Copyright © 2012 The Korean Society of Cardiology
Korean Circulation Journal
Perioperative cardiac complications, such as cardiac death, myo-
cardial infarction, unstable angina, pulmonary edema and serious
ventricular arrhythmia, are potentially avoidable causes of morbidi-
Print ISSN 1738-5520 • On-line ISSN 1738-5555
Postoperative B-Type Natriuretic Peptide Levels Associated
With Prolonged Hospitalization in Hypertensive Patients
After Non-Cardiac Surgery
Jae Hong Park, MD1, Gil Ja Shin, MD2, Jae In Ryu, MD2, and Wook Bum Pyun, MD2
1Division of Cardiology, Department of Internal Medicine, Kang Nam General Hosptial, Yongin,
2Cardiovascular Center, Department of Internal Medicine, School of Medicine, Ewha Womans Universiy, Seoul, Korea
Background and Objectives: B-type natriuretic peptide (BNP) is an important marker for the diagnosis of heart failure and is useful to-
wards predicting morbidity and mortality after non-cardiac surgery. Nevertheless, information on the relationship between postoperative
BNP levels and perioperative prognosis after non-cardiac surgery is scarce. The purpose of the study was to assess whether postoperative
BNP levels could be used as a predictor of prolonged hospitalization in elderly hypertensive patients after non-cardiac surgery.
Subjects and Methods: Ninety-seven (97) patients, aged 55 years or older (mean age: 73.12±10.05 years, M : F=24 : 73) were enrolled in
a prospective study from May 2005 through August 2010. All patients underwent total knee or hip replacement. Postoperative BNP and other
diagnostic data were recorded within 24 hours of surgery. Patients that required a prolonged hospital stay due to operative causes, such
as wound infection and re-operation, were excluded.
Results: The length of hospital stay was significantly correlated with postoperative BNP levels (p=0.031). Receiver operating characteristic
curves demonstrated postoperative BNP levels as predictors of hospital stay ≥30 days with areas under the curve of 0.774 (95% confidence
interval: 0.679-0.87, p<0.0001). A BNP cut-off value above 217.5 pg/mL had a sensitivity of 80.6% and a specificity of 66.7% for predicting
postoperative hospital stays of 30 days or more.
Conclusion: Postoperative BNP levels may predict the length of hospital stays after non-cardiac surgery in hypertensive patients. Elevated
BNP levels were associated with prolonged hospitalization after elective orthopedic surgery. (Korean Circ J 2012;42:521-527)
KEY WORDS: Natriuretic peptin, brain; Hospitalization; Postoperative period; Hypertension.
Received: August 1, 2011
Revision Received: December 2, 2011
Accepted: February 2, 2012
Correspondence: Wook Bum Pyun, MD, Cardiovascular Center, Depart-
ment of Internal Medicine, School of Medicine, Ewha Womans Universiy,
1071 Anyangcheon-ro, Yangcheon-gu, Seoul 158-710, Korea
Tel: 82-2-2650-2855, Fax: 82-2-2650-2855
• The authors have no financial conflicts of interest.
This is an Open Access article distributed under the terms of the Creative
Commons Attribution Non-Commercial License (http://creativecommons.
org/licenses/by-nc/3.0) which permits unrestricted non-commercial use,
distribution, and reproduction in any medium, provided the original work
is properly cited.
ty and mortality in patients undergoing non-cardiac surgery or vas-
cular surgery.1-3) Hypertension is a risk factor for potential coronary
artery disease. Thus, evaluation of the cardiovascular system in pa-
tients with hypertension is important to predict perioperative mor-
bidity and mortality before undertaking non-cardiac surgery. A va-
riety of scoring systems and imaging strategies have been developed
to predict such adverse cardiovascular events.4-8) However, low pre-
dictive accuracy and poor clinical utility have limited the use of risk
indices in current clinical practice and currently, there is no gold st-
andard to effectively predict postoperative complications, length
of hospital stay, or the possibility of mortality. Preoperative evalua-
tions of the cardiovascular system that use chest radiography, elec-
trocardiogram (ECG), echocardiography and laboratory studies are
limited. For example, one limitation is the timing of an evaluation; if
an evaluation is made during a time during which that particular pa-
rameter is stable, there is difficulty in detecting a small but signifi-
cant deterioration in cardiovascular functional. While echocardiog-
522 Postoperative B-Type Natriuretic Peptide and Prolonged Hospitalization
raphy has been utilized to assess cardiac risks, adding echocardio-
graphic results have not demonstrated to improve risk assessment.9)
Therefore, postoperative measurements of B-type natriuretic pep-
tide (BNP) in certification of patients for perioperative events are
clinically important but still not evaluated.
The purpose of this study is to evaluate the relationship between
post-operative BNP levels and the duration of hospital stay in hyper-
tensive patients. In addition, this study attempts to assess normal
left ventricular (LV) systolic function after elective orthopedic surgery.
Subjects and Methods
This prospective investigation was a single-center, observational
cohort study. A total of ninety-seven consecutive patients with hy-
pertension fulfilled the inclusion criteria and underwent scheduled
orthopedic surgery (total hip or knee replacement) at the author’s
university hospital from May 2005 through August 2010.
The enrolled subjects were divided into 2 groups. Group I included
patients that were hospitalization for 30 days or longer, while Group
II included patients that were hospitalized for less than thirty days.
Cardiovascular risks were evaluated before surgery for spinal, epi-
dural or general anesthesia by a cardiologist and an anesthetist ac-
cording to the American College of Cardiology/American Heart As-
sociation (ACC/AHA) guidelines.10) These operations were performed
in a usual manner without any clinical evidence of a significant flu-
id and electrolyte imbalance or cardiac failure.
This study excluded patients with the following: had undergone an
emergency operation; had a LV dysfunction (ejection fraction <50%),
renal insufficiency (serum creatinine level >2.0 mg/dL); or had a
history of ischemic heart disease, stroke, severe valvular heart dis-
ease, or peripheral vascular disease. In addition, patients were ex-
cluded patients if they had experienced a prolonged postoperative
hospital stay due to operative causes such as a wound infection, bi-
lateral operations, or re-operation. The study was approved by the
local ethics committee and written informed consent was obtained
from each study participant.
Preoperative data were obtained within 7 days before a patient’s
scheduled operation, which included demographic data, 12-lead ECG
recording, chest posteroanterior, medical and medication history,
surgical history, physical examination and other biochemical tests.
Age, gender, the presence of diabetes mellitus and dyslipidemia,
blood pressure, body mass index, pre-and-postoperative BNP and pre-
operative hemoglobin levels were verified. The following clinical data
were recorded: intravenous fluid intake, urinary output on the day of
operation, and the total amount of blood transfused.
The following postoperative evaluations were performed for
each patient within 24 hours of completing surgery: physical exami-
nation, chest PA, ECG, and laboratory tests. All patients underwent
aconventional 2-dimensional and Doppler echocardiographic exami-
nations for the assessment of ventricular systolic and diastolic func-
tions. The Framingham criteria were used for defining postopera-
tive heart failure.11)
B-type natriuretic peptide measurement and assay
Plasma BNP and hemoglobin levels were measured on preopera-
tive and postoperative day 1. A venous blood sample, taken for BNP
measurement, was collected in a tube containing lithium-heparin
and transported to the laboratory at room temperature. Patients
were asked to lie at rest in a supine position for thirty (30) minutes,
in order to eliminate any confounding effect of posture and exer-
cise on plasma levels to the extent possible, before taking a preoper-
ative blood sample. The Bayer ADVIA CentaurTM immunoassay opera-
tion (Bayer Healthcare LLC, Diagnostic division, Leverkusen, Germany)
was used to measure plasma BNP levels.
The clinical outcomes of this study were evaluated during the hos-
pitalization and follow-up periods. The primary end point was the
predictive power of BNP levels for postoperative length of hospital
stay. The secondary end point included non-cardiac death, cardiac
death, myocardial infarction, development of congestive heart fail-
ure, and re-hospitalization. Cardiac death was defined as having
experienced 1) sudden death that could not be explained by any
other non-cardiovascular complications, or 2) gradual death caused
by progressive heart failure and other known cardiac risk factors.
Myocardial infarction was defined as having a cardiac Troponin I
(cTnI) increase above the 99th percentile of the upper limit (cTnI
>0.032 ng/mL). Congestive heart failure was diagnosed by physical
examination and interpretation of chest X-ray images by a radiolo-
gist as consistent with these complications.
Normally distributed continuous variables are expressed as the
mean and standard deviation. Categorical data are presented as the
absolute value and percentage. The Student’s t-test and chi-square
test, or Fisher’s exact test, were used for normally distributed con-
tinuous and categorical variables, respectively. Variables that ap-
peared to be significant on univariate analysis were entered into the
model of multivariate analysis to determine independent factors as-
sociated with prolonged hospitalization. The odds ratios (OR) were
given with 95% confidence intervals (CI).
Jae Hong Park, et al.
To establish a BNP cut-off value with the appropriate sensitivity
and specificity, receiver operating characteristic (ROC) curves were
plotted and the area under the curve was estimated. Statistical analy-
sis was performed using Statistical Package for the Social Sciences
(SPSS). All data have been analyzed with SPSS correlation and mul-
tiple linear regression models (SPSS v.18.0; SPSS Inc., Chicago, IL, USA).
ROC curve was made using Medcalc version 9.6.
Patient characteristics and echocardiographic data
The age of patients ranged from 52 to 70 years with a mean age
of 73.12±10.05 years, while the female and male ratio was 73 : 24.
The mean duration of hospital admission was 33.24±37.37 days.
Group I had a significantly longer period of hospital duration than
Group II (64±50.54 days for Group I vs. 18.38±8.94 days for Group
II, p=0.0001). The baseline demographic data of patients were sum-
marized in Table 1. Between these 2 groups, Group I had the tenden-
cy of being older (76.48±8.46 years old for Group I vs. 71.55±10.41
years old for Group II, p=0.023). However, Group II had a higher level
of obese and a greater frequency of dyslipidemia compared to Gr-
oup I. The preoperative hemoglobin level of Group II was higher than
that of Group I (11.12±1.65 g/dL for Group I vs. 12.44±1.87 g/dL for
Group II, p=0.001). The total intravenous fluid intake or urinary out-
Table 1. Demographic and clinical characteristics of subjects
Over 30 days hospitalization (n=31)
Under 30 days hospitalization (n=66)
SBP (mm Hg)
DBP (mm Hg)
Heart rate (beat/min)
GFR (mL/min/1.73 m2)
Preoperative Hb (g/dL)
Postoperative transfusion (mL)
Intraoperative I&O (mL)
Intravenous Intake (mL)
Urinary output (mL)
Data are expressed as mean±SD or number (%) of patients. BMI: body mass index, SBP: systolic blood pressure, DBP: diastolic blood pressure, GFR: glo-
merular filter rate, BNP: B-type natriuretic peptide, Hb: hemoglobin, I&O: intake and output
Table 2. Baseline echocardiographic data of study cohort
Over 30 days hospitalization (n=31)
Under 30 days hospitalization (n=66)
Diastolic dysfunction pattern (%)
LVEF: left ventricle ejection fraction, LAVI: left ventricular volume index, LVMI: left ventricular mass index, e/e: the ratio of early transmitral flow velocity to
early diastolic septal mitral annulus velocity
524 Postoperative B-Type Natriuretic Peptide and Prolonged Hospitalization
put of Group I was more frequently maintained than that of Group
II (p=0.038 and p=0.012).
The transfusion and intraoperative Intake and Output data sh-
owed no significant differences between these 2 groups. Table 2 sh-
owed differences in echocardiographic parameters between the 2
groups; however, this difference was not statistically significant.
B-type natriuretic peptide level and prolonged hospital stay
A correlation between postoperative BNP level and prolonged
hospital stay was remarkable, as shown in Table 1. Fig. 1 shows a box-
plot of postoperative BNP levels in each group. There was a signifi-
cant difference noted in the postoperative BNP level between the
2 groups. The mean postoperative BNP level of Group I was 6483.93±
11147.79 pg/mL as compared to that of Group II was 1708.03±6118.22
pg/mL (p=0.031). The preoperative BNP levels of Group I tended to
be higher, but there was no statistical difference in the preoperative
BNP level between these 2 groups (3477.24±6796.62 pg/mL for
Group I vs. 1750.68±4510.28 pg/mL for Group II, p=0.24). Thus far,
this study has illustrated that a significant correlation was displayed
between the length of hospitalization and the postoperative BNP
Receiver operating characteristic curves demonstrated postopera-
tive BNP levels as the predictors of hospital stay of 30 days or more
with areas under the curve of 0.774 (95% CI, 0.679-0.070, p<0.001)
(Fig. 2). A BNP over 217.5 pg/mL had a sensitivity of 80.6% and spe-
cificity of 66.7% for predicting a postoperative hospital stay of 30
days or more.
Clinical outcome and predictors
Postoperative cardiac events occurred in 8 patients during the
follow-up period (8.2%): one patient with cardiac death, 2 patients
with myocardial infarction, one patient with cerebral infarction, and
4 patients required re-hospitalization due to congestive heart fail-
ure. There were 10 non-cardiac deaths, which were caused by either
disease progression or surgical complications (10.3%). There was no
statistically difference in the postoperative cardiac events between
these two groups. Using logistic regression analysis, the univariate
predictors of prolonged hospitalization were older age, postopera-
tive elevated BNP level, preoperative lower hemoglobin and intra-
venous fluid intake (Table 3).
Fig. 2. Receiver operating characteristics curve was constructed to deter-
mine the postoperative B type natriuretic peptide cut-off value for predic-
tive power of predicting the prolonged hospital stay. A cut-off of 217.5 pg/
mL yielded the maximal combined sensitivity of 80.6% and specificity of
66.7%. Area under the curve=0.774 (95% confidence interval=0.679-0.870,
p<0.0001). AUC: area under the curve, BNP: B-type natriuretic peptide.
0 20 40 60 80 100
Table 3. Univariate predictors of prolonged hospitalization
Preoperative BNP (pg/mL)
Postoperative BNP (pg/mL)
Preoperative Hb (g/dL)
Intraoperative I&O (mL)
Postoperative transfusion (mL)
CI: confidence interval, BNP: B-type natriuretic peptide, Hb: hemoglobin,
I&O: intake and output
Fig. 1. A comparison of postoperative BNP levels in patients with over 30
days hospitalization and under 30 days hospitalization. Central lines repre-
sent medians, box represent 25th and 75th precentiles. Postoperative BNP
level was higher in Group I than Group II (Group I vs. Group II: 6483.93±
1147.79 pg/mL vs. 1708.03±6118.22 pg/mL, p=0.031). BNP: B-type natri-
Duration of hospitalization
Under 30 days Over 30 days
Jae Hong Park, et al.
The only independent predictor of prolonged hospitalization th-
rough the multivariate regression analysis model adjusting for age,
postoperative BNP level, preoperative hemoglobin, postoperative
transfusion and intravenous fluid intake was a postoperative ele-
vated BNP level (OR; 1.020, 95% CI; 1.002-1.050, p=0.049) (Table 4).
This prospective study proves the value of postoperative BNP level,
which may play a role in predicting clinical outcome. Postoperative
BNP levels are significantly associated with prolonged hospital
stay, especially in hospitalization of over 30 days after non-cardiac
surgery in hypertensive patients. Nevertheless, postoperative BNP
levels are not predictive of postoperative cardiac events. The useful-
ness of the postoperative BNP cut-off level of 217.5 pg/mg was as-
sociated with an increased postoperative hospital stay.
Alternative methods of perioperative cardiac risk evaluation
Determination of preoperative risks in the elderly patients remains
an important challenge for cardiology. Several indices have been de-
veloped, including the ACC/AHA guidelines, the revised cardiac in-
dex, the Goldman index, and preoperative echocardiography. How-
ever, these indices have limitations as prognostic value and some are
quite complicated.6) As previous studies have demonstrated that
changes in N-terminal pro-B-type BNP (NT-proBNP) were related
to adverse outcomes in acute coronary syndromes and acute de-
compensated heart failure,12)13) NT-proBNP levels should contribute
to the evaluation of prognosis during the perioperative period.
The median preoperative NT-proBNP level of patients who had ex-
pired during the follow-up period was significantly higher than that
of the survivors (795 pg/mL vs. 269 pg/mL, p=0.002). The median
difference between pre- and postoperative NT-proBNP levels of
expired patients was significantly higher than that of the survivors
(5336 pg/mL vs. 665 pg/mL, p=0.010).14) Preoperative NT-proBNP
levels above the optimal discriminatory threshold of 457 pg/mL, deter-
mined by ROC curve analysis were associated with occurrences of
postoperative cardiac events (OR; 10.5, 95% CI; 1.9 to 56.6; p=0.006).15)
Another study demonstrated that both high sensitivity C-reac-
tive protein (hs-CRP) and NT-proBNP had additional value in the
prediction of postoperative cardiac events in patients undergoing
vascular surgery. In addition, a combined elevation of hs-CRP and
NT-proBNP carried a seven-fold higher risk for postoperative cardiac
Previous studies and the advantages of the B-type natriuretic
B-type natriuretic peptide was first discovered in the porcine
brain. However, it is actually secreted by both atrial and ventricular
myocytes.17) This prohormone is released during hemodynamic
stress, that is, when the ventricle is dilated, hypertrophic, or subject-
ed to increased cardiac wall tension.
Prohormone BNP is cleaved into 2 polypeptides: inactive NT-pro-
BNP and bioactive peptide BNP. BNP causes arterial vasodilation,
diuresis, and natriuresis, and reduces activities of the renin-angio-
tensin-aldosterone and the sympathetic nervous system.18)
Assays for BNP levels are commercially available and these bio-
markers for heart failure are the most extensively used. Such test-
ing is recommended among the current guidelines for hospital ad-
mission, discharge and re-hospitalization of heart failure patients.
Plasma BNP levels are powerful predictors of death and major ad-
verse cardiovascular events in patients with a stable coronary artery
disease, acute coronary syndrome, and congestive heart failure.19)20)
Recently, several studies have confirmed that elevated preopera-
tive BNP levels in patients, who had undergone non-cardiac or car-
diac surgery, were associated with increased risks for mortality and
morbidity during the follow-up period.21-24) An additional study has
suggested that preoperative BNP and/or cTnI levels might assist in
differentiating patients who are at very low risk for perioperative car-
diac events from those who would require more detailed cardiovas-
cular tests and optimization of therapies before undergoing major
A significant study concerning postoperative BNP levels as a pre-
dictor of postoperative complications and outcomes in patients after
open heart surgery was published.
Hutfless et al.26) found that the highest postoperative BNP level
had been associated with a prolonged hospital stay and one-year
mortality. They documented that there had been a significant dif-
ference in the highest postoperative BNP level between the group
that was hospitalized <10 days postoperatively and the group that
had prolonged hospital stay for 10 days or more (750 pg/mL vs. 1190
They also documented significant differences in median levels of
the highest postoperative BNP level between 11 patients who had
deceased within a year (1265 pg/mL) and patients who had under-
Table 4. Mulitivariate predictors of prolonged hospitalization
Postoperative BNP (pg/mL)
Preoperative Hb (g/dL)
Postoperative transfusion (mL)
BNP: B-type natriuretic peptide, Hb: hemoglobin, CI: confidence interval
526 Postoperative B-Type Natriuretic Peptide and Prolonged Hospitalization
gone open-heart surgery but were alive after one year (793 pg/mL)
In consideration of the mechanism of elevated BNP levels after
non-cardiac surgery, surgery by itself can cause stress such as ane-
mia, blood pressure fluctuation, fluid imbalance and activation of the
sympathetic nervous system, especially, in hypertensive patients.
B-type natriuretic peptide is released in response to ventricular
wall stress. Thus, the consideration is that increased net (including
intraoperative fluids) intravenous fluids are associated with increas-
ed postoperative BNP levels after surgery. Therefore, the assumption
is that postoperative BNP levels may be related to diastolic dysfunc-
tion of the heart.
Though small in scale, the theoretical mechanism on the increased
BNP levels postoperatively may well be explained in this manner.
In conclusion, a moderately elevated postoperative BNP level
above 217.5 pg/mL would predict delayed discharge from hospital
for these 97 hypertensive patients with normal systolic function un-
dergoing non-cardiac surgery. This study documented that postop-
erative BNP levels were not associated with perioperative cardiac
complications, but could predict the length of hospital stay after
non-cardiac surgery in hypertensive patients.
Nevertheless, this investigation could not document the fact that
preoperative BNP levels were associated with prolonged hospital
stays or cardiac events.
Measurements of postoperative BNP concentrations may aid in
monitoring or actively guiding the level of therapeutic adjustment
Post-operative BNP levels are comprehensive predictive factors
in the postoperative period that is affected by preoperative BNP lev-
els, fluid intake and output, underlying cardiovascular disease, and
multiple risk factors.
There are several limitations to this study. The first limitation is in
the interpretation of changes in BNP levels over surgery. It is the lack
of reliable estimates of volume overload and the aspect that a post-
operative elevation of the BNP level is to the result of exposure to
volume loading rather than to the progression of underlying cardiac
disease. For example, in cases of orthopedic surgery with complicat-
ed lesions that require a larger volume of transfusion, the postop-
erative BNP level would be affected without doubt.
Second, owing to the fact that preoperative BNP levels have been
noticed by clinicians prior to surgery for the purpose of managing
patients, the results have been substantially confounded.
Third, the preoperative BNP level is found to have no correlation
with prolonged hospitalization. Also, it cannot be documented that
postoperative BNP level is associated with clinical outcomes, such
as death, heart failure, or late prognosis.
Last, long-term follow-up observations and studies on the mech-
anism of how non-cardiac surgeries could affect postoperative BNP
levels are required.
This study was performed by the research fund of Ewha Womans
University (No. 2005-0997-1-1).
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