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

Evidence for the effectiveness of lipid-lowering therapy in reducing CHD risk continues to emerge. In primary prevention, clinical trials have demonstrated a benefit for middle-aged, high-risk men with high LDL cholesterol and, more recently, for men and women with "average" LDL and low HDL cholesterol. Although low HDL cholesterol, small dense LDL particles, elevated lipoprotein (a), elevated apolipoprotein B, and the dyslipidemia of the metabolic syndrome pose an increased in CHD risk in some patients, the risk reduction with lipid-lowering therapy has not been fully investigated. The CHD risk of isolated hypertriglyceridemia remains uncertain. Very high triglyceride levels, however, should be treated to prevent pancreatitis. A lipid-lowering diet and other appropriate lifestyle changes constitute safe advice for all patients with dyslipidemia. In initiating pharmacologic therapy, physicians should view potential risk reduction in the context of a patient's overall CHD risk. The selection of particular medications can be individualized, considering effectiveness evidence from clinical trials, lipid-lowering potency, adverse effects, drug interactions, costs, and patient preferences.
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PMID:Management of dyslipidemias in the age of statins. 1502 90

We investigated the biological activity of Dr. Reddy's Research Foundation (DRF) 2519, a benzoxazinone analogue of the thiazolidinedione class of compounds. In the in vitro transactivation assay, DRF 2519 showed interesting dual activation of Peroxisome Proliferator Activated Receptor (PPAR) alpha and gamma. In insulin-resistant ob/ob mouse model, DRF 2519 showed significant alleviation of insulin resistance and dyslipidemia, which is better than rosiglitazone. Fatty Zucker rats treated with DRF 2519 showed better reduction of plasma insulin, triglyceride and free fatty acid levels than those treated with rosiglitazone. In addition, these rats were able to clear plasma lipids better when challenged with exogenous lipid (i.v.). DRF 2519 treatment resulted in improved plasma lipid profiles in high-fat-fed Sprague-Dawley rats. Treated rats showed better plasma lipid clearance and hepatic triglyceride secretion. When compared to DRF 2519, fenofibrate was comparatively less efficacious while rosigltiazone showed no activity in these models. In ex vivo studies, DRF 2519 showed induction of liver acyl CoA oxidase mRNA and increase in lipoprotein lipase (LPL) protein expression and activity in adipose tissue. In the in vitro studies, DRF 2519 inhibited the lipid biosynthesis and secretion of apolipoprotein B from human hepatoma (Hep)G2 cells. It also enhanced insulin-induced relaxation of rat aortic smooth muscle. These results indicate that DRF 2519, a dual activator of PPAR-alpha and gamma, could be an interesting development candidate in the management of metabolic disorders and associated complications.
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PMID:Antidiabetic and hypolipidemic potential of DRF 2519--a dual activator of PPAR-alpha and PPAR-gamma. 1514 Jun 37

Regional body fat distribution has an important influence on metabolic and cardiovascular risk factors. Increased abdominal (visceral) fat accumulation is a risk factor for coronary artery disease (CAD), dyslipidemia, hypertension, stroke, and type 2 diabetes. The recent emphasis on treatment of the dyslipidemia of the metabolic syndrome (hypertriglyceridemia, reduced high-density lipoprotein, and increased small, dense low-density lipoprotein particle number) has compelled practitioners to consider lipid-lowering therapy in a greater number of their patients, as one in two individuals over age 50 has the metabolic syndrome. Individuals with the metabolic syndrome typically have normal low-density lipoprotein cholesterol levels, and current lipid-lowering guidelines may underestimate their cardiovascular risk. Two subgroups of patients with the metabolic syndrome are at particularly high risk for premature CAD. One, individuals with type 2 diabetes, accounts for 20-30% of early cardiovascular disease. The second, familial combined hyperlipidemia, accounts for an additional 10-20% of premature CAD. Familial combined hyperlipidemia is characterized by the metabolic syndrome in addition to a disproportionate elevation of apolipoprotein B levels. The measurement of fasting glucose and apolipoprotein B, in addition to the fasting lipid profile, can help to estimate CAD risk in patients with the metabolic syndrome.
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PMID:Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk. 1518 Oct 30

The metabolic syndrome encapsulates visceral obesity, insulin resistance, diabetes, hypertension and dyslipidaemia. Dyslipidaemia is a cardinal feature of the metabolic syndrome that accelerates the risk of cardiovascular disease. It is usually characterized by high plasma concentrations of triacylglycerol (triglyceride)-rich and apoB (apolipoprotein B)-containing lipoproteins, with depressed concentrations of HDL (high-density lipoprotein). However, lipoprotein metabolism is complex and abnormal plasma concentrations can result from alterations in the rates of production and/or catabolism of these lipoprotein particles. Our in vivo understanding of kinetic defects in lipoprotein metabolism in the metabolic syndrome has been achieved chiefly by ongoing developments in the use of stable isotope tracers and mathematical modelling. This review deals with the methodological aspects of stable isotope kinetic studies. The design of in vivo turnover studies requires considerations related to stable isotope tracer administration, duration of sampling protocol and interpretation of tracer data, all of which are critically dependent on the kinetic properties of the lipoproteins under investigation. Such models provide novel insight that further understanding of metabolic disorders and effects of treatments. Future investigations of the pathophysiology and therapy of the dyslipoproteinaemia of the metabolic syndrome will require the development of novel kinetic methodologies. Specifically, new stable isotope techniques are required for investigating in vivo the turnover of the HDL subpopulation of particles, as well as the cellular efflux of cholesterol into the extracellular space and its subsequent transport in plasma and metabolic fate in the liver.
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PMID:Lipoprotein transport in the metabolic syndrome: methodological aspects of stable isotope kinetic studies. 1522 43

Visceral obesity is frequently associated with high plasma triglycerides and low plasma high density lipoprotein-cholesterol (HDL-C), and with high plasma concentrations of apolipoprotein B (apoB)-containing lipoproteins. Atherogenic dyslipidemia in these patients may be caused by a combination of overproduction of very low density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles, and increased catabolism of HDL-apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance. Weight reduction, increased physical activity, and moderate alcohol intake are first-line therapies to improve lipid abnormalities in visceral obesity. These lifestyle changes can effectively reduce plasma triglycerides and low density lipoprotein-cholesterol (LDL-C), and raise HDL-C. Kinetic studies show that in visceral obesity, weight loss reduces VLDL-apoB secretion and reciprocally upregulates LDL-apoB catabolism, probably owing to reduced visceral fat mass, enhanced insulin sensitivity and decreased hepatic lipogenesis. Adjunctive pharmacologic treatments, such as HMG-CoA reductase inhibitors, fibric acid derivatives, niacin (nicotinic acid), or fish oils, may often be required to further correct the dyslipidemia. Therapeutic improvements in lipid and lipoprotein profiles in visceral obesity can be achieved by several mechanisms of action, including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. Clinical trials have provided evidence supporting the use of HMG-CoA reductase inhibitors and fibric acid derivatives to treat dyslipidemia in patients with visceral obesity, insulin resistance and type 2 diabetes mellitus. Since drug monotherapy may not adequately optimize dyslipoproteinemia, dual pharmacotherapy may be required, such as HMG-CoA reductase inhibitor/fibric acid derivative, HMG-CoA reductase inhibitor/niacin and HMG-CoA reductase inhibitor/fish oils combinations. Newer therapies, such as cholesterol absorption inhibitors, cholesteryl ester transfer protein antagonists and insulin sensitizers, could also be employed alone or in combination with other agents to optimize treatment. The basis for a multiple approach to correcting dyslipoproteinemia in visceral obesity and the metabolic syndrome relies on understanding the mechanisms of action of the individual therapeutic components.
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PMID:Dyslipidemia in visceral obesity: mechanisms, implications, and therapy. 1528 98

A metabolic syndrome (MetS) phenotype is characterized by insulin-resistance, atherogenic dyslipidemia, oxidative stress, and elevated cardiovascular risk and frequently involves subnormal levels of high-density lipoprotein (HDL) cholesterol. We evaluated the capacity of physicochemically distinct HDL subfractions from MetS subjects to protect low-density lipoprotein against oxidative stress.MetS subjects presented an insulin-resistant phenotype, with central obesity and elevation in systolic blood pressure and plasma triglyceride, LDL-cholesterol, apolipoprotein B, glucose, and insulin levels. Systemic oxidative stress, assessed as plasma 8-isoprostanes, was significantly higher (3.7-fold) in MetS subjects (n = 10) compared with nonobese normolipidemic controls (n = 11). In MetS, small, dense HDL3a, 3b, and 3c subfractions possessed significantly lower specific antioxidative activity (up to -23%, on a unit particle mass basis) than their counterparts in controls. In addition, HDL2a and 3a subfractions from MetS patients possessed lower total antioxidative activity (up to -41%, at equivalent plasma concentrations). The attenuated antioxidative activity of small, dense HDL subfractions correlated with systemic oxidative stress and insulin resistance and was associated with HDL particles exhibiting altered physicochemical properties (core triglyceride enrichment and cholesteryl ester depletion). We conclude that antioxidative activity of small, dense HDL subfractions of altered chemical composition is impaired in MetS and associated with elevated oxidative stress and insulin resistance. Induction of selective increase in the circulating concentrations of dense HDL subfractions may represent an innovative therapeutic approach for the attenuation of high cardiovascular risk in MetS.
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PMID:Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. 1547 92

Serum apolipoprotein B (apo B) levels were found to be significantly (p < 0.001) higher in the 27 patients with combined hyperlipidemia (144 m./dl +/- 27.6) than in the 17 normal weight normolipidemic control subjects (92 mg/dl +/- 20.6; X +/- SD). When compared to apolipoprotein A1 (apo A1) levels obtained in controls (168.5 mg/dl +/- 28.4), hyperlipidemic subjects displayed a moderate yet significant (p < 0.02) decrease of this apolipoprotein (140 mg/dl +/- 24.2). Serum apo B levels were significantly (p < 0.001) correlated with serum cholesterol concentrations and also, to a lesser degree (p < 0.01), with serum cholinesterase activity. A highly significant correlation (p < 0.001) between apo A1 and HDL cholesterol levels was also noted. The decrease ofHDL cholesterol occurring in hyperlipidemic men (-30%) was however more accentuated than the decrease of apo A1 (-18%) suggesting an enhanced transfer of cholesterol esters from HDL to VLDL and LDL. It is considered that the determination of apolipoproteins may be useful not only for the detection of risk factors for atherosclerosis, but also for a better insight concerning the mechanisms involved in the development of an atherogenic dyslipidemia.
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PMID:Apolipoproteins A1 and B levels and serum cholinesterase activity in hyperlipidemic subjects. 1552 47

Combination therapy with a statin and niacin may provide optimal therapy for patients with combined hyperlipidemia and low levels of high-density lipoprotein (HDL) cholesterol. The authors assessed the efficacy and safety of rosuvastatin monotherapy, extended-release (ER) niacin monotherapy, or rosuvastatin and ER niacin combined therapy in patients with atherogenic dyslipidemia. In a 24-week, open-label, multicenter trial, men and women aged > or =18 years with fasting levels of total cholesterol > or =200 mg/dL, HDL cholesterol > or =45 mg/dL, triglycerides 200-800 mg/dL, and apolipoprotein B > or =110 mg/dL were randomly assigned to one of four treatment groups: rosuvastatin 10-40 mg, ER niacin 0.5-2 g, rosuvastatin 40 mg plus ER niacin 0.5-1 g, or rosuvastatin 10 mg plus ER niacin 0.5-2 g. Daily doses of rosuvastatin 40 mg monotherapy reduced low-density lipoprotein (LDL) cholesterol and non-HDL cholesterol levels significantly more than did either ER niacin 2 g monotherapy or rosuvastatin 10 mg combined with ER niacin 2 g. Addition of ER niacin 1 g to rosuvastatin 40 mg did not further reduce total or non-HDL cholesterol. Triglyceride reductions were similar among the four treatment groups. ER niacin mono- and combined therapy produced significantly greater rises in HDL cholesterol and apolipoprotein A-1 than did rosuvastatin monotherapy. Rosuvastatin monotherapy was better tolerated than ER niacin taken either alone or with rosuvastatin. In this study, rosuvastatin very effectively improved the three major lipoprotein-lipid abnormalities of combined hyperlipidemia.
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PMID:Rosuvastatin alone or with extended-release niacin: a new therapeutic option for patients with combined hyperlipidemia. 1553 64

Dyslipidemia is a heterogeneous metabolic condition; high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein represent families of lipoprotein particles that differ in size and composition and vary in atherogenicity. Lipoprotein subclasses containing apolipoprotein B promote atherosclerosis, of which the most atherogenic appear to be the small, dense LDL and large very-low-density lipoprotein subclasses, while the large HDL2 subclass, which transports esterified cholesterol from the periphery to the liver, is considered the more cardioprotective. Niacin has long been known to improve concentrations of all major lipids and lipoproteins, but it also has consistently favorable effects on subclass distribution. A MEDLINE search was conducted for clinical studies reporting the effects of niacin on lipoprotein subclasses. The niacin-associated elevations in HDL cholesterol likely stem from differential drug effects on subclasses, producing favorable changes in levels of HDL2 and apolipoprotein A-I. Niacin has more moderate LDL cholesterol-lowering efficacy, but this change is associated with an increase in LDL particle size and a shift from small LDL to the less atherogenic, large LDL subclasses. In addition, it also tends to decrease concentrations of the larger very-low-density lipoprotein subclasses. Niacin confers diverse benefits with respect to both the quantity and quality of lipid and lipoprotein particles.
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PMID:The effects of niacin on lipoprotein subclass distribution. 1553 65

Growing evidence suggests an association between lipid abnormalities and fatty acid binding protein (FABP) and microsomal triglyceride transfer protein (MTP) gene variants. Our objectives were to determine whether Ala54Thr FABP2 and G-493T MTP polymorphisms are associated with increased risks of insulin resistance syndrome (IRS) in youth and/or modify the expression of accompanying dyslipidemia. Our study of 1,742 French-Canadians aged 9, 13, and 16 years did not provide evidence of a potential predisposition to IRS related to either FABP2 or MTP genotypes. However, we observed a heterogeneity of the FABP2 effect by IRS status on total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and apolipoprotein B (apoB) concentrations (P for interaction=0.045, 0.018, and 0.017, respectively). Among the metabolic components of IRS, only triglyceride (TG) displayed an interaction with FABP2 polymorphism: compared with Thr/Ala and Ala/Ala, the Thr/Thr genotype was associated with a steeper increase in TC, LDL-C, and apoB parallel to TG concentrations (P <0.001). IRS did not modify the associations between the MTP polymorphism and any of the biochemical parameters. Our study suggests that the effects of FABP2 allelic variations on lipid traits are context dependent, indicating that this variant may play an important role in cardiovascular pathogenesis in the presence of IRS or hypertriglyceridemia.
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PMID:Intestinal fatty acid binding protein and microsomal triglyceride transfer protein polymorphisms in French-Canadian youth. 1554 95


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