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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dyslipidemia plays critical roles in the pathogenesis of coronary atherosclerosis, a chronic inflammatory disease. Vascular inflammation also triggers the onset of acute complications of atherosclerosis, such as myocardial infarction. Advances in cardiovascular medicine demonstrate that lipid-lowering therapy by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) likely prevents acute coronary complications by limiting vascular inflammation. In particular, recent clinical evidence indicates aggressive lipid-lowering treatment for patients at risk. Preclinical studies also support the concept of anti-inflammatory properties of lipid lowering by either diet or statins. Therefore, dyslipidemia is the primary target of therapy for the prevention of coronary atherosclerosis and its acute thrombotic complications. Nevertheless, even aggressive statin therapy does not forestall many adverse events. Thus, current cardiovascular medicine also seeks mechanisms to mitigate vascular inflammation and atherosclerosis other than addressing low-density lipoprotein, and new therapeutic strategies beyond lipid lowering.
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PMID:Lipid lowering therapy in atherosclerosis. 1586 16

Use of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) infection is associated with the development of cardiovascular risk factors, including dyslipidemia, insulin resistance, fat redistribution, and hypertension. The results of the Data Collection on Adverse Events of Anti-HIV Drugs study showed that HAART therapy is associated with a 26% relative risk increase in the rate of myocardial infarction per year of HAART exposure. A number of studies have shown that insulin resistance often precedes lipodystrophy, suggesting that insulin resistance may be a primary feature of the metabolic syndrome in this population. The rate-limiting step in the uptake of glucose is glucose transport, and the predominant glucose transporter (GLUT) in muscle and fat is GLUT-4. Specific protease inhibitors (PIs) have been associated with decreased GLUT-4-mediated glucose transport and insulin resistance both in vitro and in vivo, whereas newer protease inhibitors may have fewer effects on insulin sensitivity. Data also suggest that endothelial dysfunction, impaired fibrinolysis, and excess inflammation may contribute to increased cardiovascular risk in the population infected with HIV. Moreover, recent data suggest that evidence for coronary atherosclerotic disease can be revealed by means of carotid intimal medial thickness (IMT) assessments in specific groups of HIV patients. Pharmacologic strategies for the prevention and/or treatment of HAART-induced dyslipidemia and abnormal glucose homeostasis include 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), resins, nicotinic acid, fibrates, and insulin-sensitizing agents. However, newer PIs such as atazanavir may result in less insulin resistance and dyslipidemia and, as part of a HAART regimen, use of atazanavir may reduce the metabolic complications associated with HAART.
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PMID:Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus. 1590 92

There is increasing evidence of cross-talk between dyslipidemia and renin-angiotensin system (RAS) in atherogenesis. Both dyslipidemia and RAS activation enhance the expression of a newly described receptor for oxidized-low density lipoprotein (ox-LDL), lectin-like ox-LDL receptor-1 (LOX-1). We postulated that the blockade of dyslipidemia with rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor and RAS with candesartan, an angiotensin II type 1 receptor blocker, would have a synergistic inhibitory effect on LOX-1 expression and atherogenesis. Apo-E knockout mice were fed a high-cholesterol diet (1% cholesterol, HC-diet) alone, or HC-diet with rosuvastatin (1mg/(kgd)), candesartan (1mg/(kgd)) or with both. Twelve weeks later the extent of atherosclerosis was determined by Sudan IV staining. Apo-E knockout mice on HC-diet had extensive atherosclerosis. Both rosuvastatin and candesartan decreased the extent of atherosclerosis (by 23 and 26%, respectively), despite the HC-diet; however, the combination of rosuvastatin and candesartan reduced atherosclerosis further (by 67%). Rosuvastatin decreased plasma levels of total cholesterol by over 50%, whereas candesartan had no effect. LOX-1 protein expression was found to be markedly up-regulated in HC-diet-fed apo-E knockout mice. While rosuvastatin and candesartan each had a small inhibitory effect on the expression of LOX-1 in the atherosclerotic tissues, the combination totally blocked the up-regulation of LOX-1. P38 mitogen-activated protein kinase (MAPK) expression and phosphorylation were increased in apo-E knockout mice, attenuated by rosuvastatin or candesartan alone, and completely blocked by the combination of the two agents. P44/42 MAPK expression and phosphorylation were not affected by the HC-diet, rosuvastatin, candesartan, or their combination. This study demonstrates the potent effect of rosuvastatin and candesartan on atherogenesis, as well as on the expression of LOX-1 and on the activation of p38 MAPK, but not p44/42 MAPK.
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PMID:Cross-talk between dyslipidemia and renin-angiotensin system and the role of LOX-1 and MAPK in atherogenesis studies with the combined use of rosuvastatin and candesartan. 1600 8

Rosuvastatin, a new hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), is approved as an adjunct to diet in patients with primary hypercholesterolemia, mixed dyslipidemia, or Fredrickson type IV hypercholesterolemia. Because of its increased affinity for the reductase, rosuvastatin reduces the low-density lipoprotein cholesterol (LDL) level more than atorvastatin, simvastatin, and pravastatin do, without additional adverse effects. In addition, cytochrome P450 isoenzymes do not extensively metabolize rosuvastatin, and inhibitors of these isoenzymes do not substantially affect it. Rosuvastatin could be a first-line option for patients requiring a reduction of 50% or more to reach the LDL goal of the National Cholesterol Education Program Adult Treatment Panel III. Rosuvastatin monotherapy may allow patients to achieve this LDL goal earlier, and it may help them avoid combination therapy or potential adverse effects of high-dose statin therapy. However, because cardiovascular disease morbidity and mortality data are lacking for rosuvastatin (but available for all other marketed statins) and because its postmarketing data are limited, rosuvastatin should be reserved for patients requiring an LDL reduction of 50% or less who cannot reach the recommended goal with other statins because of adverse effects, drug interactions, or cost.
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PMID:Rosuvastatin for the treatment of hypercholesterolemia. 1600 77

Cardiovascular disease is the leading cause of death among adults in the United States, in Europe, and in much of Asia. Despite advances in primary prevention of coronary artery disease, including early detection and treatment of dyslipidemia, one half of all myocardial infarctions and strokes occur in patients with normal serum cholesterol levels. Observations like this prompt the search for new risk factors and improved identification of individuals at high risk. One proposed risk factor is an elevated level of C-reactive protein (CRP), a marker of inflammation independent of other risk factors. The CRP assay is desirable in terms of standardization and cost. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are indicated for the treatment of dyslipidemias, but data support their protective role against cardiovascular disease beyond their effects on lipids. Statins directly affect inflammatory markers, and nearly 2 dozen randomized studies have demonstrated statins' effects on CRP. Because information regarding the role of CRP in cardiovascular disease is compelling but sometimes contradictory and because the need to reduce CRP levels is unclear, the American Heart Association and the Centers for Disease Control and Prevention presented a panel statement on the topic. Ongoing trials will assist in determining the need to reduce CRP levels to lower cardiovascular risk. An understanding of these issues is important for improving the prediction of cardiovascular risk and for intervening to reduce this risk.
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PMID:Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on high-sensitivity C-reactive protein levels. 1618 81

Diabetic nephropathy is commonly associated with dyslipidemia, but the role of lipids in the progression of this disorder remains unresolved. In particular, the role of lipid-lowering drugs, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and fibrates, as renoprotective agents is not clarified. Experimental studies have demonstrated that dietary lipids promote renal injury and that statins, independent of their lipid-lowering effects, confer renoprotection via effects on intrarenal hemodynamics and renal cytokine and chemokine expression. Clinical studies have in general been underpowered, but a recent meta-analysis and findings from the Heart Protection Study suggest that statins may be renoprotective. Nevertheless, with the convincing antiatherosclerotic effects of these agents, including in the setting of diabetes, they should be widely administered in the diabetic population with or at risk for nephropathy.
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PMID:Lipids and diabetic renal disease. 1631 96

Combined dyslipidemia is the concurrent presence of multiple abnormalities in various lipid subfractions, including elevated concentrations of low-density lipoprotein (LDL) cholesterol and triglycerides (TGs), as well as decreased concentrations of high-density lipoprotein (HDL) cholesterol. The Adult Treatment Panel III (ATP III) guidelines of the US National Cholesterol Education Program (NCEP) lowered the cut points for classification of TG levels, established non-HDL cholesterol levels as a secondary target of therapy in patients with TGs of >or=2.26 mmol/L (200 mg/dL), and defined the metabolic syndrome as a secondary target of therapy. Although 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are first-line therapy for most patients with elevated LDL cholesterol, statin monotherapy may not be sufficient to achieve recommended non-HDL cholesterol goals, and statins have only modest effects on reducing TG levels. Similarly, patients whose TG levels remain elevated despite treatment with a TG-lowering agent may require the addition of a statin to provide further TG reduction. In addition, statin therapy may be needed to offset the secondary increase in levels of LDL cholesterol that frequently results from treatment with a TG-lowering agent in patients with marked hypertriglyceridemia. In a number of small studies, the combination of statins and omega-3 fatty acids has been consistently shown to be an effective, safe, and well-tolerated treatment for combined dyslipidemia. Patients with recent myocardial infarction may also benefit from this combination. When considering risks and benefits of adding a second agent to statins for treatment of combined dyslipidemia, omega-3 fatty acids provide additional lipid improvements without requiring additional laboratory tests and do not increase risk for adverse muscle or liver effects.
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PMID:Combination therapy with statins and omega-3 fatty acids. 1691 15

Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment and prevention of coronary artery disease. However, despite increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is being paid now to combined atherogenic dyslipidemia which typically presents in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"): hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a preponderance of small, dense low-density lipoprotein particles and an accumulation of cholesterol-rich remnant particles (e.g. high levels of apolipoprotein B)--emerged as the greatest "competitor" of low-density lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP - Bezafibrate Infarction Prevention study, HHS - Helsinki Heart Study, VAHIT--Veterans Affairs High-density lipoprotein cholesterol Intervention Trial and FIELD--Fenofibrate Intervention and Event Lowering in Diabetes) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants and cholesteryl ester transfer protein inhibition. In addition, bezafibrate as pan-peroxisome proliferator activated receptor activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each regulate serum lipids by different mechanisms, combination therapy--selected on the basis of their safety and effectiveness - may offer particularly desirable benefits in patients with combined hyperlipidemia as compared with statins monotherapy.
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PMID:Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins. 1700 98

The cardiovascular benefits of therapy with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are well documented. Undertreatment of dyslipidemia remains pervasive, however, and the introduction of more-aggressive optional LDL-cholesterol targets in US guidelines only heightens the challenges of reaching the target values. Combination therapy with a statin and the cholesterol absorption inhibitor ezetimibe could help in the management of patients who have an inadequate reduction in cholesterol after making changes to lifestyle or taking statins alone. The effects of the combination on cardiovascular risk remain speculative, however, and clinical trials are in development. In this Review we consider the rationale for combination therapy in the context of achieving LDL-cholesterol goals.
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PMID:Drug insight: the role of statins in combination with ezetimibe to lower LDL cholesterol. 1712 99

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) play a prominent role in the treatment of dyslipidemia. Overall, statins are well tolerated, with a low occurrence of adverse effects. More serious reactions to statins have been reported, although they are rare (e.g., rhabdomyolysis 0.3-13.5 cases/million statin prescriptions). Combination therapy to treat dyslipidemia has become common in many patients; however, it can also increase the risk of serious adverse effects. We report the case of a patient who experienced muscle pain and elevated creatine kinase levels 16 days after the addition of ezetimibe to his atorvastatin therapy for hypercholesterolemia. Twelve days after stopping the ezetimibe, his muscle pain resolved and his serum creatine kinase level returned to baseline. This case report raises questions regarding the safety of high-dose atorvastatin and ezetimibe combination therapy and suggests that caution and careful monitoring may be warranted.
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PMID:Myopathy associated with atorvastatin-ezetimibe combination therapy. 1725 23


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