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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 'metabolic syndrome' is a special clinical entity characterized by upper body segment obesity (android obesity), together with one or more of a constellation of metabolic disorders that includes glucose intolerance, which may amount to frank diabetes mellitus, hypertension, cardiovascular lesions, hyperuricemia, and dyslipidemias (hypercholesterolemia, hypertriglyceridemia and reduced serum HDL). Recently, lipoprotein (Lp) (a) proved to be a new member in this syndrome. Lp(a) has the distinctive feature of containing apolipoprotein (a), which is a glycoprotein linked to apo B100, and has a similarity to plasminogen; it is also structurally related to LDL. Lp(a) is a macromolecular complex which is genetically determined, and has been identified as an independent risk factor for premature coronary artery disease (CAD). It is elevated in diabetic and non-diabetic android obese subjects, and aggravates the atherogenic effect of diabetes mellitus. Lp(a) is poorly influenced either by dietary measures or by hypolipidemic drugs. Unfortunately, few pharmacologic agents, such as niacin, nicotinic acid, sex hormones (estrogen and testosterone), alcohol and neomycin, affect Lp(a).
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PMID:Lipoprotein (a) in android obesity and NIDDM: a new member in 'the metabolic syndrome'. 1066 39

Patients with type 2 diabetes (formerly known as non-insulin-resistant diabetes) have a significantly increased risk of developing cardiovascular disease. Once clinical cardiovascular disease develops, these patients have a poorer prognosis than normoglycemic patients. By inducing endothelial changes, hyperglycemia contributes directly to atherosclerosis. Type 2 diabetes is also associated with atherogenic dyslipidemias. This form of diabetes, or the precursor state of insulin resistance, commonly occurs as a metabolic syndrome (formerly known as syndrome X) consisting of hypertension, atherogenic dyslipidemia and a procoagulant state, in addition to the disorder of glucose metabolism. All cardiovascular risk factors except smoking are more prevalent in patients with type 2 diabetes. In addition to exercise, weight control, aspirin therapy and blood pressure control, therapy to modify lipid profiles is usually necessary. The choice of agent or combination of statin, bile acid sequestrant, fibric acid derivative and nicotinic acid depends on the lipid profile and characteristics of the individual patient.
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PMID:Attenuating cardiovascular risk factors in patients with type 2 diabetes. 1114 70

Compelling evidence from meta-analysis of a number of clinical studies on a large aggregate of patients has established an increased level of triglycerides as an independent risk factor for atherosclerotic heart disease. The finding of triglyceride-rich lipoproteins in human atheromata has provided substantial pathophysiologic evidence for a direct role in atherogenesis. Hypertriglyceridemia is commonly embedded in the context of a metabolic syndrome that includes central obesity, insulin resistance, low levels of HDL cholesterol, and often hypertension. Hypertriglyceridemia also appears to underlie the phenomenon of small dense LDL in most instances. Therapeutic interventions must be directed at underlying obesity, insulin resistance, and diabetes when present, as well as addressing metabolic determinants of dyslipidemia per se. Diet, exercise, weight loss, and avoidance of alcohol are the cornerstones of treatment. The choice of medication should be based on the lipoprotein phenotype. Niacin, fibric acid derivatives, and omega-3 fatty acids are most useful in treating severe hypertriglyceridemia. HMG-CoA reductase inhibitors are useful in some phenotypes with moderately increased triglyceride levels. Evidence from a number of clinical trials indicates that mitigation of risk of coronary heart disease, and possibly stroke, can be effected by reducing levels of plasma triglycerides.
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PMID:A risk factor for atherosclerosis: triglyceride-rich lipoproteins. 1179 72

Updated guidelines from the National Cholesterol Education Program give greater emphasis to lipoproteins other than low-density lipoprotein cholesterol (LDL) than previous guidelines. Although statins remain first-line therapy for most patients to lower LDL, combination therapy is the next logical step in achieving goals in patients with mixed dyslipidemia or elevated LDL despite statin therapy. As the prevalence of diabetes, metabolic syndrome, and atherogenic dyslipidemia rises, the importance of treating the total lipid profile becomes even more crucial. Niacin, fibrates, and bile acid sequestrants are effective in combination with statins in lowering LDL, triglycerides, and total cholesterol levels and increasing high-density lipoprotein cholesterol (HDL). Although combination therapies may increase the risk of myopathy, both fibrate-statin and niacin-statin combinations are considered safe. In addition, niacin-statin therapy reduces atherosclerotic progression and coronary events. New pharmacologic formulations exist that will further affect treatment: a single-tablet combination of lovastatin and extended-release niacin is available, as is ezetimibe, a cholesterol-absorption inhibitor. In all, both HDL and triglyceride levels correlate with cardiovascular risk and should be considered secondary targets of therapy. Combination therapy can be safe and effective and can be constructed to affect all lipoprotein parameters.
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PMID:Treating dyslipidemic patients with lipid-modifying and combination therapies. 1274 37

The efficacy and safety profiles of various forms of niacin for treating dyslipidemia are described. Niacin is well recognized for treating dyslipidemia in adults and has been shown to be effective in reducing coronary events. It has a broad range of effects on serum lipids and lipoproteins, including lowering total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides. Niacin is the most effective lipid-modifying drug for raising high-density-lipoprotein (HDL) cholesterol levels and has been shown to lower Lp(a) lipoprotein. Niacin reduces triglycerides and very-low-density-lipoprotein and LDL cholesterol synthesis, primarily by decreasing fatty acid mobilization from adipose tissue. Niacin appears to raise HDL cholesterol by reducing hepatic apolipoprotein A-l clearance and enhancing reverse cholesterol transport. Niacin is metabolized through a conjugation or nicotinamide pathway. Standard immediate-release niacin is metabolized primarily through the conjugation pathway, which results in a high frequency of flushing. Long-acting niacin is metabolized through the nicotinamide pathway, which results in less flushing but increases the risk of hepatotoxicity. Extended-release niacin has a more balanced metabolism and causes fewer of both types of adverse effects. Improved serum lipid levels during niacin therapy have been associated with clinical and angiographic evidence of reduced coronary artery disease, especially when combined with statins. Niacin is particularly useful for managing high triglyceride and low HDL cholesterol levels as well as the lipid abnormalities associated with metabolic syndrome, including those commonly encountered in patients with diabetes. Several niacin products are available with significant differences in their safety and efficacy profiles. Health care providers must consider the differences between agents when recommending niacin for dyslipidemia treatment.
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PMID:Niacin for dyslipidemia: considerations in product selection. 1278 70

The use of niacin, alone and in combination, for the treatment of dyslipidemia in patients with or at risk for coronary heart disease (CHD), is discussed. Cardiovascular risk is independently predicted not only by high levels of low-density lipoprotein cholesterol (LDL-C), but also low levels of high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides. Moreover, we now understand that LDL particle size and number are associated with differing levels of atherogenicity. Metabolic syndrome, increasingly being recognized as a marker for elevated cardiovascular risk, is associated with atherogenic dyslipidemia characterized by low HDL-C, high triglycerides, and small, dense LDL particles. Controlled clinical studies have shown that niacin therapy effectively increases HDL-C and lowers triglyceride and LDL-C levels while causing a shift toward larger, less atherogenic LDL particles. Niacin, alone or in combination, prevents progression and promotes regression of coronary atherogenic lesions and significantly reduces CHD-related morbidity and mortality. Statin monotherapy causes modest increases in HDL-C and decreases triglycerides, while more potently reducing LDL-C. Combinations of lipid-modifying agents may better address the full spectrum of lipoprotein abnormalities in some patients. Investigations have shown that combining statin therapy with niacin results in additive improvement in the major lipids and lipoproteins and improves clinical outcome. With recently broadened treatment recommendations, it seems likely that combination therapy will be increasingly deemed the appropriate choice for addressing a range of lipid abnormalities.
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PMID:Advances in the understanding and management of dyslipidemia: using niacin-based therapies. 1290 Oct 26

Plasma levels of high-density lipoprotein-cholesterol (HDL-C) are a powerful independent cardiovascular risk factor, bearing an inverse relationship with atherosclerotic cardiovascular disease (with risk rising sharply when levels are <1.04 mmol/L). Apart from its protective role in atherosclerosis, HDL-C increases fibrinolysis, is an antioxidant to low density lipoprotein-cholesterol (LDL-C), and decreases platelet aggregability. Up to a third of patients with atherosclerotic cardiovascular disease have 'desirable' plasma levels of total cholesterol but low HDL-C levels. Benefits of treating low plasma HDL-C levels were clearly demonstrated in the Veterans Affairs HDL Intervention Trial (VA-HIT) where gemfibrozil reduced nonfatal infarcts and coronary deaths by 22%. This was achieved by a 6% increase in plasma HDL-C levels, and a 24.5% decrease in plasma levels of triglycerides, without any significant decrease in LDL-C levels. Multivariate analyses revealed the rise in plasma HDL-C levels after treatment, but not decreases in plasma levels of triglycerides or LDL-C, predicted coronary artery disease events. The typical patient under consideration in this article is one with plasma levels of HDL-C <1 mmol/L, LDL-C <3.37 mmol/L [either receiving therapeutic lifestyle changes or or LDL-C-lowering therapy comprising a hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor or bile acid sequestrant] and fasting triglycerides <2.26 mmol/L. We propose this dyslipidemia be classified as Type VI phenotype following the Frederickson and Lees classification. High-risk patients (with >/=2 risk factors for atherosclerotic cardiovascular disease, or 10-year cardiovascular risk >20%), patients with established atherosclerotic cardiovascular disease, or type 2 diabetes mellitus, or metabolic syndrome should receive pharmacotherapy. Plasma HDL-C levels >1.16 mmol/L may be considered optimal and between 1 and 1.16 mmol/L as desirable. Fibric acid derivatives, nicotinic acid, HMG-CoA reductase inhibitors, estrogens, and ethanol (not recommended as therapy) increase plasma HDL-C levels. Nicotinic acid is the most potent agent and recent reports indicate that, in contrast to gemfibrozil, it selectively increases antiatherogenic HDL subfraction, lipoprotein (Lp) AI (without apolipoprotein AII), in patients with low plasma HDL-C levels. An extended-release formulation, administered once daily, has improved the tolerability of nicotinic acid. Recent evidence also indicates that nicotinic acid may effectively correct dyslipidemia in patients with diabetes mellitus without significantly compromising glycemic control. Fibric acid derivatives and estrogen raise plasma HDL-C levels by different mechanisms of action, and these agents may be used with nicotinic acid. Combination therapy (especially HMG-CoA reductase inhibitor and nicotinic acid) should be considered in patients with atherosclerotic cardiovascular disease and low plasma HDL-C levels.
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PMID:Optimal therapy of low levels of high density lipoprotein-cholesterol. 1472 46

Combined hyperlipidemia is increasing in frequency and is the most common lipid disorder associated with obesity, insulin resistance and diabetes mellitus. It is associated with other features of the metabolic syndrome including hypertension, hyperuricemia, hyperinsulinemia and highly atherogenic subfractions of lipoprotein remnant particles including small dense low density lipoprotein-cholesterol. This review examines the mechanisms by which combined hyperlipidemia arises and the various drugs including fibric acid derivatives, hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and nicotinic acid which can be used either as monotherapy or in combination to manage it and to improve prognosis from atherosclerotic disease in diabetes mellitus, insulin resistant states and primary combined hyperlipidemia. The therapeutic approach to combined hyperlipidemia involves determination of whether the cause is hepatocyte damage or metabolic derangements. Combined hyperlipidemia due to hepatocyte damage should be treated by attention to the primary cause. In the case of metabolic dysfunction because of imbalance in glucose and fat metabolism, therapy of diabetes mellitus and obesity should be optimised prior to commencement of lipid lowering drugs. Both fibric acid derivatives and HMG-CoA reductase inhibitors can be used in the treatment of combined hyperlipidemia with fibric acid derivatives having greater effects on triglycerides and HMG-CoA reductase inhibitors on LDL-C though both have effects on the other cardiovascular risk factors. There is some evidence of benefit with both interventions in mild combined hyperlipidemias and large scale trials are underway. Fibric acid derivatives and HMG-CoA reductase inhibitor therapy can be combined with care, provided that gemfibrozil is avoided, fibric acid derivatives are given in the mornings and shorter half -life HMG-CoA reductase inhibitors are used at night. Combined hyperlipidemia emergencies occur with predominant hypertriglyceridemia in pregnancy or as a cause of pancreatitis. Therapy in the former should aim to reduce chylomicron production by a low fat diet and intervention to suppress VLDL-C secretion using omega-3 fatty acids. In the latter case, fluid therapy alone and medium chain plasma triglyceride infusions usually reduce levels satisfactorily though apheresis may be required. Blood glucose levels also need aggressive management in these conditions. Combined hyperlipidemia is likely to become an increasing problem with the increase in the prevalence of obesity and diabetes mellitus and needs aggressive management to reduce cardiovascular risk.
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PMID:Drug treatment of combined hyperlipidemia. 1472 15

Therapy with niacin (nicotinic acid) is unique in that it improves all lipoprotein abnormalities. It significantly reduces low-density lipoprotein cholesterol, triglyceride, and lipoprotein(a) levels, while increasing high-density lipoprotein cholesterol levels. This makes niacin ideal for treating a wide variety of lipid disorders, including the metabolic syndrome, diabetes mellitus, isolated low high-density lipoprotein cholesterol, and hypertriglyceridemia. Niacin-induced changes in serum lipid levels produce significant improvements in both coronary artery disease and clinical outcomes. Niacin is currently available in 3 formulations (immediate release, extended release, and long acting), which differ significantly with respect to their safety and efficacy profiles. Immediate-release niacin is generally taken 3 times a day and is associated with adverse flushing, gastrointestinal symptoms, and elevations in blood glucose levels. Long-acting niacin can be taken once daily and is associated with significantly reduced flushing, but its metabolism increases the risk of hepatotoxic effects. Extended-release niacin, also given once daily, has an absorption rate intermediate between the other formulations and is associated with fewer flushing and gastrointestinal symptoms without increasing hepatotoxic risk.
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PMID:New perspectives on the use of niacin in the treatment of lipid disorders. 1507 39

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.
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PMID:Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. 1524 16


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