Nifedipine or verapamil as sole treatment of hypertension. An intraarterial study.

Intraarterial ambulatory blood pressures were recorded prior to and during therapy with two different calcium ion antagonists, nifedipine and verapamil, in two separate groups of patients. In the first group, nine patients were studied off therapy and following a minimum of 6 weeks of nifedipine treatment (dose range, 20 to 60 mg twice daily). A second group of 16 patients followed the identical protocol but were prescribed verapamil (120 to 160 mg, three times daily). During both studies, patients underwent standardized physiological tests including tilt, isometric handgrip, and dynamic bicycle exercise. Both verapamil and nifedipine caused a reduction in blood pressure over most of the 24 hours studied. Nifedipine did not affect heart rate whereas verapamil caused a reduction of approximately 10 bpm. Nifedipine and verapamil did not induce postural hypotension, and the absolute responses to dynamic and isometric exercise were reduced. These results show the efficacy of slow channel inhibitors in the management of essential hypertension.

An evaluation of self-recorded blood pressure during drug trials.

To our knowledge, there have been no published comparisons of different techniques for measuring blood pressure during clinical trials. We undertook a comparison during clinical trials with verapamil and prazosin. During an open trial of verapamil we compared the treatment-induced blood pressure reductions as measured by clinic, intra-arterial, and self-recorded methods. The mean reduction in blood pressure was 38 +/- 13.6/20 +/- 10.1 mm Hg for clinic blood pressure, 24 +/- 17.9/16 +/- 7.3 mm Hg for self-recorded blood pressure, and 23 +/- 12.3/19 +/- 10.1 mm Hg for mean daytime intra-arterial blood pressure. During prazosin treatment the mean reduction in blood pressure was 28 +/- 21.5/18 +/- 8.5 mm Hg for clinic blood pressure, 21 +/- 20.5/6 +/- 13.7 mm Hg for self-recorded blood pressure, and 18 +/- 19.2/5 +/- 9.6 mm Hg for mean daytime intra-arterial blood pressure. There was little agreement between methods within individual patients and for group comparisons of intra-arterial or clinic methods. There was, however, good agreement between intra-arterial and self-recorded methods. This study suggests that self-recorded blood pressure recording is suitable for monitoring efficacy of antihypertensive agents in a group of patients, although caution must be exercised when interpreting the effects of therapy when measured by indirect methods in an individual patient.

Evaluation of the Remler M2000 blood pressure recorder. Comparison with intraarterial blood pressure recordings both at hospital and at home.

The Remler M2000 is a semiautomated device that has been used to collect epidemiological data and assess blood pressure variability. It has been subjected to limited evaluation in operation, however, and no studies of its accuracy away from the hospital or office environment have been undertaken. We recruited a group of 28 patients with essential hypertension who were undergoing intraarterial ambulatory blood pressure monitoring and compared the intraarterial recordings with those made with the Remler instrument both at home and in the hospital. The Remler recordings were also compared with simultaneous indirect blood pressure measurements made with the random zero sphygmomanometer. The mean difference between the Remler and intraarterial blood pressure recordings was -3/7 in the hospital and 7/0 at home. All standard deviations were greater than 10 mm Hg, indicating large between-subject variability. Overall, the relationship of the Remler M2000 readings to intraarterial pressures was as close if not closer than standard indirect sphygmomanometry and thus might provide useful data for epidemiological surveys or drug trials. It would appear that for accurate measurement of short-term blood pressure variation and 24-hour recording, intraarterial recording is the method of choice.

An intra-arterial profile of methyldopa.

The "Oxford" system for intra-arterial ambulatory blood pressure monitoring was used to monitor the blood pressure profile in 24 patients with essential hypertension who had received no therapy for 4 wk. The responses to tilt and isometric and dynamic bicycle exercise were recorded. Following the baseline study patients received methyldopa 125 mg t.i.d., which was titrated to a maximum of 500 mg t.i.d. according to blood pressure responses. The mean daily dosage was 1359 mg. Six weeks after the last dosage increment the experiment was repeated. Each patient was asked to take the total daily dosage once a day and the intra-arterial monitoring program was repeated after another 6 wk. Mean daytime intra-arterial blood pressure during three-times-daily dosing was reduced by 27/15 mm Hg; circadian curves were clearly separated during the day but not at night. Once-daily dosing did not control blood pressure as well. There was no evidence of postural hypotension and the absolute pressure response was lowered during both isometric and dynamic exercise. These results are comparable to those from similar studies with alpha- and beta-adrenoreceptor--blocking drugs.

Nifedipine tablets for systemic hypertension: a study using continuous ambulatory intraarterial recording.

The action of nifedipine tablets was examined in 17 patients with essential hypertension focusing particularly on the profile of blood pressure (BP) reduction over 24 hours resulting from both twice-daily and once-daily therapy (dose range 40 to 120 mg daily). This new formulation of nifedipine has a more prolonged and lower peak plasma level than an equivalent dose of nifedipine capsules. Our patients were fully ambulant and studied by continuous intraarterial recording techniques. BP responses during isometric and dynamic exercise testing were also observed. Within-patient comparisons of consecutive mean hourly systolic and diastolic BP showed a highly significant effect from twice-daily therapy (p less than 0.001) for nearly the entire day. Also, significantly lower BP was maintained during isometric and dynamic exercise. Mean hourly heart rates were not significantly altered. The profile of action of the single morning dose was initially similar, but its efficacy diminished from 6 P.M. to 8 A.M. on the following day. Side effects were not unduly troublesome and did not cause any patient withdrawals. Four patients developed mild ankle edema. Two others had facial flushing. Nifedipine given twice daily in tablet form, therefore, is an effective antihypertensive drug capable of lowering BP consistently over 24 hours in ambulant patients and during formal exercise testing. We suggest that this agent may be useful as initial therapy for systemic hypertension, although the tablets are not as yet widely available.

Twice-daily verapamil for hypertension: a comparison with propranolol.

Recent reports have confirmed that some slow calcium channel inhibitors have useful antihypertensive properties because they produce dilatation of the peripheral arterioles without reflex tachycardia. Verapamil is such a drug, but its clinical role in the management of hypertension is not clear. An open crossover trial was performed to compare the 24-hour profiles of blood pressure reduction after long-term therapy with a standard beta-adrenoceptor blocker, propranolol, and verapamil. Nineteen patients were studied by continuous ambulatory intraarterial recording and the order of drug administration was determined by random allocation. The drugs were administered 2 times a day and titrated according to casual clinic pressures (propranolol, 40 to 240 mg 2 times a day; verapamil, 120 to 240 mg 2 times a day). Mean hourly blood pressure and heart rate values were obtained over a 24-hour cycle and the responses to isometric and dynamic exercise were also examined. The drugs produced a uniform and comparable reduction in blood pressure throughout the day, together with a reduction in heart rate, which was greater with propranolol. Comparable effects were also seen on the pressor responses to exercise. Both drugs were equally well tolerated and caused no patient withdrawals. Thus, oral verapamil given 2 times a day shows a degree of efficacy similar to that of propranolol and provides 24-hour blood pressure control. This slow calcium channel inhibitor was well tolerated and may be used as initial therapy for hypertension.

The safety of ambulatory intra-arterial pressure monitoring: a clinical audit of 1000 studies.

Between 1973 and 1981 1000 successful studies involving ambulatory monitoring of intra-arterial blood pressure were performed using percutaneous cannulation of the brachial artery. We have reviewed the clinical effects of these studies and 35 other cases where attempted cannulation was unsuccessful. One major complication occurred, when an infected haematoma arising at the cannulation site led to the formation of a false aneurysm. In only one other case was distal pulsation diminished following the study. There were 157 reported "minor" complications in 122 studies, including haematoma, haemorrhage, transient paraesthesiae in median nerve territory, and evidence of micro-emboli. A limited study using pulsed wave Doppler ultrasound revealed no significant alteration in arterial lumen size or flow in 20 subjects. The procedure was therefore associated with a much smaller incidence of clinical problems than has been reported with other investigations involving cannulation of the brachial artery.

Twenty-four-hour blood pressure control: an intraarterial review.

Intraarterial blood pressure monitoring has shown the circadian rhythm of blood pressure control. Blood pressures tend to be highest in the morning before falling gradually during the day to a nadir at 3:00 a.m. There is a slight rise in the late afternoon that may correspond to patients' attendance at hospital for calibration of the equipment. There is a small rise in the blood pressure before awakening, and after arousal there is a rise in blood pressure to the peak level of the morning. In this article, we examine the effect of a variety of antihypertensive agents on this rhythm. In general, beta-adrenoceptor blockers appear to have less effect on nocturnal blood pressure and surge in pressure after arousal, while vasodilators, particularly alpha-adrenoceptor blockers, have a pronounced effect. These findings indicate that the rise in blood pressure before awakening and the rapid rise upon arousal appear to be due to increased alpha-adrenoceptor activity.

Is the blood pressure the same in both arms?

It is generally believed that there are blood pressure differences between the right and left arms, but most of the validation studies have used nonsimultaneous measurements. It is important to know whether there is a difference, as methodological comparisons are often made using a different technique on each arm. We have measured the blood pressure simultaneously in both arms in 91 patients, using two observers and two cuffs to provide eight measurements in a fully balanced design. The mean difference in blood pressure between the arms (left/right) was -1.3 (SE 0.4)/1.1 (SE 0.3) mmHg. Mean differences of the same magnitude were found between the two observers, and between the cuffs. Thus, no systematic difference of any consequence was found, although individual patients had mean between-arm differences in blood pressure of up to 10 mmHg. These results suggest that no significant bias is introduced in methodological comparisons that use both arms.

An evaluation of the Avionics Pressurometer III 1978 at home and in hospital.

The Avionics Pressurometer III is the only noninvasive indirect ambulatory blood pressure system which provides 24-h blood pressure measurements, but it has been subjected to limited evaluation. We report a critical evaluation comparing it to simultaneous intra-arterial blood pressures both at home and at hospital as well as during standardized exercise. Comparisons with simultaneous indirect methods were also made. Twenty-two hypertensives undergoing intra-arterial ambulatory blood pressure monitoring wore the two recorders for one day. The mean difference (standard deviation SD) for intra-arterial blood pressure--Avionics blood pressure was 2 (SD 8.6)/-14 (SD 10.3) mmHg at home and -3 (SD 15.4)/-11 (SD 12.3) mmHg at hospital. At the end of exercise the figures for the same comparison were -7 (SD 16)/0 (SD 15.6) mmHg. In general the agreement between intra-arterial and Avionics pressurometer recordings was closer for systolic than for diastolic blood pressures but there was wide variation for individuals as shown by the standard deviations about the mean difference. We did not use the recorder at night as patients complained that the noise kept them awake and so night-time blood pressures were not attainable. We do not think the recorder performed satisfactorily during physical exertion, and in view of its expense, this recorder is of limited potential value in supplying accurate information.

The effect of placebo on indirect and direct blood pressure measurements.

We have conducted a series of experiments which clearly show that intra-arterial ambulatory blood pressure is not altered by the administration of placebo. This finding is in contrast to the apparent fall in pressure that appears when the indirect (Korotkoff) method is used. The evidence suggests that the apparent fall in indirect pressure is due to abolition of the orienting reflex with time. Therefore, clinical trials of antihypertensive drugs using the intra-arterial method do not need a placebo control, whereas a placebo control is essential in all trials using the indirect technique for measuring blood pressure.

Noninvasive temporary pacemakers.

Temporary transcutaneous pacing involves passing a variable current across the chest wall synchronized to sensed electrical signals. We evaluated two systems, the Cardio-Aid and Pace-Aid both in routine, and emergency use. The Cardio-Aid was tested on 12 patients (9 routine and 3 emergency) and the Pace-Aid was tested alone in 4 patients (2 emergency and 2 routine). Both systems were tested on a further 7 patients (2 emergency and 5 routine). Overall, successful pacing was achieved in 3 out of 19 patients with the Cardio-Aid (1 emergency) and in 4 out of 11 patients with the Pace-Aid (3 emergency). The maximum current used was limited by the degree of pain experienced. These data suggest that the benefit derived from transcutaneous pacing is limited. The pain experienced by patients may be diminished by appropriate analgesics and sedation, thereby allowing a greater pacemaker output particularly in an emergency situation.

Nifedipine tablets for hypertension: a study using continuous ambulatory intra-arterial recording.

A study using continuous ambulatory intra-arterial blood pressure recording has shown that nifedipine tablets given twice daily can provide 24 hour control of blood pressure and maintain lower absolute blood pressure levels during isometric and dynamic exercise.

The role of a slow channel inhibitor, verapamil, in the management of hypertension.

The 'Oxford' system for continuous monitoring of the ambulatory blood pressure was used to assess the changes in blood pressure following therapy with the slow channel inhibitor, verapamil. Sixteen patients were studied on no therapy and following a minimum of 6 weeks therapy (dose range 120-160 mg t.d.s.). During each study patients underwent standardized physiological tests including tilt, isometric handgrip and dynamic bicycle exercise. Verapamil was demonstrated to produce a consistent reduction of blood pressure over most of the 24 h period studied but this was most marked during the day. Heart rate was also reduced. There was no postural hypotension and the absolute responses to dynamic and isometric exercise were reduced. The results demonstrate the antihypertensive efficacy of 'slow channel inhibitors' as represented by verapamil.

Myocardial dysfunction in ankylosing spondylitis.

Echocardiographic evidence has suggested abnormalities of the myocardial function in patients with ankylosing spondylitis. In this work the cardiac function in patients with ankylosing spondylitis and in normal volunteers was evaluated. Twenty four normal volunteers and 21 patients with ankylosing spondylitis aged 18-45 were studied. None had overt cardiac disease. Cardiac function was assessed at rest with echocardiography, at rest and during supine bicycle exercise using radionuclide angiography in the left anterior oblique position following equilibration with 740 MBq of technetium-99. The subjects undertook supine bicycle exercise with 30 W increments every three minutes to the point of fatigue. Comparison of data from normal volunteers and patients with ankylosing spondylitis were made using Student's t test for independent samples or the Mann-Whitney non-parametric technique, as appropriate. Subjects were matched for age, sex, height, and weight. There were no echocardiographic differences; however, global nuclide left ventricular function showed several differences between normal volunteers and patients with ankylosing spondylitis. The peak filling rate during exercise was significantly lower in patients with ankylosing spondylitis: normal volunteers 6.5 (SD 1.2); patients with ankylosing spondylitis 5.7 (1.2). The time to reach peak filling during exercise was significantly lower in patients with ankylosing spondylitis: normal volunteers 102 (22); patients with ankylosing spondylitis 120 (23). Regional analysis also showed differences between patients with ankylosing spondylitis and normal volunteers both at rest and during exercise. In the anteroseptal region the filling fraction and peak filling rate were significantly lower in patients with ankylosing spondylitis. Most of the differences (although not all) were in the variables of diastolic function. This study shows that there are subtle abnormalities in cardiac function in patients with ankylosing spondylitis. The major abnormalities are in the diastolic function, suggesting a decrease in left ventricular compliance.

Does placebo lower blood-pressure?

The effect of placebo on blood-pressure levels in 20 hypertensive patients was examined as part of a double-blind randomised controlled trial with indoramin. Blood-pressure was measured by both standard sphygmomanometry and ambulant intra-arterial monitoring. Blood-pressure reduction during the placebo phase, as measured by sphygmomanometry in the outpatient clinic, was highly significant for both systolic and diastolic pressures. In the same subjects, concomitant assessment by ambulatory monitoring showed no significant effect of placebo on intra-arterial pressure. After indoramin treatment blood-pressures measured in the clinic showed a mean reduction of 6/8 mm Hg whereas intra-arterial monitoring showed mean reductions of 18/13 mm Hg. The placebo response, therefore, appears to be an artifact of clinic blood-pressure measurement and its use as a control value in pharmacological trials may lead to serious underestimation of the efficacy of the active drug.

A study of nadolol to determine its effect on ambulatory blood pressure over 24 hours, and during exercise testing.

1 The effect of once daily nadolol therapy in sixteen ambulant patients with essential hypertension has been closely assessed during exercise and over 24 h by continuous intra-arterial recording. 2 The drug was well tolerated and showed similar efficacy to other beta-adrenoceptor blocking agents. Whilst blood pressure reduction was observed throughout the whole day, it was not uniform and lost significance during the morning period when blood pressure levels were highest. 3 This provides further evidence that the antihypertensive action of a beta-adrenoceptor drug over 24 h cannot be predicted from its plasma half-life which, with regard to nadolol, is up to 24 h. 4 An explanation for the loss of blood pressure control during the morning may be that the rapid rise in blood pressure leading to the peak levels at this time may be mediated through alpha- rather than beta-adrenergic receptors at the periphery.

Coital blood pressure in hypertensives. Cephalgia, syncope, and the effects of beta-blockade.

During the continuous monitoring of intra-arterial blood pressure in ambulant hypertensive subjects, 18 episodes of coitus were recorded in 11 subjects. Peak values of up to 300/175 mmHg found, the mean for men being 237/138 mmHg and for women 216/127 mmHg. Two patients with coital symptoms (cephalgia and syncope) showed no unusual responses and, when restudied after beta-blockade, one subject showed no reduction in peak coital blood pressure. The results complement those found previously in normal subjects and demonstrate the potential of the technique in investigating coital symptoms.

Can placebo therapy influence arterial blood pressure?

1. With standard sphygmomanometric techniques used in conjunction with continuous intra-arterial monitoring the antihypertensive effect of placebo was examined in a group of patients participating in a controlled clinical trial. 2. Twelve of the 20 patients entered completed all stages of a randomized double-blind controlled trial of placebo and indoramin. Clinic blood pressure in patients receiving placebo showed reductions which were highly significant (P less than 0.001). Simultaneous intra-arterial monitoring showed no reduction of the blood pressure over the 24 h studied. 3. The clinic pressures showed minimal reduction of blood pressure in response to indoramin therapy whereas intra-arterial pressures showed a significant fall (P less than 0.01). 4. The response of the blood pressure to placebo appears to be an artifact of the indirect sphygmomanometric method and its use as a control in this study led to under-estimation of the efficacy of indoramin.

The 24-hour ambulatory blood pressure profile with verapamil.

The blood pressure response in hypertensive subjects to chronic treatment with verapamil, a calcium antagonist (or, more precisely, a slow-channel inhibitor), was studied using the Oxford system for continuous monitoring of intraarterial blood pressure. Sixteen patients underwent continuous monitoring over a 48-hour period before and after at least 6 weeks of therapy (dose range 120-160 mg three times daily). Each monitoring period included physiologic tests designed to show the effects of different types of exercise. Verapamil produces a consistent reduction of blood pressure over 24 hours, but particularly during the day. Heart rate was similarly reduced. There was no evidence of postural hypotension, and the absolute responses to dynamic and isometric exercise were reduced. The degree of reduction of the blood pressure was consistent, suggesting that slow-channel inhibitors may be appropriate for antihypertensive therapy.