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

Hypertension in older persons is characterized by increased systolic blood pressure, and isolated systolic hypertension (ISH) is the most common type of hypertension in this population. It is thought that ISH results from age-associated vascular stiffening and reduced compliance that can be revealed and quantified by analysis of arterial pressure waveforms. Evaluation of pulse wave velocity and other related measures has shown that arterial stiffness increases with advancing age and other cardiovascular (CV) risk factors including hypertension, the metabolic syndrome, diabetes, obesity, hypercholesterolemia, and elevated C-reactive protein. Many of these relationships have been demonstrated in patients without clinical CV disease and are independent of patient age. Arterial stiffness is significantly and independently associated with both target organ damage and increased risk for CV morbidity and mortality. The mechanisms underlying age- and disease-related arterial stiffening are not fully understood. However, assessment of changes in gene expression associated with increased arterial stiffness and gene polymorphisms that increase the risk for vascular stiffening suggests that components of the renin-angiotensin system, matrix metalloproteinases, intracellular signaling, and extracellular matrix components may all be involved in this process. Interventions aimed at these targets may reduce vascular stiffness, lower systolic blood pressure, decrease the prevalence of ISH, and improve outcomes for patients (particularly older patients) with hypertension or other CV conditions.
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PMID:Vascular stiffening and arterial compliance. Implications for systolic blood pressure. 1560 34

Several lines of evidence suggest that angiotensin-converting enzyme (ACE) inhibitors and some angiotensin II receptor blockers (ARBs) may improve insulin sensitivity and decrease the risk for type 2 diabetes. It is widely assumed that the potential antidiabetic properties of these agents are largely mediated by their ability to interfere with the adverse metabolic effects of angiotensin II. However, recent studies suggest that ACE inhibitors might improve glucose metabolism primarily through effects on kinin-nitric oxide pathways. In addition, one ARB in particular, telmisartan, has been found to effectively activate the peroxisome proliferator activated receptor gamma (PPARgamma), a well-known target for insulin-sensitizing, antidiabetic drugs. Thus, the beneficial metabolic effects of some ACE inhibitors and ARBs may go well beyond their effects on the renin-angiotensin system. Moreover, the identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma modulating ability suggests new opportunities for developing third-generation ARBs and PPARgamma activators, with enhanced potential for treating hypertension, diabetes and the metabolic syndrome.
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PMID:Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin-angiotensin system. 1561 15

The metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular diseases and diabetes mellitus. Indeed, hypertension occurs approximately twice as frequently in patients with diabetes compared with in non-diabetic controls. Conversely, hypertensive patients are more likely than normotensive persons to develop diabetes. In addition, up to 75% of CVD in diabetic patients can be attributed to hypertension. Therefore, the primary goals of treating hypertensive patients with insulin resistance are prevention of type 2 diabetes and cardiovascular events. Then, what is the optimal anti-hypertensive approach to target organ protection in these patients? Several clinical trials suggest that the renin-angiotensin system (RAS) plays a pivotal role in the pathogensis of insulin resistance and CVD in diabetes. Interruption of the RAS with angiotensin-coverting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) has been shown to prevent the onset of diabetes in hypertensive patients and to reduce cardiovascular and renal disease progression in diabetic patients with hypertension. However, whether we should recommend ARBs for insulin resistant-hypertensive patients or type 2 diabetic patients without nephropathy due to its insulin-sensitizing property remains to be clarified. Recently, telmisartan, an ARB, was found to act as a patrtial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR-gamma influences the gene expression involved in carbohydrate metabolism, and pioglitazone and rosiglitazone, ligands for PPAR-gamma, improve insulin resistance in diabetic patients. Furthermore, there is a growing body of evidence that activators of PPAR-gamma exert anti-inflammatory, anti-oxidative and anti-proliferative effects on vascular wall cells, thus decreasing the risks for atherosclerosis. We hypothesize here that due to its unique PPAR-gamma-modulating activity, telmisartan will become a promising 'cardiometabolic sartan', that targets both diabetes and CVD in hypertensive patients. In this paper, we would like to propose the possible ways of testing our hypothesis. Does telmisartan reduce the development of diabetes and CVD in insulin resistant patients pretreated with maximal doses of other ARBs? Does co-treatment with an activator of PPAR-gamma attenuate the effects of telmisartan in these patients? These clinical studies will provide further information whether the beneficial cardiometabolic actions of telmisartan could be ascribed to its PPAR-gamma-inducing property.
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PMID:Telmisartan is a promising cardiometabolic sartan due to its unique PPAR-gamma-inducing property. 1561 52

The metabolic syndrome is associated with activation of the renin-angiotensin system. However, whether the coronary vascular response to ANG II is altered under this condition is unknown. Experiments were conducted in control and chronically high-fat-fed dogs with the prediabetic metabolic syndrome both in vitro (isolated coronary arterioles, 60-110 microm) and in vivo (anesthetized and conscious). We found that plasma renin activity and ANG II levels are elevated in high-fat-fed dogs and that this increase in ANG II is associated with a significant increase in ANG II-mediated coronary vasoconstriction in isolated coronary arterioles and in anesthetized open-chest dogs. The vasoconstriction to ANG II is abolished by ANG II type 1 (AT1) receptor blockade. In conscious chronically instrumented dogs, AT1 receptor blockade with telmisartan improved the balance between coronary blood flow and myocardial oxygen consumption in the high-fat-fed dogs but not in normal control dogs, i.e., the relationship between coronary venous Po2 and myocardial oxygen consumption was shifted upward, toward normal control values. Quantitative assessment of coronary arteriolar AT1 and ANG II type 2 (AT2) receptor mRNA levels by real-time PCR revealed no significant difference between normal control and high-fat-fed dogs; however, Western blot analysis showed a significant increase in AT1 receptor protein level with no change in AT2 receptor protein density. These findings indicate that AT1 receptor-mediated coronary constriction is augmented in the prediabetic metabolic syndrome and contributes to impaired control of coronary blood flow via increases in circulating ANG II and/or coronary arteriolar AT1 receptor density.
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PMID:Coronary arteriolar vasoconstriction to angiotensin II is augmented in prediabetic metabolic syndrome via activation of AT1 receptors. 1565 64

The incidence of metabolic syndrome is rapidly increasing in the United States. Metabolic syndrome is associated with increased cardiovascular morbidity and mortality, and endothelial dysfunction is an early pathogenetic event in the metabolic syndrome. Endothelial dysfunction of either the coronary, the peripheral, or the cerebral vasculature is a predictor of vascular events and appears to be a marker of uncontrolled atherosclerotic risk that adds to the burden of the genetic predisposition to cardiovascular disease. Clinically and experimentally, endothelial dysfunction can be restored by several agents, including blockers/inhibitors of the renin-angiotensin-aldosterone system, as well as statins. Nevertheless, it would be premature, and most likely inappropriate, to use improvement of endothelial function as a surrogate end point to predict reduction in cardiovascular morbidity and mortality. However, a clear understanding of the mechanisms of endothelial dysfunction in the metabolic syndrome may allow the development of preventive and early therapeutic measures targeting cardiovascular disease.
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PMID:Metabolic syndrome and endothelial dysfunction. 1574 31

When risk factors such as dyslipidemia and hypertension are inadequately controlled in subjects with the metabolic syndrome by lifestyle interventions, pharmacologic approaches are warranted. Statins are first-line pharmacotherapy for dyslipidemia due to their efficacy for lowering low-density lipoprotein (LDL) cholesterol and may also improve high-density lipoprotein (HDL) cholesterol and triglyceride levels. Fibrates and niacin may be useful in combination with a statin for additionally lowering triglycerides or raising HDL cholesterol. Adequate control of hypertension will usually require two or more drugs; agents that block the renin-angiotensin system are particularly useful in this population, given their demonstrated benefits for reducing the burden of cardiovascular events and end-stage renal disease independent of blood-pressure lowering. A multifaceted approach to risk factor management for the metabolic syndrome will have benefits for prevention of type 2 diabetes and cardiovascular disease.
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PMID:New approaches in the intensive management of cardiovascular risk in the metabolic syndrome. 1582 99

Diabetes and hypertension frequently coexist, and their combination provides additive increases in the risk of life-threatening cardiovascular events. Recent guidelines agree on the need for early, aggressive reduction of blood pressure, with a goal of <130/80 mmHg, in patients with diabetes. The mechanism that underpins the increased sensitivity of diabetic subjects to hypertension is not known, but may involve impaired autoregulation or attenuated nocturnal decrease of blood pressure. All classes of antihypertensive agents are effective in reducing blood pressure in diabetic subjects, and all show evidence of a concomitant reduction in cardiovascular risk. Although there is some evidence that agents that interrupt the renin-angiotensin system (RAS) provide greater protective effects, the data are not conclusive. However, most diabetic subjects will require combination therapy to reach goal blood pressure. Antihypertensive drugs can also significantly influence the probability that otherwise healthy individuals will develop metabolic syndrome or type 2 diabetes. While diuretics and betablockers have a prodiabetic effect, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may prevent diabetes more effectively than the metabolically neutral calcium channel blockers. Given that diabetes is an important cardiovascular risk factor, there is the potential for reductions in risk due to reduced blood pressure to be offset by an increased risk due to the development of diabetes. Such concerns should be considered in the selection of antihypertensive therapy.
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PMID:The association of hypertension and diabetes: prevalence, cardiovascular risk and protection by blood pressure reduction. 1586 15

The metabolic syndrome is defined as a condition characterized by a set of clinical criteria: insulin resistance, visceral obesity, atherogenic dyslipidemia, and hypertension. The major risk factors leading to the epidemic of this syndrome in the United States are visceral obesity, physical inactivity, and an atherogenic diet. The available current evidence suggests that the first step in management of patients with metabolic syndrome should be focused on lifestyle modifications (eg, weight loss and physical activity). The treatment should be based on two major components: behavioral change to reduce caloric intake and an increase in physical activity. A realistic goal for weight reduction should be 7% to 10% over 6 to 12 months. The general dietary recommendations include low intake of saturated fats, trans fats and cholesterol, and diets with low glycemic index. Soy protein could be more beneficial than animal protein in weight reduction and correction of dyslipidemia. Physical activity is associated with successful weight reduction and these therapeutic lifestyle changes can reduce by half the progression to new-onset diabetes in patients with metabolic syndrome. Physical activity recommendations should include practical, regular, and moderated regimens of exercise, with a daily minimum of 30 to 60 minutes. An equal balance between aerobic exercise and strength training is advised. Medication therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals. There is no single best therapy and the treatment should consist of treatment of individual component(s). Atherogenic dyslipidemia should be controlled with statins if there is concomitant increase in low-density lipoprotein cholesterol and if indicated with combination therapy, including fibrates, nicotinic acid, bile acid-binding resins, or ezetimibe. Drugs such as thiazolidinediones and renin-angiotensin system blockers are a few of the available agents in this category. Some evidence suggests that angiotensin-converting enzyme inhibitors and b blockers are more beneficial for treatment of hypertension in patients with metabolic syndrome. Patients with metabolic syndrome also have elevations in fibrinogen and other coagulation factors leading to prothrombotic state and aspirin may be beneficial for primary prevention in these patients. The new developments in the treatment of metabolic syndrome with drugs, such as peroxisome proliferator-activated receptor agonists, will broaden the horizons of the current treatment options in metabolic syndrome.
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PMID:Current Treatment Options for the Metabolic Syndrome. 1591 5

Metabolic syndrome affects approximately one quarter of population in developed countries. Its presence is a major risk for development of both type 2 diabetes (T2DM) and atherosclerosis. The prevalence of cardiovascular disease is 2-3 times higher in individuals with metabolic syndrome than in age-matched controls. Most important components of metabolic syndrome are insulin resistance with or without glucose intolerance, abdominal obesity, atherogenic dyslipidaemia, hypertension, prothrombotic state and proinflammatory state. Early identification of subjects with metabolic syndrome is very important, since they represent a target group for multiple lifestyle and pharmacological interventions. Lifestyle interventions, antiobesity drugs and drugs increasing insulin sensitivity prevented development of T2DM in subjects with impaired glucose tolerance in randomized trials. Treatment of atherogenic dyslipidaemia to the therapeutic goals defined for diabetic patients seems reasonable and both statins and fibrates could be used based on evidence from clinical trials. Treatment of hypertension should also aim for target levels similar to those in diabetic patients. Using drugs affecting renin-angiotensin II axis, as first choice seems reasonable based on evidence from clinical trials showing the ability of these drugs to prevent T2DM and decrease albuminuria.
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PMID:Metabolic syndrome in relationship to type 2 diabetes and atherosclerosis. 1595 70

The metabolic syndrome is a constellation of interrelated abnormalities that increase the risk for cardiovascular disease and progression to type 2 diabetes. The prevalence of this syndrome is increasing because of the 'obesity epidemic'. The National Cholesterol Education Program Adult Treatment Panel III defined practical criteria for the diagnosis of the metabolic syndrome and established the basic principles for its management. Also, the International Diabetes Federation recently proposed another definition. The metabolic syndrome is a secondary target for cardiovascular risk reduction. Clinicians should identify individuals with this condition, assess their cardiovascular risk and treat them by an aggressive and multifaceted approach. The most effective therapeutic intervention in patients with the metabolic syndrome should focus on modest weight reduction and regular physical activity. Adoption of a healthier diet and smoking cessation are necessary. Drug therapy may be needed to achieve recommended goals if therapeutic lifestyle changes are not sufficient. Low-density lipoprotein cholesterol is the primary target of therapy (new aggressive goals should be achieved). Statins are probably the drugs of choice. Fibrates and nicotinic acid are also useful options. Hypertension should be managed aggressively probably starting with an inhibitor of the renin-angiotensin system or a calcium channel blocker and adding a low dose of a thiazide diuretic if necessary. Aspirin should be administered if the cardiovascular risk is high. In the future acarbose, metformin, meglitinides and thiazolidinediones may be used in patients with the metabolic syndrome to delay the onset of type 2 diabetes and reduce cardiovascular risk. Such an intense and multifactorial approach is likely to reverse the bad prognosis associated with the metabolic syndrome.
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PMID:Diagnosis and management of the metabolic syndrome in obesity. 1624 14


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