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:C0242339 (dyslipidemia)
13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Newer, more effective statins are powerful agents for reducing elevated levels of low-density lipoprotein (LDL) cholesterol and thereby lowering the risk of coronary heart disease (CHD) and related adverse events. Although LDL remains the primary target of therapy for reducing CHD risk, increased interest is focusing on apolipoprotein B (apoB)-containing lipoprotein subfractions--particularly very-low-density lipoprotein (VLDL). VLDL remnants, and intermediate-density lipoproteins (IDL)--as secondary targets of therapy. Elevated apoB is known to be an important risk factor for CHD, and dysregulation of the metabolism of apoB-containing lipoproteins is involved in the progression of atherosclerosis. Statins reduce circulating concentrations of atherogenic apoB-containing lipoproteins by decreasing the production of VLDL in the liver and, thus, the production of VLDL remnants and LDL. Statins also increase the clearance of these particles through upregulation of LDL receptors in the liver. Efforts to develop statins with enhanced lipid-modifying properties are ongoing. The optimal statin would offer a high degree of inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a prolonged duration of action, hepatic selectivity for maximal upregulation of LDL receptors, and a low potential for drug-drug interactions. Recent studies have shown that rosuvastatin, a new agent in this class, demonstrates these qualities. Rosuvastatin is a highly effective inhibitor of HMG-CoA reductase, is relatively nonlipophilic, has a half-life of approximately 20 h, exhibits hepatic selectivity, has little systemic availability, and has a low potential for drug-drug interactions because of its limited degree of metabolism by the cytochrome P450 system. A recent double-blind, crossover study revealed that treatment with rosuvastatin resulted in marked reductions in apoB-containing lipoproteins in patients with type IIa or IIb dyslipidemia. By reducing the number of atherogenic lipoprotein particles, rosuvastatin decreases the atherosclerotic burden in hyperlipidemic patients at high risk for CHD and related adverse outcomes.
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PMID:New dimension of statin action on ApoB atherogenicity. 1253 16

Because of their excellent tolerability and their positive impact on lipid parameters, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have become the drugs of first choice for many patients with dyslipidemia. Rosuvastatin is an investigational statin in the U.S. with a number of favorable characteristics, which include low lipophilicity, high hepatocyte selectivity, minimal metabolism, and a low propensity for cytochrome P450 drug interactions. Rosuvastatin has been studied at doses ranging from 1 to 80 mg. In comparative clinical trials, rosuvastatin given at 5 to 10 mg/day reduced low-density lipoprotein cholesterol to a significantly greater extent than atorvastatin 10 mg/day, pravastatin 20 mg/day, and simvastatin 20 mg/day. In addition, rosuvastatin exhibited beneficial effects on other lipid parameters such as high-density lipoprotein cholesterol and triglycerides. Rosuvastatin's safety profile was demonstrated to be similar to those of other statins. Given its favorable pharmacokinetic and pharmacodynamic characteristics, rosuvastatin is likely to become a valuable addition to the statin drug class. The author reviews the pharmacologic and pharmacokinetic properties of this new statin.
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PMID:Rosuvastatin: a new HMG-CoA reductase inhibitor for the treatment of hypercholesterolemia. 1254 90

The significant age-adjusted decline in cardiovascular mortality that has occurred over the past three decades is multifactorial. However, the advent of statin therapy has markedly facilitated the optimization of dyslipidemia in patients at risk for coronary events. Statin therapy has proven to be effective in reducing morbidity and mortality in large-scale primary and secondary prevention trials. As with all therapies, the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co A) reductase inhibitors is not without clinical risks. Myopathy, albeit uncommon, was one of the earliest clinical problems associated with statin therapy. Recent data from the large-scale statin mega-trials have clarified the quantitative clinical risk-benefit relationship of reductase inhibitors relative to the induction of muscle toxicity. Histopathologic studies have clarified the potential role of statins in the syndrome of myalgias and normal creatine kinase levels. However, the precise mechanism of statin-associated muscle toxicity remains unclear and is potentially related to genetically mediated muscle enzyme defects, drug interactions, intracellular depletion of metabolic intermediates, and intrinsic properties of the statins per se.
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PMID:Statins and myotoxicity. 1257 93

Low high-density lipoprotein (HDL) cholesterol is an important predictor of risk for coronary artery disease. Although current treatment guidelines for dyslipidemia do not include specific targets for HDL cholesterol, the categorical definition of low HDL cholesterol has been changed from <35 mg/dL to <40 mg/dL. 3-hydroxy-3-methylglutaryl reductase inhibitors (statins) increase HDL cholesterol to a moderate degree. Fibrates also increase HDL cholesterol to a moderate degree and have additive effects with statins. Niacin is the most potent currently available agent for increasing HDL cholesterol, and its effects are also additive to those of statins. Other agents that increase HDL cholesterol include thiazolidinediones, estrogen, and omega-3 fatty acids. The mechanisms by which nonstatin pharmacologic agents increase HDL cholesterol are not completely understood but probably involve multiple mechanisms for each class.
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PMID:Effects of nonstatin lipid drug therapy on high-density lipoprotein metabolism. 1267 99

Patients with end-stage renal disease (ESRD) treated with dialysis have a dramatically elevated rate of cardiovascular disease (CVD) compared to the general population. Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") has been shown to markedly reduce cardiovascular risk in patients without renal failure, but their effect has not been fully studied in the dialysis population. In this article we will first discuss the known benefits of statin therapy in the general population and summarize the current guidelines for such therapy. We will then examine the evidence linking dyslipidemia and cardiac disease in the dialysis population and discuss possible pathophysiologic mechanisms by which statins could prevent cardiac disease in these patients. We will also review prior clinical studies of the effects of statins in patients on dialysis, with particular attention to the safety and efficacy of these drugs in this population. Finally, we will review how statins are currently being used in the care of dialysis patients and suggest whether an expanded utilization of these drugs could help reduce the enormously high rates of cardiac disease in this patient population.
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PMID:Are HMG-CoA reductase inhibitors underutilized in dialysis patients? 1275 74

The increasing prevalence of type 2 diabetes is a major problem for healthcare providers globally, since it is associated with serious microvascular and macrovascular complications. Although microvascular complications can be largely reduced with strict glycemic control, prevention of macrovascular disease involves a multifaceted approach that addresses all major risk factors, including dyslipidemia, hypertension, and insulin insensitivity. In particular, the treatment of diabetic dyslipidemia is a major challenge for diabetologists and cardiologists, as it is characterized by an array of lipid abnormalities. The management of diabetic dyslipidemia should initially include lifestyle approaches such as improved nutrition and weight reduction; however, the majority of patients require the addition of pharmacotherapy. Whilst insulin and/or oral hypoglycemic drugs are generally prescribed for the treatment of hyperglycemia, the addition of lipid-lowering drugs may be necessary for the control of diabetic dyslipidemia. The American Diabetes Association guidelines recommend lowering of low-density lipoprotein cholesterol (LDL-C) as a first priority. Hydroxy-methylglutaryl coenzyme A reductase inhibitors (statins) are recommended for first-line therapy in diabetic patients, since these agents are effective at reducing LDL-C levels. Whilst statins provide effective control of dyslipidemia in the majority of patients, more efficacious treatment regimens would provide greater benefit to more patients. Combination therapies may provide one solution to obtaining maximal lipid profile modifications, although the introduction of new, more efficacious agents for use as monotherapy may provide a more acceptable option, as drug combinations are often associated with poor tolerability and patient compliance.
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PMID:Statin therapy for the treatment of diabetic dyslipidemia. 1287 5

Dyslipidemia, especially elevated low-density lipoprotein cholesterol (LDL-C), increases the risk of coronary heart disease and subsequent morbidity or mortality. For more than a decade, the National Cholesterol Education Program (NCEP) has endeavored to raise awareness of the dangers of dyslipidemia and to encourage the implementation of recommended treatment strategies. However, despite this initiative, previously published NCEP targets were not met. The recently released NCEP-Adult Treatment Panel III guidelines recommend more aggressive LDL-C reduction, elevation of categorical low high-density lipoprotein binding protein, and increased monitoring of moderate triglyceride elevations. Although the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are the most powerful medications available to reduce LDL-C, studies have shown that more than half of patients treated with these drugs do not achieve therapeutic targets and the resultant decrease in coronary heart disease events. There are a number of possible reasons for this, including potency of the statins and a lack of compliance on the part of patients and providers. Another concern with the available statins is the issue of drug-drug interactions. Some of these concerns may be addressed by newer agents in this drug class that are in development. They appear to have the potential to induce even greater reductions in LDL-C and to positively affect other lipoproteins. They also have the potential for less risk of drug-drug interactions. Nurse practitioners can play a pivotal role in improving the management of dyslipidemia by ensuring the proper implementation of current guidelines, helping patients adhere to treatment protocols, and remaining abreast of developments that may pave the way toward even more effective intervention in the future.
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PMID:Managing the spectrum of dyslipidemia in primary care. 1296 79

We aimed to examine postprandial dyslipidemia in normolipidemic patients with coronary artery disease (CAD) and the effects of treatment with an hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor (atorvastatin). Subjects with angiographicaly established CAD were randomized to treatment for 12 weeks with 80 mg/d atorvastatin or placebo and the effects on markers of postprandial lipoproteins and low-density lipoprotein (LDL)-receptor binding determined. LDL-receptor binding was determined in mononuclear cells, as a surrogate for hepatic activity. Fasting levels of cholesterol (P <.001), LDL-cholesterol (P <.001), apolipoprotein (apo)B(48) (P =.019), remnant-like particle-cholesterol (RLP-C) (P =.032), and total postprandial apoB(48) area under the curve (AUC) (P =.013) significantly decreased with atorvastatin compared with placebo. Atorvastatin also significantly increased LDL-receptor binding activity (P <.001), and this was correlated with changes in fasting apoB(48) (r =.80, P =.01). We report that aberrations in chylomicron metabolism in normolipidemic CAD subjects are correctable with atorvastatin by a mechanism involving increased LDL-receptor activity. This effect may, in part, explain the cardiovascular benefit of statins used in clinical trials of CAD patients with normal lipid levels.
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PMID:Effect of atorvastatin on apolipoprotein B48 metabolism and low-density lipoprotein receptor activity in normolipidemic patients with coronary artery disease. 1456 79

Rhabdomyolysis is a life-threatening clinical and biochemical syndrome that results from injury to skeletal muscle. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been associated with myopathy and rhabdomyolysis. Although rhabdomyolysis is a rare adverse event associated with this class of drugs, their prevalent use in the management of dyslipidemia makes it increasingly important for clinicians to understand the nature of this condition. Rhabdomyolysis can occur with all statins when used alone and particularly when combined with other drugs that are themselves myotoxic or that elevate the concentration of the statin. Statins are particularly susceptible to the latter effect because of their metabolism by the CYP450 system and their low oral bioavailability. In this report, we describe a case of rhabdomyolysis and acute renal failure secondary to the interaction between danazol and simvastatin.
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PMID:Potential drug interaction between simvastatin and danazol causing rhabdomyolysis. 1471 20

Plasma levels of high-density lipoprotein-cholesterol (HDL-C) are a powerful independent cardiovascular risk factor, bearing an inverse relationship with atherosclerotic cardiovascular disease (with risk rising sharply when levels are <1.04 mmol/L). Apart from its protective role in atherosclerosis, HDL-C increases fibrinolysis, is an antioxidant to low density lipoprotein-cholesterol (LDL-C), and decreases platelet aggregability. Up to a third of patients with atherosclerotic cardiovascular disease have 'desirable' plasma levels of total cholesterol but low HDL-C levels. Benefits of treating low plasma HDL-C levels were clearly demonstrated in the Veterans Affairs HDL Intervention Trial (VA-HIT) where gemfibrozil reduced nonfatal infarcts and coronary deaths by 22%. This was achieved by a 6% increase in plasma HDL-C levels, and a 24.5% decrease in plasma levels of triglycerides, without any significant decrease in LDL-C levels. Multivariate analyses revealed the rise in plasma HDL-C levels after treatment, but not decreases in plasma levels of triglycerides or LDL-C, predicted coronary artery disease events. The typical patient under consideration in this article is one with plasma levels of HDL-C <1 mmol/L, LDL-C <3.37 mmol/L [either receiving therapeutic lifestyle changes or or LDL-C-lowering therapy comprising a hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor or bile acid sequestrant] and fasting triglycerides <2.26 mmol/L. We propose this dyslipidemia be classified as Type VI phenotype following the Frederickson and Lees classification. High-risk patients (with >/=2 risk factors for atherosclerotic cardiovascular disease, or 10-year cardiovascular risk >20%), patients with established atherosclerotic cardiovascular disease, or type 2 diabetes mellitus, or metabolic syndrome should receive pharmacotherapy. Plasma HDL-C levels >1.16 mmol/L may be considered optimal and between 1 and 1.16 mmol/L as desirable. Fibric acid derivatives, nicotinic acid, HMG-CoA reductase inhibitors, estrogens, and ethanol (not recommended as therapy) increase plasma HDL-C levels. Nicotinic acid is the most potent agent and recent reports indicate that, in contrast to gemfibrozil, it selectively increases antiatherogenic HDL subfraction, lipoprotein (Lp) AI (without apolipoprotein AII), in patients with low plasma HDL-C levels. An extended-release formulation, administered once daily, has improved the tolerability of nicotinic acid. Recent evidence also indicates that nicotinic acid may effectively correct dyslipidemia in patients with diabetes mellitus without significantly compromising glycemic control. Fibric acid derivatives and estrogen raise plasma HDL-C levels by different mechanisms of action, and these agents may be used with nicotinic acid. Combination therapy (especially HMG-CoA reductase inhibitor and nicotinic acid) should be considered in patients with atherosclerotic cardiovascular disease and low plasma HDL-C levels.
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PMID:Optimal therapy of low levels of high density lipoprotein-cholesterol. 1472 46


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