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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of lipids in the pathogenesis of focal glomerulosclerosis (FGS) was evaluated using two chemically different lipid lowering agents, clofibric acid and mevinolin. Pharmacologically, these two agents have different mechanisms of action. Clofibric acid affects both cholesterol and triglyceride metabolism, while mevinolin inhibits 3-hydroxy-3 methyl-glutaryl coenzyme A reductase, the rate limiting enzyme in cellular cholesterol synthesis. In two different models of FGS in which hyperlipidemia occurs, the obese Zucker rat and the 5/6 nephrectomy model, both agents significantly reduced FGS and albuminuria. Since glomerular hemodynamic function is normal in obese Zucker rats, these results suggested that lipids are an independent factor in the pathogenesis of FGS. Moreover, in the 5/6 nephrectomy model, the beneficial effects on glomerular structure of reducing serum lipids occurred despite persistent systemic and glomerular hypertension. Thus, we postulated that a synergistic interaction between lipids and hypertension might exist in the pathogenesis of FGS.
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PMID:The role of lipids in progressive glomerular disease. 344 53

The long-term efficacy and tolerability of simvastatin, a 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase inhibitor, was assessed during a 24-month follow-up period in 168 elderly hypercholesterolemic patients. After completing a 4 week double blind dose ranging study with simvastatin, 47 males and 122 females over 62 years of age with type II hyperlipidemia, a total cholesterol level above 6.5 mmol/l and clinically manifest cardiovascular disease were included in this extended study. A total of 159 patients completed the 12-month follow-up period and 141 patients were monitored over the full 24 months. All patients were started on 10 mg simvastatin once daily and the dosage was increased until the target levels of low density lipoprotein (LDL) cholesterol between 2.3 mmol/l (90 mg/dl) and 3.6 mmol/l (140 mg/dl) were reached. Fifty percent of patients reached the targeted LDL cholesterol goal of < 3.6 mmol/l (140 mg/dl) during the study. At study completion, 65 patients (39%) were taking 40 mg simvastatin per day, 56 patients (33%) 20 mg, 42 patients (25%) 10 mg and 5 patients (3%) only used 5 mg per day. Sixteen patients (9%) received concomitant lipid lowering therapy. Over 2 years, the mean decrease in LDL cholesterol ranged from 36% to 38%, the median decrease in triglycerides was 12% to 19% and the mean increase in high density lipoprotein (HDL) cholesterol ranged from 9% to 10%, respectively. Seven patients discontinued simvastatin because of adverse clinical or laboratory events, but only in two (1.1%) was this considered to be drug-related. Side-effects were mild and most frequently gastrointestinal in nature. Mean changes in asparate aminotransferase (AST) were not significantly different from zero and mean changes in alanine aminotransferase (ALT) and creatine phosphokinase (CPK) showed a small increase. We conclude that simvastatin is an efficacious and well-tolerated treatment for hypercholesterolemia in elderly individuals for extended periods.
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PMID:Long-term efficacy and tolerability of simvastatin in a large cohort of elderly hypercholesterolemic patients. 757 71

The hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin is used to treat hyperlipidaemia. This agent prevents the isoprenylation of some proteins involved in signal transduction processes and inhibits IgE-receptor-linked mediator release from RBL-2H3 cells. In this study the effect of in vivo and in vitro administration of lovastatin on histamine release from rat peritoneal mast cells was examined. Lovastatin (4 mg/kg/day for 2 weeks) inhibited histamine release induced by concanavalin A (con A) from rat peritoneal mast cells of Hooded-Lister rats and both homozygous lean and obese Zucker rats. In contrast, release induced by antirat IgE (anti-IgE) was only significantly inhibited in cells derived from Hooded-Lister rats and that induced by compound 48/80 was not altered. Lovastatin (20 microM, 24 h, in vitro) caused a significant inhibition of the subsequent histamine release to con A, anti-IgE and compound 48/80 but not to the calcium ionophore A 23187. It is important to determine whether such inhibitory effects are also observed after the chronic, clinical administration of lovastatin and other HMG CoA reductase inhibitors.
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PMID:Effect of in vivo and in vitro lovastatin treatment on mast cell activation. 758 Feb 88

Although combination therapy using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co-A) reductase inhibitors and fibrates is efficacious in combined hyperlipidemia, such treatment has been associated with myopathy. For this reason, we studied the effects of fluvastatin and gemfibrozil, alone or in combination, on muscle. A total of 21 patients with combined hyperlipidemia were recruited who were matched for age, body mass index, and baseline levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides, creatine phosphokinase, and myoglobin. Patients were randomized to three groups for 6-week treatment with fluvastatin at 40 mg/day, gemfibrozil at 600 mg twice daily, or a combination of the two drugs. Parameters for muscle damage were rises in levels of serum creatine phosphokinase and myoglobin compared with pre-exercise levels; these were assessed 1 hr and 8 hr after a 45 min lean body mass standardized ergometer test, which was performed before and after treatment in all patients. Biopsies from the quadriceps muscle were taken 48 hr after each test. Fluvastatin lowered total cholesterol and LDL-C by 23% and 35%, respectively (p < 0.01), with no effects on triglycerides and HDL-C. Gemfibrozil lowered triglycerides by 40% (p < 0.01) but did not lower total cholesterol or LDL-C significantly. The combination therapy decreased total cholesterol, LDL-C, and triglycerides by 28%, 29%, and 39%, respectively (p < 0.05). Pre-exercise creatine phosphokinase and myoglobin levels were not affected by treatment in any group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of combined hyperlipidemia with fluvastatin and gemfibrozil, alone or in combination, does not induce muscle damage. 760 87

The accelerated atherosclerosis in diseases associated with elevated remnant lipoprotein levels has directed interest toward the response of this lipoprotein species to lipid-lowering treatment. The effect of fluvastatin--a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor--was compared with that of placebo on parameters of remnant metabolism in 57 patients with moderate hypercholesterolemia, but not heterozygous familial hypercholesterolemia, type III hyperlipidemia, or endogenous hypertriglyceridemia. Fluvastatin therapy resulted in decreases versus baseline in plasma total cholesterol, low density lipoprotein cholesterol (LDL-C) and LDL apolipoprotein (apo) B levels of 18%, 20%, and 18%, respectively (p < 0.01). Plasma parameters related to remnant metabolism were also significantly decreased: intermediate density lipoprotein by 43% and apo E by 22% (p < 0.01). The percent decrease in plasma intermediate density lipoprotein cholesterol level was twice that of LDL-C and 50% greater than the decrease seen in very low density lipoprotein cholesterol (VLDL-C), which was decreased by 28%. Total triglycerides were reduced by 11% and VLDL apo B by 24%, whereas high density lipoprotein cholesterol (HDL-C) rose significantly by 8%, HDL2-C by 24%, and HDL3-C by 3%. There were no increases in apo A-I levels compared with placebo nor any significant change in plasma lipoprotein(a) levels. The composition of LDL and VLDL particles did not appear to be altered by therapy, as assessed by the LDL-C:LDL-B, VLDL-C:VLDL-B, or triglyceride:VLDL-B ratios.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of fluvastatin on intermediate density lipoprotein (remnants) and other lipoprotein levels in hypercholesterolemia. 760 88

Patients with non-insulin-dependent diabetes mellitus (NIDDM) have a greater risk of developing coronary heart disease than would be expected from a similar degree of hyperlipidemia in nondiabetic populations. Accelerated transfer of cholesteryl esters (CET) from high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL), a process that is associated with atherosclerosis, may be a possible explanation for this. CET, plasma lipoprotein concentration, and mass in the fasting and postprandial state have been examined in 31 hyperlipidemic patients with NIDDM before and after 8 weeks of treatment with the hydroxymethylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitor pravastatin in a double-blind, placebo-controlled, parallel group study. Body mass index, glycemic control, and blood pressure remained unaltered during the study period. Compared with placebo, pravastatin decreased fasting serum cholesterol (P < 0.001) and LDL cholesterol (P < 0.002) levels. The high basal CET (34.4 +/- 13.1 nmol.ml-1.h-1) was decreased significantly by pravastatin treatment (27.5 +/- 13.7 nmol.ml-1.h-1, P = 0.013). There was a fall in the total cholesterol, free cholesterol, and phospholipid content of the Sf 0-12, 20-60, and 60-400 lipoproteins (all P = 0.001). Lecithin: cholesterol acyl transferase activity was not altered. The postprandial increase in VLDL cholesterol 5 h after a standardized mixed meal was attenuated after pravastatin treatment (P = 0.011). Inhibition of hepatic cholesterol synthesis with an HMG-CoA reductase inhibitor in hyperlipidemic patients with NIDDM decreased serum cholesterol content of triglyceride-rich lipoprotein, thereby decreasing the transfer of cholesteryl ester from HDL to LDL and VLDL.
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PMID:Effect of treatment with a hydroxymethylglutaryl coenzyme A reductase inhibitor on fasting and postprandial plasma lipoproteins and cholesteryl ester transfer activity in patients with NIDDM. 769 16

The effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on the metabolism of apolipoprotein (apo) B-containing lipoproteins appear to differ according to the predominant lipoprotein profiles present and the condition being treated. In familial hypercholesterolemia, with isolated low density lipoprotein (LDL) elevations, the LDL-apoB elimination rate is increased by up-regulated LDL-receptors. In familial combined hyperlipidemia where very low density lipoprotein (VLDL) and LDL both may be increased and enhanced production of LDL-apoB may be present, HMG-CoA reductase inhibitors seem to diminish increased LDL-apoB production. The drug-induced decreases in LDL-apoB production could be due to decreased production of precursor VLDL-apoB or due to decreased conversion of VLDL-apoB to LDL-apoB after enhanced removal of VLDL by up-regulated LDL-receptors. To distinguish between these possibilities, we assessed the effects of HMG-CoA reductase inhibitors in another condition in which there is both apoB overproduction and accumulation of VLDL and LDL in plasma, the nephrotic syndrome. We used endogenous labeling of apoB with [13C]leucine and a multicompartmental model to calculate the metabolic parameters of apoB-containing lipoproteins. Only subjects with focal segmental glomerular sclerosis (FSGS) were included, as FSGS is a chronic, very slowly progressive form of nephrotic syndrome. A double-blind, randomized, placebo-controlled, crossover design was used. Treatment periods of 6 weeks were separated by a 2-week washout period. Of the four men studied, three had high triglyceride levels and four had high cholesterol levels. Lovastatin (20 mg/day) significantly decreased cholesterol (27.6 +/- 6%), LDL-cholesterol (27.6 +/- 9%) and plasma apoB (17.9 +/- 2.9%) (P < 0.01 for all). During the placebo period, calculation of kinetic parameters revealed VLDL-, intermediate density lipoprotein (IDL)-, and LDL-apoB overproduction and decreased VLDL-apoB fractional catabolic rate. Lovastatin significantly decreased LDL-apoB production rate in all cases (34.1 +/- 14%, P = 0.03). The decreased LDL-apoB was mainly due to a channelling of LDL precursors away from conversion to LDL (conversion of VLDL to LDL decreased from 80.6 +/- 8.3% to 55.9 +/- 17.2%, P = 0.05). Thus, lovastatin decreased LDL-cholesterol in nephrotic subjects mainly by inhibiting LDL-apoB production from VLDL.
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PMID:Physiologic mechanisms of action of lovastatin in nephrotic syndrome. 770 43

Familial xanthomatous hypercholesterolemia is a metabolic disorder associated with high LDL levels attributed to a familial defect in LDL receptor activity. We have previously shown that hyperlipoproteinemia of WHHL rabbits, considered to be a model for heritable hypercholesterolemia, was at least partly of exogenous origin. We have though studied retinyl palmitate (RP) levels 12 h after a standardized mixed meal as a simple test to detect abnormalities of intestinal-derived lipoprotein clearance in 22 familial hypercholesterolemic patients with xanthomatosis (13 of them treated by simvastatin, an HMGCoA reductase inhibitor, and 9 not treated), as compared to a control group (n = 12). Total and LDL cholesterol, plasma triglyceride and apo B levels were significantly higher in patients when compared to controls. Mean RP levels appeared higher in familial hypercholesterolemic patients, when compared to controls, with 6 among 22 patients showing clearly high vitamin A levels and 4 borderline values, whereas high triglyceride levels (> 2 g/l) were detected in only 1 patient. No patients within the group with high vitamin A levels showed an apo E2/E2 phenotype. Vitamin A levels correlated with plasma triglycerides in the whole group of subjects (r = 0.50, p < 0.05). No difference was observed in vitamin A distribution between treated and untreated hypercholesterolemic patients. Our results indicate that the clearance of RP-labeled intestinal lipoproteins is delayed in some xanthomatous familial hypercholesterolemic patients as compared with that of controls. These findings suggest that familial xanthomatous hypercholesterolemia may be heterogenous concerning physiopathological mechanisms inducing hyperlipidemia.
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PMID:Familial xanthomatous hypercholesterolemia: abnormal exogenous lipid metabolism evidenced by the vitamin A test. 771 Feb 66

The discovery and production of HMGCoA reductase inhibitor and the fundamental research work of the LDL receptor unraveled a receptor-mediated cholesterol homeostasis. HMGCoA reductase inhibitors are the most commonly prescribed class of lipid-lowering drugs in many countries. The decrease of the intracellular cholesterol caused by the inhibitor induces the compensatory increase of LDL receptor protein at liver plasma membrane. The increased receptor promotes LDL catabolism and results in decrease of plasma LDL. Serious side effects involving the liver or muscle are rare. But the risk of myopathy is increased when the drug is used with other hypolipidemic agents. A principle of the treatment of hyperlipidemia, including secondary one associated with diabetes mellitus and renal disease, by HMGCoA reductase is discussed in this review.
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PMID:[HMG-CoA reductase inhibitor for therapy of patients with hyperlipoproteinemia ]. 785 22

"Is there any safe and optimal treatment of hyperlipidemia following heart transplantation?" The problem of hypercholesterolemia following heart transplantation if often underestimated. Up to now there is no concept of therapy allowing an optimal adjustment of lipid parameters. Therapeutical trials using ion exchange resins, derivatives of nicotinic acids and fibrates were not successful due to cyclosporine A interaction, hepatotoxicity and limited efficacy of the applied substances. In a prospective, randomized and controlled trial we investigated the effects of the HMG-CoA-reductase inhibitor simvastatin in heart transplant recipients. The study included 70 patients (simvastatin n = 37, control group n = 33). 8 patients died within the first three months following heart transplantation. Purpose of the study was the adjustment of the LDL-cholesterol values in the simvastatin treated group to < or = 110 mg/dl. Following 24 months of treatment a mean LDL-cholesterol plasma level of 110 mg/dl was obtained. The corresponding mean value of the control group was 150 mg/dl. The difference between both groups was significant (p < 0.001). In the same period the mean HDL-cholesterol values increased by approx. 15% in both groups (no significant difference [p > 0.05]). The ratio of LDL/HDL-cholesterol was significant lower in the simvastatin treated group (2.28) than in the control group (2.94) (p < 0.05). There was no significant difference in Lp(a) values. No adverse side effects were observed within the observation period of 24 months, particularly no increase in the frequency of rejection episodes. Summarizing the above, we recommend low-dose simvastatin therapy as a safe and optimal treatment of hypercholesterolemia following heart transplantation.
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PMID:[Can hyperlipidemia after heart transplantation be optimally and safely treated?]. 787 99


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