Drugs 44 (Suppl. I): 12-16, 1992 0012-6667/92/0 I 00-00 12/$2.50/0 © Adis International Limited. All rights reserved. DRSUP3339
Use of Ambulatory Blood Pressure Monitoring in the Management of Antihypertensive Therapy Jean-Michel Mallion, Anne Maitre, Regis de Gaudemaris, Jean-Philippe Siche and Frederic Tremel Medecine Interne et Cardiologie, Hopital A. Michallon, Grenoble, France
Summary
The recent development of ambulatory blood pressure (ASP) monitoring techniques has improved recording of blood pressure in therapeutic trials and in the clinical setting. The application of ASP differs according to which of these 2 applications is being considered. In therapeutic trials, a placebo control is required. The large quantity of precise data acquired with ASP monitoring allows the study of a limited number of patients; it also allows individual study of patients with a 'white coat' response (i.e. elevated blood pressure in response to examination by the clinician). Analysis of data from ASP monitoring may include the following: comparison of mean blood pressure values over 24 hours, daytime or night-time, or over any other selected time period; 24-hour blood pressure profiles, or analysis hour-by-hour, giving true chronotherapy, and providing data regarding the wearing-off of a drug effect or loss of therapeutic control; analysis of blood pressure at particular times, such as on waking; or specific examination of nonresponders. In individual patients, ASP monitoring should be reserved for specific indications. It can be used before initiation oftreatment to confirm the necessity for treatment, especially in the context of hypertension at rest or the 'white coat' effect. With established treatment, ASP monitoring can be used in patients with resistant hypertension, in severe hypertension to examine loss of blood pressure control over time or inversion of the day/night cycle, and in patients with a specific illness, e.g. diabetes, in order to obtain the lowest blood pressure readings possible. Examination of these factors assists clinicians to accurately decide upon the timing and frequency of antihypertensive therapy.
Recent technological advances have led to the dev.elopment of methods for measuring ambulatory blood pressure (ABP). The benefits of ABP monitoring differ according to the population in which it is used. For example, in a clinical trial the benefits of ABP monitoring are different from those in the management of individual patients in a clinical setting. In general, a number of distinct advantages associated with ABP monitoring can be described. It is possible to analyse a variety of blood pressure measurements taken over a 24-hour pe-
riod, including 2 to 4 measurements per hour during the day and night. This allows evaluation of blood pressure both during medical consultation and during every day activity; evaluation of the differences between day and night-time blood pres. sure values; and assessment of the variations in blood pressure over 24 hours, resulting from physical activity and emotional stimuli. The form of ABP recording is determined by the possibilities of the computer software available, which may allow different analysis and pres-
13
Use of Ambulatory Blood Pressure Monitoring
entation of data; for example, a 24-hour blood pressure profile with analysis of systolic blood pressure, diastolic blood pressure and heart rate over time; or a mean blood pressure value calculated over 24 hours, or during the night-time or hourly periods, expressed as a histogram or percentage. Reference values for ABP monitoring have been established by age and sex for different socioprofessional categories (Battistella et al. 1989; Dreyer & Weber 1985; O'Brien et al. 1991). These values are different from those obtained in the clinician's office and those defined by the World Health Organization (WHO) as they are obtained from individuals performing daily activities, not those at rest. Thus, they are not epidemiologically significant at the present time. Reference values for ABP monitoring are lower at night than during the day, are lower in women than in men, and lie between those obtained in the clinician's office and those measurements recorded at home. The reproducibility of the mean of 24-hour values for ABP monitoring for a group of individuals seems excellent after 15 days to I month, if the recordings are repeated under similar conditions. Diary records are essential for repeated ABP monitoring in order to document the physical and emotional status of the individual at each recording (Trazzi et al. I 991 ).
1. Application of Ambulatory Blood Pressure Monitoring in Therapeutic Trials 1.1 Selection of Subjects Until the present time, it has been necessary to compare values of blood pressure during treatment with those obtained during placebo administration. The comprehensive data obtained using ABP monitoring allows study of smaller groups of patients, which is a major advantage in terms of cost and time (Coats et al. 1989). On the first recording using ABP monitoring, it is possible to identify patients with a 'white coat response', who may not, in fact, be hypertensive and who may exhibit a particular blood pressure
_
'"
16
I
E
S-
1
a.
III
.s ~
~ ~
o
6 4 2 O..I-.L--Systolic BP
Diastolic BP
Fig. 1. Changes in mean 24-hour systolic and diastolic ambulatory blood pressure (BP) in 10 hypertensive patients treated for 21 days with sustained release verapamil 240 mg/ day at 0800h (0) or 2000h (_) in a double-blind crossover study. Between group differences were not statistically significant.
profile and should form part of a special study group. It would seem that responses to therapy in this group are not typical of the responses of a hypertensive population (Trazzi et al. 1991). 1.2 Analysis of Results ABP monitoring facilitates comparison of mean blood pressure values over 24 hours, during the day or night, or sampling of values over a chosen number of hours (figs I and 2). The reference values used to evaluate antihypertensive effect may be pretreatment blood pressure values or reference blood pressure values according to age and sex. Thus, we can examine the effects of drug treatment over 24 hours or hourby-hour, in the form of a true diurnal analysis, in order to determine whether a drug exerts 24-hour control of blood pressure or, alternatively, to detect any loss of therapeutic control. In addition, the effect of drug treatment on blood pressure at specific times, such as in the early morning, can be examined (Muller et al. 1987). This effect is important because, at an epidemiological level, it would seem that the morning blood pressure peak may have repercussions in terms of cerebrovascular accidents, myocardial infarction and sudden death (Muller et al. 1987). Specific examination of patients deemed to be nonresponders to antihypertensive therapy shows that many are in fact 'white coat responders'.
Drugs 44 (Suppl. I) 1992
14
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0
0
2
4
6
I
I
8
U
10
14
12
16
18
'20
22
Time (hours)
Fig. 2. Changes in mean diastolic blood pressure (DBP) recorded hourly in hypertensive patients treated for 21 days in a crossover study with sustained release verapamil 240 mgfday at 0800h (0) or 2000h (_) compared with placebo values.
Some drug treatments have no lowering effect on blood pressure when resting values are normal. Indeed, in some patients an antihypertensive effect could be harmful if hypertension has been wrongly diagnosed (Weber et al. 1988).
1. Individual Applications of Ambulatory Blood Pressure Monitoring The random nature of using one blood pressure measurement during the day in order to judge the efficacy of an antihypertensive treatment is evident from the previous discussion. It is obvious that ABP monitoring cannot be applied to all hypertensive patients, but must be reserved for particular indications. 2.1 Pretreatment Applications The often significant rise in blood pressure observed during measurement by a clinician (the 'white coat effect') can lead to an erroneous diagnosis of hypertension. Measurement under more relaxed circumstances may reveal this effect, and increased pulse rate may be a good indicator of a 'white coat' reaction. Inappropriate classification
of a patient as hypertensive has major repercussions. Patients may endure severe psychological consequences and be subjected to the constraints of long term treatment. There are also secondary effects, which vary according to the medication administered, and there may be alterations in patients' quality of life. In addition, there are financial and economic costs to be considered. On the physiopathological level, some antihypertensive medication such as some calcium antagonists have no effect on blood pressure in normotensive individuals. Many other medications affect diurnal blood pressure, as they alter baseline values to a new, lower level. The consequences of reduced blood pressure levels such as circulatory disturbances (to the brain, kidney or heart) may be unfortunate; it is known that at the cardiac level coronary lesions may develop particularly as the patient gets older or when left ventricular hypertrophy is also present. 2.2 Applications During Treatment ABP monitoring is useful when hypertension as measured in the clinician's office seems resistant to treatment. In cases of severe hypertension, ABP monitoring can ensure that there is no loss of blood
Use of Ambulatory Blood Pressure Monitoring
15
pressure control over time (fig. 3), and provides information on a possible inversion of the 24-hour cycle, which may lead to a change in the administration of treatment at particular times (fig. 4).
confirming the efficacy of antihypertensive treatment. Thus, we have developed the notion of 'personalised treatment', which obliges us, whether we use ABP monitoring or not, to respect certain guidelines: the timing of rising, bedtime and mealtimes; the need to seek information about the timing and emotional effect of the daily activities of patients. These elements allow us to better define the timing and frequency of treatment.
2.3 Hypertension Associated with Another Disorder In hypertensive patients with diabetes mellitus, ABP monitoring can help to define the lowest blood pressure values possible, which is necessary if one is to determine, among other things, the correlation that may exist between the level of blood pressure and the level of microalbuminuria. ABP monitoring is also beneficial in patients with autonomic dysfunction, which may be present in patients with Shy-Drager syndrome, diabetes, in the elderly presenting with weakness, or in patients with renal failure on dialysis or following transplant, all of whom frequently show an inversion of the 24hour blood pressure cycle (Mallion et al. 1990). Finally, in patients with significant psychosensorial constraints, ABP monitoring is useful for
3. Conclusions In summary, the development of ABP monitoring has not revolutionised the management of antihypertensive treatment. However, in therapeutic trials it has allowed a better examination of the true effectiveness of treatment over a 24-hour period, particularly when drug treatment is given daily. If multiple dosage treatments are required, the precise timing of drug administration can be gauged by ABP monitoring. For the individual patient, the real interest of
240 220 200
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180
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160
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140
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120
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---~
_ _ - _ -_ _ _ _ _ -
_
-
-
_--
20 O~---r---'----.---.----r---'----.---.---~----r---'---~
0800
1000
1200
1400
1600
1800
2000
2200
0000
0200
0400
0600
Time (hours)
Fig. 3. 24-Hour ambulatory blood pressure (vertical lines) and heart rate (horizontal lines) in I hypertensive patient, showing inversion of the 24-hour cycle.
Drugs 44 (Suppi. 1) 1992
16
220 200 180 Ci
160
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140
~
120
§.
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0900
1100
1300
1500
1700
1900
2100
2300
Treatment (2000)
0100
0300
0500
0700
Treatment (0830)
Time (hours)
Fig. 4. 24-Hour ambulatory blood pressure (vertical lines) and heart rate (horizontal lines) in a hypertensive patient with administration of propranolol at 2000h and 0830h.
ABP monitoring is the possibility of identifying individuals who are not in fact hypertensive; of avoiding giving treatment in error; and of confirming the necessity for particular drug treatment in particular clinical situations such as diabetes mellitus.
References Battistella P. De Gaudemaris R, Fran,ois G, Lyon A, Gosse P, et al. Valeurs de reference de la tension arterielle en ambulatoire d'activite et de nuit. Etude multicentrique de 394 sujets normotendus au repos. Archives des Maladies du Coeur et des Vaisseaux 82: 1019-1022, 1989 Coats A, Conway J, Somers VK, lsea JE, Sleight P. Ambulatory pressure monitoring in the assessment of hypertensive therapy. Cardiovascular Drugs and Therapy 3: 303-311, 1989 Dc Gaudemaris R, Mallion J-M, Battistella p, Battistella B, Siche JP. Ambulatory blood pressure and variability by age and sex in 200 normotensive subjects: reference population values. Journal of Hypertension 5 (Suppl. 5): 429-430, 1987 Drayer JIM, Weber MA. Definition of normalcy in whole-day ambulatory blood pressure monitoring. Clinical and Experimental Hypertension 7: 195-204, 1985 Kennedy HL, Horan MJ, Sprague MK, Padgett NE, Shriver KK. Ambulatory blood pressure in healthy normotensive males. American Heart Journal 106: 717-722, 1986 Mallion JM, Siche JP, De Gaudemaris R, Maitre A. Mesure de la pression arterielle en ambulatoire. Interet et Iimites. Presse Medicale 6: 245-246. 1990
Manda G, Bertinieri G, Grassi G, Parati G, Pomidossi G, et al. Effects of blood pressure measurement by the doctor on patient's blood pressure and heart rate. Lancet 2: 695-698, 1983 Muller JE, Ludmer PL, Willich SN, Tofler GH, Aylmer G. Circadian variation in the frequency of sudden cardiac death. Circulation 75: 131-138, 1987 Nunez P, Siche JP, Maitre A, Mansour P, Pitiot M, et al. Etude chronotherapeutique du verapamil LP 240 dans I'hypertension arterielle legere Ii moderee. Archives des Maladies du Coeur et des Vaisseaux 83: 49, 1990 O'Brien E, Murphy J, Tyndall A, Atkins N, Mee F, et al. Twenty-fourhour ambulatory blood pressure in men and women age 17-80 years: the Allied Irish Bank StUdy. Journal of Hypertension 9: 355-360, 1991 Pickering TG, Harshfield GA, Devereux RB, Laragh JH. What is the role of ambulatory blood pressure monitoring in the management of hypertensive patients? Hypertension 7: 171-177, 1985 Porchet M, 8ussien JP, Waeber B, Nusserger J, Brunner HR. Unpredictability of blood pressure recorded outside the clinic in the treated hypertensive patient. Journal of Cardiovascular Pharmacology 8: 332-335, 1986 Trazzi S, Mutti E, Frattola A, Imholz B, Parati G, et al. Reproducibility of non-invasive and intra-arterial blood pressure monitoring: implications for studies on antihypertensive treatment. Journal of Hypertension 9: 115-119, 1991 Weber MA, Cheung 00, Graettinger WF, Lipson JL. Characterization of antihypertensive therapy by whole-day pressure monitoring. Journal of the American Medical Association 259: 3281-3285, 1988
Correspondence and reprints: Prof. Jean-Michel Mallion. Merlecine Interne et Cardiologie, H6pital A. Michallon, CHU BP 21738043 Grenoble, Cedex France.
Use of Ambulatory Blood Pressure Monitoring in the Management of Antihypertensive Therapy Jean-Michel Mallion, Anne Maitre, Regis de Gaudemaris, Jean-Philippe Siche and Frederic Tremel Medecine Interne et Cardiologie, Hopital A. Michallon, Grenoble, France
Summary
The recent development of ambulatory blood pressure (ASP) monitoring techniques has improved recording of blood pressure in therapeutic trials and in the clinical setting. The application of ASP differs according to which of these 2 applications is being considered. In therapeutic trials, a placebo control is required. The large quantity of precise data acquired with ASP monitoring allows the study of a limited number of patients; it also allows individual study of patients with a 'white coat' response (i.e. elevated blood pressure in response to examination by the clinician). Analysis of data from ASP monitoring may include the following: comparison of mean blood pressure values over 24 hours, daytime or night-time, or over any other selected time period; 24-hour blood pressure profiles, or analysis hour-by-hour, giving true chronotherapy, and providing data regarding the wearing-off of a drug effect or loss of therapeutic control; analysis of blood pressure at particular times, such as on waking; or specific examination of nonresponders. In individual patients, ASP monitoring should be reserved for specific indications. It can be used before initiation oftreatment to confirm the necessity for treatment, especially in the context of hypertension at rest or the 'white coat' effect. With established treatment, ASP monitoring can be used in patients with resistant hypertension, in severe hypertension to examine loss of blood pressure control over time or inversion of the day/night cycle, and in patients with a specific illness, e.g. diabetes, in order to obtain the lowest blood pressure readings possible. Examination of these factors assists clinicians to accurately decide upon the timing and frequency of antihypertensive therapy.
Recent technological advances have led to the dev.elopment of methods for measuring ambulatory blood pressure (ABP). The benefits of ABP monitoring differ according to the population in which it is used. For example, in a clinical trial the benefits of ABP monitoring are different from those in the management of individual patients in a clinical setting. In general, a number of distinct advantages associated with ABP monitoring can be described. It is possible to analyse a variety of blood pressure measurements taken over a 24-hour pe-
riod, including 2 to 4 measurements per hour during the day and night. This allows evaluation of blood pressure both during medical consultation and during every day activity; evaluation of the differences between day and night-time blood pres. sure values; and assessment of the variations in blood pressure over 24 hours, resulting from physical activity and emotional stimuli. The form of ABP recording is determined by the possibilities of the computer software available, which may allow different analysis and pres-
13
Use of Ambulatory Blood Pressure Monitoring
entation of data; for example, a 24-hour blood pressure profile with analysis of systolic blood pressure, diastolic blood pressure and heart rate over time; or a mean blood pressure value calculated over 24 hours, or during the night-time or hourly periods, expressed as a histogram or percentage. Reference values for ABP monitoring have been established by age and sex for different socioprofessional categories (Battistella et al. 1989; Dreyer & Weber 1985; O'Brien et al. 1991). These values are different from those obtained in the clinician's office and those defined by the World Health Organization (WHO) as they are obtained from individuals performing daily activities, not those at rest. Thus, they are not epidemiologically significant at the present time. Reference values for ABP monitoring are lower at night than during the day, are lower in women than in men, and lie between those obtained in the clinician's office and those measurements recorded at home. The reproducibility of the mean of 24-hour values for ABP monitoring for a group of individuals seems excellent after 15 days to I month, if the recordings are repeated under similar conditions. Diary records are essential for repeated ABP monitoring in order to document the physical and emotional status of the individual at each recording (Trazzi et al. I 991 ).
1. Application of Ambulatory Blood Pressure Monitoring in Therapeutic Trials 1.1 Selection of Subjects Until the present time, it has been necessary to compare values of blood pressure during treatment with those obtained during placebo administration. The comprehensive data obtained using ABP monitoring allows study of smaller groups of patients, which is a major advantage in terms of cost and time (Coats et al. 1989). On the first recording using ABP monitoring, it is possible to identify patients with a 'white coat response', who may not, in fact, be hypertensive and who may exhibit a particular blood pressure
_
'"
16
I
E
S-
1
a.
III
.s ~
~ ~
o
6 4 2 O..I-.L--Systolic BP
Diastolic BP
Fig. 1. Changes in mean 24-hour systolic and diastolic ambulatory blood pressure (BP) in 10 hypertensive patients treated for 21 days with sustained release verapamil 240 mg/ day at 0800h (0) or 2000h (_) in a double-blind crossover study. Between group differences were not statistically significant.
profile and should form part of a special study group. It would seem that responses to therapy in this group are not typical of the responses of a hypertensive population (Trazzi et al. 1991). 1.2 Analysis of Results ABP monitoring facilitates comparison of mean blood pressure values over 24 hours, during the day or night, or sampling of values over a chosen number of hours (figs I and 2). The reference values used to evaluate antihypertensive effect may be pretreatment blood pressure values or reference blood pressure values according to age and sex. Thus, we can examine the effects of drug treatment over 24 hours or hourby-hour, in the form of a true diurnal analysis, in order to determine whether a drug exerts 24-hour control of blood pressure or, alternatively, to detect any loss of therapeutic control. In addition, the effect of drug treatment on blood pressure at specific times, such as in the early morning, can be examined (Muller et al. 1987). This effect is important because, at an epidemiological level, it would seem that the morning blood pressure peak may have repercussions in terms of cerebrovascular accidents, myocardial infarction and sudden death (Muller et al. 1987). Specific examination of patients deemed to be nonresponders to antihypertensive therapy shows that many are in fact 'white coat responders'.
Drugs 44 (Suppl. I) 1992
14
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E
30-
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0;
25-
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20-
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c:
to r;
0
0
2
4
6
I
I
8
U
10
14
12
16
18
'20
22
Time (hours)
Fig. 2. Changes in mean diastolic blood pressure (DBP) recorded hourly in hypertensive patients treated for 21 days in a crossover study with sustained release verapamil 240 mgfday at 0800h (0) or 2000h (_) compared with placebo values.
Some drug treatments have no lowering effect on blood pressure when resting values are normal. Indeed, in some patients an antihypertensive effect could be harmful if hypertension has been wrongly diagnosed (Weber et al. 1988).
1. Individual Applications of Ambulatory Blood Pressure Monitoring The random nature of using one blood pressure measurement during the day in order to judge the efficacy of an antihypertensive treatment is evident from the previous discussion. It is obvious that ABP monitoring cannot be applied to all hypertensive patients, but must be reserved for particular indications. 2.1 Pretreatment Applications The often significant rise in blood pressure observed during measurement by a clinician (the 'white coat effect') can lead to an erroneous diagnosis of hypertension. Measurement under more relaxed circumstances may reveal this effect, and increased pulse rate may be a good indicator of a 'white coat' reaction. Inappropriate classification
of a patient as hypertensive has major repercussions. Patients may endure severe psychological consequences and be subjected to the constraints of long term treatment. There are also secondary effects, which vary according to the medication administered, and there may be alterations in patients' quality of life. In addition, there are financial and economic costs to be considered. On the physiopathological level, some antihypertensive medication such as some calcium antagonists have no effect on blood pressure in normotensive individuals. Many other medications affect diurnal blood pressure, as they alter baseline values to a new, lower level. The consequences of reduced blood pressure levels such as circulatory disturbances (to the brain, kidney or heart) may be unfortunate; it is known that at the cardiac level coronary lesions may develop particularly as the patient gets older or when left ventricular hypertrophy is also present. 2.2 Applications During Treatment ABP monitoring is useful when hypertension as measured in the clinician's office seems resistant to treatment. In cases of severe hypertension, ABP monitoring can ensure that there is no loss of blood
Use of Ambulatory Blood Pressure Monitoring
15
pressure control over time (fig. 3), and provides information on a possible inversion of the 24-hour cycle, which may lead to a change in the administration of treatment at particular times (fig. 4).
confirming the efficacy of antihypertensive treatment. Thus, we have developed the notion of 'personalised treatment', which obliges us, whether we use ABP monitoring or not, to respect certain guidelines: the timing of rising, bedtime and mealtimes; the need to seek information about the timing and emotional effect of the daily activities of patients. These elements allow us to better define the timing and frequency of treatment.
2.3 Hypertension Associated with Another Disorder In hypertensive patients with diabetes mellitus, ABP monitoring can help to define the lowest blood pressure values possible, which is necessary if one is to determine, among other things, the correlation that may exist between the level of blood pressure and the level of microalbuminuria. ABP monitoring is also beneficial in patients with autonomic dysfunction, which may be present in patients with Shy-Drager syndrome, diabetes, in the elderly presenting with weakness, or in patients with renal failure on dialysis or following transplant, all of whom frequently show an inversion of the 24hour blood pressure cycle (Mallion et al. 1990). Finally, in patients with significant psychosensorial constraints, ABP monitoring is useful for
3. Conclusions In summary, the development of ABP monitoring has not revolutionised the management of antihypertensive treatment. However, in therapeutic trials it has allowed a better examination of the true effectiveness of treatment over a 24-hour period, particularly when drug treatment is given daily. If multiple dosage treatments are required, the precise timing of drug administration can be gauged by ABP monitoring. For the individual patient, the real interest of
240 220 200
c;;
180
J:
160
.5.
140
E
!:l II> II>
120
!Q. 100
II .Q CD
80 60
-- -
40
--- ...
- - --
--
"T. _ _ -_-_
-
-
--
---~
_ _ - _ -_ _ _ _ _ -
_
-
-
_--
20 O~---r---'----.---.----r---'----.---.---~----r---'---~
0800
1000
1200
1400
1600
1800
2000
2200
0000
0200
0400
0600
Time (hours)
Fig. 3. 24-Hour ambulatory blood pressure (vertical lines) and heart rate (horizontal lines) in I hypertensive patient, showing inversion of the 24-hour cycle.
Drugs 44 (Suppi. 1) 1992
16
220 200 180 Ci
160
J:
E
140
~
120
§.
'"
Ul Ul
~
"C
0 0
ffi
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04---~----~---r----r---~~~----~--~----~--~----r-~~
0900
1100
1300
1500
1700
1900
2100
2300
Treatment (2000)
0100
0300
0500
0700
Treatment (0830)
Time (hours)
Fig. 4. 24-Hour ambulatory blood pressure (vertical lines) and heart rate (horizontal lines) in a hypertensive patient with administration of propranolol at 2000h and 0830h.
ABP monitoring is the possibility of identifying individuals who are not in fact hypertensive; of avoiding giving treatment in error; and of confirming the necessity for particular drug treatment in particular clinical situations such as diabetes mellitus.
References Battistella P. De Gaudemaris R, Fran,ois G, Lyon A, Gosse P, et al. Valeurs de reference de la tension arterielle en ambulatoire d'activite et de nuit. Etude multicentrique de 394 sujets normotendus au repos. Archives des Maladies du Coeur et des Vaisseaux 82: 1019-1022, 1989 Coats A, Conway J, Somers VK, lsea JE, Sleight P. Ambulatory pressure monitoring in the assessment of hypertensive therapy. Cardiovascular Drugs and Therapy 3: 303-311, 1989 Dc Gaudemaris R, Mallion J-M, Battistella p, Battistella B, Siche JP. Ambulatory blood pressure and variability by age and sex in 200 normotensive subjects: reference population values. Journal of Hypertension 5 (Suppl. 5): 429-430, 1987 Drayer JIM, Weber MA. Definition of normalcy in whole-day ambulatory blood pressure monitoring. Clinical and Experimental Hypertension 7: 195-204, 1985 Kennedy HL, Horan MJ, Sprague MK, Padgett NE, Shriver KK. Ambulatory blood pressure in healthy normotensive males. American Heart Journal 106: 717-722, 1986 Mallion JM, Siche JP, De Gaudemaris R, Maitre A. Mesure de la pression arterielle en ambulatoire. Interet et Iimites. Presse Medicale 6: 245-246. 1990
Manda G, Bertinieri G, Grassi G, Parati G, Pomidossi G, et al. Effects of blood pressure measurement by the doctor on patient's blood pressure and heart rate. Lancet 2: 695-698, 1983 Muller JE, Ludmer PL, Willich SN, Tofler GH, Aylmer G. Circadian variation in the frequency of sudden cardiac death. Circulation 75: 131-138, 1987 Nunez P, Siche JP, Maitre A, Mansour P, Pitiot M, et al. Etude chronotherapeutique du verapamil LP 240 dans I'hypertension arterielle legere Ii moderee. Archives des Maladies du Coeur et des Vaisseaux 83: 49, 1990 O'Brien E, Murphy J, Tyndall A, Atkins N, Mee F, et al. Twenty-fourhour ambulatory blood pressure in men and women age 17-80 years: the Allied Irish Bank StUdy. Journal of Hypertension 9: 355-360, 1991 Pickering TG, Harshfield GA, Devereux RB, Laragh JH. What is the role of ambulatory blood pressure monitoring in the management of hypertensive patients? Hypertension 7: 171-177, 1985 Porchet M, 8ussien JP, Waeber B, Nusserger J, Brunner HR. Unpredictability of blood pressure recorded outside the clinic in the treated hypertensive patient. Journal of Cardiovascular Pharmacology 8: 332-335, 1986 Trazzi S, Mutti E, Frattola A, Imholz B, Parati G, et al. Reproducibility of non-invasive and intra-arterial blood pressure monitoring: implications for studies on antihypertensive treatment. Journal of Hypertension 9: 115-119, 1991 Weber MA, Cheung 00, Graettinger WF, Lipson JL. Characterization of antihypertensive therapy by whole-day pressure monitoring. Journal of the American Medical Association 259: 3281-3285, 1988
Correspondence and reprints: Prof. Jean-Michel Mallion. Merlecine Interne et Cardiologie, H6pital A. Michallon, CHU BP 21738043 Grenoble, Cedex France.
