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)

Angiotensin-converting enzyme inhibitors (ACE-I) have been proven to be effective in reducing morbidity and mortality in patients with heart failure or post-myocardial infarction left ventricular dysfunction. Despite evidence from several large-scale randomized trials, the use of ACE-I in patients with heart failure remains relatively low. In part, the failure to achieve more widespread use of ACE-I in patients with heart failure may be due to physician's perceptions of the side effects associated with ACE-I, such as angioedema, renal dysfunction, cough, and hypotension. Many of these side effects are thought to be due to ACE-I-induced bradykinin accumulation. It is possible to inhibit the effect of angiotensin II without increasing bradykinin levels using an angiotensin II type I blocking agent such as losartan. How effective losartan is compared with an ACE-I is uncertain, however. Some of the beneficial effects of ACE-I have been attributed to bradykinin accumulation, and therefore ACE-I might have an advantage compared with an angiotensin II type I receptor antagonist such as losartan. On the other hand, angiotensin II may be produced by non-ACE-I-dependent mechanisms, which would suggest that an angiotensin II type I receptor blocking agent would be advantageous. To determine the relative safety and efficacy of an ACE-I, which results in bradykinin accumulation and inhibitors of angiotensin II, versus an angiotensin II type I receptor blocking agent, which does not result in bradykinin accumulation, we have begun the Evaluation of Losartan In The Elderly (ELITE) trial, which will compare the safety and efficacy of captopril and losartan in elderly patients with heart failure.
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PMID:Angiotensin II receptor antagonists in heart failure: rationale and design of the evaluation of losartan in the elderly (ELITE) trial. 857 52

Angiotensin-converting enzyme (ACE) inhibitors have been used for more than a decade in the treatment of chronic congestive heart failure. In recent years these agents have been used in patients who survived a myocardial infarction. However, primary care providers are often confused as to which patients would benefit the most, and as a result, these life-prolonging drugs are underutilized. The results of randomized controlled trials evaluating ACE inhibitors' effect on morbidity and mortality in patients with chronic congestive heart failure or acute myocardial infarction were evaluated. Angiotensin-converting enzyme inhibitors clearly improve survival in patients with symptomatic congestive heart failure. This survival benefit is approximately 6 months. In patients with asymptomatic systolic dysfunction, these agents also decrease the number of hospital admissions due to heart failure. Angiotensin-converting enzyme inhibitors also improve survival in all patients who experienced an acute myocardial infarction. With the plethora of evidence regarding the positive effects that this class of drugs has on the quality of life and survival of patients with systolic dysfunction, it is still unclear why clinicians are reluctant to use them more often. Primary care providers need to be educated on how to risk stratify patients to make this therapy more cost effective, and when these agents should be started.
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PMID:Angiotensin-converting enzyme inhibitors in left ventricular dysfunction. 866 6

Heart failure is associated with high rates of morbidity and mortality. Because heart failure is difficult to diagnose accurately on the basis of the history and physical examination alone, It is vital that clinical evaluation such as echocardiography be used to confirm the diagnosis. In addition, it is important to identify etiologic or predisposing factors that may be reversible. Angiotensin-converting enzyme inhibitors should be considered in all patients with a diagnosis of left ventricular systolic dysfunction, unless contraindications exist. Diuretics and digoxin are helpful in specific circumstances. Comorbid factors such as excessive alcohol intake and coronary artery insufficiency should be addressed. Patient and family education and cooperation with medical regimens can reduce morbidity and mortality.
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PMID:Management of heart failure. 910 87

Angiotensin-converting enzyme (ACE) inhibitors are now established drugs in the treatment of hypertension and heart failure. However, their use in patients after a myocardial infarction has occurred remains controversial. The major clinical question regarding ACE inhibitors is whether they should be given to all patients immediately after thrombolysis or whether their use should be restricted to a particular subgroup. This question has now been addressed in several large-scale trials of mortality after myocardial infarction, and no important new information seems likely to emerge on the issue. Clinicians must therefore decide what their practice will be on the basis of data that are currently available. The authors of the recently published Gruppo italiano per lo Studio delta Sopravvlvenza nell' infarcto Miocardico (GISSI-3) and Fourth International Study of Infarct Survival (ISIS-4) mega-trials advocate a policy of widespread and early use of ACE inhibitors in all patients after myocardial infarction occurs. However, the small mortality benefit observed from use of ACE inhibitors in these studies lacks certainly and may prove difficult to reproduce in the general population of patients who have had an infarct outside the setting of a trial. Although patients were essentially not selected apart from the exclusion of those with marked hypotension, the low 6-month and 1-year mortality figures indicate "selection" compared with the typical population of patients who have had a myocardial infarction. Furthermore, a significant long-term mortality benefit was not observed with the short-term (4- to 6-week) use of ACE inhibitors in these trials. In contrast, in the Survival and Ventricular Enlargement (SAVE), Acute Infarction Ramipril Efficacy (AIRE), and Trandopril Cardiac Evaluation (TRACE) trials, where evidence of impairment of ventricular function was used to select patients, both a marked and certain benefit regarding mortality was apparent from long-term prescription of these drugs. Importantly, the marked benefit observed in these selected patients may have been "diluted out" in the larger scale trials of unselected patients where the majority may have gained little and some may have been harmed by treatment or its withdrawal. In most of the large mortality trials the rationale for use of ACE inhibitors after myocardial infarction was stated to be their likely beneficial effect on "remodeling" of the heart after "Infarct expansion." Because adverse remodeling occurs in only a proportion of patients after a heart attack, the benefits of ACE inhibitor therapy might be predicted to be largely limited to this group, which would favor a selective policy. However, strong claims have been made that ACE inhibitors have other important actions, including prevention of myocardial infarction. If this is confirmed in a number of ongoing large-scale trials. then an even ore widespread use of these agents can be expected.
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PMID:Who should be treated with angiotensin-converting enzyme inhibitors after myocardial infarction? 867 63

Our options for the medical management of heart failure are aimed at preventing the development of the condition, relieving symptoms, modifying the underlying pathophysiology, and delaying or preventing disease progression. The principal symptoms of heart failure are edema, dyspnea and fatigue. Diuretics are effective in relieving edema, and dyspnea resulting from pulmonary edema. Once pulmonary edema has been treated relatively few agents are effective against residual exercise-induced dyspnea, possibly because of the numerous possible causes of this symptom. Angiotensin-converting enzyme (ACE) inhibitors have, however, been shown to improve dyspnoea by mechanisms that are not related to hemodynamic actions. These agents also improve skeletal muscle blood flow and function, thereby relieving fatigue in heart failure patients. Treatment strategies aimed at modifying the underlying pathophysiology or preventing disease progression have, with the exception of the ACE inhibitors, met with limited success. Large-scale trials have shown, however, that ACE inhibitors improve survival in patients with moderate or severe heart failure, and prevent the development of heart failure in asymptomatic patients. These agents, therefore, represent an important advance in the management of heart failure, and it is anticipated that new insights into their optimal use will follow as the mechanisms by which they exert their beneficial effects become clear.
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PMID:Interruption of the progression of heart failure: are ACE inhibitors the solution? 868 15

1. This review argues that the deletion (D) allele of an insertion (I)/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene is a marker for a variant associated with increased ACE expression, as well as myocardial infarction (MI) and other life-threatening conditions. 2. By examination of I/D frequency in different age groups of individuals having well-known risk factors, it appears that homozygosity for the D allele may be associated with an increased risk of premature death in subjects at high-risk of cardiovascular events. For the risk factor hypertension, the odds ratio for DD vs II in patients aged > or = 60 years was 6.6. 3. Besides in MI itself, the DD genotype appears to be also more prevalent in MI patients who develop restenosis several months after balloon angioplasty, patients with various forms of heart failure, those with ventricular hypertrophy and diabetic patients who develop nephropathy. 4. Particular genotypes of other components of the renin-angiotensin system may add to the risk conferred by the ACE DD genotype. 5. Emerging evidence therefore suggests that the ACE genotype may eventually be placed on the list of common, well-known risk factors for fatal cardiovascular events.
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PMID:Hypothesis: an angiotensin converting enzyme genotype, present in one in three caucasians, is associated with increased mortality rate. 871 89

Angiotensin-converting enzyme (ACE; EN 3.4.15.1) is a peptidyl dipeptide hydrolase that removes the carboxyl terminal His-Leu from angiotensin I to produce the octapeptide angiotensin II. In addition, ACE inactivates bradykinin, a vasodilator peptide/mediator of inflammation, as well as substance P, enkephalins and endorphins. Because of the importance of ACE and its active site-directed inhibitors in the pathogenesis and treatment of cardiovascular disorders such as hypertension and heart failure, ACE purification and assay are of clinical and commercial, as well as scientific interest. This review summarizes the historical development of ACE purification and assay methods and presents some innovative high-performance liquid chromatography-based techniques developed in our own laboratory for high yield and efficient purification and sensitive and specific assay of ACE.
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PMID:Purification and assay methods for angiotensin-converting enzyme. 881 75

Angiotensin-converting enzyme (ACE) inhibitors reduce myocardial remodeling and improve cardiac function after myocardial infarction. We investigated whether the beneficial effects of ACE inhibition were associated with changes in the levels of angiotensin and bradykinin peptides in blood, heart, lung, aorta, and kidney. Rats subjected to coronary artery ligation and selected by ECG criteria to have moderate to large myocardial infarctions (mean size, 38%) were administered perindopril (0, 20, 200, and 2,000 micrograms/kg/day) in their drinking water from the second day after surgery for 26 days. Perindopril caused a dose-related decrease in blood pressure and inhibited the development of both cardiac hypertrophy (estimated by heart weight/body weight ratio) and cardiac failure (estimated by lung weight/body weight ratio). Perindopril inhibited plasma ACE activity and increased plasma renin, with an associated decrease in plasma angiotensinogen. Plasma and all tissues showed a marked reduction in angiotensin II/angiotensin I ratio, indicating effective inhibition of ACE in plasma and tissues. Whereas heart, lung, and kidney showed dose-related decreases in angiotensin II (Ang II) levels, plasma and aortic levels of Ang II were not altered by perindopril. Perindopril increased blood bradykinin levels but did not increase bradykinin levels in heart, lung, aorta, or kidney. Heart showed a 45% increase in bradykinin levels at the highest dose of perindopril, which did not achieve statistical significance, although perindopril reduced the bradykinin(1-7)/ bradykinin-(1-9) ratio in heart, indicating inhibition of cardiac metabolism of bradykinin by perindopril. By contrast, perindopril reduced bradykinin levels in lung. These data support a role for reduced blood pressure and cardiac Ang II levels in mediating the effects of ACE inhibition after myocardial infarction but do not support a role for tissue bradykinin in this process.
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PMID:Effects of angiotensin-converting enzyme inhibition on angiotensin and bradykinin peptides in rats with myocardial infarction. 896 Oct 71

Angiotensin-converting enzyme inhibitors (ACEIs) are used increasingly for the treatment of hypertension and chronic heart failure, and they reduce mortality when given after myocardial infarction. Of the patients prescribed these drugs 0.1-0.7% develop angio-oedema, but the association is not widely recognized. In 60% of cases the onset occurs during the first week of treatment; however, it may be considerably delayed. Angio-oedema nearly always occurs on the head and neck, frequently involving the mouth, tongue, pharynx and larynx. The course is unpredictable, and attacks vary in severity from mild to fatal from laryngeal obstruction. Severe ACEI-induced angio-oedema may require emergency treatment with adrenalin and early intubation. The drug should be withdrawn in any patient who presents with ACEI-induced angio-oedema, and treatment continued with an appropriate drug of a different class. Therapy with ACEIs is contraindicated in patients with a prior history of idiopathic angio-oedema, or in patients with hereditary or acquired C1 esterase inhibitor deficiency.
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PMID:Angiotensin-converting enzyme (ACE) inhibitors and angio-oedema. 906 23

Angiotensin-converting enzyme inhibitors (ACEi) improve cardiac function and remodeling and prolong survival in patients with heart failure (HF). Blockade of the renin-angiotensin system (RAS) with an angiotensin II type 1 receptor antagonist (AT1-ant) may have a similar beneficial effect. In addition to inhibition of the RAS, ACEi may also act by inhibiting kinin destruction, whereas AT1-ant may block the RAS at the level of the AT1 receptor and activate the angiotensin II type 2 (AT2) receptor. Using a model of HF induced by myocardial infarction (MI) in rats, we studied the role of kinins in the cardioprotective effect of ACEi. We also investigated whether an AT1-ant has a similar effect and whether these effects are partly due to activation of the AT2 receptor. Two months after MI, rats were treated for 2 mo with: (a) vehicle; (b) the ACEi ramipril, with and without the B2 receptor antagonist icatibant (B2-ant); or (c) an AT1-ant with and without an AT2-antagonist (AT2-ant) or B2-ant. Vehicle-treated rats had a significant increase in left ventricular end-diastolic (LVEDV) and end-systolic volume (LVESV) as well as interstitial collagen deposition and cardiomyocyte size, whereas ejection fraction was decreased. Left ventricular remodeling and cardiac function were improved by the ACEi and AT1-ant. The B2-ant blocked most of the cardioprotective effect of the ACEi, whereas the effect of the AT1-ant was blocked by the AT2-ant. The decreases in LVEDV and LVESV caused by the AT1-ant were also partially blocked by the B2-ant. We concluded that (a) in HF both ACEi and AT1-ant have a cardioprotective effect, which could be due to either a direct action on the heart or secondary to altered hemodynamics, or both; and (b) the effect of the ACEi is mediated in part by kinins, whereas that of the AT1-ant is triggered by activation of the AT2 receptor and is also mediated in part by kinins. We speculate that in HF, blockade of AT1 receptors increases both renin and angiotensins; these angiotensins stimulate the AT2 receptor, which in turn may play an important role in the therapeutic effect of the AT1-ant via kinins and other autacoids.
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PMID:Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors. 910 37


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