Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is becoming a global epidemic in both children and adults, and it is associated with numerous co-morbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, is an independent risk factor for CVD and CVD risks have been also documented in obese children, and is associated with reduced life expectancy. A variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amount. As a whole, overweight/obesity predispose or is associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death through its impact on the cardiovascular system.
...
PMID:Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. 1662 22

The causal relationship between obesity and heart failure is broadly acknowledged; however, the pathophysiological mechanisms involved remain unclear. In this study we investigated whether human adipocytes secrete cardioactive substances that may affect cardiomyocyte contractility. We cultivated adipocytes obtained from human white adipose tissue and incubated isolated rat adult cardiomyocytes with adipocyte-conditioned or control medium. This is the first report to demonstrate that human adipocytes exhibit cardiodepressant activity with a direct and acute effect on cardiomyocyte contraction. This adipocyte-derived negative inotropic activity directly depresses shortening amplitude as well as intracellular systolic peak Ca2+ in cardiomyocytes within a few minutes. The adipocyte-derived cardiodepressant activity was dose-dependent and was completely blunted by heating or by trypsin digestion. Filtration of adipocyte-conditioned medium based on molecular mass characterized the cardiodepressant activity at between 10 and 30 kDa. In summary, adipose tissue exerts highly potent activity with an acute depressant effect directly on cardiomyocytes, which may well contribute to increased heart failure risk in overweight patients.
...
PMID:Human adipocytes attenuate cardiomyocyte contraction: characterization of an adipocyte-derived negative inotropic activity. 1687 88

Overweight (body mass index [BMI]=25-30 kg/m2) and obesity (BMI>30 kg/m2) have become mass phenomena with a pronounced upward trend in prevalence in most countries throughout the world and are associated with increased cardiovascular risk and poor survival. In patients with chronic kidney disease (CKD) undergoing maintenance hemodialysis an 'obesity paradox' has been consistently reported, i.e., a high BMI is incrementally associated with better survival. While this 'reverse epidemiology' of obesity is relatively consistent in maintenance hemodialysis patients, studies in peritoneal dialysis patients have yielded mixed results. A similar obesity paradox has been described in patients with chronic heart failure as well as in 20 million members of other distinct medically 'at risk' populations in the USA. Possible causes of the reverse epidemiology of obesity include: (1) time-discrepancies between the competing risks for the adverse events that are associated with overnutrition and undernutrition; (2) sequestration of uremic toxins in adipose tissue; (3) selection of a gene pool favorable to longer survival in dialysis patients during the course of CKD progression, which eliminates over 95% of the CKD population before they commence maintenance dialysis therapy; (4) a more stable hemodynamic status; (5) alterations in circulating cytokines; (6) unique neurohormonal constellations; (7) endotoxin-lipoprotein interactions; and (8) reverse causation. Examining the causes and consequences of the obesity paradox in dialysis patients can improve our understanding of similar paradoxes observed both for other conventional risk factors in chronic dialysis patients, such as blood pressure and serum cholesterol, and in other populations, such as patients with heart failure, cancer or AIDS or geriatric populations.
...
PMID:Obesity paradox in patients on maintenance dialysis. 1692 33

Although the adverse health consequences of obesity in the general population have been well documented, recent evidence suggests that obesity is associated with better outcomes in patients with heart failure (HF). Studies of patients with HF that specifically examined the impact of body mass index (BMI) on outcomes have suggested the existence of an "obesity paradox." However, closer examination of these studies raises important questions on the validity of the paradox. First, the diagnosis of HF in obese patients, particularly when made using clinical variables, may not be accurate; the obese patients in these studies may actually be "healthier" than their nonobese comparators. Second, the deleterious effects of cachexia, rather than the salutary ones of obesity, are likely the main reason for the inverse correlation between BMI and HF outcome, especially once the underlying biologic mechanisms behind cachexia and obesity in patients with HF are considered. Furthermore, few studies have specifically examined the more severely obese population (BMI >35 kg/m(2)) when assessing outcomes, and those that have suggest that severely obese patients may have worse outcomes than patients with normal weights or those who are mildly obese. Therefore, a "U-shaped" outcome curve according to BMI for patients with HF may actually exist, in which mortality is greatest in cachectic patients; lower in normal, overweight, and mildly obese patients; but higher again in more severely obese patients. Further prospective studies assessing the impact of more marked degrees of obesity on outcomes in patients with HF are needed to more conclusively determine whether the obesity paradox truly exists.
...
PMID:The obesity paradox: fact or fiction? 1699 80

We have demonstrated a potent and specific lipolytic effect of natriuretic peptides (NP) in human and primates' fat cells. The lipolytic effect of NP is mediated through intracellular production of cGMP and activation of the cGMP-dependent kinase 1alpha. Local infusion of atrial-NP (ANP), directly within the subcutaneous adipose tissue through a microdialysis catheter, increases lipolysis and stimulates blood flow through its vasodilating effect in lean healthy men. This effect is blunted in overweight men and can be recovered by endurance training. Intravenous infusion of physiological doses of ANP induces lipid mobilization. Higher concentrations of ANP that are encountered during heart failure also stimulate lipid oxidation. ANP activates lipolysis and free fatty acids release from adipose tissue during endurance exercise. This effect is paradoxically amplified when exercise is performed under beta-blockade treatment, because of an enhanced cardiac release of ANP. No gender differences in ANP-induced lipid mobilization during exercise have been found. Heart failure is associated with high circulating levels of NP that could participate to the progression toward cachexia. On contrary, a negative correlation between NP levels and body mass index is found in obese persons. The molecular basis of this inverse correlation is not yet demonstrated from a functional standpoint. Further studies are needed to clearly define the pathophysiological role of NP in obesity and heart failure.
...
PMID:[Physiological and pathophysiological features of the control of lipolysis and lipid mobilization by natriuretic peptides]. 1714 64

The TROPHY study was designed to show the feasibility of pharmacological prevention of hypertension with respect to the group of patients with "prehypertension" as defined by the JNC VII recommendations. This clinical trial compared candesartan 16 mg/day with placebo and the result at 4 years was a reduction in the relative risk of developing hypertension of 15.6%. The antihypertensive drug delayed the onset of hypertension in a mainly overweight masculine population. Staessen, Zhu and O'Brien's groups suggest measuring an index of arterial rigidity obtained from ambulatory blood pressure monitoring: the ambulatory arterial stiffness index (AASI). This is calculated as [1- slope of systolic/diastolic pressure]. The reference values for AASI vary with age from 0.50 to 0.70. The CAFE study, a spin-off of the ASCOT trial, showed that the central blood pressure decreased more than the peripheral blood pressure with the association amlodipine-perindopril as compared with atenolol and a thiazide diuretic. The capacity of an antihypertensive drug or an association of antihypertensives to decrease the central blood pressure could be a pertinent factor of evaluation to be taken into account in the interpretation of clinical trials. The study of the Italian cohort PAMELA showed a progressive increase in cardiovascular and global mortality with respect to the findings of increased blood pressure by one, two or three methods of measurement (at the office, at home, ambulatory) compared with patients declared normotensive by the same methods. This registry confirmed the implication of masked hypertension on cardiovascular prognosis and also showed that "white coat" hypertension was not completely benign. The "3 cities" study is a French epidemiological study of persons over 65 years of age. The control of the blood pressure of the treated elderly hypertensives was 57% in men and 70% in women when the cut-off was 160/95 mmHg and 31% for all patients in a cut-off level of 140/90 mmHg. Lafontan et al. are studying the mobilisation of fat induced by exercise, resistant to betablockers therapy and attributed to natriuretic peptides. This metabolic pathway could be of relevance in the metabolic syndrome and in cardiac failure. Renin inhibitors, such as aliskiren, are being developed. The outlook is the possible use of these drugs with ACE inhibitors or angiotensin II inhibitors, taking into account the risk/benefit ratio.
...
PMID:[The best of hypertension in 2006]. 1740 64

In myocardial ischaemia and heart failure, beta-blockers with intrinsic sympathomimetic activity (ISA) e.g. pindolol, xamoterol, bucindolol, nebivolol, have performed poorly in reducing morbidity and mortality. In both indications beta-1 blockade is the vital active ingredient. Beta-1 blockade (bisoprolol) is now an alternative first-line choice to Ace-inhibition in the treatment of heart failure. The therapeutic role of beta-blockers in hypertension is less well understood, particularly since the new recommendations in the UK from the NICE committee stating that: 1. beta-blockers are no longer preferred as a routine initial therapy, 2. the combination with diuretics is discouraged due to the risk of induced diabetes, and 3. in younger patients first-choice initial therapy should be an ACE-inhibitor. Recent data from the Framingham Heart Study and other epidemiological studies have indicated that the development of diastolic hypertension in younger subjects is closely linked to weight-increase and an increase in peripheral resistance; such subjects have a high adrenergic drive and cardiac output. In contrast, elderly systolic hypertension mostly arises de novo via poor vascular compliance. Thus in younger, probably overweight, hypertensives (including diabetics) first-line beta-blockade has performed well in preventing myocardial infarction (a fact hidden by meta-analyses that do not take age into account). Conversely, in elderly hypertensives first-line beta-blockade (atenolol) has performed poorly in reducing cardiovascular risk (due to partial beta-2 blockade atenolol evokes metabolic disturbance and does not improve vascular compliance, or effectively lower central aortic pressure or reverse left ventricular hypertrophy). Thus beta-blockers like atenolol are ill-equipped for first-line therapy in elderly hypertension. Some beta-blockers, e.g. bisoprolol (up to 10 mg/day is highly beta-1 selective) and nebivolol (beta-2/3 intrinsic sympathomimetic activity), do improve vascular compliance and cause no metabolic disturbance. Beta-blockers as second-line to low-dose diuretics (which, by improving vascular compliance and increasing sympathetic nerve activity, create an optimal environment for beta-blockade) in elderly hypertension (including diabetics) have performed well in reducing cardiovascular events (this combination has the added bonus of reducing the risk of bone fracture by about 30%). Meta-analyses which include studies where it is unclear whether a diuretic or beta-blocker was a first-line therapy will dilute the benefit stemming from first-line diuretic/second-line beta-blockade. Hypertensives (of all ages) with ischaemia are well suited to beta-blockade.
...
PMID:Are we misunderstanding beta-blockers. 1743 71

Increased body mass index (BMI), a parameter of total body fat content, is associated with an increased mortality in the general population. However, recent studies have shown a paradoxic relation between BMI and mortality in specific patient populations. This study investigated the association of BMI with long-term mortality in patients with known or suspected coronary artery disease. In a retrospective cohort study of 5,950 patients (mean age 61 +/- 13 years; 67% men), BMI, cardiovascular risk markers (age, gender, hypertension, diabetes, current smoking, angina pectoris, old myocardial infarction, heart failure, hypercholesterolemia, and previous coronary revascularization), and outcome were noted. The patient population was categorized as underweight, normal, overweight, and obese based on BMI according to the World Health Organization classification. Mean follow-up time was 6 +/- 2.6 years. Incidences of long-term mortality in underweight, normal, overweight, and obese were 39%, 35%, 24%, and 20%, respectively. In a multivariate analysis model, the hazard ratio (HR) for mortality in underweight patients was 2.4 (95% confidence interval [CI] 1.7 to 3.7). Overweight and obese patients had a significantly lower mortality than patients with a normal BMI (HR 0.65, 95% CI 0.6 to 0.7, for overweight; HR 0.61, 95% CI 0.5 to 0.7, for obese patients). In conclusion, BMI is inversely related to long-term mortality in patients with known or suspected coronary artery disease. A lower BMI was an independent predictor of long-term mortality, whereas an improved outcome was observed in overweight and obese patients.
...
PMID:Relation of body mass index to outcome in patients with known or suspected coronary artery disease. 1753 66

Over the past 20 years obesity has become a worldwide concern of frightening proportion. The World Health Organization estimates that there are over 400 million obese and over 1.6 billion overweight adults, a figure which is projected to almost double by 2015. This is not a disease restricted to adults - at least 20 million children under the age of 5 years were overweight in 2005 (WHO 2006). Overweight and obesity lead to serious health consequences including coronary artery disease, stroke, type-2 diabetes, heart failure, dyslipidemia, hypertension, reproductive and gastrointestinal cancers, gallstones, fatty liver disease, osteoarthritis and sleep apnea (Padwal et al 2003). Modest weight loss in the obese of between 5% and 10% of bodyweight is associated with improvements in cardiovascular risk profiles and reduced incidence of type 2 diabetes (Goldstein 1992; Avenell et al 2004; Padwal and Majumdar 2007). Orlistat, a gastric and pancreatic lipase inhibitor that reduces dietary fat absorption by approximately 30%, has been approved for use for around ten years (Zhi et al 1994; Hauptman 2000). There is now a growing body of evidence to suggest that Orlistat assists weight loss and that it may also have additional benefits. The aim of this review is to provide a brief update on the current literature studying the efficacy, safety and significance of the use of Orlistat in clinical practice.
...
PMID:Obesity management: update on orlistat. 1820 Aug 2

There does not appear to be a relationship between peak oxygen consumption (VO(2)) and body mass index (BMI) in patients with heart failure (HF). We assessed the hypothesis that BMI and the oxygen uptake efficiency slope (OUES) would be related. Three hundred and thirty-seven HF patients (280 male/57 female, mean age: 56.5+/-14.1 years, resting left ventricular ejection fraction: 35.1+/-14.2%, BMI: 29.3+/-6.2 kg/m(2)) underwent cardiopulmonary exercise testing where peak VO(2) and the OUES (VO(2)=a log(10)VE+b, units: L/min) were determined. Pearson product moment correlation analysis revealed that the correlation between BMI and the OUES was significant (r=0.32, p<0.001). Furthermore, the OUES was prognostically significant in normal weight (optimal threshold: <or=/>1.2, hazard ratio: 3.7, 95% confidence interval: 1.4-9.9, p=0.01), overweight (optimal threshold: <or=/>1.5, hazard ratio: 3.9, 95% confidence interval: 1.3-11.1, p=0.01) and obese (optimal threshold: <or=/>1.7, hazard ratio: 4.1, 95% confidence interval: 1.4-12.8, p=0.01) subgroups. The OUES appears to improve with body weight in patients with HF. Furthermore, the OUES appears to be a significant prognostic marker irrespective of BMI although the optimal threshold value may differ according to body weight.
...
PMID:The influence of body mass index on the oxygen uptake efficiency slope in patients with heart failure. 1823 69


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

---