Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate the contribution of candidate genes in the renin-angiotensin-aldosterone system (RAAS) in pathogenesis of essential arterial hypertension (EAH), the I/D polymorphism of ACE gene, the M235T polymorphism of the angiotensinogen gene, and the angiotensin II type 1 receptor (AGT,R) A1166C gene polymorphism in a group of children with EAH were analyzed. Fifty-scven children, aged 8-19 years. with the diagnosis of EAH were included in the association study and were compared with 57 subjects with normal blood pressure (the control group). Arterial hypertension was defined as systolic/diastolic blood pressure measurements higher than 95 age-gender-height percentile of the adopted reference values. A trend was found towards an association between the M235T angiotensinogen gene polymorphism and EAH in childhood in a dominant model (odds ratio (OR) 2.1; 95% confidence interval (CI) 0.9-5.1; P = 0.077), whereas the authors failed to demonstrate an association between the ACE I/D gene polymorphism, or the A1166C AGT1R gene polymorphism and EAH in childhood. Additionally, evidence was found of interaction between the angiotensinogen-TT genotype and obesity on the risk of EAH in childhood (OR 19.3; 95% CI 1.1-77.3; P = 0.014). In conclusion, the M235T angiotensinogen gene polymorphism is considered alone as well as in interaction with obesity to be risk factors for EAH in childhood.
 ...
PMID:Gene polymorphisms of the renin-angiotensin-aldosterone system and essential arterial hypertension in childhood. 1259 35

From 1989 to 1999, the incidence of cardiac failure appears stable but its prevalence has increased up to three folds. Obesity increases the risk of development of cardiac failure. In genetics, mutations in some proteins of muscular cells may lead to the occurrence of dilated cardiomyopathy. The interest of Brain Natriuretic Peptid was confirmed in case of acute dyspnea or diastolic dysfunction as well as its prognostic role in the functional capacity and the occurrence of sudden death. In the therapeutic field, a great disappointment came from the results of studies on omapatrilat. Despite its advantageous hemodynamic effects, this drug is not more efficacious than any ACE-inhibitor, but with much more side effects. New drugs (levosimendan, nesiritide) appear interesting in the acute heart failure. The short-term as well as long-term effects of cardiac resynchronization are confirmed. Implantable cardioverting defibrillators decrease the mortality of patients with a past history of myocardial infarction with severe left ventricle dysfunction. The artificial heart Jarvik 2000 appears to be hopeful for patients on waiting lists for heart transplantation.
 ...
PMID:[The best of cardiac failure in 2002]. 1261 58

Type 2 diabetes is becoming very common and is closely linked to physical inactivity and obesity. It is associated with clustering of coronary risk factors and 60-80% of cases have hypertension. The first therapeutic action is appropriate adjustment of life style. Anti-hypertensive therapies such as diuretics, ACE inhibitors and calcium antagonists have been effective in reducing cardiovascular events in type 2 diabetes, though calcium antagonists may be less effective than older therapies and ACE-inhibitors in reducing the risk of heart attacks and heart failure (but possibly more effective in stroke reduction). Beta-blockers (BBs) have a poor image as a potential therapy due to apparent adverse effects on surrogate end-points such as insulin-resistance. However large, controlled trials have shown BBs to be highly effective in reducing the risk of cardiovascular events and death in post myocardial infarction patients with diabetes. The UKPDS study in type 2 diabetics with hypertension showed first-line beta-blockade to be at least as effective as ACE-inhibition in preventing all primary macrovascular and microvascular end-points. The active ingredient appears to be beta-1 blockade, acting not only to lower blood pressure but also to prevent sudden death and cardiovascular damage stemming from chronic beta-1 stimulation associated with raised noradrenaline activity. By contrast, in the LIFE study atenolol was less effective than the angiotensin receptor antagonist losartan in reducing cardiovascular events and all-cause mortality in mainly elderly hypertensives with diabetes. Thus the best beta-blocker results in reducing hard cardiovascular end-points occur in hypertension studies (including the UKPDS study) involving younger/middle aged (say less than 60-65 years) patients, with relatively high sympathetic activity, relatively compliant/elastic arteries (narrow pulse-pressure) and normally functioning beta-1 receptors. In elderly hypertensive patients beta-blockers may be given as second-line therapy on the back of a low-dose diuretic (but possibly as first line agent in elderly hypertensives with prior myocardial infarction). Thus inappropriate attention to surrogate end-points can lead to faulty prescribing habits. Beta-blockers, currently severely underprescribed, should be considered as a first line therapeutic option for all diabetics with ischaemic heart disease or younger/middle aged diabetics with hypertension (but co-prescribed with low dose diuretic therapy in the elderly). The active ingredient for cardiovascular protection appears to be beta-1 blockade; optimal efficacy in lowering blood pressure and safety e.g. reducing risk of bronchoconstriction, is achieved by choosing an agent with high beta-1 selectivity.
 ...
PMID:Beta-blockers and diabetes: the bad guys come good. 1265 16

From March to July 1999, 940 private cardiologists in France recruited 100,429 patients of whom 30,430 (30%) had a previous history of atherothrombotic disease. The prevalence of patients with a previous history of Myocardial Infarction (MI), Ischemic Stroke (IS) or Peripheral Arterial Disease (PAD) was 19.7%, 7.2% and 10.7% respectively. Among patients with a history of atherothrombotic disease, myocardial infarction was the most frequent diagnosis responsible for 65% of all consultations. Each cardiologist described the secondary prevention treatment for 3 consecutive patients among whom 1 corresponded to each of the 3 atherothrombotic territories. The most frequent cardiovascular risk factors were hypercholesterolemia for myocardial infarction (77.9%), smoking for PAD (32.5%) and hypertension for IS (73.2%). Diabetes mellitus (1/4 patients), obesity (1/3) and sedentary way of life (1/3) were equally prevalent for each of the atherothrombotic territories. More than 90% of the patients received an antithrombotic drug. Antiplatelet agents were largely prescribed, anticoagulants being more frequently used for patients with atrial fibrillation, symptomatic cardiac heart failure or stroke of embolic origin. Thienopyridines represent 17.9% of the prescriptions. The prescription rate of statins after MI (58.9%) is lower than in published studies in secondary prevention. The lack of lipid measurement and the delay since last measurement are non-prescription factors. The rates of prescription are even lower in case of PAD (44.6%) or IS history (33.3%). More than half of the patients (56.6%) are treated with beta-blockers and 40.1% with ACE inhibitors. These rates are similar to what has been published. Atherothrombotic disease represents a large part of the daily activity of private cardiologists and is not limited to coronary heart disease. Despite their proven efficacy, drugs for secondary prevention for MI, except antithrombotic drugs, are insufficiently prescribed. This under-prescription is even higher in patients with PAD or IS history and may be related to the lack of clinical trials in these specific territories.
 ...
PMID:[Factors influencing secondary prevention of atherothrombotic disease in the private outpatient cardiology setting: results of the Prisma survey]. 1271 Feb 91

PDH (pyruvate dehydrogenase) is a key enzyme controlling the rate of glucose oxidation, and the availability of gluconeogenic precursors. Activation of PDH in skeletal muscle and liver may increase glucose uptake and reduce glucose production. This study describes the properties of AZD7545, a novel, small-molecule inhibitor of PDHK (PDH kinase). In the presence of PDHK2, AZD7545 increased PDH activity with an EC(50) value of 5.2 nM. In rat hepatocytes, the rate of pyruvate oxidation was stimulated 2-fold (EC(50) 105 nM). A single dose of AZD7545 to Wistar rats increased the proportion of liver PDH in its active, dephosphorylated form in a dose-related manner from 24.7 to 70.3% at 30 mg/kg; and in skeletal muscle from 21.1 to 53.3%. A single dose of 10 mg/kg also significantly elevated muscle PDH activity in obese Zucker (fa/fa) rats. Obese, insulin-resistant, Zucker rats show elevated postprandial glucose levels compared with their lean counterparts (8.7 versus 6.1 mM at 12 weeks old). AZD7545 (10 mg/kg) twice daily for 7 days markedly improved the 24-h glucose profile, by eliminating the postprandial elevation in blood glucose. These results suggest that PDHK inhibitors may be beneficial agents for improving glucose control in the treatment of type 2 diabetes.
 ...
PMID:AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates pyruvate dehydrogenase in vivo and improves blood glucose control in obese (fa/fa) Zucker rats. 1464 Oct 18

BACKGROUND AND THERAPY: The metabolic syndrome comprises a virulent and lethal group of atherosclerotic risk factors, including dyslipidemia, obesity, systemic hypertension and insulin resistance. The prevalence of the metabolic syndrome has continuously grown in industrialized and developing countries during the last decades, and affects tens of millions of people in Germany and Europe. Particularly prominent as a risk factor for the development of insulin resistance is central obesity, which is causally involved in the pathogenesis of insulin resistance in addition to genetic predisposition. The metabolic syndrome can easily be diagnosed in clinical practice (guidelines of the WHO and ATP III panel), and immediate treatment of the metabolic syndrome is mandatory because those patients are at increased risk to develop overt diabetes mellitus, coronary artery disease and stroke. The high risk for cardiovascular diseases is supported by findings that the risk for myocardial infarction in patients with insulin resistance is as high as the risk of patients after their first myocardial infarction. Intentional weight reduction reduces abdominal obesity and beneficially modulates all features of the metabolic syndrome, while the benefits of aerobic exercise training are discussed controversially. Thus, weight reduction causally undoes essential features of the metabolic syndrome, but effects are often not enduring. Therefore, the treatment of cardiovascular risk factors such as hypertension and dislipidemia is essential. Of note, antihypertensive treatment is more effective than tight glucose control to reduce cardiovascular events. Diuretics, ACE-inhibitors and angiotensin II type 1 receptor antagonists are suggested as first line therapeutics. However, at least two antihypertensives are usually necessary to achieve the suggested goals of blood pressure reduction. In conclusion, the prevalence of the metabolic syndrome is continuously growing. Due to its adverse impact on cardiovascular disease, early detection and aggressive treatment is mandatory to ensure longlasting benefits for affected patients.
 ...
PMID:[Arterial hypertension and metabolic syndrome]. 1468 1

The insulin resistance syndrome represents the co-occurrence of hyperglycaemia, hypertension, central and overall obesity, and dyslipidaemia characterised by low high density lipoprotein-cholesterol (HDL-C) and high triglyceride levels. Epidemiologic studies have revealed an increasing prevalence of the insulin resistance syndrome in elderly populations. Indeed, recent data indicate that over 40% of US adults aged > or =60 years meet current criteria for the insulin resistance syndrome. Patients with this syndrome are at increased risk for the development of both cardiovascular disease (CVD) and type 2 diabetes mellitus, two of the most significant health problems among people >65 years of age. Identification and treatment of the insulin resistance syndrome may thus represent an important approach to reducing the overall burden of morbidity and mortality in the elderly. While development of the insulin resistance syndrome is partly determined by modifiable environmental factors, there may be a genetic basis for the syndrome, with high levels of concordance among monozygotic twins. Ongoing research focusing on the pathophysiology of this syndrome has implicated insulin resistance as the central disorder underlying both the development of diabetes as well as the pro-thrombotic endothelial dysfunction characteristic of CVD. Studies aimed at reversing insulin resistance have identified weight loss, exercise and pharmacological treatment with metformin, thiazolidinediones, HMG-CoA reductase inhibitors (statins) and ACE inhibitors as potential therapies to prevent the development of type 2 diabetes. However, although insulin sensitisation may be beneficial for preventing type 2 diabetes, there are no data yet available to show whether this strategy will reduce the incidence of CVD. Increased exercise and other healthy lifestyle changes form the cornerstone of therapy for elderly patients with the insulin resistance syndrome. In addition, active identification and aggressive management of traditional cardiovascular risk factors are the current standard of care. For elderly patients, recent studies have conclusively demonstrated the safety and efficacy of pharmacological management of elevated blood pressure and cholesterol levels.
 ...
PMID:Should the insulin resistance syndrome be treated in the elderly? 1497 33

The association between erectile dysfunction (ED) and acute myocardial infarction (AMI) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, HIPAA-compliant database and includes complete medical history for more than 17 million managed care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 12,825 ED patients and an equal number of male patients without ED were included in the retrospective cohort study. Logistic regression analyses were performed to assess the adjusted risk of AMI that accounted for age at ED diagnosis, smoking, obesity and medications including ACE inhibitors, beta blockers and statins. The cohort of men with ED were observed to have a two-fold increase in the risk for AMI (OR=1.99, 95% CI=1.17, 3.38) after adjusting for age at ED diagnosis, smoking, obesity, and use of ACE inhibitors, beta blockers and statins. Some evidence of a possible trend toward increased risk was detected by age group. After controlling for the aforementioned covariates and compared to men 30-39 y of age, it was noted that patients 40-44 y of age were 3.8 times more likely to develop an AMI (OR=3.76, 95% CI=1.21, 11.7), 45- to 49-y-old men were also more than three times as likely to have an AMI (OR=3.14, 95% CI=1.03, 9.64), and 50- to 55-y-old patients had a four-fold increased risk of developing AMI (OR=4.04, 95% CI=1.39, 11.7). The risk becomes more pronounced with increasing age, indicating the need for cardiologists and internists to monitor ED patients who may not necessarily present with cardiovascular symptoms.
 ...
PMID:Should erectile dysfunction be considered as a marker for acute myocardial infarction? Results from a retrospective cohort study. 1498 80

The association between erectile dysfunction (ED) and peripheral vascular disease (PVD) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, Health Insurance Portability and Accountability Act compliant database and includes complete medical histories for more than 17 million managed-care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 12 825 ED patients and an equal number of male patients without ED were included in the retrospective cohort study. Logistic regression analyses were performed to assess the adjusted risk of PVD that accounted for age at ED diagnosis, smoking, obesity and medications including angiotensin converting enzyme (ACE) inhibitors, beta blockers and statins. The cohort of men with ED were observed to have a 75% increase in risk for PVD (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.06, 2.90) after adjusting for age at ED diagnosis, smoking, obesity and use of ACE inhibitors, beta blockers and statins. Some evidence of a possible trend towards increased risk was detected by age group. After controlling for the aforementioned covariates and compared to men aged 30-39 years, it was noted that patients aged 40-44 years were 2.1 times more likely to develop PVD (OR = 2.07, 95% CI = 0.89, 4.81), 45-49-year-old men were also more than twice as likely to have PVD (OR = 2.32, 95% CI = 1.03, 5.22), and 50-55-year-old patients had a three-fold increased risk of developing PVD (OR = 3.00, 95% CI = 1.40, 6.43). The results of this study indicate that ED may serve as a marker for PVD. The risk becomes more pronounced with increasing age, indicating the need for cardiologists and internists to monitor ED patients who may not necessarily present with cardiovascular symptoms.
 ...
PMID:Is erectile dysfunction predictive of peripheral vascular disease? 1500 59

The management of hypertension in the overweight and obese patient is a frequently encountered but under investigated clinical problem. The conventional management of such patients involves weight reduction with dietary therapy or a combined approach with dietary and anti-obesity drug therapy. However, long-term weight reduction, which is necessary to sustain blood pressure (BP) control, is not feasible in over 80% of patients. Anti-obesity therapy with orlistat has inconsistent effects on BP and may benefit only patients who have uncontrolled or non-medicated hypertension. Anti-obesity therapy with sibutramine may be associated with a modest worsening of BP control. Consequently, antihypertensive drug therapy is often required to supplement a weight reduction programme, and also in patients with severe hypertension or hypertension-associated end-organ damage. Treatment with a thiazide diuretic should be considered as first-line antihypertensive drug therapy in overweight and obese patients. ACE inhibitors or non-dihydropyridine calcium channel antagonists are reasonable alternatives where clinically indicated, or they can be used in combination with a thiazide diuretic if treatment with the diuretic alone is insufficient. If such treatment is inadequate for BP control, the addition or substitution of an alpha- or beta-adrenoceptor antagonist may be considered, although the latter can be associated with weight gain. Concurrent disease is an important determinant of first-line and supplementary antihypertensive drug therapy. Additional studies are needed to determine the long-term (>1 year) efficacy and safety of antihypertensive and anti-obesity management strategies in the overweight and obese hypertensive patient.
 ...
PMID:The management of hypertension in the overweight and obese patient: is weight reduction sufficient? 1516 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>