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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological data have suggested that the incidence of hypertensive nephrosclerosis is increasing despite the development of newer drug treatments. Recently, we studied the effects of temporary treatment of prepubescent rats with angiotensin receptor blocker (ARB) on the development of hypertensive nephrosclerosis in later life. Studies were performed using stroke-prone spontaneously hypertensive rats(SHRSP) and Dahl salt-sensitive rats(Dahl-S). In the case of SHRSP, treatment with ARB or angiotensin converting enzyme inhibitor(ACEI) from weaning to puberty(3 to 10 weeks) resulted in a continued reduction of blood pressure, and attenuation of proteinuria and renal histological changes at 30 weeks. In the case of Dahl-S, the prepubertal treatment with ARB caused a partial, but statistically significant reduction in proteinuria and renal damage. These results may be relevant for understanding the mechanisms of development of hypertension and hypertensive renal damage in these animal models.
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PMID:[Prevention of hypertensive renal damage by prepubertal treatment with ARB]. 1239 92

Angiotensin II not only is a vasoconstrictor, but it also affects cell growth and apoptosis, inflammation, fibrosis, and coagulation. Blockade of the renin-angiotensin system, either with inhibitors of the generation of angiotensin (angiotensin-converting enzyme [ACE] inhibitors) or with blockers of angiotensin receptors, reduces blood pressure and inhibits other pathophysiological actions. These other effects provide benefits in coronary heart disease, heart failure, diabetic nephropathy, and stroke beyond blood pressure reduction. These benefits were first demonstrated with ACE inhibitors. However, the mechanism of action of angiotensin receptor blockers, which block angiotensin II stimulation at the angiotensin type 1 receptor but not at the type 2 receptor, may have advantages, particularly for endothelial dysfunction and vascular remodeling, as well as cardiac and renal protection. Recent multicenter trials suggest that ACE inhibitors and angiotensin receptor blockers may reduce morbidity and mortality associated with cardiovascular and renal disease beyond blood pressure reduction. Several studies with different angiotensin receptor blockers, including comparisons with ACE inhibitors, are under way, and should provide further guidance for their clinical use.
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PMID:Vascular and cardiac benefits of angiotensin receptor blockers. 1240 36

Because treating hypertension in the elderly so effectively reduces major cardiovascular events, it is vital to diagnose this very common condition early. Much of the hypertension that occurs with aging results from stiffening of the major capacitance arteries, typically marked by high systolic and low diastolic blood pressures. Pulse pressure, derived by subtracting diastolic from systolic values, is a useful index of stiffness, but new noninvasive techniques for measurement of arterial compliance have shown that blood pressures cannot reliably predict the state of the arteries in older people. The Systolic Hypertension in the Elderly Program (SHEP) and the Systolic Hypertension in Europe (Syst-Eur) trial demonstrated that treating hypertension in the elderly with diuretics or calcium channel blockers reduces strokes and cardiac events; these results are also clearly evident in high-risk groups like diabetics. Further analysis of Syst-Eur has suggested that a calcium channel blocker reduces new-onset dementia, while follow-up data from SHEP indicate that a diuretic provides survival and stroke benefits in obese or overweight elderly hypertensives, but not in the lean. In general, comparisons of antihypertensive agents, including diuretics, beta blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers have found similar clinical end point effects. But recently, the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study, performed in patients (average age, 67) with left ventricular hypertrophy and predominant systolic hypertension, showed that the angiotensin receptor blocker losartan was significantly more effective than the beta blocker atenolol in reducing such key outcomes as strokes and new-onset diabetes. Even so, careful but effective control of blood pressure in elderly patients, including those over age 80, still remains a critical factor in preventing major cardiovascular events.
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PMID:Outcomes of treating hypertension in the elderly: a short commentary on current issues. 1250 10

Type 2 diabetes is becoming very common and is closely linked to physical inactivity and obesity. It is associated with clustering of coronary risk factors and 60-80% of cases have hypertension. The first therapeutic action is appropriate adjustment of life style. Anti-hypertensive therapies such as diuretics, ACE inhibitors and calcium antagonists have been effective in reducing cardiovascular events in type 2 diabetes, though calcium antagonists may be less effective than older therapies and ACE-inhibitors in reducing the risk of heart attacks and heart failure (but possibly more effective in stroke reduction). Beta-blockers (BBs) have a poor image as a potential therapy due to apparent adverse effects on surrogate end-points such as insulin-resistance. However large, controlled trials have shown BBs to be highly effective in reducing the risk of cardiovascular events and death in post myocardial infarction patients with diabetes. The UKPDS study in type 2 diabetics with hypertension showed first-line beta-blockade to be at least as effective as ACE-inhibition in preventing all primary macrovascular and microvascular end-points. The active ingredient appears to be beta-1 blockade, acting not only to lower blood pressure but also to prevent sudden death and cardiovascular damage stemming from chronic beta-1 stimulation associated with raised noradrenaline activity. By contrast, in the LIFE study atenolol was less effective than the angiotensin receptor antagonist losartan in reducing cardiovascular events and all-cause mortality in mainly elderly hypertensives with diabetes. Thus the best beta-blocker results in reducing hard cardiovascular end-points occur in hypertension studies (including the UKPDS study) involving younger/middle aged (say less than 60-65 years) patients, with relatively high sympathetic activity, relatively compliant/elastic arteries (narrow pulse-pressure) and normally functioning beta-1 receptors. In elderly hypertensive patients beta-blockers may be given as second-line therapy on the back of a low-dose diuretic (but possibly as first line agent in elderly hypertensives with prior myocardial infarction). Thus inappropriate attention to surrogate end-points can lead to faulty prescribing habits. Beta-blockers, currently severely underprescribed, should be considered as a first line therapeutic option for all diabetics with ischaemic heart disease or younger/middle aged diabetics with hypertension (but co-prescribed with low dose diuretic therapy in the elderly). The active ingredient for cardiovascular protection appears to be beta-1 blockade; optimal efficacy in lowering blood pressure and safety e.g. reducing risk of bronchoconstriction, is achieved by choosing an agent with high beta-1 selectivity.
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PMID:Beta-blockers and diabetes: the bad guys come good. 1265 16

For patients with diabetes mellitus (DM), chronic complications can be devastating. Cardiovascular illness, the major cause of morbidity and mortality among these patients, encompasses macrovascular disease, with heart attacks, strokes, and gangrene; and microvascular disease, with retinopathy, nephropathy, and neuropathy (somatic and autonomic). Macrovascular events occur earlier in individuals with DM than in people without DM, and the underlying pathologies are often more diffuse and severe. Diabetic arteriopathy, which encompasses endothelial dysfunction, inflammation, hypercoagulability, changes in blood flow, and platelet abnormalities, contributes to the early evolution of these events. Efforts are under way to determine interventions that may have the potential to prevent or halt the complications of DM. Tight glucose and blood pressure (BP) control is known to improve the vascular status of patients with DM by varying degrees. Use of anti-inflammatory drugs and lowering low-density lipoprotein cholesterol (LDL-C) levels are also useful. An emerging understanding of the importance of small, dense LDL-C and the anti-inflammatory effects of statins has provided new algorithms for primary prevention of macrovascular disease. Antiplatelet agents have also been shown to be effective in the secondary prevention of cardiovascular events. In the ideal world every risk factor would be addressed and each person with DM would have excellent glycemic control, low to normal BP, and a low LDL level, and would be taking an angiotensin-converting enzyme (ACE) inhibitor, together with a statin, aspirin, and clopidogrel. Under these near-perfect conditions, the emerging epidemic of macrovascular disease could be contained. Microvascular disease, however, is a consequence of hyperglycemia. For every 1% reduction in glycosylated hemoglobin it is possible to achieve a 22% to 35% reduction in the microvascular complications. BP control is vital and the liberal use of ACE inhibitors and angiotensin receptor blockers to slow the progression of renal disease should drastically reduce the incidence of blindness, dialysis, and amputations. This article provides an overview of prevention of macrovascular disease such as stroke, myocardial infarction, and peripheral arterial disease and microvascular complications such as retinopathy, nephropathy, and neuropathy in patients with DM.
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PMID:Prevention of the complications of diabetes. 1265 55

The cardiovascular continuum describes the way from risk factors to atherosclerosis, acute cardiovascular events (unstable angina and myocardial infarction), and development of terminal heart failure and its complications. Following this way, advances are reported in the therapy of acute coronary syndrome, heart failure, ventricular and supraventricular tachyarrhythmias, and stroke in patients with patent foramen ovale. The following issues are reported in detail: (1) significance of statins and statin withdrawal, glycoprotein IIb/IIIa receptor blocker, acute coronary interventions, aspirin and clopidogrel in unstable coronary syndromes, (2) pathogenesis of acute pulmonary edema associated with hypertension, (3) cardiac regeneration capability after transplantation and myocardial infarction, (4) beta-blocker therapy, efficacy of additional angiotensin receptor blocker therapy and multisite biventricular pacing in symptomatic (advanced) heart failure, (5) prognosis after ablation of the atrioventricular node in patients with atrial fibrillation, (6) primary prevention with an implantable defibrillator and resumption of driving after implantation, and (7) therapeutic options after cryptogenic stroke and patent foramen ovale.
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PMID:[Update cardiology 2001/2002-part II. From unstable coronary syndrome to terminal heart failure]. 1281 17

Hypertension is a nutritional-hygienic disease. Long-term caloric intake in excess of energy expenditures, chronic supraphysiological intake of dietary sodium, excessive alcohol consumption, and psychosocial stressors all contribute to the development of hypertension throughout the world. Elevated BP, particularly systolic BP, has been linked to multiple adverse clinical outcomes including stroke, heart failure, myocardial infarction, renal insufficiency/failure, peripheral vascular disease, retinopathy, dementia, and premature mortality. These undesirable clinical outcomes are typically, although not invariably, preceded by pressure-related target-organ injury such as left ventricular hypertrophy, renal insufficiency and proteinuria. The relation of BP and CKD and, in turn, the prevention of CKD or forestalling its progression by hypertension treatment, will be the focus of this manuscript. In hypertensive persons with reduced kidney function and/or proteinuria, lowering BP with multidrug therapy that is inclusive of pharmacologic modulators of the renin-angiotensin-aldosterone-kinin system is an effective strategy to forestall the progressive loss of kidney function. The totality of data support low therapeutic BP targets for persons with proteinuria >1 g/d. Nevertheless, in persons with CKD, even those with proteinuria below the dipstick positive level (approximately 300 mg/d or urine protein to creatinine ratio of 0.22), aggressive BP control also may be warranted because of the high risk of nonrenal cardiovascular disease. Multiple antihypertensive drugs will be required in the vast majority of patients with diabetes and/or reduced kidney function to attain BP goal. Renin-angiotensin system (RAS) modulator therapy is indicated among persons with diabetes mellitus and CKD. Available data support the use of angiotensin receptor blockers in persons with type 2 diabetes and overt nephropathy for preservation of kidney function. Among persons with type I diabetes with or without overt nephropathy, type 2 diabetes without overt nephropathy and in nondiabetic CKD, the available clinical data support the use of angiotensin-converting enzyme inhibitors as the RAS modulator of choice. Low therapeutic target BP levels <130/80 mmHg in persons with type 2 diabetes mellitus also appear warranted based on available data mostly for reducing the risk of nonrenal cardiovascular disease and overall mortality.
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PMID:Prevention of hypertension and its complications: theoretical basis and guidelines for treatment. 1281 10

Hypertension remains one of the most unmet medical needs of this century. While many drugs are available for treating hypertension, efforts are still insufficient to find potent therapeutic agents since cause for hypertension in all patients is not the same. Angiotensin-converting enzyme inhibitors (ACEIs) have emerged as an important class of drugs in the treatment of hypertension, congestive heart failure (CHF), protenuric renal disease, myocardial infarction and stroke. This class of drugs blocks the conversion of angiotensin I to angiotensin II and prevents bradykinin breakdown. However, the lack of specificity of ACEIs leads to the frequent side effects like cough and angio-oedema. Recently developed, specific non-peptide and orally active angiotensin receptor blockers (ARBs) have become the prime therapeutics as they alone or co-administration with ACE inhibitors can control the renin angiotensin disorders. This review explores recent developments in the design, synthesis, and structural modifications of ACE inhibitors as well as angiotensin receptor blockers.
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PMID:Advances in angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). 1287 Nov 64

Stroke continues to have a devastating impact on public health. Recent epidemiological studies suggest that stroke is becoming more common, perhaps due to the ageing of the population and increased survival of patients with cardiac disease. There are specific and well-defined risk factors in patients with stroke, the most important being hypertension. Treatment options to reverse the effect of acute ischaemic stroke are limited. The only approved therapy is intravenous tissue plasminogen activator (tPA). The disadvantage of tPA treatment is a rate of symptomatic haemorrhage of about 6%. Newer stroke prevention options are currently being investigated including statins, oestrogen, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). The challenge for physicians is to select the most effective intervention, and this depends on our knowledge of the underlying stroke mechanism and the patient's risk factors.
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PMID:Update on the treatment and prevention of ischaemic stroke. 1367 83

The importance of blood pressure control in stroke prevention is supported by a large body of clinical evidence. However, it is not known which antihypertensive agents are most effective in preventing stroke. As stroke is characterised by vascular remodelling and dysfunction and by effects on the cerebral circulation, selecting an agent that has a direct vascular protective effect beyond blood pressure control may be desirable. Results with the angiotensin receptor blockers (ARBs) in clinical trials (LIFE and SCOPE) support the findings in animal models that ARBs may be a promising therapeutic option for prevention of stroke and possibly, cognitive decline.
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PMID:Stroke prevention: is it possible? If so, which antihypertensive agent should be used? 1367 84


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