Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperlipidemia has been associated with the development of transplant coronary vasculopathy (TCV) in heart transplant recipients and chronic rejection in kidney transplant recipients. HMG-CoA reductase inhibitors (HMGCoARIs) are effective in treating post-transplant hyperlipidemia, but their effects on patient and graft outcome remain unclear. In a prospective randomized trial investigating pravastatin (PVS) use early after heart transplantation, we observed that PVS treated patients had a decreased incidence of clinically severe acute rejection episodes resulting in a significant improvement in one year survival (94% vs. 78% in the control group, P = 0.02), and decreases in both the incidence and progression of TCV. This observation was validated in a prospective randomized study of kidney transplant recipients where we found that PVS reduced the incidence of acute rejection episodes (25% vs. 58% in the control group, P = 0.01). In both the heart and kidney transplant recipients, taking PVS, we noted decreases in natural killer cell (NKC) cytotoxicity. In vitro studies reveal that: PVS inhibits NKC cytotoxicity; PVS acts synergistically with cyclosporine to inhibit cytotoxic lymphocyte activity; and, other HMGCoARIs inhibit T-cell proliferation and monocyte chemotaxis. In conclusion, HMGCoARIs may have immunosuppressive properties in transplant recipients that could be useful in combating acute and chronic rejection.
 ...
PMID:Dual roles of HMG-CoA reductase inhibitors in solid organ transplantation: lipid lowering and immunosuppression. 858 72

Hyperlipidemia following successful renal transplantation is a frequent and persistent disorder, and lipid abnormalities are associated with ischemic heart disease. Correlates have been found to cyclosporine and steroids as the major causes of lipid disorders. Cardiovascular disease is currently the major cause of death among renal graft recipients in the long run. Therefore, lipid lowering therapy appears to be useful in those patients without cardiovascular disease (primary prevention) and is mandatory in those with established coronary artery disease (secondary prevention). Because of the multiplicity of other cardiovascular risk factors, hyperlipidemia might only be of minor importance. On the other hand, lipids may even accelerate the development of arteriosclerosis in a preinjured vascular endothelium. Dietary modification or reduction of dietary fat is considered to be the first line of antilipemic therapy. Unfortunately, hyperlipidemia appears not to be responsive to modification of dietary fat without weight reduction. In general, patients taking immunosuppressive drugs after organ transplantation are grouped under high risk population when pharmacological intervention is selected, since only some lipid lowering drugs are safe and efficacious in short-term studies and when used with precaution. Low-dose HMG-CoA reductase inhibitor is the drug of choice for lowering LDL cholesterol. Immunosuppression withdrawal protocols have successfully been used to control massive hyperlipidemia in immunologically stable patients in the long term. Although evidence from prospective controlled intervention studies is lacking, it is reasonable to adopt the principle of a broad-based approach aimed at reducing LDL cholesterol as well as other major risk factors for cardiovascular disease in this patient population. The likelihood is that effective control of serum lipids and lipoproteins may achieve a similar beneficial reduction in absolute mortality in renal transplant recipients as already demonstrated in individuals without kidney disease but with cardiovascular damage.
 ...
PMID:Clinical utility of antilipidemic therapies in chronic renal allograft failure. 858 86

Hyperlipidemia associated with non-insulin-dependent diabetes mellitus (NIDDM) and insulin resistance is characterized by high triglyceride levels; raised levels of total low-density lipoprotein (LDL), which is made up of small, dense, cholesterol-rich particles; low levels of high-density lipoprotein (HDL); and glycosylation of apolipoproteins. Optimal drug therapy for this lipid profile is controversial. To test whether a fibrinic acid derivative (gemfibrozil) or a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (lovastatin) would produce better results in these patients, a crossover study was performed. Gemfibrozil 600 mg twice daily and, after a washout period, lovastatin 20 to 40 mg twice daily were administered to nine patients with NIDDM. Gemfibrozil significantly decreased triglyceride, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) levels, the total cholesterol:HDL ratio, and the IDL plus VLDL;HDL ratio, and significantly increased levels of HDL, HDL2, and HDL3. Lovastatin significantly decreased levels of total cholesterol, calculated LDL, directly measured LDL, IDL, total triglycerides, VLDL, and the ratios of LDL:HDL, total cholesterol:HDL, and directly measured LDL:HDL and significantly increased total HDL and HDL3 levels. Gemfibrozil was significantly more effective than lovastatin in raising total HDL and HDL3 levels and in lowering the IDL plus VLDL:HDL ratio. Lovastatin was significantly more effective than gemfibrozil in lowering total cholesterol, LDL, directly measured LDL, and the LDL:HDL and directly measured LDL:HDL ratios. In the absence of malignant hypertriglyceridemia, an HMG-CoA reductase inhibitor, rather than a fibrinic acid derivative, is indicated for the treatment of patients with dyslipidemia associated with NIDDM and insulin resistance.
 ...
PMID:A comparison of lovastatin, an HMG-CoA reductase inhibitor, with gemfibrozil, a fibrinic acid derivative, in the treatment of patients with diabetic dyslipidemia. 859 42

Hyperlipidemia is an important complication of kidney transplantation affecting up to 74% of recipients. HMG-CoA reductase inhibitors are reported to provide safe and effective treatment for this problem. A recent study suggests that pravastatin, an HMG-CoA reductase inhibitor, also decreases the incidence of both clinically severe acute rejection episodes and natural killer cell cytotoxicity after orthotopic heart transplantation. We have performed a prospective randomized pilot study of the effect of pravastatin on these same parameters after cadaveric kidney transplantation. Graft recipients were randomized to receive pravastatin after transplantation or no pravastatin (24 patients in each group) in addition to routine cyclosporine and prednisone immunosuppression. Lipid levels, acute rejection episodes and serial natural killer cell cytotoxicities were followed for 4 months after the transplant. At the end of the study period, pravastatin had successfully controlled mean total cholesterol levels (202.6 +/- 9.3 vs. 236.5 +/- 11.9 mg/dl, P < 0.02), LDL levels (107.9 +/- 6.6 vs.149.6 +/- 10.7 mg/dl, P < 0.002), and triglyceride levels (118.8 +/- 14.2 vs. 157.2 +/- 13.8 mg/dl, P < 0.05). In addition, the pravastatin-treated group experienced a reduction in the incidence of biopsy-proven acute rejection episodes (25% vs. 58%, P = 0.01), the incidence of multiple rejections episodes (P < 0.05), and the use of both pulse methylprednisolone (P = 0.01) and OKT3 (P = 0.02). Mean natural killer cell cytotoxicity was similarly reduced (11.3 +/- 1.6 vs. 20.0 +/- 2.0% lysis of K562 target cells, P < 0.002). These data suggest that pravastatin exerts an additional immunosuppressive effect in kidney transplant recipients treated with cyclosporine-based immunosuppression.
 ...
PMID:The effect of pravastatin on acute rejection after kidney transplantation--a pilot study. 863 73

The beneficial effect of cholesterol-lowering therapy for secondary prevention in patients with coronary artery disease (CAD) is well established. The therapeutic goal in this situation is a low-density lipoprotein (LDL) cholesterol level of 100 mg/dl. Cholesterol-lowering therapy will not only lead to a reduction in the progression of lesions but also and probably more importantly will reduce lesion activation and rupture and improve endothelial vasomotor function. Depending on the underlying hyperlipoproteinemia, the first choice for single drug therapy is a bile acid-binding resin or a hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor in isolated LDL hypercholesterolemia, and nicotinic acid, a fibric acid, or a HMG-CoA reductase inhibitor in combined hyperlipidemia. Combination therapy usually consists of a bile acid-binding resin with either an HMG-CoA reductase inhibitor, a fibric acid, or nicotinic acid in LDL hypercholesterolemia and nicotinic acid with a fibric acid in combined hyperlipidemia.
 ...
PMID:Drug therapy of severe hypercholesterolemia in patients with coronary artery disease. 886 Jul 8

More than $100 billion is spent in the United States each year on cardiovascular disease, primarily for hospitalizations and revascularization procedures. This is more than for any other disease state. As the clinical practice of medicine shifts from the paradigm of private practice to the managed care environment, cost-effectiveness is becoming increasingly important. A primary measure in analyzing cost-effectiveness is the cost-effectiveness ratio, or the dollar cost per unit of improvement for a given expenditure. This measure allows healthcare planners to compare completely different interventions. With approximately 52 million adult U.S. citizens having elevated low-density lipoprotein (LDL) cholesterol levels, lipid-lowering therapy---with diet or 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors---is an important consideration for primary care physicians and managed care providers. The National Health and Nutrition Examination Survey (NHANES) III indicates that 75-88% of adults who have coronary artery disease (CAD) risk factors or CAD require only a moderate (20--30%) reduction in LDL cholesterol levels to reach National Cholesterol Education Program goals. The clinical literature shows that all 4 of the currently available HMG-CoA reductase inhibitors can provide appropriate, moderate LDL cholesterol reductions within their recommended dosage ranges. For the majority of patients who need a 20--30% reduction in LDL cholesterol, fluvastatin 20 or 40 mg once daily provides the most cost-effective HMG-CoA therapy, expressed as cost of therapy per 1% LDL cholesterol reduction. For patients who need a >30% LDL cholesterol reduction, a high-dose HMG-CoA reductase inhibitor (e.g., simvastatin 20 or 40 mg/day) or a combination of a lower-dose HMG-CoA reductase inhibitor and a bile acid resin is the preferred initial therapy. Although a true cost-effectiveness analysis would incorporate morbidity and mortality data from clinical trials, analysis using intermediate endpoints, such as LDL cholesterol reduction, suggests that fluvastatin is the preferred initial HMG-CoA reductase inhibitor for the treatment of moderate hyperlipidemia.
 ...
PMID:Cost-effectiveness of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor therapy in the managed care era. 887 73

The hyperlipidemia- and atherosclerosis-prone (HAP) Japanese quail is a strain developed for the study of atherosclerosis by genetic selection from the commercially available (CA) Japanese quail. To delineate the characteristics of cholesterol metabolism in this strain, concentrations of serum lipids as well as hepatic enzyme activities were compared between HAP and CA quail. The hepatic enzymes studied are involved in the key step reaction in cholesterol metabolism: HMG-CoA reductase, ACAT, and cholesterol 7 alpha-hydroxylase. The animals were fed ad libitum with either 1% cholesterol or cholesterol-free semipurified diet for 28 days. Although a significant increase (p < 0.01) in serum cholesterol was observed in both strains on elapse of cholesterol feeding, formation of atheroma was seen exclusively in HAP quail of the cholesterol-fed group. The serum and liver cholesterol levels of HAP quail fed the cholesterol diet were significantly higher (p < 0.01) than those of CA quail. No significant differences were seen in the rate of cholesterol biosynthesis (HMG-CoA reductase activity), cholesterol ester formation (ACAT activity) and cholesterol catabolism (7 alpha-hydroxylase activity) between CA and HAP quail. Furthermore, the fecal excretions of acidic and neutral sterol showed no significant difference between strains. Although the formation of atheroma in HAP quail may be presumably due to the contribution of the marked increase in serum cholesterol level, the rate of cholesterol catabolism and synthesis in HAP quail compared well with those of CA quail. These observations suggest that the retarded rate of cholesterol biosynthesis or catabolism is not responsible for hypercholesterolemia in HAP quail.
 ...
PMID:Effect of dietary cholesterol on the activities of key enzymes of cholesterol metabolism in hyperlipidemia- and atherosclerosis-prone Japanese quail. 890 30

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.
 ...
PMID:Evaluation of fluvastatin in the treatment of hypercholesterolemia in renal transplant recipients taking cyclosporine. 897 Jun 7

The objective of this study was to compare the lifetime cost-effectiveness of HMG-CoA reductase inhibitors and fibrates for the treatment of hyperlipidemia. Estimates of lipid modification achieved due to drug therapy were based on published head-to-head comparisons of specific HMG-CoA reductase inhibitors and fibrates in randomized, double-blind studies. We used a validated coronary heart disease (CHD) prevention computer model to estimate the costs and benefits of lifelong lipid modification. The patients were middle-aged men and women who were free of CHD, with either primary type IIa or IIb hyperlipidemia. The intervention used were specific HMG-CoA reductase inhibitors and fibrates at several dosages, which reduced total cholesterol 11-34% and increased high-density lipoprotein cholesterol 1-29%. The main outcome measure was the cost per year of life saved after discounting benefits and costs by 5% annually. The lifetime cost effectiveness of HMG-CoA reductase inhibitors (fluvastatin, lovastatin, pravastatin, simvastatin) and fibrates (bezafibrate, fenofibrate, gemfibrozil) for the treatment of primary hyperlipidemia varied according to patient population, the effectiveness of each drug in modifying lipid levels, and the price of each drug. The estimates of cost per year of life saved for HMG-CoA reductase inhibitors range from $19,886 to $73,632, and $16,955 to $59,488 for fibrates according to gender and type of primary hyperlipidemia. Fluvastatin 20 mg/day was significantly more cost effective than gemfibrozil 1200 mg/day for male patients with type IIa hyperlipidemia. Simvastatin 17.3 mg/day or 20 mg/day yielded similar cost-effectiveness ratios compared with fibrates among type II hyperlipidemic patients. However, micronized fenofibrate was more cost effective than simvastatin 20 mg/day among type IIb patients. The cost effectiveness of lipid therapy varies widely and can be maximized by selecting specific drugs for specific lipid abnormalities.
 ...
PMID:A head-to-head comparison of the cost effectiveness of HMG-CoA reductase inhibitors and fibrates in different types of primary hyperlipidemia. 911 Jan 23

Atorvastatin is a synthetic HMG-CoA reductase inhibitor which lowers plasma cholesterol levels by inhibiting endogenous cholesterol synthesis. It also reduces triglyceride levels through an as yet unproven mechanism. Dose-dependent reductions in total cholesterol, low density lipoprotein (LDL)-cholesterol and triglyceride levels have been observed with atorvastatin in patients with hypercholesterolaemia and in patients with hypertriglyceridaemia. In large trials involving patients with hypercholesterolaemia, atorvastatin produced greater reductions in total cholesterol, LDL-cholesterol, apolipoprotein B and triglyceride levels than lovastatin, pravastatin and simvastatin. In patients with primary hypercholesterolaemia, the combination of atorvastatin and colestipol tended to produce larger reductions in LDL-cholesterol levels and smaller reductions in triglyceride levels than atorvastatin monotherapy. Although atorvastatin induced smaller reductions in triglyceride levels and more modest increases in high density lipoprotein (HDL)-cholesterol levels than either fenofibrate or nicotinic acid in patients with combined hyperlipidaemia, it produced larger reductions in total cholesterol and LDL-cholesterol. As with other HMG-CoA reductase inhibitors, the most frequently reported adverse events associated with atorvastatin are gastrointestinal effects. In comparative trials, atorvastatin had a similar adverse event profile to that of other HMG-CoA reductase inhibitors. Clinical data with atorvastatin are limited at present. However, with its ability to markedly reduce LDL-cholesterol levels, atorvastatin is likely to join other members of its class as a first-line agent for the treatment of patients with hypercholesterolaemia, if changes in lipid levels with atorvastatin convert to reductions in CHD mortality and morbidity. Atorvastatin may be particularly suitable for patients with heterozygous or homozygous familial hypercholesterolaemia because of the marked reductions in LDL-cholesterol experienced with the drug. Additionally, because of its triglyceride-lowering properties, atorvastatin appears to have the potential to become an appropriate treatment for patients with combined hyperlipidaemia or hypertriglyceridaemia.
 ...
PMID:Atorvastatin. A review of its pharmacology and therapeutic potential in the management of hyperlipidaemias. 912 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>