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

Dyslipidemia is a prominent feature of chronic renal failure (CRF) and a major risk factor for atherosclerosis and the progression of renal disease. CRF-induced dyslipidemia is marked by hypertriglyceridemia and a shift in plasma cholesterol from HDL to the ApoB-containing lipoproteins. Several studies have demonstrated a favorable response to administration of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors (statins) in CRF. This study was intended to explore the effect of statin therapy on key enzymes and receptors involved in cholesterol metabolism. Accordingly, CRF (5/6 nephrectomized) and sham-operated rats were randomized to untreated and statin-treated (rosuvastatin 20 mg x kg(-1) x day(-1)) groups and observed for 6 wk. The untreated CRF rats exhibited increased total cholesterol-to-HDL cholesterol ratio, diminished plasma lecithin:cholesterol acyltransferase (LCAT) and the hepatic LDL receptor, elevated hepatic acyl-CoA:cholesterol acyltransferase (ACAT), and no change in hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, or HDL receptor (SRB-1). Statin administration lowered HMG-CoA reductase activity, normalized plasma LCAT, total cholesterol-to-HDL cholesterol ratio, and hepatic LDL receptor but did not significantly change either plasma total cholesterol, hepatic cholesterol 7alpha-hydroxylase, total ACAT activity, or SRB-1 in the CRF animals. Statin administration to the normal control rats led to significant increases in plasma LCAT and hepatic LDL receptor, significant reductions of total cholesterol-to-HDL cholesterol ratio, hepatic HMG-CoA reductase activity, and cholesterol 7alpha-hydroxylase abundance with virtually no change in plasma cholesterol concentration. Thus administration of rosuvastatin reversed LCAT and LDL receptor deficiencies and promoted a shift in plasma cholesterol from ApoB-containing lipoproteins to HDL in CRF rats.
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PMID:HMG-CoA reductase inhibition reverses LCAT and LDL receptor deficiencies and improves HDL in rats with chronic renal failure. 1550 47

Cardiovascular disease is the leading cause of mortality among people with diabetes mellitus, accounting for 70% of all deaths. As the prevalence of diabetes increases significantly worldwide, greater attention must be focused on preventing cardiovascular events in this group. One contributor to this increased event rate is the characteristic pattern of dyslipidemia in diabetic patients, consisting of elevated serum triglyceride levels, decreased high-density lipoprotein levels, and an increased proportion of small, dense, low-density lipoproteins. Several pharmacologic agents have been used to treat this dyslipidemia including HMG-CoA reductase inhibitors, fibric acid derivatives, niacin (nicotinic acid), thiazolidinediones, and fish oils, as well as other non-pharmacologic measures. Currently, the most extensive data for a reduction in cardiovascular events in patients with diabetes exist for HMG-CoA reductase inhibitors. The results of these trials indicate that HMG-CoA reductase inhibitor therapy should be considered for all patients with diabetes at sufficient risk for cardiovascular events, regardless of serum low-density lipoprotein-cholesterol level. Several ongoing trials of various pharmacologic agents should help clarify the role of these agents alone and in combination with HMG-CoA reductase inhibitors in the management of diabetic dyslipidemia.
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PMID:Management of diabetic dyslipidemia: need for reappraisal of the goals. 1572 39

It is important for prevention of vascular complications in diabetics to control blood glucose, blood pressure, and dyslipidemia, and to stop smoking. Recently, it has been reported that the HMG-CoA reductase inhibitor has angiogenetic effects independent of lipid lowering effect. Moreover, gene therapy using VEGF and HGF has shown dramatic effects for peripheral arterial disease. Endothelial progenitor cells injection is also expected for treatment of ischemic heart disease.
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PMID:[Division of endocrinology and metabolism, strategy for treatment of diabetic vascular complications for physicians]. 1577 99

Atherosclerosis and its complications still represent the major cause of death in developed countries. Statins have revolutionized the treatment of dyslipidemia and demonstrated their ability to reduce and prevent coronary morbidity and mortality. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol synthesis. The effectiveness and rapidity of statin-induced decreases in coronary events led to the speculation that statins possess cholesterol-independent effects. Since mevalonate produced by the HMG-CoA reductase is not only the precursor of cholesterol, but also of non steroidal isoprenoid compounds, such as the farnesyl pyrophosphate and the geranylgeranyl pyrophosphate, statins also regulate the small signaling proteins, Ras and Rho. Thus, inhibition of these prenylated proteins might account for the non-lipid lowering effects of statins. In this review, we describe the numerous beneficial pleiotropic effects of statins that could modulate atherogenesis.
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PMID:Cholesterol-independent effects of statins in inflammation, immunomodulation and atherosclerosis. 1585 54

Dyslipidemia and progression of cardiovascular calcification (CVC) in patients with end-stage renal disease (ESRD). Cardiovascular calcification (CVC) is commonly encountered both in the general population as well as in patients with end-stage renal disease (ESRD). The etiology of CVC in patients with ESRD is multifactorial. Despite that, current debate remains narrowly focused on the role of calcium loading from calcium-based phosphate binders (CBPB) in the pathogenesis and progression of CVC. Yet, the alleged link between these binders and CVC has not been substantiated in well-designed controlled trials. In contrast, the purported role of sevelamer, a non-calcium-based phosphate binder, in slowing the progression of CVC in dialysis patients has attracted widespread attention. The beneficial effect of sevelamer on progression of calcification was thought to be due to lower calcium loading during its use. However, an alternative and possibly more likely mechanism involves sevelamer-induced lowering of LDL cholesterol. In this context, previous studies in individuals with normal renal function have documented amelioration of coronary artery calcification (CAC) with reduction of LDL-cholesterol by treatment with HMG-CoA reductase inhibitors (statins). Given that CAC is a well-accepted marker of atherosclerosis, and that high plasma cholesterol concentration is one of the main risk factors for atherosclerosis, then it is not unreasonable to suspect that CAC may be halted or even reversed by lowering of LDL cholesterol level with statin therapy. Unfortunately, the effect of lowering the LDL-cholesterol level on CAC has not been studied in patients with ESRD. Therefore, conclusions about this important topic should await the results of well-designed clinical studies that control for all factors potentially implicated in the CVC burden of patients with ESRD. In this review, I will discuss the role of various potential mechanisms involved in the pathogenesis of CVC in patients with ESRD, and emphasize the role of dyslipidemia and its treatment in this important clinical entity.
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PMID:Dyslipidemia and progression of cardiovascular calcification (CVC) in patients with end-stage renal disease (ESRD). 1588 13

Premature atherosclerotic coronary heart disease driven by multiple risk factors is a major cause of morbidity and mortality among the 6 million patients in the United States with chronic renal failure. Consensus is that kidney failure and renal transplantation patients should be treated aggressively for dyslipidemia. Major medical literature databases were searched for published information about fluvastatin, a HMG-CoA reductase inhibitor, used in patients with impaired renal function. This article characterizes the dyslipidemia observed in these clinical settings and reviews the clinical experience with fluvastatin.
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PMID:Fluvastatin in the treatment of dyslipidemia associated with chronic kidney failure and renal transplantation. 1595 41

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

A novel animal model of insulin resistance, the fructose-fed Syrian golden hamster, was employed to investigate the efficacy and mechanisms of action of rosuvastatin, a HMG-CoA reductase inhibitor, in ameliorating metabolic dyslipidemia in insulin-resistant states. Fructose feeding for a 2-week period induced insulin resistance and a significant increase in hepatic secretion of VLDL. This was followed by a fructose-enriched diet with or without 10 mg/kg rosuvastatin for 14 days. Fructose feeding in the first 2 weeks caused a significant increase in plasma total cholesterol and triglyceride in both groups (n=6, p<0.001). However, there was a significant decline (30%, n=8, p<0.05) in plasma triglyceride levels following rosuvastatin feeding (10 mg/kg). A significant decrease (n=6, p<0.05) was also observed in VLDL-apoB production in hepatocytes isolated from drug-treated hamsters, together with an increased apoB degradation (n=6, p<0.05). Similar results were obtained in parallel cell culture experiments in which primary hepatocytes were first isolated from chow-fed hamsters, and then treated in vitro with 15 microM rosuvastatin for 18 h. Rosuvastatin at 5 microM caused a substantial reduction in synthesis of unesterified cholesterol and cholesterol ester (98 and 25%, n=9, p<0.01 or p<0.05) and secretion of newly synthesized unesterified cholesterol, cholesterol ester, and triglyceride (95, 42, and 60% reduction, respectively, n=9, p<0.01 or p<0.05). This concentration of rosuvastatin also caused a significant reduction (75% decrease, n=4, p<0.01) in the extracellular secretion of VLDL-apoB100, accompanied by a significant increase in the intracellular degradation of apoB100. There was a 12% reduction (not significant, p>0.05) in hepatic MTP and no changes in ER-60 (a chaperone involved in apoB degradation) protein levels. Taken together, these data suggest that the assembly and secretion of VLDL particles in hamster hepatocytes can be acutely inhibited by rosuvastatin in a process involving enhanced apoB degradation. This appears to lead to a significant amelioration of hepatic VLDL-apoB overproduction observed in the fructose-fed, insulin-resistant hamster model.
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PMID:Effect of rosuvastatin on hepatic production of apolipoprotein B-containing lipoproteins in an animal model of insulin resistance and metabolic dyslipidemia. 1600 78

Both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as well as peroxisome proliferator-activated receptor (PPAR)alpha activators (fibrates) proved to be effective in the primary and secondary prevention of cardiovascular diseases. The benefits of hypolipemic therapy in cardiovascular diseases cannot be explained only by the lipid-lowering potential of these agents. The aim of this study was to clarify the effect of hypolipemic agents on proinflammatory cytokine release from human monocytes in relationship with their action on plasma levels of sensitive systemic marker of low-grade vascular inflammation. Plasma lipid and high-sensitivity C-reactive protein (hsCRP) levels, and the release of tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta from monocytes were assessed at baseline and 30 and 90 days following randomization of IIa dyslipidemic patients into fluvastatin or simvastatin groups and randomization of type IIb dyslipidemic patients to the micronized form of either ciprofibrate or fenofibrate. Lipopolysaccharide-stimulated monocytes from dyslipidemic patients released significantly more TNFalpha (types IIa and IIb dyslipidemias) and interleukin-1beta (type IIa dyslipidemia) in comparison with monocytes in 59 age-, sex-, and weight-matched control subjects. Their baseline hsCRP levels were also higher. Both statins and fibrates reduced the release of TNFalpha and interleukin-1beta, and lowered plasma hsCRP levels. The effects of hypolipemic agents on cytokine release and plasma hsCRP were unrelated to their lipid-lowering action. Our results have demonstrated that type IIa and IIb dyslipidemic patients exhibit the abnormal pattern of TNFalpha and interleukin-1beta production by activated monocytes. Both HMG-CoA reductase inhibitors and PPARalpha activators normalize monocytic secretion of these cytokines, and this action may partially contribute to the systemic antiinflammatory effect of hypolipemic agents. The statin- and fibrate-induced suppression of proinflammatory cytokine release from monocytes seems to play a role in their beneficial effect on the incidence of cardiovascular events.
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PMID:Monocyte release of tumor necrosis factor-alpha and interleukin-1beta in primary type IIa and IIb dyslipidemic patients treated with statins or fibrates. 1611 45

HMG-CoA reductase inhibitors (statins) are effective lipid-altering drugs for the treatment of dyslipidemia in patients with type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, crossover design trial to determine the effects of simvastatin, 80 mg/day, on plasma lipid and lipoprotein levels and on the metabolism of apolipoprotein B (apoB) in VLDL, intermediate density lipoprotein (IDL), and LDL and of triglycerides (TGs) in VLDL. Simvastatin therapy decreased TG, cholesterol, and apoB significantly in VLDL, IDL, and LDL. These effects were associated with reduced production of LDL-apoB, mainly as a result of reduced secretion of apoB-lipoproteins directly into the LDL density range. Statin therapy also reduced hepatic production of VLDL-TG. There were no effects of simvastatin on the fractional catabolic rates of VLDL-apoB or -TG or LDL-apoB. The basis for decreased VLDL-TG secretion during simvastatin treatment is not clear, but recent studies suggest that statins may activate peroxisomal proliferator-activated receptor alpha (PPARalpha). Activation of PPARalpha could lead to increased hepatic oxidation of fatty acids and less synthesis of TG for VLDL assembly.
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PMID:Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia. 1616 40


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