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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 5, September/October 2018
AFRICA
307
Multivariate logistic regression analysis confirmed that only
cystatin C level (OR: 12.311, 95% CI: 1.616–93.76,
p
=
0.015) and
age (OR: 0.925, 95% CI: 0.866–0.990,
p
=
0.023) were linked to
in-hospital deaths. Also there was a notable correlation between
plasma cystatin C and NT-proBNP levels (
r
=
0.324, 95% CI:
0.069–0.539,
p
=
0.014) and GFR (
r
=
–0.638, 95% CI: –0.770 to
–0.453,
p
<
0.001) (Table 4).
During the 36-month follow-up period, the primary endpoint
(death) occurred in 38 subjects. When we compared the admission
cystatin C levels among survivors and those who died, we did not
observe any significant difference between the two groups (
p
>
0.05) (Table 5).
Univariate and multivariate analyses were performed to
examine independent predictors of mortality for the entire
36-month follow-up period. When univariate Cox proportional
regression analysis was applied to baseline parameters, cystatin
C level was found to have no effect on mortality rate during
the 36-month follow-up period [hazard ratio (HR): 1.531,
95% CI: 0.696–3.371,
p
=
0.290], but age (HR: 0.978, 95% CI:
0.960–0.997,
p
=
0.023) and sodium level (HR: 0.927, 95% CI:
0.874–0.982,
p
=
0.010) were found to be related to mortality rate.
In the multivariate Cox proportional hazard model including
age, cystatin C, NT-proBNP and sodium levels, LVEF and
GFR variables, only admission sodium level was a significant
independent predictor of death during the 36-month follow up
(HR: 0.937, 95% CI: 0.880–0.996,
p
=
0.037) (Table 6, Fig. 1).
Discussion
This study showed that higher admission cystatin C levels among
patients with ADHF were related to in-hospital mortality rates,
and in multivariate analysis, both cystatin C level and age
were regarded as independent predictors of in-hospital death.
However, during long-term follow up, when the two groups were
compared in terms of mortality assessed on an annual basis,
sodium level was the only independent predictor of death.
The combination of acute cardiac and renal dysfunction,
termed cardiorenal syndrome,
17
is associated with unfavourable
consequences in patients with acute HF.
18
Possible mechanisms
for renal dysfunction in HF are low cardiac output, higher central
blood pressure, renin–aldosterone–angiotensin axis dysfunction,
activation of sympathetic tone, oxidative damage, and impaired
renal perfusion.
19
Therefore, assessing renal function may simply
show haemodynamic and neurohormonal perturbations in
the setting of heart failure hospitalisations but may predict
unfavourable consequences.
20
Although markers such as eGFR,
BUN and creatinine level are easily available in routine blood
tests, they may not always represent renal function properly.
21
In
this context, using cystatin C levels may provide a more reliable
assessment of renal function.
22
In some subsets of patients with chronically impaired renal
function, volume overload and haemodilution at the time of
ADHF hospitalisation may mask underlying dysfunction, while
patients with previously preserved renal function may present
with worsening renal function due to accompanying low cardiac
output and resultant low renal perfusion.
23
Therefore, since small
changes in GFR can be detected by cystatin C level,
22
it may be
preferred over standard renal function tests and may also be
Table 2. Baseline laboratory characteristics of the study population
Variables
In-hospital survivors
(
n
=
50)
In-hospital deaths
(
n
=
7)
p
-value
Fasting glucose (mg/dl)
113.6
±
48.7
124.7
±
49.1 0.559
(mmol/l)
6.30
±
2.70
6.92
±
2.73
Urea (mg/dl)
69.5
±
33.7
93.9
±
51.7 0.100
Creatinine (mg/dl)
1.15
±
0.43
1.27
±
0.61 0.784
Total cholesterol (mg/dl)
136.5
±
35.8
127.0
±
38.9 0.518
(mmol/l)
3.54
±
0.93
3.29
±
1.01
Triglycerides (mg/dl)
85.6
±
34.5
106.6
±
35.2 0.138
(mmol/l)
0.97
±
0.39
1.20
±
0.40
Sodium (mmol/l)
135.5
±
5.1
128.9
±
7.6
0.003
Potassium (mmol/l)
4.3
±
0.6
4.2
±
0.7
0.794
Haemoglobin (g/dl)
12.4
±
1.9
11.5
±
1.2
0.218
Cystatin C (mg/l)
1.22
±
0.39
1.62
±
0.62 0.023
NT-proBNP (pg/ml)
577.2
±
585.5
1101.6
±
228.7 0.001
GFR (ml/min/1.73 m
2
)
72.8
±
30.0
74.3
±
44.8 0.907
Cockcroft (ml/dk)
74.5
±
33.2
78.2
±
54.1 0.803
GFR: glomerular filtration rate, NT-proBNP: N-terminal pro-B-type natriuretic
peptide.
Table 3. Baseline echocardiographic characteristics
of the study population
Variables
In-hospital survivors
(
n
=
50)
In-hospital deaths
(
n
=
7)
p
-value
LVEDD (cm)
6.3
±
1.0
6.1
±
0.4
0.607
EF (%)
25.6
±
7.0
20.7
±
8.9
0.101
sPAP (mmHg)
43.0
±
11.5
40.9
±
10.2
0.638
EF: ejection fraction, LVEDD: left ventricular end-diastolic diameter, sPAP:
systolic pulmonary artery pressure.
Table 5. Comparison of admission cystatin C levels according
to survival, assessed on an annual basis
Cystatin C (mg/l)
Follow up
Survivor (
n
)
Deceased (
n
)
p
-value
In hospital
1.22
±
0.39 (50)
1.62
±
0.62 (7)
0.023
12 months
1.24
±
0.35 (30)
1.31
±
0.52 (27)
0.373
24 months
1.21
±
0.39 (22)
1.31
±
0.47 (35)
0.393
36 months
1.21
±
0.40 (19)
1.30
±
0.46 (38)
0.491
Table 4. Correlation analysis of the variable
Variables
r-
value
Cystatin C (95% CI)
p-
value
Lower
Upper
NT-proBNP
0.324
0.069
0.539
0.014
MDRD
–0.638
–0.770
–0.453
<
0.001
Cockcroft
–0.486
–0.663
–0.258
<
0.001
Age
0.179
–0.086
0.420
0.183
Hospitalisation time
–0.007
–0.267
–0.331
0.957
CI: confidence interval, MDRD: Modification of Diet in Renal Disease,
NT-proBNP: N-terminal pro-B-type natriuretic peptide.
Table 6. Multivariate analysis of predictors of mortality
during 36-month follow up
Independent variables
HR Wald
p
-value
95% CI
Lower
Upper
Age
0.975
2.599 0.107 0.944
1.006
Cystatin C
0.959
0.005 0.946 0.287
3.201
NT-proBNP
1.000
0.512 0.474 1.000
1.001
Sodium
0.937
4.336 0.037 0.880
0.996
LVEF
0.952
2.697 0.101 0.897
1.010
GFR
0.984
3.509 0.061 0.967
1.001
CI: confidence interval, LVEF: left ventricular ejection fraction, GFR: glomeru-
lar filtration rate, HR: hazard ratio, NT-proBNP: N-terminal pro-B-type natri-
uretic peptide.