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)

Insulin Resistance along with endothelial dysfunction give rise to a constellation of syndromes designated as IRS/MBS metabolic syndrome. Endothelial dysfunction starts early in life much before the development of structural atherosclerosis. Recent insights into vascular biology enable us to understand the molecular mechanisms underlying endothelial dysfunction, and the scope and need for prevention of "pre-clinical" coronary atherosclerosis through lifestyle modification; diet, exercise and stress management. Diminished production of nitric oxide (NO) and/or increased inactivation of NO through oxidative stress (reactive oxygen species ROS and reactive nitrogen species (RNS) are the basis of endothelial dysfunction hence increasing the bioavailability of NO and decreasing its inactivation is the aim of prevention and reversal of endothelial dysfunction. Insulin regulates constitutive NOS gene expression in endothelial cells in vivo; vasodilation is an important component of Insulin-stimulated whole body glucose uptake. Successful strategies are: PPAR alpha and gamma agonists which increase NO production in endothelium; anti-oxidants such as vit. E and C; supplementation with L-arginine, tetrahydrobiopterin-BH4 or sepiapterin (precursor of BH4), SOD mimetic tempol, statins which apart from lowering cholesterol improve NO production, selective beta1 adrenoreceptor antagonists such as nebivolol; suppression of angiotensin-mediated endothelin production by ACE inhibitors and ATR blockers; CB1 receptor blockers, PKCb inhibitors, nitric oxide donors (glyceryl trinitrate and isosorbide dinitrate), dietary supplements of EPA/DHA and regular physical exercise and control of mental stress.
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PMID:Causation, prevention and reversal of vascular endothelial dysfunction. 1805 38

Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans.
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PMID:Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans. 1851 Apr 34

We have undertaken a study on variations in cholinesterase (ChE) genes in relation to cardiovascular (CV) function and the metabolic syndrome. Peripheral and central nervous system control of cardiovascular (CV) function mediated through cholinergic pathways is critical in homeostatic maintenance of blood pressure and responsiveness to stress. For acetylcholinesterase (AChE; EC 3.1.1.7) our focus is to identify single nucleotide polymorphisms (SNPs) in the gene that are linked to cardiovascular function. For butyrylcholinesterase (BChE; EC 3.1.1.8) we examined whether BChE activity correlated with parameters of the metabolic syndrome and cardiovascular function. ChE can be found in whole blood enabling a characterization of biochemical phenotype in addition to correlating genotype with phenotypic physiologic responses. Analysis of enzymatic activity was determined spectrophotometrically in blood samples from twin and other subject registries. Correlation analysis revealed significant relationships between enzyme activity and certain CV endpoints. Linkage analysis with data from a dizygotic (DZ) twin set showed a suggestive linkage at the BChE locus, and statistical analysis revealed a high correlation between BChE activity and variables associated with cardiovascular risk and the metabolic syndrome. Pattern of within-pair twin correlations by zygosity and the ACE model-fitting findings suggest the major source of this variation (65%) is attributable to an additive genetic component. To date 19 SNPs have been identified by the re-sequencing of AChE including four nonsynonymous coding SNPs (cSNPs).
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PMID:The cholinesterases: analysis by pharmacogenomics in man. 1854 Dec 29

Antihypertensive drugs that inhibit the renin-angiotensin system (RAS) have been proposed to have additional benefits beyond their classic effects on the cardiovascular system, including reducing the risk of new-onset diabetes. Whether RAS inhibitors vary in ability to protect against new-onset diabetes is, however, unknown. The angiotensin II type 1 receptor (AT(1)) blocker telmisartan has been discovered to also activate the peroxisome proliferator-activated receptor-gamma (PPARgamma), an established antidiabetic drug target. In patients with hypertension and biochemical features of the metabolic syndrome, telmisartan has had beneficial effects on lipid and glucose metabolism. As a selective modulator of PPARgamma, telmisartan does not cause the side effects of fluid retention and weight gain associated with conventional thiazolidinedione ligands of PPARgamma. These observations raise the possibility that combined AT(1) receptor blockade and selective PPARgamma modulation with molecules such as telmisartan could provide greater protection from new-onset diabetes and cardiovascular disease than drugs that target either the RAS or PPARgamma alone. The cardioprotective and antidiabetic effects of telmisartan are being assessed in two large clinical trials, the ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomised AssessmeNt Study in ACE-I iNtolerant subjects with cardiovascular Disease (TRANSCEND).
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PMID:Beyond the classic angiotensin-receptor-blocker profile. 1858 Aug 62

Hypertension is a highly prevalent disease and a strong risk factor for cardiovascular disease in industrialized countries in Europe and North America. About 40-50% of hypertensive patients have some other cardiovascular risk factors as smoking, dyslipidemia, glucose intolerance, metabolic syndrome and diabetes. The realization of optimal therapy of these patients is a difficult task, and reaching target blood pressure values is almost impossible by monotherapy. It was realized that the simultaneous normalization of blood pressure and that of abnormal lipid profile with 2-3 or more drugs have great importance for preventing atherosclerotic complications.We started an open-formed study with about 1000 hypertensive patients complicated with dyslipidemia, visceral obesity, metabolic syndrome and diabetes type 2. The base of our therapeutic strategy was a typical poly-pharmacologic treatment with ACE inhibitor (lisinopril), calcium antagonist (amlodipine), statin (atorvastatin) and antiplatelet therapy (if it was necessary).
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PMID:[Combined antihypertensive and antilipemic therapy as one of the pillars in the poly-pharmacologic preventive strategy for patients with high cardiovascular risk]. 1880 71

1. Epidemiological aspects: There is evidence that the pandemic of DM is entering a stabilization phase, with a slight downturn in the rates of ESRD attributed to DM in the United States. 2. New pathogenic and progression mechanisms of renal disease are proposed: 1) Intraglomerular hyperpressure with phenotypical cell changes, inducing TGF-beta activation; 2) Genetic polymorphisms, with candidate genes in chromosomes 18q, 3q, 7p and others; 3) Endothelial dysfunction as an injury initiating mechanism, demonstrated in the eNOS knockout rat; 4) Isoforms of PKC molecules that favor progression of nephropathy. 3. Importance of metabolic syndrome as a progression factor of chronic renal disease. 4. Increased CV risk in patients treated with thiazolidinediones (glitazones) -Hydrosaline retention and heart failure. 5. Recent studies: ADVANCE study: Combined treatment with an ACE inhibitor (perindropil) and a diuretic (indapamide) in fixed doses helps to reduce CV risk and overall mortality.DREAM study: Ramipril does not reduce the occurrence of DM2, but does improve reversion to normoglycemia. AVOID study: Direct renin inhibitors add greater antihypertensive and antiproteinuric efficacy. 6. New therapeutic targets: Antifibrotic, anti-inflammatory and antiproteinuric effects of sulodexide, isosorbide mononitrate, PKC inhibitors and others. 7. The most effective strategy continues to be intensive, multifactorial and multidisciplinary management of the type 2 diabetic patient, as shown by long-term follow-up in the Steno-2 study.
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PMID:[Advances in diabetes mellitus, diabetic nephropathy, metabolic syndrome and cardio-vascular-renal risk]. 1884 25

The 2007 European Guidelines on Hypertension are jointly sponsored by the European Society of Cardiology and the European Society of Hypertension. Changes with respect to the previous 2003 Guidelines are few but some are significant. Perhaps the most significant change is inclusion of metabolic syndrome as a cardiovascular risk factor similar in importance to diabetes mellitus or target-organ damage. Also striking is the recognition of chronic kidney disease as a very high risk condition in hypertensive patients. Masked arterial hypertension (AHT) is included for the first time as a new entity that is present in 10-15% of cases and associated with increased cardiovascular risk. The eye fundus examination is no longer considered necessary in the diagnostic evaluation. The decision to start treatment should be based on systolic and diastolic BP values and on assessment of total cardiovascular risk. Drug therapy should be started early. The delay to check the response to nonpharmacological measures should be only some weeks and not months as was previously established. Any of the five large groups (diuretics, beta-blockers, calcium antagonists, ACE inhibitors and angiotensin II blockers) is valid for the first stage of treatment, although the choice should be individualized based on the possible risk factors and associated cardiovascular and renal disease. The guidelines place strong emphasis on drug combinations because most patients will require more than one drug for their control.
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PMID:[Novelties in the European Hypertension Guide 2007. European Society of Cardiology. European Society of Hypertension]. 1884 31

The metabolic syndrome, also known as the cardiometabolic syndrome (CMS), is a state of metabolic and vascular dysregulation that is associated with activation of the renin-angiotensin-aldosterone system (RAAS). Clinical components of the CMS include central or visceral obesity, hypertension (HTN), dyslipidemia, insulin resistance/hyperinsulinemia, and microalbuminuria that collectively convey increases in oxidative stress, inflammation, and subsequent endothelial dysfunction. The cardio-renal inflammation and oxidative stress enhanced in the CMS increases the risk for cardiovascular disease (CVD) and renal disease end-points such as stroke, congestive heart failure, and chronic kidney disease (CKD). The development of proteinuria is known to herald progressive kidney disease (e.g. CKD) and both are now well accepted as CVD risk factors. Evidence suggests a role for visceral obesity, insulin resistance/hyperinsulinemia, HTN, and other components of the CMS lead to an increased risk for proteinuria and progressive loss of renal function. Intervention with agents that block the RAAS (e.g. ACE inhibitors and Angiotensin type 1 receptor blockers) have been shown to reduce proteinuria, CKD progression, and CVD events. Herein, we will examine the relationship between RAAS intervention and reductions in CKD and CVD events.
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PMID:Renin-angiotensin-aldosterone system intervention in the cardiometabolic syndrome and cardio-renal protection. 1912 93

Combination of drugs from different classes of antihypertensives provides an additional antihypertensive effect thus minimising the probability of adverse effects related to the dose of antihypertensive. Combination therapy is indicated for the following groups of hypertensive patients: (a) all hypertensive patients whose systolic blood pressure exceeds the target systolic blood pressure value by > 20 mm Hg, or whose diastolic blood pressure exceeds the target diastolic blood pressure value by > 10 mm Hg; (b) in patients with diabetes mellitus (because the target values are < 130/80 mm Hg); (c) patients with target organ damage; (d) patients with a kidney or cardiovascular disease (patients with IHD, patients after a cerebrovascular accident); (e) patients with overall cardiovascular risk according the SCORE > or = 5%. The advantage of fixed combinations resides in the fact that they increase compliance with treatment by reducing the number of pills taken by the patients. A fixed combination of the ACE inhibitor perindopril and the calcium channel blocker amlodipine proves optimal as has been shown by the results of the ASCOT-BPLA study. The launch of the above combination on this market should therefore be welcome. The fixed combination of perindopril and amlodipine will be indicated for hypertensive patients with uncontrolled hypertension or cardiovascular risk factors. This fixed combination will also be ideal for patients with a higher risk of diabetes mellitus, i.e. patients with a higher fasting glycaemia, in patients with impaired glucose tolerance and in patients with the metabolic syndrome. We strongly believe that it will improve the control of hypertension in our hypertensive patients, and improve the cardioprotective and nephroprotective effect of hypertension therapy.
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PMID:[The combination of an ACE inhibitor and a calcium channel blocker is an optimal combination for the treatment of hypertension]. 1934 94

Increasing lifespan and progressive aging of the Polish population results in rising demands on health care. Chronic diseases with a leading position of arterial hypertension (HA) prevail in morbidity rates of adult seniors. The aim of the study is to characterize hypertension in the elderly with regard to other risk factors, complications and therapeutic control. The study was carried out in 2002 within the framework of the CINDI WHO Programme. A total of 1460 persons were randomly selected among residents of Lodz aged > or = 65 years. The response rate was 57%. All participants underwent questionnaire interview, two blood pressure (BP) measurements, anthropometric and physical examination, ECG and laboratory tests. After final verification, we analysed data collected from 828 persons (289 men and 539 women). Mean values of systolic and diastolic BP were 147.6 and 83.6 mmHg, respectively. The increase of systolic BP with age of studied seniors was observed. Hypertension was diagnosed in 669 persons (79% men, 82% women). In most cases there were systolic-diastolic or isolated systolic hypertension. About 60% of seniors with elevated BP declared suffering from HA, while 73% were under antihypertensive treatment. Normalization of BP (< 140/ 90 mmHg) was achieved in 28% of treated patients. Most often prescribed medications were: ACE-inhibitors (51%), beta-blockers (40%), calcium channel blockers (31%) and diuretics (30%). Mean values of plasma lipids and prevalence of lipid disorders were comparable in hypertensive and normotensive persons. Among patients with HA there were significantly smaller percentage of smokers (8.6% vs 18.7%, p < 0.05). The prevalence of obesity, visceral obesity and metabolic syndrome was higher in hypertensive seniors. As a result, incidents of myocardial infarction and morbidity due to coronary artery disease were twice as cantly more often hospitalised and visited family doctors (7 vs 4.6 visits/year) in comparison to normotensive subjects.
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PMID:[Arterial hypertension as a medical and social problem in the older urban population. The CINDI WHO Program study]. 1944 75


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