Prognostic significance of home blood pressure control on renal and cardiovascular outcomes in elderly patients with chronic kidney disease

Article (PDF Available)inHypertension Research 32(12):1123-9 · October 2009with15 Reads
DOI: 10.1038/hr.2009.165 · Source: PubMed
Abstract
The influence of home blood pressure (HBP) control on renal and cardiovascular outcomes is not fully defined, and the optimal blood pressure (BP) target in elderly patients with chronic kidney disease (CKD) remains unknown. To clarify the influence of HBP on the progression of CKD and the occurrence of cardiovascular events in elderly CKD patients, we recruited 104 patients with stage 3 to 5 CKD, who were > or =70 years of age. The mean follow-up duration was 39+/-15 months. HBP was measured every morning and evening for 7 consecutive days. HBP data were obtained every 6 months for 79 of these patients. There were significant correlations observed between morning systolic BP (SBP), evening SBP and the change in estimated glomerular filtration rate (eGFR) during the follow-up period (baseline/follow-up; morning r=-0.55/-0.51, evening r=-0.48/-0.38, all P<0.0001, baseline: baseline values, follow-up: mean values obtained every 6 months during the follow-up period). Stepwise multivariate regression analysis identified morning SBP and urinary protein excretion as independent predictors of a change in eGFR during the follow-up period. Cox proportional hazards analysis showed that baseline morning SBP, baseline evening SBP and follow-up morning SBP were significantly associated with an increased risk of renal events (hazard ratios; 1.04 (95% CI, 1.01-1.07), 1.06 (1.02-1.09) and 1.10 (1.04-1.17), respectively). However, Cox proportional hazards analyses showed that there was no significant association between BP and the risk of cardiovascular events. In conclusion, even among elderly CKD patients, HBP is a significant predictor of decline in renal function and the development of end-stage renal disease. In addition, the optimal target BP for elderly CKD patients needs to be clarified.

Figures

ORIGINAL ARTICLE
Prognostic significance of home blood pressure control
on renal and cardiovascular outcomes in elderly
patients with chronic kidney disease
Tomonari Okada, Toshiyuki Nakao, Hiroshi Matsumoto, Yume Nagaoka, Ryo Tomaru, Hideaki Iwasawa and
Toshikazu Wada
The influence of home blood pressure (HBP) control on renal and cardiovascular outcomes is not fully defined, and the optimal
blood pressure (BP) target in elderly patients with chronic kidney disease (CKD) remains unknown. To clarify the influence of
HBP on the progression of CKD and the occurrence of cardiovascular events in elderly CKD patients, we recruited 104 patients
with stage 3 to 5 CKD, who were X70 years of age. The mean follow-up duration was 39
±
15 months. HBP was measured
every morning and evening for 7 consecutive days. HBP data were obtained every 6 months for 79 of these patients. There were
significant correlations observed between morning systolic BP (SBP), evening SBP and the change in estimated glomerular
filtration rate (eGFR) during the follow-up period (baseline/follow-up; morning r¼0.55/0.51, evening r¼0.48/0.38, all
Po0.0001, baseline: baseline values, follow-up: mean values obtained every 6 months during the follow-up period). Stepwise
multivariate regression analysis identified morning SBP and urinary protein excretion as independent predictors of a change in
eGFR during the follow-up period. Cox proportional hazards analysis showed that baseline morning SBP, baseline evening SBP
and follow-up morning SBP were significantly associated with an increased risk of renal events (hazard ratios; 1.04 (95% CI,
1.01–1.07), 1.06 (1.02–1.09) and 1.10 (1.04–1.17), respectively). However, Cox proportional hazards analyses showed that
there was no significant association between BP and the risk of cardiovascular events. In conclusion, even among elderly CKD
patients, HBP is a significant predictor of decline in renal function and the development of end-stage renal disease. In addition,
the optimal target BP for elderly CKD patients needs to be clarified.
Hypertension Research (2009) 32, 1123–1129; doi:10.1038/hr.2009.165; published online 9 October 2009
Keywords: cardiovascular disease; chronic kidney disease; elderly patients; home blood pressure
INTRODUCTION
Japan is rapidly becoming an aged society. The prevalence of chronic
kidney disease (CKD) increases as the number of elderly individuals in
the population grows, indicating that Japan will see a rise in the
prevalence of CKD in the coming years.
1
The mean age at which
patients started chronic dialysis was 67.2 years in 2008 and has tended
to increase every year in Japan.
2
Thus, it is important to prevent the
progression of CKD to end-stage renal disease in elderly CKD patients.
Hypertension is one of the most important factors associated with
the progression of CKD. The current guidelines recommend a target
blood pressure (BP) of o140/90 mm Hg for elderly hypertensive
patients.
3,4
A further reduction in BP is recommended for CKD
patients. Several studies have shown that BP control leads to a
reduction in cardiovascular risk among elderly hypertensive
patients.
5,6
However, there are few studies regarding the influence of
BP control on the progression of CKD or cardiovascular risk in elderly
CKD patients. Thus, it is not clear whether or not strict BP control
provides benefits for elderly CKD patients. In addition, although
several studies have shown that home BP (HBP) is more predictive of
the progression of CKD than clinic BP,
7–10
the effect of HBP control
on renal outcomes has not been fully evaluated in elderly CKD
patients. Therefore, we sought to identify whether or not HBP
predicted the progression of CKD and the occurrence of cardio-
vascular events in elderly CKD patients.
METHODS
Patients
We included 104 patients treated at our department between December 2003
and March 2009 who were X70 years of age and met the eligibility criteria. The
inclusion criteria were as follows: (1) patients had to have already been
performing HBP measurements at regular intervals before participating in this
study; (2) patients had to have been treated for at least 3 months at our clinic;
(3) they had to provide a 24-h urine collection specimen; and (4) their
estimated glomerular filtration rates (eGFRs) had to be o60 mlmin
1
per
1.73 m
2
. We excluded patients who started dialysis therapy or died within a year
after study enrollment, patients with malignancies and those whose HBP data
Received 10 July 2009; revised 7 August 2009; accepted 20 August 2009; published online 9 October 2009
Department of Nephrology, Tokyo Medical University, Tokyo, Japan
Correspondence: Dr T Okada, Department of Nephrology, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo-to 160-0023, Japan.
E-mail; t-okada@tokyo-med.ac.jp
Hypertension Research (2009) 32, 11231129
&
2009 The Japanese Society of Hypertension All rights reserved 0916-9636/09 $32.00
www.nature.com/hr
were judged inaccurate or inadequate. The baseline clinical characteristics
of included patients are shown in Table 1. Underlying renal diseases were
diagnosed on the basis of medical history or renal biopsy findings.
BP measurements
Clinic BP was measured by a nurse using a validated electronic sphygmoman-
ometer (H-55, TERUMO, Tokyo, Japan) with the patients in a seated position
after at least 2 minutes of rest between 0900 hours and 1500 hours. A single
measurement was recorded. HBP was measured according to the guidelines for
HBP measurement of the Japanese Society of Hypertension (JSH).
4
BP was
measured using a semiautomatic arm device with the patients in a seated
position after at least 1 minute of rest. The nurses checked to ensure that the
patients knew how to use the devices accurately and checked the validity of the
devices. BP was measured in the morning, within 1 hour of waking and in the
evening just before bedtime. The value of a single measurement was recorded at
each of these time points. The patients recorded BP data as described above for
7 days preceding their clinic visit every 6 months. The morning and evening BP
values for each patient were calculated as the mean values of the 7 daily
measurements at each time point. Samples were collected to test patients
hemoglobin, serum albumin, creatinine and 24-h urinary protein excretion
every 6 months. All included patients provided their informed consent
regarding the use of their clinical data in this study.
Study protocol
We treated the patients according to the current guidelines for BP control
in elderly hypertensive patients. We set up a primary target BP of o140/
90 mmHg in the clinic and o135/85 mm Hg at home. Further reduction of BP
was individualized according to each patient’s characteristics. Antihypertensive
drugs were selected according to the guideline of the JSH.
11
The mean follow-
up period was 39
±
15 months with a range of 12–65 months. After the baseline
examination, the patients visited the clinic every 2–3 months. Of the 104
patients who met the initial inclusion criteria, HBP data and the aforemen-
tioned clinical data were obtained every 6 months for 79 patients. Data
regarding HBP during the follow-up period were not available for the
remaining 25 patients. Follow-up variables were defined as the mean values
obtained every 6 months for each of the 79 patients. eGFR was calculated using
the following formula: eGFR¼194Cr
1.094
age
0.287
(0.739, if female).
12
The annual change in eGFR during the follow-up period was defined by the
following formula: ((final eGFR–initial eGFR)/follow-up months12)
(ml min
1
per 1.73 m
2
per year). We examined the correlation between the
change in eGFR and BP data, and examined the independent variables that
influenced the change in eGFR by stepwise multivariate regression analysis. We
also examined the influence of BP data on the renal outcomes using Kaplan–
Meier survival curves and multivariate Cox proportional hazards analysis. A
renal event was defined as the initiation of chronic dialysis, a doubling of serum
creatinine or death.
Acute deterioration of renal function occurred in two patients before the
initiation of dialysis due to pneumonia in one patient and heart failure in the
other patient. To exclude the influence of these instances of acute deterioration
in renal function, the final eGFR was defined as that obtained during the last
visit before initiation of dialysis or death. There were no acute changes in renal
function observed during the follow-up in any included patients.
In addition, we examined the influence of BP data on cardiovascular
outcomes using Kaplan–Meier survival curves and multivariate Cox pro-
portional hazards analyses. Cardiovascular events were defined as death due
to cardiovascular causes or new onset of cardiovascular events requiring
hospitalization. They included heart failure, ischemic heart disease, arrhythmia
requiring permanent pacemaker implantation, cerebral infarction, cerebral
hemorrhage and aortic aneurysm requiring surgery. Ischemic heart disease
included definite coronary artery disease (diagnosed by coronary angiography),
myocardial infarction, percutaneous coronary interventions or coronary artery
bypass grafting.
Finally, we evaluated the association between renal and cardiovascular
outcomes and HBP measured on two consecutive days (2-day HBP). Data
for 2-day HBP was obtained from the mean values of the first and the second
day during the 7-day period preceding the clinic visit.
Treatment during the follow-up period
During the follow-up period, we changed several patients’ medication regimens
to improve their BP control. The doses or numbers of antihypertensive drugs
were increased in 46 patients during the course of the study. They were
decreased or changed to another drug in the same class in 21 patients. They
were unchanged in 29 patients and were continued not to be administered in 8
patients. Among the 46 patients who received increased doses or additional
classes of antihypertensive drugs, 30 received an angiotensin-converting
enzyme inhibitor or an angiotensin receptor blocker, 18 received a calcium
channel blocker, 23 received an a blocker and 17 received a furosemide.
Recombinant human erythropoietin was administered to 46 patients during
the follow-up period.
Dietary protein restriction was instructed from dietitian in 45 patients,
and the prescribed amount of dietary protein was 0.69
±
0.07 (0.6–0.8) g kg
1
per day.
Five patients had their drug dosages decreased because of symptomatic
orthostatic hypotension. No serious adverse events related to antihypertensive
drugs were reported during the follow-up period.
Statistics
The data were expressed as means
±
s.d. P-values of o0.05 were considered to
be statistically significant. The changes in HBP profiles were analyzed using the
Table 1 Baseline clinical characteristics
Age (years) (n) 76
±
5
70–74/75–79/80–89 46/35/23
Gender (male/female, n)68/36
Underlying renal disease (n)
Nephrosclerosis/chronic glomerulonephritis/diabetic
nephropathy/polycystic kidney disease
44/31/22/4
Cr (mg per 100 ml) 1.96
±
1.16
Estimated GFR (ml min
1
per 1.73 m
2
)32.6
±
17.2
Creatinine clearance (ml min
1
per 1.73 m
2
)41.8
±
24.5
Urinary protein excretion (g per day) 1.18
±
1.29
Hemoglobin (g per 100 ml) 11.6
±
1.6
Albumin (g per 100 ml) 4.1
±
0.4
Estimated dietary sodium intake (mEq per day) 145
±
61
Estimated dietary protein intake (g kg
1
per day) 0.94
±
0.30
Body mass index (kg m
2
)23.6
±
3.0
Number of antihypertensive drugs (n)
0/1/2/3 or more 11/27/40/26
Class of antihypertensive drugs (n)
Calcium channel blocker/angiotensin-converting
enzyme inhibitor/angiotensin receptor
blocker/a-blocker/furosemide
68/31/58/12/28
Time of administration of antihypertensive drugs
Morning/morning and evening/evening 41/50/2
Blood pressure (mm Hg)
Morning 142
±
18/75
±
10
Evening 136
±
16/70
±
9
Clinic 134
±
18/67
±
12
Patients with a history of cardiovascular events (n) 30
Ischemic heart disease/cerebral
infarction/peripheral artery disease/arrhythmia requiring
permanent pacemaker implantation/aortic aneurysm
10/10/5/5/5
Abbreviation: GFR, glomerular filtration rate.
Home blood pressure and CKD in the elderly
TOkadaet al
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Wilcoxon signed rank test. Correlations between the change in eGFR and
clinical variables were analyzed by Pearsons correlation coefficient and stepwise
multivariate regression analysis. Renal and cardiovascular outcomes were
assessed using Kaplan–Meier survival analysis and multivariate Cox pro-
portional hazards analysis. Statistical analyses were performed using the
Statview computer program (Abacus Concepts, Berkeley, CA, USA).
RESULTS
Correlations between baseline BP parameters and change in eGFR
Figure 1 shows the correlations between baseline morning systolic BP
(SBP), evening SBP, clinic SBP and the change in eGFR that occurred
during the follow-up period. There were significant correlations
observed between all BP values and the change in eGFR. The
correlation coefficient between morning SBP and eGFR change was
the highest of the various time points tested.
Correlations between baseline variables, follow-up variables and
the change in eGFR
Table 2 shows the correlations between baseline variables, follow-up
variables and the change in eGFR. The baseline variables and the mean
decline rate in eGFR were not significantly different between the 79
patients whose follow-up HBP measurements were available and the
remaining 25 patients whose follow-up HBP measurements were not
available. Baseline and follow-up SBPs, urinar y protein excretion levels
and hemoglobin levels were significantly correlated with the change in
eGFR that occurred during the follow-up period. The stepwise multi-
variate regression analysis shown in Table 2 showed that morning SBP
and urinary protein excretion, in both the baseline and follow-up data,
were significant independent variables associated with the change in
eGFR that was observed during the study.
Two-day morning SBP (both the baseline and follow-up values)
were also found to be significantly associated with the change in eGFR
that occurred during the follow-up period on stepwise multivariate
regression analysis (b¼0.41, 0.34).
The mean decline in eGFR in patients with diabetic nephropathy
was significantly greater than that in patients with other renal diseases
(3.83
±
2.41 versus 2.18
±
3.06 ml min
1
per 1.73 m
2
per year,
P¼0.006). However, all baseline morning SBP, evening SBP and
urinary protein excretion values were significantly greater in
patients with diabetic nephropathy than in patients with other
renal diseases.
Between CKD 4 and 5 patients, the meandeclineineGFRinpatients
receiving recombinant human erythropoietin (n¼38) was significantly
greater than that in patients not receiving recombinant human
Change in eGFR
(ml/min/1.73m
2
/year)
Morning SBP (mmHg)
-12
-10
-8
-6
-4
-2
0
2
4
6
8
10
80 100 120 140 160 180 200
r =0.55
p <0.0001
Evening SBP (mmHg)
-12
-10
-8
-6
-4
-2
0
2
4
6
8
10
80 100 120 140 160 180 200
r =0.48
p <0.0001
Change in eGFR
(ml/min/1.73m
2
/year)
Clinic SBP (mmHg)
-12
-10
-8
-6
-4
-2
0
2
4
6
8
10
80 100 120 140 160 180 200
r =0.30
p =0.002
Change in eGFR
(ml/min/1.73m
2
/year)
Figure 1 Correlation between baseline morning systolic blood pressure (SBP), evening SBP, clinic SBP and changes in estimated glomerular filtration rate
(eGFR).
Table 2 Correlations between baseline clinical variables, follow-up clinical variables and change in eGFR
Baseline clinical variables Follow-up clinical variables
Simple correlations
Stepwise multiple regression
Simple correlations
Stepwise multiple regression
r P-values b r P-values b
Morning SBP 0.55 o0.0001 0.48 0.51 o0.0001 0.41
Evening SBP 0.48 o0.0001 0.38 o0.0001
Clinic SBP 0.30 0.002 0.27 0.002
Morning DBP 0.16 0.1 0.09 0.44
Evening DBP 0.14 0.15 0.113 0.27
Clinic DBP 0.04 0.71 0.1 0.39
Urinary protein excretion 0.39 o0.0001 0.21 0.39 o0.0001 0.24
eGFR 0.09 0.93 0.002
a
0.95
Hemoglobin 0.21 0.03 0.27 0.01
Serum albumin 0.15 0.13 0.12 0.28
R
2
¼0.35 R
2
¼0.30
Abbreviations: DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure.
a
This means the correlation with baseline eGFR.
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TOkadaet al
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erythropoietin (n¼18) (3.16
±
2.20 versus 0.94
±
3.33 ml min
1
per
1.73 m
2
per year, P¼0.008). However, the baseline eGFR was signifi-
cantly lower and all baseline morning SBPs, evening SBPs and urinary
protein excretion levels were significantly greater in patients receiving
recombinant human erythropoietin than in those not receiving
recombinant human erythropoietin.
There were no significant differences observed in the change in
eGFR between patients receiving renin–angiotensin system inhibitors
and those not receiving these drugs.
There were no significant differences observed in the change in
eGFR among different age subgroups (o75, 75–79 and X80 years).
BP profile during the follow-up period
Among the 79 patients in whom follow-up HBP data could be
obtained, the mean baseline morning BP and evening BP were
141
±
18/75
±
10 and 136
±
15/71
±
9 mm Hg, respectively. The mean
final morning BP and evening BP were 138
±
14/72
±
10 and 134
±
13/
68
±
10 mm Hg, respectively. Only morning diastolic BP was found to
be significantly decreased from baseline (Po0.01). Among the 58
patients in whom HBP data could be obtained 2 years after the
baseline BP reading was taken, both the mean morning BP (134
±
12/
71
±
9 mm Hg) and evening BP (129
±
14/67
±
10 mm Hg) were found
to be significantly decreased as compared with the baseline BP
measurement (Po0.01 for both). A total of 43% of the patients
(n¼34) and 18% of the patients (n¼14) achieved mean morning SBP
of o135 mm Hg and 125 mm Hg, respectively. A total of 58% of the
patients (n¼46) and 25% of the patients (n¼20) achieved mean
evening SBP of o135 mm Hg and 125 mm Hg, respectively.
Urinary protein excretion profiles during the follow-up period
Overall, urinary protein excretion did not significantly change during
the follow-up period (final: 1.15
±
1.31 g per day). However, urinary
protein excretion did significantly decrease in the 39 patients whose
baseline levels were 41 g per day (baseline: 2.40
±
1.24, final:
1.91
±
1.67 g per day, P¼0.01). The proportion of patients receiving
renin–angiotensin system inhibitors was significantly higher in those
with a baseline urinary protein excretion of 41 g per day as compared
with those with a baseline urinary protein excretion of o1g per day
(82 versus 58%, P
¼0.01 by w
2
-test).
Association between renal events and SBP
Of the 104 patients included in the study, chronic dialysis was started
in 19 patients and a doubling of serum creatinine values occurred in
7 patients. A total of four patients died, and the causes of death
were heart failure in one patient, myocardial infarction in one patient
and pneumonia in two patients.
Figure 2 shows the Kaplan–Meier survival curves of renal events
based on baseline SBP. A baseline morning SBP and a baseline evening
SBP of o135 mm Hg was found to be associated with a significantly
reduced risk of renal events.
Table 3 shows the hazard ratios (HR) for renal events by SBP
categories. After excluding SBP, age, baseline eGFR and baseline
urinary protein excretion were found to be the significantly adjusted
variables associated with the risk of renal events (age: HR¼1.16
(95% CI, 1.05–1.28; Po0.01); baseline eGFR: HR¼0.87 (0.81–0.92;
Po0.001); and baseline urinary protein excretion: HR¼1.94 (1.43–
2.65; Po0.001)). These three variables remained significant even after
the baseline SBP variable was added back into the Cox models.
Both baseline morning SBP and evening SBP were significantly
associated with renal events. A baseline morning SBP of o135 mm Hg
indicated a significantly reduced risk of renal events, whereas a
baseline morning SBP of o125 mm Hg did not. Both a baseline
evening SBP of o135 mm Hg and a baseline evening SBP of
o125 mm Hg indicated a significantly reduced risk of renal events.
Clinic SBP did not affect renal outcome.
In terms of follow-up BP, morning SBP was significantly associated
with the risk of renal events. A morning SBP of o135 mm Hg tended
to reduce the risk of renal events.
The coefficients of variation for the baseline morning and evening
SBP were 5.6
±
2.5% and 6.2
±
3.4%, respectively. Neither the s.d.
values nor the coefficient of variation values for home SBP signifi-
cantly affected renal outcome in either the univariate or multivariate
Cox proportional hazards analyses.
The Cox models that included 2-day HBP as independent variable
showed that baseline morning and evening 2-day SBP were also
significantly associated with renal outcome (2-day morning SBP:
HR¼1.03 (95% CI, 1.00–1.06; P¼0.037) and 2-day evening SBP:
HR¼1.05 (1.02–1.08, P¼0.001)). Follow-up morning and evening
2-day HBP were also significantly associated with renal outcome
(2-day morning SBP: HR¼1.06 (95% CI, 1.02–1.10; P¼0.007) and
2-day evening SBP: HR¼1.07 (1.02–1.13, P¼0.009)).
Association between cardiovascular events and SBP
Among the 104 patients, a total of 15 cardiovascular events
occurred in 12 patients, including 7 incidents of heart failure, 4
ischemic heart disease events, 2 arrhythmias requiring permanent
pacemaker implantation, 1 cerebral infarction and 1 cerebral
hemorrhage.
0
20
40
60
80
100
Disease-free survival (%)
0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70
(Months) (Months)
010203040506070
(Months)
ab c
Morning systolic BP Evening systolic BP Clinic systolic BP
Disease-free survival (%)
0
20
40
60
80
100
Disease-free survival (%)
0
20
40
60
80
100
p=0.009
p=0.006
p=0.28
135 mmHg (n=65)
<135 mmHg (n=39) <135 mmHg (n=48)
135 mmHg (n=56)
140 mmHg (n=40)
<140 mmHg (n=64)
Figure 2 Kaplan–Meier curves for renal events according to baseline systolic blood pressure (BP).
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No cardiovascular events developed in any patient whose morning
SBP or evening SBP was o125 mm Hg at baseline and during the
follow-up. Figure 3 shows the Kaplan–Meier survival analysis exam-
ining cardiovascular outcomes according to baseline SBP values. There
was no significant difference in outcome noted between the group
with a baseline SBP of o135 mm Hg and the group with a baseline
SBP of 4135 mm Hg.
Table 4 shows the HR for cardiovascular events by SBP. Excluding
SBP, a history of cardiovascular events was the only significant variable
found to affect cardiovascular outcome (HR, 4.25 (95% CI, 1.24
Table 3 Hazard ratios of renal outcome by SBP
Baseline Follow-up
Hazard ratio (95% CI) P-value Hazard ratio (95% CI) P-value
Morning SBP (per 1 mm Hg) 1.04 (1.01–1.07) 0.006 1.10 (1.04–1.17) 0.001
Evening SBP (per 1 mm Hg) 1.06 (1.02–1.09) 0.0007 1.05 (1.00–1.11) 0.07
Clinic SBP (per 1 mm Hg) 1.02 (0.99–1.06) 0.17 1.04 (0.98–1.09) 0.18
Morning SBP X135 mm Hg (versus o135 mm Hg) 4.90 (1.60–15.01) 0.005 2.61 (0.86–7.93) 0.09
Morning SBP X125 mm Hg (versus o125 mm Hg) 2.63 (0.49–14.14) 0.26 1.30 (0.32–5.21) 0.71
Evening SBP X135 mm Hg (versus o135 mm Hg) 4.68 (1.72–12.75) 0.003 2.45 (0.68–8.76) 0.17
Evening SBP X125 mm Hg (versus o125 mm Hg) 4.14 (1.14–15.01) 0.03 2.52 (0.63–10.14) 0.19
Clinic SBP X140 mm Hg (versus o140 mm Hg) 2.62 (0.97–7.09) 0.06 1.73 (0.48–6.24) 0.4
Clinic SBP X130 mm Hg (versus o130 mm Hg) 1.52 (0.56–4.13) 0.41 4.31 (1.19–15.62) 0.03
Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure.
Each SBP variable was adjusted for sex, age, baseline eGFR, urinary protein excretion (UP), hemoglobin (Hb) and serum albumin (Alb). Baseline SBP was adjusted for the each baseline data of UP,
Hb and Alb. Follow-up SBP was adjusted for the each mean value of UP, Hb and Alb during follow-up.
0
20
40
60
80
100
Disease-free survival (%)
Disease-free survival (%)
Disease-free survival (%)
0
(Months)
0
20
40
60
80
100
0
20
40
60
80
100
Morning systolic BP Evening systolic BP Clinic systolic BP
p=0.35
p=0.10 p=0.38
70605040302010 0
(Months)
70605040302010 0
(Months)
70605040302010
<135 mmHg (n=39)
135 mmHg (n=65)
<135 mmHg (n=48)
135 mmHg (n=56)
<140 mmHg (n=64)
140 mmHg (n=40)
ab c
Figure 3 Kaplan–Meier curves for cardiovascular events according to baseline systolic blood pressure (BP).
Table 4 Hazard ratios of cardiovascular outcome by SBP
Baseline Follow-up
Hazard ratio (95% CI) P-value Hazard ratio (95% CI) P-value
Morning SBP (per 1 mm Hg) 1.00 (0.97–1.03) 0.97 1.00 (0.89–1.13) 0.65
Evening SBP (per 1 mm Hg) 1.03 (0.99–1.07) 0.11 1.09 (0.97–1.23) 0.16
Clinic SBP (per 1 mm Hg) 1.01 (0.98–1.05) 0.54 1.04 (0.95–1.14) 0.36
Morning SBP X135 mm Hg (versus o135 mm Hg) 1.42 (0.37–5.41) 0.61 1.91 (0.26–14.02) 0.65
Evening SBPX135 mm Hg (versus o135 mm Hg) 2.75 (0.70–10.74) 0.15 6.09 (0.77–47.97) 0.09
Clinic SBPX140 mm Hg (versus o140 mm Hg) 0.58 (0.16–2.02) 0.39 2.14 (0.16–28.65) 0.56
Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure.
Each SBP variable was adjusted for sex, age, history of cardiovascular events, baseline eGFR, hemoglobin (Hb) and serum albumin (Alb). Baseline SBP was adjusted for the each baseline data of
Hb and Alb. Follow-up SBP was adjusted for the each mean value of Hb and Alb during follow-up.
Home blood pressure and CKD in the elderly
TOkadaet al
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14.59; Po0.05)). A history of cardiovascular events remained a
significant predictor of cardiovascular outcome even when each SBP
variable was added to the Cox models. Table 4 shows that each SBP
variable was not a significant risk factor for the development of a
cardiovascular event. However, increased evening SBP tended to be
associated with an increased risk of a cardiovascular event, although it
was not statistically significant.
Cox proportional hazards analysis using 2-day HBP as independent
variable showed that 2-day HBP was not associated with cardio-
vascular outcome (data not shown).
Correlations between baseline HBP and clinic BP
Morning SBP and evening SBP were found to be significantly
correlated with clinic SBP (r¼0.42, P¼0.0001 and r¼0.34,
P¼0.0005, respectively). The correlation between 2-day HBP and
clinic BP was also found to be significant. However, the correlation
coefficients for 2-day HBP were lower than those of HBP obtained
over a 7-day period (2-day morning SBP: r¼0.37, P¼0.0001; 2-day
evening SBP: r¼0.28, P¼0.005).
DISCUSSION
We examined the prognostic significance of home SBP on the decline
in renal function or risk of end-stage renal disease in the elderly CKD
patients. These results are consistent with those of the previous studies
performed on CKD patients whose age was younger than those in the
present study.
7–10
Masked hypertension is prevalent in CKD
patients,
13,14
and older age is associated with a greater prevalence of
masked hypertension among treated hypertensive patients.
15,16
Thus,
HBP measurement might contribute to improved BP control in
elderly CKD patients.
It is possible that multiple measurement of HBP might contribute
to the superiority of its predictive value. However, the present study
showed that 2-day home SBP was also significantly associated with
renal outcome. One previous study has also examined the predictive
value of 2-day HBP for a diagnosis of CKD among the general
population.
17
Previous studies have shown the influence of BP on the risk of
cardiovascular events
18–20
and the benefit of BP control in lowering
cardiovascular risk among elderly hypertensive patients.
5,6,21
However ,
only small proportions of CKD patients were included in these studies,
and data on renal outcome are scarce in elderly CKD patients. In the
Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly
Hypertensive Patients (JATOS), there was no significant difference
noted in the incidence of renal failure between the strict treatment
group (mean final BP, 135.9/74.8 mm Hg) and the mild treatment
group (mean final BP, 145.6/78.1 mm Hg).
22
In addition, no previous
interventional studies have achieved a mean SBP of o130 mm Hg.
Thus, at present, there is no evidence that a target BP of o130/
80 mm Hg is beneficial in terms of prevention of renal events in elderly
CKD patients.
The JSH proposed a provisional target HBP of o135/85 mm Hg for
elderly persons and one of o125/75 mm Hg for CKD patients in
2009.
4
On the basis of the above BP targets, we examined the HR for a
home SBP of 4135 mm Hg as well as a home SBP of 4125 mm Hg.
We found that baseline morning or evening SBPs of 4135 mm Hg
significantly predicted an increased risk of renal events, whereas only a
baseline evening SBP of 4125 mm Hg predicted an increased risk of
renal events. Neither a follow-up home SBP of 4135 mm Hg nor a
follow-up home SBP of 4125 mm Hg was associated with an
increased risk of renal events. In the present study, we were unable
to identify an appropriate target HBP for elderly CKD patients that
could potentially reduce the risk of renal events. The validity of the
provisional target HBP for CKD patients proposed by JSH should be
verified in future studies, and further studies are necessary to
determine the most appropriate target BP for preventing renal events
in elderly CKD patients.
Chronic kidney disease is an important risk factor for cardiovas-
cular disease. Several previous studies have shown that CKD increases
cardiovascular risk among elderly hypertensive patients.
23,24
However ,
the association between BP control and cardiovascular risk has not
been clearly defined in elderly CKD patients. The present study did
not show a significant association between BP control and cardiovas-
cular risk. We propose several possible reasons for these results. First,
a history of cardiovascular events might greatly affect the occurrence
of future cardiovascular events, independent of BP control. Second,
both HBP and clinic BP were better controlled in the present study
than in previous studies. For example, the Hypertension in the Very
Elderly Trial (HYVET) showed a significant reduction in cardiovas-
cular events in the active-treatment group.
6
However, the mean
achieved BP in the active-treatment group and the placebo group
were 143.5/77.9 mm Hg and 158.5/84.0 mm Hg, respectively. The
mean value of final home SBP in the present study was almost the
same as the mean value of final SBP in the strict treatment group in
JATOS.
22
Thus, having a well-controlled BP might attenuate the
deleterious effect of hypertension on cardiovascular risk in the
present study.
The present study produced two interesting findings regarding the
possible association between BP control and cardiovascular risk. First,
an increase in home evening SBP tended to be associated with an
increased cardiovascular risk in the present study. We cannot explain
why evening BP was more closely associated with detection of a
cardiovascular risk than with morning BP. The Ohasama study found
that evening HBP, as well as morning HBP, had a strong predictive
significance for risk of stroke.
25
Second, patients with SBPs of
o125 mm Hg had no cardiovascular events in the present study.
However, it is not clear whether or not maintaining a home SBP of
o125 mm Hg has a beneficial effect on cardiovascular risk in CKD
patients. Several studies have shown that lower SBP of o120 mm Hg
has an increased risk of cardiovascular events in CKD patients.
26,27
On
the other hand, The Perindopril Protection Against Recurrent Stroke
Study (PROGRESS) has found no association between lowering the
SBP target to below 120 mm Hg and the risk of stroke in CKD
patients.
28
In the Candesartan Antihypertensive Survival Evaluation
in Japan (CASE-J) trial, the risk of cardiovascular events was sig-
nificantly higher among CKD patients who achieved an SBP of
o130 mm Hg than those without CKD who achieved the same level
of SBP.
29
In addition, the risk of cardiovascular events was increased in
the CKD patients who achieved an SBP of 130–139 mm Hg compared
with those who achieved an SBP of o130 mm Hg. These results
suggest that strict BP control might contribute to a reduction of
cardiovascular risk in CKD patients.
This study has several limitations. First, the study cohort was small
and the duration of the follow-up was relatively short. Thus, the
statistical power of this study might be limited, especially for detection
of cardiovascular risk. Second, we could not exclude the hemo-
dynamic effects of antihypertensive therapy on the change in eGFR
in patients whose antihypertensive drugs were increased during the
follow-up period. Third, the ratio of patients over 80 years old at
baseline was 22%. Thus, the distribution of age among subjects might
be inappropriate to determine the effect of age in elderly people.
Fourth, the adjustments we used for the multivariate Cox propor-
tional hazards analysis might have been insufficient. For example, data
Home blood pressure and CKD in the elderly
TOkadaet al
1128
Hypertension Research
concerning smoking habits was not available. However, we included
the main important variables in the Cox analysis, and the influence of
other clinical variables on the results might be small.
In conclusion, even among elderly CKD patients, HBP is a
significant predictor of decline in renal function and the development
of end-stage renal disease. Patients with an SBP of o125 mm Hg had
no cardiovascular events in this study, and an increase in home
evening SBP tended to be associated with an increased risk of
cardiovascular events. Further studies are needed to clarify the optimal
target BP (both at home and in the clinic) to prevent the progression
of CKD and to reduce cardiovascular risk in elderly CKD patients.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ACKNOWLEDGEMENTS
We are indebted to Professor J Patrick Barron of the Department of Interna-
tional Medical Communications Center of Tokyo Medical University for his
review of this paper.
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Home blood pressure and CKD in the elderly
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    • "Hypertension has a high impact on the decline of renal function and the development of cardiovascular disease in elderly patients.20–22 The subanalysis of Systolic Hypertension in the Elderly Program showed that SBP is a strong, independent predictor of a decline in renal function among elderly patients.21 "
    [Show abstract] [Hide abstract] ABSTRACT: We investigated the effects of aliskiren in terms of its inhibition of the renin-angiotensin-aldosterone system (RAAS) as well as that on blood pressure (BP), and renal and cardiac protection in elderly chronic kidney disease (CKD) patients with hypertension. Nineteen elderly CKD patients (nine males, ten females, aged 74.6 ± 5.8 years) were assigned to receive 150 mg/day of aliskiren added to existing antihypertensives for 6 months. Changes in plasma renin activity (PRA), angiotensin I (Ang I), angiotensin II (Ang II), aldosterone (Ald), BP, estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio (UACR), left ventricular ejection fraction (LVEF), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), and plasma brain natriuretic peptide (BNP) levels were evaluated. ALISKIREN SUPPRESSED THE RAAS AS FOLLOWS: PRA 1.3 ± 1.0 to 0.3 ± 0.3 ng/mL/hour, P < 0.05; Ang I 59.5 ± 32.1 to 26.0 ± 17.3 pg/mL, P < 0.05; Ang II 58.4 ± 62.1 to 14.3 ± 9.0 pg/mL, P < 0.05; and Ald 86.1 ± 38.3 to 80.1 ± 52.6 pg/mL, not significant (NS). Aliskiren reduced BP (153.6/77.2 ± 14.9/10.4 to 130.9/72.2 ± 15.6/9.9 mmHg, P < 0.05). It also reduced UACR (747.1 ± 1121.4 to 409.6 ± 636.8 mg/g, P < 0.05), whereas it did not change eGFR (52.1 ± 29.2 to 51.2 ± 29.3 mL/min/1.73 m(2), NS), LVEF (66.8 ± 7.9 to 66.5% ± 6.8%, NS), IVST (10.1 ± 1.8 to 9.9 ± 1.8 mm, NS), LVPWT (10.0 ± 1.6 mm to 10.0 ± 1.4 mm, NS), or BNP (48.2 ± 46.0 to 54.9 ± 41.1 pg/mL, NS). Aliskiren was effective for BP control and reduced UACR while maintaining eGFR and heart function in elderly CKD patients with hypertension.
    Full-text · Article · Sep 2012
  • [Show abstract] [Hide abstract] ABSTRACT: Hypertension Research, official publication of the Japanese Society of Hypertension, publishes papers reporting original clinical and experimental research in the field of hypertension and related cardiovascular diseases.
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  • [Show abstract] [Hide abstract] ABSTRACT: The clinical consequences of the results obtained by kidney biopsy in patients with diabetes mellitus Type 1 or Type 2 have been controversial. Our study was conducted to assess clinical symptoms and histological diagnoses in patients with diabetes mellitus Type 1 and Type 2 undergoing kidney biopsy. Observational study. The study included data from 567 consecutive renal biopsies of patients with diabetes mellitus Type 1 or 2 and chronic kidney disease (CKD) examined by standard histopathological procedures. The main outcome measures were incidence of diabetic nephropathy (DN) and glomerulonephritis (GN), predictors for the presence of both DN or GN. Approximately 70% of patients with diabetes mellitus Type 1 or 2 and evidence for CKD had DN. Glomerular diseases present in approximately 30% of patients with diabetes were predominantly immune complex GN and secondary focal glomerulosclerosis, followed by IgA-GN, which was associated with microhematuria (p = 0.01) and hypertension (p = 0.04). Only a minority had membranous GN, which was associated with nephrotic syndrome (p = 0.004). Progressive CKD predicted the presence of GN in diabetes mellitus Type 2 (r = -0.98; p = 0.02). GN is not uncommon in patients with diabetes and evidence for CKD. Kidney biopsy should therefore be considered in patients with diabetes and progressive CKD.
    Article · Sep 2011
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