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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma low density lipoprotein (LDL) plays a central role in atherogenesis, and elevated levels of LDL are associated with an increased risk of coronary heart disease (CHD). Studies have now revealed that LDL is structurally heterogeneous, based on its size and density. Patients with combined hyperlipidemia exhibit a lipid profile - the so-called atherogenic lipoprotein phenotype - that is associated with elevated triglyceride levels, low levels of high density lipoprotein and a preponderance of atherogenic, small, dense LDL particles. Such individuals are at an increased risk of CHD events, regardless of their total LDL circulating mass. Evidence suggests that when plasma triglycerides exceed a critical threshold of approximately 133 mg/dl (1.5 mmol/l), this favours the formation of small, dense LDL from larger, less dense species. Lipid-lowering agents that are capable of lowering triglyceride levels below this threshold value will cause a shift to a less dense and, therefore, less atherogenic LDL profile. This effect has been demonstrated for the HMG-CoA reductase inhibitor atorvastatin which, in addition to its ability to markedly decrease the total LDL circulating mass, can also shift the LDL profile towards less dense, larger species. This suggests that atorvastatin may also affect the atherogenic lipoprotein phenotype found in patients with combined hyperlipidemia.
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PMID:The role of small, dense low density lipoprotein (LDL): a new look. 1085 69

For patients with coronary artery disease and healthy middle-aged or older individuals with elevated cholesterol levels, treatment with cholesterol-lowering drugs reduces morbidity and sometimes mortality. Treatment reverses established atherosclerotic lesions within a relatively short period of time, suggesting that starting cholesterol-lowering drugs in adulthood is adequate for most people at risk. Children with genetic lipid disorders, including familial hypercholesterolaemia and familial combined hyperlipidaemia, may be candidates for earlier therapy. A complete assessment of risk factors should be undertaken to determine which children are at highest risk. Treatment should start with diet, because diet is an important independent protective factor for disease. The bile acid sequestrants (resins) are the only drugs approved for children and may reduce low density lipoprotein (LDL)-cholesterol levels by 15 to 20% at best. Long term tolerability is good, but many children will not take the resins because they find them unpalatable. Tablet formulations have higher acceptability. Some children require supplementation with fat soluble vitamins or folate. Although hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have not been tested in long term studies in children, safety records are excellent in adults. Short term studies show that HMG-CoA reductase inhibitors reduce LDL-cholesterol levels similarly in children and in adults. Thus, the drugs may be used in low dosages to treat some adolescents with exceptional risk of disease.
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PMID:Role of lipid-lowering pharmacotherapy in children. 1093 55

The objective of this study was to determine the effects of a country liquor (Arrack) and the equivalent quantity of ethanol on liver function and lipid metabolism in utero. Female rats of average weight 125 g were exposed to Arrack (12 ml/kg body weight/day) and ethanol (3.2 ml/kg body weight/day) for 15 days before conception and throughout gestation. On 13th day and 19th day of gestation, altered liver function and hyperlipidemia was seen in the fetus of both the treated groups. Altered liver function was evidenced by the increased activity of alcohol dehydrogenase and glutamic pyruvic transaminase or alanine amino transferase (GPT). Hyperlipidemia was caused by increased biosynthesis since the incorporation of 14C acetate to lipids and activities of HMG CoA reductase and lipogenic enzymes were elevated. Arrack seemed to potentiate the toxicity induced by alcohol indicating the role of non ethanolic portion. Hepatic functions of the 13th day fetuses were effected to a lesser degree than the 19th day hepatic liver.
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PMID:Prenatal exposure of an alcoholic beverage (Arrack) on fetal lipid metabolism in rats. 1094 14

We examined the effects of four 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (pravastatin, simvastatin, fluvastatin, and cerivastatin) on the production and expression of inflammatory cytokines and on enzyme expression involving prostaglandin and superoxide production in cultured human umbilical vein endothelial cells (HUVEC). All HMG-CoA reductase inhibitors significantly reduced interleukin-1beta and -6 mRNA expression and their protein levels in the culture medium, and also inhibited cyclooxygenase-2 mRNA expression and their protein levels. And these drugs induced peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma mRNA expression and their protein levels in HUVEC and hepatocyte. Moreover, the mRNA levels of p22phox, a 22-kD subunit and the protein levels of p47phox, a 47-kD subunit of nicotine adenine dinucleotide phosphate (NADPH) oxidase, was decreased by treatment with either simvastatin, fluvastatin or cerivastatin, and this effect was reversed by mevalonate, geranylgeraniol, farnesol, and cholesterol. The changes induced by HMG-CoA reductase inhibitors might be due to regulation of cellular cholesterol content level, cellular cholesterol metabolic pathway, and cellular PPARalpha activity, which was related with inflammation. This unique anti-inflammatory effect in addition to its hypolipidemic action, may be beneficial in preventing the vascular complications that are induced by hyperlipidemia.
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PMID:Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells. 1094 46

Abnormal lipid levels contribute significantly to the risk of coronary heart disease (CHD), which is increased further in the presence of other risk factors. The association between elevated low-density lipoprotein (LDL) cholesterol and CHD risk is well established, and large primary and secondary prevention studies of HMG-CoA reductase inhibitors (statins) have shown conclusively that lowering LDL cholesterol levels reduces CHD events and total mortality. Regardless of the intervention used (diet, surgery, drugs), reduction of plasma cholesterol has consistently produced a reduction in cardiovascular risk. Absolute benefit is greatest in those who are at highest risk initially, and trial results suggest that the lower the LDL cholesterol level achieved, at least down to LDL of 3.0 mmol/l, then the lower is the CHD event risk. Epidemiological data also point to the negative impact of other lipids on CHD risk. Low levels of high-density lipoprotein (HDL) and high levels of triglycerides (particularly in conjunction with an LDL/HDL ratio >5) are particularly strong risk factors for CHD. Thus, although prevention trials to date have primarily assessed the impact of LDL lowering on CHD events, the initial assessment of CHD risk should consider a more detailed atherogenic profile including HDL and triglyceride levels. A general approach to preventing cardiovascular disease should include strategies to reduce the overall CHD risk by lifestyle modification and management of modifiable risk factors such as smoking, hypertension and diabetes. Based on data from recent prevention studies, and because they are the most potent lipid-lowering agents available for lowering LDL cholesterol, statins have appropriately become the drug of choice for most patients with hyperlipidaemia who require drug therapy.
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PMID:Identifying patients at risk for coronary heart disease: implications from trials of lipid-lowering drug therapy. 1098 51

Diabetic nephropathy is associated with an altered lipid profile characterized by elevated triglyceride rich lipoproteins, present even in the earlier stages of the renal disease. Although many experimental studies have demonstrated a significant deleterious role for hyperlipidemia in both the initiation and progression of renal injury, data remain more conflicting in humans. A few prospective studies, mostly in type 2 diabetes, have suggested an independent role for serum cholesterol level in the subsequent development of incipient or overt diabetic nephropathy. Furthermore, studies have reported in both types of diabetes an independent deleterious influence of serum total cholesterol on the decline in renal function and/or progression of albuminuria. However, the majority of these studies were post hoc analyses of previously controlled therapeutic trials with several observational studies not confirming these findings. It remains controversial whether apolipoprotein E gene polymorphism is an important factor in the development of diabetic nephropathy. Most of the interventional studies with lipid-lowering therapy in diabetic nephropathy have used HMG CoA reductase inhibitors and have been inconclusive. This may be due to a too short follow-up or insufficient number of patients. Further larger prospective studies are therefore required to better ascertain the role of lipids in the progression of diabetic nephropathy.
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PMID:Potential influence of lipids in diabetic nephropathy: insights from experimental data and clinical studies. 1101 Dec 17

This article reviews the rationale for lipid lowering in patients who have coronary heart disease, and specifically for post-bypass patients. It has been well demonstrated that after coronary artery bypass graft surgery, atherosclerosis continues to progress in the native circulation and develops at an accelerated rate in saphenous vein bypass grafts. During the last decade, numerous clinical trials based on angiographic or clinical outcomes have clearly shown the beneficial effect of lipid lowering in coronary heart disease. Three trials (CLAS, post-CABG, and CARE) have demonstrated delayed progression of atherosclerosis in SVGs and/or a reduction of cardiac deaths, nonfatal MI, and the need for revascularization after lowering LDL-cholesterol. The recommended target of LDL cholesterol level of more than 100 mg/dl can be safely reached with diet and monotherapy using one of the statin drugs (HMG-CoA reductase inhibitors). Despite this widely-circulated information, there appears to be inadequate public and professional awareness of the importance of properly managing hyperlipidemia after coronary artery bypass graft surgery.
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PMID:Lipid lowering and coronary bypass graft surgery. 1119 21

Hypercholesterolemia is a major risk factor for the development of coronary heart disease. HMG-CoA reductase inhibitors have been used as first-line drugs because of both their superior cholesterol lowering effect and reliable safety profile. Since there are many patients whose plasma cholesterol level does not reach the therapeutic target even if reductase inhibitors are available, more effective drugs have been strongly required for a long time. Atorvastatin, one of the most recently introduced statins, produces greater plasma LDL-cholesterol reductions than other statins. This pronounced effect of atorvastatin seems to be due to its long-lasting action, presumably a reflection of longer residence time of atorvastatin and its active metabolites in the liver. Clinical trials of atorvastatin have also demonstrated marked plasma triglyceride reductions. The triglyceride reduction with atorvastatin seems to stem from the following two indirect mechanisms, limiting VLDL secretion from the liver and increase in clearance of triglyceride-rich lipoprotein via induced LDL receptors from plasma. Eleven clinical trials of atorvastatin, which have been developed in Japan, clearly demonstrated its ability to reduce LDL-C levels more strongly and in significantly more patients to LDL-C treatment goals than other reductase inhibitors with similar safety profiles. Therefore, atorvastatin adds a new dimension to the effective management of hypercholesterolemia and combined hyperlipidemia.
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PMID:[Atorvastatin (Lipitor): a review of its pharmacological and clinical profile]. 1123 99

The objective of this study was to determine the effects of country liquor Toddy and its equivalent quantity of ethanol on lipid metabolism during gestation in rats. Female rats weighing an average of 125 g were exposed to Toddy (24.5 ml/body weight/day) and ethanol (0.52 ml/kg body weight/day) for 15 days before conception and throughout gestation. On the 19th day of gestation, altered liver function and hyperlipidemia was seen in both the treated groups. Altered liver function was evidenced by the increased activity of alcohol dehydrogenase, aldehyde dehydrogenase, glutamic oxaloacetic transaminase or aspartate amino transferase (GOT), glutamic pyruvic transaminase or alanine amino transferase (GPT) and gamma glutamyl transpeptidase (GGT). Hyperlipidemia was caused by increased biosynthesis and decreased degradation of lipids. The incorporation of 14C acetate in lipids and activities of HMG CoA reductase and lipogenic enzymes were elevated and activity of LPL and bile acids contents were decreased. Toddy treated rats were more severely affected than those receiving an equivalent quantity of ethanol. Toddy seemed to potentiate the toxicity induced by alcohol indicating the role of the nonethanolic portion. Hepatic functions were also affected.
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PMID:Effect of exposure to a country liquor (Toddy) during gestation on lipid metabolism in rats. 1131 2

Fluvastatin, the first fully synthetic HMG-CoA reductase inhibitor, has been shown to reduce cholesterol in patients with hyperlipidaemia, to prevent subsequent coronary events in patients with established coronary heart disease, and to alter endothelial function and plaque stability in animal models. Fluvastatin is relatively hydrophilic, compared with the semisynthetic HMG-CoA reductase inhibitors, and, therefore, it is extensively absorbed from the gastrointestinal tract. After absorption, it is nearly completely extracted and metabolised in the liver to 2 hydroxylated metabolites and an N-desisopropyl metabolite, which are excreted in the bile. Approximately 95% of a dose is recovered in the faeces, with 60% of a dose recovered as the 3 metabolites. The 6-hydroxy and N-desisopropyl fluvastatin metabolites are exclusively generated by cytochrome P450 (CYP) 2C9 and do not accumulate in the blood. CYP2C9, CYP3A4, CYP2C8 and CYP2D6 form the 5-hydroxy fluvastatin metabolite. Because of its hydrophilic nature and extensive plasma protein binding, fluvastatin has a small volume of distribution with minimal concentrations in extrahepatic tissues. The pharmacokinetics of fluvastatin are not influenced by renal function, due to its extensive metabolism and biliary excretion; limited data in patients with cirrhosis suggest a 30% reduction in oral clearance. Age and gender do not appear to affect the disposition of fluvastatin. CYP3A4 inhibitors (erythromycin, ketoconazole and itraconazole) have no effect on fluvastatin pharmacokinetics, in contrast to other HMG-CoA reductase inhibitors which are primarily metabolised by CYP3A and are subject to potential drug interactions with CYP3A inhibitors. Coadministration of fluvastatin with gastrointestinal agents such as cholestyramine, and gastric acid regulating agents (H2 receptor antagonists and proton pump inhibitors), significantly alters fluvastatin disposition by decreasing and increasing bioavailability, respectively. The nonspecific CYP inducer rifampicin (rifampin) significantly increases fluvastatin oral clearance. In addition to being a CYP2C9 substrate, fluvastatin demonstrates inhibitory effects on this isoenzyme in vitro and in vivo. In human liver microsomes, fluvastatin significantly inhibits the hydroxylation of 2 CYP2C9 substrates, tolbutamide and diclofenac. The oral clearances of the CYP2C9 substrates diclofenac, tolbutamide, glibenclamide (glyburide) and losartan are reduced by 15 to 25% when coadministered with fluvastatin. These alterations have not been shown to be clinically significant. There are inadequate data evaluating the potential interaction of fluvastatin with warfarin and phenytoin, 2 CYP2C9 substrates with a narrow therapeutic index, and caution is recommended when using fluvastatin with these agents. Fluvastatin does not appear to have a significant effect on other CYP isoenzymes or P-glycoprotein-mediated transport in vivo.
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PMID:Clinical pharmacokinetics of fluvastatin. 1136 92


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