Stroke In Hypertensive Patients Research Articles

Principal Results of a Prospective Randomised Controlled Study: Morbidity and Mortality after Stroke — Eprosartan Compared with Nitrendipine for Secondary Prevention (MOSES)

The morbidity and mortality after stroke - eprosartan compared with nitrendipine for secondary prevention (MOSES) trial compared the effects of two antihypertensive agents in secondary prevention of stroke. The hypothesis of the trial was that in hypertensive stroke patients, for the same level of blood pressure (BP) control, eprosartan would be more effective than nitrendipine in reducing cerebrovascular and cardiovascular morbidity and mortality. A total of 710 patients were assigned to an eprosartan-based regimen and 695 to a nitrendipine-based regimen.These patients had hypertension requiring treatment and documented cerebral ischaemia or haemorrhage. They were well matched at baseline in general characteristics, BP and concomitant disease. BP was lowered to the same extent in both treatment arms, with a very similar timeframe. A high proportion of patients in both treatment arms achieved target BP. The combined primary endpoint was a composite of total mortality and total number of cardiovascular and cerebrovascular events, including recurrent events.There were 206 endpoints in the eprosartan group and 255 endpoints in the nitrendipine group.This represents a statistically significant 21% risk reduction in favour of eprosartan. Eprosartan also had advantages over nitrendipine in respect of all cerebrovascular events and first cardiovascular events.

Prognostic value of hemodynamic findings from impedance cardiography in hypertensive stroke

Impedance cardiography (ICG), a noninvasive method of hemodynamic monitoring, is a useful tool in the care of critically ill patients. Use of this technology shows promise in the hemodynamic assessment of hypertensive stroke patients. This study describes the different ICG findings of patients with hypertensive stroke and correlates parameters with patient outcome. Adult patients with stroke admitted to the intensive care unit (ICU) who were on antihypertensive medications or had hypertensive blood pressure (BP) levels at the time of admission were included. Patients were classified as having ischemic or hemorrhagic stroke on the basis of imaging studies. The ICG was done in the initial 24 h of admission using the BioZ Cardiac Output Monitor (CardioDynamics, Inc., San Diego, CA) and 18 hemodynamic parameters were analyzed. Statistical analysis was performed to assess correlation of hemodynamic findings with the type of stroke and survival to hospital discharge. Fifty-two adult patients with a mean age of 60.5 +/- 12.4 years were included. Of this population, 29 had ischemic stroke and 23 had hemorrhagic stroke. Seventeen patients died during hospital stay. Overall, noninvasive hemodynamic parameters of stroke patients showed a high systemic vascular resistance index (SVRI) and systemic vascular resistance (SVR), and decreased cardiac output (CO), stroke index (SI), and stroke volume (SV). Among the ischemic stroke group, nonsurvivors had a significantly higher mean SVRI and mean SVR compared to the survivors. In contrast, among the hemorrhagic stroke patients, nonsurvivors had a significantly lower mean SVRI and SVR compared to survivors. Except for SI and BP, there was no difference in the noninvasive hemodynamic parameters between the ischemic stroke group and the hemorrhagic stroke group. In this population of hypertensive stroke patients admitted to the ICU, ICG showed an elevated SVRI and SVR and depressed CO, SV, and SI. In the ischemic stroke group, higher SVR and SVRI were associated with in-hospital death, whereas in the hemorrhagic stroke group, lower SVR and SVRI were associated with in-hospital death. The ICG may provide significant prognostic information in patients admitted with hypertensive stroke.

What Is the Optimal Blood Pressure and Drug Therapy for Patients With Coronary Artery Disease?

THE NUMBER OF PERSONS WITH CORONARY ARTERY DISease (CAD) is increasing dramatically, with more patients surviving myocardial infarction (MI), the aging of the population, and the increasing prevalence of diabetes, obesity, and inactivity. As a result, deaths from cardiovascular disease have increased about 2.5% per year over the past decade. Yet there is a paucity of prospective randomized trial data on the relative impact of various drugs and blood pressure levels on adverse outcomes in patients with CAD. This information is critical to current management of these patients for many reasons. Past experiences have demonstrated that patients with myocardial ischemia may react differently to many drugs that otherwise appear safe (eg, nifedipine, phosphodiesterase inhibitors, antiarrhythmic agents, rofecoxib) and reducing blood pressure in patients with CAD is very complex. To this end, 2 large randomized clinical trials examining blood pressure treatment in patients with CAD provide important new information on this issue. In the first of these reports, the recently published International Verapamil-trandolapril Study (INVEST), a calcium antagonist strategy (verapamil SR-trandolapril) and a -blocker strategy (atenolol-hydrochlorothiazide) were equivalent in preventing death, MI, or stroke in hypertensive patients with CAD. Both multidrug strategies provided excellent blood pressure control (eg, 70% of patients with blood pressure 140/90 mm Hg) and were effective in decreasing angina (from 67% at study entry to 28% at 2 years) with infrequent need for revascularization (eg, 2%). But the calcium antagonist strategy was somewhat more effective in reducing angina frequency and was associated with significantly less new-onset diabetes. Furthermore, the nadir in the systolic blood pressure–adverse outcomes relationship was approximately 120 mm Hg. In this issue of JAMA, Nissen and colleagues report the results of the Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study. Patients with CAD and on-treatment blood pressure within the socalled normal range ( 140 mm Hg) were randomly assigned to receive placebo, a calcium antagonist (amlodipine), or an angiotensin-converting enzyme inhibitor (enalapril) to evaluate the effects of further blood pressure lowering. In a substudy, the authors used a novel design feature (that is likely a prototype for future studies) to directly examine blood pressure and drug effects on coronary atherosclerosis progression using intravascular ultrasound (IVUS) as pioneered by this group for lipid treatment studies. Overall the patients were very well managed, with high use of aspirin (95%) and statins (83%). Compared with placebo, amlodipine and enalapril reduced blood pressure similarly (approximately 5 mm Hg systolic) when added to -blockers (approximately three fourths of the patients) with or without diuretics (approximately one third of the patients). Results suggested that patients assigned to amlodipine fared better in terms of fewer ischemia-related events (eg, hospital admissions for angina, coronary revascularizations) with a trend for reduced death, MI, and stroke. This clinical benefit of amlodipine persisted in the subgroup with diabetes. Of more interest, progression of coronary atherosclerosis was documented in placebo-assigned patients undergoing serial IVUS evaluation. But no progression was observed with either amlodipine or enalapril, suggesting that perhaps the lower blood pressure may be more important than the class of agent used. With both active treatments combined there appeared to be no atherosclerosis progres-

Teveten™ (Eprosartan) reduces future risk in hypertensive stroke patients

"Teveten™ (Eprosartan) reduces future risk in hypertensive stroke patients." South African Family Practice, 46(10), p. 46

Cerebrovascular Risk Factors and Clinical Classification of Strokes

Cerebrovascular risk represents a progressive and evolving concept owing to the particular distribution of risk factors in patients with ischemic stroke and in light of the newest stroke subtype classifications that account for pathophysiological, instrumental, and clinical criteria. Age represents the strongest nonmodifiable risk factor associated with ischemic stroke, while hypertension constitutes the most important modifiable cerebrovascular risk factor, confirmed by a host of epidemiological data and by more recent intervention trials of primary (HOT, Syst-Eur, LIFE) and secondary (PROGRESS) prevention of stroke in hypertensive patients. To be sure, a curious relationship exists between stroke and diabetes. Although the Framingham Study, The Honolulu Heart Program, and a series of Finnish studies reported a linear relationship between improved glucose metabolism and cerebral ischemia, the clinical and prognostic profile of diabetic patients with ischemic stroke remains to be fully understood. Our group, on the basis of TOAST classification--a diagnostic classification of ischemic stroke developed in 1993 that distinguishes five different clinical subtypes of ischemic stroke: large-artery atherosclerosis (LAAS), cardioembolic infarct (CEI), lacunar infarct (LAC), stroke of other determined origin (ODE), and stroke of undetermined origin (UDE), and now extensively used in clinical and scientific context--analysed the prevalence of cerebrovascular risk factors and the distribution of TOAST subtypes in more 300 patients with acute ischemic stroke in two consecutives studies that reported the significant association between diabetes and the lacunar subtype and a better clinical outcome for diabetic patients, most likely related to the higher prevalence of the lacunar subtype. Well-confirmed are the roles of cigarette smoking, atrial fibrillation, and asymptomatic carotid stenosis as cerebrovascular risk factors. Particularly interesting seems to be the function of inflammation markers (CRP, TNF-alpha, IL-1 beta, ISPs) as potential risk factors. Still elusive remains the association between cholesterol serum levels and stroke, on the basis of the epidemiological data regarding this causative relationship, confirmed only by the results of intervention trials (4S, LIPID, CARE, HPS, ASCOT). Ultimately, cerebrovascular risk appears peculiar owing to the unique relationship between some modifiable risk factors (mainly diabetes and cholesterol) and the possible preferential association with stroke subtypes and specific cerebrovascular risks.

Clinical trial experience around the globe: focus on calcium-channel blockers.

Although certain classes of drugs appear to possess benefits apart from their blood-pressure lowering capability, reduction of blood pressure remains the single most important action of antihypertensive therapy. Calcium-channel blockers (CCBs) have long been recognized as potent agents for hypertension therapy. This is especially true for the prevention of stroke in hypertensive patients as evidenced from the Systolic Hypertension in Europe (Syst-Eur) and Systolic Hypertension in China (Syst-China) trials with a long acting dihydropyridine CCB. The same can be said for beta blockers in patients post myocardial infarction. However, most recent clinical trials have underscored the necessity of multiple drug therapy to achieve the goals of blood pressure reduction coupled with outcomes reduction. For example, the many recent large-scale clinical trials have required an average of three or more agents to achieve goal. Thus, the paradigm for hypertension management has been altered to determine the best treatment regimen rather than the best initial agent. While response rates to individual agents across a wide spectrum of patients vary little, not all drugs are equally suited as companion products. In this article, we discuss the most recent outcome trials with the long acting CCBs alone or in combination with other drugs. The evidence shows that calcium antagonists remain an important part of hypertension management, including in those individuals at risk of cardiac and cerebrovascular events.

Central intracardial and cerebral hemodynamics in hypertensive and normotensive stroke patients

Central intracardial and cerebral hemodynamics in hypertensive and normotensive stroke patients

Hypertension and clusters of risk factors in different stroke subtypes (an analysis of Hungarian patients via Budapest Stroke Data Bank).

Our aim was to determine the frequency of hypertension in the Hungarian stroke population, and to compare it with the data of other stroke registries. We attempted to find characteristic cluster-like associations between hypertension and another nine risk factors in different stroke subtypes and to ascertain the role of hypertension in leukoaraiosis, in early mortality, in stroke recurrence and in the case fatality rate up to 10 years. Risk factor profile of 500 unselected acute stroke cases of the Budapest Stroke Data Bank were analysed. We compared data of hypertensive stroke patients to those of unaffected ones. LIFEREG procedure of the SAS software package, cluster analysis, logistic regression, Pearson's correlation coefficient and Student's t-test were used as statistical methods. Hypertension was documented in 75% of the patients. The largest clusters were formed by the following groups: atherosclerotic stroke, hypertension with ischaemic heart disease; lacunar stroke and haemorrhage, hypertension with elevated serum cholesterol, cardiogenic embolism, ischaemic heart disease with atrial fibrillation. The case fatality rate was significantly higher in the group of hypertensive patients with ischaemic heart disease relative to those without it during the 10 years follow-up period. In the leukoaraiosis-group, systolic blood pressure was significantly higher than in the non-leukoaraiosis group. The rate of hypertension was higher than in other stroke registries. Hypertension appears to be the most frequent risk factor in stroke patients but case fatality rate is determined by presence or absence of ischaemic heart disease.

Influence of age, sex and blood pressure on the principal endpoints of the Nordic Diltiazem (NORDIL) Study

The aim of the Nordic Diltiazem (NORDIL) Study was to compare patients with essential hypertension receiving calcium-antagonist-based treatment with diltiazem and similar patients receiving conventional diuretic/beta-blocker-based treatment, with respect to cardiovascular morbidity and mortality. To assess the influence of age, sex, severity of hypertension and heart rate on treatment effects, in a sub-analysis. The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled, at health centres in Norway and Sweden, 10 881 patients aged 50-74 years who had diastolic blood pressure (DBP) of 100 mmHg or more. Systolic blood pressure (SBP) and DBP were decreased by 20.3/18.7 mmHg in the diltiazem group and by 23.3/18.7 mmHg in the diuretic/beta-blocker group - a significant difference in SBP (P < 0.001). The incidence of the primary endpoint - a composite of cardiovascular death, cerebral stroke and myocardial infarction - was similar for the two treatments. Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 patients in the conventional treatment group [relative risk (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99; P = 0.040], whereas there was a non-significant inverse tendency with respect to all myocardial infarction. There were significantly fewer cerebral strokes in patients receiving diltiazem in the subgroups with baseline SBP > 170 mmHg (n = 5420, RR 0.75, 95% CI 0.58 to 0.98; P = 0.032), DBP >/= 105 mmHg (n = 5881, RR 0.74, 95% CI 0.57 to 0.97; P = 0.030) and pulse pressure >/= 66 mmHg (n = 5461, RR 0.76, 95% CI 0.58 to 0.99, P = 0.041), and more myocardial infarctions in those with heart rate less than 74 beats/min (n = 5303, RR 1.13, 95% CI 1.01 to 1.87; P = 0.040). However, the tendencies for fewer strokes and greater incidence of myocardial infarction were present across subgroups when results were analysed for age, sex, severity of hypertension and heart rate, and treatment-subgroup interaction analyses were not statistically significant. Compared with a conventional diuretic/beta-blocker-based antihypertensive regimen, there were additional 25% reductions in stroke in the diltiazem-treated patients with blood pressure or pulse pressure greater than the medians, and an increase in myocardial infarction in those with heart rate less than the median. Such findings may be attributable to chance, but the consistency of, in particular, the stroke findings may also suggest an ability of diltiazem, beyond conventional treatment, to prevent cerebral stroke in hypertensive patients with the greatest cardiovascular risk.

Prior antihypertensive treatment and admission blood pressure correlated with clinical outcome and early morning presentation in hypertensive ischaemic stroke patients.

Blood pressure (BP) reduction of 5-6 mm Hg reduces the relative risk of stroke by 30-40%. This effect does not appear to depend on the antihypertensive agent used to bring about the required reduction in BP. Patients with acute ischaemic stroke often exhibit an elevated BP. These patients, who previously suffered from hypertension, have significantly higher levels of BP readings on admission with increased incidence of stroke immediately after arising. The aim of this study was to compare antihypertensive agents, especially short and long acting drugs with the measurement of BP on admission, the time of the ischaemic stroke and its clinical severity. This was studied retrospectively in 109 patients (55 females and 54 males). The mean age was 69.7 +/- 10.4 years. All the patients admitted between 1 July 1996 and 30 June 1997 for ischaemic stroke as established by brain CT scan, were studied. Of the stroke subjects not treated or treated with short acting calcium blockers, 40.8% and 44.4% of them respectively appeared to have an ischaemic stroke in the early morning hours in contrast to 20% of those treated with long acting calcium blockers (P < 0.05). The last group of patients also experienced less clinical severity. These results emphasise the need for proper 24-h control of BP and by comparison to other antihypertensive agents, the long acting calcium blockers with these subjects may prevent a sudden early morning rise in BP, which is instrumental in stroke prevention.

Abstracts of literature

Abstracts of literature

Genetic variation in the promoter region of the beta-fibrinogen gene is associated with ischemic stroke in a Japanese population.

Evidence suggests that an allelic variation in the beta fibrinogen gene may confer an increased risk of coronary artery disease and stroke. The role of the beta fibrinogen gene polymorphism and fibrinogen levels in ischemic stroke has not been determined in Japanese, who are more prone to stroke than to coronary artery disease compared with Caucasians. We investigated the associations between ischemic stroke, plasma fibrinogen level, and a HaeIII restriction fragment length polymorphism (G/A(-455)) located at -455 bp from the start of transcription of the beta fibrinogen gene in 85 hypertensive patients with ischemic stroke (stroke group), 85 hypertensive patients without ischemic stroke (nonstroke group) and in 84 normotensive subjects matched for age, sex, and smoking status recruited at an annual health examination (normotensive group). The frequency of non-cutting allele (designated A(-455) allele) in the control group was 0.07 [95% CI: 0.03-0.11]; this value was significantly lower than that previously reported in Caucasians (0.19-0.26). The A(-455) allele frequency of the nonstroke group and stroke group were 0.08 [95% CI: 0.04-0.12] and 0.15 [95% CI: 0.10-0.21]. A(-455) allele frequency of the stroke group was significantly higher than that of the control group chi2 = 5.63, P= 0.018) and the nonstroke group chi2 = 4.00, P= 0.043). The mean +/- SD fibrinogen level was significantly higher in the stroke group than that in the normotensive group (277 +9/- 64 mg/dl versus 257 +/- 52 mg/dl, P < 0.03), but that of the nonstroke group was not significantly different compared with both normotensive and stroke groups. In conclusion, the positive association between the fibrinogen genotype G/A(-455) and ischemic stroke in hypertensive patients was independent of other risk factors. These results suggest that fibrinogen A(-455) allele may be an independent risk factor for ischemic stroke in the Japanese population.

Effects of the calcium antagonist AE0047 on the development of neurological deficit and infarction after middle cerebral artery occlusion in stroke-prone spontaneously hypertensive rats.

AE0047 [4-(4-benzhydrylpiperazino)phenethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate dihydrochloride] is a new dihydropyridine calcium antagonist with protective effects against cerebral ischaemia and the occurrence of stroke in several animal models. We investigated the effects of AE0047 on focal ischaemia induced by middle cerebral artery occlusion in stroke-prone spontaneously hypertensive rats. AE0047 at a dose causing 20 or 40% systemic hypotension (1 or 3 mg kg-1) was given orally twice, 15 min and 24 h after occlusion. The neurological status of animals was investigated 2, 24 and 48 h after occlusion. Infarct area of brain was measured 48 h after occlusion. Middle cerebral artery occlusion resulted in the progressive deterioration of neurological status and large infarction in middle cerebral artery territories with 40% mortality. AE0047 dose-dependently attenuated the deterioration of neurological status, and reduced mortality to 0 or 10%. AE0047 significantly reduced infarct size and left/right hemispheric area ratio, an index of brain swelling. These results suggest that AE0047 has the ability to ameliorate ischaemic cerebral stroke in hypertensive patients.

Regional cerebral hemodynamics among hypertensive patients with lacunar infarctions during blood pressure control in subacute and chronic phases

In hypertensive acute stroke patients, the use of antihypertensive treatment is often delayed because autoregulation of cerebral blood flow (CBF) is often impaired during the first 4 weeks after large brain infarctions. However, little is known as to whether such delay is necessary in cases of small to moderate size brain infarction. We compared changes of regional CBF during antihypertensive treatment in subacute and chronic phases of lacunar infarction. Blood pressure was controlled with an angiotensin-converting enzyme inhibitor (n=6) or dihydropyridine calcium antagonist (n=8), administered orally for 2 weeks during the subacute (n=7) and chronic phases after (n=7) lacunar infarction. CBF was measured by the stable xenon-computed tomography (CT) method. Blood pressure decreased significantly from 132+/-20 mm Hg (mean+/-standard deviation) to 118+/-14 mm Hg (P<.05, paired t-test) in subacute patients and from 135+/-17 mm Hg to 113+/-12 mm Hg (P<.001, paired t-test) in chronic patients. There was no significant reduction either in mean hemispheric blood flow or in deep white matter blood flow during each phase. We conclude that mild control of blood pressure among hypertensive patients with lacunar infarctions does not produce clinically significant decreases in regional CBF during subacute phases of infarction.

Hypertension in stroke patients: Relationship with hyperinsulinaemia

Summary: In an attempt to determine the presence of hypertension in stroke patients and its relationship with hyperinsulinaemia, a case‐control study was carried out in the outpatients clinic, Department of Neurology, Sardjito General Hospital, Yogyakarta. Patients included in the study were those who had survived a stroke at least 3 months after the first attack. the exclusion criteria included: diabetes mellitus, renal failure, heart failure, malignancy, myocardial infarction, current antihypertensive and hypolidaemic treatment. Controls were selected from non‐stroke patients at the same department matching for sex and age. During the study 51 stroke patients (39 male and 12 female, aged 58.7 ± 10.3 years) and 51 controls (40 male and 11 female, aged 58.6 ± 9.8 years). There were no significant differences in baseline clinical characteristics; namely, smoking, body mass index, blood sugar and blood lipids except triglyceride (169 ± 61 vs 141 ± 60 P&lt;0.05) of cases and controls. Although there was no significant difference of fasting plasma insulin levels (9.3 ± 8.3 vs 8.3 ± 2.6 mU/L, P= &gt;0.05), significantly higher levels of postprandial insulin (94.8 ± 86.7 vs 55.2 ± 49.1 mU/L, P&lt;0.05) were found in cases than controls. There were a significantly higher levels of blood pressure, both systolic (160 ± 24 vs 131 ± 11 mmHg, P&lt;0.05) and diastolic (101 ± 13 vs 79 ± 4 mmHg, P&lt;0.05), and more frequent hypertension defined as BP ± 140/90 mmHg (72.5 vs 2.0%, P&lt;0.05) in cases than controls. No significant difference of plasma insulin levels (94.9 ± 82.3 vs 94.3 ± 119.2 mU/L, P&gt;0.05) between hypertensive and normotensive stroke patients. However, significantly higher levels of insulin (94.3 ± 119.2 mU/L vs 55.2 ± 49.1 mU/L, P&lt;0.05) were found in normotensive stroke patients than controls. the relationship between 2 h post‐prandial blood sugar levels and post‐prandial insulin levels was positive and nearly significant relationship (r=0.62, P=0.05). the relationship between mean arterial pressure (MAP) and post‐prandial insulin levels of the whole patients (cases and controls) were poor but significant (r = 0.22, P&lt;0.05). the relationship between MAP and post‐prandial insulin levels are poor and not significant both in stroke patients (r = 0.00, P&gt;0.05) and controls (r = 0.17, P&gt;0.05). the slope of both curves in both scattered diagrams seemed to be slightly different. We conclude that hypertension and post prandial hyperinsulinaemia may play a role in the genesis of stroke, while hyperinsulinaemia may an independent factor.

Effects of the angiotensin-converting enzyme inhibitor alacepril on cerebral blood flow in hypertensive stroke patients: A pilot study

In hypertensive patients with a history of stroke, inappropriate antihypertensive therapy can reduce cerebral blood flow (CBF), exposing patients to the danger of cerebral ischemia. An angiotensin-converting enzyme (ACE) inhibitor, alacepril (25 mg twice daily after meals in the morning and evening), was orally administered for 4 weeks to 12 hypertensive stroke patients, and CBF was measured using 133Xe inhalation methods before and after alacepril treatment. After 4 weeks of treatment, systolic and diastolic blood pressures decreased by 18 ± 12 mm Hg and 9 ± 5 mm Hg, respectively. The CBF increased significantly by 10.6 ± 16.5% ( P < 0.05) in the diseased cerebral hemisphere and by 12.5 ± 14.8% ( P < 0.01) in the healthy cerebral hemisphere. None of the patients had symptoms of cerebral ischemia during the treatment period. Chronic ACE inhibition is known to ameliorate the mechanics and function of cerebral arteries and improve quality of life, including cognitive function. The increase in CBF seen in our patients may reflect the reduction of cerebrovascular resistance and improvement of cerebral function. Our results suggest the potential usefulness of ACE inhibitors in antihypertensive therapy for stroke patients.

Modern Strategies to Prevent Coronary Sequelae and Stroke in Hypertensive Patients Differ From the JNC V Consensus Guidelines

In recent years, government agencies of many countries have established consensus guidelines for the evaluation and treatment of hypertension. Once published, guidelines tend to be perceived as directives by a variety of health care providers. Unfortunately, these guidelines often do not reflect the practices of most hypertension experts. This report summarizes the opinions of seven hypertension experts concerning the impact of "official" guidelines on clinical practice. In addition, the individual therapeutic recommendations of these panel members are summarized. Their different treatment strategies reflect the diversity of first rate treatment plans that aim to reduce the cardiovascular sequelae in individual patients with essential hypertension. Most importantly, not one of these seven treatment strategies followed the "preferred" treatment of the U.S. guidelines, which recommend diuretics and beta-blockers as first-line therapy. The present authors approach the treatment of hypertension as a means to reduce cardiovascular events. Thus, reduction of blood pressure is not the most important therapeutic endpoint. The panel believes that whereas many different drugs can produce effective blood pressure reduction, the modern primary goal of antihypertensive drug therapy is to select a regimen most likely to prolong the quality and duration of life. In real terms, this means that the primary goal of treatment is the prevention of the major vascular sequelae of hypertension (heart attack, ventricular remodeling, hypertrophy, heart failure, and stroke) that shorten useful life. There are a number of effective hypertensive treatments, which can be selected based on individual patient requirements. However, many consensus guidelines do not allow the flexibility required to optimize individual patient treatment. As a result, health care providers should not feel compelled to regard the preferences of "official" guidelines as the best, modern, state-of-the-art therapy for an individual patient. All seven experts who are deeply involved in the daily care of patients preferred drugs other than beta-blockers and diuretics (the Joint National Committee [JNC] choices) for first-line therapy of hypertension.

Effects of dihydropyridines on cerebral blood vessels

To evaluate the effects of dihydropyridine calcium antagonists on the cerebral circulation in stroke patients. DESIGN OF STUDIES: Mean cerebral circulation parameters were studied in chronic stroke patients with hypertension and treated acutely or chronically (2 weeks) with nicardipine or nifedipine retard. The effects of nicardipine on local cerebral blood flow were also studied in patients with a subacute brain infarction. Mean cerebral blood flow was significantly increased after a single oral administration of nicardipine but not after nifedipine retard. Both calcium antagonists reduced mean arterial pressure. Nifedipine retard acted mainly by reducing blood pressure and nicardipine mainly by reducing cerebrovascular resistance. Dihydropyridines have a beneficial effect in the control of hypertension in stroke patients.

A Review of the Short-Term Benefits of Antihypertensive Treatment With Emphasis on Stroke

Hypertension is the major underlying risk factor for stroke, and the risk of stroke increases proportionally to the rise in blood pressure. In the elderly, systolic hypertension increases the risk of stroke. Stroke in hypertensive patients may be due to Charcot-Bouchard aneurysm, to atherosclerosis of the extracranial and major cerebral arteries, or to embolism as a result of cardiac disease. Reduction of blood pressure greatly reduces the risk of stroke in severe, mild-to-moderate, and isolated systolic hypertension. The reduction in stroke risk occurs up to a year after the onset of treatment and appears to persist thereafter. The use of dihydropyridine calcium antagonists may confer further benefits in addition to those related to blood pressure reduction as these agents block the influx of calcium into ischemic brain cells, thereby limiting the extent of the infarction. However, although these effects have been impressive in experimental models, there is as yet no convincing evidence of this effect in clinical studies.

Reducing the risk for coronary events and stroke in hypertensive patients: Comments on present evidence

Therapeutic options for initial antihypertensive treatment include the four most popular classes of drugs: diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium antagonists. The practitioner must decide which agent is appropriate for each patient, the main goal of treatment being to prevent stroke and coronary events—sudden death and myocardial infarction. A 40% reduction in stroke can probably be achieved with any antihypertensive treatment, but data show that it is much more difficult to reduce the risk of coronary events. Available evidence from studies in men indicates that certain beta blockers are superior to thiazide diuretics for the prevention of coronary events. Results from the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) Trial showed that the risk for coronary events was 24% lower in patients receiving metoprolol than in patients receiving diuretics (p>0.001), with beneficial effects in smokers as well as nonsmokers. Present data might suggest that different beta blockers may have different efficacy in preventing coronary events. Clinical trials have not yet produced long-term prognostic data on the effects of ACE inhibitors or calcium antagonists on the incidence of coronary events in hypertensive patients. Pooled data on calcium antagonist therapy in postmyocardial infarction patients indicate a trend toward higher mortality with calcium antagonists than with placebo. Because of the large number of hypertensive patients at increased risk for coronary events, the reduction in coronary events observed with some beta blockers may have important implications for clinical practice. The reduced risk for coronary events is probably independent of the reduction in blood pressure. Mechanisms currently under study include antiatherosclerotic effects, antithrombotic effects, anti-ischemic effects, and antifibrillatory effects.