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)

Essential hypertension is, at least in many subjects, associated with a decrease in insulin sensitivity, whereas glycemic control is (still) normal. Metaanalyses of hypertension intervention studies revealed different efficacy of treatment on cerebral (cerebrovascular accidents [CVA]) and cardiac (coronary heart disease [CHD]) morbidity and mortality. Although CVA were reduced to an extent similar to that anticipated, the decrease in CHD was less than expected. These differences are likely to be caused by the different impact of concomitant cardiovascular risk factors, such as dyslipidemia, impaired glucose tolerance, and non-insulin-dependent diabetes mellitus on CHD and CVA. Frequently these cardiovascular risk factors are ineffectively controlled in hypertensive patients, and moreover, some of the widely used antihypertensive agents have unfavorable side effects and further deteriorate these particular metabolic risk factors. Therefore, the metabolic side effects of antihypertensive treatment have received more attention. During the past few years, studies demonstrated that most antihypertensive agents modify insulin sensitivity in parallel with alterations in the atherogenic lipid profile. Alpha1-blockers and angiotensin converting enzyme inhibitors were shown to either have no impact on or even improve insulin resistance and the profile of atherogenic lipids, whereas most of the calcium channel blockers were found to be metabolically inert. The diuretics and beta-adrenoreceptor antagonists further decrease insulin sensitivity and worsen dyslipidemia. The mechanisms by which beta-adrenoreceptor antagonist treatment exert its disadvantageous effects are not fully understood, but several possibilities exist: significant body weight gain, reduction in enzyme activities (muscle lipoprotein lipase and lecithin cholesterol acyltransferase), alterations in insulin clearance and insulin secretion, and, probably most important, reduced peripheral blood flow due to increase in total peripheral vascular resistance. Recent metabolic studies found beneficial effects of the newer vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. In many hypertensive patients, elevated sympathetic nerve activity and insulin resistance are a deleterious combination. Although conventional beta-blocker treatment was able to take care of the former, the latter got worse; the newer vasodilating beta-blocker generation seems to be capable of successfully treating both of them.
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PMID:Antihypertensive therapy and insulin sensitivity: do we have to redefine the role of beta-blocking agents? 979 45

In Eisenmenger's syndrome a central left-to-right shunt in the heart, a congenital anomaly, leads to pulmonary hypertension which subsequently causes the shunt to be reversed. The hypoxaemia resulting from a right-to-left shunt is compensated by an increase of the haemoglobin concentration due to a rise of the haematocrit. In adult patients not operated (adequately), the symptoms are the consequence of the erythrocytaemia and an increased haemorrhagic diathesis. In the long run heart failure develops. Phlebotomy is indicated for patients with haematocrits higher than 0.65 with signs of hyperviscosity and is also advised before non-cardiac surgery to improve coagulation parameters. Phlebotomy should be performed slowly (500 ml in 30-45 min) with simultaneous volume replacement. Excessive phlebotomy causes iron deficiency and spherocytosis which increase viscosity as well as the risk of CVA. Treatment consists of iron supplementation. Anticoagulation is indicated only in case of atrial fibrillation or mechanical valves. The use of acetylsalicylacid or NSAIDs is relatively contraindicated, because of abnormal haemostasis in these patients. During treatment with ACE inhibitors and other vasodilators, hypovolaemia should be avoided, because at a lower systemic blood pressure the right-to-left shunt increases and a potentially fatal cyanosis may occur.
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PMID:[Eisenmenger syndrome in adults]. 1032 Dec 57

The results of several large therapeutic cardiovascular trials were reported in 2002. The LIFE study concluded that losartan is superior compared to atenolol in terms of prevention of cardiovascular morbidity and mortality, the benefit being for CVA without changing the incidence of myocardial infarction. The OPTIMAAL study stated the disappointing results of post-infarct losartan. The IONA study represents a first demonstration with nicorandil of benefit not only in angina crises but equally on cardiac morbidity and mortality. The HPS study confirms the benefit of a statin in secondary prevention but for the first time, no matter what the initial level of LDL-cholesterol. Finally in the LIPS study, it is reported that statins reduce major cardiovascular events after coronary angioplasty. The year 2002 was marked elsewhere by imagination after the publication of the RAVEL study on coated stents delivering anti-proliferative drugs in order to avoid coronary restenosis. Three drugs were the subject of work confirming their potential significance in cardiovascular pathology: a) ezetimibe, representing a new class of cholesterol lowering drugs with which the association with statins seems especially synergic, b) nesiritide recombinant type B natriuretic peptide, whose significance was confirmed in acute cardiac insufficiency. c) levosimendan (calcium sensitisor) which moreover can be a significant treatment in cardiac decompensation as suggested by the LIDO study with a follow up of 180 days. By contrast, omapatrilate did not confirm its potential superiority over ACE inhibitors in the treatment of cardiac insufficiency. Some encouraging data were reported in 2002 in the field of therapeutic angiogenesis as much at the myocardial level as in lower limb arteritis. Finally, 2002 was marked by the publication of the WHI study which intensified suspicions regarding hormonal substitution treatment, confirming the advantage of not only secondary but perhaps primary cardiovascular prevention.
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PMID:[The best of clinical pharmacology in 2002]. 1261 62

All antagonists (sartans) are considered to be a group of pharmaceuticals with comparable indications and comparable effects as ACE inhibitors, while almost lacking the side effect ofa dry cough. Large clinical trials showed that All antagonists had a comparable (statistically insignificantly smaller) effect on so called "hard targets", i.e. mortality and morbidity, in patients with ischemic heart diseases and/or heart failure. The study of their effect in the treatment of hypertension was first limited to diabetics and patients with microalbuminuria and showed that they had a significant renoprotective effect in said cases. Large clinical trials followed, focusing on hypertension in primary as well as secondary prevention of cardiovascular diseases. Five large clinical trials focusing on All antagonists addressed cerebrovascular accidents and cognitive functions: LIFE, SCOPE, OSCAR, MOSES and POWER. The LIFE study (Losartan Intervention For Endpoint) confirmed that in 9,193 patients with proven left ventricular hypertrophy, losartan led to a lower incidence of cerebrovascular accidents or new development of diabetes mellitus than atenolol, which in turn led to statistically significant lower primary endpoint (fatality, myocardial infarction and cerebrovascular accident) (p = 0.021), while blood pressure dropped at the same rate. The SCOPE study (Study on COgnition and Prognosis in Elderly hypertensives) compared candesartan with another antihypertensive treatment in 4,937 hypertonic patients older than 70. The primary endpoint was a decrease in massive cardiovascular accidents (fatality, MI, CVA). The decrease rate reached 10.9%, which was not considered statistically significant (p = 0.19). However, statistically significant was the decrease in cerebrovascular accidents (p = 0.04). The MOSES study (Morbidity and mortality after stroke) compared eprosartan and nitrendipine in secondary prevention of cerebrovascular diseases in 1,405 patients. Blood pressure was reduced to a comparable extent without showing significant differences between the two groups. During the study period, a total of 461 primary accidents occurred: 206 in patients with eprosartan and 255 in patients with nitrendipine (p = 0.014). Cardiovascular accidents were: 77 with eprosartan and 101 with nitrendipine (p = 0.06); cerebrovascular accidents were: 102 with eprosartan and 134 with nitrendipine (p = 0.03). OSCAR study was an open study with the objective to assess the impact of eprosartan treatment on cognitive functions. Use of eprosartan was associated with a significant reduction in blood pressure from 161.9/93.1 mm Hg to 136.1/80.8 mm Hg after 6 months (p < 0.0001). The total average score of the MMSE test after the completion of the follow-up period was 27.9 - 2.9 compared to 27.1 + 3.4 at the beginning (p < 0.0001). The results of the OSCAR study support the statement that antihypertensive treatment based on drugs that target the reninangiotensin system is associated with the preservation of cognitive functions. The POWER study proved in a large unselected population the suitability and practical aspect ofa reduction in the total cardiovascular risk by means of systematic treatment of high blood pressure.
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PMID:[AII antagonists in the treatment of hypertension and prevention of CVA]. 2356 27