results in multiple pathologic lipid and lipoprotein changes, particularly in NIDDM.     

Long-term efficacy and safety of rosuvastatin 40 mg in patients with severe hypercholesterolemia

Patients with elevated low-density lipoprotein (LDL) cholesteral levels are at high risk of cardiovascular events but are often undertreated and fail to achieve lipid goals. This open-label, noncomparative, multicenter study assessed efficacy and safety of rosuvastatin 40 mg for < or =96 weeks in 1,380 patients with severe hypercholesterolemia, including heterozygous familial hypercholesterolemia. Patients > or =18 years old with fasting LDL cholesterol > or =190 and < or =260 mg/dl and triglycerides <400 mg/dl entered a 6-week dietary lead-in, before receiving rosuvastatin 40 mg for 48 weeks. An optional additional 48-week treatment period followed. The initial period had 2 primary end points: percentage of patients achieving National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III LDL cholesterol goals at 12 weeks, and long-term safety, assessed during 48 weeks by incidence and severity of adverse events (AEs) and abnormal laboratory values. Safety was the primary end point in the extension period. At 12 weeks, 83% of patients achieved NCEP ATP III LDL cholesterol goals, which were maintained during 48 and 96 weeks (81% and 84%, respectively). At 48 weeks, rosuvastatin 40 mg reduced LDL cholesterol from baseline by 52% and increased high-density lipoprotein (HDL) cholesterol by 11% (both p <0.0001). At 96 weeks, LDL cholesterol was reduced by 54% and HDL cholesterol increased by 13%. Rosuvastatin 40 mg was well tolerated during 96 weeks. The overall pattern and incidence of AEs and abnormal laboratory values were consistent with the published safety profile of rosuvastatin and higher doses of other statins. In conclusion, long-term treatment with rosuvastatin 40 mg is safe and effective in patients with severe hypercholesterolemia.     

Quantitative and qualitative serum lipoprotein analysis. Part 1. Studies in healthy men and women.

Preparative ultracentrifugal and electrophoretic analysis of serum lipoproteins was performed in 30-70-year-old healthy, fasting males (N = 80) and females (N = 77), randomly selected from the Uppsala region, Sweden. The concentrations of cholesterol and triglycerides in total serum and in VLDL,LDL and HDL lipoprotein classes are reported. Total serum, VLDL and LDL triglycerides and cholesterol concentrations increased with age, while HDL cholesterol and triglyceride concentrations did not vary with age. Overweight persons had higher total serum triglyceride, higher VLDL cholesterol and triglyceride and lower HDL cholesterol levels. The upper 90% population limit values for non-overweight males/females were: total triglycerides (mmol/l) 2.5/2.0, total cholesterol (mg/100 ml) 298/300, VLDL triglyceride 1.80/1.05, VLDL-cholesterol 32/33, LDL triglyceride 0.69/0.69, LDL cholesterol 210/218, HDL triglyceride 0.32/0.34 and HDL-cholesterol 69/93. The 2 major differences between males and females were that females had lower VLDL but higher HDL concentrations. For VLDL there was a very strong and for LDL a moderately strong positive correlation between cholesterol and triglyceride contents. In HDL however, the mearsured amounts of cholesterol and triglycerides did not correlate at all. Sinking pre-beta lipoproteins was found in about 25% of cases and a second pre-beta band floating at d 1.006, late pre-beta, was found in 35% of male and 25% of female subjects. Subjects with sinking pre-beta lipoprotein did not differ from other subjects with regard to the concentration of cholesterol and triglycerides in the 3 lipoprotein classes. Males, but not females, with the late pre-beta (LPB), had an increased amount of cholesterol in VLDL and a raised cholesterol-triglyceride ratio in this lipoprotein class. Also the LDL triglyceride level was increased in males with the late pre-beta lipoprotein.     

Effects of troglitazone on atherogenic lipoprotein phenotype in coronary patients with insulin resistance.

Insulin resistance is associated with atherogenic lipoprotein phenotype, including small dense LDL particle, hypertriglycemia and low HDL cholesterol levels. Troglitazone, a novel insulin sensitizing agent, may improve the associated lipid profile in patients with insulin resistance. We examined the effects of troglitazone (400 mg daily for 12 weeks) in 12 non-diabetic coronary patients (60+/-10 years), all of whom had hyperinsulinemic response to an oral glucose load. Troglitazone markedly reduced the insulin response. After the treatment, plasma triglycerides decreased by 32% (P<0.05), HDL cholesterol increased by 11%, (P<0.05) and LDL peak particle diameter increased from 24.7+/-0.3 to 25.5+/-0.5 nm (P<0.01). These lipidic improvements were associated with a significant rise in postheparin lipoprotein lipase levels (175+/-52 to 217+/-69 ng/ml, P<0.01). In patients with insulin resistance syndrome, troglitazone improved the atherogenic lipoprotein phenotype as well as hyperinsulinemia. Our data suggest that troglitazone therapy could reduce the atherosclerotic risk due to insulin resistance even in non-diabetic patients.     

Lipoprotein profile in men with peripheral vascular disease. Role of intermediate density lipoproteins and apoprotein E phenotypes.

BACKGROUND. The role of lipoprotein disturbances in the development of peripheral vascular disease (PVD) has not been sufficiently clarified. METHODS AND RESULTS. The relations among concentrations of intermediate density lipoproteins (IDL), apoprotein (apo) B, apo E, and other lipoproteins were studied in 102 men with PVD and 100 healthy men who formed the control group. Patients with PVD had significantly higher levels of serum triglycerides, very low density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL proteins, IDL cholesterol, and IDL triglycerides and lower levels of high density lipoproteins (HDL) than controls. Serum cholesterol and triglycerides were normal in 30 patients (cholesterol, less than 5.2 mmol/l; triglycerides, less than 2.3 mmol/l), who had significant increases in IDL triglycerides and significant decreases in HDL cholesterol compared with the 47 controls, who had normal cholesterol and triglyceride levels. Patients with more severe distal involvement showed higher cholesterol and triglycerides carried by IDL and a greater reduction in HDL cholesterol. Smoking patients with PVD showed increased VLDL cholesterol and VLDL triglycerides and lower HDL concentrations. Apo E polymorphism in our study population does not differ from that reported for other European populations. Alleles epsilon 2 and epsilon 4 had a major impact on serum triglycerides and VLDL lipids in our patients with PVD. CONCLUSIONS. Lipoprotein disturbances are a major risk factor for PVD. IDL abnormalities play an important role in the development and severity of PVD and should also be considered a vascular risk factor in normocholesterolemic and normotriglyceridemic patients.     

Acute effects of cholestyramine on serum lipoprotein concentrations in type II hyperlipoproteinaemia.

Twelve subjects with primary type IIA hyperlipoproteinaemia were treated with cholestyramine under metabolic ward conditions in order to study the timing of effects of different serum lipoprotein classes. After 1 day's treatment changes occurred in all 3 classes, i.e., very low (VLDL), low (LDL) and high (HDL) density lipoprotein classes. VLDL increased abruptly and remained constant during treatment. The ratio of cholesterol/triglycerides decreased suggesting the formation of larger particles. LDL cholesterol decreased continuously suggesting a different mechanism behind this effect than that on VLDL. LDL triglyceride remained constant indicating a relative increase of LDL1. HDL cholesterol decreased while HDL triglycerides increased. All changes made the lipoprotein pattern more "type IV-like". The findings were in agreement with an increased formation of VLDL and an increased flux of lipoprotein through the cascade VLDL-IDL-LDL1-LDL2.     

Effects of simvastatin, bezafibrate and gemfibrozil on the quantity and composition of plasma lipoproteins

Simvastatin, 10-40 mg/d (n = 11), bezafibrate, 600 mg/d (n = 6), and gemfibrozil, 1200 mg/d (n = 5) were administered for 12 weeks after a 4-week placebo period to subjects with initial plasma levels (mg/100 ml. mean +/- SD) of cholesterol (346 +/- 77), and of triglycerides (180 +/- 54). Total LDL-C plasma concentration was lowered 32% by simvastatin and 35% by bezafibrate, but only bezafibrate diminished the triglyceride (41%) and increased HDL-C plasma levels (35%). Plasma lipoprotein fractions obtained by discontinuous gradient ultracentrifugation, namely, VLDL, lighter LDL (LDL-1), heavier LDL (LDL-2) and bulk HDL were chemically analyzed. Simvastatin and bezafibrate significantly diminished the quantity of VLDL and LDL-1 particles, although barely modifying their composition. Neither drug influenced the LDL-2 plasma concentration. Bezafibrate increased the total plasma HDL level little interfering with its chemical composition. Gemfibrozil was the least effective of all drugs but decreased the lipid and protein contents and their ratios in VLDL and LDL-2.     

Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia

This multicenter, randomized, double-blind, placebo-controlled clinical study assessed the efficacy and safety of ezetimibe administered with lovastatin in primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week single-blind placebo lead-in period, 548 patients with low-density lipoprotein (LDL) cholesterol > or =145 mg/dl (3.75 mmol/L) and < or =250 mg/dl (6.47 mmol/L) and triglycerides < or =350 mg/dl (3.99 mmol/L) were randomized to one of the following, administered daily for 12 weeks: ezetimibe 10 mg; lovastatin 10, 20, or 40 mg; ezetimibe 10 mg plus lovastatin 10, 20, or 40 mg; or placebo. The primary efficacy variable was percentage decrease in direct LDL cholesterol from baseline to end point for pooled ezetimibe plus lovastatin versus pooled lovastatin alone. Ezetimibe plus lovastatin significantly improved concentrations of LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides compared with lovastatin alone (p <0.01). The coadministration of ezetimibe provided an incremental 14% LDL cholesterol decrease, a 5% HDL cholesterol increase, and a 10% decrease in triglycerides compared with pooled lovastatin alone. Ezetimibe plus lovastatin provided mean LDL cholesterol decreases of 33% to 45%, median triglyceride decreases of 19% to 27%, and mean HDL cholesterol increases of 8% to 9%, depending on the statin dose. The coadministration of ezetimibe 10 mg plus the starting dose of lovastatin (10 mg) provided comparable efficacy to high-dose lovastatin (40 mg) across the lipid profile (LDL cholesterol, HDL cholesterol, and triglycerides). Ezetimibe plus lovastatin was well tolerated, with a safety profile similar to both lovastatin alone and placebo. The coadministration of ezetimibe and lovastatin may offer a new treatment option in lipid management of patients with hypercholesterolemia.     

The effect of etophylline clofibrate on HDL subfractions

The effect of etophylline clofibrate on lipids and apolipoproteins of the high density lipoprotein (HDL) subfractions HDL2 and HDL3 as well as on very low density (VLDL) and low density lipoproteins (LDL) and the post heparin lipolytic activities (PHLA) of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) has been studied in 14 patients with type II hyperlipoproteinemia (HLP). The study was preceded by a 4-week washout phase, followed by a 6-week placebo period. During the next 12 weeks, the patients received 750 mg etophylline clofibrate per day. Then the drug was again replaced by placebo for another 6 weeks. During the study the patients were on a low fat diet poor in cholesterol with a P/S ratio over 1.0. HDL cholesterol and apoproteins increased significantly during treatment. In the first verum phase this effect was related to the rise in HDL2 components with minor changes in HDL3 concentrations, whereas in the second verum period a distinct increase of the HDL3 components could be detected. This development was accompanied by a significant increase of the LPL activities during the first 6 weeks of treatment, followed by a decrease to initially measured values after 12 weeks. The drug lowered plasma- and LDL-cholesterol levels by 19% and 22%, and plasma and VLDL triglycerides by 22% and 25%, respectively. VLDL-C apoproteins (C-I, C-II, C-III) declined by 31% with a percentage increase of apo C-II compared with apo C-I and apo C-III.     

Sequence of alcohol-induced initial changes in plasma lipoproteins (VLDL and HDL) and lipolytic enzymes in humans

The sequence of alterations in the concentration and composition of different plasma lipoproteins following alcohol intake is not known. We therefore monitored the concentrations of cholesterol, triglycerides, phospholipids, and proteins in the major lipoprotein fractions (VLDL, LDL, HDL2, and HDL3) in ten nonalcoholic healthy male volunteers who were given 5.5 g of alcohol per kilogram of body weight during 21/2 days (a weekend). In addition, lipoprotein lipase activity was measured in post-heparin plasma and in adipose tissue and hepatic lipase activity was measured in post-heparin plasma before and after the experiment. in a separate control experiment, the same subjects received meals and liquids without alcohol. Blood alcohol levels remained below 1.5 g/L. Alcohol caused a progressive increase in the fasting VLDL triglyceride and phospholipid concentrations, both of which were doubled during the experiment (P less than 0.001). In contrast, the VLDL cholesterol levels remained unchanged until the third morning, when there was a slight increase. The LDL triglyceride and phospholipid concentrations also rose without simultaneous changes in the LDL cholesterol concentration. Consistent with these changes, the HDL cholesterol concentration showed no response to alcohol during the experiment, but the HDL phospholipid level rose from 76 to 99 mg/dL (P less than 0.001). This was reflected as an increase in the HDL2 concentration from 124 to 158 mg/dL (P less than 0.01), whereas no change occurred in the HDL3 level. The increment of HDL2 concentration was due to a rise of its triglycerides, phospholipids, and apoproteins A-I and A-II but not to a rise of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional adiposity patterns in relation to lipids, lipoprotein cholesterol, and lipoprotein subfraction mass in men

Anatomical adipose tissue distribution patterns are reported to relate to plasma lipids and risk of cardiovascular disease. Waist to hip girth ratios (WHR) and subscapular 10 triceps skinfold thickness ratios (STR) were compared with percent body fat and body mass index values as correlates of plasma lipids and lipoprotein cholesterol and serum lipoprotein subfraction mass by analytic ultracentrifugation in 81 sedentary middle-aged men in a typical range of adiposity. WHR was significantly and positively correlated with plasma concentrations of triglycerides, cholesterol, and low and very low density lipoprotein (LDL and VLDL) cholesterol and inversely correlated with high density lipoprotein (HDL) cholesterol. STR followed these trends, though less strongly, in relation to plasma triglycerides, VLDL cholesterol, and HDL cholesterol. Pronounced differences were found between regional adiposity patterns in their relationships to lipoprotein subfractions, as determined by analytic ultracentrifugation. WHR was negatively correlated with HDL2 (flotation rate F(1.2) 3.5-9), positively with small LDL (S.f 0-7), intermediate density lipoprotein (S.f 12-20), and VLDL (S.f 20-400), while STR correlated with larger LDL (S.f 7-12) and larger VLDL (S.f 60-400). Overall adiposity was not significantly associated with plasma lipoprotein levels after adjusting for regional adiposity patterns. Plasma sex hormone-binding globulin and percent free testosterone were associated with regional adiposity, but did not account for the correlations between WHR and lipoproteins. WHR and STR are measures of fat distribution that correlate with plasma lipoprotein profiles consistent with cardiovascular disease risk and have different relationships to lipoprotein mass subfractions.     

Effects of atorvastatin on postprandial plasma lipoproteins in postinfarction patients with combined hyperlipidaemia

Enhanced and prolonged postprandial lipaemia is implicated in coronary and carotid artery disease. This study assessed the effects of atorvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, on postprandial plasma concentrations of triglyceride-rich lipoproteins (TRLs). Sixteen middle-aged men with combined hyperlipidaemia (baseline low density lipoprotein (LDL) cholesterol and plasma triglyceride concentrations (median (interquartile range) of 4.54 (4.17-5.26)) and 2.66 (2.04-3.20) mmol/l, respectively) and previous myocardial infarction were randomised to atorvastatin 40 mg or placebo once daily for 8 weeks in a double-blind, cross-over design. The apolipoprotein (apo) B-48 and B-100 contents were determined in subfractions of TRLs as a measure of chylomicron remnant and very low density lipoprotein (VLDL) particle concentrations (expressed as mg apo B-48 or apo B-100 per litre of plasma), in the fasting state and after intake of a mixed meal. Atorvastatin treatment reduced significantly the fasting plasma concentrations of VLDL cholesterol, LDL cholesterol and VLDL triglycerides (median% change) by 29, 44 and 27%, respectively, and increased high density lipoprotein (HDL) cholesterol by 19%, compared with baseline. The postprandial plasma concentrations of large (Svedberg flotation rate (Sf) 60-400) and small (Sf 20-60) VLDLs and chylomicron remnants were almost halved compared with baseline (mean 0-6 h plasma concentrations were reduced by 48% for Sf 60-400 apo B-100, by 46% for Sf 60-400 apo B-48, by 46% for Sf 20-60 apo B-100 and by 27% for Sf 20-60 apo B-48), and the postprandial triglyceridaemia was reduced by 23% during active treatment. In conclusion, atorvastatin 40 mg once daily causes profound reductions of postprandial plasma concentrations of all TRLs in combined hyperlipidaemic patients with premature coronary artery disease.     

Effect of Furosemide on the Lipid Abnormalities in Chronic Renal Failure

ABSTRACT. The effect of furosemide on the lipoprotein profile and the activities of postherapin plasma lipases were studied in 12 patients with chronic renal failure. The concentrations of serum total, VLDL and LDL triglycerides were significantly higher and the concentration of HDL triglyceride was significantly lower in the patients with renal failure than in healthy controls. HDL cholesterol was significantly lower in the patients than in the controls. The activity of postherapin lipoprotein lipase was significantly lower in the patients than in the controls. The introduction of furosemide induced a significant increase in the concentrations of VLDL cholesterol and VLDL triglyceride. These changes were reversed when the drug treatment was discontinued. Postherapin lipase activities were not further altered by furosemide.     

Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease

The efficacy and safety of atorvastatin 10 mg versus simvastatin 20 mg and atorvastatin 80 mg versus simvastatin 80 mg was determined in a 6-week, prospective, randomized, open-label, blinded end-point trial of dyslipidemic patients with and without coronary heart disease. A total of 1,732 patients with hypercholesterolemia and triglycerides < or =600 mg/dl (6.8 mmol/L) were randomized to receive either atorvastatin 10 mg (n = 650), simvastatin 20 mg (n = 650), atorvastatin 80 mg (n = 216), or simvastatin 80 mg (n = 216). The primary efficacy parameter was the change in low-density lipoprotein (LDL) cholesterol from baseline to week 6. Secondary efficacy parameters included the percent change from baseline to week 6 in total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, very-low-density lipoprotein cholesterol, apolipoprotein B, and the percent of patients achieving their National Cholesterol Education Program (NCEP) LDL cholesterol goal at study end. Atorvastatin had significantly greater reductions from baseline in LDL cholesterol than simvastatin in both comparator groups: atorvastatin 10 mg (37.1%) versus simvastatin 20 mg (35.4%) (p = 0.0097), and atorvastatin 80 mg (53.4%) versus simvastatin 80 mg (46.7%) (p <0.0001). Atorvastatin 10 and 80 mg also provided significantly greater reductions in total cholesterol, triglycerides, very-low-density lipoprotein cholesterol, and apolipoprotein B than simvastatin 20 and 80 mg, respectively (all p <0.05). All treatment groups had a significantly decreased LDL cholesterol/HDL cholesterol ratio from baseline (all p <0.0001). In both comparator groups a higher proportion of atorvastatin-treated patients reached their NCEP LDL cholesterol goal compared with simvastatin. All 4 study treatments were well tolerated.     

Dose-dependent effect of rosuvastatin on apolipoprotein B-100 kinetics in the metabolic syndrome

In a randomized, double-blind, crossover trial of 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week placebo wash-outs between treatments, the dose-dependent effect of rosuvastatin on apolipoprotein (apo) B-100 kinetics in metabolic syndrome subjects were studied. Compared with placebo, there was a significant dose-dependent decrease with rosuvastatin in plasma cholesterol, triglycerides, LDL cholesterol, apoB and apoC-III concentrations and in the apoB/apoA-I ratio, lathosterol:cholesterol ratio, HDL cholesterol concentration and campesterol:cholesterol ratio also increased significantly. Rosuvastatin significantly increased the fractional catabolic rates (FCR) of very-low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and LDL-apoB and decreased the corresponding pool sizes, with evidence of a dose-related effect. LDL apoB production rate (PR) fell significantly with rosuvastatin 40 mg/day with no change in VLDL and IDL-apoB PR. Changes in triglycerides were significantly correlated with changes in VLDL apoB FCR and apoC-III concentration, and changes in lathosterol:cholesterol ratio were correlated with changes in LDL apoB FCR, the associations being more significant with the higher dose of rosuvastatin. In the metabolic syndrome, rosuvastatin decreases the plasma concentration of apoB-containing lipoproteins by a dose-dependent mechanism that increases their rates of catabolism. Higher dose rosuvastatin may also decrease LDL apoB production. The findings provide a dose-related mechanism for the benefits of rosuvastatin on cardiovascular disease in the metabolic syndrome.