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)

Coronary heart disease (CHD) is the leading cause of death worldwide, and effective treatment of hyperlipidaemia can prevent development of CHD and significantly reduce the risk for cardiovascular events and mortality in this disease. The advent of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) has revolutionised the treatment of hyperlipidaemia, but many patients receiving these drugs still do not achieve their therapeutic goals. Rosuvastatin (Crestor; formerly ZD4522) is a new, potent and long-lasting inhibitor of HMG-CoA reductase that is highly selective for hepatocytes. Its pharmacokinetics permit once-daily dosing, and a lack of oxidative hepatic metabolism results in a reduced potential for drug-drug interactions. Preliminary clinical results indicate that it produces rapid dose-related reductions in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B that may exceed those achieved with other currently available statins. Increases in high-density lipoprotein cholesterol have also been observed. Rosuvastatin is also well tolerated, with no evidence of either hepato- or myotoxicity. It is hoped that new agents such as rosuvastatin may help to reduce the high global morbidity, mortality and associated costs of CHD and related vascular disorders.
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PMID:Clinical rationale for rosuvastatin, a potent new HMG-CoA reductase inhibitor. 1150 Dec 30

Cardiovascular disease (CVD) remains a major cause of death in industrialised societies, and elevated serum lipids are a significant, highly prevalent and undertreated risk factor for this condition. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have revolutionised the treatment of hyperlipidaemia, and results from large-scale, long-term clinical trials have shown that the substantial reductions in low-density lipoprotein cholesterol (LDL-C) achieved with these drugs are associated with dramatic decreases in cardiovascular risk. Results from recent comparative clinical trials that have included a new drug in this class, rosuvastatin (Crestor), have demonstrated that it is significantly superior to atorvastatin, pravastatin and simvastatin in reducing total cholesterol, LDL-C and apolipoprotein B (Apo B). It is also significantly more effective than atorvastatin in increasing high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I). Rosuvastatin was also superior to all these agents in helping patients meet European Atherosclerosis Society (EAS) and National Cholesterol Education Programme (NCEP) goals for LDL-C. The results of an increasing number of studies indicate that statins have a wide range of pleiotropic properties that almost certainly contribute to their ability to decrease cardiovascular risk and may also make them valuable for treatment of other diseases. These actions include plaque stabilisation, improvement of endothelial function, inhibition of smooth muscle cell proliferation and migration, reduction of expression of adhesion molecules, prevention of cholesterol esterification and accumulation, reduction of secretion of matrix metalloproteinases by macrophages, reduction of platelet activity, reduction of formation of thrombogenic factors, chemoprotection and induction of bone morphogenic protein-2 (BMP-2). Further exploration of these actions will provide key information about class effects and properties of specific members of this highly useful group of drugs.
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PMID:Statin therapy: rationale for a new agent, rosuvastatin. 1213 48

Rosuvastatin is a new HMG-CoA reductase inhibitor with unique pharmacologic and pharmacokinetic properties. It has additional HMG-CoA reductase enzyme-binding interactions that cause tighter binding, has substantial active transport into hepatocytes, and has the lowest IC50 for sterol synthesis in hepatocytes. Rosuvastatin 10 mg and 80 mg dosages have superior low-density lipoprotein (LDL) cholesterol-lowering efficacy as compared to atorvastatin 10 mg and 80 mg. Rosuvastatin 10 mghas also been shown to have superior LDL reductions to 20 mg of both simvastatin and pravastatin. This agent can raise high-density lipoprotein (HDL) 8% to 12% and lower triglycerides by 10% to 35%. Rosuvastatin is a hydrophilic agent with poor penetration in extrahepatic tissue such as human umbilical vein endothelial cells and fibroblasts. It also has a low potential for cytochrome P450 drug interactions and can be dosed in the morning or night. In conclusion, rosuvastatin is an agent with molecular alterations that provide it with unique pharmacologic and phannacokinetic effects. As such, it is a novel and unique HMG-CoA reductase inhibitor for the treatment of hyperlipidemia.
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PMID:A review of the pharmacologic and pharmacokinetic aspects of rosuvastatin. 1221 Dec 21

Inflammation is a major factor in atherothrombotic disease. Levels of high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation and a mediator of atherothrombotic disease, have been shown to correlate with cardiovascular disease risk. Recent findings in 27,939 healthy women in the Women's Health Study indicate that hs-CRP (1) is a stronger predictor of risk than low-density lipoprotein (LDL) cholesterol, (2) predicts elevated risk in subjects without overt hyperlipidemia, and (3) adds prognostic information to risk scoring and LDL cholesterol categories. Other data from this cohort show that hs-CRP level adds prognostic information to the diagnosis of the metabolic syndrome. Taken together with other data in men on the association of hs-CRP with vascular risk, a strong argument is provided for screening in the primary prevention population. With regard to potential treatment, statins have been found to reduce hs-CRP levels, and data from statin treatment trials raise the possibility that subjects with elevated hs-CRP levels may derive greater benefit from treatment than do patients without elevated hs-CRP. The Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial is planned to examine the effects of rosuvastatin treatment in preventing cardiovascular events in 15,000 healthy subjects with elevated hs-CRP levels in the absence of overt hyperlipidemia.
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PMID:High-sensitivity C-reactive protein and cardiovascular risk: rationale for screening and primary prevention. 1294 72

Statins are central to the government's National Service Framework (NSF) for coronary heart disease (CHD). NHS spending on statins is currently about pounds sterling 500 million per annum and rising at an annual rate of 30%. Although generally considered to be a cost-effective treatment for hyperlipidaemia and cardiovascular disease, given the high and rising expenditure on statins in the UK, there is a pressing need to ensure that the choice between available statins reflects cost-effectiveness considerations. A decision model was developed to establish the cost-effectiveness of treating new hypercholesterolaemic patients to UK and European target levels of blood total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), using rosuvastatin, atorvastatin, simvastatin, pravastatin or fluvastatin. The model was used to estimate the proportion of patients reaching target and the associated costs over a one-year period from the perspective of the NHS. The effectiveness of the alternative statins were modelled using data from the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial. Monte Carlo simulation was used to reflect uncertainty in the parameter estimates applied in the model. Rosuvastatin is demonstrated to dominate (i.e. lower costs and a higher number of patients treated to target) atorvastatin, simvastatin and pravastatin. Compared with fluvastatin, the incremental cost per additional patient to target (PTT) for rosuvastatin was pounds sterling 24 using LDL-C and pounds sterling 83 using TC. The probability that rosuvastatin is cost-effective exceeds 95%, provided the NHS is prepared to pay at least pounds sterling 35 per PTT to achieve target LDL-C cholesterol levels (pounds sterling 160 for TC). The analysis demonstrates rosuvastatin is more cost-effective than the other statins in achieving UK and European cholesterol targets.
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PMID:The cost-effectiveness of a new statin (rosuvastatin) in the UK NHS. 1468 71

Combination therapy with a statin and niacin may provide optimal therapy for patients with combined hyperlipidemia and low levels of high-density lipoprotein (HDL) cholesterol. The authors assessed the efficacy and safety of rosuvastatin monotherapy, extended-release (ER) niacin monotherapy, or rosuvastatin and ER niacin combined therapy in patients with atherogenic dyslipidemia. In a 24-week, open-label, multicenter trial, men and women aged > or =18 years with fasting levels of total cholesterol > or =200 mg/dL, HDL cholesterol > or =45 mg/dL, triglycerides 200-800 mg/dL, and apolipoprotein B > or =110 mg/dL were randomly assigned to one of four treatment groups: rosuvastatin 10-40 mg, ER niacin 0.5-2 g, rosuvastatin 40 mg plus ER niacin 0.5-1 g, or rosuvastatin 10 mg plus ER niacin 0.5-2 g. Daily doses of rosuvastatin 40 mg monotherapy reduced low-density lipoprotein (LDL) cholesterol and non-HDL cholesterol levels significantly more than did either ER niacin 2 g monotherapy or rosuvastatin 10 mg combined with ER niacin 2 g. Addition of ER niacin 1 g to rosuvastatin 40 mg did not further reduce total or non-HDL cholesterol. Triglyceride reductions were similar among the four treatment groups. ER niacin mono- and combined therapy produced significantly greater rises in HDL cholesterol and apolipoprotein A-1 than did rosuvastatin monotherapy. Rosuvastatin monotherapy was better tolerated than ER niacin taken either alone or with rosuvastatin. In this study, rosuvastatin very effectively improved the three major lipoprotein-lipid abnormalities of combined hyperlipidemia.
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PMID:Rosuvastatin alone or with extended-release niacin: a new therapeutic option for patients with combined hyperlipidemia. 1553 64

Cardiovascular disease is the leading cause of death in the US and other industrialised societies. Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is the most efficacious lipid-lowering agent of the statin class. New guidelines and recent evidence-based studies confirm the benefit of intensive reduction of low-density lipoprotein cholesterol in terms of cardiovascular risk reduction. Both naturally occurring and synthetic statins have demonstrated significant lowering of low-density lipoprotein cholesterol, the primary target of cholesterol-lowering therapy. Rosuvastatin, specifically, is a synthetic statin shown to lower low-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, non-high-density lipoprotein cholesterol and triglycerides, in addition to increasing high-density lipoprotein cholesterol. Compared with other statins, there is a similar low risk of serious muscle damage (myopathy and rhabdomyolysis), and no consistent pattern of renal failure or renal injury, despite mild transient tubular proteinuria, as seen with all statins. Therefore, rosuvastatin offers an effective alternative in the clinical management of hyperlipidaemia, while awaiting the results of ongoing cardiovascular risk reduction trials.
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PMID:Rosuvastatin: a risk-benefit assessment for intensive lipid lowering. 1614 9

The most important action of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is their ability to lower levels of low-density lipoprotein (LDL) cholesterol. Statins have proved highly effective in reducing the risk of cardiovascular events in both primary and secondary prevention studies. However, the magnitude of risk reduction associated with statins is greater than that predicted on the basis of LDL cholesterol lowering alone. A likely explanation for this effect is the anti-inflammatory action of statins. Following the observation that high-sensitivity C-reactive protein (hs-CRP) is a powerful predictor of cardiovascular events, investigators in the Cholesterol and Recurrent Events (CARE) and Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) trials demonstrated that the magnitude of risk reduction associated with statin therapy was higher among those with elevated hs-CRP levels. In addition, there is accumulating evidence that statins lower plasma levels of hs-CRP in a manner largely independent of LDL cholesterol lowering. In contrast, little benefit has been demonstrated for statin therapy in the absence of both hyperlipidemia and inflammation. Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a large multinational, long-term, double-blind, placebo-controlled, randomized clinical trial designed to assess directly whether statin therapy (rosuvastatin 20 mg/day) should be given to apparently healthy individuals with low LDL cholesterol levels but elevated hs-CRP levels--a critical issue for the prevention of cardiovascular disease. Support for the concept behind the JUPITER trial is also now available from several recent trials comparing different intensities of statin therapy on disease progression as well as clinical end points. These studies indicate that the hs-CRP level achieved after initiation of statin therapy may be as important as the LDL cholesterol level achieved. All of these data raise the possibility that hs-CRP could be used to target high-risk patients who may benefit from early statin use. Ongoing work will determine whether hs-CRP reduction, independent of LDL cholesterol reduction, results in a net clinical benefit.
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PMID:Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)--can C-reactive protein be used to target statin therapy in primary prevention? 1644 35

HMG-CoA reductase inhibitors (statins) have been shown to reduce mortality and cardiovascular morbidity in patients with hyperlipidaemia and those with coronary artery disease. However, evidence for statin treatment in patients with chronic heart failure (CHF) remains a subject of debate. Patients with heart failure were generally excluded in the existing trials and a different patient population with a distinct pattern of morbidity and treatment was studied. In addition, no safety data are available for statins in patients with heart failure, where there are potential concerns about coenzyme Q10 depletion and excessive low-density lipoprotein reduction. This review summarises the clinical and preclinical evidence for potential beneficial effects of statins in CHF. In experimental systems, statins have been shown to improve cardiac function through antioxidative and anti-inflammatory action. Statins improve endothelial function, may reduce neurohormonal activation, and stimulate endothelial progenitor cells. Some of these effects occur independently of cholesterol lowering and can be explained by inhibition of isoprenylation of signal transducing proteins of the family of Rho guanosine triphosphatases. Two ongoing controlled randomised trials (CORONA [Controlled Rosuvastatin Multinational Study in Heart Failure] and GISSI-HF [Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico--Heart Failure]) will help us to assess whether the described beneficial effects of statins in heart failure outweigh the potential negative effects and translate into the reduction of clinical endpoints.
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PMID:HMG-CoA reductase inhibitors in chronic heart failure: potential mechanisms of benefit and risk. 1645 Oct 90

Visfatin is a novel adipokine involved in the process of atherosclerosis. We assessed the effect of rosuvastatin on plasma visfatin levels in patients with primary hyperlipidemia. Eighty hyperlipidemic patients without evidence of cardiovascular disease were randomized to receive either rosuvastatin 10 mg/day or therapeutic lifestyle changes intervention. Plasma visfatin levels were determined at baseline and after 12-weeks post-randomization. Rosuvastatin induced a significant decrease in plasma visfatin levels (17.1+/-2.1 versus 15.5+/-2.0 ng/ml, P=0.03). This effect correlated with baseline visfatin levels (r=0.51, P<0.01) and was independent of any lipid-lowering actions of rosuvastatin.
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PMID:Effect of rosuvastatin treatment on plasma visfatin levels in patients with primary hyperlipidemia. 1793 20


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