Download Changes of natriuretic peptides concentration in early phase of

ORIGINAL ARTICLE
Changes of natriuretic peptides concentration in early phase of
acute myocardial infarction
Ekrema Mujarić1, Besim Prnjavorac 2 Merlina Kalajdžija-Cero3, Harun Šestić4, Almir Rošić1 Rifat
Sejdinović2, Sefveta Mustafić,5 Amila Mehmedović6
Department of Internal Medicine, Cantonal Hospital Zenica, 2Department of Internal Medicine, General Hospital Tešanj, 3Department
of Anesthesiology and Intensive Care, Cantonal Hospital Zenica, 4Department of Surgery, Cantonal Hospital Zenica, 5Department of
Laboratory Diagnostics, University Clinic Tuzla, 6Department of Gantroenterohepatology, University Clinical Center, Sarajevo; Bosnia
and Herzegovina
1
ABSTRACT
Aim To analyze a change of level of nautriuretic peptide (NT proBNP) caused by stress distension of myocardial wall in cases of
acute myocardial infarction (AIM), as a possible predictor of early
heart failure.
Methods Patients with myocardial infarction were followed up.
Standard clinical and laboratory examination, including NT proBNP, and other laboratory analyses, were performed on the day of
admission, the next day and on the eighth day of hospitalization.
Statistical analyses included variance for repeated measurement
(ANOVA), factorial multivariate analysis and test of multiple
correlations.
Corresponding author:
Besim Prnjavorac
Department of Internal Medicine, General
Hospital Tešanj
Ulica Braće Pobrić 17, 74260 Tešanj,
Bosnia and Herzegovina
Phone: +387 32 656 300;
Fax: +387 32 656 300;
E-mail: [email protected]
Original submission:
22 April 2013;
Revised submission:
05 June 2013;
Accepted:
06 October 2013.
Results The most important predictors of early heart failure in
acute myocardial infarction were age, diastolic blood pressure,
creatin kinase (CK) on admission, larger field of infarction zone
and so on. Multiple correlations showed statistically significant
correlation of age, diastolic pressure and larger zone of myocardial infarction with an increase of NT pro-BNP concentration. The
activity of CK on the day after admission was higher than on admission (p=0.02) and myocard-binding CK (CK-MB) the next
day after admission was higher than on admission (p=0.016). A
statistically significant increase was found on the next day for NT
pro-BNP in comparison with the value on admission (p=0.0049),
but the level of activity of CK was markedly decreased on the
eighth hospital day.
Conclusion The significant increase of the concentration of NT
pro-BNP during myocardial infarction is an important predictor of
early heart failure, therefore, in case of a significant increase of NT
pro-BNP in the early phase of the infraction a therapy that could
prevent clinically relevant heart failure should be administered .
Key words: ischemic heart disease, infarction, NT pro-BNP, heart
failure
Med Glas (Zenica) 2014; 11(1):7-12
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Medicinski Glasnik, Volume 11, Number 1, February 2014
INTRODUCTION
Many changes of diagnostic tools and the treatment of myocardial infarction have been seen in
last two decades. Invasive procedures, like stent
implementation, were developed as a very successful early treatment of myocardial infarction (1).
Mortality of myocardial infarction was decreased substantially after the establishment of these
procedures (2,3). Many very useful diagnostic
procedures were developed at same time. Among
others, the most important are biomarkers of tissue
damages, like any type of troponins, myoglobin
(4). All natriuretic peptides (there is a very large
family of peptides with same function), are natural products of myocardial wall during distension.
Any situation with stress distension of myocardial
wall causes a release of these peptides fibers.
Natriuretic peptides have been released as a result of distension of myocardial wall. Any stress of myocardial wall should be followed by an
increase of natriuretic peptides secretions regardless of ongoing pathophysiological events (5).
Distension of whole myocardium or any of his
part should be a provocation for release of natriuretic peptides (6). Any situation with tendency
for distension of atrial or ventricular inner spaces
should be followed by an increase in the concentration of natriuretic peptides, as the answer and
as the signal for the increase of strength of contraction of myocardium (7). There are only two
situations when natriuretic peptides were released more than usually – tendency of water overload, as it could be seen in kidney diseases with
kidney failure, or if very serious arterial hypertension was present (8). The same situation could
be present if very high resistance was present in
peripheral arterial bloodstream (9,10).
In recent literature natriuretic peptides and their
precursors have been described (11). It was noted that natriuretic activity was present in natriuretic peptides and in their precursors too (12).
Thereafter, any of natriuretic peptides and their
precursors were directed to the same receptors of
target cells (13). So, any of these members of the
family of natriuretic peptides are overlapped in
their actions and metabolism (14).
The aim of this study was to analyze the use of
results of laboratory analyses of natriuretic peptides in the prediction of early heart failure in myo-
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cardial infarction, as the most important clinical
entity of ischemic heart diseases.
PATIENTS AND METHODS
Patients with acute myocardial infarction treated
at the Intensive Care Unit (ICU) of the General
Hospital Tešanj, Bosnia and Herzegovina, were
analyzed for clinical, laboratory and markers of
myocardial tissue damage. Diagnostic procedures
for these patients were performed according to
the Guidelines of European Society of Cardiology (ESC) (15,16). Data related to risky behavior
(cigarettes smoking, food intake, alcohol intake,
physical activity) were noted as well as other risks
for myocardial infarction. Analyses of lipid status
were performed, including total cholesterol, low
(LDL) and high density cholesterol (HDL), triglycerides, fibrinogen, C-reactive protein (CRP),
blood cell count, e. g. red blood cells (RBC),
medium cell volume (MCV), hematocrite, white
blood cells (WBC), thrombocytes (Tr), as well as
troponin, myoglobin, lactate dechydrogenase activity (LDH), creatinine phosphate kinaze activity
(CPK), myocardial binding creatinine phosphate
kinaze (CK-MB). Natriuretic peptides were analyzed by performing examination of concentration
of N-terminal precursor of brain natriuretic peptide (NT pro-BNP). Important clinical parameters
were noted on admission (systolic blood pressure,
diastolic blood pressure, heart rate). All parameters were followed up according to the protocol of
ICU. Measurement of enzymes activities (LDH,
CK, CK-MB) and NT pro-BNP were followed up
on the day of admission, the first day after admission and on the eight day after admission. Inclusion
criteria involved patients with acute myocardial infarction, or the first reinfarction. Exclusion criteria
involved heart failure on III or IV class according
to NYHA (New York Heart Association) (17), or
other causes of NT pro-BNP elevation, if the level was up to three times above normal (more than
360 pg/ml) before myocardial infarction.
Statistical analyses included variance for repeated measurement (ANOVA), factorial multivariate analysis and test of multiple correlations.
RESULTS
Patients treated for myocardial infarction in ICU
during the period of one year, admitted to hospital in the period between 01. 01. 2008 and 31.12.
Mujarić et al. NT pro-BNP in myocardial infarction
2008 were analyzed. All 67 patients were treated.
The average age was 61.2 (SD 14.53) years. Forty
patients (61%) were males, and 27 (39%) were females. Males were younger (average age of 60.02
years) than women (average age 64.14) at the time
of admission. The commonest age on admission
was 51-70 years. Most patients were smokers (38
smokers versus 29 non smokers/ never smokers).
Most of the smokers used cigarettes during a long
period of time, and many of them were heavy
smokers having more than 30 cigarettes a day.
The localization of myocardial infarction was as
follows: anterior wall 7 (10.45 %), anteroseptal
10 (14.92 %), widespread size-anterior 10 (14.92
%), diaphragmal wall 33 (49%), anterolateral 3
(4.48 %) and posterolateral 4 (5.97%) cases.
The statistical method of multiple correlations
showed a statistically significant correlation of
age, diastolic blood pressure and larger zone of
myocardial infarction with the increase of NT proBNP concentration at the level of p<0.05 for any.
Blood pressure was measured on admission and
at least 6 times a day, sometimes event more
often, depending on the general patient’s status
(Table 1).
Table 1. Blood pressure according to gender
Value (SD)
Blood pressure
(mmHg)
TAS 1
TAS MAX
TAS MIN
TAD 1
TAD MAX
TAD MIN
All cases
Males
Females
140.44 (14.53)
153.51 (30.77)
105.97 (26.74)
85.82 (22.97)
93.13 (17.18)
65.00 (12.30)
130.98 (22.61)
145.24 (20.95)
107.80 (13.88)
83.41 (15.59)
90.24 (11.10)
65.24 (9.97)
155.38 (35.11)
166.54 (29.08)
103.08 (31.96)
89.61 (18.50)
97.69 (12.50)
64.61 (19.85)
SD, standard deviation; TAS1, systolioc blood pressure on admissio;
TAS MAX, maximal systolic pressure; TAS MIN, minimal sistolic
pressure; TAD1, dyastilic pressure on admission; TAD MAX, maximal diastolic pressure; TAD MIN, minimal dyastolic pressure
Parameters of myocardial damage were followed
up by analyses of CK, CK-MB, and LDH activities, and by measurement of NT pro-BNP. On
first day after admission mean activity of CK was
776.61 IU/mL (SD 1118.20). Mean level of CKMB on admission was 28.58 IU/mL. SD 30.50
(normal level less than 16 IU/mL). One day after
admission the average level of activity of CKMB was 77 IU/mL (SD 99.04). The average activity of LDH on admission was 620.44 IU/mL
(SD 569.57). One day after admission the average level of activity of LDH was 1005.05 IU/mL
(SD 883.23) (Table 2).
Table 2. Hematologic and biochemical analyzes
Value (SD)
Parameter
All cases (SD)
Males
Hb (g/L)
137.7 (17.47) 142.56 (16.09)
Htc (%)
38.90 (4.56)
39.95 (4.26)
MCV (fL)
86.44 (5.55)
87.36 (4.14)
Tr (x106/L)
237.87 (61.32) 226.49 (64.61)
Glucose on admi10.27 (5.63)
8.93 (4.50)
ssion (mmol/L)
Glucose max.
14.45 (6.61)
12.31 (6.00)
(mmol/L)
Glucose MIN
6.92 (2.67)
6.99 (2.10)
(mmol/L)
Cholesterol total
5.68 (1.27)
5.50 (0.90)
(mmol/L)
Cholesterol HDL
0.99 (0.27)
0.95 (0.24)
(mmol/L)
Cholesterol LDL
3.66 (1.21)
3.60 (1.22)
(mmol/L)
Triglicerids
1.94 (1.48)
1.85 (1.28)
(mmol/L)
Acidum uricum
356.65 (102.67) 376.44 (100.14)
(mmol/L)
HbA1c (%)
7.79 (2.47)
7.17 (1.76)
Females
127.75 (16.28)
37.17 (4.41)
84.96 (6.84)
257.17 (47.96)
12.33 (6.40)
16.73 (6.23)
6.86 (3.08)
6.00 (1.67)
1.07 (0.29)
3.78 (1.12)
2.08 (1.72)
312.12 (86.68)
8.82 (2.96)
Hb, hemoglobin concentration; Htc, hematocrit; MCV, medium cell
volume; MAX, maximal, MIN, minimal; SD, standard deviation;
HbA1c, glycosylated hemoglobin;
Mean level of NT pro-BNP on admission was
389.5 pg/mL (SD 620.79) (normal value 70-125
pg/mL for person not older than 70 years). One
day after admission the average level of NT proBNP was 1371.12 pg/mL (SD 1158.9), on the eighth day after admission the mean value of NT
pro-BNP was 786 pg/mL (SD 868.08) (Table 3).
Table 3. Changes of N-terminal precursor of brain natriuretic
peptide (NT pro-BNP) during hospitalization
NT pro-BNP (pg/mL) (SD)
Hospitalization time
On day of admission
One day after admission
Eight days after admission
All cases
Males SD Females SD
389.50
(620.79)
1371.12
(1158.91)
786.38
(860.08)
471.41
(750.46)
1391.27
(1267.87)
892.22
(960.16)
273.10
(298.93)
1337.23
(914.03)
612.50
(582.20)
SD, standard deviation
Multivariate analysis performed the stratification
of importance for an increase of NT pro-BNP of
these parameters. All the parameters were analyzed by multivariate analysis. This stratification
was as follows: age, maximal measured diastolic
pressure, and diastolic pressure on admission,
CK on admission, hemoglobin level, gender, triglycerides, maximal measured glucose level, and
localization of myocardial infarction (including
size of damaged area, high-spread infarction of
anterior wall was the most important), cholesterol level and thrombocytes.
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Medicinski Glasnik, Volume 11, Number 1, February 2014
The activity of CK one day after admission was higher than that of the day of admission at the statistical significance level of p=0.02. The difference
of the level of activity of CK-MB on the day after
admission in comparison with the admission day
was statistically significant, at the level p=0.016.
NT pro-BNP level was higher on the first day after
admission, in comparison with that on admission
at the significance level (p=0.0049).
DISCUSSION
Results of analyses of parameters of patients with
myocardial infarction showed that the average
age and gender structure were similar with those
reported in recent literature (18). It is necessary
to note that males were more vulnerable for myocardial infarction than females. But in analyses
of the followed parameters known as risk factors
for myocardial infarction, there was no complete
correlation according to the gender. Regulation
of glycemia was better in males (percentage of
HbA1c, maximal glucose level). Average cholesterol level was higher in female than in male patients. Only risky behavior of cigarette smoking
was predominant in males, so it could be concluded that the risk of smoking, which was noted in
males, was much more important than any others.
During the follow up of NT pro-BNP concentration
changes in this study a substantial increase was found the next day after admission comparing to the
day of admission, and a decrease on 8th day after
admission in almost all patients except those with
any degree of heart failure. It was noted that the
increase of NT pro-BNP concentration was higher
in patients with larger size of myocardium wall
damaged by myocardial infarction. The increase
of NT pro-BNP concentration was correlated with
age, what was described in recent literature (19).
The most important predictor for the increase of
NT pro-BNP in this study was diastolic blood
pressure even on admission, and maximal measured diastolic blood pressure during the entire period of hospitalization. A possible explanation is
10
a higher stress of end-diastolic pressure on myocardial wall in high diastolic pressure (20). It is
known that natural stimulation of release of any
cardiac natriuretic peptides, like NT pro-BNP, is
distension of myocardial wall (21-23).
Myocardial infarction described as “anterior high-spread” had a larger size of damaged myocardium than any other localization. The increase of
concentration of NT pro-NBP was in a very close
correlation with that localization of infarction, as
may be concluded in this analysis. Repercussion
on heart strength to eject blood in bloodstream
during systolic period occurred only in situations
when a larger part of myocardium was damaged.
Therefore, patients with a higher degree of increase of NT pro-BNP were at higher risk to develop
heart failure than others (24,25).
The change of NT pro-BNP concentration was
shown in the early phase of myocardial infarction. It was pointed out that the substantial increase
of NT pro-BNP was one day after admission, in
comparison with those on admission, and slowed
down on eight day after admission. A higher increase of NT pro-BNP was shown in patients with
larger size of damaged myocardium, and in patients with higher diastolic blood pressure. Patients
prone to developing higher level of NT pro-BNP
were more likely to develop heart failure, what we
took in consideration when making decisions on
early diuretic treatment of these patients.
In conclusion, recognition of early increase of
NT pro-BNT in acute myocardial infarction could be used for decision making on modalities of
early treatment of myocardial infarction, the treatment of heart failure, clinical course of myocardial infarction.
FUNDING
No specific funding was received for this research.
TRANSPARENCY DECLARATION
Competing interest: none declared.
Mujarić et al. NT pro-BNP in myocardial infarction
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Promjene koncentracije natriuretskih peptida u ranoj fazi akutnog infarkta miokarda
Ekrema Mujarić1, Besim Prnjavorac 2 Merlina Kalajdžija-Cero3, Harun Šestić4, Almir Rošić1 Rifat
Sejdinović2, Sefveta Mustafić,5 Amila Mehmedović6
1
Odjel za unutrašnje bolesti, Kantonalna bolnica Zenica, Zenica; 2Odjel za unutrašnje bolesti, Opća bolnica Tešanj, Tešanj; 3Odjel za
anesteziju, reanimaciju i intenzivno liječenje, Kantonalna bolnica Zenica, Zenica; 4Odjel za hirurške bolesti, Kantonalna bolnica Zenica,
Zenica; 5Odjel za laboratorijsku dijagnostiku, Univerzitetski klinički centar Tuzla, Tuzla; 6Klinika za gantroenterohepatologiju, Klinički
centar Univerziteta u Sarajevu, Sarajevo; Bosna i Hercegovina
SAŽETAK
Cilj rada Analizirati značaj promjene koncentracije natriuretskih peptida (u radu NT pro-BNP), uzrokovane distenzijom miokarda, kao ranih prediktora kardijalne dekompenzacije kod akutnog infarkta
miokarda.
Metode U radu su analizirani klinički i laboratorijski parametri kod bolesnika s infarktom miokarda.
Uz standardne laboratorijske analize, određivana je koncentracija NT pro-BNP i to na dan prijema, te
drugi i osmi dan hospitalizacije. Statististička je obrada rađena testom analize varijance za ponavljana
mjerenja (ANOVA), faktorijalnom multivarijantnom analizom i testom multiple korelacije.
Rezultati Stratifikacija značaja prediktora za rano srčano popuštanje pokazala je sljedeći redoslijed:
godine starosti, dijastolni krvni tlak, CK kod prijema, širina zone infarkta itd. Metoda multiple korelacije pokazala je statistički značajnu povezanost ovih parametara s porastom NT pro-BNP. Aktivnost CK
bila je veća dan poslije nego na dan prijema, uz statističku značajnost (p=0,02), dok je CK-MB također
imao veću aktivnost drugi dan nego na dan prijema (p=0,016). Nađen je statistički značajan porast koncentracije NT pro-BNT na dan nakon prijema u odnosu na vrijednost kod prijema (p=0,00049), s tim da
je nivo NT pro-BNP značajno padao nakon osmog dana liječenja.
Zaključak Značajno povišenje razine NT pro-BNP, u toku infarkta miokarda, predstavlja značajan
prediktor ranog srčanog popuštanja, pa bi se, u slučaju vrlo značajnog porasta NT pro-BNP u ranoj fazi
infarkta, trebala uključiti terapija koja će preduprijediti klinički relevantno srčano popuštanje.
Ključne riječi ishemijska bolest srca, infarkt, NT pro-BNP, srčano popuštanje
12