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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme (ACE) inhibitors have a well-established role in the management of patients with hypertension, diabetes, heart failure and myocardial infarction (MI). ACE inhibitors have been particularly well studied in acute and chronic MI with consistent and substantial survival benefits demonstrated, particularly in the higher risk groups. The recent development of angiotensin II (Ang II) receptor blockers (ARBs) as a well tolerated pharmacological therapy to more completely inhibit the actions of Ang II at the AT1-receptor level raises questions concerning comparative efficacy with the proven ACE inhibitor experience. Two major trials will provide a direct comparison of ARBs with an ACE inhibitor. The Valsartan in Acute Myocardial Infarction (VALIANT) trial is specifically designed to compare and contrast the ARB, valsartan, used both alone as well as in combination with a proven ACE inhibitor regimen, in a high risk MI population. VALIANT, with its three arms targetting 14,500 patients, is uniquely poised to determine whether the pharmacological advance in the development of ARBs confers additional clinical (survival) value in high risk MI patients.
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PMID:Will more complete inhibition of the RAAS with angiotensin receptor blockade improve survival following myocardial infarction? 1719 21

Resistant hypertension is a common medical disorder. Although the exact incidence of resistant hypertension is not established, estimates derived from recent outcome studies including the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), Valsartan Antihypertensive Long-term Use Evaluation (VALUE), and Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) emphasize that this condition may be more common than previously thought. A major advance in our understanding of the pathogenesis and management of resistant hypertension is the recognition of the importance of aldosterone. Several investigators have postulated a direct role of aldosterone excess as an important mechanism for drug resistance in hypertension. The mechanisms whereby aldosterone elevates BP are complex. It was previously thought that aldosterone produced hypertension primarily by promoting sodium retention with consequent hypervolemia. Recent studies of the effects of aldosterone on vascular smooth muscle have, however, delineated several extrarenal mechanisms whereby aldosterone produces hypertension-primarily by its direct vasoconstrictor effects and by altering vascular compliance. Consequently, aldosterone blockade constitutes an effective intervention for treating resistant hypertension.
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PMID:Resistant hypertension: prevalence and evolving concepts. 1721 48

The role of oxidative stress in the pathogenesis of vascular diseases such as hypertension has been well recognized. Angiotensin (Ang) II is regarded as a pro-oxidant because it can stimulate the production of reactive oxygen species. The purpose of this study was to evaluate whether treatment with the Ang II type 1 (AT(1)) receptor antagonist valsartan has an antioxidant effect in patients with mild to moderate hypertension. A randomized, double-blind, placebo-controlled study was conducted in 48 stage I and II hypertensive subjects. Patients were followed every 4 weeks for 12 weeks after randomization to valsartan titrated to 80 to 160 mg once or twice daily or matching placebo. The erythrocyte superoxide dismutase (SOD) activity and expression of SOD-mRNA in polymorphonuclear leukocytes were measured before and after treatment. Valsartan showed concentration-dependent inhibition of reactive oxygen species generation in polymorphonuclear leukocytes from hypertensive patients. The erythrocyte superoxide dismutase activity before treatment was more than 2 times higher in hypertensive subjects compared to normal controls. Superoxide dismutase activity decreased significantly after 12 weeks of treatment with valsartan but did not change with placebo. The amount of SOD-mRNA in the polymorphonuclear leukocytes decreased progressively over 3 months in the hypertensive subjects receiving valsartan treatment but did not change in the placebo group. The production of reactive oxygen species is increased in hypertension, and superoxide dismutase activity is increased, presumably as a compensatory mechanism. Treatment with valsartan but not placebo resulted in a progressive down-regulation of SOD-mRNA expression and a reduction in superoxide dismutase activity, suggesting antioxidant activity and a reduction of reactive oxygen species generation. These findings imply that AT(1) receptor antagonists may provide benefits to hypertensive patients beyond blood pressure reduction.
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PMID:Effects of the angiotensin II type 1 receptor antagonist valsartan on the expression of superoxide dismutase in hypertensive patients. 1732 51

Growing evidences have shown that hypertension, cardiac hypertrophy and fibrosis were associated with an overactivity of NAD(P)H oxidase. It is unknown, however, which isoform of NAD(P)H oxidase yields O(2)*(-) formation in heart and aorta in two-kidney, two-clip (2K2C) hypertensive rats in vivo and thus is responsible for the development of cardiac remodeling. We examined the pathological change of NAD(P)H oxidase homologues and tested the effect of valsartan on the cardiac remodeling in 2K2C renovascular hypertensive rats. Four weeks after male Sprague-Dawley rats accepted 2K2C or sham operation, 2K2C hypertensive (>160 mmHg) rats were divided into vehicle-treated (2K2C) and valsartan (30 mg kg(-1) per day, for 6 weeks)-treated (2K2C+Val) groups, which were compared with sham-operated controls (Sham). At week 10, 2K2C hypertensive rats showed increased serum level of angiotensin II (Ang II), MDA and blood pressure (BP), obvious cardiac hypertrophy and fibrosis, increased O(2)*(-) production and NAD(P)H oxidase activity and expression in aorta and heart. The heart in 2K2C hypertensive rats preferred to use NADH as substrate while the aorta used both NADH and NADPH. Valsartan treatment decreased BP, ameliorated cardiac hypertrophy and fibrosis, decreased O(2)*(-) production and NAD(P)H oxidase activity in aorta and heart. Nox2 and Nox4 protein expression increased in heart, while Nox1 and Nox4 increased in aorta in 2K2C hypertensive rats, which were all normalized after valsartan treatment. In conclusion, these data indicate that different Nox expression might account for substrate preference and the formation of O(2)*(-) by NAD(P)H oxidase resulting from elevated Ang II in the 2K2C model contributes to the development of renovascular hypertension and subsequent cardiac remodeling.
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PMID:Contribution of different Nox homologues to cardiac remodeling in two-kidney two-clip renovascular hypertensive rats: effect of valsartan. 1732 85

To compare the effects of valsartan and amlodipine alone or in combination on plasma norepinephrine (NE) at rest and standing for 10 minutes in patients with hypertension, 47 patients with a sitting diastolic blood pressure (BP) (DBP)>95 mm Hg and<110 mm Hg were randomized in a double-blind fashion to either valsartan or amlodipine. During the first 4 weeks of treatment, patients received a low dose of either valsartan (80 mg) or amlodipine (5 mg). The patients were force-titrated to the high dose of either drug (160 or 10 mg) for 4 weeks. After 8 weeks of therapy, those who still had a DBP>90 mm Hg (nonresponders) received combination therapy with the other drug, whereas patients with a DBP<90 mm Hg (responders) continued on monotherapy. Decreases in ambulatory BP and clinic systolic BP and DBP were significant (P<.05) after 8 weeks' therapy with no difference between the 2 groups. Amlodipine but not valsartan as monotherapy consistently increased NE levels at rest and enhanced NE levels during standing. Valsartan decreased basal NE in responders. Combination therapy with valsartan and amlodipine did not attenuate the rise in NE levels induced by amlodipine. This study indicates that therapy with amlodipine increases peripheral sympathetic basal tone and reactivity to standing in patients with hypertension, whereas valsartan does not. Combined therapy with amlodipine/valsartan did not attenuate the sympathetic activation induced by amlodipine. The hypotensive action of valsartan may be mediated in part by an inhibition of the sympathetic baroreflex in patients with hypertension.
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PMID:Effects of valsartan or amlodipine alone or in combination on plasma catecholamine levels at rest and during standing in hypertensive patients. 1734 93

Valsartan administration at bedtime as opposed to on wakening improves the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Yet to be determined is whether this administration time-dependent efficacy is a class-related feature, characteristic of all angiotensin receptor blockers or specific only to valsartan. Terminal half-life is a major difference between angiotensin receptor blockers, being largest ( approximately 24 hours) for telmisartan. This trial investigated the administration time-dependent antihypertensive efficacy of telmisartan. We studied 215 patients with hypertension (114 men and 101 women), 46.4+/-12.0 years of age, randomly assigned to receive telmisartan (80 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured for 48 hours before and after 12 weeks of treatment. The significant blood pressure reduction after treatment was similar for both groups. Bedtime administration of telmisartan, however, was more efficient than morning dosing in reducing the nocturnal blood pressure mean. The sleep time-relative blood pressure decline was slightly reduced after telmisartan on awakening but significantly increased with bedtime dosing, thus reducing the prevalence of nondipping from baseline by 76%. Telmisartan administered at bedtime, as opposed to morning dosing, improved the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Nocturnal BP regulation is significantly better achieved with bedtime dosing of telmisartan. Results from this prospective trial suggest that these beneficial features of bedtime dosing may be class related for angiotensin receptor blockers. These results should be taken into account when prescribing this class of antihypertensive medication for treatment of essential hypertension.
Hypertension 2007 Oct
PMID:Comparison of the efficacy of morning versus evening administration of telmisartan in essential hypertension. 1763 51

There has been a lot of interest about new-onset diabetes mellitus in recent hypertension trials, but the implications of diabetes development on cardiac outcomes have not been known. In the Valsartan Antihypertensive Long-Term Use Evaluation trial, 15 245 high-risk patients were followed for an average of 4.2 years. At baseline, 5250 patients were diabetic by the 1999 World Health Organization criteria, and among the 9995 nondiabetic patients, 1298 patients developed diabetes during follow-up. We have investigated the influence of diabetes development on outcomes in the Valsartan Antihypertensive Long-Term Use Evaluation trial. The patients with diabetes at baseline and new-onset diabetes were compared with patients who did not develop diabetes by a Cox regression model with adjustment for prespecified covariates (age, diabetes status, left ventricular hypertrophy, baseline coronary heart disease, and randomized study treatment). Patients with diabetes at baseline had the highest cardiac morbidity defined as myocardial infarction and heart failure with a hazard ratio of 2.20 (95% CI: 1.95 to 2.49). The patients with new-onset diabetes had significantly higher cardiac morbidity, especially more congestive heart failure, than those without diabetes, with a hazard ratio of 1.43 (95% CI: 1.16 to 1.77). This indicates that patients who develop diabetes during antihypertensive treatment have cardiac morbidity intermediate between diabetic subjects and those subjects who never had diabetes and that it is of importance to find these patients at risk of diabetes development and optimize lifestyle and medical treatment.
Hypertension 2007 Sep
PMID:Impact of new-onset diabetes mellitus on cardiac outcomes in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial population. 1802 65

We conducted 3 open-label, multiple-dose, 3-period, randomized, crossover studies in healthy subjects to assess the potential pharmacokinetic interaction between vildagliptin, a novel dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes, and representatives of 3 commonly prescribed antihypertensive drug classes: (1) the calcium channel blocker, amlodipine; (2) the angiotensin receptor blocker, valsartan; and (3) the angiotensin-converting enzyme inhibitor, ramipril. Coadministration of vildagliptin 100 mg with amlodipine 5 mg, valsartan 320 mg, or ramipril 5 mg had no clinically significant effect on the pharmacokinetics of these drugs. The 90% confidence intervals of the geometric mean ratios for area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24h) and maximum plasma concentration (Cmax) for vildagliptin, amlodipine, and ramipril (and its active metabolite, ramiprilat) were contained within the acceptance range for bioequivalence (0.80-1.25). Valsartan AUC0-24h and Cmax increased by 24% and 14%, respectively, following coadministration of vildagliptin, but this was not considered clinically significant. Vildagliptin was generally well tolerated when given alone or in combination with amlodipine, valsartan, or ramipril in healthy subjects at steady state. No adjustment in dosage based on pharmacokinetic considerations is required should vildagliptin be coadministered with amlodipine, valsartan, or ramipril in patients with type 2 diabetes and hypertension.
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PMID:Vildagliptin, a novel dipeptidyl peptidase IV inhibitor, has no pharmacokinetic interactions with the antihypertensive agents amlodipine, valsartan, and ramipril in healthy subjects. 1798 25

The influence of blood pressure on outcomes after high-risk myocardial infarction is not well characterized. We studied the relationship between blood pressure and the risk of cardiovascular events in 14 703 patients with heart failure, left ventricular systolic dysfunction, or both after acute myocardial infarction in the Valsartan in Myocardial Infarction Trial. We assessed the relationship between antecedent hypertension and outcomes and the association between elevated (systolic: >140 mm Hg) or low blood pressure (systolic: <100 mm Hg) in 2 of 3 follow-up visits during the first 6 months and subsequent cardiovascular events over a median 24.7 months of follow-up. Antecedent hypertension independently increased the risk of heart failure (hazard ratio [HR]: 1.19; 95% CI: 1.08 to 1.32), stroke (HR: 1.27; 95% CI: 1.02 to 1.58), cardiovascular death (HR: 1.11; 95% CI: 1.01 to 1.22), and the composite of death, myocardial infarction, heart failure, stroke, or cardiac arrest (HR: 1.13; 95% CI: 1.06 to 1.21). While low blood pressure in the postmyocardial infarction period was associated with increased risk of adverse events, patients with elevated blood pressure (n=1226) were at significantly higher risk of stroke (adjusted HR: 1.64; 95% CI: 1.17 to 2.29) and combined cardiovascular events (adjusted HR: 1.14; 95% CI: 1.00 to 1.31). Six months after a high-risk myocardial infarction, elevated systolic blood pressure, a potentially modifiable risk factor, is associated with an increased risk of subsequent stroke and cardiovascular events. Whether aggressive antihypertensive treatment can reduce this risk remains unknown.
Hypertension 2008 Jan
PMID:Effect of antecedent hypertension and follow-up blood pressure on outcomes after high-risk myocardial infarction. 1834 26

Angiotensin (AT) II and noradrenaline play major roles in hypertension, stroke and coronary heart disease, which are themselves interlinked. Harmful effects of AT II are not blocked solely by angiotensin-converting enzyme inhibitors, as it is now evident that AT II is generated by other enzymes such as chymase. Angiotensin II also stimulates noradrenaline release modulated by presynaptic receptors on sympathetic nerves. Numerous studies have defined the action of the AT II type 1 receptor blocker (ARB) eprosartan as controlling noradrenergic and adrenergic effects, resulting from actions on the renin-angiotensin-aldosterone system and the sympathetic nervous system. Clinical studies have been carried out to assess the effects of ARBs on morbidity and mortality. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial compared the effects of valsartan and the calcium channel blocker (CCB) amlodipine in over 15,000 patients at high risk of a cardiac event. Results showed that blood pressure was reduced by both treatments and cardiac mortality/morbidity was similar in both groups. By contrast, the Morbidity and mortality after Stroke, Eprosartan compared with nitrendipine for Secondary prevention (MOSES) study (n = 1405) generated results which differed from the VALUE study, in that blood pressure was reduced by both eprosartan and nitrendipine, but eprosartan reduced all cardiovascular and cerebrovascular events to a greater extent than nitrendipine. It is also possible that any delayed clinical benefit of eprosartan could be due to reverse cardiac remodelling. Eprosartan, by blocking AT II receptors, reducing noradrenaline release and blocking catecholamine actions, may, therefore, provide greater protection against vascular events than CCBs or other ARBs.
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PMID:Risk reduction by preventing stroke: need for blockade of angiotensin II and catecholamines? 1809 11


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