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ISSN: 1064-1963 (print), 1525-6006 (electronic)
ORIGINAL ARTICLE
Abstract Keywords
Aim: Although exaggerated blood pressure responses (EBPR) to exercise have been related to Diabetes mellitus, exercise treadmill test,
future hypertension and masked hypertension (MHT), the relationship between exercise exercise capacity, masked hypertension,
capacity and MHT remains unclear. A sedentary life style has been related to increased sedentary lifestyle
cardiovascular mortality, diabetes mellitus (DM), and hypertension. In this study, we aimed to
examine the relationship between exercise capacity and MHT in sedentary patients with DM. History
Methods: This study included 85 sedentary and normotensive patients with DM. Each patient’s
daily physical activity level was assessed according to the INTERHEART study. All patients Received 3 November 2012
underwent an exercise treadmill test, and exercise duration and capacity were recorded. Blood Revised 30 November 2012
pressure (BP) was recorded during all exercise stages and BP values 200/110 mmHg were Accepted 28 February 2013
accepted as EBPR. MHT was diagnosed in patients having an office BP 5140/90 mmHg and Published online 17 May 2013
For personal use only.
a daytime ambulatory BP 4135/85 mmHg. Patients were divided into two groups according
to their ambulatory BP monitoring (MHT and normotensive group).
Results: The prevalence of MHT was 28.2%. Exercise duration and capacity were lower in the
MHT group than in the normotensive group (p50.05) and were negatively correlated with age,
HbA1c, mean daytime BP, and mean 24 hour BP. Peak exercise systolic BP and the frequency
of EBPR were both increased in the MHT group (25.0% and 8.1%, respectively, p ¼ 0.03).
According to a multivariate regression, exercise capacity (OR: 0.61, CI95%: 0.39–0.95, p ¼ 0.03),
EBPR (OR: 9.45, CI95%: 1.72–16.90, p ¼ 0.01), and the duration of DM (OR: 0.84, CI95%:
0.71–0.96, p ¼ 0.03) were predictors of MHT.
Conclusion: Exercise capacity, EBPR, and the duration of DM were predictors of MHT in
sedentary subjects with DM.
Introduction MHT (6–10). Some studies have used the exercise treadmill
test (ETT) to evaluate DM and non-DM patients for MHT and
The combination of diabetes mellitus (DM) and hypertension
have found that an exaggerated blood pressure response to
(HT) is associated with high mortality rates due to cardio-
exercise (EBPR) is a determinant of future HT and MHT.
vascular events (1). Masked hypertension (MHT), diagnosed
in patients with office blood pressures (BP) 5140/90 mmHg
However, the relationship between exercise capacity and 14
20
MHT remains unclear (11,12).
and daily mean ambulatory BP 4135/85 mmHg (2), is related
Sedentary lifestyle is an important public health problem
to target organ damage, sustained HT, and increased cardio-
that is often neglected. Seven percent of DM cases and 6% of
vascular mortality (3,4). While the incidence of MHT is
coronary heart cases can be attributed to a sedentary lifestyle
between 7% and 17% in the general population (5), the
(13,14). However, studies of patients with sedentary lifestyles
incidence rate for MHT in DM patients has been reported to
have been extremely limited. Most studies investigating the
be as high as 47% (1). Due to its prevalence, close association
relationship between MHT and EBPR have not assessed
with other risk factors, and adverse cardiovascular events,
the daily physical activity levels of the patients. These studies
MHT can be defined as a major health problem (6). As a
enrolled a heterogeneous patient group including both
result, many studies have investigated the determinants of
sedentary and/or physically active subjects. As a result, the
current literature yields contradictory results regarding the
exercise capacity of patients with MHT (15). Also, the role
of exercise capacity in predicting MHT remains unclear.
Correspondence: Hakan Akilli, M.D., Necmettin Erbakan Universitesi
In the present study, we aimed to investigate the relationship
Meram Tip Fakultesi Kardiyoloji Sekreterligi, Meram, 42090 Konya,
Turkey. Tel: 0090-332-2237941. Fax: 0090-332-2236181. E-mail: between exercise capacity and MHT in a homogeneous group
hakanakilli@hotmail.com including sedentary patients with type 2 DM.
10 H. Akilli et al. Clin Exp Hypertens, 2014; 36(1): 9–16
of HT or antihypertensive treatment administered for any 3 minutes, it was measured again by a doctor. Resting BP
reason (e.g. palpitations, beta blockers due to arrhythmia, was measured with a mercury sphygmomanometer (ERKA,
angiotensin-converting enzyme inhibitors for renal protection, Kallmeyer Medizintechnik GmbP Co. KG, Bad Tolz,
diuretics due to edema), atrial fibrillation, a left bundle branch Germany) over the brachial artery. The appropriate cuff size
block, those having a pacemaker, orthopedic problems, or a was used for each patient. A total of four average measure-
systemic disease that would prevent completion of an ETT ments were taken during both visits, and the baseline SBP
(e.g. chronic obstructive pulmonary disease, renal failure) and DBP values were determined. All of the mean office
were excluded from the study. Patients over 70 years of age BP values for the patients included in this study were below
and patients who refused to participate in the study were also 140/90 mmHg.
excluded.
For personal use only.
each patient’s non-dominant arm, and the device was Whitney U tests were used for comparing differences between
programmed to take a measurement every 20 minutes two groups of non-parametrically distributed variables. A
during the day and every 30 minutes at night. Recordings multiple stepwise logistic regression analysis was performed
For personal use only.
for each subject were accepted if more than 80% of the raw to detect the predictors of MHT using the backward elimin-
data were valid. Average values were calculated for two ation method. The elimination criterion was defined as
periods in a single day: a six-hour period between 1 AM and having a probability above 0.10. The following covariates
6 AM (nighttime) and a 12-hour period between 9 AM and were entered into the regression model: age, gender, BMI,
9 PM (daytime). total cholesterol, HbA1C, duration of DM (years), office
SBP, exercise duration, exercise capacity, EBPR status and
Blood analysis SBP at peak exercise.
Blood samples were taken during the second visit after A power analysis was performed using the Minitab 16
12 hours of fasting. Blood samples were analyzed for fasting packet program. The sample volume was calculated as 85 to
plasma glucose, total cholesterol, triglycerides, high density determine the difference between MET and other values.
lipoprotein cholesterol (HDL-C), creatinine, complete blood The MedCalc 9.2.0.1 packet program was used to obtain
count and HbA1c. Biochemical and hematologic parameters receiver operating curves (ROC) and to determine the
were measured using an Olympus AU 600 auto-analyzer specificity, sensitivity, and negative and positive predictive
(Olympus Optical Co., Ltd., Schimatsu-Mishima, Japan) values for the exercise capacity and exercise duration
and a Bayer Advia 120 CBC counter (New Jersey, USA). parameters associated with MHT.
Total cholesterol, triglycerides, and HDL-C were analyzed
enzymatically with a Hitachi 747 analyzer (Japan). Low Results
density lipoprotein cholesterol (LDL-C) was calculated using Eighty-five sedentary patients with type 2 DM who had
the Friedewald formula (18), while creatinine clearance was resting BP 5140/90 mmHg and who were not receiving any
calculated with the Cockroft–Gault formula (19). antihypertensive therapies were included in this study. Based
on the ABPM results, the prevalence of MHT was determined
Statistical analysis
to be 28.2% (MHT group, n ¼ 24). The ABPM averages of the
All statistical analyses were performed using SPSS software remaining 61 patients were within normal limits (normoten-
version 15.0 (SPSS, Chicago, IL). Data were presented as sive group). The duration of DM within the MHT group
mean SD. The distribution for each variable was analyzed was significantly shorter. In addition, the MHT group had
using the Kolmogorov–Smirnov test. The Pearson’s correl- higher BMI and lower HDL-C levels. Demographic charac-
ation test was used for normally distributed variables while teristics and laboratory findings for the two groups are
the Spearman correlation test was used for nonparamterically summarized in Table 1.
distributed variables. The relationship between categorical Exercise duration (min) and exercise capacity (METs)
variables was determined using the 2-test. Independent values were lower in the MHT group when compared to
student’s t tests were used for comparing differences between the normotensive group [exercise duration: 8.0 1.9 versus
two groups of normally distributed variables, while Mann 9.2 1.8 min (p ¼ 0.05), respectively; and exercise capacity:
12 H. Akilli et al. Clin Exp Hypertens, 2014; 36(1): 9–16
Discussion
To our knowledge, the present study is the first to examine
the role of exercise capacity in identifying MHT in sedentary
DM subjects. A lower exercise capacity, shorter exercise
duration and an increased EBPR frequency were found in the
Figure 2. A comparison of exercise duration, exercise capacity and
EBPR. EBPR: Exaggerated blood pressure response to exercise.
MHT group when compared to the normotensive group.
The present study also revealed that exercise capacity, EBPR
and duration of DM were independent predictors of MHT in
9.1 1.8 versus 10.4 1.6 METs (p ¼ 0.02), respectively]. sedentary type 2 DM subjects.
The frequency of EBPR was significantly greater in the MHT While the prevalence of MHT is approximately 10% in the
group (25.0%) as compared to that of the normotensive group general population (20), rates of 30–47% have been reported
(8.2%) (p ¼ 0.03) (Figure 2). DBP values were higher in the among patients with DM, meaning that DM patients have a 3-
MHT group than in the normotensive group during the pre-ETT to 4-fold higher MHT incidence (1,21). In our study, the
period, and during stages 1, 2 and 3. The two groups had similar incidence of MHT was 28.2%, a value consistent with the
DBP values at peak exercise capacity and during the 3rd minute literature. MHT has been reported to be associated with many
of the recovery period. The pre-ETT and peak exercise SBP factors, such as age, male gender, smoking, alcohol con-
values were higher in the MHT group (Figure 3). The ABPM sumption, increased BMI, high-normal office BP, DM and
findings of the groups are displayed in Table 2. stress (6,22–26). In our study, both SBP and DBP were often
Exercise duration and exercise capacity were negatively higher in the MHT group when compared to the normotensive
correlated with age, HbA1c, mean daytime BP and mean group, but the differences were not statistically significant.
24 hour BP (Table 3). While univariate logistic regression Lifestyle and metabolic risk factors are also often associated
analysis revealed BMI as a predictor of MHT (OR: 1.17, CI with MHT (27–29). In this study, patients with MHT had
95%: 1.02–1.30, p ¼ 0.03), this finding was not observed with a higher BMI and lower HDL-C levels than those in the
multivariate logistic regression analysis. Multivariate logistic normotensive group. Previous studies have demonstrated
regression analysis identified DM duration, exercise capacity an association between obesity and physical inactivity (30).
DOI: 10.3109/10641963.2013.783047 Exercise capacity in predicting masked hypertension 13
Figure 3. A comparison of treadmill exercise results. (a) Systolic BP (mmHg), (b) Diastolic BP (mmHg), (c) Heart rate (beats/min). BP: Blood
pressure, *p50.05, **p50.01.
Table 2. Ambulatory BP characteristics. Table 4. The independent predictors of MHT in the multiple stepwise
Clin Exp Hypertens Downloaded from informahealthcare.com by Universitaet Zuerich on 12/28/14
Mean ABP 81.4 5.3 93.3 4.2 0.001 Exercise time 0.77 2.16 0.55–8.52 0.27
SBP 114.9 10.0 130.9 12.6 0.001 Exercise capacity 1.22 0.29 0.07–1.33 0.08
Night DBP 65.3 6.2 74.0 6.4 0.001 EBPR 2.12 8.30 1.40–15.86 0.02
Mean ABP 77.1 7.1 87.8 7.6 0.001 SBP at the peak exercise 0.001 1.00 0.98–1.03 0.98
Early morning SBP 123.0 8.5 128.6 7.5 0.11 The last step
DBP 75.3 9.0 75.4 9.9 0.97 Duration of DM 0.23 0.84 0.71–0.96 0.03
Systolic dipping (%) 6.3 7.0 6.7 8.2 0.68 Exercise capacity 0.49 0.61 0.39–0.95 0.03
Diastolic dipping (%) 10.3 8.1 11.9 7.0 0.79 EBPR 2.20 9.45 1.72–16.90 0.01
Bold values indicate significant p values. Bold values indicate significant p values.
MHT: Masked hypertension; BP: Blood pressure; SBP: Systolic blood BMI: Body mass index; DM: Diabetes mellitus; HDL-C: High-density
pressure; DBP: Diastolic blood pressure; ABP: Ambulatory blood lipoprotein cholesterol; SBP: Systolic blood pressure; EBPR:
pressure Exaggerated blood pressure response to exercise.
Exercise Exercise
Time Capacity
(n ¼ 85) (n ¼ 85)
ra,b p r p
a a
Age 0.30 0.01 0.30 0.01
BMI 0.10a 0.39 0.08a 0.45
Duration of DM 0.04b 0.72 0.03b 0.81
24 hour SBP 0.25a 0.03 0.24a 0.04
24 hour DBP 0.12a 0.33 0.13a 0.27
24 hour mean BP 0.23a 0.04 0.24a 0.04
Daytime SBP 0.19a 0.10 0.20a 0.06
Daytime DBP 0.48a 0.66 0.83a 0.46
Daytime mean BP 0.22a 0.04 0.23a 0.04
Systolic dipping 0.24a 0.04 0.19a 0.10
Diastolic Dipping 0.19a 0.10 0.15a 0.19
Total cholesterol 0.09a 0.42 0.06a 0.59
HDL-C 0.10a 0.36 0.04a 0.72
LDL-C 0.13a 0.25 0.08a 0.47
Triglyceride 0.16b 0.15 0.14b 0.20
HbA1c 0.32a 0.003 0.27a 0.01
Figure 5. Receiver operating curve of exercise duration for the masked values were significantly lower in the MHT group than in the
hypertension. normotensive group, and exercise capacity was an independ-
ent predictor of MHT. Previous studies have demonstrated
that low exercise capacity is associated with cardiovascular
Although the mechanism behind physical inactivity in obesity events and mortality in the general population (36) as well as
remains unclear, multifactorial etiology has been advocated in DM patients (37,38). MHT has been similarly associated
(31,32). In our study, univariate logistic regression analysis with increased mortality and adverse cardiovascular events
revealed BMI as a predictor of MHT; however, multivariate (4,39). However, the effect of MHT on exercise capacity is
logistic regression analysis could not demonstrate such unknown for patients with DM. Our study shows that the
an association. In addition, there was no linear relationship incidence of MHT is 57.9% among patients with exercise
For personal use only.
between exercise capacity and BMI. This finding supports the capacities 59.0 METs and is 19.7% for those with exercise
idea that the association between reduced exercise capacity capacities 9.0 METs. Previous studies have shown that
and obesity is multifactorial. Obesity may contribute to MHT can cause left ventricular hypertrophy (LVH) in patients
reduce exercise capacity in the MHT group. On the other with DM (3,22). A relationship between LVH and low
hand, an important predisposing factor of obesity has a exercise capacity has also been previously shown (40). We
sedentary lifestyle and physical inactivity in this group. could not find any data regarding the relationship between
Hence, there is a need forcomprehensive studies in this area. low exercise capacity and MHT in the current literature.
Interestingly, the duration of DM for patients with MHT Many studies have shown impaired diastolic function in
was about 2.5 years shorter than that of the normotensive DM patients (41,42). In the light of the current literature,
patients. Regression analysis identified the duration of DM as we hypothesize that MHT increases the left ventricular (LV)
an independent predictor of MHT. Previous studies have mass in DM patients, and diastolic dysfunction may be
revealed that at 6-year follow-up, 35% of patients with MHT worsened during exercise, resulting in reduced exercise
had developed sustained HT (33). Patients with a long DM capacity.
duration might have been excluded from the study due to the
types of drugs they were required to use, such as angiotensin-
Limitations of the study
converting enzyme inhibitors/angiotensin-receptor blockers
and especially those used to protect against the risk of A major limitation of this study was the small number of
nephropathy. Therefore, we hypothesize that the duration patients. However, our study is among those with the largest
of DM is shorter in the MHT group. patient sample size in the current literature and investigates
ETT is commonly used in clinical practice to predict MHT. the relationship between ETT and MHT. Our study sample
Although there are studies reporting the use of ETT to predict included both sexes. Because of the relatively small number
MHT in the general population, there are very limited data of subjects in the MHT group, a subgroup analysis according
in the DM population (11,12,14,34). However, MHT is more to gender was not performed. However, a regression model
common among patients with DM. In a study of 61 patients showed that reduced exercise capacity may predict MHT
with type 2 DM, Kramer et al. determined that peak SBP and independently from gender. The power of the study appears to
DBP values were higher among MHT patients during the ETT be sufficient. However, to generalize the results to all DM
(14). Similarly, in our study, peak SBP values were higher in patients, larger sample studies are needed. It is not reasonable
the MHT group while both groups had similar DBP values. to generalize our results to all DM patients since our study
Kramer et al. found that the MHT and normotensive groups was limited to sedentary individuals. Because of potential
had similar exercise capacities, although exercise periods false negative results from the ETT, the effects of silent
were not specified in the publication. The largest drawback of myocardial ischemia on the study results remain unclear.
the study by Kramer et al. was that the patients’ daily physical LV mass values and diastolic function, determined using
activity levels were not rated. The mean BMI of patients with echocardiography in diabetic cardiomyopathy patients, were
DOI: 10.3109/10641963.2013.783047 Exercise capacity in predicting masked hypertension 15
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