Chronobiology Inlernational Vol. 8, No. 6, pp. 45 1-459 0 1991 International Society of Chronobiology
Circadian Blood Pressure Rhythm in Primary and Secondary Hypertension
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Martin Middeke, Matthias KlugIich, and Heinrich Holzgreve Medical Policlinic, University of Munich, Munich, Germany
Summary: Circadian blood pressure variability was recorded in patients with primary hypertension and with different forms of secondary hypertension using ambulatory 24-h blood pressure measurement. A group of 20 patients with different forms of secondary hypertension was compared with a matched group of patients with primary hypertension. Although the mean 24-h blood pressure was not different between the two groups, the patients with secondary hypertension had significantly higher systolic blood pressure during sleep and higher systolic and diastolic blood pressure in the early morning, compared with the primary hypertension group. This nocturnal blood pressure fall was then investigated in various groups of patients with different forms of secondary hypertension and compared with normotensives and patients with primary hypertension. Patients with mild primary hypertension (n = 152) and with severe primary hypertension (n = 30) had the same blood pressure fall (14- 16 mm Hg systolic and diastolic) during the night (23:OO-05:OO h) as normotensives (n = 20). However, in patients with renoparenchymal hypertension (n = 29), renovascular hypertension (n = 20), hyperaldosteronism (n = 6), and hyperthyroidism (n = 14), the nocturnal blood pressure fall was significantly (p < 0.01) reduced. One patient with coarctation ofthe aorta and nine patients with primary hyperparathyroidism and elevated blood pressure had a normal circadian blood pressure profile with a normal nocturnal blood pressure fall. The heart rate decrease during the night was equal in all patient groups. Ambulatory blood pressure measurement allows blood pressure recording under everyday conditions, including nighttime. In primary hypertension the blood pressure variability exhibits the same circadian variation as in normotension, showing a marked nocturnal fall. However, in different forms of secondary hypertension, blood pressure shows a blunted circadian curve. This could have important diagnostic and therapeutic implications. Key Words: Ambulatory blood pressure measurement-Primary hypertension-Secondary hypertension.
After the early description of a diurnal blood pressure variation by Zadek (1) in 1881, Howell and Hill (2,3) observed the nocturnal fall of blood pressure in 1897 and Received July 7, 1991; accepted with revisions July 16, 1991. Address correspondence and reprint requests to Dr. M. Middeke, Medical Policlinic, Pettenkoferstr. 8a, D-8000 Munich 2, Germany.
45 1
452
M. MIDDEKE ET AL.
Chronobiol Int Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
FIG. 1. Chronobiological studies in 1922. Katsch and Pansdorf reported on “the movement of blood pressure during sleep” (4).By measuring blood pressure through the wall, they observed abnormal fluctuations during the night in patients with uremia.
1899. Thus, the main principles of the diurnal blood pressure rhythm were characterized as early as a hundred years ago. Katsch and Pansdorf(4) were the first to describe an abnormal blood pressure rhythm in five uremic patients. They measured the blood pressure through a wall separating them from the patient using an extended stethoscopetube (Fig. 1). Bock and Kreuzenbeck (5) used intraarterial blood pressure recording to determine circadian blood pressure variability. They observed a blunted 24-h rhythm in patients with malignant hypertension. In recent years several groups (6-9) described a disturbed circadian blood pressure rhythm in some secondary forms of hypertension using indirect ambulatory blood pressure measurement (ABPM). We investigated blood pressure profiles in normotensives, in patients with primary hypertension and different forms of secondary hypertension.
PATIENTS AND METHODS Study A A group of 20 patients with different forms of secondary hypertension comprising renovascular (n = 8), renoparenchymal (n = 8) hypertension, and primary hyperaldosteronism (n = 4) was compared with a group of 20 patients with primary hypertension. The secondary hypertension group included all patients with proven secondary hypertension seen in our hypertension unit during 1988. The patients with primary hypertension were matched with respect to mean 24-h blood pressure, age, and treatment status (Table 1).
Study B All patients with proven secondary hypertension, including all hypertensive patients with hyperthyroidism and primary hyperparathyroidism who underwent ABPM in our outpatient hypertension unit, were included in the study. They were compared with a normotensive group and two groups of patients, one group with Chrunobiol In[, Vul. 8,No.6, 1991
453
ABPM IN PRIMARY AND SECONDARY HYPERTENSION TABLE 1. Characteristics of 20 patients with primary hypertension and 20 patients with secondary hyperrension: age, gender, treatment status, and blood pressure values recorded with ABPM
Chronobiol Int Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
Hypertension
Primary
Secondary
20 5 6 + 11 3/17 15/5 13 2
Number Age (years) Gender (female/male) Treateda/untreated Morning and evening dose Single morning dose Blood pressure (ABPM) systolic/diastolic k SD (mmHg) 24-hr mean Daytime (06:OO- 18:OO h) Nighttime ( 1 8:OO-06:OO h) Sleeping period (0O:OO-03:OO h) 06:OO h
20 51 k 10 NS 6/14 15/5 12 3
* * *
10/9 153/97 156/100 f 9/8 149/92 14/11 138/83 15/12' 142/88 14/9'
155/97 t 15/10 155/99 k 15/9 154/95 -+ 14/10 150/90 +_ 16/11' 163/100 k 16/14d
+_
The treatment consisted of &blockers, ACE inhibitors, diuretics, and calcium-channel blockers. bpe0.001. 'p i0.001 only for diastolic blood pressure as compared to daytime blood pressure in the same group. p c 0.001 at 6:OO a.m. between the two groups.
-P FIG. 2. Twenty-four-hour blood pressure curves (systolic and diastolic+SD)in20patientswithpnmary hypertension and in 20 patients with different forms of secondary hypertension.
35
2 5
Primary Hypertension (n=20)
-
' ' ' '
210
' ' ' ' ' ' ' '
' '
' ' ' ' ' ' '
'
!a
g
2
4
175
-
4 + + + + 4
4 4
*,,++
+ '
+ ' * 4 +
1200
'
+
4-
2400 h
Chronobiol Int, Val. 8, No. 6, I991
M. MIDDEKE ET AL.
454
Chronobiol Int Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
TABLE 2. Treatment status Untreated
Single morning
Morning and evening dose
20
0
0
152 30
0 0
0 0
7 5 3 8 6 I
5 3 0 0 0 0
17 12 3 6 3 0
Normotensives Primary hypertension Mild Severe Secondary hypertension Renoparenchymal Renovascular H yperaldosteronism Hyperthyroidism Hyperparathyroidism Coarctation of the aorta
The antihypertensive treatment consisted of ACE inhibitors, calcium-channel blockers, &blockers, and diuretics.
mild and one with severe primary hypertension (Tables 2 and 3). Ambulatory blood pressure was measured over 25 h using a fully automatic recorder (SpaceLabs ABP 90202 and 90207; SpaceLabs, Redmont, WA, U.S.A.). All patients' blood pressure was measured every 20 min between 06:OO and 0O:OO h, and every 40 min between 0O:OO and 06:OO h. The time of medication and the sleeping periods were documented by the patients. The mean values and standard deviations (SD) of systolic and diastolic blood pressure over 24 h, between 06:OO and 18:OO h; 18:OO and 06:OO h; 0O:OO and 03:OO h; and at 06:OO h were calculated in the matched groups (Study A). The nocturnal blood pressure fall (blood pressure during 06:OO-22:OO h minus blood pressure during 23:OO-05:OO h) was calculated in all other groups of Study B using the statisti-
TABLE 3. Nocturnal (23:OO-05:OO h) blood pressurefall (mm Hg)
and heart rate decrease (beats/min)
Normotensive Primary hypertension Mild Severe Secondary hypertension Renoparenchymal Renovascular H yperaldosteronism Hyperthyroidism Hyperparathyroidism Coarctation of the aorta
n
Systolic
Diastolic
Systolic plus diastolic
Heart rate
20
15
14
29
10
152 30
14
14 14
28 30
11 11
29 20 6
6 7 2
14
6 16 17
15" 18' 10" 4"
8 11 11 9
32 32
12
9 1
16
9 11
8 8 16 15
=p
Circadian Blood Pressure Rhythm in Primary and Secondary Hypertension
Chronobiol Int Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
Martin Middeke, Matthias KlugIich, and Heinrich Holzgreve Medical Policlinic, University of Munich, Munich, Germany
Summary: Circadian blood pressure variability was recorded in patients with primary hypertension and with different forms of secondary hypertension using ambulatory 24-h blood pressure measurement. A group of 20 patients with different forms of secondary hypertension was compared with a matched group of patients with primary hypertension. Although the mean 24-h blood pressure was not different between the two groups, the patients with secondary hypertension had significantly higher systolic blood pressure during sleep and higher systolic and diastolic blood pressure in the early morning, compared with the primary hypertension group. This nocturnal blood pressure fall was then investigated in various groups of patients with different forms of secondary hypertension and compared with normotensives and patients with primary hypertension. Patients with mild primary hypertension (n = 152) and with severe primary hypertension (n = 30) had the same blood pressure fall (14- 16 mm Hg systolic and diastolic) during the night (23:OO-05:OO h) as normotensives (n = 20). However, in patients with renoparenchymal hypertension (n = 29), renovascular hypertension (n = 20), hyperaldosteronism (n = 6), and hyperthyroidism (n = 14), the nocturnal blood pressure fall was significantly (p < 0.01) reduced. One patient with coarctation ofthe aorta and nine patients with primary hyperparathyroidism and elevated blood pressure had a normal circadian blood pressure profile with a normal nocturnal blood pressure fall. The heart rate decrease during the night was equal in all patient groups. Ambulatory blood pressure measurement allows blood pressure recording under everyday conditions, including nighttime. In primary hypertension the blood pressure variability exhibits the same circadian variation as in normotension, showing a marked nocturnal fall. However, in different forms of secondary hypertension, blood pressure shows a blunted circadian curve. This could have important diagnostic and therapeutic implications. Key Words: Ambulatory blood pressure measurement-Primary hypertension-Secondary hypertension.
After the early description of a diurnal blood pressure variation by Zadek (1) in 1881, Howell and Hill (2,3) observed the nocturnal fall of blood pressure in 1897 and Received July 7, 1991; accepted with revisions July 16, 1991. Address correspondence and reprint requests to Dr. M. Middeke, Medical Policlinic, Pettenkoferstr. 8a, D-8000 Munich 2, Germany.
45 1
452
M. MIDDEKE ET AL.
Chronobiol Int Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
FIG. 1. Chronobiological studies in 1922. Katsch and Pansdorf reported on “the movement of blood pressure during sleep” (4).By measuring blood pressure through the wall, they observed abnormal fluctuations during the night in patients with uremia.
1899. Thus, the main principles of the diurnal blood pressure rhythm were characterized as early as a hundred years ago. Katsch and Pansdorf(4) were the first to describe an abnormal blood pressure rhythm in five uremic patients. They measured the blood pressure through a wall separating them from the patient using an extended stethoscopetube (Fig. 1). Bock and Kreuzenbeck (5) used intraarterial blood pressure recording to determine circadian blood pressure variability. They observed a blunted 24-h rhythm in patients with malignant hypertension. In recent years several groups (6-9) described a disturbed circadian blood pressure rhythm in some secondary forms of hypertension using indirect ambulatory blood pressure measurement (ABPM). We investigated blood pressure profiles in normotensives, in patients with primary hypertension and different forms of secondary hypertension.
PATIENTS AND METHODS Study A A group of 20 patients with different forms of secondary hypertension comprising renovascular (n = 8), renoparenchymal (n = 8) hypertension, and primary hyperaldosteronism (n = 4) was compared with a group of 20 patients with primary hypertension. The secondary hypertension group included all patients with proven secondary hypertension seen in our hypertension unit during 1988. The patients with primary hypertension were matched with respect to mean 24-h blood pressure, age, and treatment status (Table 1).
Study B All patients with proven secondary hypertension, including all hypertensive patients with hyperthyroidism and primary hyperparathyroidism who underwent ABPM in our outpatient hypertension unit, were included in the study. They were compared with a normotensive group and two groups of patients, one group with Chrunobiol In[, Vul. 8,No.6, 1991
453
ABPM IN PRIMARY AND SECONDARY HYPERTENSION TABLE 1. Characteristics of 20 patients with primary hypertension and 20 patients with secondary hyperrension: age, gender, treatment status, and blood pressure values recorded with ABPM
Chronobiol Int Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
Hypertension
Primary
Secondary
20 5 6 + 11 3/17 15/5 13 2
Number Age (years) Gender (female/male) Treateda/untreated Morning and evening dose Single morning dose Blood pressure (ABPM) systolic/diastolic k SD (mmHg) 24-hr mean Daytime (06:OO- 18:OO h) Nighttime ( 1 8:OO-06:OO h) Sleeping period (0O:OO-03:OO h) 06:OO h
20 51 k 10 NS 6/14 15/5 12 3
* * *
10/9 153/97 156/100 f 9/8 149/92 14/11 138/83 15/12' 142/88 14/9'
155/97 t 15/10 155/99 k 15/9 154/95 -+ 14/10 150/90 +_ 16/11' 163/100 k 16/14d
+_
The treatment consisted of &blockers, ACE inhibitors, diuretics, and calcium-channel blockers. bpe0.001. 'p i0.001 only for diastolic blood pressure as compared to daytime blood pressure in the same group. p c 0.001 at 6:OO a.m. between the two groups.
-P FIG. 2. Twenty-four-hour blood pressure curves (systolic and diastolic+SD)in20patientswithpnmary hypertension and in 20 patients with different forms of secondary hypertension.
35
2 5
Primary Hypertension (n=20)
-
' ' ' '
210
' ' ' ' ' ' ' '
' '
' ' ' ' ' ' '
'
!a
g
2
4
175
-
4 + + + + 4
4 4
*,,++
+ '
+ ' * 4 +
1200
'
+
4-
2400 h
Chronobiol Int, Val. 8, No. 6, I991
M. MIDDEKE ET AL.
454
Chronobiol Int Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
TABLE 2. Treatment status Untreated
Single morning
Morning and evening dose
20
0
0
152 30
0 0
0 0
7 5 3 8 6 I
5 3 0 0 0 0
17 12 3 6 3 0
Normotensives Primary hypertension Mild Severe Secondary hypertension Renoparenchymal Renovascular H yperaldosteronism Hyperthyroidism Hyperparathyroidism Coarctation of the aorta
The antihypertensive treatment consisted of ACE inhibitors, calcium-channel blockers, &blockers, and diuretics.
mild and one with severe primary hypertension (Tables 2 and 3). Ambulatory blood pressure was measured over 25 h using a fully automatic recorder (SpaceLabs ABP 90202 and 90207; SpaceLabs, Redmont, WA, U.S.A.). All patients' blood pressure was measured every 20 min between 06:OO and 0O:OO h, and every 40 min between 0O:OO and 06:OO h. The time of medication and the sleeping periods were documented by the patients. The mean values and standard deviations (SD) of systolic and diastolic blood pressure over 24 h, between 06:OO and 18:OO h; 18:OO and 06:OO h; 0O:OO and 03:OO h; and at 06:OO h were calculated in the matched groups (Study A). The nocturnal blood pressure fall (blood pressure during 06:OO-22:OO h minus blood pressure during 23:OO-05:OO h) was calculated in all other groups of Study B using the statisti-
TABLE 3. Nocturnal (23:OO-05:OO h) blood pressurefall (mm Hg)
and heart rate decrease (beats/min)
Normotensive Primary hypertension Mild Severe Secondary hypertension Renoparenchymal Renovascular H yperaldosteronism Hyperthyroidism Hyperparathyroidism Coarctation of the aorta
n
Systolic
Diastolic
Systolic plus diastolic
Heart rate
20
15
14
29
10
152 30
14
14 14
28 30
11 11
29 20 6
6 7 2
14
6 16 17
15" 18' 10" 4"
8 11 11 9
32 32
12
9 1
16
9 11
8 8 16 15
=p
