Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

In the therapy of hyperlipemia nicotinic acid derivates, cholestyramine, fibrate derivates and HMG-CoA-reductase inhibitors are drugs of choice. The most important drugs of each group, the mode of action and the side effects are presented. In the therapy of hypercholesterolemia HMG-CoA-reductase inhibitors alone or in special cases in combination with low dose of cholestyramine are best qualified. For the treatment of hypercholesterolemia and hypercholesterolemia fibrate derivates are recommended.
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PMID:[Drug treatment of hyperlipidemia]. 269 28

"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

The purpose of this study was to investigate the triglyceride-lowering effect of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in the combined hyperlipidemia of non-insulin-dependent diabetes mellitus (NIDDM). In this double-blind trial, 66 patients with NIDDM (24 men and 42 women, age 37-71), with low-density lipoprotein cholesterol (LDL-C) levels of 130-300 mg/dL (3.4-7.8 mmol/L) and triglyceride (TG) levels of 200-1,000 mg/dL (2.3-11.3 mmol/L) despite an 8-week period of diet modification, were randomized to receive either fluvastatin at 20 mg once daily (at night) or placebo for 6 weeks, followed by an increase of fluvastatin to 20 mg twice daily for an additional 6 weeks of treatment. After 12 weeks, fluvastatin decreased plasma levels of total cholesterol by 19.9% (p < 0.001), LDL-C by 24.3% (p < 0.001), TG by 15.3% (p < 0.01), very low-density lipoprotein cholesterol (VLDL-C) by 19.7% (p < 0.001), apolipoprotein (apo) B by 21.3% (p < 0.001), and apo E by 18.1% (p < 0.05), whereas high-density lipoprotein cholesterol (HDL-C) levels were increased by 4.6% (p < 0.05). Within the intermediate-density lipoprotein cholesterol (IDL-C) fraction, a constituent analysis revealed a total cholesterol reduction of 35% (p < 0.01). Greater decreases in TG were seen in patients who had higher levels of TG at baseline. Slight increases in glycemic indices and body weight were seen in both treatment groups. The occurrence of clinical and laboratory abnormalities was similar with both active treatment and placebo, and no myositis was observed. Slight increases in aspartate (ASAT; mean 5.6 U/L at the higher dose) and alanine (ALAT; mean 5.1 U/L at the higher dose) aminotransferases were not clinically significant. In this first, parallel-group placebo-controlled trial of a reductase inhibitor in a free-living NIDDM population, fluvastatin safely improved the combined TG, VLDL-C, IDL-C, LDL-C, and HDL-C abnormalities associated with NIDDM.
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PMID:Efficacy and safety of fluvastatin in patients with non-insulin-dependent diabetes mellitus and hyperlipidemia. 801 70

Occlusive atherosclerosis is a major cause of morbidity and mortality in renal transplant recipients. Hyperlipidemia associated with the transplanted state may be at least partially responsible for this complication and is therefore an important target of therapy. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are powerful cholesterol-lowering drugs, but their broad use in transplant recipients has been hindered by concerns about interactions with cyclosporine. Cyclosporine interferes with the elimination of these agents, increasing their plasma and tissue levels and predisposing the patient to rhabdomyolysis. Fluvastatin, the first entirely synthetic HMG-CoA reductase inhibitor, possesses a distinct pharmacologic profile, including a shorter half-life and virtually no active circulating metabolites. Therefore, it may interact differently with cyclosporine. The pharmacokinetics and safety of fluvastatin, 20 mg/day, were evaluated in 20 hypercholesterolemic renal transplant recipients also receiving cyclosporine, usually in combination with azathioprine and methylprednisolone, during the 14-week study. Fluvastatin area under the curve, maximum plasma concentration, and time to maximum plasma concentration were minimally increased in these patients, unlike findings reported for lovastatin, pravastatin, and simvastatin. This suggests that metabolism of fluvastatin may be less affected by cyclosporine than that of other reductase inhibitors. Fluvastatin was well tolerated, with no evidence of myopathy, rhabdomyolysis, or ophthalmologic abnormalities. These findings and the significant reductions in total cholesterol and low-density lipoprotein cholesterol levels and the ratio of low-density to high-density lipoproteins achieved in these patients support the broader use of fluvastatin to treat hypercholesterolemia in renal transplant recipients.
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PMID:Evaluation of fluvastatin in the treatment of hypercholesterolemia in renal transplant recipients taking cyclosporine. 897 Jun 7

We have previously demonstrated that monatepil maleate, AJ-2615, a new calcium antagonist endowed with alpha1-adrenoceptor blocking property, has antiatherosclerotic and plasma lipid-lowering effects in Japanese monkeys fed on a cholesterol-rich diet. To clarify the mechanisms on plasma lipid-lowering action, we investigated the effect of monatepil maleate in these monkeys on hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activity. Both ACAT activity and esterified cholesterol content in the livers of monkeys fed on a cholesterol-rich diet for 6 months significantly increased about 7- and 16-fold, respectively, as compared with those in monkeys fed on a standard diet. Monatepil maleate (30 mg/kg/day for 6 months, orally) inhibited the increases of ACAT activity and esterified cholesterol content by 51% and 71%, respectively. In in vitro experiments, monatepil maleate inhibited ACAT activity in a concentration-dependent manner, whereas it did not affect 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity. A kinetic analysis revealed that monatepil maleate was a noncompetitive type inhibitor of ACAT. Hepatic ACAT activity was significantly correlated to hepatic esterified cholesterol content (r = 0.775, P < .0001), to plasma very low density lipoprotein (VLDL) content (r = 0.765, P < .0001) and to plasma total cholesterol content (r = 0.573, P < .005) in the monkeys. These results suggest that ACAT-inhibiting effect of monatepil maleate plays an important role in the reduction of hyperlipidemia.
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PMID:Inhibitory effect of monatepil maleate on acyl-CoA:cholesterol acyltransferase activity in the liver of cholesterol-fed Japanese monkeys. 923 33

Exaggerated and prolonged postprandial triglyceridemia is a characteristic of patients with precocious coronary heart disease. Although large very low density lipoprotein (VLDL) particles accumulate during alimentary lipemia, the biological properties of the postprandial VLDL remain unknown. In the present study, an intravenous infusion of a chylomicron-like emulsion was given to healthy normolipidemic men to examine the effects of transient triglyceridemia in vivo on compositional and cell biological characteristics of VLDL. The postinfusion large(Svedberg flotation rate (Sf) (60-400) VLDL was found to have increased capacity to inhibit low density lipoprotein (LDL) binding to the LDL-receptor and a greater ability to suppress the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity of cultured fibroblasts compared to VLDL isolated from fasting plasma. These alterations in cellular interactions were accompanied by increases in the number of apolipoprotein (apo) E, C-I, and C-III molecules per large VLDL particle and loss of apoC-II, compositional changes similar to those observed after an oral fat load. The increase in number of apoE molecules per large VLDL particle correlated positively and significantly with the increase in the capacity of large VLDL to inhibit LDL binding to the LDL receptor (r = 0.76, P = 0.01, n = 10). In contrast, the composition of the small (Sf 20-60) VLDL particles did not change significantly, nor was the LDL receptor-mediated processing of these particles altered consistently. These observations indicate that large VLDL particles that accumulate during alimentary lipemia undergo compositional changes that render them more prone to cellular binding and uptake.
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PMID:Transient triglyceridemia in healthy normolipidemic men increases cellular processing of large very low density lipoproteins by fibroblasts in vitro. 950 2

Statins, i.e. HMG-CoA (3-hydroxymethyl-glutaryl co-enzyme A) reductase inhibitors, are widely used in the treatment of hyperlipidaemia. Several large trials published during recent years have clearly shown treatment with statins to reduce coronary heart disease morbidity and mortality rates, the beneficial effects being manifest sooner than expected. Despite the smallness of changes in lumen diameter during statin treatment, as measured with coronary angiography, the decrease in clinical events has been impressive. The question has therefore arisen of whether statins have other beneficial effects in addition to their lipid-lowering property. Several studies have been made of the effects of statin treatment on such variables as endothelial function, cellular immunity, lipoprotein oxidation, rheological factors, and the stabilisation of atherosclerotic plaque. Although the various statins differ in structure, there is a lack of comparative studies. However, available data suggest the beneficial effects of statins on other variables to be probably dependent on their primary lipid-lowering property.
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PMID:[Statins have other beneficial properties besides their cholesterol lowering effect]. 974 80

Although myopathy is considered an adverse effect of treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors and fibrates in combined hyperlipidemia, the present study was performed to investigate whether combined hyperlipidemia itself is associated with skeletal muscle pathology and whether lipid-lowering intervention has beneficial effects. To investigate whether combined hyperlipidemia is associated with skeletal muscle pathology, 10 male patients and 15 normolipidemic controls underwent a 45-minute standardized bicycle ergometer test at a load of 2 W/kg lean body mass (parallel study). One- and 8-hour postexercise increments in the plasma level of the muscle proteins creatine kinase (CK), myoglobin (Mb), and fatty acid-binding protein (FABP) were assessed as parameters for (subclinical) skeletal muscle pathology. The 8-hour postexercise increments in CK and Mb and 1-hour postexercise increment in Mb were significantly higher in patients than in controls, thus indicating increased exercise-induced muscle membrane permeability in combined hyperlipidemia. To investigate the effects of lipid-lowering intervention on skeletal muscle in combined hyperlipidemia, 21 subjects with combined hyperlipidemia were randomized double-blindly to receive 6 weeks of treatment with fluvastatin 40 mg/d, gemfibrozil 600 mg twice daily, or combination therapy. All subjects underwent an ergometer test before and after treatment. Gemfibrozil treatment alone reduced the CK increments 8 hours postexercise by 47% and the FABP increments 1 and 8 hours postexercise by 83% and 101%, respectively (all P < .05). Combined treatment reduced Mb increments 1 hour postexercise by 54% and FABP increments 8 hours postexercise by 44% (all P < .05). A highly significant correlation existed between therapy-induced changes in plasma triglycerides and changes in postexercise increments of FABP and Mb. In conclusion, combined hyperlipidemia is associated with an increased exercise-induced release of muscle proteins, which is ameliorated by triglyceride-lowering intervention. As FABP is an indicator for ischemia-induced skeletal muscle pathology, a possible explanation is the impaired muscle blood flow during hypertriglyceridemia, which may be reversed by triglyceride-lowering intervention. The mechanism and clinical relevance of these findings remain to be investigated.
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PMID:Combined hyperlipidemia is associated with increased exercise-induced muscle protein release which is improved by triglyceride-lowering intervention. 1059 82

The role of hyperlipidemia in graft coronary artery disease (GCAD) is controversial although hyper-triglyceridemia is an independent risk factor. Recent studies show that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitors decrease the incidence of GCAD in adults. The incidence of GCAD in pediatric patients is lower than in adults; it is not clear whether age-related differences in lipid metabolism account for some of this protection. This study was performed to: characterize the lipoprotein profile in children after heart transplantation; demonstrate that total cholesterol (TC) is a poor marker for underlying lipoprotein abnormalities; and to compare lipid abnormalities in patients who had been converted from cyclosporin A (CsA) to tacrolimus. Seventy-one determinations of fasting lipoprotein profiles were performed in a cohort of 28 children. Each child had at least two determinations on separate occasions. TC, low-density lipoprotein (LDL), and serum triglyceride (TG) levels were categorized as abnormal if greater than the 75th percentile for age and gender. A high-density lipoprotein (HDL) level less than the 25th percentile was considered abnormal. Immunosuppression included CsA or tacrolimus, azathioprine, and prednisone. We found that 90% of the patients studied had abnormalities of either TG or HDL. In contrast, LDL tended to be normal when adjusted for age and gender. TC was a poor indicator of any underlying abnormality in TG, LDL, or HDL. In patients converted to tacrolimus, no significant differences were found in the levels of TG, LDL or HDL compared with each patient's respective values while receiving CsA. Hence, lipoprotein abnormalities among pediatric heart transplant recipients are highly prevalent. TC is a poor screening tool in the evaluation for lipid abnormalities. Lipoprotein profiles remain statistically unchanged after conversion from CsA to tacrolimus.
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PMID:Lipoprotein abnormalities are highly prevalent in pediatric heart transplant recipients. 1093 19

Besides hyperglycemia and hypertension, a recently recognized risk factor for diabetic retinopathy (DR) appears to be hyperlipidemia. While studies using earlier generation lipid lowering agents in DR were disappointing, a randomized trial using HMG-CoA Reductase Inhibitors has strong rationale, though hitherto not attempted. The aim of the present study was to compare the HMG-CoA Reductase Inhibitor, simvastatin, with placebo in patients having DR in a double-blind randomized placebo-controlled trial. Fifty patients with diabetes mellitus (Type 1 and 2) with good glycemic control and hypercholesterolemia and having DR (non-clinically significant macular edema and visual acuity 6/24 or better) in either or both eyes were randomized to simvastatin 20-mg per day or placebo, and were followed up for 180 days. On simvastatin therapy, total cholesterol and low-density lipoprotein cholesterol (LDL-C) decreased (P < 0.001, respectively), and the level of high-density lipoprotein cholesterol (HDL-C) increased (P < 0.001). VA improved in four patients using simvastatin, (not statistically different from placebo group) and worsening of VA occurred in seven patients in the placebo group and none in the simvastatin group (P = 0.009). Fundus fluorescein angiography and color fundus photograph showed improvement in one patient in the simvastatin group, while seven patients showed worsening in the placebo group (P = 0.009). The observations of the current study suggest that the HMG-CoA Reductase Inhibitor simvastatin significantly retards the progression of retinopathy in diabetic patients with hypercholesterolemia. The potential of this class of drugs for the primary prevention of DR and other microvascular complications needs to be explored further.
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PMID:Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia. 1187 15


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