Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular mechanism involved in pulmonary vascular disease (PVD) associated with congenital heart disease (CHD) remains uncertain. Evidence suggesting that angiotensin converting enzyme plays an important role in pulmonary vascular pathology led us to hypothesize that mast cell chymase, another angiotensin I converting enzyme, also had the potential to contribute to the development of PVD in CHD. Twenty-three patients 3 mo to 45 yr of age with atrial or ventricular or both septal defects with increased pulmonary arterial blood flow and pressure, with pulmonary vascular resistance ranging from 1.3 to 8.1 units/m(2), were studied. Mast cells and mast cell chymase were immunohistochemically identified in the lung biopsy tissues obtained during corrective surgery. There was a significant difference in numbers of total mast cells between patients (n = 23) and control subjects (n = 10) with normal pulmonary circulation (p < 0.01). Moreover, chymase-containing mast cells in the lung tissues of patients with CHD showed striking differences from those of control subjects. In the patients, 72% of lung mast cells contained chymase, compared with only 15% in control subjects (p < 0.0001). Chymase-containing mast cells predominantly appeared in the media and adventitia of vessel walls. Importantly, angiotensin II was immunohistochemically detected in perivascular lesions where chymase was present, but not in the lesions where chymase was sparsely seen. Furthermore, the number of chymase-containing mast cells was correlated with pulmonary vascular resistance (r = 0.64). These findings suggest a possible role of mast cell chymase in the development of early-stage PVD in patients with CHD.
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PMID:Increased expression of mast cell chymase in the lungs of patients with congenital heart disease associated with early pulmonary vascular disease. 1050 22

Congestive heart failure is a growing public health problem and continues to be characterized by a poor prognosis. Its prevalence may be estimated at 0.4-2% of the general population with an incidence varying from 1-10% in elderly patients. This may be in part explained by the progressive aging of the population and the more effective therapeutic strategies for coronary heart disease and hypertension: since they increase the life-expectancy of patients, they favor the onset of this clinical syndrome at a more advanced age. The number of hospital admissions has also increased; mortality is 50% within 4 years of diagnosis, although patients with very severe cardiac decompensation die within 1 year. Despite the fact that with the use of the most advanced molecules created by pharmacological research (ACE inhibitors, beta-blockers, angiotensin-II-receptor antagonists) a significant reduction in morbidity and mortality as well as clear improvement of symptoms and quality of life have been obtained in diverse clinical trials, there is still no certain evidence that in the general population, mortality due to chronic heart disease has been reduced. In our opinion, several factors explain the gap between the favorable results of clinical trials and the lack of significant reduction in morbidity and mortality in clinical practice: A) the selection criteria utilized in clinical studies exclude, for the most part, patients present in general population; B) the average age of the patients included (60 years) is not representative of the overall population; C) patients with associated co-morbidity are generally excluded; D) the number of women enrolled in the trials is quite low; E) compliance is certainly better in the trials than in clinical practice; F) higher drug dosages are used in the trials than in clinical practice. To intervene in these areas and thus make the positive results obtained in the trials available to the general population is, in our opinion, the principal challenge of the future. For this task, the close collaboration and commitment of the internist, the geriatrist, the cardiologist and the family doctors is necessary so that the results reported in clinical trials may be translated into general medical practice.
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PMID:[The difficulties of translating into daily clinical practice the favorable results of clinical trials in chronic heart failure]. 1084 89

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

Older drivers have elevated crash rates and are more likely to be injured or die if they have a crash. Medical conditions and medications have been hypothesized as determinants of crash involvement. This population-based case-control study sought to identify medical conditions and medications associated with risk of at-fault crashes among older drivers. A total of 901 drivers aged 65 years and older were selected in 1996 from Alabama Department of Public Safety driving records: 244 at-fault drivers involved in crashes; 182 not at-fault drivers involved in crashes; and 475 drivers not involved in crashes were enrolled. Information on demographic factors, chronic medical conditions, medications, driving habits, visual function, and cognitive status was collected. Older drivers with heart disease (odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.0, 2.2) or stroke (OR = 1.9, 95% CI: 0.9, 3.9) were more likely to be involved in at-fault automobile crashes. Arthritis was also associated with an increased risk among females (OR =1.8, 95% CI: 1.1, 2.9). Use of nonsteroidal antiinflammatory drugs (OR = 1.7, 95% CI 1.0, 2.6), angiotensin converting enzyme inhibitors (OR = 1.6, 95 CI: 1.0, 2.7), and anticoagulants (OR = 2.6, 95% CI: 1.0, 73) was associated with an increased risk of at-fault involvement in crashes. Benzodiazepine use (OR = 5.2, 95% CI: 0.9, 30.0) was also associated with an increased risk. Calcium channel blockers (OR = 0.5, 95% CI: 0.2, 0.9) and vasodilators (OR = 0.3, 95% CI: 0.1, 1.0) were associated with a reduced risk of crash involvement. The identification of medical conditions and medications associated with risk of crashes is important for enhancing the safety and mobility of older drivers.
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PMID:Relations among chronic medical conditions, medications, and automobile crashes in the elderly: a population-based case-control study. 1098 55

Heart disease is the major cause of mortality in the developed world. Despite recent advances in the therapy of heart failure due to ACE inhibitors and beta-blockers, the prognosis of this syndrome is still poor. In the past few years, the effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) on heart morphology and function were extensively studied. Some studies dealing with experimental heart failure of animals and one controversial study dealing with human heart failure suggest positive hemodynamic effects of GH and/or IGF-I treatment. This review summarizes the physiological effects of GH/IGF-I on the myocardium, their signal transduction mechanisms, and the data currently available on the therapeutic use of these agents.
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PMID:[Hormone therapy in heart failure: growth hormone and insulin-like growth factor I]. 1102 Dec 70

Diabetes mellitus as a disease of epidemiological impact leads to diabetic cardiopathy by modulation of myocardial, vascular and metabolic components. This includes the development of a coronary microangiopathy and a decrease of diastolic and systolic function of the left ventricle as well as the development of an autonomic diabetic neuropathy. Patients with diabetes show an increased mortality concerning cardiovascular events. They more often suffer from myocardial infarction as non-diabetics mostly with a more serious course. Moreover, the post-infarction course is affected with a worse prognosis as in non-diabetics. For diagnosis of cardial involvement in diabetes electrocardiographic and echocardiographic procedures are of use. Special tests of the autonomic function complete the diagnostic ensemble. An early therapy with ACE-inhibitors and beta blocking agents as well as a strong diabetes therapy, in particular with insulin, can influence the mortality favorably. Moreover, the diagnosis and therapy of additional cardiovascular risk factors (arterial hypertension, dyslipidemia) are very important, because these are correlated with a for diabetic patients markedly increased risk of mortality. The clinical relevance of the term diabetic cardiopathy is justified by the 6 factors: macroangiopathy, microangiopathy, disturbances of the myocardial metabolism, myocardial fibrosis, autonomic diabetic neuropathy and disturbances of the coagulability. Diagnostic and therapeutic goals are discussed.
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PMID:[Cardiac complications in diabetes mellitus]. 1102 65

Viral infection of the heart is relatively common and usually of little consequence. It can, however, lead to substantial cardiac damage and severe acute heart failure. It can also evolve into the progressive syndrome of chronic heart failure. Recent studies have gone some way towards unravelling the complex mechanisms underlying the heart muscle damage that occurs after viral infection. These studies have lent support to both immune and viral mediated (independent of an immune response) cardiac damage. Acute myocarditis can present in various ways, and it may be a cause of sudden death in an otherwise healthy young adult. New treatments for viral heart disease are awaited. In the meanwhile, the haemodynamic support of patients with acute left ventricular failure caused by myocarditis should be aggressive, to allow for the possibility of spontaneous recovery. Contemporary trials of treatment in chronic heart failure secondary to dilated cardiomyopathy support the use of angiotensin converting enzyme inhibitors, beta adrenoceptor blockers, and spironolactone in such patients.
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PMID:Viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management. 1112 85

The A II antagonists (RA II antagonists) are a new group of anti-hypertensive drugs with five years of clinical use. They were investigated after the knowledge of independent ways to get angiotensin II. They block AT1 receptor. It's possible that, after AT1 block, the high plasmatic levels of AII stimulate the AT2 receptors with vasodilation and anti-proliferative activity. We are waiting for the results of several big prospective studies with RA II antagonists on cardiovascular morbidity and mortality. At present time, the first indication for its use is the appearance of cough when taking ACE inhibitors. The association of ACE inhibitors and RA II antagonists can improve some clinical conditions like dilated hypertensive cardiopathy, nephropathy or refractory hypertension.
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PMID:[ACE inhibitors versus AR II antagonists. Their role in arterial hypertension]. 1130 10

Both aspirin (acetylsalicylic acid) and ACE inhibitors are often used concomitantly, especially in patients with both heart failure and ischaemic heart disease, which is the most common underlying cause of heart failure. The safety of the association has been questioned because both drugs affect a related prostaglandin-mediated pathway. Thanks to their vasodilating properties, prostaglandins play an important role in heart failure where peripheral vasoconstriction occurs. Some of the beneficial effects of ACE inhibitors might be related to reduced degradation of bradykinin that enhances the synthesis of prostaglandins, while aspirin, through inhibiting the enzyme cyclo-oxygenase, inhibits the production of prostaglandins. To date no prospective study has been conducted to investigate the effect of long term aspirin treatment in the postinfarction period allowing the possible impact of the interaction between aspirin and ACE inhibitors upon survival to be confirmed or negated. However, the practitioner needs to know how to optimise the treatment of his or her patients. In order to stimulate arguments for and against the use of aspirin in patients with heart failure receiving ACE inhibitors, we searched MEDLINE from 1960 to 2000 using the key words heart failure, aspirin, and ACE inhibitors for English language articles and conducted a review of the available data. We report on the potential mechanisms of the interaction and the results of experimental studies on haemodynamic parameters. Results of retrospective clinical studies, subgroup analysis that were undertaken to evaluate the overall action upon haemodynamic parameters and survival of the association are summarised. Conflicting conclusions have been reported in the literature. Many explanations can be advanced to try to understand these conflicting conclusions: differences in study design (results of retrospective trials have to be interpreted with caution); differences in the choice of the evaluation parameter (problem of the clinical relevance of haemodynamic parameters); differences in the characteristics of the patient (different underlying cardiopathy, e.g. heart failure, hypertension or ischaemic cardiopathy); and differences in the type and the dosage of each treatment (especially ACE inhibitors and aspirin since an interaction might occur more often with dosage of aspirin greater than 250mg).
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PMID:Interaction between aspirin and ACE inhibitors in patients with heart failure. 1134 21

Optimal management of pregnancies for patients with acquired heart disease requires exact knowledge of the hemodynamic influence of pregnancy-related cardiovascular adaptation processes on the heart disease. Maternal and fetal risks must be carefully considered and mutually weighed. Critical time periods, during which closely networked, interdisciplinary support for the patient is essential, are primarily during the 30th to 32nd week of pregnancy. This is the period in which maximum increases in heart rate, cardiac output, and plasma volume are observed. The peripartal phase represents another critical period. Owing to the mechanically related fixation of cardiac output, stenotic valvular diseases are generally tolerated much poorer than are valvular insufficiency defects. Therapeutic objectives are reduction in heart rate and--in cases of pulmonary-venous congestion--decrease in preload. Vaginal deliveries are possible with slight to moderate valvular stenosis; cesarean section is to be preferred in more severe cases. In patients with valvular insufficiency and normal left ventricular function pregnancy is usually well tolerated. Reduction in regurgitation is even often observed owing to pregnancy-induced decrease in peripheral vascular resistance. Since ACE inhibitors and AT1 antagonists are contraindicated during pregnancy, afterload reduction can be achieved by a combination of hydralazin and nitrates, or calcium antagonists. Peripartal cardiomyopathy is rare and is associated with a high degree of maternal mortality (25-50%). Apart from the necessary consideration of pregnancy-related contraindications, therapeutic principles do not differ from those for other forms of heart failure. Most patients exhibiting hypertrophic obstructive cardiomyopathy satisfactorily pass through their pregnancies. Individual cases have been described, however, of both pregnancy-related cardiac decompensation as well as sudden death. Aortal and coronary-arterial dissections represent rare, life-endangering complications for mother and fetus: these developments can occur among predisposed patients as a result of the hormonal and hemodynamic adaptation processes during pregnancy. Close interdisciplinary collaboration and tightly networked support for patients are the prerequisite for successful management of high-risk pregnancies involving maternal heart disease.
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PMID:[Pregnancy risks in acquired heart diseases]. 1137 39


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