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atients with congestive heart failure (CHF) are frequently re-hospitalized, worsening their quality of
life, and re-hospitalization for CHF is also associated with increased mortality rates.1,2 Therefore, re-hospitalization for CHF should be avoided. Renal insufficiency
increases the risk of CHF,35 but most studies that have investigated the role of renal function in CHF have included
only subjects with no known CHF or mild-to-moderate
CHF and excluded patients with severe renal dysfunction.
Patients hospitalized for CHF have more severe disease
and impaired renal function, but little is known about the
relation between renal dysfunction and re-hospitalization
because of CHF. Thus, the aim of the present study was to
investigate whether renal dysfunction is associated with rehospitalization for CHF after successful discharge.
Methods
The study protocol was approved by the Ethics Committee of The Jikei University School of Medicine (19-092
[5023]).
Patients with CHF who had been admitted from January
(Received October 4, 2007; revised manuscript received February 3,
2008; accepted February 24, 2008)
Division of Cardiology, Department of Internal Medicine, The Jikei
University School of Medicine, Tokyo, Japan
Mailing address: Kimiaki Komukai, MD, Division of Cardiology,
Department of Internal Medicine, The Jikei University School of
Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.
E-mail: komu@jikei.ac.jp
All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp
2003 through December 2004 and followed up after discharge at the outpatient clinic were reviewed. CHF was
diagnosed by 2 or more cardiologists on the basis of the
Framingham criteria. Patients were excluded if they had
CHF complicated by acute myocardial infarction, were
undergoing or starting dialysis during the follow-up period,
or had undergone cardiac surgery during the follow-up
period. With these selection criteria, 109 patients were
enrolled. The duration of follow-up was 61,466 days
(mean, 496 days; median, 348 days).
The estimated glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease
equation6 coefficient modified for Japanese patients: estimated GFR = 0.741175 Cr 1.154 age0.203 (ml min1
1.73 m2). For women, the estimated GFR was multiplied
by a correction factor of 0.742.
The 109 patients were divided into 2 groups: decreased
renal function (estimated GFR on admission <45 mlmin1
1.73 m2; 42 patients) and preserved renal function (estimated GFR on admission 45 mlmin1 1.73 m2; 67 patients). The 2 groups were compared on the basis of age,
sex, New York Heart Association (NYHA) class on admission, prescribed anti-CHF drugs at discharge, and the rates of
coronary artery disease, valvular heart disease, cardiomyopathy, atrial fibrillation, hypertension, diabetes mellitus
(DM), dyslipidemia, anemia, systolic dysfunction, previous
hospitalization for CHF, and worsening renal function during hospitalization. Cardiomyopathy was defined according
to heart catheterization or previous diagnosis. Hypertension
was defined as systolic blood pressure 140 mmHg, diastolic
blood pressure 90 mmHg, or previous history. DM was
defined as fasting plasma glucose concentration 126 mg/dl,
Circulation Journal Vol.72, July 2008
1153
60
N
Age (years)
Gender (male, %)
Hypertension (%)
DM (%)
Dyslipidemia (%)
Underlying heart disease (%)
Ischemic heart disease
Valvular heart disease
Cardiomyopathy
Atrial fibrillation
Estimated GFR (mlmin1 1.73 m2)
Serum creatinine (mg/dl)
Worsening renal function (%)
Anemia (%)
NYHA (%)
I
II
III
IV
Systolic dysfunction (%)
Previous hospitalization with CHF (%)
Prescription at discharge (%)
ACEI/ARB
-blocker
Loop diuretics
Aldosterone blocker
Prevalence (%)
Overall
109
71.91.3
67.0
55.0
36.7
38.5
30.3
16.5
18.3
49.5
53.52.4
1.170.06
22.9
22.0
50
40
30
20
10
0
3
4
CKD stage
9.2
25.7
15.6
49.5
58.9
32.1
Re-hospitalization free
1.0
56.0
59.6
80.7
37.6
DM, diabetes mellitus; GFR, glomerular filtration rate; NYHA, New York
Heart Association; CHF, congestive heart failure; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker.
0.8
0.6
0.4
0.2
0.0
0
500
1000
1500
Days
Fig 2. Kaplan-Meier curve of re-hospitalization for congestive heart
failure.
1.0
75
0.8
Sensitivity
Re-hospitalization free
1.0
0.8
p<0.001
90
60
0.6
45
0.4
30
0.2
0.0
0.0
15
0.2
0.4
0.6
0.8
1.0
1-specificity
0.6
estimated GFR 45
0.4
estimated GFR <45
0.2
0.0
0
500
1000
Days
1500
KOMUKAI K et al.
1154
Table 2 Baseline Characteristics of Patients With Preserved Renal Function and Patients With Decreased Renal Function
N
Estimated GFR (mlmin1 1.73 m2)
Serum creatinine (mg/dl)
Worsening renal function (%)
Age (years)
Gender (male, %)
Hypertension (%)
DM (%)
Dyslipidemia (%)
Underlying heart disease (%)
Ischemic heart disease
Valvular heart disease
Cardiomyopathy
Atrial fibrillation
NYHA III (%)
Systolic dysfunction (%)
Previous hospitalization with CHF (%)
Anemia (%)
Prescription at discharge (%)
ACEI/ARB
-blocker
Loop diuretics
Aldosterone blocker
p value
42
29.51.5
1.750.10
35.7
76.51.9
66.7
66.7
47.6
35.7
67
68.71.5
0.810.03
14.9
68.91.7
67.2
47.8
29.9
40.3
(<0.001)
(<0.001)
0.018
0.004
1.000
0.075
0.069
0.689
31.0
21.4
14.3
50.0
64.3
57.1
47.6
42.9
29.9
13.4
20.9
49.3
65.7
60.0
22.4
9.0
1.000
0.299
0.453
1.000
1.000
0.842
0.011
<0.001
47.6
61.9
81.0
33.3
61.2
58.2
80.6
40.3
0.173
0.841
1.000
0.544
Hazard ratio
95%CI
p value
1.028
1.088
0.546
1.010
0.640
1.0071.050
0.6151.925
0.3220.927
0.5801.757
0.3651.119
0.009
0.772
0.025
0.973
0.117
1.057
1.970
0.907
1.275
4.105
0.798
0.982
2.418
1.030
1.361
0.5981.870
1.0583.671
0.4571.798
0.7512.164
2.3827.074
0.4611.379
0.5721.685
1.4254.103
0.5611.889
0.7512.468
0.848
0.033
0.779
0.369
<0.001
0.419
0.947
0.001
0.925
0.310
0.572
0.820
1.186
1.456
0.3380.969
0.4791.404
0.5972.354
0.8572.475
0.038
0.820
0.626
0.165
Results
The baseline characteristics of the patients are shown in
1155
Hazard ratio
95%CI
3.513
1.036
0.532
1.856
0.514
0.689
0.712
0.975
1.8646.620
1.0101.063
0.2990.947
1.0273.354
0.2501.056
0.3751.265
0.3761.351
0.4742.006
p value
<0.001
0.006
0.032
0.041
0.070
0.229
0.299
0.945
Discussion
Relation Between Renal Dysfunction and CHF
Re-Hospitalization
Our study found that renal dysfunction is an independent
predictor of re-hospitalization for CHF. Several factors may
be involved in the relationship between renal dysfunction
and CHF. One is the renin angiotensin system (RAS),
which is activated in renal dysfunction,12,13 particularly by
renal artery stenosis and renal ischemia. In renal dysfunction of any origin, the RAS is upregulated to maintain GFR
through the compensatory mechanisms of increased glomerular capillary pressure and hyperfiltration.13 Activation
of the RAS exacerbates CHF,13,14 and inhibition of the RAS
with an ACEI or ARB has been shown in many clinical trials
to improve prognosis. Inhibition of the RAS also preserves
renal function. However, ACEIs and ARBs are underused
in patients who have CHF and renal dysfunction,15,16 probably because they can lead to hyperkalemia and elevated
serum levels of creatinine.17 In the present study, the rate of
ACEI/ARB prescription did not different significantly between patients with preserved renal function and those with
decreased renal function. In addition, non-use of ACEI/ARB
and renal dysfunction were independently related to CHF
re-hospitalization. However, we did not examine doses or
serum concentrations of ACEIs and ARBs; underdosing of
ACEIs and ARBs in patients with renal dysfunction might
obscure the relationship between renal dysfunction and
re-hospitalization for CHF.
Renal dysfunction activates the sympathetic nervous system (SNS),18,19 mainly because of renal ischemia. Decreased
clearance of catecholamines is also involved. Angiotensin
II can also stimulate the SNS. Inhibition of the SNS byCirculation Journal Vol.72, July 2008
KOMUKAI K et al.
1156
Conclusion
Decreased renal function is an independent predictor of
re-hospitalization for CHF. Even after successful discharge,
careful follow-up care is needed, especially for patients with
impaired renal function.
Acknowledgements
We thank Dr Okazaki for assistance with the manuscript and Dr
Matsushima for his helpful comment, especially on the statistics.
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