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

Stroke is a leading cause of disability and death in women, despite progress in its prevention and treatment. As with coronary artery disease, the incidence of stroke rises after the menopause, in parallel with metabolic changes that add up to create an unfavourable risk factor profile for cardiovascular disease. The menopause metabolic syndrome, which includes weight gain and changes in lipids, insulin resistance, endothelial dysfunction, increased levels of homocysteine, lipoprotein (a) and several coagulation factors, may in part be attributable to estrogen deficiency, and may be reversible with hormone replacement therapy (HRT). As for blood pressure, a major detrimental risk factor for stroke, it is probably not affected by either the menopause per se or by HRT. Abundant experimental data exist indicating that estrogens have both anti-atherosclerotic and neuroprotective effects. The width or thickness of the carotid wall is a good indicator of carotid atherosclerosis; it increases after the menopause transition, and decreases with HRT. Estrogens may enhance cerebral blood flow and reduce vascular resistance. In animal models of stroke, estrogen induced anti-ischaemic effects. Several large-scale epidemiological studies have verified the concept of primary protection of stroke by HRT, though others have failed to do so. In light of these contradictory data, several recent reports were highly significant (Nurses' Health Study, HERS Study, Cancer Prevention II Trial, WEST Trial). Despite the known neural and vascular benefits of estrogen, it is uncertain whether HRT is associated with stroke protection. At present, prevention of stroke should involve proven risk reduction strategies.
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PMID:Menopause and ischaemic stroke: basic, clinical and epidemiological considerations. The role of hormone replacement. 1209 31

Factor analysis, a multivariate correlation technique, has been used to provide insight into the underlying structure of metabolic syndrome, which is characterized by physiological complexity and strong statistical intercorrelation among its key variables. The majority of previous factor analyses, however, have used only surrogate measures of insulin sensitivity. In addition, few have included members of multiple ethnic groups, and only one has presented results separately for subjects with impaired glucose tolerance. The objective of this study was to investigate, using factor analysis, the clustering of physiologic variables using data from 1,087 nondiabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). This study includes information on the directly measured insulin sensitivity index (S(I)) from intravenous glucose tolerance testing among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years at various stages of glucose tolerance. Principal factor analysis identified two factors that explained 28 and 9% of the variance in the dataset, respectively. These factors were interpreted as 1) a " metabolic" factor, with positive loadings of BMI, waist, fasting and 2-h glucose, and triglyceride and inverse loadings of log(S(I)+1) and HDL; and 2) a "blood pressure" factor, with positive loadings of systolic and diastolic blood pressure. The results were unchanged when surrogate measures of insulin resistance were used in place of log(S(I)+1). In addition, the results were similar within strata of sex, glucose tolerance status, and ethnicity. In conclusion, factor analysis identified two underlying factors among a group of metabolic syndrome variables in this dataset. Analyses using surrogate measures of insulin resistance suggested that these variables provide adequate information to explore the underlying intercorrelational structure of metabolic syndrome. Additional clarification of the physiologic characteristics of metabolic syndrome is required as individuals with this condition are increasingly being considered candidates for behavioral and pharmacologic intervention.
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PMID:Factor analysis of metabolic syndrome using directly measured insulin sensitivity: The Insulin Resistance Atherosclerosis Study. 1214 82

Micronised fenofibrate is a synthetic phenoxy-isobutyric acid derivative (fibric acid derivative) indicated for the treatment of dyslipidaemia. Recently, a new tablet formulation of micronised fenofibrate has become available with greater bioavailability than the older capsule formulation. The micronised fenofibrate 160mg tablet is bioequivalent to the 200mg capsule. The lipid-modifying profile of micronised fenofibrate 160mg (tablet) or 200mg (capsule) once daily is characterised by a decrease in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, a marked reduction in plasma triglyceride (TG) levels and an increase in high-density lipoprotein cholesterol (HDL-C) levels. Micronised fenofibrate 200mg (capsule) once daily produced greater improvements in TG and, generally, in HDL-C levels than the hydroxymethylglutaryl coenzyme A reductase inhibitors simvastatin 10 or 20 mg/day, pravastatin 20 mg/day or atorvastatin 10 or 40 mg/day. Combination therapy with micronised fenofibrate 200mg (capsule) once daily plus fluvastatin 20 or 40 mg/day or atorvastatin 40 mg/day was associated with greater reductions from baseline than micronised fenofibrate alone in TC and LDL-C levels. Similar or greater changes in HDL-C and TG levels were seen in combination therapy, compared with monotherapy, recipients. Micronised fenofibrate 200mg (capsule) once daily was associated with significantly greater improvements from baseline in TC, LDL-C, HDL-C and TG levels than placebo in patients with type 2 diabetes mellitus enrolled in the double-blind, randomised Diabetes Atherosclerosis Intervention Study (DAIS) [> or =3 years follow-up]. Moreover, angiography showed micronised fenofibrate was associated with significantly less progression of coronary atherosclerosis than placebo. Micronised fenofibrate has also shown efficacy in patients with metabolic syndrome, patients with HIV infection and protease inhibitor-induced hypertriglyceridaemia and patients with dyslipidaemia secondary to heart transplantation. Micronised fenofibrate was generally well tolerated in clinical trials. The results of a large (n = 9884) 12-week study indicated that gastrointestinal disorders are the most frequent adverse events associated with micronised fenofibrate therapy. Elevations in serum transaminase and creatine phosphokinase levels have been reported rarely with micronised fenofibrate. In conclusion, micronised fenofibrate improves lipid levels in patients with primary dyslipidaemia; the drug has particular efficacy with regards to reducing TG levels and raising HDL-C levels. Micronised fenofibrate is also effective in diabetic dyslipidaemia; as well as improving lipid levels, the drug reduced progression of coronary atherosclerosis in patients with type 2 diabetes mellitus. The results of large ongoing studies (e.g. FIELD with approximately 10 000 patients) will clarify whether the beneficial lipid-modifying effects of micronised fenofibrate result in a reduction in cardiovascular morbidity and mortality.
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PMID:Micronised fenofibrate: an updated review of its clinical efficacy in the management of dyslipidaemia. 1221 67

Coronary heart disease is a leading cause of death in industrialized nations. Hyperlipidemia with elevated serum total cholesterol, LDL cholesterol, and triglycerides is a known major cardiovascular risk factor. HDL cholesterol is considered to be protective, so low HDL cholesterol is being recognized as an independent cardiovascular risk factor that contributes to the development of atherosclerosis and related adverse cardiovascular events. The recognition of insulin resistance and metabolic syndrome is a step further in understanding these risk factors. Attempts at reducing serum cholesterol with different strategies in the past have met with limited success until the development of statins. The advent of statins has revolutionized the management of hyperlipidemia. The post-statins era has seen major clinical trials demonstrating the benefit of cholesterol reduction in the setting of both primary and secondary prevention. In general, there appears to be a 25% to 40% relative risk reduction in major adverse cardiovascular events such as death, myocardial infarction, and stroke. The recent megatrials further suggest that aggressive management of cholesterol in patients with high cardiovascular risk may be beneficial. Though the concept of the-lower-the-better may be looming, the question of "How low is good enough?" remains controversial. The results of recent megatrials such as the Heart Protection Study go a step further than the NCEP guidelines and suggest that statin therapy may benefit patients at high risk of cardiovascular disease regardless of their baseline values. We summarize the results of the available large clinical trials in our understanding of the management of dyslipidemia in a setting of primary prevention.
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PMID:Management of dyslipidemia in the primary prevention of coronary heart disease. 1235 27

Obesity is a major contributor to the prevalence of cardiovascular disease in the developed world, and yet has only recently been afforded the same level of attention as other risk factors of coronary artery disease. Obesity is a chronic metabolic disorder associated with cardiovascular disease and increased morbidity and mortality. It is apparent that a variety of adaptations/alterations in cardiac structure and function occur as excessive adipose tissue accumulates, even in the absence of comorbidities. Shifts toward a less physically demanding lifestyle are observed today throughout different populations, and this scourge associated with obesity implicates a corresponding increase in the number of individuals afflicted with the metabolic syndrome, which defines the obese patient as being "at risk." Adipose tissue is not simply a passive storehouse for fat, but an endocrine organ that is capable of synthesizing and releasing into the bloodstream a variety of molecules that may impact unfavorably the risk factor profile of a patient. Indeed, obesity may affect atherosclerosis through unrecognized variables and risk factors for coronary artery disease such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, and the prothrombotic state. By favorably modifying lipids, decreasing blood pressure, and decreasing levels of glycemia, proinflammatory cytokines, and adhesion molecules, weight loss may prevent the progression of atherosclerosis or the occurrence of acute coronary syndrome events in the obese high-risk population.
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PMID:Obesity and cardiovascular disease. 1236 92

Metabolic syndrome, insulin resistance, prediabetes, and overt type 2 diabetes mellitus are associated with an accelerated atherosclerosis (atheroscleropathy). This quartet is also associated with multiple metabolic toxicities resulting in the production of reactive oxygen species. The redox stress associated with these reactive oxygen species contribute to the development, progression, and the final fate of the arterial vessel wall in prediabetic and diabetic atheroscleropathy. The prevention of morbidity and mortality of these intersecting metabolic diseases can be approached through comprehensive global risk reduction.
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PMID:Intimal redox stress: accelerated atherosclerosis in metabolic syndrome and type 2 diabetes mellitus. Atheroscleropathy. 1239

Angiotensin II is known to inhibit the insulin-signaling pathway. On the other hand, insulin causes activation of the cardiovascular renin-angiotensin system in both cardiac cells and vascular cells(smooth muscle cells and endothelial cells). Insulin-activated tissue renin-angiotensin system leads to increased cell growth and contributes to cardiac hypertrophy and atherosclerosis. The fact that agents that inhibit the renin-angiotensin system also block insulin-mediated renin-angiotensin system expression and cell growth reinforces the potential implication of a cardiovascular insulin-renin-angiotensin system pathway. This review examines the mechanisms that connect systemic insulin resistance to the cardiovascular complications in the metabolic syndrome, especially the relation between insulin-signaling pathway and angiotensin.
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PMID:[Role of angiotensin in the metabolic syndrome and cardiovascular complications]. 1239 81

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

Obesity is a recognized risk factor for cardiovascular disease. Because the prevalence of obesity is rising in industrialized as well as developing nations, it is important to understand the mechanisms by which obesity targets the vascular system. A metabolic syndrome of insulin resistance is provoked by obesity, and this results in the dysregulation of a number of adipocyte-derived factors, which favors atherosclerosis. This review focuses on how products of the adipocyte, including free fatty acids and "adipo"-cytokines, may mediate the effect of obesity on insulin resistance and atherosclerosis.
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PMID:Molecular links between obesity and cardiovascular disease. 1242 10

Rosuvastatin, a new statin, has been shown to possess a number of advantageous pharmacological properties, including enhanced HMG-CoA reductase binding characteristics, relative hydrophilicity, and selective uptake into/activity in hepatic cells. Cytochrome p450 (CYP) metabolism of rosuvastatin appears to be minimal and is principally mediated by the 2C9 enzyme, with little involvement of 3A4; this finding is consistent with the absence of clinically significant pharmacokinetic drug-drug interactions between rosuvastatin and other drugs known to inhibit CYP enzymes. Dose-ranging studies in hypercholesterolemic patients demonstrated dose-dependent effects in reducing low-density lipoprotein cholesterol (LDL-C) (up to 63%), total cholesterol, and apolipoprotein (apo) B across a 1- to 40-mg dose range and a significant 8.4% additional reduction in LDL-C, compared with atorvastatin, across the dose ranges of the two agents. Rosuvastatin has also been shown to be highly effective in reducing LDL-C, increasing high-density lipoprotein cholesterol (HDL-C), and producing favorable modifications of other elements of the atherogenic lipid profile in a wide range of dyslipidemic patients. In patients with mild to moderate hypercholesterolemia, rosuvastatin has been shown to produce large decreases in LDL-C at starting doses, thus reducing the need for subsequent dose titration, and to allow greater percentages of patients to attain lipid goals, compared with available statins. The substantial LDL-C reductions and improvements in other lipid measures with rosuvastatin treatment should facilitate achievement of lipid goals and reduce the requirement for combination therapy in patients with severe hypercholesterolemia. In addition, rosuvastatin's effects in reducing triglycerides, triglyceride-containing lipoproteins, non-HDL-C, and LDL-C and increasing HDL-C in patients with mixed dyslipidemia or elevated triglycerides should be of considerable value in enabling achievement of LDL-C and non-HDL-C goals in the numerous patients with combined dyslipidemias or metabolic syndrome who require lipid-lowering therapy. Rosuvastatin is well tolerated alone, and in combination with fenofibrate, extended-release niacin, and cholestyramine, and has a safety profile similar to that of currently marketed statins. A large, long-term clinical trials program is under way to investigate the effects of rosuvastatin on atherosclerosis and cardiovascular morbidity and mortality.
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PMID:Rosuvastatin: a highly effective new HMG-CoA reductase inhibitor. 1248 Dec 2


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