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

The Annual Scientific Sessions of the American Heart Association is the leading scientific conference in the cardiovascular field, both for basic and clinical research in cardiology and related disclipines. This report covers the outcome of major clinical trials that were presented in the 'late-breaking' clinical trial sessions. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) investigated the angiotensin receptor blocker valsartan, the angiotensin-converting enzyme inhibitor captopril, and their combination in 14,703 survivors of an acute myocardial infarction with a reduced left ventricular ejection fraction on clinical outcome. The study demonstrated that valsartan and captopril where equally effective, whereas the combination was associated with an increased risk of side effects without further benefit. VALIANT is a landmark trial because it was the first large study that compared the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor in the setting of acute myocardial infarction. Other trials that will be summarised in this report are the Na + /H + Exchange Inhibition to Prevent Coronary Events in Acute Cardiac Conditions Trial (EXPEDITION; cariporide in coronary artery bypass graft surgery), the Reversal of Atherosclerosis with Aggressive Lipid Lowering Trial (REVERSAL; atorvastatin and pravastatin for atherosclerosis reversal), the Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation V (SPORTIF V; ximelagatran and warfarin for stroke prevention in atrial fibrillation), the Prophylactic Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularisation (PAPABEAR; amiodarone for the prevention of postoperative atrial fibrillation), the Acute and Chronic Therapeutic Impact of a Vasopressin 2 Antagonist in Congestive Heart Failure (ACTIV in CHF; vasopressin 2 antagonist tolvaptan in congestive heart failure) and Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT; fosinopril and pravastatin in microalbuminuric subjects without hypertension or hypercholesterolemia).
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PMID:American Heart Association scientific sessions. 1510 93

RhoA is commonly activated in the aorta in various hypertensive models, indicating that RhoA seems to be a molecular switch in hypertension. The molecular mechanisms for RhoA activation in stroke-prone spontaneously hypertensive rats (SHRSP) were here investigated using cultured aortic smooth muscle cells (VSMC). The level of the active form of RhoA was higher in VSMC from SHRSP than in those from Wistar-Kyoto rats (WKY). The phosphorylation level of myosin phosphatase target subunit 1 (MYPT1) at the inhibitory site was also significantly higher in SHRSP, and the phosphorylation levels in both VSMCs were strongly inhibited to a similar extent by treatment with Y-27632, a Rho-kinase inhibitor. The expression levels of RhoA/Rho-kinase related molecules, namely RhoA, Rho-kinase, MYPT1, CPI-17 (inhibitory phosphoprotein for myosin phosphatase) and myosin light chain kinase, were not different between SHRSP and WKY. Valsartan, an angiotensin II (Ang II)- type 1 receptor antagonist, selectively and significantly reduced the RhoA activation in VSMC from SHRSP. The expression levels of the Rho GDP-dissociation inhibitor (RhoGDI) and leukemia-associated Rho-specific guanine nucleotide exchange factor (RhoGEF) did not differ between SHRSP and WKY. In cyclic nucleotide signaling, cyclic GMP (cGMP)-dependent protein kinase Ialpha (cGKIalpha) was significantly downregulated in SHRSP cells, although there were no changes in the expression levels of guanylate cyclase beta and cyclic AMP (cAMP)-dependent protein kinase or the intracellular contents of cGMP and cAMP between the two rat models. These results suggest that the possible mechanisms underlying RhoA activation in VSMC from SHRSP are autocrine/paracrine regulation by Ang II and/or cGKIalpha downregulation.
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PMID:RhoA activation in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats. 1512 84

The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was designed to test whether, for the same achieved blood pressures, regimens based on valsartan or amlodipine would have differing effects on cardiovascular endpoints in high risk hypertension. But inequalities in blood pressure, favouring amlodipine, throughout the multiyear trial precluded comparison of outcomes. A technique of serial median matching, applied at 6 months when treatment adjustments intended to achieve control of blood pressure were complete, created 5006 valsartan-amlodipine patient pairs matched exactly for systolic blood pressure, age, sex, and the presence or absence of previous coronary disease, stroke, or diabetes. Subsequent combined cardiac events, myocardial infarction, stroke, and mortality were almost identical in the two cohorts, but admission to hospital for heart failure was significantly lower with valsartan. Reaching blood pressure control (systolic <140 mm Hg) by 6 months, independent of drug type, was associated with significant benefits for subsequent major outcomes; the blood pressure response after just 1 month of treatment predicted events and survival.
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PMID:Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. 1536 77

Older patients with hypertension are often inadequately treated due to misconceptions regarding reasonable goal blood pressures or concerns about treatment side effects. Adequately treating hypertension can yield impressive benefits in terms of improved morbidity and enhanced quality of life in persons of any age. Antagonists of the renin-angiotensin-aldosterone system are especially effective in older persons, many of whom have concomitant conditions such as diabetes mellitus, renal dysfunction, and other cardiovascular risk factors. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been shown to improve many of the complications of hypertension, including left ventricular hypertrophy and renal disease. Results of recent key studies such as Losartan Intervention For Endpoint Reduction in Hypertension (LIFE), Valsartan in Heart Failure Trial (Val-HeFT), Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM), and Valsartan in Acute Myocardial Infarction (VALIANT) add to the evidence that angiotensin II receptor blockers are well suited for the treatment of hypertension in older patients. These trials also indicate that they are appropriate therapy for heart failure patients and for patients who have experienced acute myocardial infarction, particularly those who are unable to tolerate an angiotensin-converting enzyme inhibitor.
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PMID:Angiotensin II receptor blockers in older patients. 1526 63

Spontaneously hypertensive stroke-prone rats (SHRSP) develop hypertension and systemic inflammation, with subsequent brain and renal disorders and early death. We tested the hypothesis that valsartan, an angiotensin II type 1 (AT1) receptor antagonist, exerts protective effects in SHRSP through its anti-inflammatory properties, even in the absence of a blood pressure-lowering effect. SHRSP fed a high-salt diet were treated with vehicle or valsartan (1-10 mg/kg/day). The vehicle-treated rats developed hypertension, proteinuria, progressive kidney disease, and, 40 +/- 5 days from the beginning of the treatment, brain damage as visualized by magnetic resonance imaging. Rats treated with 1 mg/kg/day valsartan developed brain damage after 61 +/- 3 days (p <0.01 versus vehicle-treated rats). No damage showed after 100 days in 80% of the rats treated with 10 mg/kg/day. Valsartan treatment preserved renal structure, by preventing the infiltration of inflammatory cells, and lowered renal expression of monocyte chemoattractant protein-1, transforming growth factor-beta1, and interleukin-1beta, compared with vehicle-treated SHRSP. Urinary excretion of acute-phase proteins increased in the latter but remained negligible in the drug-treated animals. Furthermore, valsartan exerted protective effects also when given after established proteinuria. In SHRSP, blockade of AT1 receptor with valsartan prevents the development of proteinuria, delays the appearance of brain damage, preserves renal structure, and increases survival under stressful conditions. Valsartan exerts its beneficial effects independently of any blood pressure fall and by means of broad anti-inflammatory actions both at local and at systemic levels. These observations indicate that the administration of AT1 receptor antagonists may be useful in pathological situations in which an anti-inflammatory effect is required.
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PMID:Anti-inflammatory effects of AT1 receptor blockade provide end-organ protection in stroke-prone rats independently from blood pressure fall. 1530 95

Type 2 diabetes mellitus is becoming a major health problem associated with excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a key objective in the near future. Besides lifestyle changes, various pharmacological treatments have proven their efficacy in placebo-controlled clinical trials, including antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity agents such as orlistat. Arterial hypertension, a clinical entity in which insulin resistance is common, is strongly associated with type 2 diabetes and may precede the disease by several years. While antihypertensive agents such as diuretics or beta-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, newer antihypertensive agents exert neutral or even slightly positive metabolic effects. Numerous clinical trials have investigated the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on insulin sensitivity in hypertensive patients, with or without diabetes, with no consistent results. Almost half of the studies with ACE inhibitors in hypertensive nondiabetic individuals demonstrated a slight but significant increase in insulin sensitivity as assessed by insulin-stimulated glucose disposal during a euglycaemic hyperinsulinaemic clamp, while the other half failed to reveal any significant change. The effects of ARAs on insulin sensitivity are neutral in most studies. Mechanisms of improvement of glucose tolerance and insulin sensitivity through the inhibition of the renin-angiotensin system (RAS) are complex. They may include improvement of blood flow and microcirculation in skeletal muscles and, thereby, enhancement of insulin and glucose delivery to the insulin-sensitive tissues, facilitating insulin signalling at the cellular level and improvement of insulin secretion by the beta cells. Six recent large-scale clinical studies reported a remarkably consistent reduction in the incidence of type 2 diabetes in hypertensive patients treated with either ACE inhibitors or ARAs for 3-6 years, compared with a thiazide diuretic, beta-adrenoceptor antagonist, the calcium channel antagonist amlodipine or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or beta1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001) in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial with valsartan compared with amlodipine. All these studies considered the development of diabetes as a secondary endpoint, except the HOPE trial where it was a post hoc analysis. These encouraging observations led to the initiation of two large, prospective, placebo-controlled randomised clinical trials whose primary outcome is the prevention of type 2 diabetes: the DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan. Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) will also investigate as a secondary endpoint whether it is possible to prevent the development of type 2 diabetes by blocking the RAS with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent consistent observations of a 14-34% reduction of the development of diabetes in hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a theoretical point of view, they emphasise that there are many aspects of the pathogenesis, prevention and treatment of type 2 diabetes that still need to be uncovered. From a practical point of view, they may offer a new strategy to reduce the ongoing epidemic and burden of type 2 diabetes.
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PMID:Prevention of type 2 diabetes mellitus through inhibition of the Renin-Angiotensin system. 1551 53

Hypertension rarely occurs in isolation, and many hypertensives have additional risk factors for cardiovascular disease in addition to elevated blood pressure. Each patient's cardiovascular disease risk profile should be determined individually, and the treatment approach tailored to each case. Cardiovascular disease risk factors and high blood pressure are closely linked, suggesting that the ideal treatment should not only lower blood pressure, but also effectively lower overall risk. This is likely to require more than one drug, and one of the most effective and safe combinations is that of an angiotensin receptor blocker with a diuretic. The completion of one of the most important trials undertaken to explore risk factors and anti-hypertensive treatment, the Valsartan long-term evaluation trial (VALUE), will certainly enhance understanding for the role of combination treatment in high-risk patients, as well as contribute to the design of rational treatments for blood pressure control.
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PMID:The case for blood pressure control in risk groups. 1552 18

We discuss combination therapy with angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics in light of the independent actions of both types of agents, and the adverse effects of both agents independently and in the context of the physiologic synergy achieved in using these agents together. ARBs counteract many of the adverse events associated with the use of thiazide diuretics and have been shown to reduce the occurrence of new-onset diabetes mellitus. We also review outcome trials in patients with hypertension (such as LIFE [Losartan Intervention For Endpoint reduction in hypertension], VALUE [Valsartan Antihypertensive Long-term Use Evaluation], and SCOPE [Study on COgnition and Prognosis in the Elderly]), in which losartan, valsartan, and candesartan cilexetil were used in combination with hydrochlorothiazide. Fixed combination ARB/hydrochlorothiazide agents make sense as initial therapy for patients in whom BP is >20/10 mm Hg above goal.
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PMID:Fixed-dose combinations in the management of hypertension: defining the place of angiotensin receptor antagonists and hydrochlorothiazide. 1563 34

Angiotensin II plays a significant role in cell growth and proliferation in model systems and in humans. Numerous studies have shown that left ventricular hypertrophy (LVH) increases the risk of coronary heart disease, congestive heart failure, stroke or transient ischemic attack; all-cause deaths, and sudden death. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has provided beneficial effects on LVH regression and on cardiac remodeling in the presence of hypertension and heart failure. The new class of ARBs appears to provide cardioprotective effects that are similar to those of the ACE inhibitors. Most of the beneficial effects provided by these agents appear to be related to a more complete blockade of the angiotensin II type 1 (AT1) receptor. However, costimulation of the angiotensin II type 2 (AT2) receptor appears to increase nitric oxide and thus causes some bradykinin-like effects. Evidence for the role of angiotensin II in promoting LVH as well as abnormal regulation of the angiotensin II signal transduction pathways in model systems and in humans has been reviewed. Secondly, the mechanisms for the beneficial effects of angiotensin II receptor blockers studied in model systems and in humans, including possible involvement in the formation of reactive oxygen species by mononuclear cells, are presented. Finally, results from large-scale interventions such as the Losartan Intervention For Endpoint reduction (LIFE) study, as well as an overview of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial involving the use of ARB in high-risk patients, are presented.
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PMID:Left ventricular hypertrophy and angiotensin II receptor blocking agents. 1563 45

A 73-year-old male ex-smoker of 10 cigarettes/day (up until 10 years ago) with a history of hypertension treated with Diovan 80 (Valsartan) was referred by his dentist. For the past 6 months the patient has presented an ulcer located in the right retromolar trigone region. In the last 2 months the patient has used chlorhexidine rinses, and is not wearing his dentures; the lesions fail to heal, however. Intraoral examination showed an ulcer in the right retromolar trigone area (Fig. 1-2), with a fibroelastic consistency. No regional lymph nodes were palpable. A panoramic X-ray study (Fig. 3), biopsy (Fig. 4-6) and CT exploration were requested.
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PMID:Peripheral ameloblastoma. 1573 55


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