Quantifying the paradoxical effect of higher systolic blood pressure on mortality in chronic heart failure

Article (PDF Available)inHeart (British Cardiac Society) 95(1):56-62 · January 2009with58 Reads
DOI: 10.1136/hrt.2007.134973 · Source: PubMed
Abstract
Although higher blood pressures are generally recognised to be an adverse prognostic marker in risk assessment of cardiology patients, its relationship to risk in chronic heart failure (CHF) may be different. To examine systematically published reports on the relationship between blood pressure and mortality in CHF. Medline and Embase were used to identify studies that gave a hazard or relative risk ratio for systolic blood pressure in a stable population with CHF. Included studies were analysed to obtain a unified hazard ratio and quantify the degree of confidence. 10 studies met the inclusion criteria, giving a total population of 8088, with 29 222 person-years of follow-up. All studies showed that a higher systolic blood pressure (SBP) was a favourable prognostic marker in CHF, in contrast to the general population where it is an indicator of poorer prognosis. The decrease in mortality rates associated with a 10 mm Hg higher SBP was 13.0% (95% CI 10.6% to 15.4%) in the heart failure population. This was not related to aetiology, ACE inhibitor or beta blocker use. SBP is an easily measured, continuous variable that has a remarkably consistent relationship with mortality within the CHF population. The potential of this simple variable in outpatient assessment of patients with CHF should not be neglected. One possible application of this information is in the optimisation of cardiac resynchronisation devices.
Quantifying the paradoxical effect of higher systolic
blood pressure on mortality in chronic heart failure
C E Raphael, Z I Whinnett, J E Davies, M Fontana, E A Ferenczi, C H Manisty, J Mayet,
D P Francis
See Editorial, p 4
International Centre for
Circulatory Health, Imperial
College London and St Mary’s
Hospital, London, UK
Correspondence to:
Dr C E Raphael, International
Centre for Circulatory Health, St
Mary’s Hospital and Imperial
College, 59 North Wharf Rd,
London, UK; claire.raphael@
gmail.com
Accepted 13 May 2008
Published Online First
15 August 2008
ABSTRACT
Background: Although higher blood pressures are
generally recognised to be an adverse prognostic marker
in risk assessment of cardiology patients, its relationship
to risk in chronic heart failure (CHF) may be different.
Objective: To examine systematically published reports
on the relationship between blood pressure and mortality
in CHF.
Methods: Medline and Embase were used to identify
studies that gave a hazard or relative risk ratio for systolic
blood pressure in a stable population with CHF. Included
studies were analysed to obtain a unified hazard ratio and
quantify the degree of confidence.
Results: 10 studies met the inclusion criteria, giving a
total population of 8088, with 29 222 person-years of
follow-up. All studies showed that a higher systolic blood
pressure (SBP) was a favourable prognostic marker in
CHF, in contrast to the general population where it is an
indicator of poorer prognosis. The decrease in mortality
rates associated with a 10 mm Hg higher SBP was 13.0%
(95% CI 10.6% to 15.4%) in the heart failure population.
This was not related to aetiology, ACE inhibitor or b
blocker use.
Conclusion: SBP is an easily measured, continuous
variable that has a remarkably consistent relationship with
mortality within the CHF population. The potential of this
simple variable in outpatient assessment of patients with
CHF should not be neglected. One possible application of
this information is in the optimisation of cardiac
resynchronisation devices.
High mortality and poor quality of life continue to
characterise a diagnosis of heart failure despite
maximal pharmacological treatment.
1
The number
of patients with heart failure will continue to rise
as the population ages and survival from myo-
cardial infarction continues to improve.
Effective measures of prognosis are required to
aid doctors with the timing of introduction of
treatments and may also be useful as a measure of
response to these treatments. Echocardiography
and cardiopulmonary exercise testing have been
shown to provide a useful measure of prognosis in
this condition. However, the availability of these
tests is still limited and repeated testing for
individual patients is often restricted by time and
cost constraints.
Systolic blood pressure (SBP) is by contrast, a
simple bedside test which is recorded routinely at
most cardiology appointments, can be tracked
longitudinally over time and requires minimal
equipment and training to assess. It therefore has
the potential to be a simple method of assessing
prognosis to enable doctors to target treatment and
potentially assess the impact therapies.
While it is well recognised that high SBP is an
adverse prognostic marker in risk assessment of
most cardiac patients,
23
its relationship with
mortality in the population with chronic heart
failure (CHF) is less clear. Management of heart
failure includes use of angiotensin converting
enzyme inhibitors (ACEi) and b blockers, both of
which have been shown to improve prognosis in
heart failure but which also lower the blood
pressure. A large cohort study in patients admitted
to hospital with acute heart failure showed that
lower blood pressure is associated with a higher
mortality.
4
However, within the population with chronic
heart failure, little prospective information has
been collected to examine the relationship between
SBP and mortality. A retrospective cohort study
showed that a lower SBP was associated with
higher mortality, although it suggested that there
is a non-linear, possibly J-shaped relationship
between SBP and mortality.
5
Several small studies,
but no large-scale studies, have looked at the
relationship between mortality and SBP.
Blood pressure is intrinsically related to the
heart’s ability to pump, and the mean arterial
blood pressure is proportional to the cardiac
output. Therefore, physiologically, there is a strong
case for blood pressure as a marker of prognosis in
heart failure.
This study therefore aimed to examine and
quantify the relationship between SBP and mor-
tality for stable patients with CHF.
METHODS
A literature search was performed using the key
words ‘‘heart failure’’ and ‘‘prognosis’’ or ‘‘mortal-
ity’’ using the Embase and PubMed databases.
These search terms were chosen to minimise bias
so that studies that did not focus on blood pressure
as the primary outcome measure and studies in
which there was a non-significant relationship
between blood pressure and mortality would be
included.
The inclusion criteria were studies performed in
a population with CHF with patients who were
medically stable for at least 1 month before entry
into the trial and had appropriate investigations
confirming their diagnosis. Patients had to have
had their SBP measured at the start of the trial.
Studies that provided sufficient statistical data
to calculate the univariate mortality hazard ratio
for a known unit change in SBP were included and
authors for studies that did not include sufficient
Heart failure and cardiomyopathy
56 Heart 2009;95:56–62. doi:10.1136/hrt.2007.134973
information were contacted to see if further information was
available. Two reviewers assessed each of the papers identified.
There were no disagreements between the reviewers over
selection of papers or extraction of data.
Statistical analysis
The univariate hazard ratios for mortality and 95% confidence
intervals were extracted from each of the included studies. Since
different papers quoted mortality hazard ratios for different
units of SBP, such as 1 standard deviation, the results were
standardised to a 10-unit increase in SBP. To do this, the
formula
was applied where HR
x
is the hazard ratio quoted in the source
document and x is the increase in SBP in mm Hg. So, for
example, for a 5-unit increase in SBP with a hazard ratio of 0.91,
x = 5 and HR
x
= 0.91, giving a standardised hazard ratio of 0.83
per 10-unit increase in SBP. The confidence intervals for each
hazard ratio were recalculated in the same way.
A fixed effects statistical analysis model was used to pool the
data. Each study was assigned a relative weight, calculated from
the reciprocal of the square of the width of the confidence
interval, where the confidence interval was expressed in
logarithmic units for a 10-unit increase in SBP. The hazard
ratios for each study were then expressed in log units, and the
weighted mean was calculated from the sum of the log of the
hazard ratio per unit SBP multiplied by the weighting for each
study. The logarithmic width of the confidence interval for the
weighted mean was 1/!(Sweight).
Two studies (Huynh
14
and Davos
12
) met the inclusion criteria
but the lower limit of the hazard ratio for mortality had been
rounded so that it was equal to the point estimate for the
hazard ratio—for example, 0.99 (0.99 to 1.00). The authors were
unable to supply more precise figures, so it was decided to assign
a lower limit confidence interval so that the confidence intervals
were symmetrical in logarithmic space around the point
estimate. This enabled these studies to be entered into the
analysis.
Heterogeneity was also assessed across the studies. To do this,
1/SE (a measure of precision) was plotted against ln(hazard
ratio per 10-unit SBP). The Spearman rank test was then used to
calculate whether there was any relationship between these
variables.
RESULTS
Identification of reports
The Medline and Embase searches for heart failure and
prognosis returned 7132 citations, 10 of which met the inclusion
criteria (table 1). This gave a total population of 8088, with
29 222 person-years of follow-up. The mean SBP across the
included studies was 124.9 mm Hg.
Relationship between SBP and mortality in CHF
In all of the studies of CHF, a higher blood pressure was found
to be associated with a better prognosis. The degree of benefit
conferred by a 10 mm Hg higher blood pressure varied between
studies. We pooled the data to produce a consensus estimate
and quantify its confidence intervals.
The pooled value for all studies included in the analysis gave a
hazard ratio of 0.885 (95% CI 0.87 to 0.90) for a 10 mm Hg
higher SBP in the population with CHF (fig 1). This equates to a
decrease in mortality of 13.0% (95% CI 10.6% to 15.4%) for a
10 mm Hg higher SBP. For a 1 mm Hg higher SBP, the decrease
in mortality is 1.2%. In the lowest tertile of papers (mean SBP
109), a 10 mm Hg higher SBP equated to an 18% decrease in
mortality, with a 10% decrease in mortality per 100 mm Hg
higher SBP in the top tertile.
Influence of ACE inhibitor and b-blocker use
Despite the difference in pharmacological treatments between
studies, there was no significant difference in the relationship
between SBP and mortality on subgroup analyses for patients
receiving different doses of b blockers (p = 0.93) or ACE
inhibitors (p = 0.49) (fig 2).
Ischaemic versus non-ischaemic causes of heart failure
The pooled value for mortality did not differ significantly when
comparing predominantly ischaemic with predominantly non-
ischaemic aetiologies (p = 0.78). Division of studies dichoto-
mously based on ejection fraction, however, did show a
significantly different hazard ratio relating mortality and blood
pressure (p = 0.006, fig 2).
Heterogeneity between studies
The Spearman rank test for heterogeneity showed no significant
evidence of heterogeneity between studies. On comparison of
hazard ratio for a 10-unit change in SBP for studies divided into
tertiles by mean SBP within the study showed a non-significant
difference in hazard ratio for the highest tertile compared with
the lowest tertile (p = 0.08) There was a non-significant
association between mean SBP within a study and standardised
hazard ratio (per 10-unit change in SBP) for that study
(p = 0.26, fig 3).
Comparison with non-heart failure studies
Five relatively recent meta-analyses of the relationship between
blood pressure and mortality in the general and/or hypertensive
population were identified.
2 3 6–8
This gave a total of over 12
million person-years of follow-up. The references for individual
trial data were extracted. The large studies and meta-analyses of
their results all showed a consistent relationship between SBP
and mortality such that a higher SBP conferred a poorer
prognosis in the non-heart failure population.
9–11
DISCUSSION
In this study we have found that a higher SBP is consistently
associated with a more favourable prognosis within the
population with CHF. This is in contrast to the rest of the
cardiac population, where a higher SBP is an adverse risk factor.
This relationship was most marked in populations with a lower
starting SBP.
Physiological relationship between SBP and mortality in CHF
A close relationship between SBP and mortality in CHF might
be expected from consideration of cardiac physiology. The mean
arterial blood pressure (MABP) is determined by the cardiac
output (CO), the systemic vascular resistance (SVR) and the
central venous pressure (CVP):
MABP = (CO 6 SVR) + CVP
In patients with cardiac disease but intact ventricular systolic
function, the MABP is mostly determined by peripheral
vasoconstriction. Therefore, if the systolic function is intact, a
higher blood pressure indicates poorer elasticity of the arteries.
Heart failure and cardiomyopathy
Heart 2009;95:56–62. doi:10.1136/hrt.2007.134973 57
Table 1 Characteristics of studies in the chronic heart failure population
Study Population P{
Patient
characteristics
No of patients
(no of events)
Mean (SD)
follow-up
(years)
Mean (SD)
SBP
(mm Hg) NYHA class Mean (SD) EF
Mean
age
Male
(%)
Aetiology
(%) b{ A{ C{ D{
Hazard ratio
for death
Lee
2006
5
DIG database;
RCT
No Patients with
stable HF and
normal sinus
rhythm
5747 (2066) 3.2 Not
recorded
II (64%)
III (36%)
28 (9) 63 77 Ischaemic (72)
Hypertensive (8)
Valvular (2)
Idiopathic (19)
Alcoholic (3)
U 95 U 81 0.89 (0.86 to
0.91) per 10 mm
Hg increase
Davos
2003
12
589 Consecutive
patients
presenting to HF
clinic
Yes Diagnosis of HF on
clinical and echo/
RV diagnosis
589 (208) 4.4 (2.1) 122.9 (34.8) I (101)
II (230)
III(152)
IV(42)
30.9 (0.73) 65 88 Not recorded 7 48.5 16.2 84.6 0.99 (0.98 to
0.99) per 1 mm
Hg increase
Robbins
1999
13
Consecutive
patients with HF
referred for
metabolic stress
testing
Yes Patients 18–70
with chronic HF
under evaluation
for heart
transplantation.
Exclusion
criteria—b blocker
or IV ionotropes
470 (71) 1.5 111 (18) Not recorded 20 (27) 52 71 47 CAD 0 86 U 79 1.4 (1.06 to
1.85) per 18 mm
Hg decrease
Huynh
2006
14
RCT Yes Patients .70 years
old. recently
discharged with HF
with >1 risk
factors for early
hospital
readmission
282 (269) 14 158 (52) 2.4 (1.0) 42.5 (19.1) 79 36 Ischaemic (56) 11 64 41 84 1.0 (0.99 to 1.0)
per 1 mm Hg
increase
Koike
2000
15
Consecutive
patients with
cardiac disease
referred for CPX
Yes Consecutive
patients with
known cardiac
disease. Exclusion
criteria—UA, MI
within 1 month,
documented lung
or cerebrovascular
disease
249 (29) 9.1 (1.7) 140 (24) I (46)
II (45)
III (9)
Not recorded 56 60 IHD (34)
Valvular (24)
Hypertensive
(23)
Other (19)
U U U U 1.01 (0.99 to
1.023) per 1 mm
Hg decrease
Rickli
2003
16
Consecutive
patients referred
to HF clinic
Yes HF with LVEF ,40
and able to perform
a CPX test
202 (44) 2.4 (1.7) 103 (17) I (7)
II (101)
III (90)
IV (4)
28 (7) 52 86 CAD (53)
DCM (34)
Valvular (2)
Hypertension (2)
Other or
combined (9)
45 99{ U 90 0.8 (0.65 to
0.98) per 10 mm
Hg increase
Continued
Heart failure and cardiomyopathy
58 Heart 2009;95:56–62. doi:10.1136/hrt.2007.134973
Table 1 Continued
Study Population P{
Patient
characteristics
No of patients
(no of events)
Mean (SD)
follow-up
(years)
Mean (SD)
SBP
(mm Hg) NYHA class Mean (SD) EF
Mean
age
Male
(%)
Aetiology
(%) b{ A{ C{ D{
Hazard ratio
for death
Cicoira
2001
17
Consecutive
patients referred
to heart failure
clinic
Yes Age .70 with a
history of
dyspnoea and
symptomatic
exercise tolerance.
Optimised medical
regimen
188 (61) 1.5 (0.6) 133 (22) Mean 2.3 (0.8) 38 (17)
(n = 105)
77 71 Ischaemic (66)
IDCM (14)
Valvular (7)
Restrictive (5)
HCM (2)
15 85 U 72 0.98 (0.96 to
0.99) per 1 mm
Hg increase
Terrovitis 2006
18
RCT Yes NYHA class II–
IV, LVEF (35%
on radionuclide
ventriculography
160 (55) 2 114 (18) I (6)
III (45)
III (42)
IV (7)
20 (9) 56 0.85 Ischaemic (46)
Non-ischaemic
(54)
28 U U 91 0.98 (0.96 to
0.99) per 1 mm
Hg increase
Pousset
2000
19
RCT Yes Clinically stable
CHF, LVEF ,45%
with at least
1 month on
constant
treatment.
Exclusions—MI in
past 3 months
117 (14) 0.64 (0.38) 123 (23) I (7)
II (62)
III (25)
IV (6)
28 (10) 55 79 IDCM (64)
CAD (28)
Anthracycline
induced (3)
Hypertension (3)
Valvular (3)
17 91 U 82 0.35 (0.18 to
0.69) per 23 mm
Hg increase
Walsh
1997
20
Patients enrolled
in clinical trials of
heart failure
drugs
Yes Symptomatic HF
for at least
2 months with
cardiomegaly on
CXR. LVEF ,35 or
an increase in
LVEDV .5.5 and
fractional
shortening ,30%
84 (43) 1.9 120* (94–
180)
II (56)
III (44)
Not recorded 64* 88 CAD (65)
Non-ischaemic
cardiomyopathy
(35)
U 23 U 100 0.97 (0.96 to
0.98) per 1 mm
Hg increase
*Median (range); {99% were receiving ACE inhibitors or angiotensin receptor blockers; {A, ACEi; b, b blockers; C, CCB; D, diuretics; P, prospective.
ACEi, angiotensin converting enzyme inhibitors; CAD, coronary artery disease; CPX, cardiopulmonary exercise test; CCB, calcium channel blockers; CHF, chronic heart failure; DCM, dilated cardiomyopathy; EF, ejection fraction; HCM, hypertrophic
cardiomyopathy; HF, heart failure; IDCM, ischaemic dilated cardiomyopathy; IHD, ischaemic heart disease; IV, intravenous; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New
York Heart Association; RCT, randomised control trial; RV, radionucleotide ventriculography; SBP, systolic blood pressure; U, unknown value (data not recorded in original study); UA, unstable angina.
Heart failure and cardiomyopathy
Heart 2009;95:56–62. doi:10.1136/hrt.2007.134973 59
As shown in numerous meta-analyses,
623
in patients
without heart failure, a higher SBP is associated with a poorer
prognosis.
The situation is entirely different within the population with
CHF. In these patients, a low blood pressure reflects a low
ejection fraction and cardiac output. The blood pressure is low
because the heart is unable to pump any more vigorously to
raise it. Therefore a higher blood pressure is associated with a
decreased mortality as it serves as an indirect measure of cardiac
function.
The MABP lies between the systolic and diastolic blood
pressures. We chose to focus on SBP as there were no data on
MABP in the studies analysed. Our study found a close and
consistent relationship between SBP and mortality in CHF,
with a higher SBP reflecting a better cardiac output and
therefore more favourable prognosis.
Bedside measures of prognosis in heart failure
To link SBP to cardiac output, we should recognise that it is the
difference between SBP and CVP that the heart is generating.
Accordingly, poor cardiac function may result in low SBP or
high CVP, or both. The prognostic value of high CVP has
long been recognised clinically, and in recent years has been
shown to have a close association with mortality.
21
The chief
attraction in blood pressure monitoring, however, is the relative
reliability of measurement, even by people with relatively brief
training.
Quantification of the relationship between SBP and mortality
The pooled value for all studies included in the analysis gave a
decrease in mortality of 13.0% (95% CI 10.6% to 15.4%) per
10 mm Hg higher SBP. The effect of a higher SBP is most
marked in populations with a lower starting SBP, with an 18%
lower mortality in the lowest tertile (mean SBP 109) and a 10%
decrease in the highest tertile (mean SBP 145) per 10 mm Hg
higher SBP. It is likely that the magnitude of effect associated
with an increase in SBP continues to diminish such that a
10 mm Hg increase from 160 to 170 mm Hg would confer a
much smaller decrease in mortality, if any. Studies included in
this analysis had a maximum SBP of 158 (Huynh
14
), where there
was a non-significant association between SBP and mortality. It
may be that a level of blood pressure is reached beyond which a
further increase confers an adverse prognosis, with a J-shaped
relationship between SBP and mortality.
Pharmacological effects on SBP
There are many factors that influence both blood pressure and
mortality in the population with CHF. Most drugs used in
management of heart failure (b blockers, ACEi, diuretics) all
serve to decrease blood pressure. In a patient with heart failure
and low blood pressure, it is difficult to establish whether the
blood pressure is low because of the advanced stage of the
disease with poor cardiac output or whether it is low because
the patient is being intensively managed pharmacologically.
The studies included in this analysis had a range of blood
pressures and a heterogeneous sample of blood pressure
lowering drugs. Despite this, there was a consistent relationship
between SBP and mortality. On subgroup analysis, the only
factor shown to affect this relationship significantly was
ejection fraction. This was in keeping with previous studies
on heart failure, which have shown that low blood pressure is
an adverse prognostic sign in patients with impaired systolic
Figure 1 Hazard ratios for mortality associated with a 10 mm Hg
increase in systolic blood pressure (SBP). In the pooled heart failure
studies, a 10 mm Hg increase in SBP implies a 13% decrease in
mortality. Conversely, in the non-heart failure population, an increase in
SBP is associated with a poorer prognosis.
Figure 2 Subgroup analyses of included studies. EF, ejection fraction;
SBP, systolic blood pressure.
Figure 3 There was a non-significant relationship between
standardised hazard ratio against the mean systolic blood pressure (SBP)
for that population (p = 0.26).
Heart failure and cardiomyopathy
60 Heart 2009;95:56–62. doi:10.1136/hrt.2007.134973
function but that it may in fact be a marker of good prognosis in
those with intact systolic function.
22
The lack of significant effect of pharmacological treatment on
the relationship between blood pressure and mortality suggests
a very powerful relationship between SBP and cardiac output,
such that it overcomes confounding factors of medical treat-
ment. This is also illustrated by the relatively consistent
relationship between SBP and mortality despite a heterogeneous
population with varying degrees of medical optimisation.
Systolic and diastolic heart failure
The studies included in this meta-analysis had a mean ejection
fraction of 28.3, indicating a population of predominantly
systolic heart failure. The study by Huynh, however, has a
mean ejection fraction of 42.5, with only 36% men and an
average SBP of 158 mm Hg. Additionally, 23% of patients in the
study by Koike had a hypertensive aetiology with a mean SBP of
140 and no EF reported. Hypertension is a common aetiology in
diastolic heart failure,
23
and these two studies may represent a
population with predominantly diastolic heart failure.
Interestingly, these are the only two studies identified where
the relationship between SBP and mortality is not significant
(HR = 0.99–1.0 in Huynh and HR = 0.99–1.023 in Koike).
Exclusion of these two studies does not alter the mean SBP
per 10-unit change in SBP, as both studies have relatively small
numbers.
Implications for clinical practice
While measurement of SBP is clearly not a substitute for
measurements of left ventricular ejection fraction and other
markers more closely associated with cardiac output, its
attraction lies in its simplicity. SBP can be routinely measured
at all outpatient visits and changes in SBP can be charted to
monitor disease progression. While echocardiographic data may
not exist before instigation of pharmacological treatment, SBP
measurements would have been taken. The prognostic implica-
tions of changes in SBP over time have not been assessed in any
study of which the authors are aware; however, this would be
useful information to collect.
Effect of antihypertensive drugs on SBP and cardiac output
While we have shown a close relationship between blood
pressure and mortality, it is obviously not our intention to
suggest that antihypertensive drugs should be omitted in
patients with heart failure. This study is entirely in keeping
with the finding that many drugs that improve prognosis in
systolic heart failure act to reduce blood pressure, including
ACEi, angiotensin receptor blockers and b blockers. The key
reason is that across a population of patients with heart failure
fully treated with these drugs the difference between their blood
pressures is driven to some extent by differences in cardiac
output.
The action of adding a prognostically beneficial vasodilator to
a patient’s treatment has the primary effect of reducing
systemic vascular resistance, allowing the cardiac output to
increase and the blood pressure to decrease. The cardiac output
increase (which might be witnessed as an increase in ejection
fraction) is beneficial, and the fall in blood pressure is a
manifestation of the relief of intense vasoconstriction.
If our study were to be extrapolated to changes in blood
pressure, it must be emphasised that it would only be possible
to do this if there were no changes in vasodilator drugs. As long
as the drug regimen were stable, a rise in blood pressure might
be a good sign after implantation (or optimisation) of a cardiac
resynchronisation therapy device.
Potential relevance to haemodynamic optimisation of cardiac
resynchronisation therapy
This consistent finding across studies in heart failure lends
indirect support to the concept of haemodynamic optimisation
of cardiac resynchronisation therapy with non-invasive blood
pressure monitoring. Rapid and reproducible algorithms for
such optimisation are now available.
24–26
These potentially
extend the haemodynamic improvements already achieved
from simply switching on the device. The landmark trials with
cardiac resynchronisation therapy showed an increase in blood
pressure, paralleling the improvements in symptoms and
survival, for patients entered into the device arm. For example
in the COMPANION trial, patients in the resynchronisation
arm initially gained approximately 2 mm Hg SBP in comparison
with the control arm, and went on to have a 18% relative
reduction (95% confidence interval 1% increase to 42%
reduction) in the combined end point of morbidity and
mortality.
27
Similarly the CARE-HF trial showed, at 3 months,
that the increment in blood pressure attributable to being in the
device arm was 5.8 (95% CI 3.5 to 8.2) mm Hg, and the
mortality reduction was 37% (95% CI 23% to 49%).
28
In each case, the increase in SBP is likely to represent an
improvement in cardiac output as a result of the resynchronisa-
tion. Since the SBP in patients with heart failure, unlike in the
general population, is more closely governed by the cardiac
output than peripheral resistance, this increase in SBP is likely to
reflect an improved cardiac output and ejection fraction.
Whether increased blood pressure is a reasonable proxy for
long-term outcomes has, however, been doubted, because of the
general perception in cardiology that lower blood pressures are
better. In this study, it becomes clear that increase in SBP, be it
from resynchronisation itself or its optimisation, need not be
assumed to be adverse, and might readily be beneficial. Of
course, specific trials would be needed to determine this beyond
doubt.
Study limitations
This type of study has many limitations. The populations
chosen were heterogeneous, with a range of ejection fractions
and mean systolic blood pressure, aetiologies and drugs, and
were carried out at different time points. However, there was
no significant association between hazard ratio and mean SBP
for the studies included (p = 0.16), which gives reassurance that
the key findings are not being driven by a small subset of
patients.
Additionally, with studies of different sample sizes there may
be effects apparent in small studies that disappear with larger
populations. However, there was no evidence of a relationship
between size of study and hazard ratio (p = 0.09). For
identification of studies to include in the analysis, there is also
the problem of publication bias, where studies that did not find
a significant relationship between mortality and blood pressure
are less likely to publish their data. This was dealt with by using
a search strategy that did not only return studies that looked at
blood pressure and mortality, but found all studies that reported
mortality data in a population with heart failure.
CONCLUSION
This study has shown that there is a close relationship between
SBP and mortality in the population with CHF. This is contrary
Heart failure and cardiomyopathy
Heart 2009;95:56–62. doi:10.1136/hrt.2007.134973 61
to the majority of cardiac disease, where a high SBP is an adverse
prognostic sign. Quantitative awareness of this relationship
between SBP and mortality may be of use in assessment or
sequential follow-up of patients or where more extensive
testing such as echocardiography is not available. It also gives
indirect support to the concept of monitoring SBP as a simple
haemodynamic marker during non-invasive haemodynamic
optimisation of cardiac resynchronisation.
Acknowledgements: All authors contributed to the planning and analysis of the
study, and interpretation of the results as well as to the writing of the paper. CER, ZIW
and JED designed and performed the literature search and studies for inclusion. MF,
EAF and CHM contributed to the statistical analysis of the results. JM and DPF
designed and managed the overall study and planned the analysis methods. All
authors approved the final manuscript. Guarantor—DPF.
Competing interests: None.
All researchers were independent of funders during the writing of this paper.
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Heart failure and cardiomyopathy
62 Heart 2009;95:56–62. doi:10.1136/hrt.2007.134973
    • "If high blood pressure (BP), body mass index and cholesterolemia represent traditional cardiovascular risk factors in the general population, they are correlated to a better prognosis in patients with chronic heart failure (HF) [1][2][3] . In a meta-analysis, Raphael and al emphasized the paradoxical effect of higher systolic BP on mortality of patients with chronic HF, showing a decrease of 13 % in cardiovascular death for an increase of 10 mmHg in systolic BP [1]. For the last decades, the prognostic impact of each determinant of BP profile such as systolic BP, diastolic BP, pulse pressure (PP), BP variability (BPV) was essentially studied in patients with hypertension [4], but few in chronic HF. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Traditional cardiovascular risk factors in the general population are usually correlated to a better prognosis in patients with chronic heart failure (HF). Most of the studies show that blood pressure variability (BPV) has noxious effect on general population but data are missing for patients with systolic HF. The aim of this study was to assess the prognostic impact of short-term blood pressure variability (BPV) in systolic HF. Methods and results We retrospectively studied 288 patients (60 ± 12 years-old; 79 % male) referred to our tertiary center of HF for the management of their systolic HF (left ventricular ejection fraction was 28 ± 9 %). All patients underwent ambulatory blood pressure monitoring (systolic BP: 110 ± 15; diastolic BP: 68 ± 10 and pulse pressure: 42 ± 11 mmHg) and the prognostic impact of BPV was collected with a mean follow-up of 4.4 ± 3.1 years. Twenty-five (9 %) patients were missing for follow-up. Among the others patients, 70 (27 %) cardiovascular events (cardiac deaths: 24 %; heart transplantation: 2 %) were recorded. By multivariate analysis BPV daytime (OR = 0.963, p = 0.033) and severe NYHA class (OR = 5.2, p < 0.0001) were found as independent predictors of cardiac event. Patients with a systolic daytime BPV under a cut-off value of 19 mmHg had the poorest prognosis with an OR for cumulative events of 1.65 (IC95 % 1.1–2.7; p < 0.04). Conclusion BPV is simple tool and a predictor of cardiac events in patients with systolic HF.
    Full-text · Article · Dec 2016
    • "Most BP lowering drugs such as diuretics, beta-blockers, ACE inhibitors, and angiotensin receptor blockers are effective in the prevention of heart failure [46]. Low BP in patients with systolic dysfunction and HTN is associated with poor CV outcomes, despite high BP being a risk factor for heart failure [47]. Few studies have investigated patients with heart failure and low BP because most prospective randomized studies did not include patients with low BP. "
    [Show abstract] [Hide abstract] ABSTRACT: Different treatment strategies are suggested for special situations. Hypertension is common in the elderly and frequently accompanied by or complicates other clinical conditions such as metabolic syndrome, coronary artery disease, heart failure, stroke, diabetes mellitus and chronic kidney disease.
    Full-text · Article · Dec 2015
    • "Nevertheless, in-hospital mortality can't be accounted for all the difference in the long term mortality, as the difference in the mortality rate became higher in the long term follow-up (Fig. 2). Data regarding SBP in patients diagnosed with acute or chronic HF and reduced systolic function has been carefully considered, and has been found to demonstrate an inverse relation between on admission SBP and mortality [3,5,6,14] . However, less data regarding the association between SBP on admission and mortality is available for patients with PSF. "
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Heart failure is a major cause of death and disability and poses a significant public health concern. Approximately half of the patients admitted with heart failure, have preserved left ventricular ejection fraction. The association between systolic blood pressure (SBP) and long-term outcome in this group has not been well established. Aim: The aim of our study is to evaluate the association between admission SBP and short term and long-term mortality outcomes in patients with heart failure and preserved systolic function. Methods: 1230 consecutive patients presenting with preserved left ventricular (LV) systolic function (defined as an LV ejection fraction ≥40%) were included in this survey. Patients were divided into quartiles according to admission SBP: low admission SBP (<127mmHg), intermediate admission SBP (128-145mmHg), high admission SBP (146-170mmHg) and very-high admission SBP (>170mmHg). Primary outcome included in hospital, one and four year mortality rates. Results: Elevated admission SBP was found to be associated with improved short and long-term mortality (HR=0.25 95% CI - 0.09-0.7, p=0.007 and HR=0.7 95% CI - 0.56-0.88, p=0.002 for the highest versus low SBP group, respectively). This finding was most notable in patients with acute heart failure and patients with ejection fraction≥50%. Conclusion: Elevated admission SBP is associated with a favorable short and long-term outcome in patients with heart failure and preserved systolic function. Key message: Low admission SBP is an independent predictor for short and long-term mortality in patients with HF and PSF.
    Full-text · Article · Oct 2015
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