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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic syndrome is a constellation of interrelated abnormalities that increase the risk for the development of cardiovascular disease and type 2 diabetes. Together with obesity and dyslipidaemia, hypertension is one of the basic elements of the metabolic syndrome. Current guidelines do not provide specific recommendation for pharmacological management of the hypertensive patients with metabolic syndrome. Recent trials have consistently shown that therapy involving beta-blockers and diuretics may have some negative impact on metabolic and haemodynamic disorders present in metabolic syndrome. Several lines of evidence support the use of angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers as the appropriate first-line therapy and calcium channel blockers, as the second, in the patients with metabolic syndrome.
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PMID:[Metabolic syndrome in patients with hypertension]. 1721 93

Arterial hypertension is frequently associated with type 2 diabetes mellitus, and both of these diseases are the major risk factors for cardiovascular complications. During the past few years, a number of large randomized clinical trials examined the frequency of new onset diabetes mellitus during administration of antihypertensive drugs. Application of ACE inhibitors or angiotensin receptor blockers reduces the risk for the onset of diabetes mellitus by 20-27%, and calcium channel blockers by 16%. Despite some uncertainties, novel studies have demonstrated an increased risk for cardiovascular complications related to new onset diabetes mellitus. The duration of patient monitoring is also an important factor, as the onset of diabetes-related complications is closely associated with the duration of this disease. Considering all above, the aim of preventing the onset of diabetes is to recognize patients with an increased risk. The risk factors include basal glycemia, positive family history for diabetes mellitus, obesity, metabolic syndrome, and some ethnic groups (South Asia, the Caribbeans). Therefore, increased-risk patients should be subjected to therapy with ACE inhibitor, angiotensin receptor blocker, or calcium channel blocker as the first drug of choice. For these patients, application of thiazides and beta blockers or the combination of these two drugs is not advantageous. However, such a view poses a dilemma whether thiazide diuretics should be the first choice in the treatment of hypertension.
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PMID:[Antihypertensive agents and the risk of new onset diabetes mellitus]. 1721 94

The metabolic syndrome or cardiovascular dysmetabolic syndrome is characterized by obesity, central obesity, insulin resistance, atherogenic dyslipidemia, and hypertension. The major risk factors leading to this syndrome are physical inactivity and an atherogenic diet and cornerstone clinical feature is abdominal obesity or adiposity. In addition, patients usually have elevated triglycerides, low HDL cholesterol, elevated LDL cholesterol, other abnormal lipid parameters, hypertension, and elevated fasting blood glucose. Impaired fibrinolysis, increased susceptibility to thrombotic events, and raised inflammatory markers are also observed. Given that India has the largest number of subjects with type-2 diabetes in the world it can be extrapolated that this country also has the largest number of patients with the metabolic syndrome. Epidemiological studies confirm a high prevalence. Therapeutic approach involves intervention at a macro-level and control of multiple risk factors using therapeutic lifestyle approaches (diet control and increased physical activity, pharmacotherapy - anti-obesity agents) for control of obesity and visceral obesity, and targeted approach for control of individual risk factors. Pharmacological therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals. Anti-obesity drugs such as sibutramine and orlistat can be tried to reduce weight and central obesity and jointly control the metabolic syndrome components. Other than weight loss, there is no single best therapy and treatment should consist of treatment of individual components of the metabolic syndrome. Newer drugs such as the endocannabinoid receptor blocker,rimonabant, appear promising in this regard. Atherogenic dyslipidemia should be controlled initially with statins if there is an increase in LDL cholesterol. If there are other lipid abnormalities then combination therapy of statin with fibrates, nicotinic acid, or ezetimibe should be considered. For insulin resistance, drugs such as thiazolidinediones and renin-angiotensin system blockers are available. Available evidence suggests that angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBS) may be more beneficial for treatment of hypertension in patients with metabolic syndrome compared to others as these drugs also prevent development of diabetes. 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 (PPAR) agonists and cannabinoid receptor-1 antagonists, will broaden the horizons of the current treatment options. Fixed-dose combination polypharmacy using a single pill is an interesting concept that needs to be evaluated in long-term prospective trials in such patients.
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PMID:Management issues in the metabolic syndrome. 1721 77

The metabolic syndrome (MetS) is a strong predictor of cardiovascular morbidity and mortality, as well as new Type 2 diabetes. MetS consists of visceral obesity, elevated blood pressure, impaired glucose metabolism, atherogenic dyslipidaemia (elevated triglycerides and low levels of high-density lipoprotein cholesterol), as well as other metabolic abnormalities. The underlying pathophysiology seems to be largely, but not uniquely, attributable to insulin resistance. Existing antihypertensive drugs were designed to lower blood pressure rather than to modify the metabolic abnormalities associated with hypertension. This review considers the role of renin-angiotensin system inhibition and especially the use of angiotensin receptor blockers (ARBs) in the treatment of hypertension in MetS. There are differences among ARBs. Among them is the uricosuric effect of losartan. Furthermore, telmisartan may function as a partial agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma).
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PMID:The role of renin-angiotensin system inhibition in the treatment of hypertension in metabolic syndrome: are all the angiotensin receptor blockers equal? 1722 34

A new concept has been proposed to capture the flow of events and chain reactions associated with cardiovascular risk: the metabolic domino. The metabolic domino differs for each individual based on their genetic predisposition. Lifestyle changes are the first dominoes to fall, which lead to obesity and insulin resistance, followed by postprandial hyperglycemia, hypertension, and hyperlipidemia. Atherosclerosis then begins, and diabetes occurs once the domino for impairment of insulin secretion has toppled. Progression of the atherosclerotic process can lead to cardiovascular events such as ischemic heart diseases or cerebrovascular disorders. Preclinical and clinical data indicate that treatments which inhibit the renin angiotensin system, such as angiotensin receptor blockers, can suppress the onset of diabetes and, when administered even earlier in the metabolic domino, reduce the development of hypertension in at-risk individuals. The inhibition of inflammation with thiazolidinedione can also block the sequence of events leading to cardiovascular outcomes, as was shown with pioglitazone in the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive).
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PMID:Metabolic domino: new concept in lifestyle medicine. 1724 76

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Lifelong environmental factors (eg, salt intake, obesity, alcohol) and genetic factors clearly contribute to the development of hypertension, but it has also been established that stress in utero may program the later development of the disease. This phenomenon, known as fetal programming can be modeled in a range of experimental animal models. In maternal low protein diet rat models of programming, administration of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists in early life can prevent development of hypertension, thus implicating the renin-angiotensin system in this process. Here we show that in this model, expression of the AT(1b) angiotensin receptor gene in the adrenal gland is upregulated by the first week of life resulting in increased receptor protein expression consistent with the increased adrenal angiotensin responsiveness observed by others. Furthermore, we show that the proximal promoter of the AT(1b) gene in the adrenal is significantly undermethylated, and that in vitro, AT(1b) gene expression is highly dependent on promoter methylation. These data suggest a link between fetal insults to epigenetic modification of genes and the resultant alteration of gene expression in adult life leading ultimately to the development of hypertension. It seems highly probable that similar influences may be involved in the development of human hypertension.
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PMID:Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. 1733 36

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a key regulator of lipid metabolism and energy balance implicated in the development of insulin resistance and obesity. The identification of putative natural and synthetic ligands and activators of PPAR-gamma has helped to unravel the molecular basis of its function, including molecular details regarding ligand binding, conformational changes of the receptor, and cofactor binding, leading to the emergence of the concept of selective PPAR-gamma modulators (SPPARgammaMs). SPPARgammaMs bind in distinct manners to the ligand-binding pocket of PPAR-gamma, leading to alternative receptor conformations, differential cofactor recruitment/displacement, differential gene expression, and ultimately differential biological responses. Based on this concept, new and improved antidiabetic agents for the treatment of diabetes are in development. This review summarizes the current knowledge on the mechanism of action and biological effects of recently characterized SPPARgammaMs, including metaglidasen/halofenate, PA-082, and the angiotensin receptor antagonists, recently characterized as a new class of SPPARgammaMs.
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PMID:Selective Modulators of PPAR-gamma Activity: Molecular Aspects Related to Obesity and Side-Effects. 1738 69

Increased visceral adiposity, is an emerging cardiovascular risk factor. There is now a compelling need to quantify visceral adipose tissue not only for diagnostic purposes, but also for therapeutic interventions with weight reduction drugs or pharmaceuticals targeted to adipose tissue, as well as anti-obesity medications, thiazolidinediones, fibrates, angiotensin receptor blockers, highly active antiretroviral therapy and hormone replacement therapy. Among visceral adipose tissues, growing evidences suggest that cardiac adiposity may play an important role in the development of an unfavorable cardiovascular risk profile. Recent papers suggest that epicardial fat, index of cardiac and visceral adiposity, could locally modulate the morphology and function of the heart. The close anatomical relationship between epicardial adipose tissue and the adjacent myocardium should readily allow local paracrine interactions between these tissues. Echocardiography has been recently proposed for the direct assessment of epicardial adipose tissue. Echocardiographic assessment of epicardial fat may be a helpful tool not only for diagnostic purposes, as marker of visceral adiposity and inflammation, but also for therapeutic interventions with drugs that can modulate the adipose tissue. In this article, epicardial adipose tissue's structure, function, method of assessment and reliability as a diagnostic tool and potential therapeutic target is reviewed.
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PMID:Epicardial adipose tissue as new cardio-metabolic risk marker and potential therapeutic target in the metabolic syndrome. 1762 50

Metabolic syndrome (MetSyndr), a constellation of abnormalities [obesity, glucose intolerance, insulin resistance (IR), dyslipidemia (low HDL-cholesterol, high LDL-cholesterol and triglycerides (TG)], and elevated blood pressure (BP)], increases the risk of cardiovascular (CV) disease and premature death. From 10% to 30% of the adult population in industrialized countries has MetSyndr, which effectively predicts the development of type 2 diabetes mellitus (T2D) and CV disease. Because of the complex etiology of MetSyndr, a multi-targeted, integrated therapeutic approach is required to simultaneously treat high BP, obesity, lipid disorders and T2D (if present), to fully protect CV, cerebrovascular and renal systems. If lifestyle modification (weight control, diet, exercise, smoking cessation, moderation of alcohol intake) is ineffective, pharmaco-theraphy should be added to treat simultaneously the lipid- and non-lipid CV risk factors. Patients with HTN and MetSyndr should be started on angiotensin-converting enzyme (ACE) inhibitors, unless contraindicated. The ACE inhibitors and angiotensin receptor blockers (ARBs) reduce the odds of developing new onset T2D and also decrease albuminuria. The ACE inhibitors provide cardioprotective and renoprotective benefits beyond their effect on BP; they also improve IR. The ARBs are renoprotective in addition to being cardioprotective. Long-acting calcium channel blockers are also recommended in hypertensive patients with MetSyndr; these drugs also improve IR. Thiazides (at low doses) and selected ss-blockers can be given to patients with HTN and MetSyndr. Celiprolol in combination with diuretics has a favorable effect on glucose tolerance and IR in patients with HTN and MetSyndr, and spironolactone added to ACE inhibitor or ARB therapy provides additional reno- and CV protective benefits in patients with diabetic nephropathy. Carvedilol, a ss-blocker with vasodilating properties, added to ACE inhibitor or ARB therapy, is effective in preventing worsening of microalbuminuria in patients with HTN and MetSyndr; it also improves IR and glycemic control. Most patients eventually require two or more antihypertensive drugs to reach BP goal. It is recommended that therapy in patients whose BP is more than 20/10 mm Hg above target at diagnosis be initiated with a combination of antihypertensive drugs, administered either as individual drugs or as fixed-dose formulations. Treatment with fixed-dose combinations, such as irbesartan + hydrochlorothiazide provides good BP control in more than two-thirds of hypertensive patients with MetSyndr. Lipid and BP targets are reached in a high percent of patients with HTN and CV disease treated with a combination of amlodipine + atorvastatin. In conclusion, hypertensive patients with the MetSyndr be treated aggressively for each component of the syndrome to provide CV, cerebrovascular and renal protection.
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PMID:Metabolic syndrome: treatment of hypertensive patients. 1766 15

The regulation of blood glucose levels involves a finely tuned relationship between insulin sensitivity, hepatic glucose output, and production of insulin. The cardiometabolic syndrome includes in its definition criteria a disturbance of normal glucose tolerance and implies development of both insulin resistance and beta-cell dysfunction. There is now abundant evidence pointing toward a central role of dysregulation of the beta-cell function and mass in the development of impaired glucose tolerance. Mechanisms implicated in beta-cell dysfunction include genetic abnormalities, prenatal and early postnatal insults, and environmental events along with obesity, dyslipidemia-lipotoxicity, glucotoxicity, oxidative stress, chronic low-grade inflammation, amyloid deposition, and activation of the local renin-angiotensin system. Novel therapeutic characteristics of known medications such as metformin, thiazolidinediones, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and novel medications such as exendin-4 promise encouraging possibilities to battle against the cardiometabolic syndrome and the future development of cardiovascular disease.
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PMID:The role of beta-cell dysfunction in the cardiometabolic syndrome. 1767


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