Geoffrey Brigden

Ambulatory intra-arterial blood pressure in normal subjects

It has been suggested that ambulatory blood pressure monitoring is superior to casual cuff methods in predicting cardiovascular events, but lack of reference data from a normal population seriously limits this methods clinical applicability. We therefore performed 24-hour intra-arterial ambulatory blood pressure (BP) monitoring in 50 normal volunteers (cuff BP less than 140/90 mm Hg) whose ages ranged from 18 to 74 years. There were 30 men and 20 women in the study, but there was no significant difference between the sexes with respect to age, cuff BP, or body mass index. A diurnal variation in BP was observed, qualitatively similar to that seen in hypertensive individuals, including a prewaking BP rise. Mean daytime intra-arterial pressures differed little between the sexes (124/74 mm Hg for women and 127/76 mm Hg for men, p = NS), but was lower at night in women than in men (96/52 versus 102/59 mm Hg, respectively; p less than 0.02 for diastolic pressure). Based on this group of subjects, we defined the upper limit of normal daytime BP in both men and women as 150/90 mm Hg and the upper limit of mean nighttime BP as 130/80 mm Hg for men and 115/65 mm Hg for women. The lower nighttime pressures in women compared with their male counterparts with similar daytime pressures may explain why women appear to tolerate similar levels of BP better than men.

Carvedilol for systemic hypertension

Twenty-four hour profiles of intraarterial ambulatory blood pressure (BP) and heart rate were significantly reduced by administration of carvedilol, a new beta-blocker with vasodilating properties. Twelve patients were given carvedilol, 25 mg twice daily for 2 weeks; the dose was then increased to 50 mg twice daily if the target BP was not achieved. After 4 weeks of therapy, mean daytime reduction in BP was 25 +/- 3 mm Hg systolic and 19 +/- 3 mm Hg diastolic, and mean reduction in heart rate was 22 +/- 3 beats/min. BP at the peak of isometric exercise and during dynamic exercise was also significantly reduced. Radionuclide measurements showed that left ventricular ejection fraction was not affected by treatment, but there was a significant reduction in systolic and diastolic volumes. The drug was well tolerated. This clinical trial suggests that carvedilol will be a useful first-line drug for treatment of essential hypertension, and its vasodilating action may have a more favorable effect on left ventricular function than conventional beta-blocking drugs.

24-hour blood pressure control with the once-daily calcium antagonist amlodipine.

The efficacy and toleration of once-daily amlodipine (5-10 mg) was studied in 11 patients with mild to moderate hypertension. Continuous intra-arterial blood pressure monitoring was used to study the effects of amlodipine over a 24-h period. Following a 2-week placebo run-in period, amlodipine was given initially as a single-blind 5-mg dose for 2 weeks and increased to 10 mg if required to control blood pressure for a further 4 weeks. Twenty-four-hour intra-arterial blood pressure recordings made after 6 weeks of treatment with amlodipine revealed that amlodipine effectively reduced blood pressure throughout the whole 24-h period without altering the normal circadian pattern. The mean daytime blood pressure was reduced from 165/103 to 147/89 mm Hg (p < 0.05) and the mean nighttime blood pressure was reduced from 137/79 to 121/69 mm Hg (p < 0.05). There was no significant change in heart rate. The mean supine blood pressure measured sphygmomanometrically was reduced from 169/103 mm Hg after placebo to 153/98 mm Hg after 2 weeks of treatment and to 145/92 mm Hg at the end of the study. The results of isometric and dynamic exercise testing showed that amlodipine decreased blood pressure, with no postural decrease on tilting and no change in the proportional increase in blood pressure at peak exercise. Amlodipine was well tolerated although one patient developed ankle edema that would have required discontinuation had she not already completed the study. This study has shown that amlodipine effectively reduced blood pressure for 24 h after once-daily dosing and was well tolerated.

Effectiveness of the once-daily calcium antagonist, lacidipine, in controlling 24-hour ambulatory blood pressure

The efficacy of the new once-daily dihydropyridine calcium antagonist, lacidipine, in reducing ambulatory intraarterial blood pressure (BP) was examined in 12 untreated hypertensive patients. The intraarterial recording was commenced 24 hours before the first 4-mg dose and was continued for a further 24 hours thereafter. After dose titration and chronic therapy, a second 24-hour ambulatory BP recording was made. There was a steady onset of drug action, maximal at 2 hours, but with reflex tachycardia after the first dose. Chronic administration reduced BP throughout the 24-hour period, without tachycardia. Mean daytime reduction in BP was 20 mm Hg systolic (p less than 0.005) and 12 mm Hg diastolic (p less than 0.02). Mean nighttime reduction was 8-mm Hg systolic (p less than 0.05) and 6-mm Hg diastolic (difference not significant). There was no postural decrease in BP on 60 degrees head-up tilting and hypotensive action was maintained during isometric exercise (reduction at peak of 32/18 mm Hg, p less than 0.05) and throughout dynamic exercise (reduction at peak of 23/14 mm Hg, p less than 0.05). Lacidipine is an effective once-daily antihypertensive agent, with good control of stress response.

Effects of noninvasive ambulatory blood pressure measuring devices on blood pressure

Abstract It is well recognized that the act of blood pressure (BP) measurement may influence the level of BP. 1 This “cuff response” is attributed to an alerting reaction; it does not decrease with repeated measurement, and is worse in the presence of a doctor than in the presence of a nurse. 2 This suggests that the major component of the reaction is not discomfort from inflation of the cuff, and this is supported by the fact that BP usually increases before the cuff is applied. These observations have led to the assumption that ambulatory cuff BP devices do not provoke such effects. This is implicit in the high reproducibility of measurements in groups of subjects that has been observed with some modern machines, 3 although this could simply reflect the reproducibility of the alerting response. This issue has only been addressed in subjects confined to bed for relatively brief periods. 4 No account has been taken of the possibility of effects on patients trying to sleep at night, or of the overall impact of wearing such devices. Ambulatory BP monitors are coming into wide use for the assessment of hypertensive subjects before and after treatment. This follows observations that ambulatory measurements are better prognostic indicators than casual readings. 5 This study tests the hypothesis that wearing an ambulatory cuff BP monitor might, in itself, alter BP by increasing discomfort, influencing activity or sleep patterns, or by promoting an alerting response.

Assessment of 'once daily' verapamil for the treatment of hypertension using ambulatory, intra-arterial blood pressure recording.

SummaryA new, slow release formulation of verapamil, “verapamil o.d.” was administered to 12 patients with essential hypertension.Drug administration was started at a dose of 240 mg and increased to 480 mg after 2 weeks of treatment if the cuff blood pressure response was unsatisfactory.The drug reduced the daytime intra-arterial blood pressure significantly from 180.7/106.8 mm Hg to 157.3/89.4 mm Hg. The daytime heart rate fell from 88.1 to 71.8 beats/min. The nighttime blood pressure decreased from 155.7/87.2 mm Hg to 140.5/75.3 mm Hg. The nocturnal heart rate decreased from 62.8 to 57 beats/min. Hourly plots of mean systolic and diastolic pressure showed a significant reduction of systolic pressure for 21 of 24 h and of diastolic pressure for all 24 h following a single morning dose. The drug modified the absolute blood pressure and heart-rate response during both forms of exercise, but did not alter the magnitude or rate of blood pressure change. The tilt-test produced no evidence of postural hypotension.Only one patient experienced any side effects whilst taking the drug.These results indicate good 24-h blood pressure control and reduced exercise blood pressure levels during treatment with this new formulation of verapamil. The reduced frequency of drug administration should improve patient complicance with treatment of hypertension.

CIRCADIAN VARIATION AND BLOOD PRESSURE : RESPONSE TO RAPID WEIGHT LOSS BY HYPOCALORIC HYPONATRAEMIC DIET IN OBESITY

Ambulatory intra-arterial blood pressure was monitored in 15 obese hypertensive and 10 obese normotensive subjects weighing more than 30% of their ideal body weight. Measurements were taken before and after 1 month in hospital on a diet of 330kCal/day designed to ensure 34 g protein and 65 mmol sodium. Mean +/- s.d. body mass index in the whole group fell from 40.8 +/- 7.6 to 37.2 +/- 7.4 kg/m2 (P less than 0.0001). Daytime intra-arterial blood pressure fell from 176 +/- 19/102 +/- 14 to 162 +/- 16/95 +/- 14 mmHg (P less than 0.0005 and P less than 0.002) in the hypertensive group and from 141 +/- 15/82 +/- 5 to 131 +/- 13/79 +/- 4 mmHg (P less than 0.005 for systolic pressure) in the normotensive group. Circadian variation of systolic intra-arterial blood pressure comparing the mean daytime with the mean night-time blood pressure recordings showed a day-night difference of 27 +/- 10 mmHg in the normotensive group compared with 12 +/- 13 mmHg in the hypertensive group (P less than 0.01). This trend was reversed after weight loss, when the normotensive group showed a day-night difference of 20 +/- 13 mmHg compared with 18 +/- 17 mmHg in the hypertensive group. Thus, circadian variation of systolic intra-arterial blood pressure in the hypertensive group was significantly (P less than 0.01) reduced compared with the normotensive group prior to, but not after, weight loss. These data show that, in obese subjects, weight loss produced a significant reduction in ambulatory intra-arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

First dose response and 24-hour antihypertensive efficacy of the new once-daily angiotensin converting enzyme inhibitor, ramipril.

The reduction in blood pressure (BP) after the first dose and after 8 weeks of treatment with a new once-daily angiotensin converting enzyme (ACE) inhibitor, ramipril, was examined in 12 untreated hypertensive patients, using ambulatory intraarterial BP monitoring. The first period of monitoring began 24 hours before the first dose was given, and continued for 24 hours afterwards. A second 24-hour period of monitoring was carried out after 8 weeks of treatment, commencing immediately after the morning dose. Angiotensin II levels and serum drug levels were measured at 0, 2, 6 and 24 hours after the acute dose. BP decreased progressively from the first hour after the first dose, reached a maximum in the fifth hour (p less than 0.001) and then the effect diminished. The maximum reduction of systolic BP in any patient was 64 mm Hg, the minimum 4 mm Hg. Blood pressure was significantly (p less than 0.05) reduced throughout the 24 hours after dosing, with a mean daytime reduction of 13/12 mm Hg, and a mean nighttime reduction of 15/7 mm Hg. Angiotensin II levels were significantly (p less than 0.02) and maximally reduced by 2 hours after administration, but the reduction was no longer significant after 24 hours. Serum drug levels were also maximal 2 hours after administration. The trial population could be clearly divided into groups of good and poor responders on the basis of BP reduction. The angiotensin II levels were higher before treatment, and decreased further, in all patients with a good response than in those with a poor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Carvedilol for systemic hypertension.

Summary: Twenty‐four hour profiles of intraarterial ambulatory blood pressure (BP) and heart rate were significantly reduced by administration of carvedilol, a new &bgr;‐blocker with vasodilating properties. Twelve patients were given carvedilol, 25 mg twice daily for 2 weeks; the dose was then increased to 50 mg twice daily if the target BP was not achieved. After 4 weeks of therapy, mean daytime reduction in BP was 25 ± 3 mm Hg systolic and 19 ± 3 mm Hg diastolic, and mean reduction in heart rate was 22 ± 3 beats/min. BP at the peak of isometric exercise and during dynamic exercise was also significantly reduced. Radionuclide measurements showed that left ventricular ejection fraction was not affected by treatment, but there was a significant reduction in systolic and diastolic volumes. The drug was well tolerated. This clinical trial suggests that carvedilol will be a useful first‐line drug for treatment of essential hypertension, and its vasodilating action may have a more favorable effect on left ventricular function than conventional &bgr;‐blocking drugs.

Twenty-four hour ambulatory blood pressure profile of a new, sustained-release preparation of nicardipine

SummaryThe 24-hour blood pressure (BP) profile of a new sustained-release preparation of nicardipine was assessed in 16 patients with essential hypertension (supine cuff diastolic BP>95 mmHg). Twenty-four hour ambulatory intraarterial BP monitoring (Oxford system) before treatment revealed a mean (SD) daytime BP of 174 (19) mmHg systolic and 105 (8) mmHg diastolic, and a mean nighttime BP of 142 (26) mmHg systolic and 83 (12) mmHg diastolic. Sustained release nicardipine (60 mg) was administered twice daily for 4–6 weeks and the ambulatory BP monitoring repeated. No significant change in heart rate occurred throughout the 24-hour period. However, there was a significant reduction (p<0.0001) in the mean daytime BP of 21 (13) mmHg systolic and 12 (9) mmHg diastolic and of mean nighttime BP of 21 (15) mmHg systolic and 13 (11) mmHg diastolic. A similar reduction in hourly mean BP occurred throughout the whole 24-hour period, including the steep early morning rise in BP. Although vasodilatory-type side effects occurred, they were generally mild to moderate and transient. This preparation produces a significant reduction in BP throughout the 24-hour period without reflex tachycardia.