Clin. Cardiol. 15 (Suppl. 11) 11-6-11-9 (1992)
The Role of Ambulatory Blood Pressure Monitoring in Research PRINCE ZACHARIAH, M.D., Ph.D.
Mayo Clinic Jacksonville,Jacksonville, Florida, USA
Summary: Ambulatory blood pressure monitoring has a significant research role. It documents normal daily blood pressure variations and provides data regarding the relationship between essential hypertension and the circadian cycle. It permits comparisons between normotensive and hypertensive individuals, racial groups, males and females, differingage p u p s , and various clinical categories.It may be a better predictor of hypertension-associatedend-organ changes than clinic or office measurement. It allows quantitative analysis of the high blood pressure load over time. Ambulatory blood pressure monitoring can distinguish between borderline and true hypertension, can evaluate episodic hypertension, and can assess the effectiveness of antihypertensive drug therapy.
Key words: ambulatory blood pressure monitoring, hypertension research, antihypertensive drug efficacy, targetorgan changes Introduction Ambulatory blood pressure monitoring (ABPM) offers special help in at least three basic research areas. It provides data on normal daily blood pressure patterns. It makes possible comparisons of levels of blood pressure between normotensive and hypertensive individuals and patients with other disease states. Finally, ABPM throws light on the possible correlations between levels of blood
Address for reprints: Prince Zachariah, M.D., Ph.D. Mayo Clinic Jacksonville 4500 San Pablo Road Jacksonville, FL 32224, USA
pressure and end-organ changes, particularly with regard to the cardiovascular system.
Normal Blood Pressure Patterns Twenty-four hour blood pressure monitoring reveals a pattern in which early morning blood pressures, starting from around 4:OOor 500 a.m., normally tend to rise steeply, together with the heart rate. During the daytime work hours, blood pressures appear to remain high, spontaneously declining to a fairly low level in the evening. The nadir of blood pressure occurs during early sleep, from about 11:00 p.m. to 3:OO a.m. This diurnal pattern remains the same for normal individuals and for hypertensive patients. The difference is in the severity of the pressure elevations. This diurnal or circadian pattern changes somewhat with age. ABPM data indicate that mean systolic blood pressure begins to rise, starting at about age 40, even in apparently normotensive subjects. Mean diastolic blood pressure tends to remain the same with age, except that in men there is a slight and nonsignificant elevation in the ~ O Sde, clining slowly in the 70s. This has been reported by a number of investigators from different parts of the world.
Hypertensive Blood Pressure Patterns If one uses ABPM to compare borderline hypertensive patients with established hypertensive patients, blood pressures in hypertensives will be predictably high and the circadian pattern of early morning surges and evening declines will be&maintained,but at higher levels than those seen in normotensive subjects. This significantelevation of blood pressure in the morning is of concern, in that hypertensive patients may be at higher risk for myocardial infarction or stroke. The incidence of these and other untoward cardiac events is well-known to be highest in the early morning hours. In one ABPM comparison of age-matched normotensive and hypertensive men, Drayer et al.* found that the difference between daytime and nighttime blood pressures
11-7
P. Zachariah: ABPM in research
TABLEI Comparison of averages of blood pressures (mmHg) obtained during various periods of blood pressure monitoring in normotensive and hypertensive men
Whole-day average
Daytime average
Nighttime average
8:OO-1O:OO A.M. average
120+ 11 75 f 7
126+ l l a 79 f 7a
107 f 10n 67 8*
125 f 11“
140 f 18 92f 12
I45
+ 18a
I32 21a 86 13a
Normotensive
(n=29) Systolic blood pressure Diastolic blood pressure Hypertensive (n=29) Systolic blood pressure Diastolic blood pressure
96+ l l a
*
+ +
+
80 7“
+
147 24a 97 f 13a
aplo5 mmHg) demonstrated normal diastolic blood pressures (< 90 mmHg). This is in accord with findings reported by other investigators as well as with our own finding that from 20 to 22% of our patients with abnormal clinic blood pressures have normal daytime blood pressures on ABPM. Apart from this particular clinical application, ABPM is a valuable tool in research. For example, ABPM comparisons between black and white subjects find their ambulatory systolic and diastolic blood pressures to be similar in the daytime but not at night. In white subjects, blood pres-
sures tend to be lower than those of the black subjects between the hours of 8:OO p.m. and 8:OO a.m. This underlines the importance of monitoring certain patients at night in order to be sure that their blood pressures are adequately controlled.
Correlations with ABPM and End-Organ Damage Monitoring blood pressure provides data concerning the relationship between blood pressure elevation and endorgan damage. We compared left ventricular mass (LVM) in untreated white and black hypertensive patients in association with their diurnal blood pressure levels. The black patients demonstrated by echocardiography a mean LVM index 9 g/m2 greater than the white patient index. This suggests that the ventricular hypertrophy may be related to the significant elevation in nighttime pressures seen in the black patients. Such an interpretation involves the controversial concept of blood pressure load. Blood pressure load is the percentage of elevated ABPM readings in a given period, that falls above the 140/90 mmHg criterion, or any other arbitrary criterion, of the upper limit of normal blood pressure. The basic assumption is that only a quantitative measure of the “real-time” effect of blood pressure, not random averages of three measurements taken at disparate and nonphysiologic intervals, can assess accurately the effect of high blood pressure on end organs. Table II shows the ABPM-derived blood pressure loads in 126 male and female normal subjects in various age groups. Eleven percent of the approximately 100 systolic readings were greater than 140 mmHg in the male 20-29 year age group, and 30%in those men older than 70 years. There is no significant change in diastolic blood pressure load with aging. No less than about 2 or 3% and no more than 10% of the diastolic blood pressure readings in all age groups were greater than 90 mmHg. The patterns in systolic and diastolic blood pressure loads were similar in the female subjects.
11-8
Clin. Cardiol. Vol. 15 (Suppl. 11), October 1992
TABLE II Mean awake blood pressure load by age (%) (N=126) 20-29 Male Systole Diastole Female Systole Diastole
30-39
40-49
50-59
60-69
270
TABLE 111 Relationship of blood pressure to left ventricular relative wall thickness Correlation coefficient with:
11 6
11 6
6 6
20 9
22 7
30 2
6 2
8 3
6 6
6 4
13 5
22 6
One of the utilities of ABPM is to investigatecontrol of blood pressure and duration of drug action, as well as dose response. We studied hypertensive patients by ABPM under treatment with a long lasting angiotensin-converting enzyme (ACE) inhibitor lisinopril and compared the readings with those in patients receiving placebo. We found that the proportion of diastolicblood pressures greater than 90 mmHg in the placebo group was considerable during daytime but smaller during sleep. Treatment with lisinopril produced a downward shift in these numbers, indicating that the ACE inhibitor was effective. The diastolic blood pressures during sleep were considerably lower in the treated group. Thus, ABPM provides a useful tool to evaluate the effectiveness of treatment. The correlations between blood pressure recordings and end-organ changes, both in the clinic as well as by ABPM, are significant. There are data relating to ABPM and such changes with regard to cardiac function as well as left ventricular hypertrophy. There are very little data, however, correlating ABPM measurements and vascular or renal ~.~ proteinuria and ABPM changes. Two ~ t u d i e scomparing recordings, clearly demonstrate a better correlation than office-measured pressures. Vascular compliance also tends to correlate best with ABPM.7 Devereux et al.* attempted to correlate LVM index with ABPM and office measurement. Table I11 demonstrates the closer correlation they found between ABPM measurements and LVM index than between physician-measured blood pressures and LVM index. Other investigators have reported closer correlations of ABPM versus clinic measurements with LVM. White and associates9observed awake systolic and diastolic blood pressures, comparing ABPM with casual measurement in patients with never-treated hypertension. Such patients reflect a more reliable study population for these comparisons than those who are treated and then removed from treatment for the purposes of study. The office-measured systolic and diastolic blood pressures correlation coefficients with elevated LVM index were .13 and .05, respectively, while the awake ABPM correlation coefficients were .54 and .58, respectively. These results indicate a far better result for ABPM versus casual office measurement. Table IV summarizes their findings as to the correlation coefficients of ABPM and casual measurement with a number of cardiac variables.
Physician-measured Automatic recorder Clinic Work Home Sleep Miscellaneous Total
n
Systolic pressure
Diastolic pressure
100
.24'
.I1
98 60 99 67 74 100
.36' .44c .33c .24a .48" .34c
.3gC .59"
.26h .35" .46" .37c
ap
The Role of Ambulatory Blood Pressure Monitoring in Research PRINCE ZACHARIAH, M.D., Ph.D.
Mayo Clinic Jacksonville,Jacksonville, Florida, USA
Summary: Ambulatory blood pressure monitoring has a significant research role. It documents normal daily blood pressure variations and provides data regarding the relationship between essential hypertension and the circadian cycle. It permits comparisons between normotensive and hypertensive individuals, racial groups, males and females, differingage p u p s , and various clinical categories.It may be a better predictor of hypertension-associatedend-organ changes than clinic or office measurement. It allows quantitative analysis of the high blood pressure load over time. Ambulatory blood pressure monitoring can distinguish between borderline and true hypertension, can evaluate episodic hypertension, and can assess the effectiveness of antihypertensive drug therapy.
Key words: ambulatory blood pressure monitoring, hypertension research, antihypertensive drug efficacy, targetorgan changes Introduction Ambulatory blood pressure monitoring (ABPM) offers special help in at least three basic research areas. It provides data on normal daily blood pressure patterns. It makes possible comparisons of levels of blood pressure between normotensive and hypertensive individuals and patients with other disease states. Finally, ABPM throws light on the possible correlations between levels of blood
Address for reprints: Prince Zachariah, M.D., Ph.D. Mayo Clinic Jacksonville 4500 San Pablo Road Jacksonville, FL 32224, USA
pressure and end-organ changes, particularly with regard to the cardiovascular system.
Normal Blood Pressure Patterns Twenty-four hour blood pressure monitoring reveals a pattern in which early morning blood pressures, starting from around 4:OOor 500 a.m., normally tend to rise steeply, together with the heart rate. During the daytime work hours, blood pressures appear to remain high, spontaneously declining to a fairly low level in the evening. The nadir of blood pressure occurs during early sleep, from about 11:00 p.m. to 3:OO a.m. This diurnal pattern remains the same for normal individuals and for hypertensive patients. The difference is in the severity of the pressure elevations. This diurnal or circadian pattern changes somewhat with age. ABPM data indicate that mean systolic blood pressure begins to rise, starting at about age 40, even in apparently normotensive subjects. Mean diastolic blood pressure tends to remain the same with age, except that in men there is a slight and nonsignificant elevation in the ~ O Sde, clining slowly in the 70s. This has been reported by a number of investigators from different parts of the world.
Hypertensive Blood Pressure Patterns If one uses ABPM to compare borderline hypertensive patients with established hypertensive patients, blood pressures in hypertensives will be predictably high and the circadian pattern of early morning surges and evening declines will be&maintained,but at higher levels than those seen in normotensive subjects. This significantelevation of blood pressure in the morning is of concern, in that hypertensive patients may be at higher risk for myocardial infarction or stroke. The incidence of these and other untoward cardiac events is well-known to be highest in the early morning hours. In one ABPM comparison of age-matched normotensive and hypertensive men, Drayer et al.* found that the difference between daytime and nighttime blood pressures
11-7
P. Zachariah: ABPM in research
TABLEI Comparison of averages of blood pressures (mmHg) obtained during various periods of blood pressure monitoring in normotensive and hypertensive men
Whole-day average
Daytime average
Nighttime average
8:OO-1O:OO A.M. average
120+ 11 75 f 7
126+ l l a 79 f 7a
107 f 10n 67 8*
125 f 11“
140 f 18 92f 12
I45
+ 18a
I32 21a 86 13a
Normotensive
(n=29) Systolic blood pressure Diastolic blood pressure Hypertensive (n=29) Systolic blood pressure Diastolic blood pressure
96+ l l a
*
+ +
+
80 7“
+
147 24a 97 f 13a
aplo5 mmHg) demonstrated normal diastolic blood pressures (< 90 mmHg). This is in accord with findings reported by other investigators as well as with our own finding that from 20 to 22% of our patients with abnormal clinic blood pressures have normal daytime blood pressures on ABPM. Apart from this particular clinical application, ABPM is a valuable tool in research. For example, ABPM comparisons between black and white subjects find their ambulatory systolic and diastolic blood pressures to be similar in the daytime but not at night. In white subjects, blood pres-
sures tend to be lower than those of the black subjects between the hours of 8:OO p.m. and 8:OO a.m. This underlines the importance of monitoring certain patients at night in order to be sure that their blood pressures are adequately controlled.
Correlations with ABPM and End-Organ Damage Monitoring blood pressure provides data concerning the relationship between blood pressure elevation and endorgan damage. We compared left ventricular mass (LVM) in untreated white and black hypertensive patients in association with their diurnal blood pressure levels. The black patients demonstrated by echocardiography a mean LVM index 9 g/m2 greater than the white patient index. This suggests that the ventricular hypertrophy may be related to the significant elevation in nighttime pressures seen in the black patients. Such an interpretation involves the controversial concept of blood pressure load. Blood pressure load is the percentage of elevated ABPM readings in a given period, that falls above the 140/90 mmHg criterion, or any other arbitrary criterion, of the upper limit of normal blood pressure. The basic assumption is that only a quantitative measure of the “real-time” effect of blood pressure, not random averages of three measurements taken at disparate and nonphysiologic intervals, can assess accurately the effect of high blood pressure on end organs. Table II shows the ABPM-derived blood pressure loads in 126 male and female normal subjects in various age groups. Eleven percent of the approximately 100 systolic readings were greater than 140 mmHg in the male 20-29 year age group, and 30%in those men older than 70 years. There is no significant change in diastolic blood pressure load with aging. No less than about 2 or 3% and no more than 10% of the diastolic blood pressure readings in all age groups were greater than 90 mmHg. The patterns in systolic and diastolic blood pressure loads were similar in the female subjects.
11-8
Clin. Cardiol. Vol. 15 (Suppl. 11), October 1992
TABLE II Mean awake blood pressure load by age (%) (N=126) 20-29 Male Systole Diastole Female Systole Diastole
30-39
40-49
50-59
60-69
270
TABLE 111 Relationship of blood pressure to left ventricular relative wall thickness Correlation coefficient with:
11 6
11 6
6 6
20 9
22 7
30 2
6 2
8 3
6 6
6 4
13 5
22 6
One of the utilities of ABPM is to investigatecontrol of blood pressure and duration of drug action, as well as dose response. We studied hypertensive patients by ABPM under treatment with a long lasting angiotensin-converting enzyme (ACE) inhibitor lisinopril and compared the readings with those in patients receiving placebo. We found that the proportion of diastolicblood pressures greater than 90 mmHg in the placebo group was considerable during daytime but smaller during sleep. Treatment with lisinopril produced a downward shift in these numbers, indicating that the ACE inhibitor was effective. The diastolic blood pressures during sleep were considerably lower in the treated group. Thus, ABPM provides a useful tool to evaluate the effectiveness of treatment. The correlations between blood pressure recordings and end-organ changes, both in the clinic as well as by ABPM, are significant. There are data relating to ABPM and such changes with regard to cardiac function as well as left ventricular hypertrophy. There are very little data, however, correlating ABPM measurements and vascular or renal ~.~ proteinuria and ABPM changes. Two ~ t u d i e scomparing recordings, clearly demonstrate a better correlation than office-measured pressures. Vascular compliance also tends to correlate best with ABPM.7 Devereux et al.* attempted to correlate LVM index with ABPM and office measurement. Table I11 demonstrates the closer correlation they found between ABPM measurements and LVM index than between physician-measured blood pressures and LVM index. Other investigators have reported closer correlations of ABPM versus clinic measurements with LVM. White and associates9observed awake systolic and diastolic blood pressures, comparing ABPM with casual measurement in patients with never-treated hypertension. Such patients reflect a more reliable study population for these comparisons than those who are treated and then removed from treatment for the purposes of study. The office-measured systolic and diastolic blood pressures correlation coefficients with elevated LVM index were .13 and .05, respectively, while the awake ABPM correlation coefficients were .54 and .58, respectively. These results indicate a far better result for ABPM versus casual office measurement. Table IV summarizes their findings as to the correlation coefficients of ABPM and casual measurement with a number of cardiac variables.
Physician-measured Automatic recorder Clinic Work Home Sleep Miscellaneous Total
n
Systolic pressure
Diastolic pressure
100
.24'
.I1
98 60 99 67 74 100
.36' .44c .33c .24a .48" .34c
.3gC .59"
.26h .35" .46" .37c
ap
