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

Hypertension is a very common disease and represents a major risk factor for cardiovascular adverse events such as stroke and heart failure. In recent years, a big effort has been put into detecting and treating patients with hypertension. Several classes of drugs acting by different pharmacological mechanisms can be chosen for the treatment of hypertension. However, the long term use of all anti-hypertensive agents is sometimes limited by the occurrence of adverse effects. Thanks to continuous pharmacological research, new compounds are regularly developed and become available in clinical practice. Recently, several new, nonpeptide, orally active angiotensin II receptor antagonists have reached the market. Today, these substances represent the most specific way to block the renin angiotensin system. Numerous studies have now demonstrated that these angiotensin II antagonists are as effective as ACE inhibitors, calcium antagonists, beta-blockers or diuretics in lowering blood pressure in patients with hypertension. Given the increasing use of angiotensin II receptor antagonists in the treatment of hypertension, it is important to review their safety and tolerability. Based on the actual level of knowledge, the striking feature of this class of agents is their favourable safety and tolerability profile which appears to be equivalent to that observed with placebo. Indeed, so far, no clear class-specific adverse effect has been attributed to the angiotensin II receptor antagonists. Thus, if angiotensin II antagonists prevent target organ damage and reduce the morbidity and mortality of patients with hypertension, they may well become a first-line treatment of hypertension.
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PMID:Comparative safety and tolerability of angiotensin II receptor antagonists. 1043 51

There have been some prospective randomized studies which compared primary angioplasty with intravenous thrombolysis in patients with an acute myocardial infarction (AMI). However, a substantial number of patients with AMI who would not have been included in those trials are treated with one of these two therapeutic options. To describe the proportions, characteristics, and outcome of these patients treated with primary angioplasty or thrombolysis we analyzed the data of the prospective "Maximal Individual Optimized Therapy for Acute Myocardial Infarction" (MITRA) trial. Out of 3308 patients treated with primary angioplasty or thrombolysis, 737 (22.3%) belonged to one of the following groups, not included in current randomized trials: Left bundle branch block, non-diagnostic first ECG, pre-hospital delay > 12 hours or unknown pre-hospital delay. Primary angioplasty was performed in 158/737 (21.4%) and thrombolysis received 579/737 (78.6%) of the patients. There were only minor differences regarding patients' characteristics and concomitant diseases between the two groups. Patients treated with primary angioplasty were 3 years younger (62 years median versus 65 years median (p < 0.036). They also more often showed overt heart failure at admission compared to patients treated with thrombolysis (primary angioplasty: 3.2% versus thrombolysis: 8.9%, OR = 0.34, 95% CI: 0.13-0.86). In-hospital time to intervention was 1 1/2 hours longer in patients treated with primary angioplasty (156 minutes median versus 47 minutes median, p = 0.001). beta-blockers were more often used with primary angioplasty compared to thrombolysis (70.31% versus 55.9%; OR = 1.87, 95% CI: 1.28-2.72), as well as ACE inhibitors (62% versus 49.9%; OR = 1.64, 95% CI: 1.14-2.35). Hospital mortality (8.2% versus 16.4%; OR = 0.46, 95% CI: 0.25-0.84), as well as a combined endpoint of death, reinfarction, postinfarction angina, advanced heart failure, and stroke (24.1% versus 42.3%, OR = 0.43, 95% CI: 0.29-0.64) were lower in patients treated with primary angioplasty compared to those treated with thrombolysis. Logistic regression analysis showed primary angioplasty to be independently associated with a lower rate of the combined endpoint (OR = 0.73, 95% CI: 0.59-0.91), after adjusting for confounding parameters. All subgroups showed a more favorable outcome in patients treated with primary angioplasty. In clinical practice, patients with AMI, not included in current randomized trials comparing primary angioplasty with thrombolysis, account for 22% of all patients with AMI treated with one of those two therapies. Primary angioplasty seems to be associated with a lower event rate compared to thrombolysis in these patients. This has to be confirmed by a prospective randomized trial.
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PMID:[Primary dilatation versus thrombolysis in patients with acute myocardial infarct, not included in randomized studies. Results of the MITRA Study. Maximal Individual Optimized Therapy for Acute Myocardial Infarct]. 1044 12

The present study was undertaken to examine the effects of the ACE (angiotensin converting enzyme) inhibitor imidapril, on the brain, when administered after the onset of stroke in a stroke-prone substrain of spontaneously hypertensive rats (SHRSP). Learning deficits and induced lesions in the brain as well as in the kidneys and heart were investigated in detail. SHRSP were divided into two groups with or without salt loading at the age of 4 weeks. The salt loading was performed for 7-9 weeks to increase the incidence of stroke. Within 24 h after the first observation of stroke, animals were subsequently treated with 5 mg/kg imidapril orally once a day or the vehicle for up to the age of 27 weeks. Imidapril attenuated progression of neurological abnormalities such as irritability, hyperkinesia and motor dysfunction, and increased survival rate. In three-panel runway testing, learning deficits did not develop significantly in the imidapril-treated group, and was comparable to that in the non-salt-loaded/non-stroke group. Imidapril reduced oedema formation in the cortex, hippocampus and striatum, and also suppressed lesion formation in the kidneys and heart. Imidapril thus suppressed progression of neurological deficits with loss of learning ability following onset of stroke, and also suppressed formation of oedema in the brain and decreased the number of lesions in other organs. Imidapril-induced reduction of cerebrovascular damage, which presumably occurs in the brain after stroke, may account for the inhibitory effects of imidapril on lesion formation and learning impairment.
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PMID:Post-stroke treatment with imidapril reduces learning deficits with less formation of brain oedema in a stroke-prone substrain of spontaneously hypertensive rats. 1045 89

The effect of beta-blockade on left ventricular (LV) remodeling, when added to angiotensin-converting enzyme inhibition (ACEI) after anterior myocardial infarction (MI), is incompletely understood. On day 2 after coronary ligation-induced anteroapical infarction, 17 sheep were randomized to ramipril (ACEI, n = 8) or ramipril and metoprolol (ACEI-beta, n = 9). Magnetic resonance imaging was performed before and 8 wk after MI to measure changes in LV end-diastolic, end-systolic, and stroke volume indexes, LV mass index, ejection fraction (EF), and regional percent intramyocardial circumferential shortening. (123)I-labeled m-iodobenzylguanidine (MIBG) and fluorescent microspheres before and after adenosine were infused before death at 8 wk post-MI for quantitation of sympathetic innervation, blood flow, and blood flow reserve in adjacent and remote noninfarcted regions. Infarct size, regional blood flow, blood flow reserve, and the increase in LV mass and LV end-diastolic and end-systolic volume indexes were similar between groups. However, EF fell less over the 8-wk study period in the ACEI-beta group (-13 +/- 11 vs. -22 +/- 4% in ACEI, P < 0.05). The ratio of adjacent to remote region (123)I-MIBG uptake was greater in ACEI-beta animals than in the ACEI group (0.93 +/- 0.06 vs. 0.86 +/- 0.07, P < 0.04). When added to ACE inhibition after transmural anteroapical MI, beta-blockade improves EF and adjacent regional sympathetic innervation but does not alter LV size.
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PMID:Beta-blockade improves adjacent regional sympathetic innervation during postinfarction remodeling. 1051 78

A disproportionate increase in SBP over DBP has been recognized for many years as a frequent accompaniment of aging. Initially this was considered to be benign, risk free and potentially dangerous to treat. Study over the years has shown that it is not benign and that antihypertensive therapy can reduce the risks of stroke, myocardial infarction, congestive heart failure and cardiovascular death. Currently, the drugs most widely recommended for this purpose are the thiazide diuretics, long acting dihydropiridine calcium channel antagonists, ACE inhibitors, and beta blocking agents. There may be a special place for nitrates, since these agents are very effective in increasing arterial distensibility--a primary abnormality of the disorder--but a formal study of their effectiveness has not been done. Concern about diastolic hypotension during therapy suggests that treatment to lower the blood pressure in this disorder should be carried out gradually with the aim of reducing the SBP toward normal while avoiding diastolic hypotension.
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PMID:Clinical studies and therapeutic trials in systolic hypertension. 1052 66

It is clear that antihypertensive regimens based on a low dose thiazide diuretic are effective for the primary prevention of stroke, particularly in older patients. In patients with diabetes mellitus who are at a higher risk of stroke, low dose thiazide diuretics and ACE inhibitors are of benefit. In those with isolated systolic hypertension, long-acting dihydropyridine calcium antagonists, in addition tolow dose thiazide diuretics, have also been shown to significantly reduce stroke risk. However, to attain sufficient lowering of blood pressure (BP) to most effectively reduce the risk of stroke (i.e. to levels of 140-150/80-85 mm Hg or lower and perhaps to <140/<80 mm Hg in patients with diabetes mellitus) combination therapy will be required. Immediately following stroke BP tends to fall spontaneously and therapy is probably not required in the great majority of patients during the first few days poststroke. If treatment is required shortly after this period, agents with a slow and gentle onset of action appear to be preferable; some preliminary data suggest that ACE inhibitors, despite lowering systemic BP, have no significant effect on cerebral blood flow. However, there is little clinical outcome data to clearly define the role of antihypertensive treatment in the early poststroke period. Whether existing antihypertensive therapy should be continued following stroke is also unclear, but such decisions may be influenced by factors such as the actual BP level, other indications for treatment (e.g. angina pectoris or cardiac failure) or the presence of dysphagia. There is more evidence to suggest that, some weeks to months following stroke (particularly a minor stroke), lower rather than higher BP is favourable, and better control of high BP with therapy reduces stroke recurrence.
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PMID:Antihypertensive therapy in the prevention of stroke: what, when and for whom? 1055 36

Hypertension is currently defined in terms of levels of blood pressure associated with increased cardiovascular risk. A cut-off of 140/90 mm Hg is accepted as a threshold level above which treatment should at least be considered. This would give a prevalence of hypertension of about 20% of the adult population in most developed countries. Hypertension is associated with increased risk of stroke, myocardial infarction, atrial fibrillation, heart failure, peripheral vascular disease and renal impairment. Hypertension results from the complex interaction of genetic factors and environmental influences. Many of the genetic factors remain to be discovered, but environmental influences such as salt intake, diet and alcohol form the basis of nonpharmacological methods of blood pressure reduction. Investigation of the individual hypertensive patient aims to identify possible secondary causes of hypertension and also to assess the individual's overall cardiovascular risk, which determines the need for prompt and aggressive therapy. Cardiovascular risk can be determined from (i) target organ damage to the eyes, heart and kidneys; (ii) other medical conditions associated with increased risk; and (iii) lifestyle factors such as obesity and smoking. Secondary causes of hypertension are individually rare. Screening tests should be initially simple, with more expensive and invasive tests reserved for those in whom a secondary cause is suspected or who have atypical features to their presentation. The main determinants of blood pressure are cardiac output and peripheral resistance. The typical haemodynamic finding in patients with established hypertension is of normal cardiac output and increased peripheral resistance. Treatment of hypertension should initially use nonpharmacological methods. Selection of initial drug therapy should be based upon the strength of evidence for reduction of cardiovascular mortality in controlled clinical trials, and should also take into account coexisting medical conditions that favour or limit the usefulness of any given drug. Given this approach, it would be reasonable to use a thiazide diuretic and/or a beta-blocker as first-line therapy unless there are indications to the contrary. Individual response to given drug classes is highly variable and is related to the underlying variability in the abnormal pathophysiology. There are data to suggest that the renin-angiotensin system is more important in young patients. The targeting of this system in patients under the age of 50 years with a beta-blocker (or ACE inhibitor), and the use of a thiazide diuretic (or calcium antagonist) in patients over 50 years, may enable blood pressure to be controlled more quickly.
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PMID:Pathoaetiology, epidemiology and diagnosis of hypertension. 1067 92

Angiotensin II is considered to have angiogenic properties. Nevertheless, several authors reported an increase in coronary capillary density after treatment with ACE inhibitors. The aim of the present study was to evaluate the effect of treatment with low doses of ACE inhibitor perindopril, low doses of the diuretic indapamide, or a combination of the two on microvascular structure in hearts from stroke-prone spontaneously hypertensive rats (SHR-sp). Young adult male SHR treated with indapamide (0.24 mg/kg/day), perindopril (0.76 mg/kg/day), or both were compared with untreated animals after 8 or 14 weeks of treatment. Survival of SHR-sp was significantly increased after treatment. Only perindopril alone or in combination with indapamide significantly decreased blood pressure and cardiac mass. Treatment also significantly increased capillary and myocyte densities but arteriolar density tended to decrease. External and internal diameters significantly increased in treated animals while arteriolar thickness remained the same. Thus, thickness in vessels of the same size was the greatest in untreated animals, followed by indapamide- and perindopril-treated rats with the thinnest walls in rats with combined treatment, and the treatment resulted in a significant increase in the lumen to wall ratio. Capillary and arteriolar growth responses in treated animals seem to indicate that the two are independently regulated processes. Treatment with indapamide alone at this dosage did not significantly influence most responses but in combination with perindopril it strengthened the effect of perindopril.
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PMID:The effect of treatment with low dose ACE inhibitor and/or diuretic on coronary microvasculature in stroke-prone spontaneously hypertensive rats. 1068 30

The presence of hypertension in individual patients confers significant risk in terms of coronary artery disease, myocardial infarction, stroke and congestive heart failure. However, it is also a modifiable risk factor, as risk may be decreased through either lifestyle changes or pharmacotherapy to reduce the elevated blood pressure. Over the past 3 decades, there has been strenuous debate among clinical scientists regarding the role played by racial background in both the pathogenesis and response to pharmacotherapy. A number of studies, such as the third National Health and Nutrition Examination Survey (NHANES III) have demonstrated a higher prevalence of hypertension in black populations. The Hispanic Health and Nutrition Examination Survey (HHANES) suggested that the prevalence of hypertension in Hispanics of Caribbean descent was similar to that of African Americans, while Mexican Americans had lower rates of the disease. It appears that the pathophysiological consequences of elevated blood pressure may also be more severe in black patients. Thus, these patients will have a worse prognosis than their white counterparts at any given blood pressure level. The incidence of end-stage renal disease has been reported to be as much as 17 times more common in African American patients. A number of individual factors have been postulated for these differences including increased sodium intake, differences in sodium handling, decreased potassium intake, decreased calcium intake, elevated fasting insulin levels, lower levels of plasma renin activity and urinary kallikrein excretion. These differences in prevalence and pathophysiology have resulted in recommendations for differential therapeutic approaches in the treatment of hypertension. A major trial conducted in the Veteran Affairs Medical Centers in the USA noted that African Americans are generally more responsive to diuretics and calcium channel blockers than to ACE inhibitors or beta-blockers. However, it has been reported that this resistance may be overcome by increasing the dose of these agents. It has been postulated that these differences may be related to lower plasma renin activity noted in the black population, since diuretics and calcium channel blockers appear to be better suited to this population. These differential therapeutic recommendations will be reviewed in light of our current knowledge of the disease.
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PMID:Effect of race on hypertension and antihypertensive therapy. 1070 94

The combination therapy with ACE inhibitors, angiotensin II type 1 (AT(1)) receptor antagonists, or calcium channel antagonists may exert more beneficial effects on cardiovascular diseases than monotherapy. Perindopril, candesartan cilexetil, or amlodipine alone or the combination of low doses of each agent was administered orally to stroke-prone spontaneously hypertensive rats (SHRSP) for 4 weeks to compare the hypotensive or cardiovascular effects. Although perindopril (2 mg/kg), candesartan cilexetil (2 mg/kg), or amlodipine (3 mg/kg) alone caused comparable hypotensive effects in SHRSP, monotherapy with perindopril or candesartan decreased left ventricular (LV) weight; mRNA levels for atrial natriuretic factor, skeletal alpha-actin, and collagen types I and III; and aortic weight and platelet-derived growth factor-beta receptor tyrosine phosphorylation to a greater extent than monotherapy with amlodipine. Although monotherapy with a low dose (0.2 mg/kg) of perindopril or candesartan cilexetil did not significantly reduce the LV mRNA levels and aortic platelet-derived growth factor-beta receptor phosphorylation of the SHRSP, combination therapy at such a low dose normalized these parameters more potently than the use of amlodipine (3 mg/kg) alone. Although perindopril or candesartan cilexetil alone at 0.05 mg/kg did not decrease the blood pressure of the SHRSP, such a low dose of combination therapy decreased LV weight and atrial natriuretic factor mRNA levels of the SHRSP to a greater extent than amlodipine alone or amlodipine combined with perindopril or candesartan cilexetil. Our results provide evidence that suggests the combination of an ACE inhibitor and an AT(1) receptor antagonist may be more effective in the treatment of cardiac and vascular diseases than the combination of a calcium channel blocker with an ACE inhibitor or an AT(1) receptor antagonist or monotherapy with each agent.
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PMID:Cardiovascular effects of combination of perindopril, candesartan, and amlodipine in hypertensive rats. 1072 May 93


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