Article

Blood pressure variability assessed by home measurements: A systematic review

Hypertension Research (Impact Factor: 2.66). 02/2014; 37(6). DOI: 10.1038/hr.2014.2
Source: PubMed

ABSTRACT

Accumulating evidence suggests that day-by-day blood pressure (BP) variability assessed using self-measurements by patients at home (HBPV) provides useful information beyond that of average home BP. This systematic review summarizes the current evidence on day-by-day HBPV. A systematic literature search (PubMed) revealed 22 eligible articles. Independent prognostic value of day-by-day HBPV for cardiovascular events and total mortality was demonstrated in two outcome studies, whereas novel indices of variability had minimal or no independent prognostic ability. Although findings are not consistent among the studies, the evidence suggests that HBPV has an independent role in the progression of preclinical cardiac, arterial and renal damage and is affected by age, gender, average BP and heart rate level, antihypertensive treatment, antihypertensive drug class and other factors. However, there is large diversity among the available studies in the home BP monitoring protocols, the indices used to quantify HBPV and the end points selected for evaluation. Overall, these preliminary data largely based on heterogeneous studies indicate an important and independent role of day-by-day HBPV in the pathogenesis of hypertension-induced cardiovascular damage. Yet, fundamental questions remain unanswered, including the optimal variability index, the optimal home monitoring schedule required, the threshold that defines increased HBPV and the impact of treatment-induced variability change on organ damage and cardiovascular events. Until these questions are adequately addressed in future studies, HBPV should largely remain a research issue with limited practical value for individual patients.Hypertension Research advance online publication, 20 February 2014; doi:10.1038/hr.2014.2.

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Available from: Gianfranco Parati, May 08, 2014
ORIGINAL ARTICLE
Blood pressure variability assessed by home
measurements: a systematic review
George S Stergiou
1
, Angeliki Ntineri
1
, Anastasios Kollias
1
, Takayoshi Ohkubo
2
, Yutaka Imai
3
and
Gianfranco Parati
4,5
Accumulating evidence suggests that day-by-day blood pressure (BP) variability assessed using self-measurements by patients
at home (HBPV) provides useful information beyond that of average home BP. This systematic review summarizes the current
evidence on day-by-day HBPV. A systematic literature search (PubMed) revealed 22 eligible articles. Independent prognostic
value of day-by-day HBPV for cardiovascular events and total mortality was demonstrated in two outcome studies, whereas novel
indices of variability had minimal or no independent prognostic ability. Although findings are not consistent among the studies,
the evidence suggests that HBPV has an independent role in the progression of preclinical cardiac, arterial and renal damage
and is affected by age, gender, average BP and heart rate level, antihypertensive treatment, antihypertensive drug class
and other factors. However, there is large diversity among the available studies in the home BP monitoring protocols, the
indices used to quantify HBPV and the end points selected for evaluation. Overall, these preliminary data largely based on
heterogeneous studies indicate an important and independent role of day-by-day HBPV in the pathogenesis of hypertension-
induced cardiovascular damage. Yet, fundamental questions remain unanswered, including the optimal variability index, the
optimal home monitoring schedule required, the threshold that defines increased HBPV and the impact of treatment-induced
variability change on organ damage and cardiovascular events. Until these questions are adequately addressed in future studies,
HBPV should largely remain a research issue with limited practical value for individual patients.
Hypertension Research advance online publication, 20 February 2014; doi:10.1038/hr.2014.2
Keywords: cardiovascular prognosis; home blood pressure; self-measurement; target organ damage; variability
INTRODUCTION
Accumulating evidence suggests that increased variability of blood
pressure (BP) exerts additional stress on the cardiovascular system
independent of its average value, resulting in increased risk of target
organ damage and cardiovascular events.
The clinical relevance of BP variability was first demonstrated
by assessing 24-h beat-to-beat variability using intra-arterial
monitoring.
1
More recent studies showed that non-invasive
intermittent reading-to-reading 24-h ambulatory BP variability also
provides additional prognostic information beyond that of average
ambulatory BP.
2
Moreover, retrospective analyses of outcome studies
demonstrated that visit-to-visit systolic BP variability assessed by
repeated measurements in office visits is a strong predictor of stroke
independent of the average BP.
3–5
Finally, day-to-day BP variability
based on self-home BP measurements has also been shown to provide
independent prognostic information beyond that of average home
BP (HBP).
6
Despite the fact that reading-to-reading, visit-to-visit and day-to-
day BP variability assessed by ambulatory, office and home
measurements, respectively, have all been shown to predict cardio-
vascular event risk, they probably represent different components
of BP variability, may reflect different mechanisms, are likely to
provide different information on cardiovascular regulation and
might have different clinical implications that are still poorly
understood.
7
Self-home BP monitoring is widely available in several countries
and is well accepted by hypertensive patients.
8
Thus, it has been
suggested that in clinical practice, the assessment of BP variability
by self-home measurements (HBPV) might be more feasible as well
as more reliable and cost-effective than office or ambulatory
BP variability measurements and more appropriate for repeated
assessment in the long-term follow-up of treated hypertension.
9
The objective of this paper is to perform a systematic review of
the evidence on HBPV and, especially, to present data on the
methodology applied for its evaluation and its clinical prognostic
relevance. Moreover, the strengths and weaknesses of current research
on HBPV are summarized, together with the remaining research
questions and the potential for clinical application.
1
Hypertension Center, STRIDE Hellas-7, Third Department of Medicine, University of Athens, Sotiria Hospital, Athens, Greece;
2
Teikyo University School of Medicine, Tokyo,
Japan;
3
Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan;
4
Department of Health Sciences, University of Milano-Bicocca, Milan, Italy and
5
Department of Cardiology, S. Luca Hospital, IRCCS Istituto Auxologico Italiano, Milan, Italy
Correspondence: Professor GS Stergiou, Hypertension Center, STRIDE Hellas-7, Third University Department of Medicine, Sotiria Hospital, 152 Mesogion Avenue, Athens 11527,
Greece.
E-mail: gstergi@med.uoa.gr
Received 18 August 2013; Received 22 November 2013; accepted 27 November 20 13
Hypertension Research (2014), 1–8
&
2014 The Japanese Society of Hypertension All rights reserved 0916-9636/14
www.nature.com/hr
Page 1
MATERIALS AND METHODS
A systematic literature search was performed by two investigators (AN and AK)
independently at PubMed database up to J une 2013 using the keywords ‘home’,
‘blood pressure’ and ‘variability’. Disagreements were discussed with senior author.
Additional articles were searched from the reference lists of identified articles.
Studies eligible for review were those presenting original data from cross-
sectional or longitudinal studies in adults and examining day-by-day HBPV in
terms of the following issues: (i) methodologies applied to evaluate and
quantify the HBPV, (ii) relationship of HBPV with indices of preclinical target
organ damage, (iii) prognostic value of HBPV in terms of cardiovascular
morbidity and mortality, (iv) factors associated with HBPV and (v) effects of
antihypertensive drug treatment on HBPV.
RESULTS
HBPV evidence overview
The overall search identified 190 potentially relevant articles. Twenty-
two articles reported data from original studies and were included in
the review (Figure 1).
6,10–30
Fifteen (68%) of these publications are
derived from studies conducted in Japan.
6,10–11,14–20,22–25,30
Five
6,10–13
studies investigated the prognostic relevance of HBPV, 6
14–19
its
association with indices of target organ damage (cardiac, arterial and
renal), 13
11,13,15,20–29
factors affecting HBPV and 8
11,13,15,18,20,23,24,30
the effects of antihypertensive drug treatment on HBPV (some
provided data on more than one of these issues).
In terms of design, most of the studies were cross-sectional,
14,15–17,20–29
some had several months follow-up
18,19,30
and few had almost 10-year or
longer follow-up .
6,10–13
The study samples ranged from 26 to 2944
individuals and either included subjects with h ypertension, diabetes,
nephropath y or were drawn from general population.
There was wide diversity among the studies in the protocol used
for HBP evaluation, in terms of (i) the time of the day (morning
measurements only, average of morning and evening measurements,
and morning and evening measurements analyzed separately), (ii) the
number of HBP readings taken per occasion (range from 1 to 5) and
(iii) the number of HBP monitoring days (range from 2 to 26).
In regard to the methodology applied to evaluate and quantify the
HBPV, again there is large diversity among studies in the parameters
used, including standard deviation (SD) and/or coefficient of varia-
tion (CV) of all
14,16–19,22–25,27–30
HBPs, or of morning HBPs,
6,10,20
or
SD of morning or evening HBP readings of a single occasion
15
and
SD of morning minus evening HBP difference,
12,21,26
day-by-day
HBPV (morning and evening),
12,21,26,27
and first-second HBP
measurement difference per occasion,
12,21,26
or average real
variability (ARV),
11,13,19
variability independent of mean (VIM),
11,13
maximum minus minimum HBP difference (MMD)
11,13
and
maximum BP value
14,18
which reflects the BP instability.
Prognostic value of HBPM
Five relevant articles were identified based on general population
samples (Table 1).
6,10–13
Three papers reported data from the same
study in Japan (Ohasama).
6,10–11
In the Ohasama study, high day-by-
day HBPV was associated with increased total, cardiovascular and
stroke mortality, independently of the average HBP and other
cardiovascular risk factors.
6
Systolic HBPV was associated with
cerebral infraction in ever, but not in never smokers.
10
Morning
VIM and ARV, independent of BP level, predicted total and
cardiovascular mortality in all of the participants.
11
However, being
treated with BP lowering drugs undermined the predictive value of
morning VIM in terms of total mortality, and in untreated
participants only morning VIM predicted total mortality and only
evening VIM predicted cardiovascular mortality.
11
None of the new
HBPV indices predicted stroke incidence and for all or cause-specific
fatal combined with nonfatal outcomes the incremental predictive
value of VIM, MMD and ARV over and beyond the average HBP level
was minimal.
11
It should be mentioned, however, that the Ohasama
study included residents from a Japanese rural community, a
population quite different from Western populations in terms of
hypertension-related cardiovascular complications. Moreover, HBPV
was calculated using single measurement readings obtained in a
median period of 26 days, which is a different schedule than in
European studies. In the Finn-Home study, where duplicate HBP
readings were taken twice daily for 7 consecutive days in a random
population sample of 1866 Finnish subjects, HBPV again predicted
cardiovascular events and total mortality, and increased morning
HBPV was an independent predictor of cardiovascular events.
12
Another study in 2944 subjects in Belgium with 12-year follow-up
failed to show predictive ability of novel indices of HBPV for
cardiovascular mortality and morbidity.
13
However, this was not a
typical HBP monitoring study, because home measurements were
taken by nurses who visited the participants homes, and thus its
results cannot be considered when focusing on HBPV. The latter
study has additional drawbacks due to limited number of HBP
readings (10 readings obtained in two home visits 2–4 weeks apart)
and the potential of observer bias and intra- and inter-
observer variability (auscultatory measurements using mercury
sphygmomanometers).
13
Association of HBPV with target organ damage
Six relevant studies were identified: five based on cross-sectional data
analyses and one with follow-up data (Table 2).
14–19
One cross-
sectional study in 356 untreated hypertensives who were instructed to
take triplicate HBP measurements at 15-min intervals in the morning
38 articles:
Relevant reviews,
commentaries,
statements
61 articles:
Irrelevant
41 articles:
BP variability was not
evaluated with HBP
measurements but with
other methods
3 articles:
Only home heart
rate variability was
assessed
25 articles:
Relevant but not within
the study scope (e.g. Not
day-by-day variability)
190 articles: identified
22 articles: eligible for inclusion in the review
Figure 1 Flowchart of process for selection of articles. BP, blood pressure;
HBP, home BP.
Home blood pressure variability
GS Stergiou et al
2
Hypertension Research
Page 2
and the evening for 14 consecutive days, reported independent
association of systolic HBPV and maximum systolic HBP with left
ventricular mass index.
14
Regarding to arterial damage, only
maximum systolic HBP was shown to be independently associated
with carotid intima–media thickness.
14
The same study failed to show
an association of HBPV with urinary albumin/creatinine ratio, yet the
latter was independently associated with maximum systolic HBP.
14
However, the use of maximum systolic HBP of 14-day HBP
monitoring as a measure of BP variability raises concerns about its
reproducibility and its adequacy to reflect short- or long-term BP
variability.
14
A study in 332 diabetic subjects showed that morning
systolic HBPV on one occasion was higher in patients with
proteinuria, and was independently, yet weakly, associated with
pulse wave velocity.
15
However, aiming to improve patients
compliance to the measurement procedure, this study obtained
home readings at 15-s intervals. Another study in 858 type 2
diabetics demonstrated an association of HBPV with proteinuria,
independent of other known risk factors.
16
Finally, one study reported
an independent association of low estimated glomerular filtration rate
with systolic BP variability in 268 diabetics with microalbuminuria,
17
whereas another paper in 310 hypertensives showed systolic BP
variability and maximum systolic BP to be associated with urinary
albumin excretion.
18
A single study with 3-year follow-up in 135
patients with nephropathy failed to show a significant association of
HBPV with the progression of chronic kidney disease.
19
However , it
should be mentioned that the aforementioned study included single
BP readings per occasion and did not use uniform devices for HBP
monitoring. In addition, the investigators reported that in a
Table 1 Studies assessing the prognostic value of home blood pressure variability
Study Population (n)
Follow-up
(years)
HBP
(time/n/days) HBPV measure End points Main findings
Kikuya et al.
(Ohasama)
6
General 2455 11.9 m/1/26 SD, CV Mortality total, CVD,
stroke, non-CVD,
cardiac
Day/day S/D BPV independently associated with mTotal, CVD,
stroke mortality (not cardiac)
Hashimoto et al.
(Ohasama)
10
Men without
stroke 902
13.1 m/1/26 SD stroke according to
smoking status
S-BPV associated with cerebral infarction in ever, not in never
smokers
Asayama et al.
(Ohasama)
11
General 2421 12 m&e/1/26 VIM, MMD, ARV CVD, total mortality m SBP: VIM, ARV predicted total and CVD mortality in all. VIM
predicted CVD mortality in treated and total mortality in untreated;
m MMD not predictive. e SBP: only VIM predicted CVD mortality in
all and in untreated. None of the new indices predicted stroke.
VIM, MMD and ARV not incrementally predictive of outcome over
and beyond mean SBP (minimal impact)
Johansson et al.
(Finn-Home)
12
General 1866 7.8 m&e/2/7 SD m–e, day/day
(m&e), 1st–2nd
CVD, total mortality BPV m–e, m day/day independent predictors of CVD events. SBPV
m–e, m day/day, 1st–2nd predicted total mortality
Schutte et al.
13
General 2944 12 a/5/2 visits
(2–4 weeks;
nurses)
VIM, MMD, ARV CVD mortality,
morbidity
Not predictive of total and CVD mortality, or CVD events
Abbreviations: ARV, average real variability; BP, blood pressure; BPV, BP variability; CV, coefficient of variation; CVD, cardiovascular disease; day/day, day-by-day; e, evening; HBP, home BP; HBPV,
home BPV; m, morning; MMD, difference between maximum and minimum BP; n, number; S, systolic; SD, standard deviation; VIM, variability independent of mean; a, differing.
Table 2 Association of home blood pressure variability with target organ damage
Study Population (n) Follow-up (years) HBP (time/n/days) HBPV measure End points Main findings
Matsui et al.
14
356 HTN untreated Cross-sectional m&e/3/14 SD, Max LVMI
IMT
Day/day S-BPV independently associated with
LVMI.
Max SBP independently associated with LVMI.
Day/day S-BPV not associated with IMT.
Max SBP independently associated with IMT
Fukui et al.
15
332 DM2 Cross-sectional m&e/3/14 SD m or e PWV m S-SD (single occasion) independently
associated with PWV
Okada et al.
19
135 CKD 3-5 3 m&e/1/7 SD, CV, ARV CKD progression No correlation with eGFR change or renal events
Nishimura et al.
17
268 DM2 þ MAU 3 baseline data m&e/1/7 SD eGFR Low eGFR independently correlated with S-SD
Fukui et al.
15
332 DM2 Cross-sectional m&e/3 /14 SD m or e Proteinuria m S-SD (single occasion) higher in patients with
proteinuria
Ushigome et al.
16
858 DM2 Cross-sectional m&e/ 3/14 CV Proteinuria mS-CV in patients with proteinuria. CV of m SBP,
m DBP, e SBP independent predictors of UAE
Hoshide et al.
18
310 HTN 0.5 baseline data m&e/3/7 SD, Max UAE S-SD and max SBP associated with UAE
Matsui et al.
14
356 HTN untreated Cross-sectional m&e/3/14 SD, Max Ur Alb/Cr Day/day S-BPV not associated with Ur Alb/Cr.
Max SBP correlated with Ur Alb/Cr in all
Abbreviations: ARV, average real variability; BP, blood pressure; BPV, BP variability; CKD 3–5, chronic kidney disease stage 3–5; CV, coefficient of variation; DM2, diabetes mellitus type-2;
e, evening; eGFR, estimated glomerular filtration rate; HBP, home BP; HBPV, home BPV; HTN, hypertensives; IMT, carotid intima–media thickness; LVMI, left ventricular mass index; m, morning;
MAU, microalbuminuria; Max: maximum; n, number; PWV, pulse wave velocity; S, systolic; SD, standard deviation; UAE, urinary albumin excretion; Ur Alb/Cr, urinary albumin/creatinine ratio;
m,elevated.
Home blood pressure variability
GS Stergiou et al
3
Hypertension Research
Page 3
considerable proportion of the participants, treatment was modified
during the follow-up aiming to achieve a BP control.
19
Thus, the BP
lowering effect and the action of different antihypertensive drugs
might have largely influenced the change in HBPV and estimated
glomerular filtration rate.
19
Factors associated with HBPV
Thirteen articles investigated factors associated with HBPV
(Table 3) .
11,13,15,20–29
Advanc ed age,
13,15,20–23,29
female gender ,
11,20–22,24–25
elevated mean BP,
13,15,20–22
low body mass index,
13,20
low heart
rate,
15,20,22,24
high heart rate variability,
20,22,24
excessive alcohol
intake,
21–22
smoking,
25
history of peripheral artery disease,
13
cardiovascular disease,
21
diabetes mellitus,
21
diabetic nephropathy,
24
pulsewavevelocity,
15
sedentary lifestyle,
22
treated hypertension
11,23
and treatment with beta-blockers,
13,15
all have been associated with
increased HBPV. HBPV appeared to be higher in the evening than in
the morning.
23–24
In a single study, HBPV was correlated with self-
reported insomnia and sleep duration.
26
A population study in 1701
elderly subjects showed that HBPV was similar in masked and
sustained hypertensives and higher than in normotensives and
white-coat hypertensives.
27
Moreover, a study in 26 borderline
hypertensives failed to correlate HBPV with personality/behavioral
variables such as anxiety and anger.
28
Finally, another study in a
random population sample from Belgium demonstrated that diastolic
BP variability is inversely correlated with self-rated physical activity in
men, and that women living in working class area presents lower
systolic BP variability.
29
Effects of antihypertensive treatment on HBPV
Six cross-sectional studies reported data on the effect of drug
treatment of HBPV (Table 4). Baseline evaluation in the Ohasama
study revealed that HBPV was higher in treated than in untreated
hypertensives.
11,23
One study in diabetics and another in general
population reported that BP variability was greater in those receiving
beta-blockers.
13,15
Other studies showed that treatment with alpha-
blocker seemed to be related with lower HBPV,
15
whereas treatment
with an angiotensin II receptor blocker (ARB) and not with a calcium
channel blocker (CCB) was associated with higher systolic BP
variability in patients treated for o1year.
20
Short duration of
treatment
20
and increased number of antihypertensive drugs
24
were
associated with greater HBPV.
Two longitudinal studies investigated the effect of drug treatment of
HBPV. The combination of an ARB with a CCB was found to be
more effective in lowering systolic HBPV than the ARB/thiazide
combination.
30
Furthermore, the pulse wave velocity change induced
by the ARB/CCB treatment (6 months) was independently associated
with the change in systolic HBPV.
30
However, in another study, based
on a post hoc analysis of data from a small population sample,
treatment-induced change in urinary albumin excretion (6 months)
was not associated with that of systolic HBPV. Nevertheless, the
follow-up period was too short to demonstrate the impact of BP
variability decline on organ damage evolution.
DISCUSSION
There is an increasing interest and accumulating evidence on HBPV,
with the majority of the studies performed in Japan and published in
Table 3 Factors associated with home blood pressure variability (cross-sectional analyses)
Study Population (n) HBP (time/n/days) HBPV measure Main findings
Asayama et al.
(Ohasama)
11
General 2421 m&e/1/26 VIM, MMD, ARV m BPV in treated vs. untreated. Morning, not evening CV, VIM, MMD
m in females
Fukui et al.
15
DM2 332 m&e/3 /14 SD m or e Age, average m S-BP, HR, PWV correlated with SD of m SD (single
occasion). Age, average e S-BP, PWV correlated with SD of e S-SD
Schutte et al.
13
General 2944 a/5/2 visits (2-4 weeks;
nurses)
VIM, MMD,ARV m S-BPV: Males, older age, mS-BP, kBMI, PAD history, b-blocker use
Ishikura et al.
20
HTN treated 1933 m/1/14 SD, CV m BPV: Females, Age, BP, HRV. kBPV: HR, BMI, treatment duration
Johansson et al.
(Finn-Home)
26
General 1908 m&e/2/7 SD m-e, day/day (m&e),
1st-2nd
m BPV: Insomnia.mBPV: Insomnia and short sleep duration.mSme,
day/day, m day/day: long sleepers. S m, D day/day: short sleepers
Johansson et al.
(Finn-Home)
21
General 1908 m&e/2/7 SD m-e, day/day (m&e),
1st-2nd
m m–e BPV: Age, CVD, DM, high BPV. mBPV: Age, mAlcohol, mBP,
m1st–2nd BPV: Age, female, CVD, mBP
Kato et al.
(Ohasama)
22
General 1215 m&e/1/26 SD, CV m BPV: Age, Females, mBP, low HR, elevated HRV. meBPV:Alcohol
intake; Sedentary lifestyle
Imai et al.
(Ohasama)
23
General 1207 m&e/1/26 SD m BPV: evening than morning; Treated than untreated; Age
Okada et al.
24
CKD 368 m&e/1/7 CV m m S-CV: Females, diabetic nephropathy, number of anti-HTN
drugs, mHR, mHRV
Kawabe et al.
25
HTN from a company
605
m&e/3/ 7 SD, CV m m S-CV: Smokers, Females
Cacciolati et al.
27
Elderly 1701 m&e/3/3 7 a indexes m BPV: sustained and masked HTN vs. Normotension & White-coat
HTN (treated and untreated)
Schneider et al.
28
Borderline HTN 26 m&e/1/7 SD BPV not increased in the high HBP group and not predicted by any of
the psychometric factors (anger, anxiety)
Staessen et al.
29
General 784 a/5/2 visits (nurses) SD, CV BPV increases with advancing age. Men: D-BPV inversely correlated
with self-rated physical activity. Women: kS-BPV when living in a
working class area
Abbreviations: ARV, average real variability; BMI, body mass index; BP, blood pressure; BPV, BP variability; CKD, chronic kidney disease; CV, coefficient of variation; CVD, cardiovascular disease;
D, diastolic; day/day, day-by-day; DM2, diabetes mellitus type-2; HBP, home BP; HBPV, home BPV; HTN, hypertensives; HR, heart rate; HRV, HR variability; MMD, difference between maximum
and minimum BP; n, number; PAD, peripheral artery disease; PWV, pulse wave velocity; S, systolic; SD, standard deviation; VIM, variability independent of mean; m, elevated; k, decreased;
a, differing.
Home blood pressure variability
GS Stergiou et al
4
Hypertension Research
Page 4
the last 3 years. These studies have addressed most of the clinically
relevant aspects of HBPV and showed encouraging preliminary
results. However, at the present time, the available evidence is still
limited and the large heterogeneity in BP measurement protocols and
HBPV indices used in these studies does not allow a meta-analysis to
be performed.
The current evidence suggests that HBPV: (i) appears to offer
prognostic information independent of average HBP, (ii) has an
independent role in the evolution and progression of preclinical
cardiac, arterial and renal damage and (iii) is affected by age, gender,
BP level, heart rate, antihypertensive treatment, antihypertensive drug
class and other factors.
The outcome data relating HBPV with cardiovascular events’ risk
and total mortality (Table 1) are probably the most meaningful for
clinical relevance, yet are essentially derived from two studies
(Ohasama and Finn-Home), are based on post hoc analyses, and
tested several different end points and indices of HBPV. A meticulous
evaluation including novel indices of variability (VIM, MMD and
ARV) revealed minimal additional value beyond that of average
HBP.
11
The evidence in regard to the association of HBPV with preclinical
organ damage (Table 2) is mainly based on cross-sectional analysis,
yet most of these studies have been specifically designed for this
purpose. Overall, these data suggest an independent association of
HBPV with organ damage, with most of the studies assessing renal
indices and scarce data on cardiac and arterial indices. In particular,
Matsui et al. examining the relation of HBPV with all the above end
points in 356 untreated hypertensives demonstrated that both day-by-
day systolic HBPV and maximum systolic HBP are independently
associated with left ventricular mass index.
14
However , only
maximum systolic HBP was an independent determinant of carotid
intima–media thickness, indicating that carotid atherosclerosis might
be mainly influenced by transient BP fluctuations rather than by
typical fluctuations of day-by-day BP variability.
14
On the other hand,
findings about renal damage coincided with those of Hoshide et al.,
18
suggesting a weak association of urinary albumin excretion with
day-by-day HBPV and maximum systolic BP. The latter study, in a
post hoc analysis of data from a small population sample, although
showed a significant correlation between baseline urinary albumin
excretion and HBPV, failed to show a reduction of normo- and
microalbuminuria after treatment-induced reduction in HBPV.
18
On
the contrary, studies by Fukui et al.
15
and Ushigome et al.
16
in diabetic
subjects demonstrated a significant association between HBPV and
proteinuria. The small effect of maximum systolic HBP on renal
indices might be explained by the autoregulatory renal mechanisms
that prevent transient BP fluctuations to be transmitted to glomerular
capillary circulation and affect glomerular function.
14
Regarding the
conflicting findings in patients with normo- or microalbuminuria
compared with those with proteinuria, it has been suggested that
urinary albumin excretion in the range of normo- to micro-
albuminuria may not be a reliable index of renal damage and its
progression.
31
Okada et al.
19
also reported the absence of association
between HBPV and nephropathy progression in 135 patients with
chronic kidney disease. However, it should be considered that chronic
renal disease has been mainly associated with alterations in short-term
BP variability, especially with elimination or inversion of circadian BP
variation, which has been attributed to sympathetic hyperactivity
(neurohormonal changes due to renal failure)
32
and impaired aortic
and carotid baroflexes (uremia-related increase in arterial calcification
and stiffness).
33,34
Thus, because 24 h ambulatory BP monitoring was
not used, meaningful abnormalities in BP variability might have been
missed.
34
Undoubtedly, BP variability is a rather complex phenomenon.
From a physiological point of view, it reflects the influences of
increased sympathetic drive and reduced arterial and cardiopulmon-
ary reflexes.
35–37
Moreover, impaired arterial compliance, humoral
factors (angiotensin II, bradykinin, endothelin-1, insulin and nitric
oxide), blood viscosity, behavioral changes (physical activity, sleep,
postural changes and so on), emotional factors and even climatic
changes might contribute in the generation of BP fluctuations.
35,38
Table 4 Effects of antihypertensive treatment on home blood pressure variability
Study Population (n)
Duration
(years) HBP (time/n/days)
HBPV
measure Main findings
Imai et al.
(Ohasama)
23
General
1207
Cross-sectional m&e/1/26 SD BPV: treated4untreated
Asayama et al.
(Ohasama)
11
General
2421
12
Baseline data
m&e/1/26 VIM,
MMD, ARV
BPV: treated4untreated
Schutte et al.
13
General
2944
12
Baseline data
a/5/2 visits (2–4 weeks; nurses) VIM,
MMD, ARV
Treatment with beta-blocker correlates with S-BPV
Fukui et al.
15
DM 2
332
Cross-sectional m&e/3/14 SD m or e m or e S-SD (single occasion) lower with alpha-blockers than
without. e S-SD higher with beta-blockers than without
Ishikura et al.
20
HTN treated
1933
Cross-sectional m/1/14 SD, CV Not on amlodipine and on ARB associated with m S-BPV
(only in patients treated for o12 months). Treatment
duration: negative association with BPV
Matsui et al.
30
HTN treated
olmesartan 12
weeks 207
0.5 m&e/3/5 SD S-SD decreased more with add-on CCB than TZD. CCB
group: PWV change associated with S-BPV change
Hoshide et al.
18
HTN
310
0.5 m&e/3/7, before and 6 months after
candesartanþ TZD
SD, max Treatment-induced kUAE not associated with that of SD or
max SBP
Okada et al.
24
CKD
368
Cross-sectional m&e/1/7 CV Number of anti-HTN drugs associated with mmS-CV
Abbreviations: ARB, angiotensin II receptor antagonists; ARV, average real variability; BP, blood pressure, BPV, BP variability; CCB, calcium channel blockers; CKD, chronic kidney disease; CV,
coefficient of variation; DM2, diabetes mellitus type 2; e, evening; HBP, home BP; HBPV, home BPV; HTN, hypertensives; m, morning; max, maximum; MMD, difference between maximum and
minimum BP; n, number; PWV, pulse wave velocity; S, systolic; SD, standard deviation; TZD, thiazide diuretics; UAE, urinary albumin excretion; VIM, variability independent of mean; a, differing.
Home blood pressure variability
GS Stergiou et al
5
Hypertension Research
Page 5
More specifically, mid-term day-by-day HBPV might also be due to
limited accuracy of self-measurements, the imperfect stability of BP
control in treated patients due to improper titration/dosing of
medication or poor patients compliance with the prescribed
regimen (dose omission, delay in drug intake and so on).
35
Nevertheless, multiple other factors have been shown to affect
HBPV in secondary analyses of relevant studies (Table 3). Some of
them, such as age, gender, BP level, treatment status and heart rate
have been consistent in several studies, which implies a true
association. The impact of aging on BP variability is probably due
to impaired baroreceptor sensitivity, a condition that promotes
transient BP fluctuations due to exaggerated pressor response to
mental and physical stimuli.
22
Moreover, advanced age is
accompanied by arterial stiffness, a condition of decreased arterial
compliance that also attenuates baroreflex function and contributes to
increased BP variability.
22
The evidence on the effect of antihypertensive drugs on HBPV
is rather limited (Table 4), yet the findings of a favorable effect
of CCBs but not of beta-blockers is consist ent with data fo r office
and ambulatory BP variability,
4
which imp lies common
mechanisms influencing HBPV as for office and ambulatory BP
variability. This was demonstrated by Rothwell et al.
4
in the
ASCOT-BPLA (Anglo-Scandinavian C ardiac Outcomes Trial
Blood Pressure Lowering Arm) in high-risk hypertensives and
also in the Medical Research Council trial in el derly
hypertensives. It should be mentioned that the se results are based
on post hoc analyses on selective population samples and, due to
methodological limitations, the ASCOT-BPLA analysis had to rely
on interindividual BP variation that was arbitrarily used as
surroga te measure of intraindividual BP variabi lity.
7
However, the
similarity of these findings with those obtained by HBP
measurements implies common mechanisms influencing HBPV as
for office and ambulatory BP variability.
The favorable effects of CCBs, and particularly of amlodipine, on
BP variability have been attributed to their vasodilating effects on
peripheral muscular arteries that lead to decreased peripheral
resistance and arterial stiffness with subsequent improvement of
arterial baroflex sensitivity, as well as to the long duration of action
(amlodipine). Moreover, there is evidence that amlodipine might
lead to decreased BP variability by suppressing arterial stiffening
via anti-inflammatory and antioxidant effects (Limit Occurrences of
Thrombosis (CAMELOT) Study).
20,39
The findings by Ishikura et al.
20
reporting increased HBPV with of ARB use in patients treated
for o12 months conflict with previous studies demonstrating
antiatherogenic properties and suppression of sympathetic activity
of this drug class.
20,40–42
In addition, the different effects of CCBs and
ARBs on HBPV during the first year of treatment was not apparent
thereafter.
20
This observation might indicate that prolonged
antihypertensive therapy might stabilize BP variation, probably by
reducing arterial stiffness.
20
Interestingly, the effect of antihypertensive
drugs on HBPV may be largely affected by the duration of treatment,
with long-term treatment resulting in decreased HBPV irrespectively
of the class of antihypertensive drugs used.
20
On the other hand, in
the studies of Schutte et al.
13
and Fukui et al.,
15
the use of beta-
blockers was associated with elevated HBPV. This finding might be
attributed to vasoconstriction, increased peripheral resistance and
reduced compliance of the elastic arteries. However, in the same
population Fukui et al.
15
found that alpha-blockers exhibit opposite
effects on BP variability, which might be explained by the suppressing
action of alpha-blockers on the autonomic nervous system
activation.
15
The findings by Matsui et al.
30
that the addition of a CCB instead
of a thiazide in a treatment regimen with an inhibitor of the renin
angiotensin system led to greater decrease of HBPV, whereas the ARB/
thiazide combination did not alter the magnitude of HBPV, may
imply that the use of renin–angiotensin inhibitors may be related with
increased BP variability whereas the use of thiazide with lower BP
variability (yet higher than that of CCB). Another meaningful point is
that plasma aldosterone concentration was reported to be increased
only after treatment with the ARB/thiazide combination.
30,43
Taking
into account that elevated aldosterone levels impair baroreceptor
sensitivity in humans,
44
this drug-induced aldosterone excess may
explain why the ARB/thiazide group was associated with lesser decline
in HBPV.
30
In the absence of direct comparisons of HBPV with office and
ambulatory BP variability, it is not known whether there are
important differences in the information provided by these measures,
whether their predictive role is complementary, or whether one of
them allows more accurate prediction of risk. Preliminary data
suggest that there are differences in the levels of office, home and
ambulatory BP variability and moderate correlation among them, yet
there is fair agreement (60–70%) among the three methods in
detecting subjects with high BP variability defined as those at the
highest SD quartile by each method.
45
Moreover, the change in HBPV
after one year of antihypertensive treatment appeared to be superior
to that of office or ambulatory BP variability in predicting the
treatment-induced change in left ventricular mass index or pulse wave
velocity.
46
Although these data require confirmation and more research is
needed, from the practical point of view HBPV appears to be the most
feasible method for the evaluation of variability, given the wide
availability of HBP monitors and the good acceptance of this method
by hypertensive patients for long-term use.
9
Regarding office BP
variability assessed in repeated visits, although it was proved to be
successful in the context of outcome trials
3,4
or surveys,
5
it might be
impractical for routine clinical use due to poorly standardized office
measurements and to the long time required for multiple visits.
Regarding the 24-h ambulatory BP variability, in a retrospective
analysis of the ASCOT-BPLA study it appeared to be inferior to the
visit-to-visit office BP variability in terms of their impact on vascular
events,
4
although the results of many observational studies, some of
which including follow-up data, have emphasized that 24-h
ambulatory BP variability is significantly associated with organ
damage and cardiovascular events over and above the impact of
increased average BP levels.
47
An analysis of the International
Database on Ambulatory Blood Pressure in Relation to Cardio-
vascular Outcome (IDACO) including 8938 subjects, showed that
24-h ambulatory BP variability, although significantly predictive of
cardiovascular risk, did not provide a significant contribution to risk
stratification over and beyond average ambulatory BP,
2
but the results
of such analysis might have been biased by different methodological
features of ambulatory BP monitoring performed in the different
countries included. In spite of the interesting information provided by
ambulatory BP monitoring, however, it has to be acknowledged that
this approach is still not widely available and may not be suitable for
repeated use in the long-term follow-up.
Even if it is decided that HBPV is the optimal measurement
method for the evaluation of BP variability between days and/or
visits, several fundamental research questions need to be addressed
before this approach can be proposed for clinical application. Studies
are needed to show (i) which index more accurately represents the
impact of HBPV on the cardiovascular system, (ii) which is the
Home blood pressure variability
GS Stergiou et al
6
Hypertension Research
Page 6
optimal HBP monitoring schedule that gives a reproducible and
reliable assessment of HBPV, (iii) which threshold defines increased
HBPV in terms of its association with organ damage and cardiovas-
cular disease and (iv) whether treatment-induced changes in HBPV
affect target organ damage and cardiovascular event risk. Until these
research questions are adequately addressed and a practical and
efficient approach for applying this challenging concept in clinical
practice is agreed, HBPV assessment should largely remain a research
issue with little practical value for individual patients.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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  • Source
    • "In day-by-day home BP variability, the evidence is also rather limited and shows a favourable effect of CCBs (amlodipine, in particular) but not of í µí»½-blockers, which is consistent with data from office and ambulatory BP variability , implying that there are common mechanisms influencing home-based variability as for office and ambulatory BP variability [39]. Our data are in contradiction with these favourable effects of CCBs on home BP variability, which have been attributed to many intrinsic features such as their vasodilating effects on peripheral muscular arteries, decreased peripheral resistance, increased baroreflex sensitivity, reduced arterial stiffness, and long elimination half-lives. "
    [Show abstract] [Hide abstract] ABSTRACT: Background. The morning home blood pressure (BP) rise is a significant asymptomatic target organ damage predictor in hypertensives. Our aim was to evaluate determinants of home-based morning-evening difference (MEdiff) in Argentine patients. Methods. Treated hypertensive patients aged ≥ 18 years participated in a cross-sectional study, after performing home morning and evening BP measurement. MEdiff was morning minus evening home average results. Variables identified as relevant predictors were entered into a multivariable linear regression analysis model. Results. Three hundred sixty-seven medicated hypertensives were included. Mean age was 66.2 (14.5), BMI 28.1 (4.5), total cholesterol 4.89 (1.0) mmol/L, 65.9% women, 11.7% smokers, and 10.6% diabetics. Mean MEdiff was 1.1 (12.5) mmHg systolic and 2.3 (6.1) mmHg diastolic, respectively. Mean self-recorded BP was 131.5 (14.1) mmHg systolic and 73.8 (7.6) mmHg diastolic, respectively. Mean morning and evening home BPs were 133.1 (16.5) versus 132 (15.7) systolic and 75.8 (8.4) versus 73.5 (8.2) diastolic, respectively. Significant beta-coefficient values were found in systolic MEdiff for age and smoking and in diastolic MEdiff for age, smoking, total cholesterol, and calcium-channel blockers. Conclusions. In a cohort of Argentine medicated patients, older age, smoking, total cholesterol, and use of calcium channel blockers were independent determinants of home-based MEdiff.
    Full-text · Article · Dec 2014 · International Journal of Hypertension
  • [Show abstract] [Hide abstract] ABSTRACT: Blood pressure levels in clinical office tend to be variable. Therefore 2 times measurements of blood pressure with interval of 1-2 minutes have been advocated by guidelines (JSH 2014). Furthermore we have tried 5 times measurements with 1 minute interval for obtaining reliable blood pressure of upper arms in clinical office using oscillometric method (HEM 8723, Omron). In this study 193 outpatients(99 males, 94 females) aged 18-90 were recruited. By first diastolic blood pressure levels 4 groups were divided: 60-69 mmHg (21males, 22 females), 70-79(27, 23), 80-89(22, 22), 90-99(21, 17), who accepted any antihypertensive drugs in 36.8% of males and 33% of females. Outpatients without drug (8 males, 10 females) were also examined, who showed 90-99 mmHg of first diastolic blood pressure. From these 2 observations 5th measurement tended to show greater lowering of diastolic blood pressure levels as compared with 2nd-3rd ones, especially in females. Then the differences between home blood pressure (early morning) and office blood pressure levels of the same day were small in males but great in females, showing higher levels of female office blood pressures than male ones.
    No preview · Article · Jan 2014
  • No preview · Article · Jun 2014 · Journal of Hypertension
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