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 prominent use of fibric acid derivatives has lessened over the years because of unimpressive results in major clinical trials, safety concerns, and the emergence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Clofibrate was widely used in the 1970s, but after publication of results from two major trials demonstrating only modest reductions in the rate of coronary heart disease (CHD) and concerns regarding an increase in the frequency of gallstones and overall mortality, its use subsided dramatically. With the introduction of gemfibrozil in the 1980s came a renewed interest in the class, which was also supported by the published results of the Helsinki Heart Study; however, despite a significant reduction in CHD events and a sound safety profile, overall mortality was comparable to that with placebo. Again, in the 1990s, awareness of the fibrates was heightened with the availability of fenofibrate and the findings of another major trial using gemfibrozil, the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT), which demonstrated impressive results in reducing cardiovascular events. To further strengthen the VA-HIT results, numerous post hoc analyses were performed on the data of major trials of fibrate therapy among patients with mixed dyslipidemia, with similar findings. Recently, however, data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were published, indicating mixed results. Nearly 40 years after the introduction of the fibrates, practitioners are still contemplating the role of these agents in the treatment of CHD.
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PMID:Fibrates: what have we learned in the past 40 years? 1731 52

The MS is associated with increased morbidity and mortality for cardiovascular disease (CVD). MS is represented not only by metabolic alteration such as hyperglycemia, and hyperlipemia but also by a chronic pro-inflammatory state. Another responsible in the formation and progression of CVD is the so-called endothelial dysfunction, which is linked to insulin resistance itself. The common denominator of the MS is insulin resistance. The most convincing evidence for the existence of MS comes from the cluster analysis which outlines four main factors: the "metabolic factor", the "pressure factor", the "lipid factor" and the "obesity factor". It is clear that the presence of the MS appears to identify a substantial additional cardiovascular risk on top of the individual risk factors. The studies available in the literature have pointed out the beneficial effects, in terms of cardiovascular mortality, of the treatment with inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins): this reduction of risk has been observed despite the fact that high triglyceride and low high-density lipoprotein (HDL)-cholesterol levels, but not hypercholesterolemia, are the main features of the dyslipidemia observed in patients with MS. Yet, despite a normal low-density lipoprotein (LDL)-cholesterol level, patients with MS are at high risk for future CVD. For this reason, their treatment with statins is mandatory.
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PMID:Diabetes and metabolic syndrome (MS). 1731 35

Appropriate management of lipids is a central component of risk reduction in patients with coronary artery disease (CAD). According to the most recent guidelines, low-density lipoprotein cholesterol (LDLC) is the principal target of lipid-lowering therapy and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the mainstay of this therapy. The actual target level of LDL lowering is being reassessed in light of recent clinical trials. Once appropriate LDL lowering has been achieved, treatment of other targets such as high-density lipoprotein cholesterol (HDLC), triglycerides, and non-HDLC should be considered. In addition to dyslipidemia, multiple observational studies suggest that inflammatory markers such as C-reactive protein (CRP) are associated with risk of cardiovascular events and that treatment with statins may lower CRP levels. However, there are insufficient data at this time supporting treatment of CRP as a principal target in CAD.
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PMID:Treatment goals for the management of lipids and inflammation for patients with coronary artery disease. 1737 71

During the last two decades, numerous studies have demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) diminish the risk of cardiovascular morbidity and mortality. Although these studies have focused primarily on the ability of statins to lower circulating levels of low-density lipoprotein cholesterol, more recent research has shown that statins may protect the vasculature via pleiotropic effects not directly related to lipid lowering. These include adjustments in cell-signaling pathways that play a role in atherogenesis and that affect the expression of inflammatory elements, curtail oxidative stress, and enhance endothelial function. More recently, researchers have begun to explore whether these agents exert similar beneficial effects in renal parenchymal and renovascular disease. This review examines the available evidence that dyslipidemia may augment the inflammatory reaction of cytokines in patients with renal disease and that statins may improve renal dysfunction by altering the response of the kidney to dyslipidemia, even in persons with end-stage renal disease on dialysis or with renal transplantation. In this context, some data suggest that statin-mediated alterations in inflammatory responses and endothelial function may reduce proteinuria and the rate of progression of kidney disease.
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PMID:HMG-CoA reductase inhibitors and the kidney. 1749 67

This article presents a series of take-home statements, compiled by a multidisciplinary steering committee, concerning significant aspects of macrovascular disease in patients with diabetes mellitus, including the extent of risk, pathogenetic mechanisms, and optimal management for risk reduction. The discussion focuses in particular on the impact of diabetes medications beyond blood glucose control. In summary, these statements are as follows: (1) Patients with diabetes have an increased risk for cardiovascular disease that contributes to decreased life expectancy; (2) prognosis after a cardiovascular event is poorer in patients with diabetes; (3) pathogenetic mechanisms include insulin resistance, endothelial dysfunction, dyslipidemia, chronic inflammation, procoagulability, and impaired fibrinolysis; (4) management of established cardiovascular risk factors, for example with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and antihypertensive therapy, reduces cardiovascular event rates in diabetes; (5) correction of hyperglycemia can reduce macrovascular event rates, but the coupling to hyperglycemia is less tight for macrovascular events than it is for reduction of microvascular complications; (6) patients with diabetes should be screened for additional cardiovascular risk factors and appropriate interventions should be initiated; (7) results of observational and interventional studies have indicated that some insulin sensitizers appear to reduce the incidence of cardiovascular events and improve survival; (8) thiazolidinediones have beneficial effects on metabolism that may improve cardiovascular risk, and a randomized clinical trial in patients with advanced atherosclerosis indicates that addition of pioglitazone to therapy for hyperglycemia may reduce the incidence of cardiovascular events such as myocardial infarction and stroke.
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PMID:Optimizing cardiovascular outcomes in diabetes mellitus. 1782 44

Platelet activation and aggregation are central processes in the pathophysiology of coronary heart disease. Mean platelet volume (MPV), a determinant of platelet activation, is a newly emerging risk marker for atherothrombosis. Rosuvastatin, a new hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), is approved as an adjunct to diet in patients with dyslipidemia. In this study, we evaluated the effects of rosuvastatin on the MPV levels in patients with uncontrolled primary dyslipidemia with hypolipidemic treatment. We selected 30 age, sex and body mass index matched patients with uncontrolled primary dyslipidemia and hypolipidemic diet treatment and 30 normolipidemic healthy subjects. Dyslipidemic patients were treated with 10 mg/day rosuvastatin for 12 weeks. Metabolic parameters and MPV were measured at baseline and after rosuvastatin treatment in dyslipidemic group. At baseline, the dyslipidemic group had significantly higher MPV levels than in the healthy control group (8.4 +/-1.2 fl vs. 8.1 +/-0 1.0 fl, p < 0.005). The level of MPV decreased significantly after rosuvastatin treatment from a mean of 8.4 +/- 1.2 fl to 8.1 +/- 1.3 fl, (p < 0.001). The changes in MPV levels with rosuvastatin treatment were not correlated to changes in plasma lipids (p > 0.05). In addition to its well-known hypolipidemic effect, rosuvastatin also possesses significant anti-platelet activation properties. This antiplatelet effect of rosuvastatin treatment could play a role in reducing cardiovascular complications in primary hyperlipidemic patients.
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PMID:The effect of rosuvastatin treatment on the mean platelet volume in patients with uncontrolled primary dyslipidemia with hypolipidemic diet treatment. 1785 72

Evidence of the effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) within continuum of atherothrombotic conditions and particularly in the treatment and prevention of coronary heart disease (CHD) is well established. Large-scale, randomized, prospective trials involving patients with CHD have shown that statins reduce the clinical consequences of atherosclerosis, including cardiovascular deaths, nonfatal myocardial infarction and stroke, hospitalization for acute coronary syndrome and heart failure, as well as the need for coronary revascularization. Direct testing of varying degrees of low-density lipoprotein (LDL)- cholesterol lowering has now been carried out in 4 large outcomes trials: PROVE IT-TIMI 22, A to Z, TNT and IDEAL. However, the question whether more aggressive LDL-cholesterol lowering by high-dose statins monotherapy is an appropriate strategy is still open: higher doses of statins are more effective mainly for the prevention of the nonfatal cardiovascular events but such doses are associated with an increase in hepatotoxicity, myopathy and concerns regarding noncardiovascular death. Moreover, despite the increasing use of statins, a significant number of coronary events still occur and many such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is now being paid to combined atherogenic dyslipidemia which typically presented in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or 'lipid quartet') - hypertriglyceridemia, low high-density lipoprotein (HDL)-cholesterol levels, a preponderance of small, dense LDL particles and an accumulation of cholesterol-rich remnant particles - emerged as the greatest 'competitor' of LDL-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP, HHS, VAHIT and FIELD) 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, CETP inhibitors and omega-3 fatty acids. Particularly, ezetimibe/statins combinations provide superior lipid-modifying benefits compared Tenenbaum/Fisman/Motro/Adler 128 with any statins monotherapy in patients with atherogenic dyslipidemia. Atherogenic dyslipidemia is associated with increased levels of chylomicrons and their remnants containing 3 main components: apolipoprotein B-48, triglycerides and cholesterol ester of intestinal origin. Reduction in accessibility for one of them (specifically cholesteryl ester lessening due to ezetimibe administration) could lead to a decrease of the entire production of chylomicrons and result in a decrease of the hepatic body triglycerides pool as confirmed in number of clinical studies. However, the ENHANCE study showed no difference in the progression of carotid atherosclerosis between ezetimibe/simvastatin vs. simvastatin alone over a 2-year period. Conclusions regarding ezetimibe/statins combinations should not be made until the three large clinical outcome trials will be completed within the next 2-3 years. In addition, bezafibrate as a pan-PPAR activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism, insulin sensitivity and pancreatic beta cell protection. Because fibrates, niacin, ezetimibe, omega-3 fatty acids and statins each regulate serum lipids by different mechanisms, combination therapy - selected on the basis of their safety and effectiveness, could be more helpful in achieving a comprehensive lipid control as compared with statins monotherapy.
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PMID:Optimal management of combined dyslipidemia: what have we behind statins monotherapy? 1823 Sep 60

Combination therapy for patients with coronary artery disease (CAD) is often indicated as a significant number of patients receiving 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy continue to have high residual risk. Combination drug therapy is also indicated for patients at high risk, including those with combined hyperlipidemia and dyslipidemia with diabetes mellitus. Effectively managing CAD and achieving optimal therapeutic targets, especially in patients at high risk, frequently requires the use of aggressive therapeutic interventions. In this article, the authors review the use of combination therapy as a strategy for risk reduction in CAD.
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PMID:Reducing the residual risk of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor therapy with combination therapy. 1837 38

Niacin (nicotinic acid), the most effective available pharmacotherapy for increasing high-density lipoprotein cholesterol, also lowers triglycerides and hence may be useful, alone or in combination with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), to offset residual cardiovascular risk in patients with mixed or diabetic dyslipidemia. We conducted a review of published consensus guidelines since 2000 and an English-language PubMed search of prospective, randomized controlled trials and open-label studies from January 1, 1990, through December 31, 2007, concerning the effects of niacin, alone or in combination with statins, on glycemic regulation in dyslipidemic patients (with or without diabetes mellitus). For search terms, we used the title words niacin or nicotinic acid and key words including diabetes, diabetic, dyslipidemia, glucose, glycemic, HbA1c, hemoglobin, hyperglycemia, human, insulin, postprandial, and safety. Retrospective and observational studies, case reports, and case studies were excluded. On the basis of our analysis, the effects of niacin (< or =2.5 g/d), alone or in combination with statins, on fasting glucose (an increase of 4%-5%) and hemoglobin A1c levels (an increase of < or =0.3%) are modest, transient or reversible, and typically amenable to adjustments in oral hypoglycemic regimens without discontinuing niacin. Niacin therapy was infrequently associated with incident diabetes or the need for new insulin prescriptions. Studies showed important clinical benefits of niacin or niacin-statin regimens despite modest effects on glucose control. On a population basis, significant reductions in incidences of cardiovascular events and the degree of atherosclerotic progression associated with long-term niacin (or niacin-statin) therapy in patients with diabetic dyslipidemia outweigh the typically mild effects of this therapy on glycemic regulation. Consensus guidelines recommend monitoring glycemic control after initiating niacin treatment or increasing its dosage.
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PMID:Effects of niacin on glucose control in patients with dyslipidemia. 1838 Sep 93

Reducing high levels of plasmatic lipoids (LDL-cholesterol and triglycerides) is one of the most important steps in the prevention and treatment of cardiovascular diseases. In the majority of cases, treatment based on lifestyle changes (changes in dietary habits, more physical activity) is not sufficient and pharmacotherapy becomes necessary. Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are a well tolerated first-choice drug in patients with dyslipidemia. However, great variability of statin effects has been observed in different patients on the same therapy, and the cause clearly resides in different genetic characteristics of each individual, influencing the effect of therapy. The influence of different genetic variants has been described, but the control of response to hypolipidemic therapy is most likely subject to polygenic control. The analysis of multiple gene combinations may help detect the "hyper-" and "hypo-" responders, i.e. individuals with a good response to treatment (allowing for starting with a lower dose of the drug), and those with an insufficient response to treatment (in whom statin shall not be the drug of first choice), or it may help detect the patients who are more likely to develop severe adverse events. Studies with different designs describe that for instance genes (and their variants) for cytochromes, apolipoprotein E and A1 and cholesterol 7alpha-hydroxylase may be important genetic determinants of the effect of pharmacological treatment of dyslipidemia and play a role in the individualisation of treatment.
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PMID:[Statin pharmacokinetics]. 1839 Jan 12


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