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

Nicotinic acid and its derivative, Acipimox, have been widely used in the treatment of hyperlipidemia. Pharmacological studies have demonstrated that they exert the beneficial effect through the activation of a Gi-protein-coupled receptor on adipocyte, which has remained elusive to date. Here we show that a novel GPCR, designated HM74b because of its high similarity to HM74, is a receptor for nicotinic acid. HM74b mRNA is found in human, murine, and rat adipose tissues. Nicotinic acid and Acipimox inhibit forskolin-stimulated intracellular cAMP accumulation in human HM74b-expressing cells and activate GTP gamma S binding in a dose-dependent manner. [3H]Nicotinic acid specifically binds to HM74b-expressing membrane and its binding is replaced by Acipimox. This finding will open a new phase of research on the physiological role of nicotinic acid and will be a clue to develop novel antihyperlipidemic drugs.
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PMID:Molecular identification of nicotinic acid receptor. 1264 12

Combined hyperlipidemia is increasing in frequency and is the most common lipid disorder associated with obesity, insulin resistance and diabetes mellitus. It is associated with other features of the metabolic syndrome including hypertension, hyperuricemia, hyperinsulinemia and highly atherogenic subfractions of lipoprotein remnant particles including small dense low density lipoprotein-cholesterol. This review examines the mechanisms by which combined hyperlipidemia arises and the various drugs including fibric acid derivatives, hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and nicotinic acid which can be used either as monotherapy or in combination to manage it and to improve prognosis from atherosclerotic disease in diabetes mellitus, insulin resistant states and primary combined hyperlipidemia. The therapeutic approach to combined hyperlipidemia involves determination of whether the cause is hepatocyte damage or metabolic derangements. Combined hyperlipidemia due to hepatocyte damage should be treated by attention to the primary cause. In the case of metabolic dysfunction because of imbalance in glucose and fat metabolism, therapy of diabetes mellitus and obesity should be optimised prior to commencement of lipid lowering drugs. Both fibric acid derivatives and HMG-CoA reductase inhibitors can be used in the treatment of combined hyperlipidemia with fibric acid derivatives having greater effects on triglycerides and HMG-CoA reductase inhibitors on LDL-C though both have effects on the other cardiovascular risk factors. There is some evidence of benefit with both interventions in mild combined hyperlipidemias and large scale trials are underway. Fibric acid derivatives and HMG-CoA reductase inhibitor therapy can be combined with care, provided that gemfibrozil is avoided, fibric acid derivatives are given in the mornings and shorter half -life HMG-CoA reductase inhibitors are used at night. Combined hyperlipidemia emergencies occur with predominant hypertriglyceridemia in pregnancy or as a cause of pancreatitis. Therapy in the former should aim to reduce chylomicron production by a low fat diet and intervention to suppress VLDL-C secretion using omega-3 fatty acids. In the latter case, fluid therapy alone and medium chain plasma triglyceride infusions usually reduce levels satisfactorily though apheresis may be required. Blood glucose levels also need aggressive management in these conditions. Combined hyperlipidemia is likely to become an increasing problem with the increase in the prevalence of obesity and diabetes mellitus and needs aggressive management to reduce cardiovascular risk.
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PMID:Drug treatment of combined hyperlipidemia. 1472 15

My grandmother used to caution me. "An ounce of prevention is worth a pound of cure." That saying is certainly applicable to coronary heart disease (CHD). CHD remains a major cause of death in the United States today despite modern medical technology. The primary results of CHD, myocardial ischemia and myocardial infarct, when not deadly, often mean a seriously impaired lifestyle. However, since the 1960s, we have known that there were identifiable risk factors related to CHD. One of the major modifiable risk factors is an elevated lipoprotein level (e.g., hyperlipidemia), and today, we have an armament of lipid-lowering medications that are one means of preventing CHD for many individuals. In this article, the major classes of medications with lipid lowering effects are examined. Some of these medications are not new, but with the knowledge that the earlier they are used the more effective they may be, increasing numbers of people are now using nicotinic acid, bile acid-binding resins, fibric acid derivatives, or reductase inhibitors. As a result of the increased focus on lipid-lowering medications, nurses caring for middle-age and older adults are seeing and will continue to see larger numbers of their patients with prescriptions for these drugs. Nurses who are knowledgeable about the many antilipidemics on the market today will be more prepared to answer patient's questions and educate patients about reducing risk of CHD. A brief overview of the physiology of lipid metabolism, the pathophysiology of atherosclerosis, and risk factors for CHD make the rational for using these medications more understandable. Recommendations for early identification of individuals at risk for CHD are identified. In this Part 1 of a two-part series, two of the four major classes of lipid-lowering drugs are examined by looking at the mechanism of action and possible side effects of selected drugs in these classes. In Part 2 (May/June 2004), the other two classes of antilipidemic drugs will be examined and the recommendations of the National Cholesterol Education Program for clinical management of high blood cholesterol will be reviewed.
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PMID:An ounce of prevention. Drugs used to treat hyperlipidemia (Part 1). 1499 54

The inbred HcB19 mouse strain expresses a truncated form of thioredoxin interacting protein and is phenotypically characterized by fatty liver and elevated plasma triglycerides and VLDL. Recently, these mice have been proposed as an animal model for familial combined hyperlipidemia. The aim of the present study was identification of hepatic proteins specifically associated with the presence of fatty liver. Eighteen differential proteins were detected in whole-liver homogenate from HcB19, or the parental strain C3H, using 2D electrophoresis, and 11 of those were successfully identified by mass spectrometry. Five of the identified differential proteins were mitochondrial, two peroxisomal, two cytosolic, and two secretory. Four differential proteins were novel in the fatty liver proteome [i.e., aconitase, succinate dehydrogenase, propionyl CoA carboxylase alpha chain (PCCA), and 3-hydroxyanthranilate 3,4 dioxygenase (3HAAO)]. Of these, PCCA and 3HAAO are of particular interest because of their known functions in nicotinic acid metabolism (3HAAO) and ketogenesis (PCCA). We have newly identified several differential proteins in the hepatic proteome of mice with fatty liver, including PCCA and 3HAAO, and confirmed differential expression of previously reported proteins. These individual proteins, PCCA and 3HAAO, can be important in development of fatty liver or in the expression of hyperlipidemia.
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PMID:Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19. 1506 90

The past 20 years have seen considerable advances in the field of organ transplantation that have together led to a notable increase in survival rates and a reduction in postoperative morbidity of transplant recipients. However, these advances have been accompanied by the appearance of other complications of transplantation, such as post-transplant hyperlipidaemia, hypertension and graft coronary vasculopathy (GCV). GCV is an accelerated form of atherosclerosis in transplanted hearts that has proven to be one of the most important late complications of heart transplantation and is the single most limiting factor for long-term survival. The most important factors favouring the development of hyperlipidaemia after heart transplantation are inappropriate diet in combination with reduced physical activity, adverse effects of immunosuppressive therapy (ciclosporin [cyclosporin], corticosteroids) and polygenic hypercholesterolaemia in combination with ischaemic cardiomyopathy. The treatment of hyperlipidaemia in heart transplant recipients results in a variety of complications and side effects. In particular, interactions between lipid-lowering drugs and immunosuppressive therapy have been observed. Early attempts at treatment with bile acid binding agents and nicotinic acid derivatives often proved insufficiently effective, and led to unacceptable adverse effects and significant disturbances of ciclosporin metabolism. Fibric acid derivatives provided moderate reductions in triglyceride and total cholesterol levels that were mostly--with the exception of gemfibrozil--accompanied by significant impairment of renal function. Probucol achieved only an unsatisfactory reduction in low-density lipoprotein (LDL) cholesterol. Omega-3 fatty acids lower cholesterol levels and improve endothelial function in heart transplant recipients; however, the significance of these effects is still under discussion. As in the general patient population, use of HMG-CoA reductase inhibitors (statins) achieved significant reductions in cholesterol levels. Use of these substances has resulted in significantly extended long-term survival times, significantly less GCV and fewer severe graft rejections. Selective cholesterol absorption inhibitors, administered with or without statins, could provide another treatment option for heart transplant patients with hypercholesterolaemia. In severe familial hypercholesterolaemia, which is rarely observed in heart transplant recipients, treatment with statins can be combined with extracorporeal cholesterol elimination procedures such as heparin induced extracorporeal LDL cholesterol precipitation (HELP). HELP enables total cholesterol levels to be kept within any desired target range, and has been used successfully and without adverse effects in heart transplant recipients.
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PMID:Management of hyperlipidaemia associated with heart transplantation. 1513 86

It is well known now that hypolipidemic therapy is able to inhibit development of atherosclerosis. This decreases the rate of coronary complications. However, the problem of adequate pharmacotherapy duration has not been solved yet, as long-term treatment may provoke side effects. This study compared efficacy of hyperlipidemia (HLE) correction by long-term hypolipidemic diet (HD) and pharmacotherapy (PT) in patients with ischemic heart disease (IHD). 93 HLE patients with IHD aged 50-65 years entered the study. Enduracin used for 16-24 weeks (Endurance Products Company, USA) in a dose 1500 mg/day has reduced cholesterol by 15.7%, low density lipoproteins--by 19.2%, triglycerides--by 26%. High density lipoproteins rose by 15.7%. Besafibrat (Germany) in a dose 600 mg/day is indicated for patients with isolated hypertriglyceridemia (reduced triglycerides by 41.2%). Enduracin is indicated for patients with moderate levels of atherogenic serum lipids in isolated and combined HLE if fibrates are contraindicated. Diet lowered LDLP and VLDLP insignificantly and did not change HDLP. Prolongation of diet did not enhance the effect this allowing using diet therapy as background treatment.
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PMID:[Comparative efficiency of prolonged diet and drug therapies for hyperlipidemias in patients with ischemic heart disease]. 1523 46

Many studies have shown that niacin and Cr exert combined effects. Significant beneficial effects in serum lipid levels following Cr supplementation have been reported. Niacin decreases total plasma levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol and increases high-density lipoprotein cholesterol. In this study, 12-mo-old female Swiss albino rats were used. They were randomly divided into four groups. The animals of group I (control) were fed with pellet chow. Group II was fed with pellet chow and treated with 250 microg/kg CrCl3.6H2O and 100 mg/kg niacin for 45 d, by the gavage technique. The rats of group III were fed with lipogenic diet consisting of 2% cholesterol, 0.5% cholic acid, and 20% sunflower oil added to the pellet chow and given 3% alcoholic water for 60 d. Group IV was fed with the same lipogenic diet, and 15 d after, the experimental animals were made hyperlipemic; they were treated with 250 microg/kg CrCl3.6H2O and 100 mg/kg niacin by gavage technique for 45 d. On d 60, liver and blood samples were taken from the animals. The sections were examined under light and electron microscopes. Serum total lipid and cholesterol levels were determined by spectrophotometric methods. The aim of the present study was to examine whether combined treatment with Cr and niacin have beneficial effects on the liver of animals fed with lipogenic diet. In this study, beneficial effects of combined treatment with niacin and Cr(III) were evaluated. We conclude that a combination of Cr and niacin decrease total cholesterol and total lipid levels in serum significantly. In addition, it can be said that niacin and Cr can regenerate some of the hepatocytes. This study reveals that combined treatment is a better specific drug in hyperlipemia.
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PMID:Beneficial effects of combined treatment with niacin and chromium on the liver of hyperlipemic rats. 1556 52

Patients with diabetes mellitus have a 2- to 4-fold increased risk of atherosclerotic cardiovascular, peripheral vascular, and cerebrovascular disease, which are the leading causes of morbidity and mortality in this population. Several epidemiological studies have shown an association between diabetic dyslipidemia, which is characterized by hypertriglyceridemia, low levels of high density lipoprotein-cholesterol, postprandial lipemia and small, dense low density lipoprotein-cholesterol (LDL-C) particles, and the occurrence of cardiovascular disease. Other studies have established the beneficial effects of lipid lowering on the reduction of major coronary events in diabetic patients. The recent National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines emphasize diabetes as a coronary heart disease risk equivalent. The NCEP ATP III states that elevated LDL-C is a major risk factor for coronary heart disease, and the primary goal of risk-reduction therapy is the reduction of LDL-C levels to 100 mg/dL. This article defines and describes diabetic dyslipidemia and its etiology and pathogenesis, as well as reviewing guidelines and recommendations for treatment of this disorder. Treatment of diabetic dyslipidemia includes 1) lifestyle modifications: physical activity and a diet low in saturated fats and cholesterol and high in complex carbohydrates and fiber; and 2) pharmacological treatment with (i) oral antihyperglycemic agents: metformin and thiazolidinediones; (ii) weight reduction drugs: orlistat and sibutramine and; (iii) lipid-lowering drugs: HMG-CoA reductase inhibitors, fibric acid derivatives, nicotinic acid, and bile acid sequestrants.
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PMID:Pathogenesis and management of diabetic dyslipidemia. 1596 59

Several potent drugs are currently available for the treatment of hyperlipidemia. These pharmacotherapies include bile acid sequestrants, HMG-CoA reductase inhibitors (commonly referred to as 'statins'), fibrates and nicotinic acid. Combination therapy to reduce plasma cholesterol levels in hyperlipidemic patients is becoming more popular, as concerns about toxicity resulting from the long-term used of systemically acting drugs are raised. One of the more widespread combinations used to reduce plasma cholesterol levels is that of a bile acid sequestrant and a statin. Combinations of bile acid sequestrants with either niacin or fibrates have been found to be very effective in patients with mixed hyperlipidemia, since the triglyceride-lowering effect of niacin or a fibrate complements the cholesterol-lowering effect of the sequestrant. One major advantage of combination therapy is the ability to reduce the dose of each component to more tolerable levels for the patient. An additional advantage is the reduced cost to achieve the cholesterol reduction goal, as the dose response is relatively good at greatly reduced doses for each component.
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PMID:Bile acid sequestrants: their use in combination with other lipid-lowering agents. 1616 Sep 34

We investigated the effects of a combined treatment with chromium (Cr) and niacin on the spleen, tongue, and lens tissues in terms of lipid peroxidation (LPO), glutathione (GSH), serum catalase (CAT), lactate dehydrogenase (LDH), serum cholesterol, and total lipid levels in normal and hyperlipemic rats. In this study, female 1-year-old Swiss albino rats were used. The rats were randomly divided into four groups. Group I rats (control) were fed with standard pellet chow. Group II rats were fed a lipogenic diet in which 2% cholesterol, 0.5% cholic acid, and 20% sunflower oil were added and were given 3% alcoholic water for 60 days. Group III rats were fed with the same lipogenic diet and were treated with a dose of 250 microg/kg body weight CrCI3 x 6H2O and 100 mg/kg body weight niacin, for 45 days, by gavage. The rats in group IV were fed with pellet chow and treated with 250 microg/kg body weight CrCI3 x 6H2O and 100 mg/kg body weight niacin, by gavage, for 45 days. After 2 weeks, the animals showed symptoms of hyperlipemia. On the 60th day, tissue and blood samples were taken. We have observed decreased CAT activity and GSH levels, increased LDH activity, cholesterol, total lipid, and LPO levels in hyperlipemic rats. Niacin and Cr administration to hyperlipemic rats increased tissue GSH levels and CAT activity and decreased tissue LPO levels and LDH activity, cholesterol, and total lipid levels compared with hyperlipemic rats. We conclude that the administration of a combination of niacin and chromium has a protective effect against oxidative damage to tongue, lens, and spleen tissues as a result of hyperlipemia.
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PMID:The effect of combined treatment with niacin and chromium (III) chloride on the different tissues of hyperlipemic rats. 1693 39


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