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

In 2001 the National Cholesterol Education Program (NCEP) released its Adult Treatment Panel (ATP) III report. This was an evidence-based report that upgraded cholesterol management guidelines. The update was made possible by a series of large, cholesterol-lowering clinical trials. These trials demonstrated strongly the efficacy and safety of cholesterol reduction in both primary and secondary prevention of coronary heart disease (CHD). The major recommendations of the report were several. Low-density lipoprotein (LDL) cholesterol continued to be identified as the major target of cholesterol-lowering therapy. However, more emphasis was given to HDL cholesterol and triglycerides as important targets for management. The concept of CHD risk equivalents was introduced. A CHD risk equivalent represents an absolute risk for future CHD events equal to that in persons with established CHD. Diabetes was identified as a CHD risk equivalent, requiring more intensive LDL-lowering therapy. Finally, the report placed more emphasis on the metabolic syndrome as a major, multiplex risk factor requiring increased clinical attention.
Am J Cardiol 2002 Oct 17
PMID:Approach to lipoprotein management in 2001 National Cholesterol Guidelines. 1241 77

Traditional risk factors for coronary artery disease (CAD) predict about 50% of the risk of developing CAD. The Adult Treatment Panel (ATP) III has defined emerging risk factors for CAD, including small, dense low-density lipoprotein (LDL). Small, dense LDL is often accompanied by increased triglycerides (TGs) and low high-density lipoprotein (HDL). An increased number of small, dense LDL particles is often missed when the LDL cholesterol level is normal or borderline elevated. Small, dense LDL particles are present in families with premature CAD and hyperapobetalipoproteinemia, familial combined hyperlipidemia, LDL subclass pattern B, familial dyslipidemic hypertension, and syndrome X. The metabolic syndrome, as defined by ATP III, incorporates a number of the components of these syndromes, including insulin resistance and intra-abdominal fat. Subclinical inflammation and elevated procoagulants also appear to be part of this atherogenic syndrome. Overproduction of very low-density lipoproteins (VLDLs) by the liver and increased secretion of large, apolipoprotein (apo) B-100-containing VLDL is the primary metabolic characteristic of most of these patients. The TG in VLDL is hydrolyzed by lipoprotein lipase (LPL) which produces intermediate-density lipoprotein. The TG in intermediate-density lipoprotein is hydrolyzed further, resulting in the generation of LDL. The cholesterol esters in LDL are exchanged for TG in VLDL by the cholesterol ester tranfer proteins, followed by hydrolysis of TG in LDL by hepatic lipase which produces small, dense LDL. Cholesterol ester transfer protein mediates a similar lipid exchange between VLDL and HDL, producing a cholesterol ester-poor HDL. In adipocytes, reduced fatty acid trapping and retention by adipose tissue may result from a primary defect in the incorporation of free fatty acids into TGs. Alternatively, insulin resistance may promote reduced retention of free fatty acids by adipocytes. Both these abnormalities lead to increased levels of free fatty acids in plasma, increased flux of free fatty acids back to the liver, enhanced production of TGs, decreased proteolysis of apo B-100, and increased VLDL production. Decreased removal of postprandial TGs often accompanies these metabolic abnormalities. Genes regulating the expression of the major players in this metabolic cascade, such as LPL, cholesterol ester transfer protein, and hepatic lipase, can modulate the expression of small, dense LDL but these are not the major defects. New candidates for major gene effects have been identified on chromosome 1. Regardless of their fundamental causes, small, dense LDL (compared with normal LDL) particles have a prolonged residence time in plasma, are more susceptible to oxidation because of decreased interaction with the LDL receptor, and enter the arterial wall more easily, where they are retained more readily. Small, dense LDL promotes endothelial dysfunction and enhanced production of procoagulants by endothelial cells. Both in animal models of atherosclerosis and in most human epidemiologic studies and clinical trials, small, dense LDL (particularly when present in increased numbers) appears more atherogenic than normal LDL. Treatment of patients with small, dense LDL particles (particularly when accompanied by low HDL and hypertriglyceridemia) often requires the use of combined lipid-altering drugs to decrease the number of particles and to convert them to larger, more buoyant LDL. The next critical step in further reduction of CAD will be the correct diagnosis and treatment of patients with small, dense LDL and the dyslipidemia that accompanies it.
Am J Cardiol 2002 Oct 17
PMID:Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. 1241 79

The seminal studies of Brown and Goldstein (Science 1986;232:34-47) coupled with the findings of the Framingham study revolutionized our understanding of the metabolic basis for vascular disease. These studies led to the widespread use of the coronary risk lipid profile, which uses the total cholesterol/high-density lipoprotein (HDL) ratio (or low-density lipoprotein [LDL]/HDL ratio) in predicting risk for vascular disease and as a tool for therapeutic management of patients at risk for vascular disease. However, although these methods are predictive of coronary artery disease (CAD) in general, it is also well known that the extent of occlusive disease and CAD varies greatly between individuals with similar cholesterol and HDL lipid profiles. For this reason, the National Cholesterol Education Program Expert Panel revised these guidelines and now recommends monitoring LDL and HDL cholesterol in the context of coronary heart disease risk factors and "risk equivalents." In addition, more recent findings indicate that specific alterations in individual lipoprotein subclasses may account for the variations in CAD in subjects with similar lipid profiles. For example, a preponderance of small, dense LDL particles correlates with a marked increase in risk for myocardial infarction independent of LDL levels. In particular, the association of small, dense LDL with elevated triglycerides (large, less dense VLDL) and reduced HDL has been defined as the atherogenic lipoprotein profile, and the key metabolic defect driving this profile may be elevated levels of triglycerides, specifically large, less dense VLDL. In an attempt to explain the physiologic basis for lipoprotein variations, this review describes the basic metabolic scheme underlying the traditional view of lipoprotein metabolism and physiology. It then examines the identity and role of the various lipoprotein subfractions in an attempt to distill a working model of how lipoprotein abnormalities might account for vascular disease in general and the metabolic syndrome in particular.
J Nucl Cardiol
PMID:The physiology of lipoproteins. 1246 89

Patients with combined dyslipidemia are at high risk for coronary artery disease and often require combination drug therapy to achieve lipid levels recommended by the US National Cholesterol Education Program's third Adult Treatment Panel (ATP III). In addition to recommendations for low-density lipoprotein (LDL) cholesterol and triglyceride levels, ATP III established non-high-density lipoprotein (HDL) cholesterol goals for individuals with triglycerides >or=2.26 mmol/L (>or=200 mg/dL). It also introduced certain criteria for the diagnosis of the metabolic syndrome, a clustering of risk factors (abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated blood pressure, impaired fasting glucose) that increases cardiovascular risk and is common in patients with combined dyslipidemia. Statin monotherapy has been shown to benefit these patients, and additional benefit may be obtained by combination therapy that provides greater reductions in both LDL cholesterol and triglycerides as well as greater increases in HDL cholesterol. However, combining a statin with either niacin or a fibrate may increase the risk for myopathy and therefore requires careful monitoring and evaluation of the risk-benefit ratio for each patient. Moreover, combination therapy may be associated with increased drug costs and decreased patient compliance. Recently developed agents that may improve the effectiveness of combination therapy include ezetimibe-a cholesterol absorption inhibitor-and a formulation that combines extended-release niacin and lovastatin in a single pill. Clinical trials are needed to determine the optimal treatment in patients with combined dyslipidemia.
Am J Cardiol 2002 Nov 20
PMID:Combination therapy for combined dyslipidemia. 1246 37

The cardiovascular metabolic syndrome is a family of risk factors that predispose patients to develop diabetes and cardiovascular disease. Indeed, macrovascular, not microvascular, disease is the leading cause of death in these patients. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) exert both direct and indirect (cholesterol-lowering) effects on the vasculature. Clinical trials have shown that these agents reduce cardiovascular disease and cerebrovascular disease in persons with diabetes. However, their beneficial effects on diabetic dyslipidemia do not account for all of the observed risk reduction. Positive effects on nitric oxide metabolism, inflammation, coagulability, and adhesion of cells to the vascular endothelium likely contribute to the mechanism of action of these agents. These pleiotropic effects of statins on the vasculature will be discussed in this review.
Am J Cardiol 2003 Feb 20
PMID:Effects of statins on the vasculature: Implications for aggressive lipid management in the cardiovascular metabolic syndrome. 1261 94

The constellation of risk factors known as the metabolic syndrome increases the risk of coronary artery disease at any low-density lipoprotein (LDL) cholesterol level. We performed an exploratory analysis of data from 5 trials to study the effects of rosuvastatin 10 mg on lipid levels and ratios in hypercholesterolemic patients (LDL cholesterol > or =160 mg/dL and <250 mg/dL) who met a modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definition of the metabolic syndrome. Of 580 patients completing 12 weeks of treatment with rosuvastatin 10 mg, 194 (33%) met the definition of the metabolic syndrome by exhibiting > or =3 of the following: body mass index >30; triglycerides > or =150 mg/dL; high-density lipoprotein (HDL) cholesterol <40 mg/dL in men and <50 mg/dL in women; blood pressure > or =130/> or =85 mm Hg or receiving current medication for hypertension; and fasting blood glucose > or =110 mg/dL. Patients with the metabolic syndrome had higher triglyceride, non-HDL cholesterol, apolipoprotein B, and lipid ratios, and lower HDL cholesterol and apolipoprotein A-I levels, at baseline compared with patients without the metabolic syndrome. In patients with the metabolic syndrome, rosuvastatin 10 mg improved LDL cholesterol (-47%), non-HDL cholesterol (-43%), non-HDL cholesterol/HDL cholesterol ratio (-47%), apolipoprotein B (-37%), apolipoprotein B/apolipoprotein A-I ratio (-40%), triglycerides (-23%), apolipoprotein A-I (+7%), and HDL cholesterol (+10%)-in a manner similar to that in hypercholesterolemic patients who did not meet these criteria. Among patients who met the metabolic syndrome criteria and who had triglycerides > or =200 mg/dL, 64% met their ATP III non-HDL goals.
Am J Cardiol 2003 Mar 06
PMID:Efficacy of rosuvastatin 10 mg in patients with the metabolic syndrome. 1264 42

Hyperlipidemia is commonly observed in patients with type 2 diabetes and is also characteristic of the metabolic syndrome. We discuss the lipoprotein abnormalities in type 2 diabetes and the relation of triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to insulin resistance and diabetes. We also present a case study of a diabetic woman with hyperlipidemia and coronary artery disease.
Am J Cardiol 2003 Apr 03
PMID:Management of patients with diabetic hyperlipidemia. 1267

The metabolic syndrome, or insulin resistance syndrome, is associated with increased risk for cardiovascular disease and related mortality and has an estimated age-adjusted US prevalence of 23.7%. Dyslipidemia in the syndrome is characterized by hypertriglyceridemia, low high-density lipoprotein cholesterol, and small, dense low-density lipoprotein (LDL) particles in the context of normal/slightly elevated LDL cholesterol. Outcomes in treatment studies in or including diabetic patients suggest that a variety of therapies may be of benefit in reducing cardiovascular risk in patients with the metabolic syndrome, including physiologic therapies and pharmacologic treatments, such as aspirin, antihypertensive therapy, anti-ischemic therapy, and lipid-modifying therapies. The recently updated National Cholesterol Education Program Adult Treatment Panel III guidelines identify the metabolic syndrome as a secondary target of lipid-lowering therapy after LDL cholesterol reduction and recommend use of weight reduction and increased physical activity to address underlying risk factors as well as therapies to address specific lipid and nonlipid risk factors.
Am J Cardiol 2003 Apr 03
PMID:Treatment for patients with the metabolic syndrome. 1267 1

The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines for lipid-lowering therapy to reduce coronary heart disease (CHD) risk contain a number of features that distinguish them from the previous ATP guidelines. These new features include modifications in lipid/lipoprotein levels considered optimal, abnormal, or reflective of risk; increased focus on primary prevention through use of Framingham risk scoring to define risk in persons with multiple lipid/nonlipid risk factors; and increased focus on the association of the metabolic syndrome with CHD risk. The introduction of the category of CHD risk equivalents-including persons with atherosclerotic disease, diabetes, or 10-year CHD risk > 20% based on Framingham scoring-results in an increase over previous guidelines in the proportion of patients categorized as being at high risk and therefore eligible for more intensive low-density lipoprotein cholesterol (LDL-C)-lowering therapy. Use of the new secondary therapeutic target of non-high-density lipoprotein cholesterol should improve management of lipid risk factors in patients who have elevated triglyceride levels after LDL-C goals have been met. These new features of the NCEP ATP III guidelines should improve identification and treatment of patients with dyslipidemias associated with CHD risk.
Clin Cardiol 2003 Apr
PMID:New features of the National Cholesterol Education Program Adult Treatment Panel III lipid-lowering guidelines. 1270 35

The objective of the present study was to examine concordance/discordance among 4 atherogenic indexes of cardiovascular risk: plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, and apolipoprotein B-100 (apoB). Analyses were conducted in a cohort of 2,103 men without coronary artery disease (CAD) at the onset of the Quebec Cardiovascular Study. Although there were strong and highly significant correlations among the 4 risk indexes (0.78 < r < 0.97), only 50% of all subjects had concordant apoB and LDL cholesterol levels (i.e., values that fell into the same quintile of the population distribution). Moreover, concordance/discordance was not the same throughout the range of both variables; it was greater at the extremes of their respective distributions (65%), but significantly less in the midpoints (<40%). ApoB appeared to be more concordant with non-HDL cholesterol than with LDL cholesterol, although >1/3 of all subjects had discordant levels. Kappa analysis confirmed that there was only fair agreement between apoB and total or LDL cholesterol (0.38 and 0.36, respectively) and only moderate agreement between non-HDL cholesterol and apoB (0.47). Finally, a significant proportion of subjects (528 of 2,103) who had disproportionately higher apoB levels than would have been predicted based on their LDL cholesterol concentrations was more obese and manifested several features of the metabolic syndrome. They also had a significantly increased cardiovascular risk. In summary, plasma apoB and the various cholesterol indexes are complementary rather than competitive indexes of atherosclerotic risk and provide further evidence as to why measurement of apoB should be part of a standard lipoprotein assessment of CAD risk.
Am J Cardiol 2003 May 15
PMID:Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk. 1274 98


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