Ambulatory intraarterial blood pressure in essential hypertension. Effects of age, sex, race, and body mass--the Northwick Park Hospital Database Study.

Twenty-four-hour recordings of intraarterial blood pressure (IABP) from 723 untreated hypertensive patients were analyzed for the effects of age, sex, race, and body mass index on the level of IABP and its circadian variation. Age had a highly significant positive relationship (P < .001) with the cuff systolic and diastolic blood pressures, with regression coefficients (SE) of +0.83 (0.07) and -0.24 (0.04) mm Hg/year, respectively. There was a similar (P < .001) positive relationship between age and 24-h mean systolic IABP, measuring +0.71 (0.07) mm Hg/year, but 24-h mean diastolic IABP did not increase significantly with age. There was a significant (P < .001) inverse relationship between age and 24-h mean heart rate (HR), at -0.17 (0.03) beats/min/year. Nocturnal fall in systolic and diastolic IABP, calculated as the difference between daytime and nighttime mean IABP, had a significant (P < .001) negative relationship with age. Nocturnal fall in HR, calculated similarly, also significantly (P < .001) decreased with age. Age did not affect long-term systolic and diastolic IABP variability but did decrease long-term HR variability significantly (P < .001). Hypertensive men and women of similar age, had comparable daytime mean systolic and diastolic IABP (P = .15 and P = .03 respectively), but women had significantly (P < .001) lower nighttime mean systolic and diastolic IABP than men. The nocturnal fall in systolic and diastolic IABP was significantly (P < .002) greater in women as compared to men. Women also had significantly (P < .01) greater long-term systolic and diastolic IABP variability than men. Women had significantly (P < .001) greater 24-h, daytime mean and nighttime mean HR than men. Twenty-four-hour, daytime and nighttime mean IABP were all significantly higher (P < .01) in Afro-Caribbeans as compared to whites and Asians. No significant differences were observed in the magnitude of nocturnal IABP fall or long-term IABP variability between the three races. Asians and Afro-Caribbeans had significantly (P < .001) lower nocturnal HR falls and long-term HR variability (P < .01) than whites. Body mass index (BMI) did not relate directly to the level of daytime blood pressure, clinic cuff, or daytime mean IABP, in either men or women. BMI did have a highly significant (P < .001) positive relationship with nighttime mean IABP in men, but not in women. The degree of nocturnal fall of IABP had a significant (P < .001) inverse relationship with BMI in hypertensive men.

Intra-arterial monitoring of the antihypertensive effects of once-daily amlodipine.

Amlodipine is a dihydropyridine calcium antagonist with a long elimination half life making it suitable for once-daily dosing. This study used sphygmomanometric and intra-arterial ambulatory blood pressure (BP) monitoring to confirm the antihypertensive effect of a once-daily dose of amlodipine over the dosing interval. After a 2-week single-blind placebo run in, amlodipine was administered to 11 patients at a starting dose of 5 mg daily for 2 weeks increasing to 10 mg daily for a further 4 weeks if diastolic blood pressure (DBP) measured sphygmomanometrically was not < 90 mmHg or decreased by > 10 mmHg from baseline values. Intra-arterial blood pressure recordings for 24-hour periods were made at the end of the placebo run in and on completion of the active treatment phase. The effects of isometric and dynamic exercise and head-up tilting (60 degrees) on BP and heart rate were measured during ambulatory monitoring. Mean supine cuff BP was 169/104 mmHg (n = 11) at the end of the placebo treatment period and was reduced to 153/95 mmHg (n = 11) after 2 weeks of amlodipine treatment and 146/92 mmHg (n = 11) after 6 weeks of amlodipine treatment. There was no significant change in heart rate. Intra-arterial ambulatory monitoring showed that BP was controlled for the whole dosing interval with once-daily doses of amlodipine. The normal circadian pattern of BP changes was not altered. BP was reduced by amlodipine during exercise and physiological tests, but there was no postural hypotension and the BP and heart rate responses to exercise were not blunted.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Haemodynamic advantage of the Valsalva manoeuvre during heavy resistance training.

A nuclear probe was used to assess beat-to-beat changes in relative cardiac output in eight elite athletes during isometric exercise. Three subjects underwent simultaneous intra-arterial blood pressure recording. Stroke volume fell by 68 +/- 4% during Valsalva's manoeuvre alone, but by 42 +/- 9% with simultaneous isometric handgrip. Blood pressure changes during isometric handgrip were significantly modified by simultaneous Valsalva's manoeuvre. In particular no late strain phase fall or post-strain overshoot in blood pressure was seen, hence there was no baroreceptor-mediated fall in heart rate. Maximum Valsalva's manoeuvres in athletes invoked extreme falls in cardiac output and blood pressure which were attenuated by simultaneous isometric handgrip. The mechanism of this may be twofold: increased venous tone maintains stroke volume; and/or increased arteriolar tone maintains blood pressure.

Safety and pharmacokinetics of ioversol in healthy volunteers.

Ioversol 320, a new nonionic iodinated contrast medium, was injected intravenously into 24 healthy male volunteers using saline as a control. Physical examination, vital signs, electrocardiogram, biochemical and hematological data were recorded before and at intervals after injection. No significant changes were observed. Seventeen volunteers reported no side effects; six volunteers had mild transitory symptoms considered to be related to the contrast medium. The authors conclude that broader clinical trials can be safely conducted to determine safety and tolerability of ioversol.

Baroreceptor, not left ventricular, dysfunction is the cause of hemodialysis hypotension.

Many patients with chronic renal failure experience profound hypotension during hemodialysis. This has been attributed both to autonomic and ventricular dysfunction. In an attempt to distinguish which, if either, is important in this role, we assessed both autonomic and left ventricular function in 10 such patients. Cardioactive medication was stopped 24 hours prior to the investigations. Autonomic function was assessed from day/night blood pressure and heart rate variation and from the hemodynamic response to tilting and the Valsalva maneuver using an intra-arterial ambulatory monitoring technique. Left ventricular function was assessed scintigraphically both before and during hemodialysis. Day/night variation was significantly reduced in the patients with chronic renal failure (BP 13/7 +/- 8/6 mmHg, HR 5 +/- 4) compared with a control population (BP 36/28 +/- 10/5 mmHg, HR 19 +/- 6). Nine patients had a "square wave" response to the Valsalva maneuver. Both of these abnormalities are usually seen in patients with heart failure and are attributed to volume overload and a consequent failure of baroreceptor response. Blood pressure fell during hemodialysis (mean fall 40/22 +/- 20/10 mmHg) in all patients, but heart rate did not change (-2 +/- 16) despite the hypotension. All patients had a normal or high resting ejection fraction (mean 66%, range 55-79%), and there was no change during dialysis. This indicates that the hypotension was not due to left ventricular dysfunction in this group of patients, but to a failure of the baroreceptor response to volume depletion during hemodialysis.

24 h blood pressure control with the once daily calcium antagonist, amlodipine.

1. Amlodipine is a novel calcium antagonist which, although pharmacologically similar to other dihydropyridine calcium antagonists, has a long plasma half-life, permitting steady state blood levels to be achieved with a once-daily dose regimen. 2. We have performed a study to examine the effects of this drug on the blood pressure of hypertensive patients over a 24 h period. After a placebo run-in, the drug was administered to 11 patients at a starting dose of 5 mg, and increased to 10 mg after 2 weeks of treatment if the cuff diastolic blood pressure response was unsatisfactory. Cuff measurements were made at entry, after 2 weeks treatment with placebo, after 2 weeks on amlodipine 5 mg once daily, and after a further 4 weeks on amlodipine 5 mg or 10 mg once daily. Intraarterial blood pressure recordings were made at the end of the placebo phase and at completion of the study. 3. Mean supine blood pressure measured sphygmomanometrically was 168/103 (n = 11) mm Hg at entry, 169/104 (n = 11) mm Hg at the end of the placebo phase, 153/95 (n = 11) mm Hg after 2 weeks of treatment and 146/92 (n = 11) mm Hg at the end of the study. Blood pressure curves plotted for each phase of the study revealed an effective 24 h duration of action. Mean daytime blood pressure was reduced from 165/103 to 147/89 mm Hg (P less than 0.05, n = 10), and mean night-time blood pressure was reduced from 137/79 to 121/69 mm Hg (P less than 0.05, n = 10).(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)

Intra-arterial ambulatory blood pressure monitoring can save your life--or, acute haemodynamic response to a murderous assault.

A patient undergoing intra-arterial blood pressure monitoring was attacked by a burglar armed with a knife. The knife was turned aside by the transducer/perfusion unit, which continued to monitor his heart rate and blood pressure throughout. A pronounced "fight or flight" response was recorded.

Is there a relationship between ambulatory intra-arterial blood pressure and left ventricular function?

The relationship between ambulatory intra-arterial blood pressure and left ventricular ejection fraction was examined in a group of 23 untreated hypertensive subjects who underwent concurrent radionuclide ventriculography. All patients had a normal ejection fraction at rest (range, 50-80%), and no significant correlation was found between blood pressure and resting ejection fraction. Sixty-one percent of patients failed to increase their ejection fraction by 5% on exercise; the mean daytime systolic pressure (168 +/- 15 mm Hg) was lower in this group than in those who had a normal exercise response (188 +/- 17 mm Hg; p less than 0.005). Thirty percent of patients had left ventricular hypertrophy based on electrocardiographic criteria; this group had a higher mean blood pressure (189 +/- 20 mm Hg) than the remainder (170 +/- 15 mm Hg; p less than 0.05). A closer correlation was demonstrated between blood pressure and ejection fraction response to exercise in the group with left ventricular hypertrophy (r = 0.8) than in the group without hypertrophy (r = 0.3). These results failed to demonstrate a linear relationship between blood pressure and ejection fraction. However, a relationship between the height of blood pressure and the development of left ventricular hypertrophy was shown, and myocardial response to exercise was increased in patients with left ventricular hypertrophy.

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-blocking drug 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.

Effect of labetalol on indices of myocardial necrosis in patients with suspected acute infarction.

The role of combined alpha and beta blockade as a means of limiting infarct size has been studied in a randomised controlled trial using labetalol. Only 166 of 630 (26%) consecutive patients admitted to a cardiac care unit with suspected myocardial infarction were deemed suitable for inclusion; most of the remainder had delayed admission to hospital, were over the age limit of 75, or had complications which precluded the use of labetalol. Those on active treatment received a loading dose followed by a slow intravenous infusion over six hours, and oral therapy for the subsequent five days. Doses were adjusted to maintain systolic pressure in the range 100 to 120 mmHg. The control group received only conventional therapy. Labetalol caused lowering of the blood pressure and heart rate during the phase of intravenous treatment, but little effect occurred subsequently because oral dosage was constrained by low systolic pressures. The group that received active treatment had significantly greater release of CKMB enzyme. Little difference was observed in R wave scores or ejection fraction. Only low doses of labetalol can be used for most patients with acute myocardial infarction. Labetalol cannot be recommended as routine treatment for normotensive patients admitted to hospital with suspected infarction.

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.