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)

The metabolic syndrome consists of a cluster of metabolic disorders, many of which promote the development of atherosclerosis and increase the risk to develop cardiovascular disease. The metabolic syndrome is characterized by atherogenic dyslipidemia (elevated triglycerides, increased small dense low-density lipoproteins, and decreased high-density lipoproteins), hypertension, insulin resistance and obesity. To decrease the risk of cardiovascular disease events decreasing body weight by ingesting a healthy diet, increasing physical activity, cessation of smoking and managing dyslipidemia are recommended. Pharmacological treatment of dyslipidemia is based on different drug classes. For LDL-cholesterol-lowering mainly statins and for triglyceride-lowering mainly fibrates are used. In primary and secondary prevention trials of heart disease they have shown to reduce the incidence of coronary artery disease or coronary events by 25-60 percent. Statins reduce mainly LDL-cholesterol levels by competitive inhibition of HMG-CoA reductase but have also shown to reduce fasting and postprandial triglyceride levels. Fibrates effectively reduce fasting and postprandial lipemia, shift the distribution of LDL particles towards less dense particles and increase HDL-cholesterol. Thus fibrates particularly address components of the metabolic syndrome and features of diabetic dyslipidemia. However studies still are needed showing definite evidence on differential therapy in lipid lowering based on prospective controlled trials with endpoints of macro- and microangiopathy in diabetic patients.
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PMID:Treatment of dyslipoproteinemia in the metabolic syndrome. 1145 42

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

The first choice of therapy for nephrotic syndrome is steroid, and cyclosporin A(CyA) or other immunosuppressants are selected for steroid resistant or recurrent cases. Nephrotic syndrome accompanies hyperlipidemia for which HMG-CoA reductase inhibitors are mainly used. On the other hand, probucol is used in cases showing inadequate effects or some adverse reactions under treatment with HMG-CoA reductase inhibitors. Recently, we experienced several cases whose blood levels of CyA were decreased to about half that before the combined use of probucol, and concomitant administrations were discontinued. Based on these cases, we considered that the use of probucol should be prescribed in patients with nephrotic syndrome accompanying hyperlipidemia giving preference to CyA treatment. In cases of unavoidable usage of probucol, CyA dose adjustments are required on the basis of frequent CyA blood level monitoring.
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PMID:[Effect of probucol on the concentration of cyclosporin A in patients with nephrotic syndrome]. 1172 57

Flavonoids from Emblica officinalis and Mangifera indica effectively reduce lipid levels in serum and tissues of rats induced hyperlipidemia. Hepatic HMG CoA reductase activity was significantly inhibited in rats fed E. officinalis flavonoids. But increase of this enzyme was observed in rats administered M. indica flavonoids. LCAT showed elevated levels in rats fed flavonoids from E. officinalis and M. indica. The degradation and elimination of cholesterol was highly enhanced in both the groups. In E. officinalis, the mechanism of hypolipidemic action is by the concerted action of inhibition of synthesis and enhancement of degradation. In the other group (M. indica) inhibition of cholesterogenesis was not encountered but highly significant degradation of cholesterol was noted, which may be the pivotal factor for hypolipidemic activity in this case. Though the mechanisms differ in the two cases, the net effect is to lower lipid levels.
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PMID:Flavonoids from Emblica officinalis and Mangifera indica-effectiveness for dyslipidemia. 1174 99

Pravastatin is a potent inhibitor of HMG-CoA reductase and is effective in lowering serum lipid levels. Recent studies have shown that pravastatin also reduces oxidative modification of LDL and decreases albuminuria in patients with diabetes. To determine the possible benefit of pravastatin on the diabetic kidney, we have measured the effects of pravastatin on the proliferation and the production of superoxide and fibronectin, and the expression of fibronectin mRNA of glomerular mesangial cells stimulated by oxidized-LDL and high glucose. Our results demonstrated that the [(3)H]-labeled thymidine uptake of mesangial cells decreased after oxidized-LDL stimulation (50 microg/ml, 6 h) and increased after high glucose stimulation (25 mM, 48 h). The production of superoxide and fibronectin and the expression of fibronectin mRNA of glomerular mesangial cells were all significantly increased after stimulation with either oxidized-LDL or high glucose, or the combination of oxidized-LDL and high glucose. Pravastatin (100 microM, 48 h) alone had no effect on unstimulated cells. However, pravastatin significantly reversed thymidine uptake, inhibited the production of superoxide and fibronectin, and inhibited the expression of fibronectin mRNA of glomerular mesangial cells after stimulation with either oxidized-LDL or high glucose. Our results indicate that pravastatin may effect as an antioxidant and may suppress fibronectin synthesis of glomerular mesangial cells in diabetic patients with hyperlipidemia.
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PMID:Pravastatin suppress superoxide and fibronectin production of glomerular mesangial cells induced by oxidized-LDL and high glucose. 1175 31

Accumulating evidences in recent major clinical studies have shown the importance of anti-hyperlipidemic treatment in preventing atherosclerotic cardiovascular diseases. Lipid-lowering drugs can be divided into HMG-CoA reductase inhibitors (statins), bile-acid sequestrants (resins), nicotinic acid, fibrates and probucol. Among them, statins had revolutionary impact on the treatment of hyperlipidemia since pravastatin, which was developed in Japan, was launched in 1989. Several lipid-lowering drugs are now under development in Japan, including pitavastatin, rosuvastatin, F-1394 (ACAT inhibitor), CS-505 (ACAT inhibitor) and NO-1886 (LPL activator). In this review, characteristics of these new lipid-lowering drugs will be discussed.
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PMID:[Lipid-lowering drugs]. 1177 57

Recent studies have proposed an association between hyperlipidemia and venous thromboembolism (VTE). We review the epidemiological evidence linking dyslipidemia with VTE and examine several possible underlying mechanisms. We discuss the possible role of HMG CoA reductase inhibitors (statins) in the prevention and treatment of VTE and suggest future directions for research.
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PMID:The role of dyslipidemia and statins in venous thromboembolism. 1180 91

Reducing elevated levels of low-density-lipoprotein cholesterol (LDL-C) significantly reduces the incidence of coronary heart disease (CHD) events and mortality in hypercholesterolemic patients. CHD risk reduction is proportional to LDL-C reduction. Despite this knowledge, many physicians are not applying existing treatment guidelines to the extent required to achieve target LDL-C levels. Target LDL-C levels are not achievable for most patients without drug therapy. Based on their lipid-lowering abilities, safety, and tolerability profiles, the HMG-CoA reductase inhibitors (statins) are the first-line pharmacotherapeutic agents for hypercholesterolemia. The ability of statins to reduce CHD events and total mortality in primary- and secondary-prevention patients also supports this assertion. For combined dyslipidemia, statin monotherapy is a reasonable initial approach in patients with moderate hypertriglyceridemia because statins effectively lower both LDL-C and triglycerides. Fibrates or niacin are effective therapies for severe hypertriglyceridemia. Resins are moderately effective in isolated hypercholesterolemia, and are a useful alternative to statins in pregnant women or patients with liver disease. For severe hyperlipidemia that does not respond to single drug therapy, combination drug therapy may be required. This article reviews the various manifestations of dyslipidemia and assesses the most efficacious treatments.
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PMID:Pharmacotherapy of dyslipidemia. 1185 60

During the last decades, transplantation has become an established tool for the treatment of terminal organ failure. Beside immunological factors, hyperlipidemia is the main problem after heart transplantation, causing rapid transplant coronary artery disease (TxCAD) and poor long-term prognosis at the beginning of the transplantation. Heart transplant recipients are now effectively treated with lipid lowering substances, of which HMG-CoA-reductase inhibitors are the most potent. However, treatment with these substances correlates with an increased risk for the development of rhabdomyolysis due to therapy with the immunosuppressive cyclosporine A. Our study monitored the safety and efficacy of treatment with the HMG-CoA reductase inhibitor fluvastatin in heart transplant recipients compared to healthy controls. We investigated 10 patients receiving immunosuppressive therapy consisting of cyclosporine A, prednisone, and azathioprine who had increased concentrations of LDL-cholesterol (LDL-C), and 10 age-matched healthy controls. The patients were treated with 40 mg/day fluvastatin for 4 weeks and 20 mg/day for 4 additional weeks. Control individuals received 40 mg/day fluvastatin for 4 weeks only. Parameters of fluvastatin pharmacokinetics (maximum concentration of the drug (C(max.)), time (t(max.)) to reach C(max.), area under the concentration vs. time curve (AUC(0h-24h)), elimination half-life time (t(1/2))), apparent total body clearance (CL), blood cyclosporine A concentration, plasma lipids, and safety parameters were determined in both study groups at the beginning of the study and after 4 weeks. The latter were determined in the patient group also after 8 and 12 weeks. Treatment with 40 mg/day fluvastatin caused a significant decrease in total cholesterol (patients: 5.47 +/- 1.32 mmol/L vs. 7.30 +/- 1.83 mmol/L; controls: 4.69 +/- 0.64 mmol/L vs. 5.81 +/- 0.72 mmol/L), LDL-C (patients: 3.28 +/- 1.25 mmol/L vs. 5.00 +/- 1.85 mmol/L; controls: 2.58 +/- 0.63 mmol/L vs. 3.50 +/- 0.70 mmol/L), and triglycerides (patients: 1.99 +/- 0.77 mmol/L vs. 2.50 +/- 1.00 mmol/L; controls: 1.24 +/- 0.46 mmol/L vs. 1.72 +/- 0.67 mmol/L) in both study groups, whereas HDL-C was not significantly changed (patients: 1.29 +/- 0.35 mmol/L vs. 1.17 +/- 0.32 mmol/L; controls: 1.55 +/- 0.30 mmol/L vs. 1.53 +/- 0.26 mmol/L). Values of C(max.) and AUC(0h-24h) were higher in the patient group than in the control group (day 1, patients vs. controls, C(max.): 869.4 +/- 604.0 ng/mL vs. 211.9 +/- 113.9 ng/mL; AUC(0h-24h): 1948.8 +/- 1347.9 ng/mL*h vs. 549.4 +/- 247.4 ng/mL*h), whereas the corresponding value of CL was lower in the patient group (33.3 +/- 24.5 L/h vs. 107.9 +/- 95.8 L/h), and the values of t(max.) and t(1/2) showed no differences. In addition, values of C(max.) and AUC(0h-24h) after administration of 40 mg/day fluvastatin for 4 weeks in both groups were slightly higher than at the beginning, whereas the value of CL was slightly lower (day 28, patients vs. controls, C(max.): 1530.4 +/- 960.4 ng/mL vs. 254.7 +/- 199.8 ng/mL; AUC(0h-24h): 2615.3 +/- 1379.4 ng/mL*h vs. 841.8 +/- 421.4 ng/mL*h; CL: day 28, 21.4 +/- 15.3 L/h vs. 61.5 +/- 36.6 L/h). Except for an intermittent increase of creatine kinase, safety parameters showed no increases within the observation period. Our data suggest that fluvastatin effectively lowers plasma concentrations of cholesterol and LDL-C in patients after heart transplantation, however, the metabolism of fluvastatin is affected by concomitant therapy with cyclosporine A. Serum concentrations of fluvastatin should be monitored in cases of concomitant therapy with other substances interfering in the metabolism by competing cytochrome enzymes.
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PMID:Pharmacokinetics and pharmacodynamics of fluvastatin in heart transplant recipients taking cyclosporine A. 1190 37

The developments and trends of antihyperlipidemic drugs and their effects on the mortality of coronary heart disease in Japan were investigated. The developed drugs available for hyperlipidemia were recorded with their approval dates by the Ministry of Health and Welfare (Table 1). 1. Antihyperlipidemic drugs have been developed since the late 1950s. Useful drugs among them include the fibrate series and the statin (HMG-CoA reductase inhibitor) series. Clofibrate, developed in 1965, was the first fibrate drug, and pravastatin sodium (Mevalotin(R) Sankyo Co.), developed in 1989, was the first statin drug. They have sure effectiveness for lowering serum cholesterol and triglyceride. But they induce an unfavorable side-effect, rhabdomyolisis, especially after the continuous or simultaneous use of both. The other drug classes using hyperlipidemia include various different types, e.g., probucol, nicotinates, anion exchange resins, ethyl icosapentate, and dextran sodium sulfate. Despite their mild activities, the low incidence of adverse effects make them suitable for supplementary use with fibrates or statins. 2. "Guideline for Diagnosis and Treatment of Hyperlipidemia in Adult" was presented by the Japan Atherosclersis Society in 1997. The standard criteria of serum cholesterol and triglyceride levels in Japanese adults were proposed. The hypercholesterolemia is the state of more than a 220 mg/dl level of serum cholesterol, and hypertriglyceridemia is of more than a 150 mg/dl level of serum triglyceride. The pharmacotherapy should be applied for a high serum level of cholesterol exceeding 240 mg/dl. But the standard routine formula of drug therapy were not indicated in the present guideline. 3. Epidemiological surveys show that hyperlipidemia induces coronary heart diseases in the United States, European countries, and Japan. The mortality of all heart disease patients in Japan increased rapidly from the late 1960s, but the mortality resulting from coronary heart disease was suppressed from 1968. This suppression continued throughout 1994 when artificial statistical changes occurred. It may be due to the newly developed antihyperlipidemic drugs, e.g., the clofibrate group, the statin series, and others (Fig.2).
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PMID:[A 50-year history of new drugs in Japan: the developments and trends of antihyperlipidemic drugs]. 1196 19


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