Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article summarizes an important study published in 2006 in the field of the prevention of diabetes mellitus. It is the DREAM study which evaluate the therapeutic effects of rosiglitazone and ramipril versus placebo in the prevention of type 2 diabetes in high risk patients: glucose intolerance or impaired fasting glucose. In this clinical study, more than 5000 patients were followed during 3 years. The risk of diabetes was reduced with rosiglitazone of 62% (NNT 9). In the field of negative effects the risk of cardiac insufficiency was multiplied by 7 (NNH 250) but stayed a rare event (to 0,5% of the treated subjects). The ramipril had no preventive effect for the prevention of type 2 diabetes but induced a higher frequency of return towards the normoglycaemia. This treatment can be recommended for these high risk subjects.
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PMID:[The DREAM of diabetes prevention]. 1735 38

The prevalence of heart failure and diabetes are both increasing: 25 to 30% of patients with heart failure suffer from diabetes, and the latter aggravates heart failure. The presence of macro- or micro-angiopathy, cardiac neuropathy or renal failure worsens the clinical pattern and disturbs treatment strategies. Doppler-echocardiography and the dosage of BNP can probably help to detect and consequently to treat prematurely heart failure in the diabetic patient. The usual treatments in heart failure have similar or lower efficacy in the diabetic patient, and treatment intolerance is frequent. Treatments used for diabetes can be handled with difficulty in case of heart failure (metformin, glitazones). In the future, it is therefore extremely important: 1--to prevent the occurrence of diabetes in patients with glucose intolerance; 2--in diabetic patients, to prematurely detect cardiac dysfunction and optimally control diabetes, in order to avoid its occurrence; 3--and finally, in diabetic patients with heart failure, to optimize the medical treatment, in order that these patients have similar benefits compared to non-diabetic patients with heart failure. The ACE-inhibitors and angiotensin-2 antagonists seem to have an important role. Treatments breaking the glycation bridges, as well as statins, appear as interesting therapeutic options. Finally, the exact role of myocardial revascularization, either by angioplasty or surgery, might probably be important.
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PMID:[Diabetes and heart failure, a fatal association]. 1789 36

Cachexia is a complex syndrome. The main components of this pathological state are anorexia and metabolic abnormalities, such as glucose intolerance, fat depletion and muscle protein catabolism among others. The aim of the present article is to review the recent therapeutic approaches that have been designed to fight and counteract muscle wasting in different pathological states such as cancer, AIDS and chronic heart failure.
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PMID:Novel approaches to the treatment of cachexia. 1819 Aug 67

The clinical use of HIV protease inhibitors is associated with insulin resistance and other metabolic changes that increase long-term cardiovascular risk. Since the failing heart has increased reliance on glucose, the influence of drug exposure on glucose homeostasis, myocardial glucose uptake, cardiac function, and survival was determined in TG9 mice, an established transgenic model of dilated cardiomyopathy generated by cardiac-specific overexpression of Cre-recombinase, as these animals progressed to overt heart failure. Beginning on day of life 75, TG9 mice and nontransgenic littermate controls were given a daily 10 mg/kg intraperitoneal injection of HIV protease inhibitors (ritonavir, lopinavir/ritonavir 4:1, atazanavir, atazanavir/ritonavir 4:1) or vehicle. Glucose tolerance testing, measurement of in vivo myocardial 2-deoxyglucose uptake, and echocardiography were performed before and 30 min following drug administration. The progression of dilated cardiomyopathy in TG9 animals was accompanied by impaired glucose tolerance, which was acutely exacerbated by exposure to ritonavir. Ritonavir and lopinavir precipitated acute, decompensated heart failure and death from pulmonary edema in TG9 mice. However, atazanavir, which does not inhibit glucose transport, had no effect. These studies demonstrate that, in the presence of dilated cardiomyopathy, HIV protease inhibitors that impair glucose transport induce acute, decompensated heart failure. The potential for HIV protease inhibitors to contribute to or exacerbate cardiomyopathy in human patients warrants further investigation.
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PMID:HIV protease inhibitors that block GLUT4 precipitate acute, decompensated heart failure in a mouse model of dilated cardiomyopathy. 1825 5

Urotensin II (UTII) is recently discovered neurohumoral factor influencing function and structure of the myocardium and remodeling of the vessels, and it may contribute to pathogenesis of chronic congestive heart failure. The aim of the study was estimation of plasma concentration of UTII in patients with chronic congestive heart failure. The investigations were performed on 79 patients (37 women and 42 men) aged 43-87 yr. (mean 69.2 +/- 9.8 yr.) and 15 healthy individuals. In all patients, echocardiographic examination of the left ventricle structure and function was performed and serum concentration of electrolytes and creatinine were measured. Plasma levels of UTII were determined before treatment and after 1 week, 2 and 4 weeks of treatment using RIA Peninsula Lab. Inc. Plasma level of UTII in patients suffering from chronic congestive heart failure was significantly lower than in healthy individuals before the treatment and after achieving compensation of the circulatory system using standard treatment, independently from sex, kind of heart failure (systolic-diastolic or diastolic) or coexistence arterial hypertension or pulmonary hypertension, ischemic heart disease or diabetes and impaired glucose tolerance. Treatment of chronic congestive heart failure resulted in a transient increase in UTII concentration except for patients with diastolic heart failure or diabetes. Only patients without ischemic heart disease have a permanent increase in UTII concentration at the time of the treatment. After achieving compensation of the circulatory system in the patients suffering from systolic-diastolic heart failure, UTII concentration was significantly lower than in the patients suffering from diastolic heart failure, in the patients suffering from ischemic heart disease significantly lower than in patients without ischemic heart disease, in the patients with arterial hypertension significantly higher than in those with normal arterial tension, in group of the patients with pulmonary hypertension lower than in group of the patients without pulmonary hypertension and significantly higher in group of the patients suffering from diabetes or impaired glucose tolerance than in group of the patients without this metabolic disorders.
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PMID:[Plasma urotensin II level in patients with chronic congestive heart failure]. 1863 21

Patients with type 2 diabetes mellitus (T2DM) have a 2-fold to 4-fold greater risk of cardiovascular mortality than nondiabetic individuals. The overall mortality rate of patients with T2DM is approximately twice that of people without diabetes. The excess in-hospital mortality of these patients is primarily due to an increased risk of congestive heart failure. Reduced compensatory ability of the noninfarcted myocardium and an underlying abnormality in the myocardial substrate metabolism (referable to the diabetic state) may also contribute to poor outcomes. Insulin resistance (IR) is a significant predictor of cardiovascular mortality and morbidity across a spectrum of glucose tolerance. Cardiac mass increases across the range of IR in subjects without diabetes, as well as across the range of glucose intolerance in subjects with diabetes. In one study, elevated fasting plasma glucose was an independent predictor of hospitalization for heart failure. Optimization of cardiac metabolism could become a new target for therapeutic intervention in patients with ischemic heart disease and diabetes.
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PMID:Myocardial glucose transport and utilization: a target for therapeutic intervention. 1866 Jul 31

Until recently, humans consumed a diet high in potassium. However, with the increasing consumption of processed food, which has potassium removed, combined with a reduction in the consumption of fruits and vegetables, there has been a large decrease in potassium intake which now, in most developed countries, averages around 70 mmol day-1, i.e. only one third of our evolutionary intake. Much evidence shows that increasing potassium intake has beneficial effects on human health. Epidemiological and clinical studies show that a high-potassium diet lowers blood pressure in individuals with both raised blood pressure and average population blood pressure. Prospective cohort studies and outcome trials show that increasing potassium intake reduces cardiovascular disease mortality. This is mainly attributable to the blood pressure-lowering effect and may also be partially because of the direct effects of potassium on the cardiovascular system. A high-potassium diet may also prevent or at least slow the progression of renal disease. An increased potassium intake lowers urinary calcium excretion and plays an important role in the management of hypercalciuria and kidney stones and is likely to decrease the risk of osteoporosis. Low serum potassium is strongly related to glucose intolerance, and increasing potassium intake may prevent the development of diabetes that occurs with prolonged treatment with thiazide diuretics. Reduced serum potassium increases the risk of lethal ventricular arrhythmias in patients with ischaemic heart disease, heart failure and left ventricular hypertrophy, and increasing potassium intake may prevent this. The best way to increase potassium intake is to increase the consumption of fruits and vegetables.
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PMID:Beneficial effects of potassium on human health. 1872 13

Patients with impaired glucose tolerance (IGT) have increased risk for developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Lifestyle modification and medication can prevent or delay progression to diabetes (PD), but whether such interventions also reduce the risk of CVD has not been rigorously tested. The Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is a multinational, randomized, double-blind, 2 x 2 factorial trial in subjects with IGT (on a screening oral glucose tolerance test [OGTT]) aged > or = 50 years with known CVD or aged > or = 55 years with > or = 1 CVD risk factor. Enrollment began in January 2002 and was completed January 2004, with 9,518 patients randomized to receive 1 of 4 possible treatment combinations as follows: nateglinide with valsartan, nateglinide with valsartan-placebo, nateglinide-placebo with valsartan, or nateglinide-placebo with valsartan-placebo. All subjects are participating in a clinic-based and telephone-based lifestyle intervention aimed at reducing weight and dietary fat and increasing physical activity. The 3 coprimary end points are new onset of T2DM, a "core" composite of major cardiovascular events (death, myocardial infarction, stroke, or hospitalization for heart failure), and an "extended" composite including the components of the core composite plus coronary revascularization and hospitalization for unstable angina. The study was designed to evaluate whether reducing postprandial hyperglycemia, blockade of the renin-angiotensin-aldosterone system, or both interventions reduce the risk of T2DM or cardiovascular events in patients with IGT.
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PMID:Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial. 1894 90

The intracellular signaling mechanisms underlying the pathogenesis of cardiac diseases are not fully understood. We report here that selective deletion of Shp2, an SH2-containing cytoplasmic tyrosine phosphatase, in striated muscle results in severe dilated cardiomyopathy in mice, leading to heart failure and premature mortality. Development of cardiomyopathy in this mouse model is coupled with insulin resistance, glucose intolerance, and impaired glucose uptake in striated muscle cells. Shp2 deficiency leads to upregulation of leukemia inhibitory factor-stimulated phosphatidylinositol 3-kinase/Akt, Erk5, and Stat3 pathways in cardiomyocytes. Insulin resistance and impaired glucose uptake in Shp2-deficient mice are at least in part due to impaired protein kinase C-zeta/lambda and AMP-kinase activities in striated muscle. Thus, we have generated a mouse line modeling human patients suffering from cardiomyopathy and insulin resistance. This study reinforces a concept that a compound disease with multiple cardiovascular and metabolic disturbances can be caused by a defect in a single molecule such as Shp2, which modulates multiple signaling pathways initiated by cytokines and hormones.
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PMID:Deletion of Shp2 tyrosine phosphatase in muscle leads to dilated cardiomyopathy, insulin resistance, and premature death. 1900 Oct 90

Progressive ventricular hypertrophy can lead to the development of insulin resistance, a feature of both chronic kidney disease and heart failure. Here we induced uremia in adult male Sprague-Dawley rats using a remnant kidney model and studied the expression of glucose transporters. As expected, the reduction of nephron mass resulted in impaired renal function, cardiac hypertrophy, glucose intolerance, hyperinsulinemia, anemia, and hypertension. Insulin sensitivity was significantly reduced in the uremic animals as determined by oral glucose tolerance tests. After six weeks of uremia, at a point when cardiac hypertrophy had been established, left ventricle tissue had a marked increase in the expression of GLUT4 (insulin-dependent glucose transporter 4), consistent with hypertrophic remodeling, but not GLUT1 (insulin-independent glucose transporter 1). However, although uremic animals had systemic insulin resistance and glucose intolerance, there was no evidence of impaired GLUT4 translocation in the heart at 6 weeks of uremia, suggesting that other mechanisms may underpin insulin resistance in the uremic heart.
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PMID:Insulin resistance and altered glucose transporter 4 expression in experimental uremia. 1917 56


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