Comparison of the Ambulatory Blood Pressure Variability in Diabetic Hypertensive Muhammad Rizwan Ishaque et al

Ann. Pak. Inst. Med. Sci. 2009; 5(3): 174-177 174

Original Article


Comparison of the Ambulatory Blood
Pressure Variability in Diabetic
Hypertensive and Non Diabetic
Hypertensive patients


Background: Diabetes mellitus and hypertension are a critical combination for the
development of both macro and microvascular disease. Short term blood pressure (BP)
variability is associated with increased cardiovascular events in both diabetic and non
diabetic subjects. Diabetic patients are particularly prone to have increased BP variability
and its adverse consequences.
Objective: To examine the possible difference in the short-term BP variability assessed as
the standard deviation, between diabetic and non-diabetic hypertensives.
Study Design: Cross sectional study.
Place and Duration: The study was conducted in Diabetic clinic and Cardiology
outpatient department (OPD) of Sheikh Zayed Hospital, Lahore from March 2009 to July
2009.
Patients and Methods: This study examined 60 patients, with 30 diabetic HTN (18 men
and 12 women, mean age 53.54.2 years)and 30 non diabetic HTN (16 men and 14 women,
mean age 47.83.2 years). Their 24 hr ambulatory BP was monitored and the short term BP
variability was assessed as standard deviation from the mean 24 hr systolic and diastolic
BP. The difference between two groups was measured through Independent Sample t
test. P 0.05 was taken as significant.
Results: Diabetic HTN had a significantly greater 24-hr systolic and diastolic BP variability
than nondiabetic HTN (16.83 mmHg vs. 14.60 mmHg, p < 0.04; 15.55 mmHg vs. 12.85 mmHg,
p < 0.03, respectively). Interestingly it was noted that fasting blood glucose level was found
to be raised in patients with increase BP variability.
Conclusion: These results demonstrate that BP variability is increased in diabetic
hypertensives.
Key Words: Dibetes mellitus. Hypertension. BP variability.

Muhammad Rizwan Ishaque*
Sayem Ahmed**
Imran Abid***

*Specialist Registrar
**Trainee Registrar (M.D Cardiology)
***Trainee Registrar (FCPS Cardiology)

Cardiology Department,
Sheikh Zayed Hospital,/ FPGMI,
Lahore.
























Address for Correspondence:
Dr. Muhammad Rizwan Ishaque,
Specialist Registrar,
Cardiology Deptt. Sheikh Zayed/ FPGMI,
Lahore.

Introduction

Diabetes and hypertension are a critical
combination for the development of both macro and
microvascular disease. In people with type II diabetes,
the prevalence of hypertension is 50% at the time of
diagnosis, increasing to 80% in the presence of
microalbuminuria and to more than 90% with
macroalbuminuria.
1

Presently, diabetic patients are rapidly
increasing in numbers, and cardiovascular
complications are the most common cause of death in
patients with diabetes.
2
Thus it would be of considerable
value to identify the precise mechanism involved in the
cardiovascular events associated with diabetes.
Ambulatory blood pressure monitoring has
allowed an easier and more accurate determination of
circadian rhythm of blood pressure under different
pathophysiological conditions. Ambulatory blood
pressure monitoring allows the acquisition of information
not only on the average of 24 hour blood pressure, but
also on the variations that characterize the blood
pressure values in the course of daily life. Ambulatory
blood pressure monitoring has also allowed an easier
and more accurate determination of the circadian
rhythm of the blood pressure under different
pathological conditions, and has enabled to evaluate the
effects of antihypertensive drugs.
3-4

The short term blood pressure variability is
Comparison of the Ambulatory Blood Pressure Variability in Diabetic Hypertensive Muhammad Rizwan Ishaque et al
Ann. Pak. Inst. Med. Sci. 2009; 5(3): 174-177 175
estimated as the standard deviation of beat to beat
blood pressure obtained by intra arterial monitoring or
the standard deviation of non - invasively monitored
ambulatory blood pressure.
5
Blood pressure variability
has been shown to depend on sympathetic vascular
modulation and on changes in arterial dispensability.
Although the pathophysiological significance of blood
pressure variability has not been elucidated in detail yet
previous studies have shown that an increase in systolic
blood pressure variability is associated with progression
of carotid artery wall lesions and the rate of
cardiovascular complications independently of increased
average blood pressure values and suggested that
increased systolic BP variability is an independent
predictor of cardiovascular events in general
population.
6
This circadian rhythm of blood pressure in
patients with diabetes has been found to have a blunted
nocturnal dipping in blood pressure, which is associated
with autonomic neuropathy and nephropathy.
6
The loss of nocturnal dipping in blood pressure
is considered to be the risk factor for the progression of
the nephropathy itself, and to be of prognostic value with
respect to target organ damage and cardiovascular
morbidity in both diabetic and hypertensive patients.
7

However, the factor involved in the blood pressure
variability observed in diabetic patients are not
elucidated and may themselves play an important role in
the cardiovascular complications in diabetic patients.
8,9

More and better evidence on BP variability could lead to
a more precise understanding of the pathogenesis of
hypertension with diabetes.
The aim of this study is to examine the
difference in blood pressure variability between
hypertensive subjects with or without diabetes.

Patients and Methods

The study was conducted in Cardiology
department of Sheikh Zayed Hospital/ Postgraduate
Medical Institute,Lahore during the period of March
2009 to July 2009. A total of 60 hypertensive patients,
30 type2 diabetics (diagnosed for at least 5 years) and
30 non diabetic, were selected. Blood pressure was
optimally (<140/90 mmHg) controlled by
pharmacological treatment in both groups. Individuals
known to have secondary hypertension or chronic renal
failure (Serum creatinine >2mg / dl) were excluded.
Patients with type1 diabetes, type2 diabetics with
serious comorbidity requiring hospitalization and
gestational diabetics were also excluded. After
explaining the nature of study and procedure, and
having informed consent, instructions were given in full
detail. Before taking clinic BP measurement, patients
were asked to relax in a quiet room for 15 minutes.
Blood pressure was then measured in both the arms.
The arm with higher reading was selected if BP in this
arm was 10 mmHg more than the other arm, while the
non dominant side was selected if the difference was
<10 mmHg. The oscillometric ambulatory blood
pressure device (Tonoport V/2 CE 0482, Ref. 2001589-
038) was then applied to the subject for the duration of
24 hours. He / she was also provided with a diary (with
printed instructions in Urdu and English) to write down
his / her activities. Waking hours were from 6 am to 10
pm while sleeping hours were from 10 pm to 6 am. The
device was preset to take readings every 30 minutes
during waking hours and hourly during sleeping hours.
There was an expected margin of error of 20% because
of ambulatory nature of the device. Results were
recorded on a pre designed proforma{ TC \l1 }.
The analysis of the data was performed with
SPSS (Statistical Package for Social Sciences) version
14.
Gender and the drugs being taken were the
qualitative variables of the study, which were presented
as percentages. Age, blood pressure at clinic,
ambulatory blood pressure, and laboratory finding
(S/Creatinine, BUN, S/Albumin, S / Total Protein, S/uric
acid, Fasting Lipid Profile, Fasting Blood Glucose level,
and Hb) were quantitative variables of the study and
were presented as Mean SD.
The difference between two groups was
measured through Independent Sample t test. P
0.05 was taken as significant.

Results

Out of 60 patients, 30 were diabetic HTN (18
men and 12 women, mean age 53.5 years)and 30 non
diabetic HTN (16 men and 14 women, mean age 47.8
years). The comparative results in both groups were as
follows:
Comparison of laboratory findings between the
Diabetic HTN and Non-Diabetic HTN Groups
The diabetic HTN group had a significantly older
age (p = 0.019) and higher fasting blood glucose (p =
0.001) (see Table I). There were no significant
differences for the other laboratory findings between the
two groups
Comparison of findings of ambulatory BP
monitoring between the Diabetic HTN and Non-
Diabetic HTN Groups
On ambulatory BP monitoring, no significant
differences were found between the patients groups
regarding 24-hr, daytime, and nighttime ambulatory
systolic and diastolic average BP.
However, the diabetic HTN group had
significantly higher values of 24-hr systolic and diastolic
BP variability than the non-diabetic HTN group (16.83
mmHg vs. 14.60 mmHg, p =0.04 and, 15.55 mmHg vs.
12.85 mmHg, p = 0.03 respectively ;)

Comparison of the Ambulatory Blood Pressure Variability in Diabetic Hypertensive Muhammad Rizwan Ishaque et al
Ann. Pak. Inst. Med. Sci. 2009; 5(3): 174-177 176
Table I: Demographics of patients
DM/HTN Non-DM/HTN P value
Number of
patients
30 30

AGE 53.54.2 48.73.2 0.019
Serum Total
Proteins
53.54.2 48.73.2 0.019
Serum
creatinine
0.95+0.04 0.88+0.03 0.18
Bloood urea
nitrogen(g/dl)
15.32.5 13.61.6 0.08
Fasting blood
glucose (mg/dl)
124.7+6.9 945.5 0.001
Serum total
cholesterol
(mg/dl)
172 +8.0 1667.0 0.18
Hemoglobin
(g/dl)
13.1+1.0 12.02.3 0.055
Abbreviations: DM = diabetic hypertensives group, non-DM = non-diabetic
hypertensives group;

Table II: Comparison of 24hr systolic BP
variability
DM Non DM P value
16.83(mmHg) 14.60(mmHg) 0.04

Table III: Comparison of 24hr diastolic BP
variability
DM Non DM P value
15.55(mmHg) 12.85(mmHg) 0.03

Discussion

Although sympathovagal balance is reported to
be a major determinant of BP variability in healthy
subjects, BP variability is also affected by
atherosclerotic changes in the vascular wall in patients
with cardiovascular disease.
10
The increase in BP
variability may be partly explained by the diminished
baroreflex function associated with increased stiffness
and reduced compliance of large elastic arteries.
11
In
this respect, BP variability has been attracting attention
as a possible predictable marker for atherosclerotic
disease development, progression, and long-term
prognosis.
12
Several previous studies showed that in
diabetic patients, especially with nephropathy, there was
an absence of nighttime BP falling and decrease in HR
variability due to functional impairments of autonomic
nervous system.
13-15
It was previously reported that
nighttime BP variability is increased in end-stage
diabetic nephropathy patients with coronary artery
disease.
16
In our study, we focused on BP variability and
its affecting factors in hypertensives with diabetes.
The results of this study show that the mean BP
values throughout the day were controlled equally in
both groups. The degree of nocturnal fall of BP was also
similar in both groups and patients of both groups were
classified as non-dippers according to the established
definition. However, interestingly, 24-hr BP variability
was significantly increased in the diabetic HTN group.
Several mechanisms may contribute to the
increase in BP variability in the diabetic HTN group
observed in our study. It is possible that renal functional
state is related to BP variability in connection with
volume state and various presser systems.
17
In addition,
they previously examined a difference in the 24-hr BP
profile between hypertensives with diabetic nephropathy
(DN) and those with non-diabetic glomerulopathy (non-
DN) in an end-stage renal disease population, and
showed that DN patients had a significantly higher
nighttime systolic BP than patients with non-DN in spite
of similar daytime BP levels.
18
As noted, the results of analysis in this study
demonstrated that fasting blood glucose was
significantly and independently related to 24-hr
systolic/diastolic BP variability.
Thus, the results of our study suggested that
fasting bloodglucose, rather than renal functional state,
is one of the determinants of BP variability in
hypertensive subjects, and an elevated blood glucose
level may be a reason for the increased BP variability in
the diabetic HTN group.
Previously, the Ohasama study reported that
age, BP, pulse pressure, and BMI were independently
and positively associated with BP variability in
normotensives.
19

Several other studies also showed BP variability
to be regulated by sympathovagal balance and arterial
distensibility. Therefore, it is possible that BP variability
is directly regulated by blood glucose or indirectly
modulated by the activation of sympathetic nerve activity
induced by hyperglycemia.
Interestingly, hyperglycemia is reported to
increase the activity of local renin-angiotensin system
and expression of angiotensin II type I receptor
expression in vascular wall, promoting the development
of arterial wall hypertrophy and fibrosis.
20

Thus, there is possibility that arterial compliance
was more reduced in diabetic hypertensives than in non-
diabetic hypertensives.
Previous studies showed that elevated fasting
blood glucose is more closely related to brachial-ankle
pulse wave velocity in elderly people
20
and in ARIC
study elevated fasting blood glucose contributed to the
increase in arterial stiffness in middle aged people.


Therefore, elevated fasting blood glucose may
contribute to increased BP variability in hypertensives
through the reduction of arterial compliance. In this
context, the therapeutic maneuvers available, such as
improvement of hyperglycemia by anti-diabetic agents,
may be important for the decrease in BP variability.
20
Thus, we would like to suggest that diabetic
Comparison of the Ambulatory Blood Pressure Variability in Diabetic Hypertensive Muhammad Rizwan Ishaque et al
Ann. Pak. Inst. Med. Sci. 2009; 5(3): 174-177 177
hypertensives need not only BP control but also strict
control of the fasting blood glucose level to efficiently
achieve decrease in BP variability.
Limitations of our study include the small patient
number, the cross sectional analysis, being under
antihypertensive medication, and the lack of
cardiovascular reflex tests to link the increased BP
variability with autonomic neuropathy. Further study on
BP variability in diabetic hypertensives without
nephropathy and normotensive patients with diabetes
mellitus, as well as on the interaction between fasting
blood glucose and BP variability, is needed to clarify
these important issues.

Conclusion

Diabetic hypertensives as compared to their non
diabetic counterparts show increased 24 hour BP
variability. Raised fasting blood glucose levels are
associated with increased BP variability in diabetic
patients.
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