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)

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

Hypertension, including isolated systolic hypertension, is one of the major risk factors for stroke and coronary heart disease in elderly subjects, and is a common antecedent of heart failure, because it increases the risk either directly through increased after-load or indirectly as a risk factor for acute myocardial infarction. The proportion of people aged 65 and above is increasing. It is well documented that hypertension treatment in elderly patients reduces cardiovascular morbidity and mortality more than could be expected from the results of trials in middle-aged subjects. Most of the trials on old and new antihypertensive drugs have yielded similar results. Nevertheless, evidence in subjects above 80 years of age is still limited. Hypertension (systolic-diastolic) and isolated systolic hypertension should be treated in elderly patients, starting with low doses of medication, particularly diuretics alone or in combination with beta-blockers or angiotensin-converting enzyme inhibitors. Isolated systolic hypertension could also be treated with a long-acting calcium antagonist starting with low doses. The large therapeutic studies, because of the limitations imposed upon conclusions by the selection and exclusion criteria, by the statistical techniques that established the trial designs and by other study-related constraints, cannot be applied to all elderly patients seen in daily practice. Specifically patients may differ in age, severity of illness, presence of morbidity and a myriad of other clinical nuances. Non-pharmacological measures such as lifestyle modifications (losing weight, limiting alcohol intake, reducing sodium intake and exercise), should be instituted or improved if they existed, to maximise the benefit and minimise the risk inherent in pharmacological treatment. A medical approach may reconcile the results of these large therapeutic studies with 'real life' quality of life and patients' preferences in order to improve treatment compliance.
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PMID:Large therapeutic studies in elderly patients with hypertension. 1198 92

With aging there are changes in the cardiovascular system, which result in alterations in cardiovascular physiology. The changes in cardiovascular physiology must be differentiated from the effects of pathology, such as coronary artery disease, that occur with increasing frequency as age increases. The changes with age occur in everyone but not necessarily at the same rate, therefore accounting for the difference seen in some people between chronologic age and physiologic age. The changes in the cardiovascular system associated with aging are a decrease in elasticity and an increase in stiffness of the arterial system. This results in increased afterload on the left ventricle, an increase in systolic blood pressure, and left ventricular hypertrophy, as well as other changes in the left ventricular wall that prolong relaxation of the left ventricle in diastole. There is a dropout of atrial pacemaker cells resulting in a decrease in intrinsic heart rate. With fibrosis of the cardiac skeleton there is calcification at the base of the aortic valve and damage to the His bundle as it perforates the right fibrous trigone. Finally there is decreased responsiveness to beta adrenergic receptor stimulation, a decreased reactivity to baroreceptors and chemoreceptors, and an increase in circulating catecholamines. These changes set the stage for isolated systolic hypertension, diastolic dysfunction and heart failure, atrioventricular conduction defects, and aortic valve calcification, all diseases seen in the elderly.
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PMID:Cardiovascular physiology-changes with aging. 1250 9

The normal aging process is often accompanied by arterial wall stiffening and by a decrease in myocardial compliance. These processes contribute to isolated systolic hypertension and diastolic heart failure, which lead to substantial morbidity and mortality among older individuals. Patients with diabetes manifest arterial stiffening and diastolic dysfunction at a younger age. This leads to the concept that the mechanism that underlies changes in vascular mechanical properties during aging is accelerated in diabetes. The Maillard reaction or advanced glycation of proteins occurs slowly in vivo with normal aging and at an accelerated rate in diabetes. Advanced glycation end-products (AGEs) that form during the Maillard reaction are implicated in the complications of aging and diabetes. The formation of AGEs on vascular wall and myocardial collagen causes cross-linking of collagen molecules to each other. This leads to the loss of collagen elasticity, and subsequently a reduction in arterial and myocardial compliance. Aminoguanidine, an inhibitor of AGE formation, is effective in slowing or preventing arterial stiffening and myocardial diastolic dysfunction in aging and diabetic animals. In aged and diabetic animals, agents that can chemically break pre-existing cross-linking of collagen molecules are capable of reverting indices of vascular and myocardial compliance to levels seen in younger or non-diabetic animals. These studies suggest that collagen cross-linking is a major mechanism that governs aging and diabetes-associated loss of vascular and cardiac compliance. The development of AGEs cross-link breakers may have important role for future therapy of isolated systolic hypertension and diastolic heart failure in these conditions.
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PMID:Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes. 1254 24

Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure. To assess its usefulness in older patients with systolic hypertension and widened pulse pressure, we compared the effects of eplerenone with amlodipine, on clinic blood pressure (BP) and pulse pressure and in a subset of the patients, ambulatory BP, vascular compliance, and urinary albumin excretion. The study involved 269 patients > or =50 years of age who were randomly assigned to either eplerenone (50 to 200 mg daily) or amlodipine (2.5 to 10 mg daily) in a double-blind titration to effect design. After 24 weeks of therapy, reductions in clinic systolic BP were similar for both treatments (eplerenone, -20.5+/-1.1 mm Hg; amlodipine, -20.1+/-1.1 mm Hg). Reductions in clinic diastolic BP were modestly larger on amlodipine (-6.9+/-0.7 mm Hg) compared with eplerenone (-4.5+/-0.7 mm Hg) (P=0.014). Pulse pressure was also reduced similarly from baseline by the 2 treatment groups (eplerenone, -15.9 mm Hg versus amlodipine, -13.4 mm Hg, P=0.07). Changes from baseline in pulse wave velocity after 24 weeks of therapy were statistically similar for eplerenone and amlodipine. In patients with microalbuminuria at baseline (>30 mg albumin/g creatinine), eplerenone reduced the urinary albumin/creatinine ratio by 52% compared with a reduction of 10% by amlodipine (P=0.04). Thus, eplerenone was as effective as amlodipine in lowering systolic BP and pulse pressure as well as pulse wave velocity in older patients with widened pulse pressure hypertension. Furthermore, eplerenone reduced microalbuminuria to a greater extent than amlodipine in this older patient group.
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PMID:Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. 1475 24

Although recent trials have shown that antihypertensive treatment can bring about a reduction in stroke, coronary heart disease, heart failure and renal disease, the situation is no longer improving. This is due to the fact that the percentage of hypertensive patients with satisfactory blood pressure is still very poor. International guidelines on hypertension indicate the importance of assessing the absolute risk of patients and the use of a lower dose of drugs to improve the efficacy-tolerability profile. Diuretics used at lower dosage than in the past are effective in reducing morbidity and mortality and continue to be drugs of first choice in the treatment of hypertension. Indapamide sustained release (Natrilix SR) 1.5 mg has an antihypertensive effect equivalent to indapamide immediate release 2.5 mg with a 50% reduction in incidence of serum potassium levels <3.4 mmol/l. Natrilix SR has proved to have a neutral effect both on lipid and glucose profiles and to reduce microalbuminuria in diabetic hypertensive patients. Recent multicentre European clinical trials have shown that Natrilix SR decreases diastolic blood pressure to <90 mmHg in about 75% of patients treated for 1 year. In elderly patients with isolated systolic hypertension, Natrilix SR has been proven to be as effective as amlodipine 5 mg and significantly more effective than hydrochlorothiazide 25 mg. Natrilix SR produces regression of left ventricular hypertrophy which, in the Left ventricular hypertrophy: Indapamide Versus Enalapril study was greater than that induced by enalapril. Natrilix SR represents an appropriate choice not only as a first-line drug in many hypertensive patients but also in at-risk patients like the elderly, subjects with other cardiovascular risk factors, target organ damage, diabetes, or impaired renal function.
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PMID:Clinical role of Natrilix SR in the treatment of at-risk hypertensive patients. 1276 62

The presence of isolated systolic hypertension in elderly subjects predisposes to the development of coronary artery disease, myocardial infarction, heart failure, cardiovascular events, stroke and cardiovascular mortality. Whether pharmacologic management of isolated systolic hypertension in the elderly is justified or not has not received attention until the recent years. In this era of the practice of evidence based medicine it is important to review the results of clinical trials about the management of isolated systolic hypertension involving thousands of elderly patients. The main trials and their results will be presented. These demonstrate a 17% reduction in total mortality, 25% reduction in cardiovascular mortality, 37% reduction in stroke and a 25% reduction in myocardial infarction for those patients under pharmacologic treatment.
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PMID:Clinical trials in isolated systolic hypertension in the elderly. 1286 38

In this review, the effect of aging on the body's vascular system is considered in terms of potential mechanisms involved in target organ damage. First, the effects of aging on body fluid compartments, including changes that occur in subdivisions of the interstitial space (quite heterogeneous among organs), are described, with particular reference to the macromolecular composition of the fluid compartments. Second, the structure and function of different segments of the vascular system during aging are examined, with emphasis on: (1) large arterial conduits responsible for isolated systolic hypertension; (2) arteries most responsible for peripheral resistance (the "resistance arteries"); (3) microcirculation networks, including the vasa vasorum; and (4) large collecting veins that can have such an important effect on the cardiac output. Third, a detailed discussion is provided of the heterogeneous macromolecular composition of interstitial fluid compartments that are involved in the critical traffic of vital substrates, including pharmacologic agents, in transit from the systemic circulation to the various organs. The strategic position of interstitial fluid compartments, situated as they are between microcirculation networks and vital organs, is considered to be critically involved in the morbidity and mortality caused by the vascular diseases afflicting elderly persons. Finally, with respect to "physiological" and/or "morbid" aging, a re-examination is undertaken of the target organ damage observed in elderly individuals who suffer from isolated systolic hypertension, type II diabetes mellitus, peripheral vascular disease, chronic heart failure, and renal failure. Potentially new and noninvasive approaches available to clinicians for early detection of large artery rigidity are considered, along with the possible benefits of nonpharmacologic and/or pharmacologic interventions.
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PMID:Impact of aging on the body's vascular system. 1457 61

Cardiovascular disease is the main cause of serious illness and death in the United States. Increasing age is a strong predictor of cardiovascular events, driven largely by such major conditions as hypertension and diabetes mellitus. Systolic hypertension probably reflects progressive stiffening of large and small arteries; close to 90% of all Americans will have this diagnosis by their 80s. Regardless of age, systolic hypertension is a powerful risk factor for stroke, heart failure, and other cardiovascular outcomes. Treating hypertension in the elderly sharply decreases the probability of these events. Clinical trial evidence does not include patients with stage 1 systolic hypertension (140-159 mm Hg), although the results in stage 2 are so convincing that it is very reasonable (as concluded by national guidelines committees) to extrapolate benefits and recommend treatment to patients in the less-severe group. Whereas evidence of treatment benefits in patients aged 80 years and older is limited, sufficient octogenarians have been studied to confidently assert that strokes, at least, can be prevented. Another potentially important benefit that is yet to be fully confirmed is that treating hypertension in older people may also reduce the incidence of dementia.
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PMID:Treating hypertension in the elderly: protagonist viewpoint. 1461 Mar 85

Cardiac failure is the leading cause of hospital admission after 65 years of age. Several studies have confirmed the frequency of cardiac failure with normal systolic function ("diastolic" cardiac failure) in the elderly (nearly half the cases). The cause is commonly isolated systolic hypertension. The pulsed pressure depends on ventricular ejection, arterial rigidity and the precocity of reflected pulse waves. In the elderly, the pulse pressure is a powerful predictive factor for mortality and adverse cardiovascular events (acute coronary syndromes, cardiac failure and cerebrovascular accidents). Patients with isolated systolic hypertension or an increased pulsed pressure usually have left ventricular hypertrophy or concentric remodelling, abnormal relaxation, alteration of hypertrophied myocytes with increased myocardial oxygen consumption and subendocardial ischaemia, especially when the coronary reserve is reduced. The decrease of the diastolic blood pressure reduces the presence of coronary perfusion. Moreover, an increase in the pulsed pressure predisposes to coronary atherosclerosis. These patients are very symptomatic on exercise because they do not have a reserve of preload and easily develop acute pulmonary oedema after a volume overload (increased salt intake, postoperative rehydratation). A recent study showed that the left ventricular ejection fraction was preserved during acute pulmonary oedema of hypertensive patients. The diagnosis of "diastolic" cardiac failure is often suspected by elimination (clinical signs of cardiac failure with a normal left ventricular ejection fraction), and echographers have proposed many criteria to detect abnormal relaxation, filling or distensibility of the left ventricle. Mortality would seem to be half that of systolic cardiac failure. Treatment should normalise the hypertension, ischaemia, tachycardia, and maintain or reestablish sinus rhythm, but it remains empirical.
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PMID:["Diastolic" heart failure and pulsed pressure]. 1462 35


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