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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The availability of orally active specific angiotensin receptor antagonists (AT1 antagonists) has opened new therapeutic choices and provided probes to test the specific role of the renin-angiotensin system in the pathogenesis of cardiovascular disease. 2. The data available so far suggest that the antihypertensive efficacy of angiotensin receptor antagonists is comparable to that of angiotensin-converting enzyme (ACE) inhibitors. This provides further evidence that this latter class of drugs exerts its effect mainly through blockade of the renin-angiotensin enzymatic cascade. As expected, the association of a diuretic exerts an equally strong additive effect to the antihypertensive efficacy of both classes of drugs. 3. The most common side effect of ACE inhibitors, dry cough, does not occur with AT1 antagonists, which confirms the long-held view that this untoward effect of the ACE inhibitors is due to renin-angiotensin-independent mechanisms. 4. Long-term studies with morbidity/mortality outcome results are needed, before a definite position can be assigned to this newcomer in the orchestra of modern antihypertensive drugs. Notwithstanding, this new class of agents already represents an exciting new addition to our therapeutic armamentarium.
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PMID:Experience with angiotensin II antagonists in hypertensive patients. 899 54

The essential problem of the vicious circle leading to end-stage cardiovascular disease is atherosclerosis. This paper focuses on the functional changes centred on the endothelium that accompany the development of atherosclerosis, examining in particular pathological alterations in the L-arginine/nitric oxide (NO) pathway. Changes in the NO system are associated with altered platelet and monocyte interactions with the vessel wall, abnormal vasoconstriction and altered vascular structure. Diabetes, hyperglycaemia, hypertension and hypercholesterolaemia are all involved in this process. Endothelin is a vasoconstrictor peptide produced by endothelial cells which is upregulated under these conditions. Normalising endothelial function could involve platelet inhibition, lipid-lowering agents to prevent foam cell formation and decrease the lipid load of the blood vessel wall, and agents to interfere with some of the mechanisms involved in vasoconstriction, proliferation and migration, including ACE-inhibitors and angiotensin receptor antagonists, and possibly new tools such as endothelin receptor antagonists.
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PMID:The internist and the vessel wall. 917 1

Hypertension is a major problem throughout the developed world. Although current antihypertensive treatment regimens reduce morbidity and mortality, patients are often noncompliant, and medications may not completely normalize blood pressure. As a result, current therapy frequently does not prevent or reverse the cardiovascular remodeling that often occurs when blood pressure is chronically elevated. Blockade of the renin-angiotensin system (RAS) is effective in controlling hypertension and treating congestive heart failure. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) inhibit the activity of the RAS, but these two classes of antihypertensive medications have different mechanisms of action and different pharmacologic profiles. Angiotensin-converting enzyme inhibitors block a single pathway in the production of angiotensin II (Ang II). In addition, angiotensin I is not the only substrate for ACE. The ACE inhibitors also block the degradation of bradykinin that may have potential benefits in cardiovascular disease. Bradykinin is, however, the presumed cause of cough associated with ACE inhibitor therapy. Data from clinical trials on ACE inhibitors serve to support the involvement of the RAS in the development of cardiovascular disease. Angiotensin receptor blockers act distally in the RAS to block the Ang II type 1 (AT1) receptor selectively. Thus, ARBs are more specific agents and avoid many side effects. Experimental and clinical trials have documented the efficacy of ARBs in preserving target-organ function and reversing cardiovascular remodeling. In some instances, maximal benefit may be obtained with Ang II blockade using both ARBs and ACE inhibitors. This review describes clinical trials that document the efficacy of ARBs in protecting the myocardium, blood vessels, and renal vasculature.
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PMID:Angiotensin receptor blockers: evidence for preserving target organs. 1128 62

Extensive animal studies and a growing number of human clinical trials have now definitively demonstrated the central role of the renin-angiotensin-aldosterone system in the expression and modulation of cardiovascular disease. In contrast to the original hypothesis, the benefits of angiotensin antagonism do not emanate from the antihypertensive effect alone. Subsequent extensive investigations of angiotensin blockade suggest that the benefits of this approach may also result from the pharmacologic alteration of endothelial cell function and the ensuing changes in the biology of the vasculature. The more recent availability of direct antagonists of the AT(1) angiotensin receptor has introduced an element of doubt into this realm of clinical decision making. The receptor antagonists and the more widely studied converting-enzyme inhibitors share many endpoint attributes. Nevertheless, the partially overlapping mechanisms of action for the two classes of angiotensin antagonists confer distinct pharmacologic properties, including side effect profiles, mechanisms of action, and theoretic salutary effects upon the expression of cardiovascular disease. The current review will attempt to contrast the biology of angiotensin converting-enzyme inhibition with angiotensin II receptor antagonism. A discussion of the differential effects of these drug classes on endothelial cell function and on the modulation of vascular disease will be utilized to provide a theoretic framework for clinical decision making and therapeutics.
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PMID:Formulating clinical strategies for angiotensin antagonism: a review of preclinical and clinical studies. 1133 Oct 59

Microalbuminuria (MA) is defined as persistent elevation of albumin in the urine, of 30-300 mg/day (20-200 microg/min). These values are less than the values detected by routine urine dipstick testing, which does not become positive until protein excretion exceeds 300-500 mg/day. Use of the albumin-to-creatinine ratio is recommended as the preferred screening strategy for all diabetic patients. MA is measured in spot morning urine obtained from the patient in the office and sent for measurement of both albumin and creatinine. A value above 0.03 mg/mg suggests that albumin excretion is above 30 mg/day and therefore MA is present. MA should be checked annually in everyone, and every 6 months within the first year of treatment to assess the impact in patients started on antihypertensive therapy. MA is an established risk factor for renal disease progression in type 1 diabetes and its presence is the earliest clinical sign of diabetic nephropathy. In addition, a number of studies suggest that MA is an important risk factor for cardiovascular disease and defines a group at high risk for early cardiovascular mortality in both type 2 diabetes and essential hypertension. MA also signifies abnormal vascular permeability and the presence of atherosclerosis. Among nondiabetic patients with essential hypertension, MA is associated with higher blood pressures, increased serum total cholesterol, and reduced serum high-density lipoprotein cholesterol. Thus, taken together these data support the concept that the presence of MA is the kidney's notice to the physician/patient that there is a problem with the vasculature. MA can be reduced, and progression to overt proteinuria prevented, by aggressive blood pressure reduction. The National Kidney Foundation recommends that blood pressure levels be maintained at or below 130/80 mm Hg in anyone with diabetes or renal disease. This should be accomplished with antihypertensive agents that prevent the rise in MA and hence prevent development of proteinuria. Such agents are angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and, to a lesser extent, Beta blockers, non-dihydropyridine calcium antagonists, and diuretics. In summary, the presence of MA is a marker of endothelial dysfunction and a harbinger of markedly enhanced cardiovascular risk. All patients with diabetes and/or hypertension should be screened for the presence of microalbuminuria with use of spot morning urine. To maximize prevention of MA development, the following goals should be instituted: 1) blood pressure should be maintained at less than 130/80 mm Hg and a low-salt, moderate-potassium diet instituted; 2) in diabetics, HbA1c should be kept at less than 7%; 3) in obese patients, a weight loss program should be implemented, with a goal BMI of less than 30; and 4) the physician and patient, working together, should maintain low-density lipoprotein cholesterol at less than 120 mg/dL, and less than 100 mg/dL if diabetes is present. (c)2001 by Le Jacq Communications, Inc.
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PMID:Microalbuminuria: what is it? Why is it important? What should be done about it? 1141 91

Improvements in the death rate from coronary heart disease and in the control of hypertension have leveled off in recent years, reversing a trend toward steady improvement that began in 1972. Of the roughly 20% of Americans who suffer from hypertension, only 29% achieve adequate control (<140/90 mm Hg) with treatment and nearly half receive no treatment at all. Poor adherence to therapy doubtless plays a key role in this failure. As a major cause of poor adherence, tolerability becomes an extremely important element in any discussion of effective antihypertensive treatment. Despite their efficacy in treating hypertension, diuretics, beta-blockers, and calcium channel blockers have all been associated with numerous side effects, including increased serum lipid levels, insulin resistance, and edema. With the introduction of the angiotensin converting enzyme (ACE) inhibitors, patients were able to achieve blood pressure goals with fewer side effects. These agents, however, cause an irritating cough in up to 19% of patients. A newer class of drugs, the angiotensin receptor blockers (ARB), have similar effects to the ACE inhibitors, but their highly selective nature produces even fewer side effects. Eprosartan is a structurally unique ARB. Like the other ARB, this promising new agent has a side effect profile similar to placebo, and its response rate rivals or exceeds that of enalapril. Although it remains to be seen whether the ARB can significantly reduce morbidity and mortality from cardiovascular disease, preliminary data from the Evaluation of Losartan in the Elderly (ELITE) trial appear to be promising.
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PMID:Issues in hypertension: drug tolerability and special populations. 1145 11

The presence, and in many cases the regulated synthesis, of components of the renin-angiotensin system have been demonstrated in multiple tissues, indicating the existence of tissue angiotensin-generating systems. These vary with respect to which renin-angiotensin system components are synthesized locally and which are taken up from plasma. Enzymes unrelated to the classical renin-angiotensin system may also contribute to tissue angiotensin synthesis. However, based on the available data, the prevailing opinion that kidney-derived renin is in all cases the only physiologically relevant renin in tissues must be revised. Also there is evidence indicating a role for tissue angiotensin systems in the pathogenesis of cardiovascular disease and in cardiovascular structural remodeling. The angiotensin-regulated synthesis of aldosterone in cardiac tissue has been described, suggesting the possibility that a renin-angiotensin-aldosterone system exists in the heart. In addition, intracellular (intracrine) sites of angiotensin action have been reported. Some of these findings have implications for therapeutics and, in particular, for the use of angiotensin converting-enzyme inhibitors and angiotensin receptor blockers. Finally, tissue angiotensin systems outside the cardiovascular system also appear to be physiologically relevant.
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PMID:The clinical implication of tissue renin angiotensin systems. 1170

Angiotensin II (ANG II) is a pleiotropic vasoactive peptide that binds to two distinct receptors: the ANG II type 1 (AT(1)) and type 2 (AT(2)) receptors. Activation of the renin-angiotensin system (RAS) results in vascular hypertrophy, vasoconstriction, salt and water retention, and hypertension. These effects are mediated predominantly by AT(1) receptors. Paradoxically, other ANG II-mediated effects, including cell death, vasodilation, and natriuresis, are mediated by AT(2) receptor activation. Our understanding of ANG II signaling mechanisms remains incomplete. AT(1) receptor activation triggers a variety of intracellular systems, including tyrosine kinase-induced protein phosphorylation, production of arachidonic acid metabolites, alteration of reactive oxidant species activities, and fluxes in intracellular Ca(2+) concentrations. AT(2) receptor activation leads to stimulation of bradykinin, nitric oxide production, and prostaglandin metabolism, which are, in large part, opposite to the effects of the AT(1) receptor. The signaling pathways of ANG II receptor activation are a focus of intense investigative effort. We critically appraise the literature on the signaling mechanisms whereby AT(1) and AT(2) receptors elicit their respective actions. We also consider the recently reported interaction between ANG II and ceramide, a lipid second messenger that mediates cytokine receptor activation. Finally, we discuss the potential physiological cross talk that may be operative between the angiotensin receptor subtypes in relation to health and cardiovascular disease. This may be clinically relevant, inasmuch as inhibitors of the RAS are increasingly used in treatment of hypertension and coronary heart disease, where activation of the RAS is recognized.
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PMID:Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide. 1170

Proven cardiovascular benefit from angiotensin-converting enzyme (ACE) inhibition is a cornerstone of evidence-based medicine. The first study to show dramatic benefits from ACE inhibition was the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS-I), in which a 31% decrease in the rate of death was observed in patients with severe heart failure at the end of 1 year of enalapril treatment (p = 0.001). This result led to large long-term studies-including Survival and Ventricular Enlargement (SAVE), Acute Infarction Ramipril Efficacy (AIRE), Trandolapril Cardiac Evaluation (TRACE), and Study of Left Ventricular Dysfunction (SOLVD)-which verified that ACE inhibition decreases heart failure, myocardial infarction (MI), and mortality, and that striking benefit could be observed within 30 days. Short-term studies of patients in the acute phase of a heart attack verified that ACE inhibition provided rapid benefits. A meta-analysis of short-term (up to 8 weeks) studies of ACE inhibition (including CONSENSUS-II, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico [GISSI]-3, International Study of Infarct Survival [ISIS]-4, and the Chinese Captopril Study [CCS]-1) demonstrated that post-MI risk was reduced by 10% within the first day of treatment. The immediacy of the benefit suggested that ACE inhibition not only improved cardiovascular function in failing hearts but also affected important mechanisms in patients without overt heart failure. Effects on more general mechanisms of heart disease suggested that patients with problems other than hypertension or heart failure might benefit from ACE inhibitors. The Heart Outcomes Prevention Evaluation (HOPE) study investigated the hypothesis that ACE inhibition would confer benefits to patients who were at high risk for cardiovascular events, but who were without left ventricular dysfunction or heart failure. Long-term reductions in MI, stroke, cardiac arrest, and heart failure, as well as improvements in mortality, were observed in this population after treatment with ACE inhibitors. Substudies of the HOPE study revealed that ACE inhibition reduced progression of atherosclerosis and improved myocardial remodeling. Taken together, these studies provide evidence that supports treatment of a broad population of patients at risk for cardiovascular events with ACE inhibitors. The next step is to combine ACE inhibition with other treatments to maximize patient benefit. The Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) will compare the efficacy of an ACE inhibitor (ramipril) with an angiotensin receptor blocker (telmisartan), and determine whether these treatments in combination will further reduce morbidity and mortality from cardiovascular disease.
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PMID:Angiotensin II and trials of cardiovascular outcomes. 1183 5

Cardiovascular disease is a growing global health threat due in part to demographic shifts, in particular the growing elderly population in which cardiovascular disease is highly likely to develop. Older individuals have numerous coexisting conditions that contribute to increased risk for morbidity and mortality. In the past, physicians primarily used diastolic blood pressure (BP) as the indicator for measuring relative risk. However, since the early 1970s observational studies have found that systolic BP rather than diastolic BP is a better predictor of cardiovascular events, particularly in the older population. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) recommended specific goals for the treatment of hypertensive patients. Specifically, JNC-VI reinforced the notion of more aggressive BP goals for patients at the greatest risk for an event. The approach to patients who are not at goal is different from earlier guidelines. Therapy is now aimed at building therapeutic regimens. Currently, there are five classes of agents that have been shown to reduce the morbidity and mortality associated with cardiovascular and renal disease: diuretics, beta-blockers, angiotensin converting enzyme inhibitors, calcium antagonists, and angiotensin receptor blockers. If a patient is not at goal and there is no response to an agent from one of these classes or troublesome side effects develop, then and only then should that drug be stopped and a different one used. Otherwise, a multidrug regimen is constructed and additional agents added in logical fashion. A majority of patients with higher risk can attain control at the specified BP goal safely and effectively by using a combination of agents.
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PMID:Risk stratification of older patients. 1212 Oct 9


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