Biomed & Pharmacother (1991) 45.327-332 0 Elsevier. Paris
327
Focus
Clinical utility and prognostic value of ambulatory monitoring A Pescini’,
bloo
ressure
A Simoni*
‘Cenlro Na:ionale Trasfusione Sangue, Laboralorio Centrale-Croce Rossa Italiana. via Rama::ini IS, 00151 Rome; ‘Divisione Osservaz’one Uomini. Policlinico Umberto I. Universitd di Roma “La Sapienza”, Rome, Italy (Received 1 July 1991: accepted I4 August 1991)
Summary - Ambulatory blood pressure monitoring is a useful procedure in the diagnosis and management of hypertension. in the assessment of anti-hypertensive drugs and as a means of predicting outcome in hypertension. With ambulatory blood pressure monitoring is possible to detect usual variability of blood pressure, circadian rhythms and the response to environmental influences in both normotensive and hypertensive subjects. A number of clinical conditions are better evaluated with this procedure than with conventional measurements, eg white-coat hypertension (the rise of blood pressure in the physician’s office). borderline hypertension, episodic hypertension and secondary hypertension. Multiple readings improve the precision of the estimate of blood pressure profile of the patient and allow a precise evaiuatio,l of blood pressure load to which a palient is exposed throughout 24 h. Ambulatory blood pressure monitoring is closely related to the incidence of cardio- and cerebrovascular events and to the prevalence and the degree of target-organ damage. Casual and ambulatory blood pressure readings are not alternative but complementary tools for clinical management of hypertension and for assess-
ment of the prognostic risk of hypertension. ambulatory blood pressure monitoring I hypertension / clinical use / prognosis
RCumd - Utilite clinique et valeur diagnostique du monitoring ambulatoire de la pression arterielle. Le monitoring atnhulatoire de la pression ardrielle est une nkthode utile au diagnostic et ci la prise en charge de l’hypertension, h I’Pvaluation des nrfidicanrents anti-hypertenseurs ainsi qu’ci I’Pvaluation du pronostic de la ntaladie. C&e ri cette technique de surveillance. il est possible dc de’tecter les variations tensionnelles habituelies, les rytltmes circadiens et les rkponses aux influences estkrieures chez IE sujet nornrotcndu conune chez I’hypertcndu. De nombreuses situations cliniques peuvent btinkficier aver cette technique d’une e’valuation tneilleure qu’avec les mesures traditionnelles de la tension, notamment I’hypertcnsion de la blouse hlanche (I’tVe’vation de la tension au cabinet du mt!decin), les hypertensions limitcs. l’hypertension Ppisodiquc. I’hypertension secondaire. Les lectures multiples anu%orent la prkision dans I’tQude au profil tensionnel chcz le malade ct autorise une Pvaluation prkise de la charge tensionnelle ci laquelle est exposi un malade tout au long des 24 henres. Les donnfcs du monitoring tensionnet anrbulatoire se correient e’troitement aver l’incidence des accidents cardio et r~r~bro~lasctrlaires~ ainsi qu’avec la prfivaience et I’itnportance de I’alte’ration des organes cibles. monitoring ambulatolre de la pression arterielle I hypertension / utilisations en clinique I pronostic
Introduction The use of sphygmomanometry for measurement of blood pressure (bp), introduced by Riva-Rocci at the end of last century, has remained, until today, the standard technique in clinical practice for the diagnosis of hypertension and the assessment of treatment regimens. Various factors may alter the accuracy and validity of casual measure-
ments of bp taken in the office or in the hospital by physicians: the observer bias, the variability of bp with circadian rhythms, the response to environmental factors, the alerting reaction of the patient. A device capable of measuring ambulatory bp, non invasively, can reduce the effects of these factors and may now be recognized as a major advance in the clinical management of hypertension.
328
A Pescini et al
Ambulatory blood pressure monitoring (ABPM) is a technique by which frequent bp and heart rate measurements can be made over 24-48 h, with limited interference to the subjects’ activities. The recorder is fully automated and uses a standard cuff that is placed around the upper arm and inflated at preprogrammed intervals of 2-60 min. Mean and median systolic and diastolic arterial pressures for the daytime, the night-time and the full 24-h period are estimated by auscultatory or oscillometric methods. All data that have been accumulated within the device’s memory system are unloaded into a microcomputer for storage and analysis [ 161. Non-invasive ambulatory monitoring has demonstrated a high correlation with intra-arterial and sphygmomanometriz measurement [2, 261. ABPM is being used to confirm the diagnosis of hypertension, to assess the severity of the disease, to predict the clinical course in the patient and to guide the use of pharmacological therapy.
ABPM in diagnosis and management of hypertension ABPM provides information not easily obtained by an observer: it can determine the short and long-term bp variability - circadian rhythm; the highest values during the early morning: a marked and prolonged bp fall during sleep (the range during the day and the night may be more than 30 mmHg); and marked and short-lasting bp rises during emotional stimuli, including those elicited when bp is assessed by the physician [14]. In hypertensive patients this pattern is usually preserved; the day-night differences are significantly higher in the hypertensive than in the normotensive subjects [ 121. In erderly, in malignant hypertension and in many forms of secondary hypertension (autoilomic dysfunction, Cushing, preeclampsia, cardiac and renal organ damage) there is no fall in bp in night and this finding has a prognostic value [9]. ABPM has proved to be an excellent way of detecting white-coat hypertension, the alerting reaction of the patient in the physician’s office that induces a transient bp rise, which is present in about IO-30% of subjects with elevated office bp and is more common among women [ 151.
The average rise in systolic and diastolic blood pressures upon patients* visit to a doctor’s room is 17 and 7 mmHg respectively. The pressure rise is accompanied by a rise in the heart rate, about 3 beats per min [34]. This transient pressor response may introduce an obvious error in determining patient’s actual bp profile; for most white-coat hypertensives ABPM demonstrated that other regularly recurring forms of stress, such as work, do not result in elevated bp [43]. In these subjects ABPM may help to avoid an overestimate of bp levels and unnecessary drug treatment. Ambulatory pressures are lower than pressure measured in the doctor’s office in 80% of patients referred for an evaluation of hypertension, the disparity between office and ambulatory pressures tending to increase with increasing levels of casual bp [25]. A further study has demonstrated that while conventionally measured bp tends to be lower than ambulatory daytime pressure in normotensive populations, this relationship is reversed in patients with hypertension [5]. Some people who appear normotensive when evaluated in the office are hypertensive when studied with ABPM [21]; eg patients with high normal bp in the office (diastolic bp, 85 to 89 mmHg) with target organ disease (left ventricular hypertrophy, hypertensive retinopathy, abnormal renal function) need ABPM to demonstrate high readings in association with physical or mental stress, such as work-related stress [17]. ABPM may help to identify those truly hypertensive patients who are most likely to benefit from antihypertensive therapy and it may resolve the differences between office and home bp measurements. In patients with mild or borderline hypertension and at low risk of developing cardiovascular complications, ABPM has shown that up to 40% of subjects have pressures low enough to withhold anti-hypertensive treatment [ 16, 271. A screening strategy that reduces the number of subjects initially identified as having mild hypertension and needing drug therapy can lead to a substantial reduction in health care costs [32]. ABPM is useful in episodic hypertension associated with adrenergic excess (pheochromocytoma) or with anxiety syndromes. Careful matching of activities and emotions with ambulatory bp recordings often aids in the diagnosis of these forms of episodic hypertension 1171.
Ambulatory
blood pressure monitoring
Average 24 h pressure and daytime pressure, the mean sleep-period pressure and the range of ambulatory bp increase with the stages of hypertension [IO]. ABPM indicates the severity and characteristics of hypertension more precisely than does casual bp and a further use for this technique is in hypertensives with confirmed left ventricular hypertrophy and an increased incidence of complex ventricular arrhythmias and sudden cardiac death [ 161. It is difficult to establish a stable baseline pressure from which to assess pharmacological drug effects. The major advantage of ABPM is that it provides multiple unbiased bp measurements for decision making: it may direct anti-hypertensive therapy to those with higher average pressures; aggressive treatment of this group might be more effective in achieving a reduction in long-term cardiovascular morbidity, by tailoring therapy to the individual patient and reducing side-effects (eg transient hypotension) [16]. Patients could be protected both from prescription of too many drugs and from lowering bp too far. Whole day bp documents efficacy and duration of action of treatment, make it possible to recommend appropriate frequencies of drug administration and to avoid excessive doses of anti-hypertensive agents. In hypertension clinics, in therapeutic trials or in the general population, 25% of hypertensive patients are resistant to anti-hypertensive therapy. ABPM will demonstrate the degree and duration of anti-hypertensive drug action in these individuals [17, 281. A study has shown that essential hypertensive patients who are difficult to control with multiple drugs in the clinic are not as hypertensive in their home environment, whereas uncontrolled patients with renal hypertension remain uniformly hypertensive in their home and hospital environments [35].
Prognostic aspects of ABPM The true bp is conceptualized as the average or integrated level of pressure over time, and also as the bp that is ultimately responsible for the adverse effects of hypertension [27]. Because the variability of bp and the tendency for office blood pressures to be unrepresentative of the entire pressure load over 24 h, the measurement of ambulatory bp adds another important predictor or risk [24]. The incidence of car-
329
diovascular morbidity and mortality and the development of target-organ complications of hypeI’tenSiOII correlate better with ABPM than with casual measurements [26. 311. Clinicians have a tendency to round off bp readings to the nearest “5” or “o”, a phenomenon known as terminal digit preference [20]. But a long-term difference of 5-6 mmHg in usual diastolic bp is associated with about 35-4096 less stroke and 20-25% less coronary heart disease 141. ABPM improves the reliability and reproducibility of the estimate of a subject’s usual bp and overcomes all forms of observer bias [3]. Moreover, it has been calculated that the true relationship between cardiovascular mortality and the usual average bp is about 60% steeper than the observed relationship [ 1I]. The true slope is only underestimated by 20% when ABPM is used [3]. The morbidity of hypertension and the prevalence of end-organ damage can be related to the average bp level or to certain pressor episodes (the alerting response [14] or to overall bp variability [22] or to bp load [42]. Longitudinal studies are required to finally determine the independent prognostic significance of these parameters. Until now several observations are available: i) higher day-time blood pressures are associated with a higher rate of cardiovascular morbid events and death than lower day-time blood pressures [23]; ii) hypertensive patients losing nocturnal bp reduction might be at higher risk of cerebrovascular complications and a greater degree of left ventricular hypertrophy [ 181. In unselected hypertensive patients an ambulatory bz decline from day to night is associated with a lower left ventricular muscle mass; therefore, a nocturnal reduction of systolic and diastolic bp by more than 10% of daytime values could delay or prevent the development of cardiac left ventricular hypertrophy [38]; iii) the early morning rise of bp and heart rate is accompanied by hemodynamic, rheological and biochemical alterations which together may contribute to the increased frequency of vascular complications during the morning hours (sudden cardiac death, myocardial infarction, stroke and transient ischaemic events) 1301; iv) it has been demonstrated that the independent prognostic power of ambulatory systolic bp especially the residual ambulatory pressure: the difference between the observed and the predicted or calculated ambulatory bp from the office pressure, when other selected risk factors are statistically controlled.
330
A Pest ini et al
In a large sample of hypertensive patients, followed for = 5 years, those with lower residual ambulatory systolic blood pressure tended to have longer periods of survival without new cardiovascular events 1241. ABPM is superior to casual pressure measurements in predicting latent cerebrovascular disease because abnormalities on magnetic resonance imaging are significantly associated with the average systolic pressucz recordings, particularly during sleep [33]. The ambulatory bp levels discriminate between patients who developed complications rapidly and those in whom the development of events is delayed [26]. Left ventricular mass can be accurately measured by echocardiography and this measurement has been shown to be: a strong predictor of prognosis; an index of the severity and duration of hypertension; and a predictor of cardiovascular events [6]. Some studies indicate the superiority of ABPM over multiple casual office blood pressures in predicting left ventricular wall thickness and mass, an independent prognostic marker [ 13, 281. Average daily bp [40], systolic bp, 24 h average systolic and diastolic bp [28, 371, bp during work and bp during physical or mental activity [7], derived from ABPM, are superior to casual bp in predicting an increased left ventricular mass index. The percentage of elevated bp values that includes both the awake and asleep periods is predictive of cardiac target-organ involvement in patients with mild to moderate hypertension [39]. An echographic examination of the left ventricle should be recommended in hypertensive patients with 24 h bp means disproportionally high relative to casual bp [37]. Another study showed that in patients hypertensive in the physician’s office but normotensive on the basis of ABPM, the left ventricular mass index was not different from that of normotensive control subjects and lower than in patients with higher ambulatory bp values [40]. ABPM allows a more precise and reliable evaluation of the pressure overload (bp load is defined as the percentage of systolic and diastolic readings more than 140 and 90 mmHg, respectively) on the heart and the vessels: among mildy hypertensive patients with bp daily loads of over 40%, the incidence of left ventricular hypertrophy or decreased diastolic function is quite high and drug
therapy appears warranted; for those patients with bp loads ranging from 20 to 40%, no definitive advice can be given but they may require drug therapy to prevent the developmeni of more severe hypertension or the sequelae of chronic pressure overload [41]. The bp load is equal or superior to the average ambulatory bp value in predicting left ventricular and atria1 mass index and rapid left ventricular filling. The average daily pressure load (defined as the percentage of bp values > 140/90 while awake and 120/80 during sleep) delineates groups at high and low risk of developing hypertensive heart disease [39]. ABPM has been confirmed to be superior to traditional bp in also reflecting the initial structural cardiovascular abnormalities associated with incipient hypertension in a population of normotensive subjects with hypertensive parents [14. 291. Other target-organ involvement also correlates better with ABPM than casual bp: 24 h urine albumin and N-acetyl$D-glucosaminidase, microalbuminuria, arterial distensibility and compliance (by pulse wave velocity) [ 1, 8, 191. The evidence that ABPM can improve the assessment of prognosis for hypertension is encouraging but incomplete because further prospective controlled studies are required. For the time being, office bp remains the primary indicator of prognosis [31].
Conclusions Ambulatory blood pressure monitoring avoids the inherent limitations of clinic pressure, by increasing the number of readings and taking readings outside the clinic setting, which are more representative of the patient’s actual bp profile. Studies are required to describe the distribution of ABPM parameters for all age-sex strata in general population and the normal values in certain populations eg pediatrics, pregnant women [31]. Internationally accepted normal values for 24 h bp are required. ABPM in hypertensive patients may be a potentially useful and convenient method for the better diagnosis of hypertension by abolishing the alerting reaction. Longitudinal studies should be undertaken to determine which ambulatory profiles are associated with an increased cardiovascular risk and what transformations of ambulatory
Ambu~aro~ blood pressure moo~te~ag
profiles induced by anti-hypertensive therapy are associated with a reduction in that risk [17J. Furthermore, the hypothesis that treatment is clearly indicated above certain levels of ambulatory bp needs to be tested- Ambu~ato~ bp profiles need to be better cha~cter~~ed espe~~~ly for those su&@cts who appear to be at a low risk on the basis of casual bp deie~~n~t~on [321. ABPM may not be necessary for the routine evaluation of all hypertensive patients, but appears to have certain benefits in selected ru;searchand clinical situations. A number of clinical conditions are better eva& uated with ABPM rban witb convention measurements but a cost-benefit model is stiif needed to use the technique appropriately and effectively. Now it seems highly cost-effective for persons in~t~a~~y classified as having mild hypertension. Despite the importance of age, off~ffice pressure, and evidence of previous complications in inffue~cin~ prognosis, ABPM is correlated with the degree of target-organ d~age and cardiovascular morbidity and modality. The evidence that ABPM can improve the assessment of prognosis for hypertension needs a prospective controlled study to firmty establish the relationship between ambulatory bp and clinical prognosis and to address the question of whetber ambulator bp is a signi~~antly better p~di~tor of ca~iovas~u~ar events than o&e bp an~or adds to the p~d~~tion offered by office bp E3X,433. Longitudinal studies are required to determirre the independent prognostic significance of bp variability, the alerting response, day-night difference, mean daytime and night-time bp levels. Interaction among multiple risk factors is important for prognosis; ABPM cannot therefore be used as a sate index of risk but must be considered in ~on~u~~tjo~ with other possible accelerators of athe~sclerosis f26f. Casual and ambulatory bp readings are not alternative but complemenrary tools for diagnosis and management of hypertension and for assessment of the risk in an individual patient and in clinical trials.
1 Asmar RG, Bruttel PC, Pannier EM, Laco&?y PJ,
Safar ME (192%)Arteriat distensibility and ambulatory blood pressure monitoring in ess@rttialhypertension. Am J CardiD 61, 1066 2 Baumgart P, Walgerp, Jurgens U, Rabn KH (19901 Reference data for ambulatory blood Pressure mania
331
taring: what resuhs are equivalent to the established limits of Offlce blood pmssure? Km Wocitm&tr 14), 723 COS@AJS (I%?) Rep~duc~b~iity or variat@ty of cssual and ~bn~~~ blood Pressme data: jmpliitions for clinical triais. f ~~~~e~ 8 @uppl6) 57 Collins R, Pete R, ~a~rna~ S, ffr?txert P, Fiebacb NH, Eberlein RA, Godwin 5, @&bash N, Taylor J% ffenttekens CH (1990) Btoad pressure, strati. and coronaryheart disease. iI. Short-term reductions in blood pressure: overview of randomized drug trials in their epidem~~o~ca~ context. Lancer 335,82? COX f, O’MalleyK, Atkins N, O’Brien E Cl991) A ~rn~~o~ of the t~o~fo~-~ur blood pressue proFIle in ~~o~~ive and h~~e~~ve subjects. J averred 9, 53 Devereux RB f1989) Irnp~~a~~e of left ventric;ulrtr mass as a predictor of cardiovascular morbidity in bypcrtension. Atn .I Hyperms 2, 650 Devereux RB. Pickering TG (1990) ReIatjonsb~~b& tween amb~ato~ or exercise blood Pressure and Ieft v~~~~ui~ structure: p~~os~~ ~mpI~cat~ns.J Zfy68(
3
4
5
6
7
~e~~~ns8, 125
8 Giaconi S, lxvanti C, Pommd B (3989) MhxoaIbuminuriaand easuai and ambuIato~ blood ptessuro monitoring in nomrotensives and in patients with borderline and mild essential hypertension. Am J iYyptwtm 2, 259 9 Imai Y, Abe K, Munakata M? Sakuma H, Hasbim~t~ J, lmai K, Sekino H, ~os~~~a~aK
327
Focus
Clinical utility and prognostic value of ambulatory monitoring A Pescini’,
bloo
ressure
A Simoni*
‘Cenlro Na:ionale Trasfusione Sangue, Laboralorio Centrale-Croce Rossa Italiana. via Rama::ini IS, 00151 Rome; ‘Divisione Osservaz’one Uomini. Policlinico Umberto I. Universitd di Roma “La Sapienza”, Rome, Italy (Received 1 July 1991: accepted I4 August 1991)
Summary - Ambulatory blood pressure monitoring is a useful procedure in the diagnosis and management of hypertension. in the assessment of anti-hypertensive drugs and as a means of predicting outcome in hypertension. With ambulatory blood pressure monitoring is possible to detect usual variability of blood pressure, circadian rhythms and the response to environmental influences in both normotensive and hypertensive subjects. A number of clinical conditions are better evaluated with this procedure than with conventional measurements, eg white-coat hypertension (the rise of blood pressure in the physician’s office). borderline hypertension, episodic hypertension and secondary hypertension. Multiple readings improve the precision of the estimate of blood pressure profile of the patient and allow a precise evaiuatio,l of blood pressure load to which a palient is exposed throughout 24 h. Ambulatory blood pressure monitoring is closely related to the incidence of cardio- and cerebrovascular events and to the prevalence and the degree of target-organ damage. Casual and ambulatory blood pressure readings are not alternative but complementary tools for clinical management of hypertension and for assess-
ment of the prognostic risk of hypertension. ambulatory blood pressure monitoring I hypertension / clinical use / prognosis
RCumd - Utilite clinique et valeur diagnostique du monitoring ambulatoire de la pression arterielle. Le monitoring atnhulatoire de la pression ardrielle est une nkthode utile au diagnostic et ci la prise en charge de l’hypertension, h I’Pvaluation des nrfidicanrents anti-hypertenseurs ainsi qu’ci I’Pvaluation du pronostic de la ntaladie. C&e ri cette technique de surveillance. il est possible dc de’tecter les variations tensionnelles habituelies, les rytltmes circadiens et les rkponses aux influences estkrieures chez IE sujet nornrotcndu conune chez I’hypertcndu. De nombreuses situations cliniques peuvent btinkficier aver cette technique d’une e’valuation tneilleure qu’avec les mesures traditionnelles de la tension, notamment I’hypertcnsion de la blouse hlanche (I’tVe’vation de la tension au cabinet du mt!decin), les hypertensions limitcs. l’hypertension Ppisodiquc. I’hypertension secondaire. Les lectures multiples anu%orent la prkision dans I’tQude au profil tensionnel chcz le malade ct autorise une Pvaluation prkise de la charge tensionnelle ci laquelle est exposi un malade tout au long des 24 henres. Les donnfcs du monitoring tensionnet anrbulatoire se correient e’troitement aver l’incidence des accidents cardio et r~r~bro~lasctrlaires~ ainsi qu’avec la prfivaience et I’itnportance de I’alte’ration des organes cibles. monitoring ambulatolre de la pression arterielle I hypertension / utilisations en clinique I pronostic
Introduction The use of sphygmomanometry for measurement of blood pressure (bp), introduced by Riva-Rocci at the end of last century, has remained, until today, the standard technique in clinical practice for the diagnosis of hypertension and the assessment of treatment regimens. Various factors may alter the accuracy and validity of casual measure-
ments of bp taken in the office or in the hospital by physicians: the observer bias, the variability of bp with circadian rhythms, the response to environmental factors, the alerting reaction of the patient. A device capable of measuring ambulatory bp, non invasively, can reduce the effects of these factors and may now be recognized as a major advance in the clinical management of hypertension.
328
A Pescini et al
Ambulatory blood pressure monitoring (ABPM) is a technique by which frequent bp and heart rate measurements can be made over 24-48 h, with limited interference to the subjects’ activities. The recorder is fully automated and uses a standard cuff that is placed around the upper arm and inflated at preprogrammed intervals of 2-60 min. Mean and median systolic and diastolic arterial pressures for the daytime, the night-time and the full 24-h period are estimated by auscultatory or oscillometric methods. All data that have been accumulated within the device’s memory system are unloaded into a microcomputer for storage and analysis [ 161. Non-invasive ambulatory monitoring has demonstrated a high correlation with intra-arterial and sphygmomanometriz measurement [2, 261. ABPM is being used to confirm the diagnosis of hypertension, to assess the severity of the disease, to predict the clinical course in the patient and to guide the use of pharmacological therapy.
ABPM in diagnosis and management of hypertension ABPM provides information not easily obtained by an observer: it can determine the short and long-term bp variability - circadian rhythm; the highest values during the early morning: a marked and prolonged bp fall during sleep (the range during the day and the night may be more than 30 mmHg); and marked and short-lasting bp rises during emotional stimuli, including those elicited when bp is assessed by the physician [14]. In hypertensive patients this pattern is usually preserved; the day-night differences are significantly higher in the hypertensive than in the normotensive subjects [ 121. In erderly, in malignant hypertension and in many forms of secondary hypertension (autoilomic dysfunction, Cushing, preeclampsia, cardiac and renal organ damage) there is no fall in bp in night and this finding has a prognostic value [9]. ABPM has proved to be an excellent way of detecting white-coat hypertension, the alerting reaction of the patient in the physician’s office that induces a transient bp rise, which is present in about IO-30% of subjects with elevated office bp and is more common among women [ 151.
The average rise in systolic and diastolic blood pressures upon patients* visit to a doctor’s room is 17 and 7 mmHg respectively. The pressure rise is accompanied by a rise in the heart rate, about 3 beats per min [34]. This transient pressor response may introduce an obvious error in determining patient’s actual bp profile; for most white-coat hypertensives ABPM demonstrated that other regularly recurring forms of stress, such as work, do not result in elevated bp [43]. In these subjects ABPM may help to avoid an overestimate of bp levels and unnecessary drug treatment. Ambulatory pressures are lower than pressure measured in the doctor’s office in 80% of patients referred for an evaluation of hypertension, the disparity between office and ambulatory pressures tending to increase with increasing levels of casual bp [25]. A further study has demonstrated that while conventionally measured bp tends to be lower than ambulatory daytime pressure in normotensive populations, this relationship is reversed in patients with hypertension [5]. Some people who appear normotensive when evaluated in the office are hypertensive when studied with ABPM [21]; eg patients with high normal bp in the office (diastolic bp, 85 to 89 mmHg) with target organ disease (left ventricular hypertrophy, hypertensive retinopathy, abnormal renal function) need ABPM to demonstrate high readings in association with physical or mental stress, such as work-related stress [17]. ABPM may help to identify those truly hypertensive patients who are most likely to benefit from antihypertensive therapy and it may resolve the differences between office and home bp measurements. In patients with mild or borderline hypertension and at low risk of developing cardiovascular complications, ABPM has shown that up to 40% of subjects have pressures low enough to withhold anti-hypertensive treatment [ 16, 271. A screening strategy that reduces the number of subjects initially identified as having mild hypertension and needing drug therapy can lead to a substantial reduction in health care costs [32]. ABPM is useful in episodic hypertension associated with adrenergic excess (pheochromocytoma) or with anxiety syndromes. Careful matching of activities and emotions with ambulatory bp recordings often aids in the diagnosis of these forms of episodic hypertension 1171.
Ambulatory
blood pressure monitoring
Average 24 h pressure and daytime pressure, the mean sleep-period pressure and the range of ambulatory bp increase with the stages of hypertension [IO]. ABPM indicates the severity and characteristics of hypertension more precisely than does casual bp and a further use for this technique is in hypertensives with confirmed left ventricular hypertrophy and an increased incidence of complex ventricular arrhythmias and sudden cardiac death [ 161. It is difficult to establish a stable baseline pressure from which to assess pharmacological drug effects. The major advantage of ABPM is that it provides multiple unbiased bp measurements for decision making: it may direct anti-hypertensive therapy to those with higher average pressures; aggressive treatment of this group might be more effective in achieving a reduction in long-term cardiovascular morbidity, by tailoring therapy to the individual patient and reducing side-effects (eg transient hypotension) [16]. Patients could be protected both from prescription of too many drugs and from lowering bp too far. Whole day bp documents efficacy and duration of action of treatment, make it possible to recommend appropriate frequencies of drug administration and to avoid excessive doses of anti-hypertensive agents. In hypertension clinics, in therapeutic trials or in the general population, 25% of hypertensive patients are resistant to anti-hypertensive therapy. ABPM will demonstrate the degree and duration of anti-hypertensive drug action in these individuals [17, 281. A study has shown that essential hypertensive patients who are difficult to control with multiple drugs in the clinic are not as hypertensive in their home environment, whereas uncontrolled patients with renal hypertension remain uniformly hypertensive in their home and hospital environments [35].
Prognostic aspects of ABPM The true bp is conceptualized as the average or integrated level of pressure over time, and also as the bp that is ultimately responsible for the adverse effects of hypertension [27]. Because the variability of bp and the tendency for office blood pressures to be unrepresentative of the entire pressure load over 24 h, the measurement of ambulatory bp adds another important predictor or risk [24]. The incidence of car-
329
diovascular morbidity and mortality and the development of target-organ complications of hypeI’tenSiOII correlate better with ABPM than with casual measurements [26. 311. Clinicians have a tendency to round off bp readings to the nearest “5” or “o”, a phenomenon known as terminal digit preference [20]. But a long-term difference of 5-6 mmHg in usual diastolic bp is associated with about 35-4096 less stroke and 20-25% less coronary heart disease 141. ABPM improves the reliability and reproducibility of the estimate of a subject’s usual bp and overcomes all forms of observer bias [3]. Moreover, it has been calculated that the true relationship between cardiovascular mortality and the usual average bp is about 60% steeper than the observed relationship [ 1I]. The true slope is only underestimated by 20% when ABPM is used [3]. The morbidity of hypertension and the prevalence of end-organ damage can be related to the average bp level or to certain pressor episodes (the alerting response [14] or to overall bp variability [22] or to bp load [42]. Longitudinal studies are required to finally determine the independent prognostic significance of these parameters. Until now several observations are available: i) higher day-time blood pressures are associated with a higher rate of cardiovascular morbid events and death than lower day-time blood pressures [23]; ii) hypertensive patients losing nocturnal bp reduction might be at higher risk of cerebrovascular complications and a greater degree of left ventricular hypertrophy [ 181. In unselected hypertensive patients an ambulatory bz decline from day to night is associated with a lower left ventricular muscle mass; therefore, a nocturnal reduction of systolic and diastolic bp by more than 10% of daytime values could delay or prevent the development of cardiac left ventricular hypertrophy [38]; iii) the early morning rise of bp and heart rate is accompanied by hemodynamic, rheological and biochemical alterations which together may contribute to the increased frequency of vascular complications during the morning hours (sudden cardiac death, myocardial infarction, stroke and transient ischaemic events) 1301; iv) it has been demonstrated that the independent prognostic power of ambulatory systolic bp especially the residual ambulatory pressure: the difference between the observed and the predicted or calculated ambulatory bp from the office pressure, when other selected risk factors are statistically controlled.
330
A Pest ini et al
In a large sample of hypertensive patients, followed for = 5 years, those with lower residual ambulatory systolic blood pressure tended to have longer periods of survival without new cardiovascular events 1241. ABPM is superior to casual pressure measurements in predicting latent cerebrovascular disease because abnormalities on magnetic resonance imaging are significantly associated with the average systolic pressucz recordings, particularly during sleep [33]. The ambulatory bp levels discriminate between patients who developed complications rapidly and those in whom the development of events is delayed [26]. Left ventricular mass can be accurately measured by echocardiography and this measurement has been shown to be: a strong predictor of prognosis; an index of the severity and duration of hypertension; and a predictor of cardiovascular events [6]. Some studies indicate the superiority of ABPM over multiple casual office blood pressures in predicting left ventricular wall thickness and mass, an independent prognostic marker [ 13, 281. Average daily bp [40], systolic bp, 24 h average systolic and diastolic bp [28, 371, bp during work and bp during physical or mental activity [7], derived from ABPM, are superior to casual bp in predicting an increased left ventricular mass index. The percentage of elevated bp values that includes both the awake and asleep periods is predictive of cardiac target-organ involvement in patients with mild to moderate hypertension [39]. An echographic examination of the left ventricle should be recommended in hypertensive patients with 24 h bp means disproportionally high relative to casual bp [37]. Another study showed that in patients hypertensive in the physician’s office but normotensive on the basis of ABPM, the left ventricular mass index was not different from that of normotensive control subjects and lower than in patients with higher ambulatory bp values [40]. ABPM allows a more precise and reliable evaluation of the pressure overload (bp load is defined as the percentage of systolic and diastolic readings more than 140 and 90 mmHg, respectively) on the heart and the vessels: among mildy hypertensive patients with bp daily loads of over 40%, the incidence of left ventricular hypertrophy or decreased diastolic function is quite high and drug
therapy appears warranted; for those patients with bp loads ranging from 20 to 40%, no definitive advice can be given but they may require drug therapy to prevent the developmeni of more severe hypertension or the sequelae of chronic pressure overload [41]. The bp load is equal or superior to the average ambulatory bp value in predicting left ventricular and atria1 mass index and rapid left ventricular filling. The average daily pressure load (defined as the percentage of bp values > 140/90 while awake and 120/80 during sleep) delineates groups at high and low risk of developing hypertensive heart disease [39]. ABPM has been confirmed to be superior to traditional bp in also reflecting the initial structural cardiovascular abnormalities associated with incipient hypertension in a population of normotensive subjects with hypertensive parents [14. 291. Other target-organ involvement also correlates better with ABPM than casual bp: 24 h urine albumin and N-acetyl$D-glucosaminidase, microalbuminuria, arterial distensibility and compliance (by pulse wave velocity) [ 1, 8, 191. The evidence that ABPM can improve the assessment of prognosis for hypertension is encouraging but incomplete because further prospective controlled studies are required. For the time being, office bp remains the primary indicator of prognosis [31].
Conclusions Ambulatory blood pressure monitoring avoids the inherent limitations of clinic pressure, by increasing the number of readings and taking readings outside the clinic setting, which are more representative of the patient’s actual bp profile. Studies are required to describe the distribution of ABPM parameters for all age-sex strata in general population and the normal values in certain populations eg pediatrics, pregnant women [31]. Internationally accepted normal values for 24 h bp are required. ABPM in hypertensive patients may be a potentially useful and convenient method for the better diagnosis of hypertension by abolishing the alerting reaction. Longitudinal studies should be undertaken to determine which ambulatory profiles are associated with an increased cardiovascular risk and what transformations of ambulatory
Ambu~aro~ blood pressure moo~te~ag
profiles induced by anti-hypertensive therapy are associated with a reduction in that risk [17J. Furthermore, the hypothesis that treatment is clearly indicated above certain levels of ambulatory bp needs to be tested- Ambu~ato~ bp profiles need to be better cha~cter~~ed espe~~~ly for those su&@cts who appear to be at a low risk on the basis of casual bp deie~~n~t~on [321. ABPM may not be necessary for the routine evaluation of all hypertensive patients, but appears to have certain benefits in selected ru;searchand clinical situations. A number of clinical conditions are better eva& uated with ABPM rban witb convention measurements but a cost-benefit model is stiif needed to use the technique appropriately and effectively. Now it seems highly cost-effective for persons in~t~a~~y classified as having mild hypertension. Despite the importance of age, off~ffice pressure, and evidence of previous complications in inffue~cin~ prognosis, ABPM is correlated with the degree of target-organ d~age and cardiovascular morbidity and modality. The evidence that ABPM can improve the assessment of prognosis for hypertension needs a prospective controlled study to firmty establish the relationship between ambulatory bp and clinical prognosis and to address the question of whetber ambulator bp is a signi~~antly better p~di~tor of ca~iovas~u~ar events than o&e bp an~or adds to the p~d~~tion offered by office bp E3X,433. Longitudinal studies are required to determirre the independent prognostic significance of bp variability, the alerting response, day-night difference, mean daytime and night-time bp levels. Interaction among multiple risk factors is important for prognosis; ABPM cannot therefore be used as a sate index of risk but must be considered in ~on~u~~tjo~ with other possible accelerators of athe~sclerosis f26f. Casual and ambulatory bp readings are not alternative but complemenrary tools for diagnosis and management of hypertension and for assessment of the risk in an individual patient and in clinical trials.
1 Asmar RG, Bruttel PC, Pannier EM, Laco&?y PJ,
Safar ME (192%)Arteriat distensibility and ambulatory blood pressure monitoring in ess@rttialhypertension. Am J CardiD 61, 1066 2 Baumgart P, Walgerp, Jurgens U, Rabn KH (19901 Reference data for ambulatory blood Pressure mania
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taring: what resuhs are equivalent to the established limits of Offlce blood pmssure? Km Wocitm&tr 14), 723 COS@AJS (I%?) Rep~duc~b~iity or variat@ty of cssual and ~bn~~~ blood Pressme data: jmpliitions for clinical triais. f ~~~~e~ 8 @uppl6) 57 Collins R, Pete R, ~a~rna~ S, ffr?txert P, Fiebacb NH, Eberlein RA, Godwin 5, @&bash N, Taylor J% ffenttekens CH (1990) Btoad pressure, strati. and coronaryheart disease. iI. Short-term reductions in blood pressure: overview of randomized drug trials in their epidem~~o~ca~ context. Lancer 335,82? COX f, O’MalleyK, Atkins N, O’Brien E Cl991) A ~rn~~o~ of the t~o~fo~-~ur blood pressue proFIle in ~~o~~ive and h~~e~~ve subjects. J averred 9, 53 Devereux RB f1989) Irnp~~a~~e of left ventric;ulrtr mass as a predictor of cardiovascular morbidity in bypcrtension. Atn .I Hyperms 2, 650 Devereux RB. Pickering TG (1990) ReIatjonsb~~b& tween amb~ato~ or exercise blood Pressure and Ieft v~~~~ui~ structure: p~~os~~ ~mpI~cat~ns.J Zfy68(
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~e~~~ns8, 125
8 Giaconi S, lxvanti C, Pommd B (3989) MhxoaIbuminuriaand easuai and ambuIato~ blood ptessuro monitoring in nomrotensives and in patients with borderline and mild essential hypertension. Am J iYyptwtm 2, 259 9 Imai Y, Abe K, Munakata M? Sakuma H, Hasbim~t~ J, lmai K, Sekino H, ~os~~~a~aK
