AJH
2005; 18:446 – 451
Original Contributions
Circadian Blood Pressure Variation in
Morbidly Obese Hypertensive Patients
Undergoing Gastric Bypass Surgery
Leszek Czupryniak, Janusz Strzelczyk, Maciej Pawlowski, and Jerzy Loba
Background: Impaired blood pressure (BP) variation,
often found in obesity and hypertension, is associated with
increased cardiovascular risk. The effect of obesity surgery
on BP variation is unknown. We performed this study to
investigate the effect of gastric bypass surgery on circadian
BP variation in morbidly obese hypertensive subjects.
Methods: The study group consisted of eight patients
(mean age 35.0 ⫾ 9.1 years), with impaired circadian BP
rhythm. Controls were eight well-matched subjects (34.6 ⫾
9.8 years) with normal BP rhythm. All patients underwent
gastric bypass surgery. The 24-h ambulatory BP measurements were performed before (baseline) and 8 weeks after
gastric bypass surgery.
Results: Mean body weight in the study group and
controls decreased from baseline of 129.0 ⫾ 21.9 kg
and 134.1 ⫾ 27.2 kg to 116.7 ⫾ 21.1 kg (by 9.5% ⫾
2.1%) and 121.6 ⫾ 25.7 kg (by 9.3% ⫾ 1.7%) after the
surgery, respectively (P ⬍ .0001 v baseline). Mean
24-h, daytime, and night-time BP values decreased significantly and similarly in both groups. In the study
group mean 24-h systolic and diastolic BP decreased
from 154.7 ⫾ 12.3 mm Hg and 105.6 ⫾ 8.1 mm Hg to
138.5 ⫾ 9.3 mm Hg and 90.8 ⫾ 6.7 mm Hg and in
controls from 158.2 ⫾ 16.5 mm Hg and 106.2 ⫾ 10.0
mm Hg to 136.3 ⫾ 10.8 mm Hg and 92.9 ⫾ 6.3 mm Hg
(P ⬍ .0001 v baseline), respectively. Circadian BP
rhythm in the study group returned to the normal profile
(mean systolic nocturnal fall increased from 4.0% ⫾
2.4% to 16.4% ⫾ 4.0% and diastolic, from 5.1% ⫾
3.0% to 17.3% ⫾ 5.5%; P ⬍ .0001 v baseline), whereas
it remained normal in the controls.
Conclusions: Surgery-induced body weight loss in
morbidly obese hypertensive subjects with impaired
circadian BP variation is not only associated with BP
reduction, but also with the restoration of normal BP
rhythm. Am J Hypertens 2005;18:446 – 451 © 2005
American Journal of Hypertension, Ltd.
Key Words: Obesity, obesity surgery, circadian blood
pressure variation, blood pressure monitoring, cardiovascular risk.
n human physiology, the night-to-day ratio of mean
blood pressure (BP) is between 0.8 and 0.9, and it
has been accepted to label the persons in whom
mean BP does not fall at night by at least 10% of mean
daytime values as nondippers.1 It is well known that
hypertensive patients occasionally manifest the loss of
normal diurnal variation of BP.2,3 This phenomenon is
even more prevalent in obese patients.4,5 It has been demonstrated that nondippers are at increased risk of endorgan damage, particularly renal and cardiovascular
complications,6,7 on top of typical risk associated with
mere hypertension. As hypertension and obesity themselves are important risk factors for vascular damage, the
need for effective means of reversing physiologic BP
variation, in addition to lowering its elevated values, is
I
apparent. We have previously shown that pharmacologic
treatment may restore normal BP rhythm.8
Gastric bypass is an established surgical method of
obesity treatment.9 Since its introduction in 1963 by Mason, it has gained a strong position among various surgical
methods used in morbidly obese subjects; their number of
gastric bypass surgery exceeded 100,000 annually.10 Gastric bypass is one of the most effective methods for obesity
treatment, also one of the very few leading to maintained
weight loss.9 It has also been shown that this type of
obesity surgery exerts the most significant effect on such
metabolic complications of obesity as hypertension and
diabetes.11 Thus far, no reports on the effect of gastric
bypass-induced weight reduction on impaired BP rhythm
has been published. Therefore, we aimed at assessing
Received July 28, 2004. First decision October 18, 2004. Accepted
October 23, 2004.
From the Departments of Diabetology and Metabolic Diseases (LC,
MP, JL) and General and Transplant Surgery (JS), Barlicki University
Hospital No 1, Medical University of Lodz, Lodz, Poland.
Address correspondence and reprint requests to Dr. Leszek Czupryniak, Barlicki University Hospital No 1, Medical University of Lodz,
Kopcinskiego 22, 90-153 Lodz, Poland; e-mail: [email protected]
0895-7061/05/$30.00
doi:10.1016/j.amjhyper.2004.10.029
© 2005 by the American Journal of Hypertension, Ltd.
Published by Elsevier Inc.
AJH–April 2005–VOL. 18, NO. 4, Part 1
24-h BP RHYTHM AND EFFECT OF GASTRIC BYPASS
447
Table 1. Detailed characteristics of all the patients at baseline and 8 weeks after bariatric surgery
Body mass (kg)
Nondippers
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Dippers
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Change in
body weight
BMI (kg/m2)
Gender
Age
(years)
Height
(m)
At
baseline
After
surgery
kg
%
At
baseline
After
surgery
Female
Female
Female
Female
Female
Male
Male
Male
37
23
46
31
31
48
25
39
1.52
1.74
1.60
1.71
1.70
1.82
1.86
1.71
90
108
124
140
125
155
150
140
77.5
98.5
112.5
131.0
113.0
141.5
135.0
124.5
⫺12.5
⫺9.5
⫺11.5
⫺9.0
⫺12.0
⫺13.5
⫺15.0
⫺15.5
⫺13.9
⫺8.8
⫺9.3
⫺6.4
⫺9.6
⫺8.7
⫺10.0
⫺11.1
39.0
35.7
48.4
47.9
43.3
46.8
43.4
47.9
33.5
32.5
43.9
44.8
39.1
42.7
39.0
42.6
Female
Female
Female
Female
Female
Male
Male
Male
41
23
46
27
33
49
25
33
1.64
1.71
1.68
1.70
1.59
1.79
1.86
1.76
119
112
105
126
115
162
178
156
104.5
102.0
96.0
114.0
102.0
147.0
162.0
145.5
⫺14.5
⫺10.0
⫺9.0
⫺12.0
⫺13.0
⫺15.0
⫺16.0
⫺10.5
⫺12.2
⫺8.9
⫺8.6
⫺9.5
⫺11.3
⫺9.3
⫺9.0
⫺6.7
44.2
38.3
37.2
43.6
45.5
50.6
51.5
50.4
38.9
34.9
34.0
39.4
40.3
45.9
46.8
47.0
BMI ⫽ body mass index.
whether gastric bypass surgery and thus induced weight
loss have any effect on circadian BP variation in morbidly
obese hypertensive subjects with normal or impaired 24-h
BP rhythm.
Methods
Study Population
Study group consisted of eight morbidly obese hypertensive patients (five women, three men, aged from 23 to 48
years, mean 35.0 ⫾ 9.1 years), with impaired circadian BP
rhythm (ie, nondippers), in whom gastric bypass surgery
was performed in the course of their obesity therapy. For
the purpose of this study nondippers were selected from a
cohort of subjects with impaired BP rhythm followed up at
our department for the past 5 years, which means that their
nondipping status was well established at least a year
before the study, as they had their BP variation assessed at
least once in the past. Eight gender-, age-, body weight-,
and antihypertensive treatment-matched morbidly obese
hypertensive patients (five women, three men, aged 23 to
49 years, mean 34.6 ⫾ 9.8 years) with normal BP rhythm
(ie, dippers), in whom gastric bypass was also conducted,
served as controls.
Morbid obesity was defined as a body mass index
(BMI; body mass divided by the height expressed in
meters squared) exceeding 35 kg/m2. Mean baseline body
weight of the study group and controls was 129.0 ⫾ 21.9 kg
and 134.1 ⫾ 27.2 kg, and BMI 44.0 ⫾ 4.7 kg/m2 and 45.2
⫾ 5.5 kg/m2, respectively. The patients’ detailed characteristics are shown in Table 1.
Hypertension was defined as the permanent use of
antihypertensive agents. All patients enrolled into the
study took one to four antihypertensive agents for at least
one year, and they included angiotensin-converting enzyme inhibitors (ACEI; captopril, enalapril, perindopril),
calcium channel blockers (CCB; amlodipine, nitrendipine), ␤-blockers (BB; metoprolol, atenolol), and diuretics
(D; indapamide, aldosteron antagonist, frusemide). The
distribution of the drugs used and their combinations was
as follows: ACEI alone or ACEI⫹D or ACEI⫹CCB or
ACEI⫹D⫹CCB⫹BB, and the numbers of the study group
and control patients treated with them were identical in
both groups: 2/3/2/1 and 2/3/2/1, respectively. After the
surgery the drug doses were decreased in accordance with
BP reduction after surgery-induced weight loss; however,
drugs themselves were not discontinued as we aimed at
keeping the drug-related modification of cardiovascular system function stable to the maximum extent possible. Baseline BP values in both groups are shown in the Table 2.
All the subjects gave their informed consent for the
participation in the study and the protocol was approved
by the Bioethics Committee of the Medical University of
Lodz, Poland.
BP Variation Assessment
The 24-h ambulatory BP measurements (ABPM) assessing circadian BP variation were performed with the use of
a portable automated computer-programmed oscillometric
device, ABP Mobil-O-Graph (I.E.M., Stolberg, Germany),
validated according to British Hypertension Society and
Association for the Advancement of Medical Instrumentation criteria, having obtained B/A grade for systolic and
17.3 ⫾ 5.5*
18.9 ⫾ 6.8†
16.4 ⫾ 4.0*
17.2 ⫾ 5.7†
78.2 ⫾ 4.0*
77.1 ⫾ 5.6*
Nocturnal fall (%) ⫽ [1 ⫺ (night-time/daytime values)] ⫻ 100.
* Significantly different from baseline, P ⬍ .0001; † Significantly different from baseline, P ⬍ .01.
121.2 ⫾ 6.8*
120.0 ⫾ 7.4*
94.6 ⫾ 6.7*
95.1 ⫾ 6.0*
90.8 ⫾ 6.7*
92.9 ⫾ 6.3*
138.5 ⫾ 9.3*
136.3 ⫾ 10.8*
145.0 ⫾ 11.3*
144.9 ⫾ 10.6*
Diastolic
5.1 ⫾ 3.0
15.0 ⫾ 4.1
Systolic
4.0 ⫾ 2.4
13.6 ⫾ 3.2
Diastolic
101.4 ⫾ 5.2
92.8 ⫾ 5.0
Systolic
150.0 ⫾ 11.1
143.1 ⫾ 9.5
Diastolic
106.8 ⫾ 6.3
109.2 ⫾ 7.2
Systolic
156.2 ⫾ 13.2
165.6 ⫾ 16.1
Diastolic
105.6 ⫾ 8.1
106.2 ⫾ 10.0
Systolic
154.7 ⫾ 12.3
158.2 ⫾ 16.5
Measurement at
baseline
Nondipper
Dippers
After surgery
Nondippers
Dippers
24-h (mm Hg)
Daytime (mm Hg)
Night-time (mm Hg)
Nocturnal fall (%)
24-h BP RHYTHM AND EFFECT OF GASTRIC BYPASS
Table 2. Mean (⫾SD) 24-h, daytime, and night-time systolic and diastolic BP values at baseline and after bariatric surgery
448
AJH–April 2005–VOL. 18, NO. 4, Part 1
diastolic measurements.12 Because the monitor was designed to measure BP in individuals whose arm circumference was not more than 49 cm, those with arm
circumference ⱖ50 cm were not included into the study.
Our protocol followed the recommendations of the 1990
Consensus Conference and the latest recommendations of
the British Hypertension Society.13,14 The recorder was set
to take a BP and pulse measurement every 20 min in the
daytime and every 30 min at night. The measurements
were done on working days of average activity. According
to commonly agreed standards,13,14 the daytime period
was defined as the interval between 7 AM and 10 PM and the
night-time period as between 10 PM and 7 AM, which
reflects the habits of the average Polish population. In
addition, the patients were instructed to follow the same
daytime and night-time hours. All measurements were
performed in the outpatient setting, before and after hospital stay associated with the surgery. The ABPM results
were considered adequate for evaluation when the number
of valid readings was equal or exceeded 75% of those
programmed. The reading, editing, and analysis of data
provided by the recorder were done by the Mobil-O-Graph
interface. Each subject underwent two 24-h ABPMs: the
first, within a week before the gastric bypass surgery and
the second, 8 weeks after surgery. Patients, who in their
first measurement, failed to produce minimum 10% decrease in night-time systolic or diastolic BP were diagnosed as nondipper. The second measurement was planned
to be performed after the operation wound healed and
body weight loss occurred, which was decided to be 8
weeks after the surgery. We also arranged for the confirmatory ABPM approximately 1 year after surgery. All
measurements started and finished approximately at 9 AM.
Obesity Surgery
Bariatric surgery is routinely performed for morbidly
obese patients with BMI more than 40 kg/m2. However,
individuals with comorbidities related to obesity such as
diabetes, hypertension, or musculoskeletal problems are
eligible for gastric bypass surgery if their BMI exceeds
35 kg/m2.15
Gastric bypass surgery was performed according to the
Greenville gastric bypass technique, a modification of the
procedure described originally by Mason.15 The surgery
has been described in details elsewhere.16 In short, the
stomach was divided transversely using TA-B 90 stapler
(Autosuture–Tyco Corp., Mansfield, MA) about 3 cm below the cardia. The pouch created from the upper part of
stomach by the staple line had a volume of about 30 to 50
mL. In the next step this compartment was anastomosed
directly with the Roux loop of small bowel created by
division of jejunum, about 40 cm from the ligament of
Treitz. Anastomosis between upper part of stomach and
the loop of jejunum was meticulously hand sewn with
nonabsorbable continuous stitches. The Roux-en-Y je-
AJH–April 2005–VOL. 18, NO. 4, Part 1
24-h BP RHYTHM AND EFFECT OF GASTRIC BYPASS
Body Weight (kg)
200
150
100
non-dippers
dippers
50
0
2
4
6
8
10
12
Months after Gastric Bypass
FIG. 1 Body weight in both studied groups (mean ⫾ SD) during 12
months after gastric bypass surgery. Arrows indicate the time of
24-h ABPMs.
juno-jejunostomy was completed using the absorbable
stitches.
Statistical Analysis
The differences between means of the BP measurements
and body weight within groups, after confirming the normal distribution of the data with Shapiro-Wilk test, were
calculated with the use of a paired, and between groups, an
unpaired Student t test. In instances where data did not
show normal distribution, nonparametric Mann-Whitney
U test was used. Values for P ⬍ .05 were considered
significant. STATISTICA version 5.1 PL software package (Tulsa, OH) was used for the analysis.
Results
Changes in body weight were similar in both groups. Mean
body weight in the study group and controls on 54 ⫾ 5 days
and 53 ⫾ 5 days after the gastric bypass surgery decreased
significantly from 129.0 ⫾ 21.9 kg and 134.1 ⫾ 27.2 kg to
116.7 ⫾ 21.1 kg and 121.6 ⫾ 25.7 kg, respectively (P ⬍
.0001 v baseline). Accordingly, BMI decreased in both
groups by 4.2 ⫾ 0.9 kg/m2 and 4.3 ⫾ 0.8 kg/m2 to 39.8 ⫾
5.0 kg/m2 and 40.9 ⫾ 5.2 kg/m2, respectively. This change
in body weight yielded mean body weight loss of 12.3% ⫾
2.3% (9.5% ⫾ 2.1% of baseline weight) in nondippers and
12.5% ⫾ 2.5% (9.3% ⫾ 1.7%) in dippers. The subjects
continued to lose weight after the study; 6 months after
the surgery they lost on average 22% to 25% of their
baseline body weight (28.5 kg [22.1%] and 34.0 kg
[25.3%], respectively), and 28% to 31% (36.3 kg
[28.1%] and 41.8 kg [31.2%], respectively) 12 months
after the surgery (Fig. 1).
On average, each ABPM provided 62 valid measurements. Second measurement was performed in the study
group and controls on mean 54 ⫾ 5 days and 53 ⫾ 5 days,
respectively, after the surgery. Mean 24-h, daytime, and
night-time BP values decreased significantly and similarly in
both groups. For instance, in nondippers mean 24-h systolic
and diastolic BP decreased from 154.7 ⫾ 12.3 mm Hg and
449
105.6 ⫾ 8.1 mm Hg to 138.5 ⫾ 9.3 mm Hg and 90.8 ⫾ 6.7
mm Hg, respectively, whereas in dippers the respective
values were 158.2 ⫾ 16.5 mm Hg and 106.2 ⫾ 10.0 mm
Hg at baseline and 136.3 ⫾ 10.8 mm Hg and 92.9 ⫾ 6.3
mm Hg at follow-up (P ⬍ .0001 v baseline). Moreover, we
noted that circadian BP rhythm in all patients from the
nondipper group returned to its normal, unblunted profile
(mean systolic nocturnal fall increased from 4.0% ⫾ 2.4%
to 16.4% ⫾ 4.0% and diastolic, from 5.1% ⫾ 3.0% to
17.3% ⫾ 5.5%; P ⬍ .0001 v baseline). In contrast, in the
controls BP rhythm remained normal throughout the study
period, although it might be of interest that the night-time
BP fall—already physiologic—increased in this group,
too: systolic from 13.6% ⫾ 3.2% to 17.2% ⫾ 5.7% and
diastolic from 15.0% ⫾ 4.1% to 18.9% ⫾ 6.8%; P ⬍ .01
v baseline). No significant changes in mean 24-h, daytime,
or night-time heart rate were noted in any of the groups.
To confirm the restoration of BP rhythm, we performed
ABPM 11 to 12 months after surgery. Six of eight study
group patients and five controls agreed to have ABPM
performed at that time, and the ABPM results consistently
showed that all of them remained dippers.
Changes in antihypertensive treatment after surgery
were parallel in both groups, the practice being the decrease of the dosage of the drugs used at baseline (with the
number and type of antihypertensive agents remaining
unchanged), which reflected BP decrease after surgeryinduced body weight loss. Subsequently, as at baseline, at
the end of the study the distribution of antihypertensive
drug classes was similar in both groups. The drug doses,
however, were on average reduced by 50% to 75%, and
the reduction was necessary in all patients and was done
for all drugs.
No significant postoperative complications were noted
in any of the subjects. The detailed results are shown in the
Tables 1 and 2.
Discussion
Loss of nocturnal BP decrease is associated with the
increased risk of stroke, left ventricular hypertrophy, and
silent cerebrovascular damage.17,18 It was shown that nondippers exhibit a higher incidence of cardiovascular morbidity and mortality.19 Obese patients are among those in
whom the phenomenon of nondipping is found more often,
regardless of the presence of hypertension.4,5
Morbid obesity, defined as BMI ⱖ35 kg/m2, is one of
the most important and best documented risk factors for a
variety of diseases, including cardiovascular disease, cancer, heart and respiratory failure, bone degenerative disorders, all leading to poor quality of life and excessive
early mortality.19 In the past two decades bariatric surgery,
with gastric bypass as a most frequently method used,10
has gained significant attention and has now an unquestionable role in the treatment of obesity9,15; also because it
has become an increasingly safe procedure.16
It has been repeatedly shown that even a moderate
450
24-h BP RHYTHM AND EFFECT OF GASTRIC BYPASS
weight loss, around 3% to 5% of initial body weight,
achieved with either surgical or nonsurgical means, results
in a significant reduction of BP. This favorable, concomitant to body weight loss, outcome of bariatric surgery is of
utmost importance as majority of morbidly obese patients
suffer from hypertension, sometimes of considerable severity.20 Our observation confirms this beneficial effect of
body weight loss on BP values.
To the best of our knowledge, no reports on the effect
of surgery-induced body weight loss on BP profile in
subjects with blunted BP rhythm have been published. The
effect of hypocaloric diet on BP variation have been documented,21 and it is of interest that even relatively small
weight reduction achieved with dietary treatment (3.6 to
3.7 kg) had noticeable impact on BP values and rhythm.
Our results clearly show that apart from the decrease in
BP values, gastric bypass surgery eventually leads to early
restoration of normal BP variation. This effect of obesity
surgery on BP regulation adds up to the already long list of
other beneficial results of weight loss-inducing operations.22 It should be noted, nonetheless, that the increase in
night-time BP dip was not confined only to the study
subjects, but also to the control group, where its extent was
less spectacular, but yet noticeable. Moreover, this effect
occurred early in the postoperative course, and was not
closely associated with concomitant BP reduction as the
latter had much weaker relation to BP profile in the control
group. It should be noted that we did not include a placebo
(not treated with surgery) group in our study because of
high reproducibility of ABPM, especially when the number of daily measurements amount to 40 – 60.23 It has
therefore been suggested that there might be no need to use
placebo methods when using ABPM, and in that respect, we
followed the recommendations of Mallion et al.24
Due to the purely clinical design of the study, one can
only speculate on the possible causes of the BP rhythm
restoration we noted. This phenomenon has been attributed to the decrease in sympathetic or increase in parasympathetic activity, decrease in BP volume, or the use of
some pharmacologic agents.2,3,6,8,25 As the BP variation
returned to its normal profile within several weeks after
the surgery, it might be speculated that decreased food
intake, together with decreased salt ingestion might be
responsible not only for the BP decrease, but also by the
reversal of its profile.
Recently we have suggested that endothelial dysfunction might be implicated in the pathogenesis of impaired
BP variation.26 Obesity per se induces endothelial dysfunction; therefore, weight loss might promote improvement in the function of the endothelium and thus help
restore physiologic BP rhythm.27 Improved sleep function
resulting from significant weight loss might be another
explanation of our findings.5,28 Eventually, all of these
changes should translate into the change in autonomic
nervous function activity, which apparently enabled restoration of the normal 24-h BP variation in the morbidly
obese.2,3,6
AJH–April 2005–VOL. 18, NO. 4, Part 1
Another link between gastric bypass and BP regulation
might be suggested by the results of the studies by Kellum
et al,11 and more recently Yamamoto et al29,30 and Clements et al.31 These studies have shown that the secretion of
gastrointestinal hormones, mainly glucagon-like peptide-1
(GLP-1) and gastric inhibitory polypeptide (GIP), is altered after gastric bypass,31 and these hormones may regulate BP acting through central autonomic control sites.30
Further studies in this relatively new area of research
might cast more light on the complicated issue of the
regulation of BP variation.
Our study, however, has some important limitations
and its results should be interpreted with caution. The
study sample was relatively small; however, the observation that BP rhythm was restored in all nondipping morbidly obese patients somewhat makes the results more
reliable. Moreover, it may be argued that changes in
antihypertensive therapy introduced a confounding factor
to the understanding of the results. However, during the
8-week follow-up we decreased the doses of antihypertensive agents so as to avoid clinically significant hypotension in the patients, but we did not change the very drugs
(meaning we neither stopped a drug nor introduced a new
one), therefore we have not influenced the mechanisms
affected by the use of pharmacotherapy. And, more important, despite a decrease in the dosage of antihypertensive treatment, we observed both the decrease in BP values
and the increase in night-time BP fall, which excludes the
effect of the drugs on the restoration of normal BP variation.
In conclusion, surgery-induced body weight loss in
morbidly obese hypertensive subjects with impaired circadian BP variation is not only associated with BP reduction, but also with the restoration of normal BP rhythm.
Whether the latter adds significantly to the therapeutic
profile of bariatric surgery and whether this effect is longlasting remain to be clarified.
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