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ORIGINAL ARTICLE
Division of Cardiology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei,
Taiwan, ROC; 2Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei,
Taiwan, ROC; 3Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei,
Taiwan, ROC; 4Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, ROC;
5
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC and 6Institute of
Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC
Keywords: ambulatory blood pressure monitoring; cardiovascular events; mortality; pulse pressure
Introduction
The relation between blood pressure (BP) and the
risk of cardiovascular disease (CVD) is direct, graded
and continuous over a wide range.1 Although BP
measurement at the clinic is currently the standard
of reference, there is considerable debate as to
the most appropriate method of assessing BP in
different clinical settings. Clinic BP measurements
may be inappropriate for a number of reasons
including inaccuracies in measurement technique
and artificial increases in BP produced by whitecoat effects.2 Many studies have confirmed superiority of 24-h ambulatory BP monitoring (ABPM)
over office or clinic BP measurement in predicting
Correspondence: Professor J-W Chen, Department of Medical
Research and Education, Taipei Veterans General Hospital,
No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, ROC.
E-mail: jwchen@vghtpe.gov.tw
7
These authors contributed equally to this work.
Received 1 February 2010; revised 24 April 2010; accepted 21
June 2010; published online 5 August 2010
Methods
Study population
All of the patients were followed up in our outpatient clinics on regular basis, such as every 13
months. Information about clinical events was
obtained from the hospital charts or telephone
interview. Outcome variables were (1) all-cause
Data analysis
Statistical analysis was performed using SPSS software (version 15.0, SPSS Inc, Chicago, IL, USA). All
data were expressed as frequency (percentage) or
meanstandard deviation or median with interquartile ranges. Parametric continuous data between
untreated and treated groups were compared by
unpaired Students test, and nonparametric data
used the MannWhitney test. Categorical data
between untreated and treated groups were compared with w2-test, with Yates correction or Fishers
exact test as appropriate. The association between
each office and ambulatory BP parameters and
outcome events was tested using Cox proportional
hazards regression models. Each office and ambulatory BP parameter was adjusted for baseline variables: age, gender, smoking, concomitant medications
(antihypertensive and lipid-lowering agents), DM,
previous MI, previous stroke, congestive heart failure
and hyperlipidemia. In further models, the office BP
and ambulatory BP, and ambulatory SBP and PP were
included into the same model for competition.
Statistical significance was inferred at a two-sided
P-value of o0.05.
Results
Patient characteristics at baseline in 412 participants
Untreated (N 233)
Treated (N 179)
P-value
Baseline characteristics
Age (years)
Male (n (%))
Bodyweight (kg)
Height (cm)
BMI (kg m2)
Smoking (n (%))
59.314.0
252 (61.2%)
67.511.9
161.78.4
25.83.6
84 (20.4%)
57.014.3
145 (62.2%)
67.311.8
162.08.2
25.63.6
52 (22.3%)
62.313.0
107 (59.8%)
67.812.0
161.38.6
26.03.6
32 (17.9%)
o0.001
0.612
0.668
0.404
0.205
0.267
148.521.6
88.113.9
60.417.9
147.721.4
89.313.8
58.417.2
149.521.9
86.713.8
62.818.6
0.426
0.061
0.017
134.614.1
82.711.2
51.911.2
136.614.1
84.611.4
52.011.2
128.616.5
77.311.8
51.312.2
134.713.7
84.710.8
50.09.3
137.013.7
86.710.9
50.39.2
128.115.6
78.911.5
49.210.3
134.414.6
80.211.2
54.312.9
136.114.7
81.911.6
54.213.0
129.417.7
75.311.9
54.113.9
0.826
o0.001
o0.001
0.530
o0.001
o0.001
0.431
0.002
o0.001
179 (43.4%)
65 (15.8%)
95 (23.1)
117 (28.4%)
32 (7.8%)
53 (13.2%)
35 (15.4%)
179 (100.0%)
65 (36.3%)
95 (53.1%)
117 (65.4%)
32 (17.9%)
18 (10.3%)
0.137
Comorbidity (n (%))
DM
Previous MI
Previous stroke
CHF
Hyperlipidemia
47 (11.5%)
7 (1.7%)
25 (6.1%)
32 (7.8%)
185 (45.0%)
20 (8.6%)
2 (0.9%)
14 (6.0%)
9 (3.9%)
106 (45.7%)
27 (15.2%)
5 (2.8%)
11 (6.1%)
23 (12.8%)
79 (44.1%)
0.039
0.247
0.963
0.001
0.753
Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index; BP, blood pressure;
CCB, calcium channel blocker; CHF, congestive heart failure; DBP, diastolic blood pressure; DM, diabetes mellitus; MI, myocardial infarction;
PP, pulse pressure; SBP, systolic blood pressure.
Table 2 Adjusted hazard ratios for outcome with office, daytime, nighttime and 24-h blood pressure
No. of events
Office BP (1 s.d.)
Office SBP
Office DBP
Office PP
All-cause mortality
CV mortality
NCV mortality
CVD
CHD
Stroke
45
12
33
42
17
25
1.05 (0.771.43)
0.69 (0.471.02)
1.31 (0.951.80)
Ambulatory BP
24 h
24-h SBP (1 s.d.)
24-h DBP (1 s.d.)
24-h PP (1 s.d.)
Daytime
Daytime SBP (1 s.d.)
Daytime DBP (1 s.d.)
Daytime PP (1 s.d.)
Nighttime
Nighttime SBP (1 s.d.)
Nighttime DBP (1 s.d.)
Nighttime PP (1 s.d.)
1.07 (0.581.97) 1.09 (0.751.58) 1.06 (0.761.46) 1.44 (0.882.35) 0.85 (0.551.31)
0.70 (0.301.62) 0.69 (0.451.07) 0.77 (0.521.13) 0.87 (0.461.63) 0.72 (0.431.18)
1.28 (0.692.36) 1.42 (0.962.10) 1.25 (0.901.74) 1.73 (1.032.90)* 0.99 (0.641.55)
1.49 (1.112.00)w 1.67 (0.913.06) 1.44 (1.012.04)* 1.63 (1.202.22)w 1.54 (0.952.50) 1.74 (1.142.63)w
0.89 (0.601.34) 0.73 (0.291.79) 0.97 (0.611.54) 1.18 (0.801.74) 0.91 (0.491.67) 1.45 (0.872.40)
1.77 (1.332.35)z 2.03 (1.163.56)* 1.67 (1.182.38)w 1.70 (1.242.31)w 1.89 (1.173.04)w 1.57 (1.022.40)*
1.41 (1.041.90)* 1.70 (0.933.11) 1.31 (0.921.87) 1.69 (1.232.33)w 1.74 (1.072.83)* 1.68 (1.082.60)*
0.81 (0.541.22) 0.73 (0.301.76) 0.85 (0.531.35) 1.19 (0.801.76) 0.98 (0.531.81) 1.38 (0.832.28)
1.72 (1.292.28)z 2.07 (1.183.62)* 1.59 (1.122.26)* 1.71 (1.252.35)w 2.03 (1.273.24)w 1.51 (0.972.34)
1.56 (1.192.04)w 1.34 (0.732.46) 1.68 (1.222.30)w 1.36 (1.011.81)* 1.10 (0.661.83) 1.53 (1.062.22)*
1.17 (0.821.67) 0.69 (0.301.58) 1.39 (0.942.06) 1.14 (0.801.61) 0.75 (0.411.38) 1.44 (0.942.22)
1.72 (1.312.28)z 1.75 (1.003.05)* 1.73 (1.232.45)w 1.43 (1.051.94)* 1.43 (0.872.33) 1.39 (0.932.08)
Abbreviations: BP, blood pressure; CHD, coronary heart disease; CV, cardiovascular; CVD, cardiovascular disease; DBP, diastolic blood pressure;
NCV, noncardiovascular; PP, pulse pressure; SBP, systolic blood pressure.
Data are hazard ratios (95% confidence intervals) for each 1 s.d. higher blood pressure. Hazard ratios were also adjusted for baseline
characteristics including age, gender, smoking, concomitant medications (antihypertensive and lipid-lowering drugs), diabetes mellitus, previous
myocardial infarction, previous stroke, congestive heart failure and hyperlipidemia.
Significance of hazard ratios: *Po0.05; wPo0.01; zPo0.001.
Table 3 Adjusted hazard ratios for outcome with ambulatory systolic BP and PP
All-cause mortality
CV mortality
NCV mortality
CVD
CHD
Stroke
0.98 (0.511.90)
1.86 (0.993.48)
0.97 (0.651.45)
1.44 (0.982.11)
0.93 (0.661.30)
1.69 (1.222.34)w
1.33 (0.792.23)
1.43 (0.842.42)
0.71 (0.451.12)
1.95 (1.273.00)w
1.01 (0.521.99)
2.32 (1.234.38)w
1.18 (0.761.83)
1.55 (1.032.33)*
1.03 (0.721.48)
1.74 (1.242.45)w
1.44 (0.822.53)
1.77 (1.043.02)*
0.81 (0.501.31)
1.76 (1.102.80)*
0.65 (0.202.13)
2.87 (0.958.70)
0.90 (0.501.63)
1.83 (0.983.42)
1.26 (0.782.04)
1.41 (0.862.31)
0.88 (0.411.91)
2.09 (0.954.63)
1.65 (0.883.12)
1.07 (0.562.03)
0.66 (0.212.10)
2.87 (0.988.40)
0.78 (0.441.40)
1.96 (1.063.64)*
1.31 (0.802.14)
1.40 (0.862.27)
0.99 (0.452.17)
2.04 (0.944.45)
1.59 (0.852.99)
1.08 (0.582.02)
0.49 (0.151.66)
3.13 (0.999.91)
1.35 (0.772.38)
1.32 (0.722.43)
1.12 (0.691.81)
1.30 (0.782.16)
0.64 (0.281.47)
2.07 (0.884.85)
1.59 (0.882.90)
0.95 (0.501.79)
Abbreviations: BP, blood pressure; CHD, coronary heart disease; CV, cardiovascular; CVD, cardiovascular disease; NCV, noncardiovascular;
PP, pulse pressure; SBP, systolic blood pressure.
Data are hazard ratios (95% confidence intervals) for each 1 s.d. higher blood pressure. Hazard ratios were also adjusted for baseline
characteristics including age, gender, smoking, concomitant medications (antihypertensive and lipid-lowering drugs), diabetes mellitus, previous
myocardial infarction, previous stroke, congestive heart failure and hyperlipidemia.
Significance of hazard ratios: *Po0.05; wPo0.01; zPo0.001.
Discussion
The main findings of this study are that ABPM
parameters have more predictive value in long-term
prognosis than office BP in both treated and
untreated hypertensive patients. Further, ambulatory PP parameters seem more predictive than
ambulatory SBP parameters. To our knowledge, this
could be the first study to show the significant
prognostic impacts of ambulatory PP parameters,
even superior to ambulatory SBP, on both all-cause
and CV mortality in clinical hypertension. Besides,
24-h ambulatory PP may be the single most
prognostic parameter, as it could predict all the
long-term CV and non-CV clinical outcomes in
hypertensive patients.
Our findings are partially in line with the very
first report that ABPM is a better predictor of
morbidity than in-office BP measurement.15 Given
the potential inaccuracies in measurement technique and artificial increases in BP produced by
white-coat effects,2 office or clinic BP measurement
could be inferior to ABPM in predicting hypertension-induced organ damage or clinical outcome.36
In the current study, office BP parameters including
SBP, DBP and even PP failed to predict any clinical
outcome. On the other hand, ambulatory BP parameters such as 24 h, daytime and nighttime PP
predicted not only CVD and mortality but also nonCV and all-cause mortality, suggesting their broad
prognostic impacts in hypertensive patients.
Previous European studies have shown that
ambulatory BP, over and above the conventional
BP, could predict the CV risk and mortality in
untreated hypertensives.4,16 Besides, ABPM also
offers more accurate prognostic information of CV
outcomes than office readings in treated hypertensive subjects.3,16 In this study, although treated
patients were older with more comorbidity than
the untreated patients, ABPM parameters could
still predict the mortality and CVD in both groups.
In treated hypertensives, the results remained
unchanged after adjusting for concomitant antihypertensive medication.
Regarding the fact that which BP parameter is
most prognostic, the answers were varied among
different studies. Several epidemiological studies
reported that PP is a useful predictor for CV
morbidity and mortality, especially in old people.17,18 However, recent cohort studies including
older people showed that the relationship of PP to
mortality from total CVD and CHD was less strong
than those of other BP indexes.19,20 In a metaanalysis, PP was found to be less informative in
the prediction of CHD and stroke mortality than SBP
or DBP.1 Recent studies also showed the complex
associations of PP with all-cause and CV mortality,
depending on age, SBP and DBP, and discouraged
the use of PP for diagnostic or therapeutic decisions.21 However, the PP in these studies was mainly
derived from office BP. In this study, although office
Conflict of interest
The authors declare no conflict of interest.
Acknowledgements
This work was supported by grants including V95A011, V97C1-125 and V98A-015 from the Taipei
Veterans General Hospital, Taiwan, ROC.
References
1 Lewington S, Clarke R, Qizilbash N, Peto R, Collins R,
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meta-analysis of individual data for one million
adults in 61 prospective studies. Lancet 2002; 360:
19031913.
2 Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J,
Hill MN, et al., Subcommittee of Professional and
Public Education of the American Heart Association
Council on High Blood Pressure Research. Recommendations for blood pressure measurement in humans
and experimental animals: Part 1: blood pressure
measurement in humans: a statement for professionals
from the Subcommittee of Professional and Public
Education of the American Heart Association Council
on High Blood Pressure Research. Hypertension 2005;
45: 142161.
3 Clement DL, De Buyzere ML, De Bacquer DA, de
Leeuw PW, Duprez DA, Fagard RH, et al., Office
versus Ambulatory Pressure Study Investigators. Prognostic value of ambulatory blood-pressure recordings
in patients with treated hypertension. N Engl J Med
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