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)

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

Apolipoprotein E (apo E) deficiency (or its abnormalities in humans) is associated with a series of pathological conditions including dyslipidemia, atherosclerosis, Alzheimer's disease, and shorter life span. The purpose of this study was to characterize these conditions in apo E-deficient C57BL/6J mice and relate them to human disorders. Deletion of apo E gene in mice is associated with changes in lipoprotein metabolism [plasma total cholesterol (TC) (>+400%), HDL cholesterol (-80%), HDL/TC, and HDL/LDL ratios (-93% and -96%, respectively), esterification rate in apo B-depleted plasma (+100%), plasma triglyceride (+200%), hepatic HMG-CoA reductase activity (-50%), hepatic cholesterol content (+30%)], decreased plasma homocyst(e)ine and glucose levels, and severe atherosclerosis and cutaneous xanthomatosis. Hepatic and lipoprotein lipase activities, hepatic LDL receptor function, and organ antioxidant capacity remain unchanged. Several histological/immunohistological stainings failed to detect potential markers for neurodegenerative disease in the brain of 37-wk-old male apo E-KO mice. Apo E-KO mice may have normal growth and development, but advanced atherosclerosis and xanthomatosis may indirectly reduce their life span. Apo E plays a crucial role in regulation of lipid metabolism and atherogenesis without affecting lipase activities, endogenous antioxidant capacity, or appearance of neurodegenerative markers in 37-wk-old male mice.
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PMID:Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans. 1172 38

Cerivastatin is a synthetic and enantiomerically pure 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. It has been recognized for its high pharmacologic potency, uncomplicated pharmacokinetic profile, and low drug-interaction potential. The efficacy of cerivastatin has been demonstrated in a number of clinical trials involving patients with primary hypercholesterolemia and mixed dyslipidemia. Cerivastatin was found to have dose-dependent reduction in total cholesterol and low-density lipoprotein (LDL) cholesterol. At the 0.4 mg daily dose, cerivastatin was found to lower LDL cholesterol by approximately 35% (mean reductions of 33-39%). The triglyceride-lowering effect of cerivastatin is also dose dependent; however, there is a much stronger association between baseline triglyceride levels and the triglyceride-lowering effect of cerivastatin. A dosage of 0.4 mg daily has been shown to reduce triglycerides by a mean of 28% in patients with baseline triglyceride levels of > 300 mg/dL. At the time of its initial approval by the US Food and Drug Administration (FDA) in 1997, cerivastatin was available only in 0.2 mg and 0.3 mg strengths. The recent FDA approval of the 0.4-mg strength dose has made cerivastatin a more competitive drug in lipid-lowering efficacy among the HMG-CoA reductase inhibitors.
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PMID:Cerivastatin. 1172 45

Compelling evidence from meta-analysis of a number of clinical studies on a large aggregate of patients has established an increased level of triglycerides as an independent risk factor for atherosclerotic heart disease. The finding of triglyceride-rich lipoproteins in human atheromata has provided substantial pathophysiologic evidence for a direct role in atherogenesis. Hypertriglyceridemia is commonly embedded in the context of a metabolic syndrome that includes central obesity, insulin resistance, low levels of HDL cholesterol, and often hypertension. Hypertriglyceridemia also appears to underlie the phenomenon of small dense LDL in most instances. Therapeutic interventions must be directed at underlying obesity, insulin resistance, and diabetes when present, as well as addressing metabolic determinants of dyslipidemia per se. Diet, exercise, weight loss, and avoidance of alcohol are the cornerstones of treatment. The choice of medication should be based on the lipoprotein phenotype. Niacin, fibric acid derivatives, and omega-3 fatty acids are most useful in treating severe hypertriglyceridemia. HMG-CoA reductase inhibitors are useful in some phenotypes with moderately increased triglyceride levels. Evidence from a number of clinical trials indicates that mitigation of risk of coronary heart disease, and possibly stroke, can be effected by reducing levels of plasma triglycerides.
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PMID:A risk factor for atherosclerosis: triglyceride-rich lipoproteins. 1179 72

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

The progress in the use of HAART for the treatment of HIV-infected individuals has been limited by the development of viral resistance and the maintenance of viral latency. New therapeutic strategies geared toward improvement in the host's immune response are now being considered. We found that IFN-gamma induces CIITA through the JAK-STAT pathway and inhibits HIV-1 replication in latently infected cells. Its effect appears to be mediated through the reciprocal action of Tat and CIITA. With this beneficial effect, IFN-gamma and its inducers can be considered as an adjunct to the currently available therapy. We also addressed the safety of using simvastatin, an HMG-CoA reductase inhibitor, to treat dyslipidemia often associated with the use of protease inhibitors. Simvastatin did not show any unfavorable effects on HIV replication, thus could be used safely unless there are any drug interactions when administered.
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PMID:Inhibitory effects of IFN-gamma on HIV-1 replication in latently infected cells. 1186 48

There are several reports in literature implicating cholesterol metabolism in the pathogenesis of neuronal degenerations, oncogenesis, functional neuropsychiatric disorders and multiple sclerosis. Biosynthesis of cholesterol takes place by the isoprenoid pathway, which also produces digoxin, an inhibitor of membrane Na(+)-K+ ATPase. Inhibition of this enzyme results in intracellular Mg++ deficiency which can influence cholesterol metabolism. Digoxin also influences transport of tryptophan and tyrosine which are precursors of various neurotransmitters. Alterations in digoxin, membrane Na(+)-K+ ATPase and also in neurotransmitters have been reported in the disorders mentioned above. In view of this, serum lipid profile, activity of plasma HMG CoA reductase (the major rate limiting step in the isoprenoid pathway), RBC membrane Na(+)-K+ ATPase activity, serum Mg++ concentration, concentration of digoxin and concentration of serum neurotransmitters were studied in some neuropsychiatric disorders. The serum serotonin level was increased while that of serum dopamine and noradrenaline was reduced. Serum digoxin levels were high and RBC membrane sodium-potasium ATPase activity and serum magnesium were reduced. There was a reduction in HDL cholesterol and increase in plasma triglycerides (pattern similar to insulin resistance and syndrome X) in most of the disorders studied. The HMG CoA reductase activity was high, the serum total cholesterol was increased while RBC membrane cholesterol was reduced in most of the cases. The significance of increased digoxin with consequent inhibition of membrane Na(+)-K+ ATPase in relation to changes in cholesterol metabolism and insulin resistance type of dyslipidemia is discussed in this paper.
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PMID:Membrane Na+ K+ ATPase inhibition related dyslipidemia and insulin resistance in neuropsychiatric disorders. 1188 68

Dyslipidaemia and hypertension contribute to an excess risk of coronary heart disease (CHD) in patients with type 2 diabetes. A number of landmark primary and secondary prevention trials have demonstrated that lipid-lowering therapy with HMG-CoA reductase inhibitors (statins), and antihypertensive therapy with angiotensin-converting enzyme inhibitors and calcium channel blockers (CCBs), reduce CHD risk in the non-diabetic population. However, many questions remain unanswered about the use of these therapies in patients with type 2 diabetes. To address the most important of these questions, several major trials are under way that will provide more data on the benefits of lipid-lowering and antihypertensive therapy in type 2 diabetes. These include studies of atorvastatin, an established member of the statin class, with over 22 million patient-years' experience and an excellent safety profile. Similarly, the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) will determine the efficacy of the CCB, amlodipine, in patients with concomitant type 2 diabetes and hypertension.
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PMID:Answering the unanswered questions: ongoing trials of statins and antihypertensives in type 2 diabetes. 1222 28

Patients with combined dyslipidemia are at greatly increased coronary heart disease (CHD) risk. The threat of rhabdomyolysis with dual pharmacologic treatment (hepatic hydroxymethyl glutaryl coenzyme A [HMG-CoA] reductase inhibitors plus fibric acid derivatives) has tended to limit therapy in patients with combined dyslipidemia to a choice of one or the other drug. Judgment of the potential benefits of either agent has rarely taken into account their effect on the postprandial accumulation of highly atherogenic, triglyceride (TG)-rich, remnant lipoprotein particles (RLPs). Because this information could be of substantial clinical relevance, we addressed this question in patients with type 2 diabetes and combined dyslipidemia by comparing the effects of gemfibrozil versus HMG-CoA reductase inhibitors (statins) on both fasting and postprandial lipid and lipoprotein concentrations. For this purpose, 22 patients with type 2 diabetes and combined dyslipidemia were randomized to treatment with either a statin or gemfibrozil for 3 months. Glycemic control was similar in both groups at baseline and did not change in response to treatment. Baseline lipid and lipoprotein concentrations were also similar in the 2 treatment groups, but the responses to therapy were quite different. Statin-treated patients had a statistically significant decrease in low-density lipoprotein (LDL) cholesterol concentration (156 mg/dL to 96 mg/dL, P <.001), whereas there was no change in patients treated with gemfibrozil. In contrast, there was a statistically significant decrease (P <.05) in plasma TG concentrations (116 mg/dL) in gemfibrozil-treated individuals, without any change in subjects treated with statins. However, the decrease in total integrated postprandial plasma RLP response measured hourly from 8 AM to 4 PM was not different in patients treated with either gemfibrozil (-43%) or statins (-34%). These results indicate that statin treatment, in addition to its beneficial effect on hypercholesterolemia, was as effective as gemfibrozil in reducing postprandial accumulation of triglyceride-rich, atherogenic RLPs in patients with type 2 diabetes and combined dyslipidemia. As such, the clinical utility of statin monotherapy in the treatment of combined dyslipidemia may have been underestimated.
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PMID:Comparison in patients with type 2 diabetes of fibric acid versus hepatic hydroxymethyl glutaryl-coenzyme a reductase inhibitor treatment of combined dyslipidemia. 1237 Aug 58


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