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

In order to characterize the metabolic syndrome it becomes necessary to establish a number of diagnostic criteria. Because of its impact on cardiovascular morbidity/mortality, considerable attention has been focussed on the dyslipidemia accompanying the metabolic syndrome. The aim of this review is to highlight the fundamental aspects of the pathophysiology, diagnosis, and the treatment of the metabolic syndrome dyslipidemia with recommendations to clinicians. The clinical expression of the metabolic syndrome dyslipidemia is characterized by hypertriglyceridemia and low levels of high-density lipoprotein-cholesterol (HDL-C). In addition, metabolic syndrome dyslipidemia is associated with high levels of apolipoprotein (apo) B-100-rich particles of a particularly atherogenic phenotype (small dense low-density lipoprotein-cholesterol [LDL-C]. High levels of triglyceride-rich particles (very low-density lipoprotein) are also evident both at baseline and in overload situations (postprandial hyperlipidemia). Overall, the 'quantitative' dyslipidemia characterized by hypertriglyceridemia and low levels of HDL-C and the 'qualitative' dyslipidemia characterized by high levels of apo B-100- and triglyceride-rich particles, together with insulin resistance, constitute an atherogenic triad in patients with the metabolic syndrome. The therapeutic management of the metabolic syndrome, regardless of the control of the bodyweight, BP, hyperglycemia or overt diabetes mellitus, aims at maintaining optimum plasma lipid levels. Therapeutic goals are similar to those for high-risk situations because of the coexistence of multiple risk factors. The primary goal in treatment should be achieving an LDL-C level of <100 mg/dL (or <70 mg/dL in cases with established ischemic heart disease or risk equivalents). A further goal is increasing the HDL-C level to >or=40 mg/dL in men or 50 mg/dL in women. A non-HDL-C goal of 130 mg/dL should also be aimed at in cases of hypertriglyceridemia. Lifestyle interventions, such as maintaining an adequate diet, and a physical activity program, constitute an essential part of management. Nevertheless, when pharmacologic therapy becomes necessary, fibrates and HMG-CoA reductase inhibitors (statins) are the most effective drugs in controlling the metabolic syndrome hyperlipidemia, and are thus the drugs of first choice. Fibrates are effective in lowering triglycerides and increasing HDL-C levels, the two most frequent abnormalities associated with the metabolic syndrome, and statins are effective in lowering LDL-C levels, even though hypercholesterolemia occurs less frequently. In addition, the combination of fibrates and statins is highly effective in controlling abnormalities of the lipid profile in patients with the metabolic syndrome.
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PMID:Management of dyslipidemia in the metabolic syndrome: recommendations of the Spanish HDL-Forum. 1735 65

High-density lipoprotein (HDL) is conventionally believed to possess many features that protect against atherosclerosis. However, these lipoproteins may be modified in certain individuals and/or circumstances to become pro-inflammatory. The ability of HDL to inhibit or paradoxically to enhance vascular inflammation, lipid oxidation, plaque growth, and thrombosis reflects changes in specific enzyme and protein components. The anti-inflammatory and pro-inflammatory functional properties of HDL can now be assessed using cell-based and cell-free assays. Acute or chronic systemic inflammation and the metabolic syndrome appear to render HDL pro-inflammatory. In contrast, statins and experimental agents such as apolipoprotein A-1 mimetics render HDL more anti-inflammatory. The 2 main classes of existing drugs for HDL modification are fibric acid derivatives, also known as "fibrates," and niacin- containing compounds. In several controlled and prospective intervention studies, patients with low HDL-C and additional risk factors benefited from treatment with fibrates or niacin. However, an increase in HDL-C did not lead to a decrease in cardiovascular events in all trials.
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PMID:HDL function as a target of lipid-modifying therapy. 1740 Dec 96

In a randomized, double-blind, crossover trial of 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week placebo wash-outs between treatments, the dose-dependent effect of rosuvastatin on apolipoprotein (apo) B-100 kinetics in metabolic syndrome subjects were studied. Compared with placebo, there was a significant dose-dependent decrease with rosuvastatin in plasma cholesterol, triglycerides, LDL cholesterol, apoB and apoC-III concentrations and in the apoB/apoA-I ratio, lathosterol:cholesterol ratio, HDL cholesterol concentration and campesterol:cholesterol ratio also increased significantly. Rosuvastatin significantly increased the fractional catabolic rates (FCR) of very-low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and LDL-apoB and decreased the corresponding pool sizes, with evidence of a dose-related effect. LDL apoB production rate (PR) fell significantly with rosuvastatin 40 mg/day with no change in VLDL and IDL-apoB PR. Changes in triglycerides were significantly correlated with changes in VLDL apoB FCR and apoC-III concentration, and changes in lathosterol:cholesterol ratio were correlated with changes in LDL apoB FCR, the associations being more significant with the higher dose of rosuvastatin. In the metabolic syndrome, rosuvastatin decreases the plasma concentration of apoB-containing lipoproteins by a dose-dependent mechanism that increases their rates of catabolism. Higher dose rosuvastatin may also decrease LDL apoB production. The findings provide a dose-related mechanism for the benefits of rosuvastatin on cardiovascular disease in the metabolic syndrome.
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PMID:Dose-dependent effect of rosuvastatin on apolipoprotein B-100 kinetics in the metabolic syndrome. 1741 70

Dietary plant sterols supplementation has been demonstrated in some studies to lower plasma total and LDL cholesterol in hypercholesterolemic subjects. The cholesterol lowering action of plant sterols remains to be investigated in subjects with the metabolic syndrome. In a randomized, crossover study of 2 x 4 week therapeutic periods with oral supplementation of plant sterols (2 g/day) or placebo, and two weeks placebo wash-out between therapeutic periods, we investigated the effects of dietary plant sterols on lipoprotein metabolism in nine men with the metabolic syndrome. Lipoprotein kinetics were measured using [D3]-leucine, gas chromatography-mass spectrometry and compartmental modeling. In men with the metabolic syndrome, dietary plant sterols did not have a significant effect on plasma concentrations of total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, apolipoprotein (apo) B, apoA-I or apoA-II. There were no significant changes to VLDL-, IDL-, LDL-apoB or apoA-I fractional catabolic rates and production rates between therapeutic phases. Relative to placebo, plasma campesterol, a marker of cholesterol absorption was significantly increased (2.53 +/- 0.35 vs. 4.64 +/- 0.59 mug/ml, p < 0.05), but there was no change in plasma lathosterol, a marker of endogenous cholesterol synthesis. In conclusion, supplementation with plant sterols did not appreciably influence plasma lipid or lipoprotein metabolism in men with the metabolic syndrome. Future studies with larger sample size, stratification to low and high cholesterol absorbers and cholesterol balance studies are warranted.
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PMID:Dietary plant sterols supplementation does not alter lipoprotein kinetics in men with the metabolic syndrome. 1804 21

The aim of the study was to investigate the role of serum C-reactive protein (CRP) level as a risk factor in predicting metabolic syndrome (MS), hypertension, atherogenic dyslipidemia, type 2 diabetes mellitus, and coronary heart disease. We prospectively evaluated 1270 men and 1320 women, aged 30 to 89 years, who had serum CRP determinations and a mean 4.3 years' follow-up. The CRP values were log-transformed for calculations. Metabolic syndrome was defined by the Adult Treatment Panel III criteria modified for male abdominal obesity. Prediction of outcome was performed by excluding from analysis the particular outcome variable existing at baseline examination. Smoking men had higher age-adjusted estimated CRP concentrations (P < .001), whereas smoking women had lower CRP (P = .027) than never smokers. Risk of developing an elevated (> or =2 mg/L) CRP was predicted significantly by baseline CRP in both sexes and by apolipoprotein (apo B), current smoking, and family income in men, when adjusted for 5 further variables. Baseline CRP levels predicted atherogenic dyslipidemia when adjusted for age, baseline dyslipidemia values, and apo B tertiles and predicted incident hypertension independent of age, waist circumference, and smoking status. After adjustment for sex, age, and the 5 MS components, CRP predicted newly developing MS, with a hazard ratio (HR) of 1.16 (95% confidence interval, 1.02-1.32). When adjusted for sex, age, baseline glucose, waist circumference, and apo B tertiles, diabetes was significantly predicted by CRP in women (HR, 1.31) alone. Sex- and age-adjusted CRP level identified also those that progressed to diabetes independent of a fasting glucose >100 mg/dL (HR, 1.39; 95% confidence interval, 1.21-1.59), although not in men. In the prediction of incident coronary heart disease, CRP contributed to 7 established risk factors including waist circumference with a significant 1.18-fold HR. C-reactive protein is both an independent significant predictor and a risk factor of cardiometabolic risk among Turkish adults, additive to MS components, whereby risk is modulated by sex, smoking habit, and apo B.
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PMID:Serum C-reactive protein is an independent risk factor predicting cardiometabolic risk. 1819 Oct 50

The role of inflammation in atherosclerotic disease is well established, but the role of autoantibodies against modified apolipoprotein (apo) B-100 remains unclear. The metabolic syndrome is associated with a proinflammatory state, a predominance of small dense low-density lipoprotein (LDL) particles, and an increased risk for atherosclerotic diseases. Previous studies have shown specific autoantibodies against modified apo B-100 (within LDL) to be related to human atherosclerotic disease. The objective of the present study was to investigate whether autoantibodies against modified apo B-100 are related to parameters of the metabolic syndrome, such as small dense LDL. Two hundred ninety-one healthy men were investigated for different metabolic, anthropometric, and inflammatory variables; LDL peak particle size; and distribution of LDL in 4 subfractions. Subjects were grouped according to LDL peak size > or = 23.5 nm (pattern A, n = 230) or <23.5 nm (pattern B, n = 61). Immunoglobulin (Ig) G and IgM antibodies against 2 aldehyde-modified peptide sequences, denoted as 45 and 210, within apo B-100 were quantified. Levels of IgG(45), but not the other autoantibodies, were significantly higher in pattern B individuals (with a predominance of small dense LDL particles) compared with pattern A (P < .01). Relationships for both IgG(45) and IgG(210) with parameters typically associated with the metabolic syndrome were found. Only IgG(45) tended to be higher in individuals with the metabolic syndrome compared with those without (P = .07). We conclude that subjects with a predominance of small dense LDL particles have elevated concentrations of IgG(45) in the circulation, which reflect an activated immune response to a specific epitope of modified apo B-100.
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PMID:Autoantibodies against modified apolipoprotein B-100 in relation to low-density lipoprotein size and the metabolic syndrome in otherwise healthy men. 1824 8

The aim of study was to investigate the role of serum total (TPL) and high-density lipoprotein phospholipids (HDL-pl) as a risk factor in coronary heart disease (CHD) and metabolic syndrome (MS). In a random sample, total and HDL-pl were measured in 1088 and 642 adults from Turkey, respectively, who have a high prevalence of MS; this was done with an enzymatic method that measures total phosphatidylcholine, sphingomyelin, and lysophosphatidylcholine. Serum TPL and HDL-pl levels were significantly higher in women (TPL, 2.8 mmol/L; HDL-pl, 1.21 mmol/L) than in men. Strong correlations existed between serum TPL levels and non-HDL cholesterol (HDL-C), triglycerides, apolipoprotein (apo) B, complement C3, and gamma-glutamyltransferase. Non-HDL-C, HDL triglyceride, and apo A-I were strongly correlated with HDL-pl. Linear regression analyses revealed HDL-C, apo B, triglycerides, diabetes, and female gender as independent significant determinants of TPL levels in adults. HDL-C and impaired glucose regulation were sole significant variables, together contributing one-quarter of serum HDL-pl. Individuals with MS or diabetes had significantly higher TPL concentrations. The gender- and age-adjusted odds ratio (OR) of TPL for MS was 1.73 (95% confidence interval, 1.35-2.21), whereas the multiadjusted OR of HDL-pl per 1 SD increment corresponded to a significantly reduced independent MS likelihood by 26% in women (and 18% in the entire group). The multiadjusted OR of HDL-pl for CHD in men and women combined was 0.32 (P = .057) corresponding to a reduced CHD likelihood by 32% per 1 SD increment of HDL-pl. Plasma TPL levels point to an adverse relationship to MS, whereas their role in CHD risk needs further investigation. HDL-pls, in contrast, mark substantial protection from MS as well as from CHD.
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PMID:Serum total and high-density lipoprotein phospholipid levels in a population-based study and relationship to risk of metabolic syndrome and coronary disease. 1831 19

Five lines of evidence justify comprehensive lipoprotein management over aggressive low-density lipoprotein (LDL) lowering alone in most cases of cardiovascular disease (CVD) prevention. First, lipoprotein lipid transport consists of a single, recycling system involving very-low-density lipoprotein, LDL, and high-density lipoprotein (HDL). Single lipid interventions affect all lipoprotein classes to varying degrees. These effects can be expanded by using different drug classes in combination. Second, observational studies support the unitary nature of lipoprotein risk. A family of curves describes increasing CVD risk from increasing LDL as other risk factors are present. Conversely, a family of curves describes increasing CVD risk from decreasing levels of HDL in mirror image to LDL. The LDL and HDL risks are additive. Third, clinical trials that raise HDL and lower triglyceride ameliorate CVD, as does lowering LDL. Lowering LDL prevents heart disease, but by only 22%-36% with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor therapy. Studies indicate that better CVD prevention is obtained when drugs for triglyceride and HDL reduction are combined with LDL reduction. Fourth, HDL and its apolipoprotein (apo), apo A-I, as well as apo A-I analogues, decrease atherosclerosis. Each modality decreases atherosclerosis in animal models, and apo A-I Milano acutely decreases human coronary luminal stenosis. Apo A-I analogues have similar promise. Fifth, combined hyperlipidemia is the most common lipid disorder, has the strongest risk for CVD, and combines elevated LDL, hypertriglyceridemia, and low HDL. This condition requires the comprehensive treatment approach described above. In conclusion, 5 lines of evidence justify comprehensive diet and drug treatment for combined hyperlipidemia and, at lesser LDL elevations, the atherogenic dyslipidemias of obesity, diabetes mellitus, and the metabolic syndrome.
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PMID:Comprehensive lipid management versus aggressive low-density lipoprotein lowering to reduce cardiovascular risk. 1837 42

Dyslipoproteinaemia is a cardinal feature of the metabolic syndrome that accelerates atherosclerosis. It is usually characterised by high plasma concentrations of triglyceride-rich and apolipoprotein (apo) B-containing lipoproteins, with depressed concentrations of high-density lipoprotein (HDL). Dysregulation of lipoprotein metabolism in these subjects may be due to a combination of overproduction of very-low-density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles, and increased catabolism of HDL apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance that increases the flux of fatty acids from adipose tissue to the liver, the accumulation of fat in the liver, the increased hepatic secretion of VLDL-triglycerides and the remodelling of both low-density lipoprotein (LDL) and HDL particles in the circulation; perturbations in lipolytic enzymes and lipid transfer proteins contribute to the dyslipidaemia. Our in vivo understanding of the kinetic defects in lipoprotein metabolism in the metabolic syndrome has been chiefly achieved by ongoing developments in the use of stable isotope tracers and mathematical modelling. Knowledge of the pathophysiology of lipoprotein metabolism in the metabolic syndrome is well complemented by extensive cell biological data. Nutritional modifications and increased physical exercise may favourably alter lipoprotein transport in the metabolic syndrome by collectively decreasing the hepatic secretion of VLDL-apoB and the catabolism of HDL apoA-I, as well as by increasing the clearance of LDL-apoB. Pharmacological treatments, such as statins, fibrates or fish oils, can also correct the dyslipidaemia by several mechanisms of action including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. The complementary mechanisms of action of lifestyle and drug therapies support the use of combination regimens to treat dyslipidaemia in the metabolic syndrome.
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PMID:Lipoprotein kinetics in the metabolic syndrome: pathophysiological and therapeutic lessons from stable isotope studies. 1851 4

Remnant lipoprotein can be measured by immunoseparation assay and polyacrylamide gel disc electrophoresis; however, these methods have some problems, such as a lack of specificity and being technically complicated. Recently, a new method, the remnant lipoprotein cholesterol homogeneous assay(RemL-C), has been established. In this study, we evaluated the basal performance of RemL-C assay. One hundred and fifty patients with diabetes mellitus were enrolled in this study. RemL-C level was higher in the midband (+) group than in the midband (-) group (p<0.01), and a strong correlation was observed between RemL-C level and remnant lipoprotein level measured by conventional method (r=0.89, p<0.01). RemL-C level correlated positively with triglyceride(TG) (r=0.94, p<0.01) and total cholesterol(TC) (r=0.39, p<0.01), negatively with high density lipoprotein(HDL-C) (r=-0.35, p<0.01) and positively with apolipoprotein (apo) CII, and apoE (apoCII: r=0.59, p<0.01, apoE: r=0.71, p<0.01). In particular, RemL-C level correlated strongly with TG and apoE. RemL-C level was significantly higher in patients with combined hyperlipidemia compared to patients with other hyperlipidemias (p<0.01). When the serum of a patient with combined hyperlipidemia was separated by sepharose 4B gel filtration, the fraction showing peak RemL-C level was observed between the fraction corresponding to VLDL and the fraction corresponding to LDL. Furthermore, the peak of RemL-C corresponded to the peak of apoE. Moreover RemL-C level correlated negatively with preheparin serum lipoprotein lipase mass that is a marker of metabolic syndrome (r=-0.30, p<0.01). These results suggest that the measurement of remnant lipoprotein by RemL-C assay reflects the quantity of intermediate-density lipoprotein. Since RemL-C measurement can be run on an automated clinical analyzer permitting quick and high throughput measurement, RemL-C levels may be useful in the screening of hyperlipidemia.
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PMID:[Remnant lipoprotein cholesterol level measured by homogeneous assay reflects the quantity of intermediate-density lipoprotein]. 1854 84


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