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 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heredity of cholesterol absorption and synthesis was studied in siblings of hypercholesterolemic probands with low and high serum cholestanol to cholesterol ratio (assumed to indicate low and high absorption of cholesterol, respectively). Cholesterol synthesis was assayed with sterol balance technique and measuring serum cholesterol precursor to cholesterol ratios (synthesis markers of cholesterol), and cholesterol absorption with measuring dietary cholesterol absorption percentage and serum plant sterol and cholestanol to cholesterol ratios (absorption markers of cholesterol). In the siblings of the low absorption families, cholesterol absorption percentage and ratios of absorption markers were significantly lower, and cholesterol and bile acid synthesis, cholesterol turnover, fecal steroids and ratios of synthesis markers significantly higher than in the siblings of the high absorption families. The ratios of absorption and synthesis markers were inversely interrelated, and they were correlated with cholesterol absorption and synthesis in the siblings. In addition, low absorption was associated with high body mass index, low HDL cholesterol, and serum sex hormone binding globulin levels, suggesting that low absorption was associated with metabolic syndrome. Intrafamily correlations were significant for serum synthesis markers, cholestanol, triglycerides, and blood glucose level. In conclusion, cholesterol absorption efficiency and synthesis are partly inherited phenomena, and they can be predicted by the ratios of non-cholesterol sterols to cholesterol in serum.
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PMID:Inheritance of cholesterol metabolism of probands with high or low cholesterol absorption. 1223 79

Coronary heart disease (CHD) is a common, costly, and undertreated disorder in the United States, and dyslipidemia is one of its most important modifiable risk factors. Recently, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) published updated guidelines for the treatment of lipid disorders, greatly expanding the number of patients eligible for therapy. In the new recommendations, several significant changes have been made in the identification and management of patients at risk for CHD. Although ATP III maintains that low-density lipoprotein (LDL) cholesterol should be the primary target of lipid-lowering therapy, it identifies non-high-density lipoprotein (HDL) cholesterol (total cholesterol minus HDL cholesterol) as a secondary target in patients with elevated triglycerides. Patients with > or = 2 CHD risk factors should now be assessed for 10-year absolute CHD risk based on the Framingham Point Scale to identify those who require more aggressive treatment. The guidelines also designate a new category, CHD risk equivalent, which recognizes that certain patients have the same high risk as those with established CHD. Diabetes is now identified as a CHD risk equivalent, as are other forms of atherosclerotic disease and multiple risk factors comprising a CHD 10-year risk of > 20%. New lipoprotein classifications are given, and increased emphasis is placed on the metabolic syndrome, a constellation of metabolic risk factors, as a marker for CHD risk. Since adherence poses a major challenge in the management of patients with or at risk for CHD, the new guidelines provide physicians with several strategies for increasing patient compliance. The new guidelines should help physicians better identify and manage patients at risk for CHD, help more patients reach their lipid goals, and thereby decrease cardiovascular morbidity and mortality.
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PMID:New therapeutic options in the National Cholesterol Education Program Adult Treatment Panel III. 1224 Jul 1

The Third Report of the National Cholesterol Education Program's Adult Treatment Panel (ATP III) has an extensive section on nonpharmacologic therapy for those with abnormal blood lipids. ATP III focused on the high-saturated fat atherogenic diet, obesity, and sedentary lifestyle and recommended a program of therapeutic lifestyle change (TLC). This review discusses several issues, including 1) why ATP III changed from the Step I and Step II diets to TLC; 2) the benefits of keeping trans fatty acid intake low and the addition of viscous fiber and plant stanol/sterol esters to reduce low-density lipoprotein cholesterol beyond that seen with the Step II diet; 3) the de-emphasis on total fat and a sharper focus on the kinds of fat ingested in the new guidelines; 4) the endorsement of regular physical activity and weight loss as important first steps in reversing the unwanted metabolic effects of the metabolic syndrome; and 5) the emphasis of health-promoting aspects of the diet that include, among other things, fish and omega-3 fatty acids. At all stages of TLC, ATP III encourages the referral to registered dietitians or other qualified nutritionists for medical nutrition therapy. TLC and the ATP III guidelines should provide guidance to practitioners who wish to get low-density lipoprotein cholesterol to goal (whether or not drugs are used), prevent or treat the metabolic syndrome, and improve the overall health of the patient.
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PMID:Therapeutic lifestyle change and Adult Treatment Panel III: evidence then and now. 1236 90

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.
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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.
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PMID:Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. 1241 79

The World Health Organization (WHO) and the National Cholesterol Education Program (NCEP) recently proposed definitions for the metabolic syndrome. Little is known of their validity, however. The authors assessed the sensitivity and specificity of the definitions of the metabolic syndrome for prevalent and incident diabetes mellitus in a Finnish population-based cohort of middle-aged men (n = 1,005) followed for 4 years since the late 1980s. Four definitions based on the WHO and NCEP recommendations were compared. All definitions identified persons at high risk for developing diabetes during the 4-year follow-up (odds ratios = 5.0-8.8). The WHO definition including waist-hip ratio > 0.90 or body mass index >or= 30 kg/m(2) was the most sensitive (0.83 and 0.67) and least specific (0.78 and 0.80) in detecting the 47 prevalent and 51 incident cases of diabetes. The NCEP definition in which adiposity was defined as waist girth > 102 cm detected only 61% of prevalent and 41% of incident diabetes, although it was the most specific (0.89 and 0.90). The WHO definition seems valid as judged by its relatively high sensitivity and specificity in predicting diabetes. The NCEP definition including waist > 102 cm also identifies persons at high risk for diabetes, but it is relatively insensitive in predicting diabetes.
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PMID:Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. 1244 65

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.
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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.
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PMID:Combination therapy for combined dyslipidemia. 1246 37

The National Cholesterol Education Program recognizes the importance of the metabolic syndrome and has published guidelines for its diagnosis. Weight loss, physical activity, and treatment of the individual risk factors constitute the main strategies for treatment. For now, the goals and methods of treating hypertension and dyslipidemia are the same in people with the metabolic syndrome as in the general population. Thiazolidinedione drugs increase insulin sensitivity, but their use in the metabolic syndrome is only speculative at present. We recommend they be used only as indicated to treat diabetes mellitus.
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PMID:A truly deadly quartet: obesity, hypertension, hypertriglyceridemia, and hyperinsulinemia. 1254 72

Coronary heart disease (CHD) remains the leading cause of death in the United States with more than 40% of all deaths each year directly attributed to the disease. Current evidence suggests that early identification and aggressive modification of risk factors offer the most promising approach to reducing the burden of CHD. Dyslipidemia has been identified as the primary risk factor leading to the development of CHD. It is estimated that nearly 65 million Americans require some form of lipid-modification therapy. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) set of guidelines released in May 2001 provides physicians with evidence-based recommendations on the classification, diagnosis, and treatment of lipid disorders. New features of the guidelines include a scoring system for calculating CHD risk, as well as the identification of CHD risk equivalents, lower treatment target goals, and an emphasis on conditions conferring a higher risk for CHD, such as the metabolic syndrome. The ATP III emphasis on risk assessment substantially increases the number of patients considered at risk for CHD and will expand the number eligible for lifestyle and drug interventions. This article highlights the new recommendations and reviews the impact of ATP III on osteopathic physicians.
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PMID:The national cholesterol education program adult treatment panel ill guidelines. 1257 22


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