Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
...
PMID:The role of ACE inhibitors in the treatment of hypertensive elderly patients. 1120 Oct 13

More than 50% of hypertensive patients are aged above 65 years. Physiopathology of essential hypertension is different in the elderly as compared with the young adult. Furthermore, not only are concomitant diseases statistically more frequent in the elderly, but the aging process in itself produces several specific changes in target organs. Several trials have shown that treatment of hypertension in the elderly, including the 'old elderly', is highly beneficial in terms of reduced morbidity and mortality. The therapy used in all these major intervention trials consisted of diuretics and/or beta-blockers. Recently, the Systolic Hypertension in Europe study and the HOT study extended the list of antihypertensive agents with proven beneficial effects on cardiovascular outcomes to dihydropyridine calcium antagonists. Dihydropyridine calcium antagonists, such as lacidipine, have been advocated as first-choice agents for the treatment of hypertension in the elderly on grounds that: a) they may be more active in lowering blood pressure because of the predominantly low renin status in the elderly hypertensives; b) they may be better tolerated because the side effects related to the activation of the sympathetic system may be less frequent as a consequence of the attenuation of baroreflexes during aging; and c) they may have beneficial effects on a variety of concomitant cardiovascular diseases which are frequently present in the elderly. These assumptions are, however, not always proven in the clinical practice. Only well-designed prospective comparative trials may solve this issue. STOP-2, NICS-EH, HYVET, SCOPE and SHELL are acronyms of ongoing clinical trials specifically designed in the elderly hypertensive. The SHELL study assesses the benefits of lacidipine compared with chlortalidone on the prevention of cardiovascular events. The effects of lacidipine (vs atenolol) on the development and progression of carotid atherosclerosis are also being currently investigated in the ELSA study.
...
PMID:The potential advantages of a modern antihypertensive therapy in the elderly. 1134 57

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.
...
PMID:How far should we lower blood pressure in the elderly. 1171 98

Recent trials have helped to clarify indications for the initial pharmacological therapy of hypertension. Both the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and World Health Organization-international Society of Hypertension (WHO-ISH) recommendations should be revised. The more recent trials indicate that: (1) diuretics and beta-blockers appear to be as effective in reducing overall morbidity/ mortality as other agents (Swedish Trial in Old Patients with Hypertension [STOP-2], United Kingdom Prospective Diabetes Study [UKPDS], Intervention as a Goal in Hypertension Treatment [INSIGHT], Nordic diltiazem [NORDIL]); (2) the use of an a-blocker results in more cardiovascular events, especially congestive heart failure, when compared with a diuretic (Antihypertensive Therapy and Lipid Lowering Heart Attack Trial [ALLHAT]); (3)the use of an angiotensin-converting enzyme (ACE) inhibitor results in fewer myocardial infarctions and episodes of heart failure than calcium channel blockers in the elderly and in diabetic patients (Fosinopril vs. Amlodipine Cardiovascular Events Randomized Trial [FACET], Appropriate Blood Pressure Control in Diabetes [ABCD], STOP-2) - other data (Captopril Prevention Project [CAPPP]) suggest that the use of an ACE inhibitor is preferred in diabetic patients; (4) overall cardiovascular events are similar with calcium channel blockers compared with a diuretic - however, there are fewer strokes with non-dihydropyridine calcium channel blockers (NORDIL) and a trend towards an increase in heart failure and myocardial infarctions with either a dihydropyridine or non-dihydropyridine calcium channel blockers compared with a diuretic (INSIGHT, NORDIL); (5) angiotensin receptor blockers (ARBs) will decrease proteinuria and slow progression of renal disease in type 2 diabetic patients when compared with regimens that do not include an ARB or an ACE inhibitor (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL], Irbesartan Type II Diabetic Nephropathy Trial [IDNT], Irbesartan Type II Diabetes with Microalbuminuria [IRMA Il]). The debate over initial therapy may be moot. High-risk hypertensive patients should probably be treated initially with combination therapy, one of which should be a diuretic. The use of diuretics and beta-blockers as well as ACE-inhibitors alone or with a diuretic should be considered as initial therapy (a change from JNCVI). Alpha-blockers should be reserved for special situations, i.e. prostatic hypertrophy (in contrast to WHO-ISH recommendations). An ACE-inhibitor or ARB, usually along with a diuretic, can be considered as preferred therapy in hypertensive diabetic patients. Some data suggest equal or greater reduction in strokes with a calcium channel blocker than other medications.
...
PMID:Current recommendations for the treatment of hypertension: are they still valid? 1199 97

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.
...
PMID:[Antihypertensive treatment for patients with hypertension and diabetes type II--current clinical research]. 1293 58

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.
...
PMID:[Progress in the prevention of type 2 diabetes]. 1474 78

The STOP-NIDDM Trial has shown that acarbose treatment in subjects with impaired glucose tolerance is associated with a significant risk reduction in the development of diabetes, hypertension and cardiovascular complications. Kaiser and Sawicki have accused the investigators of the STOP-NIDDM Trial of major biases in the conduct of the study, of manipulating the data and of conflict of interest. The aim of this paper is to present data and explanations refuting these allegations. In the STOP-NIDDM Trial, 61 subjects were excluded from the efficacy analysis before unblinding for legitimate reasons: failure to satisfy major entry criteria (n=17) and lack of post-randomisation data (n=44). Blinding and randomisation were carried out by an independent biostatistician. Titration of placebo/acarbose is well described in the protocol and in the study design paper. Of the study population, 9.3% had a fasting plasma glucose of > or =7.0 mmol/l at screening and could have been diabetic according to the new diagnostic criteria. However, even if these subjects are excluded, patients having acarbose treatment still saw a significant risk reduction in the development of diabetes (p=0.0027). The changes in weight are consistent in different publications and are related to different times of follow-up and assessment. Weight change does have an effect on the development of diabetes, but acarbose treatment is still effective even after adjusting for this (p=0.0063). The cardiovascular endpoints were a clearly designated assessment in the original protocol, and only those defined in the protocol and ascertained by the independent Cardiovascular Event Adjudication Committee were used in the analysis. Hypertension was defined according to the most recent diagnostic criteria. The STOP-NIDDM Trial results are scientifically sound and credible. The investigators stand strongly behind these results demonstrating that acarbose treatment is associated with a delay in the development of diabetes, hypertension and cardiovascular complications in a high-risk population with IGT.
...
PMID:Acarbose for the prevention of Type 2 diabetes, hypertension and cardiovascular disease in subjects with impaired glucose tolerance: facts and interpretations concerning the critical analysis of the STOP-NIDDM Trial data. 1515 Jun 89

Most individuals with arterial hypertension or congestive heart failure are insulin-resistant and at a higher risk of developing type 2 diabetes (T2DM). The inhibition of the renin-angiotensin system (RAS), using an angiotensin converting enzyme inhibitor (ACEI) or a selective angiotensin receptor AT1 blocker (ARB), may exert favourable metabolic effects capable of preventing T2DM in high risk individuals. We performed a meta-analysis of randomised clinical trials (RCTs) assessing the effects of RAS inhibition on the incidence of new cases of T2DM in patients with arterial hypertension or congestive heart failure. Ten RCTs with cardiovascular prognosis as primary endpoints analysed the incidence of T2DM as secondary endpoints or as post-hoc analysis after a mean follow-up of 1 to 6 years: five with an ACEI and five with an ARB, compared with a placebo (n=4) or a reference drug (beta-blocker or diuretic: n=5; amlodipine: n=2). Eight RCTs concerned hypertensive patients: STOP Hypertension-2 (lisinopril or enalapril vs beta-blocker or diuretic), CAPPP (captopril vs thiazide or beta-blocker), HOPE (ramipril vs placebo), ALLHAT (lisinopril vs chlorthalidone and lisinopril vs amlodipine), LIFE (losartan vs atenolol), SCOPE (candesartan vs placebo), ALPINE (candesartan vs placebo) and VALUE (valsartan vs amlodipine). Two RCTs concerned patients with congestive heart failure: SOLVD (enalapril vs placebo) and CHARM-overall programme (candesartan vs placebo). Overall, 2 675 new cases of T2DM (7.40%) were observed in the group of 36 167 patients receiving a treatment with ACEI or ARA as compared with 3 842 events (9.63%) in the group of 39 902 control patients. A mean weighed relative risk reduction of new T2DM of 22% (95% CI: 18, 26; p<0.00001) was observed after RAS inhibition. The beneficial effect was similar with ACEIs and with ARBs as well as in patients with hypertension and in those with heart failure, and was also present whatever the comparator (placebo or beta-blockers/diuretics or amlodipine). The number needed-to-treat to avoid one new case of T2DM averaged 45 patients over 4-5 years. In conclusion, RAS inhibition consistently and significantly reduces the incidence of T2DM in individuals with arterial hypertension or with congestive heart failure. Considering the pandemic of T2DM, such pharmacological approach deserves further attention among the strategies aiming at preventing T2DM.
...
PMID:Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. 1567 18

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, diabetes, and atherogenic dyslipidemia. Recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome itself has been associated with endothelial dysfunction, one of the initial steps in the process of atherosclerosis. Postprandial hyperglycemia, one of the characteristic features of insulin resistance, induces oxidative stress generation and elicits vascular inflammation and platelet activation, thus being involved in the pathogenesis of atherosclerosis. A recent multicenter, placebo-controlled randomized trial, STOP-NIDDM trial, revealed that acarbose (Glucobay R), an alpha-glucosidase inhibitor, improved postprandial hyperglycemia and subsequently reduced the risk of development of type 2 diabetes in patients with impaired glucose tolerance (IGT). In this study, acarbose treatment was also found to slow the progression of intima-media thickness of the carotid arteries, a surrogate marker for atherosclerosis, and to reduce the incidence of cardiovascular diseases and newly diagnosed hypertension in subjects with IGT. Acarbose significantly reduced body mass index and waist circumference in these patients over 3 years. Furthermore, a meta-analysis of seven long-term studies has also shown that intervention with acarbose prevents myocardial infarction and cardiovascular diseases in type 2 diabetic patients. In this analysis, glycemic control, triglyceride levels, body weight and systolic blood pressure was also significantly improved during acarbose treatment. These observations suggest that prevention of postprandial hyperglycemia by acarbose may be a promising therapeutic strategy for reducing the increased risk for diabetes, hypertension, dyslipidemia, obesity, and cardiovascular diseases in patients with the metabolic syndrome. Acarbose improves postprandial hyperglycemia by delaying the release of glucose from complex carbohydrates in the absence of an increase in insulin secretion. Therefore, we would like to hypothesize here that this improvement in glucose metabolism could be associated with amelioration in insulin sensitivity, thus explaining the above-mentioned beneficial cardiometabolic actions of acarbose. Large clinical trials will provide us with more definite information whether acarbose treatment can improve insulin sensitivity and resultantly reduce the risk of diabetes, hypertension and cardiovascular diseases in patients with the metabolic syndrome.
...
PMID:Inhibition of postprandial hyperglycemia by acarbose is a promising therapeutic strategy for the treatment of patients with the metabolic syndrome. 1589 33

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, and diabetes. There is a growing body of evidence to show that nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of insulin resistant patients with the metabolic syndrome. Indeed, insulin resistance increases adipocyte lipolysis and subsequently elevates circulating free fatty acids, thus stimulating the accumulation of fatty acids in the liver (hepatic steatosis). Fatty acids elicit reactive oxygen species generation, thereby promoting disease progression to NASH by both lipid peroxidation and inflammatory cytokine production. Postprandial hyperglycemia, one of the characteristic features of insulin resistance, also induces oxidative stress generation, being involved in dysfunction of pancreatic beta cells and vascular wall cells in the metabolic syndrome. Recently, STOP-NIDDM trial revealed that acarbose (Glucobay), an alpha-glucosidase inhibitor, improved postprandial hyperglycemia and subsequently reduced the risk of development of type 2 diabetes and newly diagnosed hypertension in patients with impaired glucose tolerance. In this study, acarbose treatment was also found to reduce body mass index and waist circumference in these patients. Furthermore, a meta-analysis of seven long-term studies has also shown that intervention with acarbose improved triglyceride levels, body weight and systolic blood pressure and subsequently prevented myocardial infarction in type 2 diabetic patients. Since acarbose improves postprandial hyperglycemia by delaying the release of glucose from complex carbohydrates in the absence of an increase in insulin secretion, the beneficial aspects of acarbose could be ascribed to improvement of insulin sensitivity in these patients. Given the pathological link between NASH and insulin resistance, we would like to hypothesize here that acarbose may become a promising therapeutic strategy for the treatment of patients with NASH. Does acarbose treatment improve steatohepatitis histologically? Is the extent of histological improvement by acarbose parallel to that of insulin sensitivity in these patients? Large clinical trials will provide us with more definite information whether acarbose treatment can improve insulin sensitivity and resultantly reduce the risk of progression of liver diseases in patients with NASH.
...
PMID:Acarbose is a promising therapeutic strategy for the treatment of patients with nonalcoholic steatohepatitis (NASH). 1592 16


<< Previous 1 2 3 4 5 6 7 Next >>