Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dyslipidemia, characterized by elevated serum levels of triglycerides and reduced levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol, has been recognized in patients with human immunodeficiency virus (HIV) infection. It is thought that elevated levels of circulating cytokines, such as tumor necrosis factor-alpha and interferon-alpha, may alter lipid metabolism in patients with HIV infection. Protease inhibitors, such as saquinavir, indinavir and ritonavir, have been found to decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with a syndrome of fat redistribution, insulin resistance, and hyperlipidemia. Elevations in serum total cholesterol and triglyceride levels, along with dyslipidemia that typically occurs in patients with HIV infection, may predispose patients to complications such as premature atherosclerosis and pancreatitis. It has been estimated that hypercholesterolemia and hypertriglyceridemia occur in greater than 50% of protease inhibitor recipients after 2 years of therapy, and that the risk of developing hyperlipidemia increases with the duration of treatment with protease inhibitors. In general, treatment of hyperlipidemia should follow National Cholesterol Education Program guidelines; efforts should be made to modify/control coronary heart disease risk factors (i.e. smoking; hypertension; diabetes mellitus) and maximize lifestyle modifications, primarily dietary intervention and exercise, in these patients. Where indicated, treatment usually consists of either pravastatin or atorvastatin for patients with elevated serum levels of LDL-C and/or total cholesterol. Atorvastatin is more potent in lowering serum total cholesterol and triglycerides compared with other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but it is also associated with more drug interactions compared with pravastatin. Simvastatin and lovastatin are significantly metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended for coadministration with protease inhibitors. A fibric acid derivative (gemfibrozil or fenofibrate) should be used in patients with primary hypertriglyceridemia. However, it must be kept in mind that protease inhibitors, such as nelfinavir and ritonavir, induce enzymes involved in the metabolism of the fibric acid derivatives and may, therefore, reduce the lipid-lowering activity of coadministered gemfibrozil or fenofibrate. In certain patients HMG-CoA reductase inhibitors may be used in combination with fibric acid derivatives but patients should be carefully monitored for liver and skeletal muscle toxicity. Select patients may experience improvements in serum lipid levels when their offending protease inhibitor(s) is/are exchanged for efavirenz, nevirapine, or abacavir; however each patient's virologic and immunologic status must be taken closely into consideration.
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PMID:Management of protease inhibitor-associated hyperlipidemia. 1472 85

Dyslipidemia is a major factor responsible for coronary heart disease and its reduction decreases coronary risk in patients with diabetes mellitus. However, the association of dyslipidemia with microvascular complications and the effect of intervention with lipid-lowering therapy in diabetes have been less investigated. We present the systematic review of association and intervention studies pertaining to dyslipidemia and microvascular disease in diabetes and also review possible mechanisms. Dyslipidemia may cause or exacerbate diabetic retinopathy and nephropathy by alterations in the coagulation-fibrinolytic system, changes in membrane permeability, damage to endothelial cells and increased atherosclerosis. Hyperlipidemia is associated with faster decline in glomerular filtration rate and progression of albuminuria and nephropathy. Recent evidence also suggests a role of lipoprotein(a) in progression of retinopathy and nephropathy in patients with diabetes mellitus. Lipid-lowering therapy, using single agents or a combination of drugs may significantly benefit diabetic retinopathy and diabetic nephropathy. In particular, hydroxymethyl glutaryl coenzyme A reductase inhibitors may be effective in preventing or retarding the progression of microvascular complications because of their powerful lipid-lowering effects and other additional mechanisms. However, most of the data are based on short-term studies, and need to be ascertained in long-term studies. Until more specific guidelines are available, aggressive management of diabetic dyslipidemia, according to currently accepted guidelines, should be continued for the prevention of macrovascular disease which would also benefit microvascular complications.
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PMID:The role of lipids in the development of diabetic microvascular complications: implications for therapy. 1472 67

One of the central functions of the kidney is to excrete low molecular weight, water soluble, plasma, waste products into the urine, whereas macromolecules, the size of albumin and larger, are retained. The flow of the glomerular filtrate is thought to follow an extracellular route, passing through the endothelial fenestrae, then across the glomerular basement membrane and finally through the slit diaphragm between the foot processes of podocytes. Recently it has been hypothesized that microalbuminuria leading to proteinuria and to end stage renal disease (ESRD) is mainly due to an altered glomerular fitration barrier at podocyte level. The "conditio sine qua non" for the development of diabetic ESRD is hyperglycemia. However, arterial hypertension and abnormalities of blood lipid concentrations and structure are also an important antecedent of such complication in diabetes mellitus. Interestingly it has been suggested that hyperglycemia, arterial hypertension and dyslipidemia cause disorderes of albumin excretion rate by damaging podocyte and slit diaphragm protein scaffold with over production of and extracellular release of oxygen radical species at glomerular level. The present review will briefly discuss recent reports which describe the relationship between blood glucose and lipid abnormalities and the occurrence and progression of renal damage in diabetes mellitus. More particularly we will give evidence that the risk of a rapid decline of glomerular function abruptly increases when glycated hemoglobin is steadily higher than 7.5% and postprandial blood glucose is above 200 mg/dL. Eventually we will analyze recent reports showing that treatment with statins, the inhibitors of hydroxymethylglutaryl-coenzyme A reductase, ameliorate the course of renal function in type 2 diabetic patients. It is not yet fully understood whether this effect is due to the lowering of the circulating levels of low density lipoproteins (LDL) or to an improved endothelial function or to lower patterns of LDL oxidation.
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PMID:Blood glucose and lipid control as risk factors in the progression of renal damage in type 2 diabetes. 1473

Dyslipidemia and vascular inflammation play critical roles in the onset of acute coronary syndromes including myocardial infarction. Recent advances in cardiovascular medicine demonstrate that lipid-lowering therapy by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) prevents acute coronary complications, probably by limiting inflammation in atheroma. Although a number of studies have suggested various effects of statins on vascular dysfunction independent of lipid lowering, the clinical benefits of such effects are not established as yet.
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PMID:Effects of statin therapy on vascular dysfunction. 1523 17

Dyslipidemia is a prominent feature of chronic renal failure (CRF) and a major risk factor for atherosclerosis and the progression of renal disease. CRF-induced dyslipidemia is marked by hypertriglyceridemia and a shift in plasma cholesterol from HDL to the ApoB-containing lipoproteins. Several studies have demonstrated a favorable response to administration of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors (statins) in CRF. This study was intended to explore the effect of statin therapy on key enzymes and receptors involved in cholesterol metabolism. Accordingly, CRF (5/6 nephrectomized) and sham-operated rats were randomized to untreated and statin-treated (rosuvastatin 20 mg x kg(-1) x day(-1)) groups and observed for 6 wk. The untreated CRF rats exhibited increased total cholesterol-to-HDL cholesterol ratio, diminished plasma lecithin:cholesterol acyltransferase (LCAT) and the hepatic LDL receptor, elevated hepatic acyl-CoA:cholesterol acyltransferase (ACAT), and no change in hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, or HDL receptor (SRB-1). Statin administration lowered HMG-CoA reductase activity, normalized plasma LCAT, total cholesterol-to-HDL cholesterol ratio, and hepatic LDL receptor but did not significantly change either plasma total cholesterol, hepatic cholesterol 7alpha-hydroxylase, total ACAT activity, or SRB-1 in the CRF animals. Statin administration to the normal control rats led to significant increases in plasma LCAT and hepatic LDL receptor, significant reductions of total cholesterol-to-HDL cholesterol ratio, hepatic HMG-CoA reductase activity, and cholesterol 7alpha-hydroxylase abundance with virtually no change in plasma cholesterol concentration. Thus administration of rosuvastatin reversed LCAT and LDL receptor deficiencies and promoted a shift in plasma cholesterol from ApoB-containing lipoproteins to HDL in CRF rats.
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PMID:HMG-CoA reductase inhibition reverses LCAT and LDL receptor deficiencies and improves HDL in rats with chronic renal failure. 1550 47

Atherosclerosis and its complications still represent the major cause of death in developed countries. Statins have revolutionized the treatment of dyslipidemia and demonstrated their ability to reduce and prevent coronary morbidity and mortality. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol synthesis. The effectiveness and rapidity of statin-induced decreases in coronary events led to the speculation that statins possess cholesterol-independent effects. Since mevalonate produced by the HMG-CoA reductase is not only the precursor of cholesterol, but also of non steroidal isoprenoid compounds, such as the farnesyl pyrophosphate and the geranylgeranyl pyrophosphate, statins also regulate the small signaling proteins, Ras and Rho. Thus, inhibition of these prenylated proteins might account for the non-lipid lowering effects of statins. In this review, we describe the numerous beneficial pleiotropic effects of statins that could modulate atherogenesis.
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PMID:Cholesterol-independent effects of statins in inflammation, immunomodulation and atherosclerosis. 1585 54

Dyslipidemia is frequent in patients with renal failure and in transplant recipient patients. This lead to a wide use of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with impaired renal function or in patients treated with cyclosporine as post-transplantation immunosuppressive therapy. As a result, it is crucial for those patients' physicians to be aware of how to handle these drugs when renal function is impaired and/or when cyclosporine is co-administered. Most statins have an extensive hepatic elimination and the renal route is usually a minor elimination pathway. However, pharmacokinetic alterations have been described for some of these drugs in patients with renal insufficiency. Cyclosporine is a widely used immunosuppresive therapy in solid organ transplant patients and drug-drug interactions are likely to occur when statins and cyclosporine are administered together. Those interactions may theoretically result in increased statins and/or cyclosporine serum levels with potential muscle and/or renal toxicity. As a result, caution is warranted if concurrent administration is performed. In this review, we synthesized the data from the literature on (1) the pharmacokinetics and dosage adjustment of atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin in patients with renal failure and (2) the potential drug-drug interactions between these drugs and cyclosporine in transplant recipient patients.
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PMID:Statins' dosage in patients with renal failure and cyclosporine drug-drug interactions in transplant recipient patients. 1586 Mar 77

Cardiovascular disease (CVD) is the leading cause of death worldwide. Many serious cardiovascular (CV) events occur in individuals with no prior manifestation of the disease, and often result in death. Awareness of the contributions of various risk factors to the occurrence of CVD is growing. Asymptomatic individuals with multiple risk factors at low or moderate levels can be at greater risk for CVD than those with a single risk factor at a high level. Dyslipidemia and hypertension are two risk factors that commonly coexist and are modifiable through lifestyle changes and/or medications. Recent trials with hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated that aggressive cholesterol-lowering therapy in patients without known atherosclerotic disease, but at high risk for CVD with relatively normal low-density lipoprotein cholesterol (LDL-C) levels (< 130 mg/dL), can significantly reduce the number of coronary events experienced by these patients. This subset of at-risk patients is better served by this approach than by treatment solely based on degree of dyslipidemia.
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PMID:Primary prevention trials: lessons learned about treating high-risk patients with dyslipidemia without known cardiovascular disease. 1600 78

Rosuvastatin, a new hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), is approved as an adjunct to diet in patients with primary hypercholesterolemia, mixed dyslipidemia, or Fredrickson type IV hypercholesterolemia. Because of its increased affinity for the reductase, rosuvastatin reduces the low-density lipoprotein cholesterol (LDL) level more than atorvastatin, simvastatin, and pravastatin do, without additional adverse effects. In addition, cytochrome P450 isoenzymes do not extensively metabolize rosuvastatin, and inhibitors of these isoenzymes do not substantially affect it. Rosuvastatin could be a first-line option for patients requiring a reduction of 50% or more to reach the LDL goal of the National Cholesterol Education Program Adult Treatment Panel III. Rosuvastatin monotherapy may allow patients to achieve this LDL goal earlier, and it may help them avoid combination therapy or potential adverse effects of high-dose statin therapy. However, because cardiovascular disease morbidity and mortality data are lacking for rosuvastatin (but available for all other marketed statins) and because its postmarketing data are limited, rosuvastatin should be reserved for patients requiring an LDL reduction of 50% or less who cannot reach the recommended goal with other statins because of adverse effects, drug interactions, or cost.
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PMID:Rosuvastatin for the treatment of hypercholesterolemia. 1600 77

Coronary heart disease (CHD) is the leading cause of death in the United States. Dyslipidemias, like decreased high-density lipoprotein (HDL) and increased low-density lipoprotein (LDL), have been linked through epidemiologic and experimental studies with the development of atherosclerosis and an increased risk of CHD. The introduction of various classes of lipid-lowering drugs, especially the hydroxymethylglutaryl-coenzyme-A-reductase inhibitors (statins), has allowed for effective treatment of hyperlipidemia. This article reviews the following nonpharmacologic approaches to hyperlipidemia: LDL apheresis, surgery, the emergence of HDL as a therapeutic target, gene therapy, and finally, the possibility of developing a vaccine against atherosclerosis.
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PMID:Nonpharmacologic approaches for the treatment of hyperlipidemia. 1610 86


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