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)

Diuretics were used in most of the major trials that demonstrated that lowering the blood pressure reduced cardiovascular morbidity and mortality. Nevertheless in the second half of the eighties, there were misgivings about the widespread use of thiazide diuretics, driven in part by the relative failure of the large trials to reduce myocardial infarction-to the extent predicted by large scale epidemiological studies. There was much attention on metabolic side effects of thiazide diuretics including dyslipidaemia, glucose intolerance, hypokalaemia, hyperuricaemia, and then microalbuminuria particularly in diabetic subjects. These issues were current when JNC (IV) (1988) and the WHO-ISH guidelines (1989) were being written. Three major clinical trials SHEP, STOP and MRC published in the early nineties established that thiazide diuretics alone, or in combination with beta blockers, did reduce cardiovascular morbidity and mortality in elderly subjects with hypertension. All guidelines published since 1993 include diuretics among the first line drugs. Possibly the most important factor in the restoration of diuretics has been the use of progressively lower doses that minimise the metabolic side effects. Diuretics are effective as monotherapy in the treatment of mild essential hypertension and of isolated systolic hypertension in elderly subjects. They are very useful in combination with beta blockers or with ACE inhibitors. They should be avoided in patients with gout and should not be used as first line drugs in patients with diabetes. They should only be used with caution in young obese subjects with dyslipidaemia and increased risk of coronary artery disease, facing many decades of treatment for hypertension. However there is no doubt that diuretics are effective, cheap and have a central role in the control of hypertension in all communities around the world.
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PMID:[Role of diuretics in the treatment of hypertension: from large controlled trials to international guidelines]. 895 12

Since most developed countries have an ageing population, the prevalence of hypertension is increasing. This age-driven increase in cardiovascular risk is an important factor contributing to the increasing burden of mortality and morbidity associated with cardiovascular disease. Today, there is a strong rationale for an aggressive approach to hypertension since antihypertensive treatment has been shown to reduce cardiovascular mortality and morbidity in the elderly. It is likely that increasing emphasis will be placed on control of isolated and borderline systolic hypertension, which are the predominant forms of hypertension in elderly patients. The recent second Swedish Trial in Old Patients with Hypertension (STOP-Hypertension-2) represents an important contribution to the literature since it shows that newer antihypertensive agents, such as angiotensin converting enzyme (ACE) inhibitors and calcium antagonists, are as effective as older agents in reducing cardiovascular mortality and morbidity in elderly patients.
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PMID:The problem of hypertension in the elderly. 1105 64

The second Swedish Trial in Old patients with Hypertension (STOP-Hypertension-2) was conducted to compare the effects of "newer" antihypertensive therapies (angiotensin converting enzyme [ACE] inhibitors and calcium antagonists) and established therapies (beta-blockers and diuretics) on cardiovascular mortality and morbidity in elderly hypertensive patients. A total of 6614 patients were randomized to receive conventional treatment, ACE inhibitors or calcium antagonists, and followed for a mean of 5 years. The primary endpoint was a combination of fatal stroke, fatal myocardial infarction and other fatal cardiovascular disease; secondary endpoints were a combination of fatal or non-fatal stroke or myocardial infarction, and other cardiovascular mortality. The three treatments produced similar reductions in supine systolic blood pressure. There were no significant differences in the risk of cardiovascular events between patients receiving conventional therapy and those receiving newer therapies. All three treatments were well tolerated. The STOP-Hypertension-2 results thus add to the extensive literature showing the benefits of blood pressure reduction in elderly hypertensive patients. Moreover, they are consistent with current management guidelines which emphasise the importance of the achieved blood pressure reduction in the prevention of cardiovascular events.
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PMID:Results of the STOP-Hypertension-2 trial. 1105 67

The 1999 hypertension management guidelines issued by the World Health Organization and the International Society of Hypertension emphasize the importance of blood pressure reduction in the prevention of cardiovascular events. Furthermore, they conclude that the benefits of treatment are due to blood pressure lowering per se, rather than to any specific antihypertensive therapy. The results of the second Swedish Trial in Old Patients with Hypertension (STOP-Hypertension-2) are consistent with these recommendations, since in this trial angiotensin converting enzyme (ACE) inhibitors and calcium antagonists reduced blood pressure to the same extent as conventional therapy with beta-blockers and diuretics in elderly hypertensive patients, and the three treatments produced similar reductions in the risk of cardiovascular events. Furthermore, a first subgroup analysis of cardiovascular mortality showed that the three treatments seemed equally effective in diabetic patients. The STOP-Hypertension-2 data, therefore, are fully consistent with the 1999 hypertension management guidelines, and underline the advantages offered by both older and newer antihypertensive therapies.
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PMID:The outcome of STOP-Hypertension-2 in relation to the 1999 WHO/ISH hypertension guidelines. 1105 68

Hypertension has a high prevalence among elderly patients. Randomised trials have already demonstrated that treating healthy older persons with hypertension is highly efficacious. Nevertheless some questions have arisen. On the one hand the generalizability of these trial results, particularly for older persons with serious medical comorbidities and poor functional status, is not clear. On the other hand different antihypertensive drugs have shown to be effective. Which drug for which patient? Even data from randomised intervention trials showing that the treatment affects cardiovascular morbidity and mortality, were missing, ACE inhibitors have been used for more than a decade to treat high blood pressure. For a younger population the captopril prevention project showed no differences between ACE inhibitors and conventional antihypertensive treatment (diuretics, beta-blocker) concerning the primary endpoints (myocardial infarction, stroke and other cardiovascular death). The STOP-2 study also confirmed these results for elderly patients. When treating elderly patients one must be aware of physiological changes with age and the comorbidities. Of significance among this patient group is declining renal function. Admissions for uraemia that are related to the use of ACE inhibitors are still commonplace, although many cases are preventable by monitoring renal function, but guidelines are still missing. Concerning the comorbidities ACE inhibitors have benefits compared to other antihypertensive drugs, especially in cases of heart failure, diabetes and coronary heart disease.
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PMID:The role of ACE inhibitors in the treatment of hypertensive elderly patients. 1120 Oct 13

In the last few years several large intervention trials have addressed the treatment of hypertension in the elderly and how far blood pressure should be lowered in such patients. The positive results of intervention against high blood pressure in the elderly has resulted in a positive attitude towards treatment and today this is an accepted and highly effective medical intervention. Both stroke and coronary morbidity have been shown to be positively affected as has total mortality. The specific issue, how far to lower blood pressure in the elderly was probably best addressed in the Hypertension Optimal Treatment (HOT) stduy in which about a third of the patients, i.e. >6,000 patients, were > or =65 years of age. In most of the early intervention studies of antihypertensive treatment in elderly patients diuretics or beta-blockers or the two in combination were used as the therapy by which blood pressure was lowered. However, novel therapies, in particular calcium antagonists, have shown benefits of the same magnitude as the older therapies, e.g. in the STONE trial, the Syst-Eur study, the Syst-China study and the STOP-Hypertension-2 study. In the latter study a regimen based on either of two ACE inhibitors was also shown to be equally effective as conventional treatment, based on diuretics and/or betablockers, in the elderly. These trials will be briefly reviewed here as will the SCOPE study which is an ogoing trial in which hypertensive patients aged 70-89 years are being treated with an angiotensin II receptor antagonist under double-blind and placebo-controlled conditions. It can be concluded that a wealth of information, based on large intervention trials, has been accumulated during the last decade. It is quite obvious that the elderly hypertensive patients benefit from antihypertensive treatment to at least the same extent as the young and middle-aged. It appears that blood pressure ought to be lowered down to normotensive values also in the elderly in order to minimize their risk if cardiovascular complications, although more studies would be welcome to address this issue specifically in the elderly.
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PMID:How far should we lower blood pressure in the elderly. 1171 98

The importance of type 2 diabetes is due to its high prevalence, the difficulties in achieving optimal glucose control (financial, time, quality of life) and the high frequency of chronic microvascular and macrovascular complications that add very significantly to the morbidity, mortality and overall cost of the disease. Numerous risk factors have been identified that predict the future onset of type 2 diabetes in individuals and an early stage of the disease (impaired glucose tolerance) can often be identified. Insulin resistance is central to the pathogenesis and is initially compensated by an increased insulin secretion. Over time, insulin secretion progressively fails and diabetes appears. Several approaches have been proposed for the prevention of diabetes. Lifestyle changes (nutritional therapy and physical activity) have been shown to reduce the frequency of diabetes in small studies and are being assessed in the NIH-funded Diabetes Prevention Trial. Metformin, which reduces insulin resistance and hyperinsulinaemia, is being assessed in this same trial. Acarbose, which has been shown to reduce post-prandial insulin secretion and improve insulin resistance, is being assessed in the STOP-NIDDM trial. The ACE inhibitor ramipril has been shown in the HOPE study to reduce the appearance of diabetes by one third when given to patients with vascular disorders and this class of agents has been shown to improve insulin resistance. Another very promising approach is the use of thiazolidinediones (rosiglitazone, pioglitazone) to improve the insulin resistance and possibly preserve the beta cells by reducing the need for increased insulin secretion. These lifestyle changes and medications have been shown to be safe in the treatment of type 2 diabetes. There is a high probability that one of these approaches will be effective in delaying or preventing type 2 diabetes, and prevention may become a clinical reality in the near future.
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PMID:Prevention of type 2 diabetes. 1196 30

The frequency of arterial hypertension occurrence in polish population amounts to 30-40%, among diabetics is significantly higher-70%. According to the WHO/ISH Guidelines all hypertensive patients with diabetes are included into the "high risk group" independent of hypertension stage. Pharmacological treatment of hypertension is this group of patients has a particular meaning. Among hypertensive patients the degree of blood pressure lowering is more effective for cardiovascular risk reduction than choice of drug. This fact is well documented in clinical trials comparing antihypertensive efficacy of old and new antihypertensive drugs (for example UKPDS, STOP 2, INSIGHT). From the other point of view renal protection and metabolic benefits, as well as reduction of target organ damage are more advantageous for angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and calcium antagonists than for diuretics and beta-blockers. Despite fast progress in clinical research on new antihypertensive drugs (especially AT1 receptor inhibitors) ACE-I seem to still remain still the "first choice" for hypertensive diabetics. Adequate blood pressure control among diabetic hypertensives is of special importance and usually needs appropriate combined antihypertensive therapy. Our review presents detailed information about treatment advantages and disadvantages of drugs from different antihypertensive classes in light of current clinical trials and international guidelines.
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PMID:[Antihypertensive treatment for patients with hypertension and diabetes type II--current clinical research]. 1293 58

EFFICACY OF CALCIUM ANTAGONISTS: Calcium-channel blockers (CCBs) have long been recognized as potent agents for hypertensive therapy, with substantial blood pressure reduction in all age groups and races. CCBs improve endothelial function, may positively influence atherosclerosis in carotid arteries, reduce left ventricular hypertrophy, and hypertrophy of the resistance vessels, and improve arterial compliance. They do not adversely affect lipids and serum glucose. USE IN PRACTICE: CCBs are also a heterogenous class of drugs composed of the phenylalkylamine verapamil, the benzothiazepine diltiazem, and the large group of dihydropyridines (DHPs) with the prototype nifedipine, and an increasing number of newer agents (e. g. nitrendipine, nisoldipine, amlodipine, felodipine, lacidipine and lercanidipine). DHPs are primarily vasodilators, lowering blood pressure by decreasing peripheral vascular resistance at the level of the small arterioles which can be followed by an autonomic counterregulation especially in drugs with a rapid onset of action. This is markedly reduced or abolished in the treatment with the modern long acting DHPs and is also not the case in the treatment with non-DHPs. Prospective randomized controlled outcome studies demonstrated a significant reduction in stroke in elderly patients with isolated systolic hypertension compared with placebo (Syst-Eur [Syst-China]), and no significant differences in cardiovascular mortality and combined morbidity compared with diuretics, beta blockers or ACE-Inhibitors (STOP-2, INSIGHT, NORDIL, ALLHAT, INVEST). To normalize the blood pressure it is mostly necessary to combine antihypertensive drugs. Here are CCBs ideal partners for a therapy with ACE-inhibitors, AT1 antagonists or beta blockers (DHP) and diuretics (verapamil). With respect to the antihypertensive differential therapy the author recommends CCBs based on studies with the evidence grade 1-3; especially for elderly hypertensives (with isolated systolic neuhypertension and a high risk of stroke), for patients with COPD and asthma bronchiale, Raynaud's syndrome or Prinzmetal-angina, patients with diastolic function disturbances including diastolic heart failure or hypertensives with massive left ventricular hypertrophy (in combination with ACE or AT1 inhibitors).
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PMID:[Differential therapy with calcium antagonists]. 1468 11

Type 2 diabetes mellitus is a major health problem associated with excess morbidity and mortality. Defects in the action and/or secretion of insulin are the two major abnormalities leading to development of glucose intolerance. Any intervention in the impaired glucose tolerance phase that reduces resistance to insulin or protects the beta-cells, or both, should prevent or delay progression to diabetes. The natural history of type 2 diabetes includes a preceding period of impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) which provides an opportunity for targeted intervention within large communities. As the prevalence of this metabolic disorder is rapidly increasing and current treatment fails to stabilise the disease in most patients, prevention should be considered as a key objective in the near future. Lifestyle intervention studies have consistently shown that quite modest changes can reduce the progression from IGT to diabetes by 50-60%. The Diabetes Prevention Program (DPP) randomised trial has shown that a combined program of weight loss, improvement of diet and increase of physical exercise lowers the risk for development of type 2 diabetes by 58% compared with placebo. It may, however, not be possible to translate these successful findings to larger cohorts or maintain the lifestyle changes longer term. This has lead to consideration of pharmacotherapy. Benefits have been found for metformin, acarbose and troglitazone. Treatment with metformin was less effective than lifestyle modifications, resulting in an average reduction of risk for development of type 2 diabetes by 31% compared with placebo. Similarly, acarbose in the STOP-NIDDM trial reduced the risk of developing type 2 diabetes in patients with IGT by 25%. Remarkably, cardiovascular event rates, in particular myocardial infarction, were significantly reduced when acarbose was used instead of placebo in subjects with glucose intolerance. The ACE inhibitors captopril (CAPPP) or ramipril (HOPE) and the Angiotensin-II receptor antagonist losartan (LIFE) have been shown to reduce the appearance of diabetes by one third when given to patients with hypertension. Since many hypertensive patients are insulin-resistant and have an increased risk in developing type 2 diabetes, the protective effect of these classes of antihypertensive drugs might be explained by their antiinsulin-resistance effects.
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PMID:[Progress in the prevention of type 2 diabetes]. 1474 78


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