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At least 739 records · Page 41Linked to original sources
PubMed2006

Lower target blood pressures are safe and effective for the prevention of recurrent stroke: the PROGRESS trial.

OBJECTIVE: To explore the likely optimum blood pressure (BP) level for patients with a history of cerebrovascular disease. METHODS: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, placebo-controlled trial that established the beneficial effects of BP lowering in 6105 patients with cerebrovascular disease. The present study comprises two series of post hoc analyses. The first was designed to investigate the effects of randomized treatment on recurrent stroke by baseline BP levels, and the second was a corresponding observational analysis investigating the association between achieved follow-up BP levels and recurrent stroke risk. RESULTS: Analyses of the randomized treatment comparisons showed that BP lowering with combination therapy produced similar risk reductions in each of four subgroups defined by baseline BP of less than 120, 120-139, 140-159, and 160 mmHg or greater (P homogeneity = 0.5). The effects of single-drug therapy were also comparable across these subgroups (P homogeneity = 0.2), but consistently greater benefits were observed with combination compared to single-drug therapy. The analyses of achieved follow-up BP showed that the lowest risk of recurrence was among the one-quarter of participants with the lowest follow-up BP levels (median 112/72 mmHg), and that risks rose progressively with higher follow-up BP levels. Minor side-effects were progressively more common at lower BP levels (P homogeneity = 0.04), but there was no excess of serious complications (all P homogeneity > 0.2). CONCLUSION: These analyses provide no evidence of a J-curve relationship between BP level and stroke risk among patients with cerebrovascular disease, and identify no patient group among whom more intensive BP lowering would not be expected to produce greater risk reductions.

Aged↗
PubMed2006

Pulse pressure reduction and cardiovascular protection.

Brachial pulse pressure (PP) is now a well-established cardiovascular risk factor. Central rather than peripheral PP should be measured to determine the 'true' haemodynamic effects of antihypertensive agents on target organs. Peripheral PP, measured at the brachial artery, does not reflect central PP (either carotid or ascending aorta), because their determinants are different and pathophysiological conditions and drugs may change central PP without changing peripheral PP. Central PP (i.e. carotid artery or ascending aorta) has shown an independent predictive value for all-cause mortality in patients with end-stage renal disease and in the hypertensive patients of the CAFE study. Antihypertensive treatment has repeatedly demonstrated its ability to prevent cardiovascular events. Whether the effect on cardiovascular events in clinical trials comparing two pharmacological classes or two therapeutic strategies is, at least partly, the result of differential effects on PP remains to be demonstrated. It is therefore of major importance to determine which therapeutic strategies may differentially lower central PP, and in turn reduce cardiovascular events. In clinical practice, lowering PP is often a difficult task, particularly in diabetic hypertensive individuals. In the PARADIS study, we aimed to determine, in a population of hypertensive patients with both type 2 diabetes and PP greater than 60 mmHg, which clinical characteristics predict the fall in PP on treatment and a reduction in cardiovascular events. The reinforcement of therapeutic measures, including a fixed low-dose perindopril/indapamide combination, made possible the effective lowering of PP and cardiovascular events in type 2 diabetic hypertensive patients, under conditions of usual care by general practitioners and specialists.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

4-aminopyridine activates potassium currents by activation of a muscarinic receptor in feline atrial myocytes.

1. The effects of 4-aminopyridine (4-AP) on action potentials, macroscopic membrane currents and single-channel recording from cardiac left atrial myocytes of the adult cat were studied using the whole-cell and cell-attached configurations of the patch-clamp technique. 2. 4-AP (1 mM) produced a hyperpolarization of the resting membrane potential and a shortening of action potential duration. Under voltage-clamp conditions, we have found that 4-AP increased a background current and a delayed rectifier outward current. These effects were antagonized by atropine. In addition, both effects seemed to be mediated through a pertussis toxin-sensitive G protein. 3. The background current induced by 4-AP displayed properties that are highly similar to those of the inwardly rectifying potassium current activated by acetylcholine (IK(ACh)). The time-dependent potassium current activated by 4-AP has kinetic and pharmacological properties different from those of the delayed rectifier potassium current previously identified in cardiac myocytes. 4. The activation of the delayed rectifier-like potassium current could be explained by the activation of a novel muscarinic receptor subtype in which acetylcholine acts as the antagonist. Another possibility is that 4-AP activates IK(ACh) in a time- and voltage-dependent manner.

4-Aminopyridine↗
PubMedDate not supplied

Effects of short-term norepinephrine infusion on plasma catecholamines, renin, and aldosterone in normal and hypertensive man.

The acute responsiveness of plasma catecholamine, renin (PRA), and aldosterone levels to exogenous norepinephrine was studied under placebo conditions and following renin (PRA), and aldosterone levels to exogenous norepinephrine was studied under placebo conditions and following renin-angiotensin activation by diuretic pretreatment in 25 normal subjects and 34 patients with borderline-to-moderate essential hypertension. Norepinephrine infusion caused increases in plasma norepinephrine (PNE) that correlated with the infused norepinephrine dose (p < 0.001); this relationship was similar in normal and hypertensive subjects and unaltered by diuretic therapy. Plasma epinephrine and dopamine levels were unchanged during norepinephrine infusion. Norepinephrine infusion at pressor doses stimulated PRA (p < 0.01). The PRA responses correlated with the dose of infused norepinephrine (p < 0.0025), and norepinephrine-stimulated PRA correlated with basal PRA (p < 0.001). These norepinephrine-PRA relationships were unaltered by diuretic treatment and similar in normal and hypertensive subjects. In both groups, norepinephrine also caused a similar increase in plasma aldosterone (p < 0.05) under placebo conditions, but not following diuretic therapy. These findings demonstrate that an acute increase in the blood levels of the adrenergic neurotransmittor, norepinephrine, causes mild but distinct stimulation of plasma renin and aldosterone levels. Renin release in response to exogenous norepinephrine is not enhanced following renin-angiotensin activation by diuretic pretreatment. The responsiveness of the renin-angiotensin-aldosterone system to an acute norepinephrine input seems to be intact in essential hypertension.

Adolescent↗
PubMed2005

[Comparison of therapeutic strategies in the management of hypertension].

Guidelines for the treatment of hypertension recommend reducing blood pressure to below 140/90 mmHg. However, there is little to guide the clinician on which pharmacological strategy to pursue: monotherapy with stepped-care, sequential monotherapy, or the initial use of combination therapy. The STRATHE study was designed to clarify this issue by comparing the three strategies. A low-dose combination of perindopril/indapamide was significantly superior to either stepped-care or sequential monotherapy in terms of reducing systolic blood pressure and in the percentage of patients achieving normalisation without adverse effects. Pulse pressure showed a trend to greater reductions with the low-dose combination. Although there must be caution about extrapolating these results to other combinations, which may not have the same pharmacological properties, the STRATHE study has shown that initiating antihypertensive therapy with a low-dose combination has advantages over the two other classical therapeutic strategies.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Efficacy and tolerability of the perindopril/indapamide combination therapy for hypertension: the PRIMUS study.

BACKGROUND: Tight blood pressure (BP) control is required to reduce cardiovascular morbidity and mortality. OBJECTIVE: To evaluate the efficacy and tolerability of the first line combination perindopril/indapamide in hypertension in daily practice. DESIGN AND METHODS: In this prospective, open-label, observational trial, 1892 general practitioners in Germany recruited patients with hypertension (n = 8023; mean age 59.6 years, 48.1% males, body mass index 27.6 kg/m2, systolic BP >or= 140 mmHg and/or diastolic BP >or= 90 mmHg) between October 2002 and December 2004. Patients received perindopril 2 mg/indapamide 0.625 mg for 12 weeks. BP measured in the general practice setting, safety, and tolerability were evaluated after 4 and 12 weeks. RESULTS: At baseline, most patients had moderate to severe hypertension (78%); initial BP was 164.6/95.8 mmHg. At inclusion, 38% of the patients were newly diagnosed hypertensives (mean BP 166.1/97.2 mmHg) and 58% of patients had uncontrolled BP despite preexisting antihypertensive treatment (163.5/94.9 mmHg). Previous treatment consisted of beta-blockers (49.5%), ACE inhibitors (36.4%), calcium-antagonists (29.3%), diuretics (28.8%), AT-I receptor antagonists (7.1%), and other treatments (8.1%). In the entire study cohort, treatment with perindopril/indapamide significantly decreased systolic BP (27.9 mmHg), diastolic BP (13.7 mmHg), and pulse pressure (14.2 mmHg), compared with baseline (p < 0.0001); 96% of patients responded to treatment and in 50% of patients BP was normalized (< 140/90 mmHg). Treatment dose was doubled in 9.5% of patients. Similar results were found in various subgroup analyses (newly diagnosed patients, the elderly, and patients with isolated systolic hypertension, additional cardiovascular risk factors, associated diseases, or target organ damage). The most frequent adverse events (< 1% of patients) were dry cough and nausea. CONCLUSIONS: The open-label, observational study PRIMUS, extends the existing evidence that the first line combination treatment of hypertension with perindopril/indapamide is effective, safe, and well tolerated in a representative cross-section of patients with newly diagnosed or pretreated but uncontrolled hypertension in daily practice.

Adult↗
PubMed1983

Treatment of mild hypertension and the problem of compliance.

The results of the majority of the on-going large-scale studies in patients with hypertension underline the importance of lowering diastolic blood pressure to levels below 90 mmHg and the benefits, in terms of reduced morbidity and mortality, of the treatment even of those with mild hypertension. Because the patient with mild hypertension is generally asymptomatic, treatment must not only be effective but also have minimal side-effects and a simple regimen to ensure patient compliance. The step-care approach to the treatment of such patients and the drugs of choice are reviewed briefly.

Adrenergic beta-Antagonists↗