Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure, and glycemia in accordance with current standards of care, patients with dyslipidemia remain at high residual risk of vascular events. Atherogenic dyslipidemia, characterized by elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease (CVD), type 2 diabetes mellitus, or metabolic syndrome and contributes to both macrovascular and microvascular residual risk. However, atherogenic dyslipidemia is largely underdiagnosed and undertreated in clinical practice. The Residual Risk Reduction Initiative (R3i) was established to address this highly relevant clinical issue. The aims of this position paper are (1) to highlight evidence that atherogenic dyslipidemia is associated with residual macrovascular and microvascular risk in patients at high risk for CVD, despite current standards of care for dyslipidemia and diabetes; and (2) to recommend therapeutic intervention for reducing this residual vascular risk supported by evidence and expert consensus. Lifestyle modification with nutrition and exercise is an important, effective, and underutilized first step in reducing residual vascular risk. Therapeutic intervention aimed at achievement of all lipid targets is also often required. Combination lipid-modifying therapy, with the addition of niacin, a fibrate, or omega-3 fatty acids to statin therapy, increases the probability of achieving all lipid goals. Outcomes studies are in progress to evaluate whether these combination treatment strategies translate to a clinical benefit greater than that achieved with statins alone. The R3i highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual risk of CVD events and microvascular complications among patients with dyslipidemia receiving therapy for high levels of LDL cholesterol and for diabetes in accordance with current standards of care.
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PMID:The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia. 1906 18

We investigated lipid and lipoprotein abnormalities in SHRSP fatty rats as a new animal model of metabolic syndrome. We examined differentially expressed genes in the liver, one of the major tissues contributing to lipid metabolism. Using gel filtration high performance liquid chromatography, increased cholesterol concentrations of small particle size low-density lipoprotein (LDL) fractions were observed in SHRSP fatty rats, whereas the Zucker Fatty strain did not show a similar elevation of cholesterol content. Existence of apolipoprotein B in these fractions was confirmed by Western blotting. The small particle size of the LDL fractions was significantly decreased by a 4-week fenofibrate treatment. Microarray analysis identified seventeen genes that were significantly upregulated and ten that were significantly decreased in liver tissues of SHRSP fatty rats compared with levels in SHRSP rats. Stearoyl-coenzyme A desaturase 1, fatty acid synthase, ATP citrate lyase, and sterol regulatory element binding factor 1 genes were among the upregulated genes. These findings suggest that SHRSP fatty rats carry small dense LDL like particles which is a common lipid abnormality in the metabolic syndrome. Three of ten genes upregulated in liver tissues of SHRSP fatty rats play a role in this metabolic abnormality and are a therapeutic target of this metabolic syndrome.
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PMID:Atherogenic dyslipidemia and altered hepatic gene expression in SHRSP.Z-Leprfa/IzmDmcr rats. 1921 48

Although popular diets focus on weight loss and their favorable biochemical and physiological effects, fewer investigations have evaluated the biological impact of these diets during weight maintenance. To study this issue, three popular diets-Atkins, South Beach, and Ornish-were tested in a randomized and counterbalanced crossover study between January and December 2006. Participants completed each of the three 4-week isocaloric dietary intervention phases followed by a 4-week washout period. They were weighed weekly and caloric adjustments made if weight change exceeded 1 kg. At the completion of each dietary phase, 3-day food records were analyzed, fasting blood sampled, and brachial artery reactivity testing performed. Eighteen adults completed all three isocaloric dietary phases. During the South Beach and Ornish maintenance phase, there were significant reductions in low-density lipoprotein cholesterol (11.8%; P=0.01, 16.6%; P=0.0006, respectively) compared to prediet baseline. In addition, in contrast to the Atkins maintenance phase, significant reductions in low-density lipoprotein cholesterol and apolipoprotein B levels were observed after the South Beach (P=0.003, P=0.05; repeated measures analyses of variance) and Ornish maintenance phases (P=0.0004, P=0.006, repeated measures analyses of variance). Brachial artery testing revealed an inverse correlation between flow-mediated vasodilatation and intake of saturated fat (r=-0.33; P=0.016). These data suggest that during weight maintenance, less favorable biological effects are observed during a simulated, high-fat Atkins diet when compared to the South Beach and Ornish diet. The findings support additional study in subjects with visceral obesity and the metabolic syndrome, in whom an increased risk of coronary disease at baseline may be accentuated with chronic consumption of a diet that exhibits unfavorable effects on lipids and endothelial function.
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PMID:Comparative effects of three popular diets on lipids, endothelial function, and C-reactive protein during weight maintenance. 1969 29

Hepatic oxidative stress and lipid peroxidation are common features of several prevalent disease states, including alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), a common component of the metabolic syndrome. These conditions are characterized in part by excessive accumulation of lipids within hepatocytes, which can lead to autocatalytic degradation of cellular lipids giving rise to electrophilic end products of lipid peroxidation. The pathobiology of reactive lipid aldehydes remains poorly understood. We therefore sought to investigate the effects of 4-hydroxynonenal (4-HNE) and 4-oxononenal (4-ONE) on the transport and secretion of very low-density lipoprotein using HepG2 cells as a model hepatocyte system. Physiologically relevant concentrations of 4-HNE and 4-ONE rapidly disrupted cellular microtubules in a concentration-dependent manner. Interestingly, 4-ONE reduced apolipoprotein B-100 (ApoB) secretion while 4-HNE did not significantly impair secretion. Both 4-HNE and 4-ONE formed adducts with ApoB protein, but 4-HNE adducts were detectable as mono-adducts, while 4-ONE adducts were present as protein-protein cross-links. These results demonstrate that reactive aldehydes generated by lipid peroxidation can differ in their biological effects, and that these differences can be mechanistically explained by the structures of the protein adducts formed.
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PMID:Lipid aldehyde-mediated cross-linking of apolipoprotein B-100 inhibits secretion from HepG2 cells. 1939 38

We prospectively studied the effects of fast food-based hyperalimentation on insulin sensitivity and components of the metabolic syndrome and analyzed this with respect to sex. Twelve nonobese men and 6 nonobese women (26 +/- 6.6 years old), and an age-matched control group were recruited. Subjects in the intervention group aimed for 5% to 15% weight increase by doubling their regular caloric intake based on at least 2 fast food meals a day while also adopting a sedentary lifestyle for 4 weeks (<5000 steps a day). Weight of subjects in the intervention group increased from 67.6 +/- 9.1 to 74.0 +/- 11 kg (P < .001), with no sex difference with regard to this or with respect to changes of total abdominal fat volumes or waist circumferences. Fasting insulin (men: before, 3.8 +/- 1.7 microU/mL; after, 7.4 +/- 3.1 microU/mL; P = .004; women: before, 4.9 +/- 2.3 microU/mL; after, 5.9 +/- 2.8 microU/mL; P = .17), systolic blood pressure (men: before, 117 +/- 13 mm Hg; after, 127 +/- 9.1 mm Hg; P = .002; women: before, 102 +/- 5.1 mm Hg; after, 98 +/- 5.4 mm Hg; P = .39), serum low-density lipoprotein cholesterol, and apolipoprotein B increased only in the men of the intervention group. The sex differences in the metabolic responses to the intervention were linked to a considerable difference in the fat accumulation pattern; 41.4% +/- 9.2% of the increase of the fat volume in the abdominal region was accumulated intraabdominally in men and 22.7 +/- 6.5% in women (P < .0001). This study thus showed that women are protected, compared with men, against developing intraabdominal obesity when adopting a standardized obesity-provoking lifestyle. Our findings suggest that it is not different lifestyles and/or behaviors that underlie the fact that men have a higher cardiovascular risk at the same level of percentage of body fat than women.
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PMID:Men develop more intraabdominal obesity and signs of the metabolic syndrome after hyperalimentation than women. 1939 60

The hypertriglyceridemic waist phenotype, the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria, and the International Diabetes Federation (IDF) criteria have been proposed as screening tools to identify subjects with features of the metabolic syndrome and therefore at increased cardiometabolic risk. The aim of the present study was to compare the ability of these 3 clinical approaches to identify individuals at increased cardiometabolic risk as suggested by the presence of deteriorated markers such as hyperinsulinemia, elevated apolipoprotein B levels, small low-density lipoprotein particles, high C-reactive protein concentrations, and low adiponectin levels. For that purpose, physical and cardiometabolic characteristics of a sample of 272 white men recruited for various metabolic investigations were studied. The hypertriglyceridemic waist phenotype was defined as having both a high waist circumference (>or=90 cm) and increased fasting triglyceride levels (>or=2.0 mmol/L). Having at least 3 of the 5 NCEP-ATP III criteria or waist circumference of at least 94 cm plus any 2 of the 4 additional IDF criteria was also used to identify individuals at increased cardiometabolic risk. A large proportion of men with the hypertriglyceridemic waist phenotype also met the NCEP-ATP III (82.7%) or IDF (89.2%) criteria. Men with the hypertriglyceridemic waist phenotype were characterized by alterations in their lipoprotein-lipid profile that included small low-density lipoprotein particles, increased apolipoprotein B and insulin levels, as well as reduced adiponectin concentrations, which were similar to individuals meeting the NCEP-ATP III or the IDF criteria. Moreover, the Framingham risk score of men meeting any of the 3 screening tools criteria was higher and was similar across the 3 approaches (4.2, 3.8, and 3.7, respectively). These results suggest that hypertriglyceridemic waist may be as discriminant as the NCEP-ATP III or the IDF criteria and could be used as an initial screening approach to identify individuals with deteriorated cardiometabolic risk markers.
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PMID:The hypertriglyceridemic waist phenotype versus the National Cholesterol Education Program-Adult Treatment Panel III and International Diabetes Federation clinical criteria to identify high-risk men with an altered cardiometabolic risk profile. 1948 69

Patients with the metabolic syndrome are at an increased risk of cardiovascular disease and might require intensive lipid therapy. Many patients remain at the starting dose of lipid therapy and might not be titrated up to a higher dose. The present double-blind, randomized, 6-week study assessed the lipid-lowering efficacy of ezetimibe/simvastatin 10/20 mg versus atorvastatin 10 or 20 mg, and ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in 1,128 patients with hypercholesterolemia and the metabolic syndrome. The primary end point was the percentage of change from baseline in low-density lipoprotein (LDL) cholesterol. Additional end points included changes in other lipids, lipoprotein ratios, high-sensitivity C-reactive protein, and attainment of prespecified lipid levels. Significantly greater improvements in the levels of LDL cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, and lipid/lipoprotein ratios resulted with ezetimibe/simvastatin compared with atorvastatin at all specified dose comparisons (p <0.001). The attainment of prespecified LDL cholesterol and non-high-density lipoprotein cholesterol levels was also significantly greater with ezetimibe/simvastatin than with atorvastatin at all dose comparisons (p <0.05). High-density lipoprotein cholesterol increases were significantly greater with ezetimibe/simvastatin 10/20 mg than with atorvastatin 10 mg (p <0.05) and ezetimibe/simvastatin 10/40 mg than with atorvastatin 40 mg (p <0.01). The changes in triglycerides, very low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein were similar for both treatments. The incidence of liver, muscle, and gastrointestinal-, hepatitis- and allergic reaction/rash-related adverse events were low and generally similar to those in previous studies of ezetimibe/simvastatin and/or atorvastatin. In conclusion, ezetimibe/simvastatin was more likely to result in lipid treatment end points than atorvastatin and was generally well tolerated at the doses compared in our patients.
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PMID:Lipid-altering efficacy and safety of ezetimibe/simvastatin versus atorvastatin in patients with hypercholesterolemia and the metabolic syndrome (from the VYMET study). 2042 79

Epidemiological evidence supports the use of non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B-100 (apoB), and low-density lipoprotein particles as markers of atherogenic risk. Treatment guidelines also identify these as additional targets of lipid-modifying intervention in patients with elevated triglycerides (TG). Even when TG are only moderately elevated, many patients on statin monotherapy who have achieved targets for low-density lipoprotein cholesterol (LDL-C) fail to reach non-HDL-C treatment goals, and even fewer reach apoB goals. Combination lipid-modifying therapy is therefore indicated for comprehensive lipid management, particularly in patients with type 2 diabetes and metabolic syndrome in whom LDL-C levels are often considered 'optimal'. Of the available options, adding either a niacin, fibrate or omega-3 fatty acids provides greater opportunity to achieve non-HDL-C and apoB targets, given complementary profiles of lipid-modifying activity and supported by evidence from clinical studies. Improvement in lipid control and reduction in atherogenic risk could be anticipated to translate to benefits in clinical outcomes.
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PMID:Management of non-high-density lipoprotein abnormalities. 1954 70

Recent epidemiologic studies have revealed that hypertriglyceridemia is associated with atherosclerosis independent of other coronary risk factors. However, it is difficult to select patients at high risk for coronary artery disease using only serum triglyceride levels compared with low-density lipoprotein cholesterol levels since multiple factors are associated with elevating triglycerides. Atherosclerotic diseases with high triglyceride levels can be found in patients with familial combined hyperlipidemia, diabetes mellitus, and metabolic syndrome, in which remnant lipoproteins accumulate in the circulating blood. Recent researches have paid attention to remnant lipoproteins as atherogenic particles with the development of methods for measuring remnant cholesterol levels and apolipoprotein B-48 levels directly from human serum. Measurement of these parameters in addition to serum triglycerides may help to distinguish high-risk patients and enable us to prevent or suppress the progression of atherosclerotic diseases in those patients. However, questions remain to be answered to evaluate the significance of remnant lipoproteins. Here, we focus on three issues: the underlying problems in measuring remnant lipoprotein cholesterol, the assessment of postprandial hyperlipidemia as an atherogenic condition, and finally a review of our experimental and clinical findings about the mechanisms by which remnant lipoproteins induce atherosclerosis.
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PMID:Remnant lipoproteins as strong key particles to atherogenesis. 1955 22

Common polymorphism of the apolipoprotein A5 gene (APOA5, c.553G>T) related to metabolic syndrome components, insulin resistance, and carotid atherosclerosis remains unclear. We investigated the associations of the APOA5 c.553G>T gene with various metabolic syndrome components and carotid artery atherosclerosis among family members. A total of 661 participants who provided complete genotyping and carotid artery measures were included in this study. Participants with APOA5 c.553T carrier (GT and TT) were more likely to have higher levels of triglycerides and apolipoprotein B, as well as lower levels of high-density lipoprotein (HDL) cholesterol, than participants with the GG genotype. Individuals who carried T alleles had an increased risk of a high level of triglycerides (multivariate odds ratio [OR], 3.86; 95% confidence interval [CI], 1.98-7.55; P<0.0001) and low levels of HDL cholesterol (OR, 2.32; 95% CI, 1.40-3.86; P=0.0012) compared with those without T alleles. The age was an effect modifier for the association between APOA5 genotype and smoking, alcohol drinking, obesity, and lipid profiles, including total, HDL, and low-density lipoprotein (LDL) cholesterol; triglycerides; and apolipoproteins. In addition, the association between APOA5 genotype and hypertriglyceridemia was significant only in adult groups (OR, 3.53; 95% CI, 1.79-6.94), and the association between APOA5 genotype and low HDL cholesterol was stable in young adolescents (OR, 2.39; 95% CI, 1.19-4.78) and adults (OR, 2.20; 95% CI, 1.17-4.15). Our findings indicated that the APOA5 c.553G>T polymorphism is associated with high triglycerides and low HDL cholesterol but not with other metabolic syndrome components or carotid atherosclerosis in this ethnic Chinese population.
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PMID:Association between sequence variant of c.553 G > T in the apolipoprotein A5 gene and metabolic syndrome, insulin resistance, and carotid atherosclerosis. 1966 89


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