Efficacy, safety, and effects on quality of life of bisoprolol/hydrochlorothiazide versus amlodipine in elderly patients with systolic hypertension.

BACKGROUND: Several studies have shown the benefits of antihypertensive treatment in elderly patients in terms of cardiovascular morbidity and mortality rate reduction. Low-dose drug combinations may be of interest in treating older subjects. A randomized, multicenter, double-blind, parallel group study was conducted to compare the efficacy and safety of bisoprolol 2.5 mg/hydrochlorothiazide 6.25 mg (n = 84) to amlodipine 5 mg (n = 80) in isolated systolic hypertension in patients older than 60 years. METHODS: After a 2- to 4-week placebo washout period, both drugs were administered once daily and taken for 12 weeks. Blood pressure was measured 24 hours after treatment administration. RESULTS: Systolic and diastolic blood pressure changes from baseline to week 12 were similar for both the bisoprolol and amlodipine groups (-20. 0/-4.5 mm Hg and -19.6/-2.4 mm Hg, respectively). Overall adverse events for bisoprolol and amlodipine were 39% and 40%, respectively. Changes in quality of life scores were +2.5 for bisoprolol and +3.2 for amlodipine, with a positive change indicating improvement. CONCLUSIONS: This study demonstrates comparable efficacy and tolerability of bisoprolol 2.5 mg/hydrochlorothiazide 6.25 mg and amlodipine 5 mg. The low-dose combination of bisoprolol and hydrochlorothiazide may be an appropriate alternative for elderly patients with systolic hypertension.

Improvement of internal jugular vein cannulation using an ultrasound-guided technique.

OBJECTIVE: To determine whether ultrasound guidance can help operators to improve the results of jugular vein access in the ICU. DESIGN: Prospective, randomized study. SETTING: General Intensive Care Unit of a University Hospital. PATIENTS: Seven-nine patients were assigned to internal jugular vein cannulation using anatomical landmarks alone (control group, n = 42) or with ultrasound guidance (ultrasound group, n = 37). INTERVENTION: All cannulations were performed by junior house staff under the direct supervision of a senior physician. In the ultrasound group, an ultrasonography (7.5 MHz) was used and the transducer was covered by a sterile sheath. The placement and direction of the cannulating needle were determined on the ultrasound image. MEASUREMENTS AND RESULTS: Internal jugular vein cannulation was successful in 37/37 (100%) patients in the ultrasound group and in 32/42 patients (76%) in the control group (p < 0.01). Average access time was longer in the control group (235 +/- 408 s vs 95 +/- 174 s, p = 0.06) and carotid artery puncture occurred in five patients in each group (p = 0.83). Jugular cannulation was successful at the first attempt in 26% in the control group and 43% in the ultrasound group (p = 0.11). Thirty-two patients (86%) in the ultrasound group and 23 patients (55%) in the control group (p < 0.05) were cannulated within 3 min. The cannula could therefore not be inserted within 3 min in 19 patients (45%) in the control group. Failure was explained by thrombosis (n = 1), small caliber of the internal jugular vein (< 5 mm, n = 3), abnormal vascular relations (n = 3). Among the ten primary failures of cannulation, an internal jugular vein catheter was able to be inserted in four cases by an experienced physician on the side initially selected and with ultrasound guidance in two cases. The catheter was inserted into the contralateral internal jugular vein under ultrasound guidance in the remaining four cases. CONCLUSION: Ultrasound guidance improved the success rate of jugular vein cannulation in ICU patients. Our results suggest that ultrasound guidance should be used when the internal jugular vein has not been successfully cannulated within 3 min by the external landmark-guided technique.

Diagnostic and therapeutic implications of transesophageal echocardiography in medical ICU patients with unexplained shock, hypoxemia, or suspected endocarditis.

OBJECTIVE: To evaluate the diagnostic and therapeutic implications of transesophageal echocardiography (TEE) in intensive care patients. DESIGN: Comparative study. SETTING: A 10-bed general intensive care unit. PATIENTS: Between 1 January 1992 and 31 May 1993, 61 patients prospectively identified with shock (n = 14), severe, unexplained hypoxemia (Partial pressure of oxygen in arterial blood/fractional inspired oxygen < 200) (n = 31), or suspected endocarditis (n = 16) underwent a TEE examination to supplement transthoracic echocardiography (TTE) examination. INTERVENTIONS: The results of each TEE examination were compared with the clinical findings and TTE data. TEE examinations were classified as follows: 0, TEE results were similar to TTE results; 00, TEE examination resulted in exclusion of suspected abnormalities; 1, TEE revealed a new but minor diagnosis compared to the TTE diagnosis; 2, TEE revealed a new major diagnosis not requiring a change of treatment; 3, TEE results revealed a new major diagnosis requiring an immediate change of treatment. RESULTS: Intraobserver reliability of the TEE classification was confirmed by a 100% concordance and interobserver reliability was evaluated as an 84% concordance. Results of the TEE classification were: class 0, n = 21 (34%); class 00, n = 13 (21%); class 1, n = 7 (12%); class 2, n = 8 (13%); class 3, n = 12 (20%). Therapeutic implications of TEE in class 3 patients were cardiac surgery in 5 patients (2 cases of acute mitral regurgitation, 2 valvular abscesses, and 1 hematoma compressing the left atrium), discontinuation of positive end-expiratory pressure in 1 ventilated patient with an atrial septal defect, weaning off mechanical ventilation in 1 patient with an atrial septal defect, prescription of antimicrobial therapy in 3 patients with endocarditis, and prescription of anticoagulant therapy in 2 patients with left atrial thrombus. No difficulty inserting the transducer was observed in any of the 61 patients studied. The only noteworthy complication was a case of spontaneously resolving atrial fibrillation. CONCLUSION: TEE is safe and well tolerated and is useful in the management of patients in the intensive care unit with shock, unexplained and severe hypoxemia, or suspected endocarditis when TTE is inconclusive.

Antihypertensive therapy and wave reflections.

Studies of pulsatile arterial hemodynamics have emphasized that the pulsatile component of pulse pressure has two important characteristics: (i) it increases from central to peripheral arteries for a similar value of mean arterial pressure, and (ii) it is dominantly influenced by the amplitude and timing of the backward pressure wave. Although these important aspects of wave reflections have been poorly investigated in the field of hypertension, they may be easily studied noninvasively in humans on the basis of the analysis of the pulse wave contour of carotid and aortic blood pressure. Increased wave reflections returning toward the thoracic aorta during systole may have deleterious consequences on the structure and function of the heart. Some (but not all) antihypertensive drugs may contribute to decrease and/or to delay wave reflections in association with blood pressure reduction.

Effects of antihypertensive drugs on large artery compliance.

The changes in arterial compliance following drug treatment have been studied mainly in hypertension. Physiologically, reduced arterial compliance independently affects blood pressure through an increase in systolic pressure and a decrease in diastolic pressure at any given value of mean arterial pressure. This review summarizes the pharmacological studies performed in recent years on the ability of antihypertensive drugs to modify arterial compliance. For the same decrease in mean arterial pressure, antihypertensive drugs may have differential effects improving arterial compliance (calcium channel blockers, converting enzyme inhibitors, alpha-blockers and some beta-blockers) or causing no change (dihydralazine, diuretics, propranolol) with resulting consequences on cardiac structure and function.

[Absence of labetalol interference on urine metanephrine determination in hypertensive patients]. / Absence d'interférence du labétalol sur la détermination des métanéphrines urinaires chez l'hypertendu.

The dosage of urinary catecholamines and their metabolites is a main element of diagnosis in the research of a pheochromocytoma in patients with high blood pressure. The literature reports high values of these compounds in patients treated with labetalol (an alpha/beta-blocker). An analytical interference has been evoked to explain these misleading results, which have not been observed with other beta-blockers. The goal of this work was to look for this eventual analytical interference in the dosage of urinary metanephrine by reversed phase liquid chromatography coupled with electrochemical detection, in patients with high blood pressure. Eighteen hypertensive patients, 52 +/- 14 years old, were included in the study. In 8 patients, a dosage of metanephrine, normetanephrine and creatinine on a 24 hours urine sample was performed before (D1) and 24 hours after (D3) the prescription of labetalol (200 mg twice a day). In the other group, labetalol was not prescribed but dosage was made in the same conditions. Urinary excretion of these compounds (metanephrine+normetanephrine) divided by urinary creatinine was not modified in the treated group (0.16 +/- 0.08 vs 0.14 +/- 0.04), nor in the reference group (0.17 +/- 0.08 vs 0.17 +/- 0.08). This study shows that administration of labetalol in patients with essential hypertension does not interfere with urinary metanephrine and normetanephrine determination after 48 hours of treatment. This implies that research for a pheochromocytoma is possible in patients with hypertension and receiving labetalol, by using reversed phase liquid chromatography coupled with an electrochemical detector for the dosage of urinary metanephrine and normetanephrine.

Ambulatory blood pressure measurement, smoking and abnormalities of glucose and lipid metabolism in essential hypertension.

OBJECTIVE: Casual (mercury sphygmomanometer) and ambulatory blood pressure measurements were determined in 61 subjects with sustained essential hypertension. DESIGN: Patients were classified into three subgroups: smokers or non-smokers; patients with or without hyperglycemia; and patients with or without plasma lipoprotein abnormality. Mean casual blood pressure were shown to be identical in these three subgroups. RESULTS: When ambulatory blood pressure was analyzed, smokers exhibited a significant increase in pulse pressure exclusively during the activity period, whereas diastolic blood pressure and mean arterial pressure (MAP) were not modified in comparison with controls. Patients with abnormal plasma glucose showed a significant increase in systolic and pulse pressure during both activity and non-activity periods, with a slight increase in MAP during the activity period. Patients with and without plasma lipid abnormality displayed similar ambulatory blood pressure. CONCLUSION: The study provides evidence that, in spite of similar casual blood pressure levels among smokers and non-smokers, as well as among those with elevated fasting glucose levels, smokers and patients with hyperglycemia have a higher systolic and pulse pressure during 24-h monitoring, pointing to the possible role of cyclic stress in the deterioration in the structure of the hypertensive arterial wall.

Comparison of forearm plethysmographic methods with brachial artery pulsed Doppler flowmetry in man.

Blood flow in the forearm was evaluated using simultaneous measurements of pulsed Doppler flowmetry and strain-gauge plethysmography in 32 normal subjects and 91 patients with sustained essential hypertension. The two determinations of blood flow were strongly correlated (r = 0.58). Measurements with strain-gauge plethysmography reflected changes in blood flow velocity but were poorly correlated with changes in arterial diameter as measured by pulsed Doppler flowmetry. The latter method permits evaluation of instantaneous variations in blood flow velocity and detection of active modifications of arterial diameter.

Sodium and large arteries in hypertension. Effects of indapamide.

Epidemiologic studies evaluating arterial pulse wave velocity together with blood pressure indicate that: (1) salt intake has an independent effect on arteriolar tone and arterial wall properties, with the former indirectly and the latter directly contributing to increased arterial stiffness with age; and (2) normotensive adult subjects who follow a low sodium diet have reduced arterial stiffness and this effect is independent of blood pressure. Conversely, in elderly persons with isolated systolic hypertension, isotonic saline infusion causes a predominant increase in systolic pressure due to an increase in the stiffness of the arterial wall. The diuretic indapamide produces a decrease in blood pressure without significant change in brachial artery diameter. The result indicates a shift of the pressure-diameter curve, reflecting for the first time in humans a pharmacologic effect of the drug on arterial vessel. Furthermore, diuretic drugs may increase arterial distensibility and compliance in hypertensive patients, but this effect seems to be more pronounced in older than in younger subjects. In the latter, either activation of the sympathetic nervous system or potassium depletion, or both, might counteract the improvement in arterial distensibility caused by blood pressure reduction and sodium depletion. Based on epidemiologic, clinical, and pharmacologic studies, this critical review suggests that, in patients with essential hypertension, changes of sodium intake in diet or administration of diuretics, or both, affect the status of large arteries independently of blood pressure changes.

Effects of indapamide on the quality of life of hypertensive patients.

This study analyzed the variation in the parameters characterizing the quality of life and well-being of hypertensive patients treated with indapamide. Thirty patients (10 men and 20 women; mean age, 52.5 +/- 2.1 years, SEM) were selected after a three-week observation period during which patients received placebo. They all had essential hypertension, defined as a diastolic blood pressure between 95 and 120 mm Hg. After the three-week placebo treatment period, indapamide was prescribed as single-agent therapy at a dose of one tablet per day (2.5 mg) for three months. The quality of life and the feeling of well-being of the treated subjects were analyzed on the basis of two self-assessment scales completed by patients and on the responses to a clinical observation scale completed during the consultation by the doctor. The decrease in blood pressure was significant (p less than 0.01) by the first month of treatment and the blood pressure was controlled (diastolic blood pressure less than 90 mm Hg) in 79.3 percent of patients by the third month. Statistical analysis of the modifications in the different scores demonstrated a significant improvement between the start and the end of the indapamide treatment period for the three types of scales (p less than 0.01). Analysis of the results also confirmed the homogeneous and significant concordance between the improvement in the responses to the doctor and patient scales. These results on the improvement in quality of life and well-being observed with indapamide demonstrate the importance of taking these aspects into consideration in the drug treatment for permanent essential hypertension.

Systolic hypertension in patients with arteriosclerosis obliterans of the lower limbs.

Intraarterial blood pressure, brachial artery compliance and diameter, and pulse wave velocity were determined in 20 patients with arteriosclerosis obliterans of the lower limbs (AOD) in comparison with 10 age- and sex-matched controls. With the same mean arterial pressure as in controls, patients with AOD exhibited a significant increase in systolic pressure and decrease in diastolic pressure, resulting in an increase in pulse pressure. While brachial artery diameter and pulse wave velocity remained nearly within the normal range, arterial compliance was significantly reduced and was negatively correlated with the level of pulse pressure. The study provided evidence that: atherosclerotic modifications in patients with AOD are associated with an increase in pulse pressure, which predominates on the increase in mean arterial pressure, increased pulse pressure is related to decreased arterial compliance, which reflects intrinsic modifications of the viscoelastic properties of the arterial wall.

Pulse pressure in sustained essential hypertension: a haemodynamic study.

Central and forearm haemodynamics were studied in 73 middle-aged male subjects: 14 normotensive controls and 59 patients with sustained essential systolic/diastolic hypertension. Hypertensives were divided into two groups: pulse pressure within the normal range (40-60 mmHg; group I) or above 60 mmHg (group II) for the same level of mean arterial pressure (MAP). Indices of systemic and forearm arterial compliance and distensibility for the same age and MAP were reduced to the same extent in group I and II. In contrast, the peak systolic blood flow velocity of the brachial artery, cardiac output (CO) and stroke volume (SV) were significantly greater in group II than in group I. Systemic and forearm vascular resistances were significantly increased in group I but remained within the normal range in group II. The study provided evidence that, in middle age, there is a group of hypertensive patients characterized by a disproportionate increase in pulse pressure for the level of MAP. The elevation of the pulsed component of blood pressure (BP) reflects a relative hyperkinesia with an increase in CO and arteriolar vasodilatation. The subsequent increase in systolic pressure is produced by a combination of reduced arterial distensibility and increased SV.

Captopril + hydrochlorothiazide 24 h ambulatory monitoring effects.

The purpose of this study was to evaluate over a 24 h period the antihypertensive effect of captopril 50 mg + hydrochlorothiazide (HCTZ) 25 mg once a day in mild to moderate hypertension. Ambulatory recordings over 24 h of the blood pressure using the Spacelabs system were performed, at the end of a 15-day placebo period and after giving captopril + HCTZ for 45 days. Captopril + HCTZ significantly decreased (P less than 0.001) systolic and diastolic blood pressures for both the diurnal period (8 h to 22 h) and the nocturnal period (22 h to 8 h). No change in heart rate was observed. For further analysis, the mean hour values of blood pressure and heart rate were calculated. A constant decrease of the systolic and diastolic blood pressure throughout the 24 h was obtained after captopril + HCTZ without any change in heart rate and in nyctohemeral variations. The study provided evidence that, in patients with mild to moderate essential hypertension, captopril + HCTZ once a day decreased systolic and diastolic blood pressure all day long without any change in the heart rate and the blood pressure nyctohemeral cycle.

Changes in arterial distensibility produced by converting enzyme inhibitors in hypertensive humans.

Converting enzyme inhibitors enhance arterial compliance in hypertensive humans. The enhancement is due not only to an increase in arterial diameter and volume but also to an increase in arterial distensibility. The latter effect reflects the drug action on arterial smooth muscle tone rather than the lower stretch due to the blood pressure reduction. The improvement in the buffering function of large arteries in hypertensives may contribute to produce a more important decrease in systolic pressure and a better reversion of cardiac hypertrophy.