Marinette Porchet

Ambulatory blood pressure recordings. Reproducibility and unpredictability.

The accuracy of blood pressure readings taken by the portable semiautomatic blood pressure recorder Remler M 2000 was investigated in 101 unselected, untreated volunteers. On the average, pressures recorded during usual daily activities were lower by approximately 10 mm Hg than pressures measured in the office. However, individual ambulatory pressures could not be predicted from office readings, and the difference varied among the volunteers from +14 to -43 mm Hg. The reproducibility of office and ambulatory pressures was investigated in 84 subjects. There was a highly significant correlation between pressure levels determined at a 3- to 4-month interval with both the conventional auscultatory method in the office and the Remler ambulatory recorder. These data demonstrate that the Remler M 2000 ambulatory blood pressure recorder, when used properly, provides reproducible blood pressure profiles during customary daily activities. The ambulatory pressure recorder seems particularly useful for a baseline evaluation of the usual daily blood pressure, which in the individual subject differs in a highly unpredictable manner from the blood pressure measured at the physicians office.

Individual responses to converting enzyme inhibitors and calcium antagonists.

This study was designed to assess whether the acute blood pressure response of an individual hypertensive patient to a calcium antagonist or an angiotensin converting enzyme (ACE) inhibitor is a good predictor of the long-term efficacy of these drug classes in this particular patient. The concept that good responses to ACE inhibitors and calcium antagonists may be mutually exclusive was also tested. Sixteen patients were included in a randomized crossover trial of enalapril, 20 mg daily, and diltiazem, 120 mg daily, for 6 weeks each. Blood pressure was measured by ambulatory blood pressure recording. During the washout phase, the acute effect of nifedipine, 10 mg p.o., and enalaprilat, 5 mg i.v., was evaluated. Nifedipine and enalaprilat reduced blood pressure equally well. The long-term blood pressure reduction induced by enalapril and diltiazem was similar. The acute blood pressure response to a given drug was not a good predictor of the result obtained with long-term therapy. No age dependency of the antihypertensive effect of either drug class was apparent. There was no evidence that a good response to one drug excluded a similarly good response to the other.

Single and repeated dosing of the converting enzyme inhibitor perindopril to normal subjects

The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril (S9490‐3) was evaluated in 18 normotensive men. In three subjects the pressor response to exogenous angiotensin I was tested. A 8 mg oral dose reduced the pressor response by >80%. Single oral perindopril doses of 2, 4, 8, and 16 mg were given to groups of five subjects each. Eight and 16 mg decreased plasma ACE activity within 4 hours to <10% of control; 72 hours later, plasma ACE activity was still reduced by at least 40%. Doses of 4 and 8 mg po once a day were then given for 8 days to two groups of six subjects. Four hours after the first and the last morning doses, plasma angiotensin II, aldosterone, and plasma ACE activity fell significantly, whereas blood angiotensin I and plasma renin activity rose. There was no evidence of drug accumulation. No significant change in blood pressure or heart rate was observed. Thus in normotensive subjects, perindopril seems an effective, orally active, long‐lasting ACE inhibitor.

Ambulatory blood pressure recording to identify hypertensive patients who truly need therapy

Ambulatory blood pressure profiles were obtained with the Remler system, a portable semi-automatic blood pressure recorder, in 245 untreated patients considered by their physician to be hypertensive. The average blood pressures recorded during the usual daily activities of the patients were greater than 140 mmHg for the systolic and greater than 89 mmHg for the diastolic in only 96 (39%) and 107 (44%) of them respectively. Blood pressure monitoring in ambulatory patients appears to be useful for the practitioner to detect those patients who require antihypertensive therapy. Possibly, unnecessary therapy of only seemingly hypertensive patients may be avoided by this technique.

Unpredictability of blood pressures recorded outside the clinic in the treated hypertensive patient

Summary: Ambulatory blood pressure profiles were obtained with the Remler M2000, a portable semiautomatic blood pressure recorder, in 38 chronically treated hypertensive patients who continued to have blood pressures measured by their physician >140 mm Hg systolic and >89 mm Hg diastolic. On the average, ambulatory recorded blood pressures were significantly lower (151/94 ± 26/13 mm Hg; mean ± SD) than those determined at the clinic not only by a physician (179/109 ± 22/11 mm Hg), but by a nurse (163/101 ± 24/10 mm Hg). Individual mean recorded ambulatory blood pressures could be predicted neither from office readings obtained by a physician nor from those measured by a nurse. Because of this unpredictability of blood pressures prevailing outside the clinic, ambulatory blood pressure monitoring seems to be very useful, if not necessary, in assessing the efficacy of antihypertensive drugs. By this technique, it may be possible to select patients who do not need a change of treatment although their blood pressure levels remain persistently elevated in the physicians office.

Blood Pressure Response to Antihypertensive Therapy: Ambulatory versus Office Blood Pressure Readings

Blood pressure readings obtained by the physician in his office and ambulatory blood pressures recorded with the semi-automatic Remler device, were compared during a controlled antihypertensive drug trial. Either timolol or methyldopa was administered in in double-blind fashion to 30 patients with uncomplicated essential hypertension. All exhibited a diastolic office blood pressure greater than 95 mmHg at the end of a four-week placebo period. All patients then received a combination of hydrochlorothiazide (25 mg/day) and amiloride (2.5 mg/day). After four weeks of diuretic therapy, timolol (10 mg/day, n = 14) or methyldopa (250 mg/day, n = 16) were added randomly for six weeks. The dose of all antihypertensive agents was doubled after two weeks of therapy with diuretics combined with timolol (n = 7) or methyldopa (n = 16) because of the persistence of diastolic blood pressure levels greater than 90 mmHg at the office. When assessed in the office, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels were lower in the patients given timolol (P less than 0.05 for the diastolic). With both regimens, the blood pressure response measured outside the clinic during usual daily activities could not be predicted from that observed with office blood pressure readings. Furthermore the magnitude of the drug induced blood pressure decrease was more reproducible in time when determined outside the clinic. These data suggest that ambulatory blood pressure monitoring is more precise in evaluating the efficacy of antihypertensive therapy than office blood pressure measurement.

Effects of SCH 34826, an orally active inhibitor of atrial natriuretic peptide degradation, in healthy volunteers

Atrial natriuretic peptide is cleared from plasma by clearance receptors and by enzymatic degradation by way of a neutral metalloendopeptidase. Inhibition of neutral metalloendopeptidase activity appears to provide an interesting approach to interfere with metabolism of atrial natriuretic peptide to enhance the renal and haemodynamic effects of endogenous atrial natriuretic peptide. In this study, the effects of SCH 34826, a new orally active neutral metalloendopeptidase inhibitor, have been evaluated in a single‐blind, placebo‐controlled study involving eight healthy volunteers who had maintained a high sodium intake for 5 days. SCH 34826 had no effect on blood pressure or heart rate in these normotensive subjects. SCH 34826 promoted significant increases in excretion of urinary sodium, phosphate, and calcium. The cumulative 5‐hour urinary sodium excretion was 15.7 ± 7.3 mmol for the placebo and 22.9 ± 5, 26.7 ± 6 (p < 0.05), and 30.9 ± 6.8 mmol (p < 0.01) for the 400, 800, and 1600 mg SCH 34826 doses, respectively. During the same time interval, the cumulative urinary phosphate excretion increased by 0.3 ± 0.4 mmol after placebo and by 1.5 ± 0.3 (p< 0.01), 1.95 ± 0.3 (p < 0.01), and 2.4 ± 0.4 mmol (p < 0.001) after 400, 800, and 1600 mg SCH 34826, respectively. There was no change in diuresis or excretion of urinary potassium and uric acid. The natriuretic response to SCH 34826 occurred in the absence of any change in plasma atrial natriuretic peptide levels but was associated with a dose‐dependent elevation of urinary atrial natriuretic peptide and cyclic guanosine monophosphate. These results demonstrate that neutral metalloendopeptidase inhibition with SCH 34826 can produce natriure‐sis and phosphate excretion in volunteers receiving a high‐salt diet maybe by reducing the renal atrial natriuretic peptide metabolism.

Blood Pressure Variability in Ambulatory Hypertensive Patients: Effect of β-Blocking Agents and/or Diuretics

Using a semiautomatic device (Remler), ambulatory blood pressure was recorded in ambulatory hypertensive patients who were either untreated (n = 55) or treated chronically with β-blocking agents (n = 28), diuretics (n = 42), or a combination of both (n = 75). In all patients, one blood pressure reading was obtained during usual activities every 30 min for 12 h. The selection of untreated patients was based on clinic measurements (two to three repeated blood pressures of > 140/89 mm Hg). The mean systolic and diastolic blood pressures averaged from all patients over the whole day did not differ significantly among the groups, ranging from 133.7 to 141 mm Hg for the systolic and from 83.8 to 88.4 mm Hg for the diastolic. The variability of blood pressure, reflected by the difference between the average of the three highest and the three lowest values of the day, was not different among the four groups and ranged from 41.4 to 50.6 mm Hg for the systolic and from 30.1 to 34.4 mm Hg for the diastolic. Similarly, variability expressed as the standard deviation of the mean of all blood pressures measured during the day did not differ among the groups. In all groups, blood pressure was highest in the morning and lowest in early afternoon, and tended to rise again in the late afternoon. Thus, blood pressure variability of hypertensive patients is not changed by antihypertensive therapy with β-blocking agents and/or diuretics.

Calcium entry blockade attenuates the acute blood pressure rise induced by cigarette smoking.

The purpose of this study was to assess whether the administration of a calcium entry blocker can prevent the acute blood pressure rise induced by cigarette smoking. Seven male habitual smokers were included. After 45 min of equilibration, they took in randomized single-blind fashion at a 1 week interval either a placebo or nifedipine, 10 mg p.o. Thirty minutes thereafter, the subjects smoked within 10 min two cigarettes containing 1.4 mg of nicotine each. In addition to heart rate and skin blood flow (laser Doppler method), blood pressure of the median left finger was monitored continuously for 100 min using a noninvasive device (Finapres). Nifedipine induced an increase in skin blood flow that was not influenced by smoking. This skin blood flow response was observed although nifedipine had by itself no effect on systemic blood pressure. The calcium antagonist markedly attenuated the blood pressure rise induced by cigarette smoking. However, it tended to accentuate the heart rate acceleration resulting from inhalation of nicotine-containing smoke.

Accuracy, reproducibility and usefulness of ambulatory blood pressure recording obtained with the Remler system

The Remler M2000, a portable semi-automatic blood pressure recorder, was used to measure ambulatory blood pressure during customary daily activities of normotensive and hypertensive subjects. Systolic and diastolic pressures measured simultaneously by this device and by the conventional auscultatory method were closely related throughout the day, after an acute physical exercise as well as at rest. In unselected, untreated subjects, the average of the recorded pressures was most often lower than pressures measured in the office, but ambulatory pressures could not be predicted from office readings. There was a highly significant correlation between pressure levels determined at a 3 to 4 month interval with both the conventional auscultatory method in the office and the Remler system. In hypertensive patients who were either untreated or treated chronically with beta-blocking agents, diuretics or a combinaton of both drugs, a clear diurnal variation of blood pressure was revealed by the ambulatory recordings, the lowest levels being reached in the early afternoon. Neither this diurnal variation nor blood pressure variability was influenced by antihypertensive therapy. The Remler system was also used to evaluate blood pressure outside the physician’s office in untreated subjects considered by their physician to be hypertensive. The average of blood pressures recorded during the usual daily activities of the subjects were > 140 mmHg for the systolic and > 89 mmHg for the diastolic in only 39% and 44% of them, respectively. Thus, the Remler system provides accurate, reproducible blood pressure profiles in the ambulatory state which are not predictable based on office blood pressure measurements. It seems particularly useful for identifying those patients who, although hypertensive in the physician’s office, remain normotensive during usual daily activities.