Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Future trends in hypertensive treatment have to rely on our past and present experience with antihypertensive drugs as well as on emerging concepts of blood pressure regulation, on which some new drugs in the "pipeline" are based. Early detection of hypertension, before organ manifestations particularly in the heart, the kidney and the vessels occur, remain mandatory since in most of the patients with mild and moderate hypertension the high blood pressure is not diagnosed at all or treated inadequately. Prevention of cardiac, vascular, renal or metabolic complications has always been better for the patient and less costly than their repair or reparation. Our present treatment goals have often not reached far enough. Normalisation of blood pressure demonstrates only surrogate efficacy of our treatment. Our ultimate goal has to be improvement of total or cerebrovascular or cardiovascular and cardiac mortality. Important steps on that road are the prevention or reparation of cardiac hypertrophy, of the increased extracellular matrix and collagen deposition, the conservation of vascular integrity including both coronary and systemic microangiopathy and macroangiopathy. For the patient this means integrated care of his associated disorders that is of coronary artery disease, diabetes mellitus, lipid disorders, overweight and the metabolic syndrome. True health efficacy (= reduction of total or cerebro- and cardiovascular mortality) has been demonstrated so far only by blood pressure reduction with diuretics (thiazides) and beta-blockers in long term studies, whereas sufficient surrogate efficacy, the lowering of blood pressure, has been demonstrated with almost all the others drugs either in mono- or in combinationtherapy. Together with ACE-inhibitors, which have demonstrated their prognostic value in patients with heart failure of different causes, thiazides (as the most representative diuretic) and betablockade can be considered first line drugs in the treatment of hypertension. Long-term mortality trials for ACE-inhibitors in hypertension are needed, however, to prove that the anticipated benefit from the heart failure megatrials can also be taken for granted for hypertensive patients without coronary artery disease as well. All other drugs should not or not yet be considered first line medication, although treatment behavior in the US and in Europe shows wide-spread use of calcium antagonists in short- and long-acting dihydropyridine type hypertensive patients. No peer reviewed journal has so far published a randomized double-blind trial with the endpoint of total or cardiovascular mortality in hypertension using calcium antagonists. A recent case control study, as well as the preliminary data from MIDAS and GLANT, for which event rates are available in abstract form, suggest that short acting calcium-antagonists of the dihydropyridine type, though controlling blood pressure well, are not reducing mortality but show a trend to increase cardiovascular events particularly when given in higher doses. In contrast the unpublished data from a Chinese megatrial with dihydropyridines (STONE) demonstrate effective blood pressure reduction and benefit in mortality in a population that differs from patients in Europe and in the USA because of the low prevalence of coronary artery disease. No randomized, double blindly acquired data on mortality as the primary end of antihypertensive treatment are yet available for verapamil, diltiazem and the new class of longer acting calciumantagonists. Only when speculating from trials with calcium antagonists in coronary artery disease e.g. the DAVIT II study, one could imagine so far that prognostic benefit may be expected from drugs that do not or very little activate the adrenergic and the renin-angiotensin-aldosterone system and the baroreceptors and reduce or at least maintain heart rate. The need for double blind, randomized trials with the different Ca-antagonists is obvious, before a further w
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PMID:[Retrospective studies and prospects of therapy for hypertension]. 858 97

The issue as to whether antihypertensive drugs may exert some antiatherosclerotic effect, at least partly independent of blood pressure lowering, has been explored in several experimental models of atherosclerosis, and a large body of evidence has been obtained in favor of a specific antiatherosclerotic action of calcium antagonists and ACE-inhibitors. On the clinical side, several studies are investigating the problem in hypertensive patients in whom progression of carotid intima-media thickness (IMT) and atherosclerotic plaques is explored by sensitive quantitative B-mode ultrasound techniques. The MIDAS has indicated a slower progression, at least in the first six months, of carotid plaques in isradipine treated patients than in diuretic-treated ones. However, MIDAS as a pioneer study has been particularly valuable in giving information on the rate of growth of IMT in hypertensive patients and on the best end-point to use in carotid ultrasound trials. Baseline data of the ongoing studies ELSA and VHAS have so far provided evidence of the very high prevalence of carotid atherosclerosis among hypertensive patients, an observation that makes the evaluation of the antiatherosclerotic action of some antihypertensive agents even more important. Finally, the PHYLLIS trial using a factorial design, beside exploring the antiatherosclerotic action of an ACE-inhibitor vs a diuretic, intends to evaluate the possible benefits of associating antihypertensive therapy with lipid lowering by a statin on the progression of carotid atherosclerosis.
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PMID:Antiatherosclerotic effects of antihypertensive drugs: recent evidence and ongoing trials. 874 37

Calcium antagonists are indicted as a potential trigger of a variety of complications spanning from myocardial infarction to bleeding and cancer. Three randomised controlled trials, the MIDAS, the FACET and the ABCD trial, seem to suggest that the risk for myocardial infarction is increased in diabetics on calcium antagonists. These trials in aggregate totalled only 92 cardiovascular events and it is possible that the observed differences were due to random errors. Most of the patients of the ABCD trial discontinued the medication to which they were initially randomised before the end of the study, which raised the possibility of systematic bias. In both the MIDAS and ABCD studies cardiovascular events were secondary end-points and the apparent adverse effects were identified only by subgroup analyses. Furthermore, in both studies, patients in the control groups were being treated with ACE inhibitors. The lack of a placebo group makes it impossible to establish whether the observed effects were due to the harmful influence of calcium antagonism or to the favourable effects of ACE inhibition. New data abstracted from the PIUMA database show that the rate of total cardiovascular and cardiac events did not differ between diabetics on calcium antagonists and diabetics not using these drugs. These new data are in keeping with findings in the HOT study where an impressive degree of cardiac protection was observed in diabetic patients on felodipine.
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PMID:Calcium channel blockers in diabetic subjects: innocent at last? 1078 56

Novel N-tuple topological/geometric cutoffs to consider specific inter-atomic relations in the QuBiLS-MIDAS framework are introduced in this manuscript. These molecular cutoffs permit the taking into account of relations between more than two atoms by using (dis-)similarity multi-metrics and the concepts related with topological and Euclidean-geometric distances. To this end, the kth two-, three- and four-tuple topological and geometric neighbourhood quotient (NQ) total (or local-fragment) spatial-(dis)similarity matrices are defined, to represent 3D information corresponding to the relations between two, three and four atoms of the molecular structures that satisfy certain cutoff criteria. First, an analysis of a diverse chemical space for the most common values of topological/Euclidean-geometric distances, bond/dihedral angles, triangle/quadrilateral perimeters, triangle area and volume was performed in order to determine the intervals to take into account in the cutoff procedures. A variability analysis based on Shannon's entropy reveals that better distribution patterns are attained with the descriptors based on the cutoffs proposed (QuBiLS-MIDAS NQ-MDs) with regard to the results obtained when all inter-atomic relations are considered (QuBiLS-MIDAS KA-MDs - 'Keep All'). A principal component analysis shows that the novel molecular cutoffs codify chemical information captured by the respective QuBiLS-MIDAS KA-MDs, as well as information not captured by the latter. Lastly, a QSAR study to obtain deeper knowledge of the contribution of the proposed methods was carried out, using four molecular datasets (steroids (STER), angiotensin converting enzyme (ACE), thermolysin inhibitors (THER) and thrombin inhibitors (THR)) widely used as benchmarks in the evaluation of several methodologies. One to four variable QSAR models based on multiple linear regression were developed for each compound dataset following the original division into training and test sets. The results obtained reveal that the novel cutoff procedures yield superior performances relative to those of the QuBiLS-MIDAS KA-MDs in the prediction of the biological activities considered. From the results achieved, it can be suggested that the proposed N-tuple topological/geometric cutoffs constitute a relevant criteria for generating MDs codifying particular atomic relations, ultimately useful in enhancing the modelling capacity of the QuBiLS-MIDAS 3D-MDs.
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PMID:N-tuple topological/geometric cutoffs for 3D N-linear algebraic molecular codifications: variability, linear independence and QSAR analysis. 2770 4