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

Hypertension is common and increases the risk of death from coronary artery disease and cerebral vascular disease. The reason for treating hypertension is to prevent the long-term complications of this disorder. Many studies of antihypertensive therapy have produced only modest reductions in coronary events; in particular, with the use of beta-blockers. Clinical trials and meta-analyses have shown a lesser effect of these drugs on primary prevention of coronary events, cardiovascular and total mortality with respect to other antihypertensive approaches based on the use of low-dose diuretic therapy, especially in the elderly, even if the reduction of stroke and heart failure (HF) were similar. New beta-blockers with vasodilating properties due to the capacity to enhance the release of endothelial nitric oxide, then lessening a contributory mechanism to the pathogenesis of atherosclerosis as endothelial damage and dysfunction, seem to possess considerable potential in the treatment of hypertension, particularly in terms of improvement of cardiovascular outcome of patients. In HF, there is now considerable interest in the therapeutic use of beta-blockade. Some recent clinical trials have demonstrated conclusive evidence of the beneficial effects of beta-blocker therapy on survival in chronic HF. As a result of these data, beta-blocker therapy has become part of standard therapy for patients with chronic HF, in addition to angiotensin-converting enzyme-inhibitors and diuretics. The treatment is, in general, well tolerated. There are, however, some unanswered questions. One is whether some beta-blockers may be better than others. The major mortality benefit is probably a class-effect of beta1-adrenoceptor blockade, but the differences between beta-blockers might be clinically relevant. For example, it is under debate whether ancillary properties of some beta-blockers, such as the capability of exerting antioxidant effects or enhancing the nitric oxide production, may contribute to the clinical effects of these drugs. Future clinical trials will report over the next few years and help to answer the question about differences in mortality effects among types of beta-blocking agents, thus correctly defining the precise role of these drugs in the wide spectrum of cardiovascular disease.
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PMID:Beta-blockade in hypertension and congestive heart failure. 1181 89

The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial is a large clinical trial of omapatrilat, a vasopeptidase inhibitor, in patients with stage 1 isolated systolic hypertension (ISH). OPERA is the first study to examine whether effective antihypertensive treatment can provide survival and clinical end point benefits in older persons with this common condition. This 5-year multinational, randomized, double-blind, parallel-group, placebo-controlled, forced-titration study will be conducted in approximately 12,600 subjects randomized by approximately 1100 study centers worldwide over a recruitment period of approximately 2 years. The primary objective of OPERA is to determine whether treatment with once-daily omapatrilat (target dose 40 mg) will reduce cardiovascular (CV) morbidity and mortality in older (> or = 65 years) men and women with enhanced risk for atherosclerotic events due to stage 1 ISH plus other risk factors for which currently there is no evidence-based requirement for treatment. Blood pressure inclusion criteria are systolic blood pressure (SBP) 140 to 159 mm Hg (SBP 125 to 139 mm Hg in diabetic individuals) and diastolic blood pressure (DBP) <90 mm Hg. The primary end point is defined as the composite of fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, fatal/nonfatal heart failure, and other CV mortality. Secondary end points include the individual components of the primary end point, CV mortality, and major cardiovascular end points, as well as effects on cognitive function and initiation of treatment for diabetes. Additional analyses will be conducted in men and women, in diabetic patients, in different risk classes and according to prior evidence of vascular disease.
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PMID:Design of the Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial. 1186 57

The Heart Outcomes Prevention Evaluation (HOPE) study was designed to test the hypotheses that two preventive intervention strategies, namely angiotensin-converting enzyme (ACE) inhibition or vitamin E, would improve morbidity and mortality in patients at high risk of cardiovascular events compared with placebo. This review addresses the ACE inhibitor (ACE-I) (ramipril) arm of the study, both on the trial population as a whole, and on the large diabetic subgroup. Patients were included in the study who were considered to be at high risk of future fatal or non-fatal cardiovascular events, by virtue of their age (>55 years), existing or previous cardiovascular disease, or diabetes. Diabetics had at least one other risk factor, either known vascular disease or other factors such as cigarette smoking, high cholesterol or hypertension. Ramipril or placebo was added to concomitant medication, which included, in a substantial proportion of patients, antihypertensive drugs (excluding ACE-I), lipid-lowering agents or aspirin. As a result, despite a history of hypertension in nearly 50% of patients, blood pressure (BP) at baseline was normal and the reduction in BP attributable to ramipril modest (a fall of 3-4 mmHg systolic BP and 1-2 mmHg diastolic). The trial was stopped early on the advice of the Data Monitoring Committee because of convincing evidence of the benefit of ramipril treatment on the combined primary endpoint of cardiovascular death, non-fatal myocardial infarct (MI) and non-fatal stroke (14% vs. 17.8% on ramipril and placebo, respectively; relative risk reduction 22%, p<0.001). This comprised a risk reduction of 32% for stroke, 20% for MI, 26% for cardiovascular death and 16% for all-cause mortality, as well as a reduction in the risk of several other endpoints including heart failure and revascularisation procedures. The results among the 3577 diabetic subjects were even more striking, with a reduction of 25% in the combined primary endpoint. This reduction in the combined endpoint and in particular the reduction in MI far exceeded that which would be expected from the modest fall in BP. Furthermore, a multiple regression analysis of the diabetic subgroup showed similar relative risk reductions even after allowing for the effects of the fall in BP. Possible explanations for the non BP-mediated benefits of ramipril include reduction of angiotensin II-induced intimal and vascular smooth muscle proliferation and possible plaque stabilisation. The HOPE study results show that it is both safe and beneficial to lower BP that is already within the 'normal' range, particularly in patients with known vascular risk factors. This should greatly extend the use of ACE-I to a wider group of patients - not only those with left ventricular dysfunction, hypertension or diabetic microalbuminuria, but to the sort of high-risk patients who are currently given prophylactic treatment with aspirin.
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PMID:The HOPE Study (Heart Outcomes Prevention Evaluation). 1196 89

The most common etiologies for mitral regurgitation (MR) include mitral valve prolapse syndrome, coronary artery disease, infective endocarditis, rheumatic heart disease, collagen vascular disease, and, recently, anoretic drugs have also been reported to cause MR. In chronic severe MR, forward cardiac output is maintained for the development of afterload reduction with increase in compensatory left ventricular (LV) end-diastolic volume and LV ejection fraction. It is well established that some patients with asymptomatic mitral regurgitation develop irreversible contractile dysfunction of the LV, which is often masked by the afterload-reducing effect of the regurgitant flow; cardiologist have to use some variables, like LV chamber elastance, LV End-Systolic dimensions and volumes, left atrial area combined with ejection fraction, in their clinical evaluations tube able to predict surgery mortality. Careful and periodic evaluation of left ventricular function and size is essential to optimize the timing of surgical intervention in these patients. After symptoms occur, outcome is improved with surgical interventions compared to medical therapy, with a reported survival of only 45% at 5 years without surgical intervention. Vasodilators, diuretics, and recently, angiotensin receptor antagonists have been used in MR medical therapy. Long-term carvedilol therapy in patients with chronic heart failure may prevent or partially reverse progressive left ventricular dilatation. Concomitant by, it has been associated with recovery of diastolic reserve and a decrease in mitral regurgitation.
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PMID:[Heart failure and pure mitral failure. Prognostic impact and its best treatment]. 1200 70

Patients with atherosclerotic renal artery stenosis may develop hypertension, recurrent pulmonary edema and chronic renal failure, but have a much higher risk of dying from stroke or myocardial infarction than of progressing to end-stage renal disease. Indeed, atherosclerotic renal artery stenosis typically occurs in high risk patients with coexistent vascular disease elsewhere. Recent controlled trials comparing medication to revascularization have shown that only a minority of such patients can expect hypertension cure, whereas the results of trials designed to document the ability of revascularization to prevent progressive renal failure are not yet available. Revascularization should be undertaken in patients with atherosclerotic renal artery stenosis and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition, especially if their renal resistance--index before revascularization is less than 80. With or without revascularization, medical therapy using antihypertensive agents, statins and aspirin is necessary in almost all cases.
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PMID:[Management of atherosclerotic renal artery stenoses]. 1207 Aug 43

The peptide endothelin plays a significant role in a wide array of pathological conditions, including primary pulmonary hypertension and pulmonary arterial hypertension associated with collagen vascular disease. These are life-threatening conditions that can severely compromise the function of the lungs and heart. Inhibiting the actions of endothelin by blockade of its receptors provides a new and effective approach to therapy for patients with these conditions. Bosentan (Tracleer ) is the first orally-active dual endothelin receptor antagonist and has recently been approved in the US, Canada, Switzerland and the EU for the treatment of pulmonary arterial hypertension. Bosentan significantly improves exercise capacity, symptoms and functional status in patients with this disease and also slows clinical deterioration, which may be indicative of a delay of disease progression. Results from large-scale studies of bosentan in patients with pulmonary arterial hypertension and chronic heart failure have established its long-term safety and tolerability profiles. The introduction of the dual endothelin receptor antagonist bosentan has provided an essential treatment for pulmonary arterial hypertension and ongoing trials are evaluating its potential role in the management of other endothelin-mediated disease states.
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PMID:Bosentan: a dual endothelin receptor antagonist. 1208 9

Endothelial production of nitric oxide (nitrogen monoxide, NO) has become a major research area in vascular biology. Some of the most important effects that NO exerts in the vascular wall are potentially vasoprotective, because these effects maintain important physiological functions such as vasodilation, anticoagulation, leucocyte adhesion, smooth muscle proliferation, and the antioxidative capacity. During the last 2 decades it has become apparent that a variety of diseases are associated with an impairment of endothelium-dependent NO activity. One of the major causes is believed to be an increased production of reactive oxygen species, in particular superoxide, which have been shown to interfere with many steps of the NO--cyclic guanosine monophosphate (cGMP) pathway. This phenomenon has been found in diverse conditions such as atherosclerosis, hypertension, diabetes, hypercholesterolemia, heart failure, and cigarette smoking. The aim of this review is to examine the cellular and molecular mechanisms whereby NO exerts potentially vasoprotective effects and to discuss pharmacologic approaches targeting the NO pathway in view of their potential to improve endothelial function and to reduce the progression of atherosclerotic vascular disease. We conclude that there is compelling evidence for vasoprotective actions of NO which are mediated by cGMP-dependent and cGMP-independent mechanisms. These effects may contribute to the beneficial effects of established drugs such as ACE inhibitors or statins. Unfortunately, clinical data on the effect of long-term treatment with nitrates on the progression of coronary artery disease are lacking. Finally, L-arginine or new activators of the NO pathway may become therapeutic options in the future.
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PMID:Vasoprotection by nitric oxide: mechanisms and therapeutic potential. 1212 64

Arterial hypertension and diabetes are potent independent risk factors for cardiovascular, cerebral, renal and peripheral (atherosclerotic) vascular disease. The prevalence of hypertension in diabetic individuals is approximately twice that in the non-diabetic population. Diabetic individuals with hypertension have a greater risk of macrovascular and microvascular disease than normotensive diabetic individuals. Hypertension is a major contributor to morbidity and mortality in diabetes, and should be recognized and treated early. Type 2 diabetes and hypertension share certain risk factors such as overweight, visceral obesity, and possibly insulin resistance. Life-style modifications (weight reduction, exercise, limitation of daily alcohol intake, stop smoking) are the foundation of hypertension and diabetes management as the definitive treatment or adjunctive to pharmacological therapy. Additional pharmacological therapy should be initiated when life-style modifications are unsuccessful or hypertension is too severe at the time of diagnosis. All classes of antihypertensive drugs are effective in controlling blood pressure in diabetic patients. For single-agent therapy, ACE-inhibitors, angiotensin receptor blocker, beta-blockers, and diuretics can be recommended. Because of concerns about the lower effectiveness of calcium channel blockers in decreasing coronary events and heart failure and in reducing progression of renal disease in diabetes, it is recommended to use these agents as second-line drugs for patients who cannot tolerate the other preferred classes or who require additional agents to achieve the target blood pressure. The choice depends on the patients specific treatment indications since each of these drugs have potential advantages and disadvantages. In patients with microalbuminuria or clinical nephropathy, both ACE-inhibitors and angiotensin receptor blockers are considered first line therapy for the prevention of and progression of nephropathy. Since treatment is usually life-long, cost effectiveness should be included in treatment evaluation.
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PMID:[Treatment of hypertension in type 2 diabetes mellitus--2002 update]. 1223 35

Locomotor disability, as defined by difficulties in activities of daily living related to lower limb function, can be the consequence of diseases and impairments of the cardiovascular, pulmonary, nervous, sensory and musculoskeletal system. We estimated the associations between specific diseases and impairments and locomotor disability, and the proportion of disability attributable to each condition, controlling for age and comorbidity. The Rotterdam Study is a prospective follow-up study among people aged 55 years and over in the general population. Locomotor disability in 1219 men and 1856 women was assessed with the Stanford Health Assessment Questionnaire. Diseases and impairments were radiological osteoarthritis, pain of the hips and knees, morning stiffness, fractures, hypertension, vascular disease, ischemic heart disease, stroke, heart failure, chronic obstructive pulmonary disease (COPD), depression, Parkinson's disease, osteoporosis, diabetes mellitus, overweight, and low vision. Adjusted odds ratios, etiologic and attributable fractions were calculated for locomotor disability. The occurrence of locomotor disability can partly be ascribed to joint pain, COPD, morning stiffness, diabetes and heart failure in both men and women. In addition in women osteoarthritis, osteoporosis, low vision, fractures, stroke and Parkinson's disease are significant etiologic fractions. In men with morning stiffness, joint pain, heart failure, diabetes mellitus, and COPD a significant proportion of their disability is attributable to this impairment. In women this was the case for Parkinson's disease, morning stiffness, low vision, heart failure, joint pain, diabetes, radiological osteoarthritis, stroke, COPD, osteoporosis, and fractures of the lower limbs, in that order. We conclude that locomotor complaints, heart failure, COPD and diabetes mellitus contribute considerably to locomotor disability in non-institutionalized elderly people.
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PMID:Determinants of locomotor disability in people aged 55 years and over: the Rotterdam Study. 1238 Jul 18

In people with diabetes, renal disease tends to progress from microalbuminuria to clinical proteinuria to renal insufficiency. Little evidence has been published for the nondiabetic population. This study retrospectively analyzed changes of proteinuria over 4.5 yr in the HOPE (Heart Outcomes and Prevention Evaluation) study, which compared ramipril's effects to placebo in 9297 participants, including 3577 with diabetes and 1956 with microalbuminuria. This report is restricted to 7674 participants with albuminuria data at baseline and at follow-up. Inclusion criteria were known vascular disease or diabetes plus one other cardiovascular risk factor, exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (>1+), and serum creatinine >2.3 mg/dl (200 microM). Baseline microalbuminuria predicted subsequent clinical proteinuria for the study participants overall (adjusted odds ratio [OR], 17.5; 95% confidence interval [CI], 12.6 to 24.4), in participants without diabetes (OR, 16.7; 95% CI, 8.6 to 32.4), and in participants with diabetes (OR, 18.2; 95% CI, 12.4 to 26.7). Any progression of albuminuria (defined as new microalbuminuria or new clinical proteinuria) occurred in 1859 participants; 1542 developed new microalbuminuria, and 317 participants developed clinical proteinuria. Ramipril reduced the risk for any progression (OR, 0.87; 95% CI, 0.78 to 0.97; P = 0.0146). People without and with diabetes who are at high risk for cardiovascular disease are also at risk for a progressive rise in albuminuria. Microalbuminuria itself predicts clinical proteinuria in nondiabetic and in diabetic people. Ramipril prevents or delays the progression of albuminuria.
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PMID:Development of renal disease in people at high cardiovascular risk: results of the HOPE randomized study. 1259 99


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