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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For about a century there has been recognition that calcium and lipids bind to one another in the gut, each interfering with the other's absorption. Calcium also causes malabsorption of bile acids, which is likely to contribute further to malabsorption of fat. High dietary calcium intakes may also have stimulatory effects on lipolysis. These mechanisms provide a basis for hypothesising that calcium supplementation may impact on circulating lipid concentrations, and there is now a significant amount of observational and trial data indicating that this is the case. The largest randomised controlled trial of calcium effects on lipids was carried out in 223 healthy postmenopausal women, and found that low density lipoprotein-cholesterol (LDL-C) decreased 6.3% and high density lipoprotein-cholesterol (HDL-C) increased by 7.3% at 1-year. The resultant 16.4% increase in HDL-C/LDL-C ratio would be predicted to reduce cardiovascular event rates by 20-30%, which is consistent with the available observational data. There are no trial data addressing this question and it is possible that other lipid-lowering agents, such as hydroxymethylglutaryl coenzyme A reductase inhibitors, might impact on cardiac event rates by mechanisms other than by lowering cholesterol levels. Therefore, caution is appropriate in incorporating these findings into clinical practice, but the balance of evidence suggests that calcium is a cost-effective adjunct to the dietary management of hyperlipidaemia.
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PMID:Effects of calcium supplementation on circulating lipids: potential pharmacoeconomic implications. 1471 41

Accumulating evidence indicates that hypertriglyceridemia (HTG) is a risk factor for cardiovascular disease. This increased risk is probably substantially mediated through the metabolic interrelationships between serum triglyceride (TG) levels and other risk factors, such as the atherogenic lipid profile (low high density lipoprotein-cholesterol levels and elevated small dense low density lipoprotein levels), insulin resistance, a prothrombotic propensity and low grade systemic inflammation. TG-lowering strategy in patients with HTG encompasses dietary modification and pharmacological agents, such as fibric acid derivatives, fish-oil and hydroxymethylglutaryl coenzyme A reductase inhibitors, which have, besides their known effects on the atherogenic lipid profile, beneficial effects on other determinants of cardiovascular disease. However, in spite of data from trials investigating fibric acid derivative-induced reduction in coronary events in patients with distinct types of hyperlipidemia, no specific trials have been performed that investigated this risk reduction in patients with HTG, in whom other cardiovascular risk factors are clustered as well. Small-scale studies on determinants of cardiovascular disease in patients with HTG and post-hoc analyses of the Helsinki Heart, Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial and Bezafibrate Infarction Prevention trials in patients with high serum TG levels suggest a drug-induced reduction in cardiovascular events. However, a specific trial should be conducted to investigate the effects of lipid-lowering therapy on clinical end-points in patients with HTG of defined types.
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PMID:Hypertriglyceridemia: associated risks and effect of drug treatment. 1472 4

Since the rat is an atherosclerosis-resistant species, the study of atherosclerosis using rats is limited. The present study was undertaken to develop an atherosclerotic model in rats, to investigate the effect of nitric oxide (NO) inactivation and hyperlipidemia, and to evaluate the effect of pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitor, on NO inactivation and on hyperlipidemia-induced changes in the cardiovascular system. Four-month-old male spontaneously hypertensive hyperlipidemic rats (SHHR) and Sprague-Dawley (SD) rats were used to study 1) the effect of the period of treatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/L) on high fat diet (HFD)-treated SHHR and SD rats, and 2) the effect of pitavastatin (Pit, 0.3 mg/kg/day) on the changes in the aorta of L-NAME- and HFD-treated SHHR and SD rats. L-NAME administration for 1 month then HFD feeding for 2 months markedly increased the deposition of lipids and the thickness of the endothelium in SHHR. Continuous L-NAME treatment with HFD produced severe injury and stripped of endothelium in both strains. The plasma total cholesterol of L-NAME + HFD-treated and L-NAME + HFD + Pit-treated SHHR was significantly higher than that of control SHHR. Lipid deposition, however, was comparatively less in the aorta of L-NAME + HFD + Pit-treated SHHR. The concentration of cholesterol in the aorta of control SHHR was significantly lower than that in the aorta of L-NAME + HFD-treated SHHR, whereas that of L-NAME + HFD + Pit-treated SHHR was the same as that in control SHHR. These data indicated that Pit blocked lipid deposition in the aorta of L-NAME + HFD treated SHHR without changing plasma lipid profiles. In conclusion, NO inactivation and HFD induce lipid deposition in the endothelium, and the HMG-CoA reductase inhibitor blocks the deposition in SHHR.
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PMID:Anti-lipid deposition effect of HMG-CoA reductase inhibitor, pitavastatin, in a rat model of hypertension and hypercholesterolemia. 1496 17

The metabolic syndrome is associated with increased morbility and mortality for cardiovascular disease. This syndrome is determined not only by metabolic alterations such as hyperglycemia, and hyperlipidemia but also by a chronic proinflammatory state. Another culprit in the formation and progression of vascular disease is the so-called endothelial dysfunction which is linked to insulin resistance itself. The common denominator of the metabolic syndrome is insulin resistance. The most convincing evidence for the existence of a syndrome comes from the cluster analysis which outlines four main factors: the "metabolic factor", the "pressor factor", the "lipid factor", and the "obesity factor". It is clear that the presence of the metabolic syndrome appears to identify a substantial additional cardiovascular risk above 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 risk reduction has been observed despite the fact that high triglyceride and low HDL cholesterol levels, but not hypercholesterolemia, are the main features of the dyslipidemia observed in patients with this syndrome. Yet, despite a normal LDL cholesterol level, patients with this syndrome are at high risk for future cardiovascular events: for this reason treatment with statins is mandatory.
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PMID:[Diabetes and multimetabolic syndrome]. 1498 43

Alcoholics usually suffer from malnutrition and are especially deficient in micronutrients like vitamin C, selenium and Zn. In the present study, combined effects of selenium and ascorbic acid on alcohol-induced hyperlipidemia were studied in guinea pigs. Four groups of male guinea pigs were maintained for 45 days as follows: control (1 mg ascorbate (AA)/100 g body mass/day), ethanol (900 mg ethanol/100 g body mass + 1 mg AA/100 g body mass/day), selenium+ascorbic acid [(25 mg AA + 0.05 mg Se)/100 g body mass/day], ethanol+selenium+ascorbic acid [(25 mg AA + 0.05 mg Se + 900 mg ethanol)/100 g body mass/day]. Co-administration of selenium and ascorbic acid along with alcohol reduced the concentration of all lipids, as also evidenced from the decreased activities of hydroxymethylglutaryl-CoA reductase and enhanced activities of plasma lecithin cholesterol acyl transferase and lipoprotein lipase. Concentrations of bile acids were increased. We conclude that the supplementation of Se and ascorbic acid reduced alcohol induced hyperlipidemia, by decreased synthesis and increased catabolism.
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PMID:Combined effect of selenium and ascorbic acid on alcohol induced hyperlipidemia in male guinea pigs. 1505 Sep 22

Coronary artery disease in the transplanted heart, also known as cardiac allograft vasculopathy, is one of the major causes of mortality late after heart transplantation. There are multiple immune and nonimmune risk factors associated with this disease process, one of which is hyperlipidemia. Use of lipid-lowering agents, specifically 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) was initially reported to have outcomes benefit and possibly immunosuppressive effects in a single-center study of heart transplant recipients. Other subsequent studies have supported this beneficial effect. Hyperlipidemia is associated with immune activity, particularly with respect to oxidation-sensitive signaling pathways. By lowering lipids, statins can ameliorate this immune activity, but it has been a matter of contention as to whether statins have cholesterol-independent immune-modulating effects. In two recent papers, cholesterol-independent immune effects of statins have been reported, including repressed induction of major histocompatibility complex class II by interferon-gamma, and selective blocking of leukocyte function antigen 1, both of which reduce the activation of T lymphocytes. The clinical reports demonstrating outcomes benefits in heart transplant recipients and recent laboratory publications that report an immunomodulatory effect of statins provide a firm scientific rationale to support the routine use of statins in heart transplant patients.
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PMID:Statins and cardiac allograft vasculopathy after heart transplantation. 1586 21

Cardiovascular disease is the leading cause of death in the US and other industrialised societies. Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is the most efficacious lipid-lowering agent of the statin class. New guidelines and recent evidence-based studies confirm the benefit of intensive reduction of low-density lipoprotein cholesterol in terms of cardiovascular risk reduction. Both naturally occurring and synthetic statins have demonstrated significant lowering of low-density lipoprotein cholesterol, the primary target of cholesterol-lowering therapy. Rosuvastatin, specifically, is a synthetic statin shown to lower low-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, non-high-density lipoprotein cholesterol and triglycerides, in addition to increasing high-density lipoprotein cholesterol. Compared with other statins, there is a similar low risk of serious muscle damage (myopathy and rhabdomyolysis), and no consistent pattern of renal failure or renal injury, despite mild transient tubular proteinuria, as seen with all statins. Therefore, rosuvastatin offers an effective alternative in the clinical management of hyperlipidaemia, while awaiting the results of ongoing cardiovascular risk reduction trials.
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PMID:Rosuvastatin: a risk-benefit assessment for intensive lipid lowering. 1614 9

The metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular diseases and diabetes mellitus. There is a growing body of evidence to show that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, reduce cardiovascular-related morbidity and mortality in patients with or without coronary artery disease. Recent clinical observations argue for a simple strategy of considering routine statin therapy for patients with type 2 diabetes. Furthermore, statin therapy is also found to be effective in allowing LDL-cholesterol goal achievement in hypercholesterolemic high-risk patients with the metabolic syndrome. However, the effects of statins on the pathogenesis of the metabolic syndrome remain to be elucidated. Several types of statins are commercially available now. Among them, pravastatin is unique because it is the only statin that has been shown to have protective role against the development of diabetes in a large clinical trial. Moreover, a recent clinical study revealed that pravastatin treatment improved insulin sensitivity in 25 women with the metabolic syndrome with impaired glucose intolerance. These observations let us to speculate that pravastatin is a promising strategy for the treatment of hypercholesterolemic patients with the metabolic syndrome. It may improve the insulin sensitivity in these patients and subsequently prevent the development of type 2 diabetes. In this paper, we would like to propose the possible ways of testing our hypothesis as follows. (1) Does pravastatin treatment improve insulin resistance in patients of the metabolic syndrome or in insulin resistant hypertensive or obese patients? If the answers are yes, are these beneficial effects of pravastatin superior to those of other anti-hyperlipidemic statins with equihypolipidemic properties? (2) Does pravastatin treatment actually reduce the development of diabetes in these insulin resistant patients? At that time, does pravastatin treatment increase serum levels of adiponectin, a key adipokine with insulin-sensitizing property? How about the effects of pravastatin treatment on adipokines that could elicit insulin resistance such as tumor necrosis factor-alpha? These clinical studies will provide further information whether pravastatin treatment can improve insulin resistance and subsequently reduce the development of diabetes in insulin resistant patients with the metabolic syndrome.
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PMID:Protective role of pravastatin in the pathogenesis of the metabolic syndrome. 1617 51

Endothelial dysfunction contributes to mechanisms of atherogenesis and its clinical manifestations, including coronary heart disease. Cardiovascular risk factors have been linked directly to a loss of endothelial function, such as endothelium-dependent nitric oxide (NO) release, resulting in abnormal vasodilation in response to various stimuli. There is evidence that multiple risk factors, including hypertension and hyperlipidemia, lead to a synergistic effect on endothelial dysfunction, likely through oxidative stress mechanisms. Damage to the endothelium leads to reduced NO bioavailability and facilitates vessel wall permeability to low-density lipoprotein. Certain agents, including the antihypertensive drug amlodipine and the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) atorvastatin, are known to influence endothelial function and NO bioavailability directly; these properties may contribute to clinical benefits. Recent experimental evidence at the cellular level indicates that these agents stimulate NO release from human endothelial cells in a highly synergistic fashion. The clinical implications of these observations are discussed in this article in the context of cardiovascular risk factor management strategies.
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PMID:A rationale for combination therapy in risk factor management: a mechanistic perspective. 1635 9

The most important action of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is their ability to lower levels of low-density lipoprotein (LDL) cholesterol. Statins have proved highly effective in reducing the risk of cardiovascular events in both primary and secondary prevention studies. However, the magnitude of risk reduction associated with statins is greater than that predicted on the basis of LDL cholesterol lowering alone. A likely explanation for this effect is the anti-inflammatory action of statins. Following the observation that high-sensitivity C-reactive protein (hs-CRP) is a powerful predictor of cardiovascular events, investigators in the Cholesterol and Recurrent Events (CARE) and Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) trials demonstrated that the magnitude of risk reduction associated with statin therapy was higher among those with elevated hs-CRP levels. In addition, there is accumulating evidence that statins lower plasma levels of hs-CRP in a manner largely independent of LDL cholesterol lowering. In contrast, little benefit has been demonstrated for statin therapy in the absence of both hyperlipidemia and inflammation. Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a large multinational, long-term, double-blind, placebo-controlled, randomized clinical trial designed to assess directly whether statin therapy (rosuvastatin 20 mg/day) should be given to apparently healthy individuals with low LDL cholesterol levels but elevated hs-CRP levels--a critical issue for the prevention of cardiovascular disease. Support for the concept behind the JUPITER trial is also now available from several recent trials comparing different intensities of statin therapy on disease progression as well as clinical end points. These studies indicate that the hs-CRP level achieved after initiation of statin therapy may be as important as the LDL cholesterol level achieved. All of these data raise the possibility that hs-CRP could be used to target high-risk patients who may benefit from early statin use. Ongoing work will determine whether hs-CRP reduction, independent of LDL cholesterol reduction, results in a net clinical benefit.
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PMID:Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)--can C-reactive protein be used to target statin therapy in primary prevention? 1644 35


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