IMPACT OF ON ADMISSION OSMOLALITY ON MAJOR ADVERSE

CARDIOVASCULAR EVENTS IN ACUTE MYOCARDIAL INFARCTION

PATIENT

COVER PAGE
A graduating paper
Submitted to the board of examiners as
partial fulfillment of the requirement of
Bachelor Degree in Faculty of Medicine
Universitas Gadjah Mada

By:
ACINTYA SEKAR MAHARDHIKA
12/338670/KU/15329

FACULTY OF MEDICINE
UNIVERSITAS GADJAH MADA
YOGYAKARTA
2015

APPROVAL PAGE

IMPACT OF ON ADMISSION OSMOLALITY ON MAJOR ADVERSE

CARDIOVASCULAR EVENTS IN ACUTE MYOCARDIAL INFARCTION
PATIENT

by
ACINTYA SEKAR MAHARDHIKA
12/338670/KU/15329

Tested and approved on November 10th 2015

Team of Graduating Paper Examiner

Material advisor

Methodology advisor

dr.Anggoro Budi Hartopo,

M.Sc.,Sp.PD.,Ph.D.
NIP: 19780718 201012 1 004

dr. Vita Yanti Anggraini,

M.Sc.,Sp.PD.,Ph.D.
NIP: 19630913 199003 2 001

Examiner

dr.Vina Yanti Susanti, M.Sc., SP.PD., Ph.D.

NIP: 1120110065

ii

AUTHENTICITY STATEMENT
IMPACT OF ON ADMISSION OSMOLALITY ON MAJOR ADVERSE
CARDIOVASCULAR EVENTS IN ACUTE MYOCARDIAL INFARCTION
PATIENT

By
Acintya Sekar Mahardhika
12/338670/KU/15329

The graduating paper is a scientific paper produced by

my individual work and based on my knowledge. It does
not contain material written by other person as the
requirement for graduation in Universitas Gadjah Mada
or the other tertiary institution except certain parts
that there writer quoted as reference by following the
appropriate way and writing ethics of the common
scientific paper.
If, in the future, it is proven that this statement is
untrue, it is fully the writers responsibility.

Yogyakarta, November 10th 2015

Writer

Acintya Sekar Mahardhika

12/338670/KU/15329

iii

PREFACE

I would first like to thank Allah SWT without whom

nothing is possible. I would like to express my deep
gratitude to my supervisors dr. Anggoro and dr. Vita
for

spending

much

time

in

helping

me

writing

this

graduating paper, as well as dr. Vina as my expert

examiner.

They

are

all

hard-working

doctors

and

believe their academic achievements will continue to

increase.
Big appreciation to my graduating paper partners,
Brilliant Winona Jhundy and Andanu Progoto Ersa for all
the helps, suggestions and entertainments in doing this
paper.
My

deepest

gratitude

for

my

best

friends

who

became my family Dira Mediani, Valerie Hirsy Putri,

Anindya Larasati, Saraswati Anindhita, Muhammad Ivan
Aulia Sani, R. Sureswara Agrawijaya, Aghnia Amalia.
Immeasurable appreciation for my partner in crime,
Adrian Raditya, without you, I dont know if medical
dream would ever become real.
Last but not least, I dedicated all my works for
my beloved family, thank you for being the angels of my
sweet little heaven, thank you for all the supports no
matter what the condition.
Yogyakarta, November 10th 2015

Acintya Sekar Mahardhika

iv

TABLE OF CONTENTS
COVER PAGE...................................................................................................................... i
APPROVAL PAGE ............................................................................................................. ii
AUTHENTICITY STATEMENT ....................................................................................... iii
INDEX OF ABBREVIATIONS ........................................................................................ x
ABSTRACT .........................................................................................................................xi
CHAPTER I ....................................................................................................................... 1
INTRODUCTION ................................................................................................................ 1
A.

Background..................................................................................................... 1

B.

Problem Formulation ............................................................................... 3

C.

Objectives..................................................................................................... 3

D.

Research Authenticity .......................................................................... 3

E.

Study Benefit ............................................................................................. 3

CHAPTER II..................................................................................................................... 5
LITERATURE REVIEW .................................................................................................... 5
A.

Literature Review .................................................................................... 5

1.

Acute Myocardial Infarction ........................................................ 5

2.

Osmolality and Myocardial Infarction .................................. 7

3.

Risk Factors Related Cardiovascular Events .................. 12

4.

Major Adverse Cardiac Event ...................................................... 15

B.

Basic Theory .............................................................................................. 17

C.

Hypothesis................................................................................................... 18

D.

Theoretical Framework

E.

Conceptual Framework ........................................................................... 19

................................................................... 19

CHAPTER III ................................................................................................................ 20

METHODOLOGY ................................................................................................................ 20
A.

Type and Study Design ........................................................................ 20

B.

Time and Study Setting ...................................................................... 20

C.

Study Subjects ......................................................................................... 20

D.

Sample Size ................................................................................................ 21

E.

Study Instrument .................................................................................... 23

F.

Measurement and Collection Method............................................ 23

G.

Research Variable .................................................................................. 24

H.

Operational Definition ...................................................................... 24

I.

Statistical Analysis ........................................................................... 29

J.

Ethical Consideration ........................................................................ 30

CHAPTER IV................................................................................................................... 31
A.

RESULT AND DISCUSSION ............................................................................ 31

CHAPTER V ..................................................................................................................... 43
CONCLUSION AND SUGGESTION ............................................................................... 43
A.

Conclusion................................................................................................... 43

B.

Suggestion................................................................................................... 43

REFERENCES................................................................................................................... 44
APPENDIX ....................................................................................................................... 53

vi

INDEX OF TABLE
Table 1

Binary logistic analysis of Osmolality based on MACE .. 32

Table 2 . Characteristics of patients after grouping based on the

osmolality level ............................................... 34
Table 3 . Comparison of characteristics between patients with MACE
and patients without MACE ...................................... 37
Table 4. Binary logistic analysis of Age based on MACE ......... 38
Table 5. Binary logistic analysis of Onset based on MACE ....... 38
Table 6. Binary logistic analysis of Hemoglobin based on MACE .. 38
Table 7. Binary logistic of BUN based on mACE .................. 38
Table 8. Binary logistic analysis of variables with p-value less
than 0.05 ...................................................... 39
Table 9 ........................................................ 53
Table 10 ....................................................... 53
Table 11 ....................................................... 54
Table 12 ....................................................... 54
Table 13 ....................................................... 54
Table 14 ....................................................... 54
Table 15 ....................................................... 55
Table 16 ....................................................... 55
Table 17 ....................................................... 56
Table 18 ....................................................... 56
Table 19 ....................................................... 56
Table 20 ....................................................... 56
Table 21 ....................................................... 57
Table 22 ....................................................... 57
Table 23 ....................................................... 58
Table 24 ....................................................... 58
Table 25 ....................................................... 58
Table 26 ....................................................... 59
Table 27 ....................................................... 59

vii

Table 28 ....................................................... 59

viii

INDEX OF FIGURE
Figure 1. Incidence of MACE in the research.................................... 36

ix

INDEX OF ABBREVIATIONS

Abbreviation
ACS
AMI
ATPase
aVF
aVL
BUN
CAD
CK-MB
CKD
df
dl
ECG
ESRD
Exp(B)
ICCU
kg
LL
MACE
mEq/l
mg
mm
mmol
mOsmol
NSTEMI
NYHA
PCI
STEMI
VF
VT
WHO

Full Citation
Acute Coronary Syndrome
Acute Myocardial Infarction
Adenosine Triposphatase
Augmented Voltage Foot
Augmented Voltage Left
Blood Urea Nitrogen
Coronary Artery Disease
Creatinin Kinase MB
Chronic Kidney Diseasae
Degree of freedom
deciliter
Electrocardiogram
End Stage Renal Disease
Exponentiation of B coefficient
Intensive CardioCare Unit
kilogram
Log Likelihood
Major Adverse Cardiac Event
Milliequivalent per liter
milligram
millimeter
millimol
milliosmol
Non-ST Elevation Myocardial Infarction
New York Heart Association
Percutaneous Coronary Intervention
ST Elevation Myocardial Infarction
Ventricular Fibrilation
Ventricular Tachycardia
United Nation World Health Organization

IMPACT OF ON ADMISSION OSMOLALITY ON MAJOR ADVERSE

CARDIOVASCULAR EVENTS IN ACUTE MYOCARDIAL INFARCTION
PATIENT
AcintyaSekar Mahardhika, Anggoro Budi Hartopo, Vita
Yanti Anggraini
Faculty of Medicine, Universitas Gadjah Mada

ABSTRACT
Background: The main cause of death around the world is
cardiovascular disease. According to WHO, in 2008 there
are 17.3 million deaths caused by cardiovascular
disease, with 7.3 million is the result of myocardial
infarction. Some studies suggested that there is an
association between elevated blood glucose and BUN on
admission and mortality due to acute myocardial
infarction. As plasma glucose, BUN, and sodium are the
main component of osmolality, we should also analyze
the effect of on admission osmolality on clinical
endpoints in AMI patient. Previous studies show that
the value of osmolality significantly related with
clinical outcome in ACS patient.
Objective: The objective of this research is to
investigate the influence of increasing osmolality on
to the incidence of MACE in AMI patients hospitalized
in ICCU
Method:
The
objective
of
this
research
is
to
investigate the influence of increasing osmolality on
to the incidence of MACE in AMI patients hospitalized
in ICCU.
Results:This study is an observational study. The study
design is a prospective cohort. The study is a part of
the
previous
study
conducted
in
Department
of
Cardiology and Vascular Medicine. Plasma osmolality was
calculated using concentration of sodium, plasma
glucose, and blood urea nitrogen on admission.
Conclusion:There
is
strong
association
between
increasing value of on admission osmolality and the
increasing of MACE occurrence.
Key Words: osmolality, AMI, MACE

xi

CHAPTER I
INTRODUCTION
A.
The

main

cause

Background
of

death

around

the

world

is

cardiovascular disease, and is frequently associated

with acute myocardial infarction. According to WHO, in
2008

there

are

17.3

million

deaths

caused

by

cardiovascular disease, with 7.3 million (42% of all

cardiovascular

deaths)

is

infarction.

Cardiovascular

around

of

10%

the

the

result

disease

disability

of

give

adjusted

myocardial

contribution
life

years

(DALYs) lost in low-middle income countries and around

18% of DALYs lost in high-income countries (Anonymous,
2012).
In

clinical

setting,

serum

biomarkers

are

popularly used for risk estimation, since biomarkers

are

sensitive

and

specific

for

acute

myocardial

infarction (AMI). Some studies suggested that there is

an

association

admission

and

between
mortality

elevated
due

to

plasma
acute

glucose

on

myocardial

infarction. Other than plasma glucose, elevated blood

urea nitrogen (BUN) is highly predictive for mortality,
myocardial infarction, and stroke. As plasma glucose,
BUN, and sodium are the main component of osmolality,

we

should

also

analyze

the

effect

of

on

admission

osmolality on clinical endpoints in AMI patient.

Previous studies show that the value of osmolality
significantly
patient.
function.

related

Osmolality
There

relationship

is

between

with

is

clinical

closely

also

related

reported

worsening

outcome
with

that

kidney

in

ACS

kidney

there

is

function

a
in

patient of decompensate heart failure and poor clinical

outcome (Klein et al., 2008). Osmolality higher than
296 mosmol/kg at the time of admission shows increase
risk of death 2.4 folds higher (Bhalla et al., 2000).
Osmolality consists of three component, glucose,
BUN, and sodium. Each of the components of osmolality
shows

significant

relationship

with

MACE

(Major

Adverse Cardiovascular Event). Hyperosmolality caused

by hyperglycemia show deleterious effect on survival of
patient with ACS (Rohla et al., 2014). The increase of
BUN as the largest contributor of osmolality can become
a

large

predictor

of

death,

recurrent

myocardial

infarction, and congestive heart failure after 30 days

among ACS patient (Kirtane et al., 2005). As plasma
glucose, BUN, and sodium are the main components of
osmolality, we should also analyze the effect of on
admission

osmolality

on

clinical

endpoints

in

AMI

patient, which probably will give benefit in predict

the outcome of AMI patients since the early.
B.
Does

the

prognostic

Problem Formulation

increase

value

for

of

osmolality

developing

have

Major

the

Adverse

Cardiovascular Events (MACE) in AMI patients?

C.

Objectives

The objective of this research is to investigate

the influence of increasing osmolality on the incidence
of MACE in AMI patients hospitalized in ICCU.
D.

Research Authenticity

During

searching

of

previous

review

there

no

other

research.

is

Therefore,

it

studies

finding
is

and

literature

related

considered

to

this

that

this

research is the first research studying about relation

of osmolality and MACE in AMI.
E.
This

research

Study Benefit
is

expected

to

bring

additional

source of information in predicting factor of prognosis

in AMI patients. In addition, this research is also
expected to give reference to other researcher which is
interested
osmolality.

to
This

investigate
research

further
will

also

about

plasma

answer

the

clinician

speculation

about

the

role

of

measuring

plasma osmolality in AMI, because this factor is still

less considered in management of AMI patient.

CHAPTER II
LITERATURE REVIEW
A.
1.

Literature Review

Acute Myocardial Infarction

In

cardiovascular

disease

there

is

an

ischemic

heart disease as the subtype. Ischemic heart disease

itself then divided into two groups of patient, chronic
coronary

artery

disease

(CAD)

and

acute

coronary

syndrome (ACS). Further, ACS is divided into three,

non-ST segment elevation acute myocardial infarction
(NSTEMI),

ST

segment

elevation

acute

myocardial

infarction (STEMI), and unstable angina pectoris (UAP)

(Theroux, 2011).
Acute coronary syndrome (ACS) occurs due to the
imbalance
cardiac

between
muscle.

condition,

such

oxygen
The
as

supply

factors
vigorous

decrease

perfusion

pressure

severely

decreased

in

anemia

(Lilly,

2011).

pathophysiology

of

ACS

blood

has

and

that

demand

underlying

exercise,
due

to

oxygen
The

of

the
this

stress,

and

hypotension,

and

content

due

understanding

undergone

to
of

remarkable

change. Previously it consider as cholesterol storage

disease that currently known as atherosclerosis (Libby
& Theroux, 2005). The all region of infarction in ACS

is

caused

by

the

development

of

culprit

coronary

atherosclerotic plaque. Thrombosis is one of the major

causes

of

AMI.

Thrombosis

occurs

because

of

two

different processes. The first process is the extension

of

endothelial

denudation

so

that

large

areas

of

subendothelial connective tissue surface are exposed.

In that area thrombus is formed and adhere forming
plaque

surface.

disruption.

The

second

process

is

plaque

Here the plaque cap disrupt and exposed

the lipid core into blood in the lumen of the artery.

The

lipid

core

is

highly

thrombogenic;

consist

of

tissue fragment, fragments of collagen, and crystalline

surface

that

help

accelerate

coagulation

(Davies,

2000). Furthermore the disrupted plaque then travelled

along

the

smaller

blood

vessel

stream

such

as

until

finally

coronary

artery

stop
and

in

the

forming

vessel obstruction that leading to ischemia.

Patient is diagnosed as AMI based on the clinical
presentation, electrocardiographic findings, and serum
biomarker of myocardial damage. ECG in patients with
STEMI

shows

mm

elevation

II,III,aVF and I aVL,

left

bundle

troponin

I,

branch

block

myoglobin,

and

in

more

than

lead

2 mm in V1-V6 and/or new

(LBBB).
CK-MB

Cardiac

also

marker

increases

in

patients with STEMI aND will be no ST-segment elevation

in NSTEMI(Leonard, 2011).
2. Osmolality and Myocardial Infarction
Total

body

water

is

different

between

men

and

women, and it is decreasing due to aging. Around 50-60%

of

total

body

weight

is

water;

two-third

of

it

is

intracellular fluid, while one-third is extracellular

fluid. One-fourth of extracellular fluid is located in
intravascular space. The changes in body fluid may be
due to the loss of water, either from intracellular or
extracellular space. The changes of body fluid are best
evaluated from the changes of body weight (Guyton &
Hall, 2011).
Solute concentration of body fluid is measured by
osmolality.

Osmoles

per

kilogram

osmolality;

osmoles

per

liter

osmolality.

physiological

of

of

water

is

solution

is

concentration

of

solute

normally is 285-295 mOsmol/kg. The two measurements of

osmolality

and

osmolality

are

clinically

interchangeable. Tonicity refers to osmolytes that is

impermeable

toward

cell

membrane.

The

difference

of

osmolyte concentration across cell membrane leads to an

osmosis and the shift of fluid, stimulation of thirst,
and

secretion

of

antidiuretic

hormone

(ADH).

Other

substances that easily permeate cell membranes such as

urea and ethanol are ineffective osmoles, because they
do

not

cause

fluid

shift

crossing

the

fluid

compartments (McPhee et al., 2015).

The

estimation

obtained

from

of

the

value

formula,i.e.

of

osmolality

osmolality

2Na

is
+

(glucose/18) + (BUN/2.8), (Na is sodium, BUN is blood

urea nitrogen) (Brubacher et al., 2001). Based on the
formula, the important determinants of osmolality are
sodium,

glucose

and

urea

nitrogen

level.

Therefore,

their value should be gained from the laboratory result

and incorporated into the formula.
There are some factors that can cause the changes
of

those

three

components,

whether

increasing

or

decreasing. First component is sodium. Sodium is the

primary
pumped
through

extracellular
out

to

and

fluid

entered

Na+/K+-ATPase

cation.
from

channel

in

Sodium

can

extracellular
the

cell

be

space

membrane.

When the sodium pumped into the intracellular, there

will be amount of potassium that is pumped out toward
the extracellular space. Acute change in serum sodium
will produce free shifting of water into and out of
extracellular space until osmolality equilibrates in

this compartment (Richard, 2011). The rise of sodium

level is defined as hypernatremia.
Hypernatremia
concentration

>

is

defined

145mEq/l.

as

plasma

Hypernatremia

sodium

indicates

decrease in total body water relative to sodium and is

invariably
though

associated

total

body

with

sodium

plasma
content

hyperosmolality
may

be

normal,

decreased, or increased (Arora, 2013). It may be caused

by a primary gain in sodium or an excess of water.
Another source of sodium gaining is hyperaldosteronism,
Cushings syndrome, or excessive hypertonic saline or
sodium

bicarbonate

decrease

of

sodium

administration.
is

defined

Conversely,
as

the

hyponatremia.

Hyponatremia occur when the ratio of solute body water

content is altered by parallel changes in serum sodium
and

osmolality.

Generally

hyponatremia

defined

as

serum sodium concentartion < 135 to 136 mmol/L and

devided into 2 types, dilutional or depletional (Oren,
2005).
Mostly hyponatremia cases are caused by reduced
renal excretion of water with continued water intake or
by

sodium

loss

from

urine.

Hyponatremia

is

usually

asymptomatic and most of the cases are associated with

low

serum

osmolality

(Guyton

&

Hall,

2011).

10

Hyponatremia is a common hospital-acquired electrolyte

disorder and is often related with high mortality and
morbidity
disease.

due
In

to

progression

some

research

of

previous

mention

that

underlying

hyponatremia

shown become a predictor of cardiovascular mortality

among

patient

with

heart

failure

(Goldberg

et

al.,

2004). Hyponatremia also induced by diuretic medication

in congestife heart failure patien.
The

second

component

is

blood

glucose.

Blood

glucose levels fluctuated depend on food intake varies

over a 24-hour period. Normal range of fasting blood
glucose is between 70-100 mg/dl. The result outside
this

range

could

be

indicated

as

blood

glucose

regulation dysfunction which usually occurs in diabetes

mellitus patient (James & McFadden, 2004). From the
previous study reported that glycaemia correlate with
short-term

and

long-term

associated

with

endothelial

prognosis.

Hyperglycemia

dysfunction,

platelets

hyperactivity, microvascular dysfunction, increase of

cytokine activity, increase level of free fatty acid,
and increase oxidative stress level, where all these
factors adversely affect outcomes in AMI. There is also
an addition, an increase of on admission plasma glucose
is a major independent predictor of in-hospital and

11

long-term outcome of the patient with AMI (Nesto &

Lago, 2015).
The
patient

use

of

shows

insulin

in

significant

treating
change

hyperglycemic
in

osmolality

component. In the research conducted by DeFronzo et al

shows

there

was

no

significant

alteration

of

blood

glucose concentration with the remaining 96-99% blood

glucose

alert.

Plasma

sodium

concentration

shows

no

significant change, while the mean sodium clearance and

sodium excretion were both significantly change during
administration

of

insulin.

There

was

also

an

association between time of insulin administration and

insulin

effect

to

Insulin

effect

was

the

electrolytes

significant

in

in
the

body
first

fluid.
30-60

minutes after administration and increasing during 6090 and 90-120 minutes collection period (DeFronzo et
al., 1974)
The third component is blood urea nitrogen. Blood
urea nitrogen normal range I s lie between 5 to 20
mg/dl, or 1.8 to 7.1 mmol/L, but normal range may vary
depending on the reference range used by the lab and
age (Hall et al., 1990). Generally, a high blood urea
nitrogen level related to kidney dysfunction. Another
factors causing elevation of blood urea nitrogen level

12

are urinary tract obstruction, congestive heart failure

or

recent

dehydration,

heart

attack,

severe

gastrointestinal

burns,

and

high

bleeding,

protein

diet

(Guyton & Hall, 2011). Higher concentration of BUN was

associated with the increase in mortality at 30 days
and

throughout

the

follow

up

period.

Patient

with

higher BUN were have increase chance to have recurrent

myocardial infarction and congestive heart failure by
30 days, were likely to undergo revascularization, were
more likely to had stroke, and also had more frequent
adjudicated bleeding event (Kirtane et al., 2005). A
study about correlation between on admission osmolality
with all-cause of death in ACS patient has already been
done with the result of

strong association between

admission osmolality and all-cause death in ACS patient

undergoing PCI (Rohla et al., 2014)
3. Risk Factors Related Cardiovascular Events
Chronic kidney disease (CKD) is a progressive loss
of renal function for months to years periods that
shows symptoms of uremia when GFR is reduce about 1015% from normal (Kasper et al., 2005). Hypertension is
the most common symptom that occurs first in CKD. From
many previous studies already showed that there was
strong

correlation

between

renal

failure

and

13

cardiovascular events. Around 50% of patients with endstage

renal

disease

cause

(Schiffrin

(ESRD)

et

al.,

die

from

2007).

cardiovascular

The

relationship

between renal disease and cardiovascular mortality has

also

been

shown

mostly

increasing

in

patients

with

stage 3 to 4 CKD (GFR < 60 mL/min per 1.73 m2) rather

than progress to ESRD (Levin et al., 1996).
The most principal pathophysiological mechanisms
involved in the association of CKD and cardiovascular
event has been appointed to be endothelial dysfunction.
Many of traditional and non-traditional cardiovascular
risk factors that affect endothelial function can be
found

in

correlation

with

CKD.

Another

related

condition such as obesity, diabetes, and hypertension

are presence in renal dysfunction (Amann et al., 2006).
Endothelial dysfunction is recognized as the initial
mechanism

of

atherosclerosis

formation.

Endothelial

dysfunction that occur both in small and large arteries

is

present

2004).

Another

endothelial
mechanism

in

renal

disease

experimental

dysfunction
lead

(Endemann

to

give

study

Schiffrin,

showed

contribution

progression

(Fujihara et al., 1995).

&

of

renal

to

that
the

disease

14

Beside

endothelial

dysfunction,

hypertension

represents a strong risk factor for CVD in CKD. Sodium

retention due to CKD activated renin-angiotensin system
has been recognized as the most important mechanism in
the elevation of blood pressure in patient with kidney
disease (Guyton et al., 1999). Renin-Angiotensin system
occurs in many types of renal disease. Angiotensin II
leads to generation of superoxide anion and play a role
to endothelial dysfunction and vascular remodelling and
growth by stimulates NADPH oxidase (Touyz & Schiffrin,
2004).
Elevation
recognized

of

as

one

cardiovascular
circulating
protein

inflammatory
of

event.

serum

risk

The

inflammatory

(CRP),

the

markers

also

factors

increasing

markers

amyloid

A,

such

been
casing

level

as

of

C-reactive

interleukin-6,

and

interleukin-1 receptor antagonist are commonly seen in

ACS. Those elevations correlate with in-hospital and
short-term
There

adverse

are

atherogenesis

some

prognosis

(Libby

triggers

for

process

such

as

et

al.,

2002).

inflammations

oxidize

in

lipoproteins,

dyslipidaemia, hypertension, obesity, and infection.

Prevalence of endothelial dysfunction, low-grade
inflammation,

and

dyslipidaemia

associated

with

15

incipient and progressive renal disease explain fast

progression

of

atherosclerosis

and

together

with

hypertension explain the high prevalence of coronary

ischemia and cardiovascular events in CKD.
4.

Major Adverse Cardiac Event

In

Indonesia,

the

management

of

AMI

patients

almost meet the protocol and proven that the prognosis

become well after undergoing the treatment. But still
there are some cases that usually is called as major
adverse

cardiovascular

events

(MACE)

emerging

even

after a careful treatment. The exact definition for

this term often varies depending on the specific study.
The definition of MACE that use today by clinician at
the broadest level includes end points that reflect
safety

and

effectiveness

approaches (Hollabaugh
by

Kern

et

coronary
procedural

al

myocardial

various

treatment

et al., 2008). A book written

defined

intervention

with

MACE
(PCI)

following
include

infarction,

percutaneous
death,

emergent

peri-

coronary

artery bypass graft surgery (CABG), significant vessel

dissection or perforation, cerebrovascular accident, or
vasvular complication. At first the use of the term
MACE is refer to evaluate net effect, in which the
net effect refer to potential utility (effectiveness)

16

and hazardousness (safety), acute on new intervention.

But as time goes the use of term MACE has shifted into
reporting intermediate- to long term-effect, even when
a person is not interested on evaluate net effect of a
particular intervention (Hollabaugh

et al., 2008).

Major adverse cardiac events are a clinical end

points that occurring either in hospital or within 7
days of the PCI. MACEs including death, MI, or urgent
target

vessel

revascularization

(Steinhubl

et

al.,

2001). The incidence of the 3 event as a combination

has

decreased

over

time

due

to

the

improvement

of

technology, operator experience, and pharmacology in

treating AMI patient that undergoing PCI (Kern et al.,
2006). At the narrowest, it has the same meaning with
coronary event, which refers to adverse events caused
by disease processes affecting the coronary arteries.
These may include what are termed hard events such as
deaths that are attributed to coronary artery disease
and

nonfatal

occasionally

myocardial
soft

revascularization

for

events

infarctions
such

progressive

as

but

also

angina

coronary

or

artery

disease (OConnor et al., 2010). As reported, the rates

of in hospital mortality due to in hospital MACE is 1-

17

2%, urgent or emergent CABG generally <2%, and Q-wave

myocardial infarction are 1-2% (Kern et al., 2006).
The risk factors in having in hospital MACE are
divided

as

clinical

and

procedural

factors.

Risk

factors included in clinical factors are multi-vessels

disease, decrease left ventricle (shock), comorbidity
(renal

insufficiency,

peripheral

vascular

disease),

age, gender, and MI within 24 hours. Procedural factors

such

as

thrombus,

lesion

characteristics

bifurcation),

(urgent/emergent),

and

(length,

procedural

intra-procedural

associated
circumstance
complication

(abrupt vessel closure, significant dissection) (Dorros

et al., 1983).

B.

Basic Theory

Based on the literature review, it may be concluded

that:
1.

Acute coronary syndrome (ACS) occurs due to the

imbalance between oxygen supply and demand of the
cardiac muscle.

2.

Solute concentration of body fluid is measured by

osmolality.

physiological

concentration

solute normally is 285-295 mOsmol/kg.

of

18

3.

Based on the formula, the important determinants

of

osmolality

are

sodium,

glucose

and

urea

nitrogen level. formula,i.e. osmolality = 2Na +

(glucose/18) + (BUN/2.8).
4.

Major

adverse

clinical

end

hospital

or

including

cardiac
points

within

death,

events

that
7

MI,

occurring

days
or

(MACEs)

of

the

urgent

are

either
PCI.

target

a
in

MACEs
vessel

revascularization.

C.
1.

Null

hypothesis:

osmolality

Hypothesis
An

associate

elevation
with

of

major

on

admission

adverse

cardiac

events in Acute Myocardial Infarct patient.

2.

Alternative

hypothesis:

An

elevation

of

on

admission osmolality does not associate with major

adverse cardiac events in Acute Myocardial Infarct
patient.

19

D.

E.

Theoretical Framework

Conceptual Framework

20

CHAPTER III
METHODOLOGY

A.

Type and Study Design

This study is an observational study. The study

design is a prospective cohort. The study is a part of
the

previous

study

conducted

in

Department

of

Cardiology and Vascular Medicine Faculty of Medicine

Universitas Gadjah Mada (Hartopo et al., 2014).
B.

Time and Study Setting

This research was conducted during 2013-2015. The

research

was

done

in

Emergency

Unit

and

Intensive

Coronary Care Unit of Dr. Sarjito Hospital, Yogyakarta.

The data analysis was conducted in Yogyakarta, 2015.
C.

Study Subjects

The target population of this research is patients

with acute myocardial infarction whom are hospitalized
and treated in the Intensive Coronary Care Unit (ICCU).
The source population for the study is patients with
AMI whom are hospitalized and treated in the ICCU RSUP
Dr. Sarjito, Yogyakarta, Indonesia. The subjects for
the study are the source population whom satisfy the
research criteria.

21

D.

Sample Size

The subjects are sampled in sequence (consecutive

sampling)

since

this

sampling

method

is

easier

to

employ during the research and it is less opportunity

for intentional or unintentional manipulation by the
data analysis process or errors due to confusion.
Inclusion
patient

with

criteria
AMI,

both

for

the

STEMI

and

subjects

are:

(1)

whom

are

NSTEMI,

diagnosed according to the PERKI criteria and ACC/AHA

guideline, (2) the onset of chest pain is not more than
24 hours before admission, (3) patients by the age of
18-75 years, and (4) patients willing to participate in
the study by confirming an informed consent. Exclusion
criteria are: (1)patients with a history of: chronic
kidney disease stage IV-V, chronic heart failure NYHA
class > II, known valvular heart disease and cirrhosis
hepatic, (2) patients with comorbid factors:
diabetic

patients

thromboembolism,
(ketoacidosis

treated
and

diabetic

or

with

sepsis,

insulin,

venous

decompensated

diabetics

hyperglycemic

hyperosmolar

state), (3) patients with malignancy and (4) patients

use loop diuretics in daily basis.
Based on literature review there is no study
before about the relationship between the increasing of

22

osmolality with incidence of MACE. This research will

perform sample size calculation using 100 patients to
get the minimum representative sample size.
Sample size needed in this research is calculated
based on the following formula:
Optimum allocation when n is constant for random
sampling stratified by proportion

n1= sample for group 1

N1= total sample from group 1
P1= proportion of n1 from total sample based on osmolality
Q1 = 1-P1
n = total sample for calculating minimal sample size

23

From the calculation minimal sample size used for

each

group

is

69

for

group

(subject

with

normoosmolality and having MACE) and 31 for group 2

(subject with hyperosmolality and having MACE)
E.
Instruments

Study Instrument

that

are

used

in

the

research

including (1) case report form to record demographic

data,

clinical

laboratory

and

outcome

data,

(2)

software for statistical analysis.

F.

Measurement and Collection Method

The subjects are sampled consecutively. Subjects

whom meet the criteria are recorded in case report
form.

Data

that

is

recorded

are

demographic

data

including age, gender, smoking history, hypertension,

diabetes
admission

mellitus,

and

clinical

ischemic

data

heart

including

disease.
systolic

On
and

diastolic blood pressure and heart rate. On admission

laboratory

data

including

(1)

routine

blood

test:

hemoglobin, leukocyte, platelet, and erythrocyte, (2)

blood

chemical

nitrogen

(BUN)

examination:
and

random

creatinine,

glucose,

(3)

urea

electrolyte

examination: sodium, potassium, and chloride and (4)

cardiac enzyme examination: CK-MB and troponin I
Plasma osmolality value is determined by formula:

24

Osmolality= 2Na + BUN/2.8 + GDS/18

Major adverse cardiovascular events are determined
during

hospitalization

cardiovascular
failure,

events

in

namely

cardiogenic

ICCU.

Major

mortality,

shock,

adverse

acute

resuscitated

heart
lethal

arrhythmia (VT/VF) and reinfarction.

G.
Independent

Research Variable

variable

is

plasma

osmolality

on

admission. Dependent variable is major adverse cardiac

event.

Confounding

variables

in

variables

exclusion

(controllable)

criteria,

these

controlled by excluded from the research.

are

criterias
Confounding

variables (uncontrollable) are age, gender, diabetes,

dyslipidemia, and onset of chest pain.
H.
1.

Operational Definition

Plasma osmolality

Plasma

osmolality

is

concentration

measure

of

all

chemical particles found in the fluid part of blood

(Keane & OToole, 2013). Plasma osmolality is measured
by formula Osmolality= 2Na + BUN/2.8 + GDS/18
2.

Major Adverse Cardiac Event (MACE)

MACE is a composite of mortality, acute heart failure,

cardiogenic

shock,

resuscitated

lethal

(VT/VF) and reinfarction (Hartopo, 2013).

arrhythmia

25

3. Acute myocardial infarction

There is evidence of myocardial necrosis with clinical
presentation, electrocardiographic findings, and serum
biomarker of myocardial damage. ECG in patients with
STEMI

shows

mm

elevation

II,III,aVF and I aVL,

left

bundle

troponin

I,

branch

block

myoglobin,

and

in

more

than

lead

2 mm in V1-V6 and/or new

(LBBB).
CK-MB

Cardiac

also

marker

increases

in

patients with STEMI aND will be no ST-segment elevation

in NSTEMI (Lilly, 2011)
4. Onset of angina
Time from the patient begin to feel the symptom of
angina until patient presentation in emergency room.
5. Blood pressure
Blood pressure is the pressure of the blood within the
arteries. It is produced primarily by the contraction
of the heart

muscle. Its measurement is recorded by

two numbers, systolic and diastolic. Blood pressure was

recorded twice during early presentation, by adult-size
cuff sphygmomanometer during supine position.
6. Chronic kidney disease
Chronic kidney disease is a progressive loss of renal
function for more than 3 months that shows symptoms of
uremia when GFR is reduce about 10-15% from normal.

26

Chronic

kidney

disease

is

determined

as

elevated

creatinine and BUN levels more than 3 months (Schiffrin

et al., 2007).
7. Congestive heart failure
Heart failure is inability or failure of the heart to
adequately

meet

the

needs

of

organ

and

tissue

for

oxygen on nutrients. The congestive sign and symptom at

daily

activity

was

recorded.

Sign

of

congestion

is

divided based on which side of the heart involved. Sign

of left-sided congestion are diaphoresis, tachycardia,
tachypnea, pulmonary rales, loud P2, S3 gallop, and S4
gallop. Symptoms of left-sided congestion are dyspnea,
orthopnea, paroxysmal nocturnal dyspnea, and fatigue.
Sign

of

right-sided

distention,

congestion

hepatomegaly,

and

are

jugular

peripheral

venous
edema.

Symptoms of right-sided congestion are peripheral edema

and

right

upper

quadrant

discomfort

due

to

hepatic

enlargement (Lilly, 2011).

8. Diabetes mellitus (DM)
Diabetes

mellitus

disorders

that

compromises
share

the

group

common

of

metabolic

phenotype

of

hyperglycemia. DM is classified into DM type 1 and type

2. Diagnostic criteria of DM include of fasting plasma
glucose 7.0 mmol/L (126 mg/dL), symptom of diabetes

27

plus random blood glucose concentration 11.1 mmol/L

(200 mg/dL), and 2 hours plasma glucose 11.1 mmol/L
(200 mg/dL) during a 75 g oral gucose tolerance test
(Longo et al., 2008).
9. Valvular heart disease
Valvular heart disease is characterized by damage to or
defect in one of the four heart valves: the mitral,
aortic,

tricuspid

or

pulmonary.

The

confirmation

of

diagnosis is based on echocardiography (Lilly, 2011).

10. Cirrhosis hepatic
Cirrhosis hepatic is a chronic disease of the liver
characterized
lobular

and

by

fibrosis,

vascular

disorganization

architecture,

and

of

the

regenerating

nodules of hepatocytes. Previous abdominal ultrasound

confirmed the diagnosis (Longo et al., 2008).
11. Sepsis
Sepsis is systemic illness caused by microbial invasion
into

normal

potentially

sterile
life

parts

of

threatening

the

body.

It

complication

is
of

a
an

infection. Sign of sepsis were body temperature above

38.8C or below 36C, heart rate more than 90 times per
minutes,

respiratory

rate

more

than

20

times

per

minutes, and probable or confirmed infection (Longo et

al., 2008).

28

12. Ketoacidosis diabetic

Diabetic

ketoacidosis

is

an

acute,

major,

life-

threatening complication of diabetes that, mostly type

1

diabetes.

This

condition

is

metabolic state characterized by

complex

disorder

blood glucose > 250

mg/dL, anion gap > 10, bicarbonate level < 15 mEq/L,

blood pH < 7.3, and ketonemia (Longo et al., 2008).
13. Hyperglycemic hyperosmolar state
Hyperglycemic hyperosmolar state is a serious metabolic
derangement

that

occurs

in

mellitus characterized by
plasma

osmolality

>

315

patients

with

diabetes

serum glucose > 600 mg/dL,

mOsm/kg,

bicarbonate

>

15

mEq/L, and blood pH > 7.3 (Longo et al., 2008).

14. Hypertension
Hypertension is a condition of systolic blood pressure
of 140 mmHg or more, or a diastolic blood pressure of
90 mmHg or more, or taking antihypertensive medication
(Longo et al., 2008).
15. Current smoker
Current smoker is someone who has smoked greater than
100

cigarettes

(including

hand

rolled

cigarettes,

cigar, cigarillos) in their lifetime and has smoked in

the last 28 days.
16. Malignancy

29

Malignancy
ability

refers

to

to

spread

cancerous
to

other

cell

that

sites

in

have
the

the
body

(metastasize) or to invade nearby (locally) and destroy

tissues.

Malignant

cells

tend

to

have

fast,

uncontrolled growth and do not die normally due to

changes in their genetic makeup (Kumar et al., 2015).
I.

Statistical Analysis

Descriptive statistics are performed in baseline

variables
Discrete

and

stratified

characteristics

by
are

cut

off

of

expressed

osmolality.

as

frequency

counts as percentages, differences between groups were

determined

with

characteristics

the
are

chi-squared

expressed

as

test.
mean

Continuous

and

standard

deviation or median and quartiles, the differences in

those variables were examined with the Kruskal-Wallis.
Parametric test used in this research is logistic
regression due to both of the variables are nominal
data. Univariate analysis between osmolality and MACE
and

multivariate

analysis

of

variables

with

under 0.05 were done using binomial regression.

p-value

30

J. Ethical Consideration
Ethical clearance for the research has been obtained
from Medical and Health Research Committee Faculty of
Medicine
research.

Universitas

Gadjah

Mada

for

the

current

31

CHAPTER IV
A. RESULT AND DISCUSSION

In this research total subjects used are 167 males

and 37 females. The main data needed from the raw data
is osmolality data (blood sugar, sodium, and BUN) and
MACE. The MACEs are observed over a period of time
since the first time patient admitted in ICCU until
patient

discharged.

population

without

This
control

research

only

population,

has

one

because

the

researcher only aims to observing whether there is an

association between the increase values of on admission
osmolality with the increase of MACE occurrence.
Data were collected for approximately 2 years from
a span of years 2013 to 2015. With total 201 subjects,
there are 2 groups of subjects normoosmolal indicating
the value of osmolality under 295.0 mOsmol with total
137 subjects and hyperosmolal indicating the values of
osmolality over 295.0 mOsmol with total 64 subjects.
We used logistic regression binary logistic type
to analyze the association between osmolality and MACE.
The

logistic

independent

regression

variable

(MACE)

was

used

represent

because
as

both

binominal

32

data. The result of the analysis is the coefficient of

constant contribution give very high significance in
predicting MACE occurrence (Wald 78.64, p < 0.001).
After analyzing variables that include in the equation
the next step is analyzing variable that not included
in the equation. The analysis showed the score is 6.174
with

significance

0.013.

The

result

shown

in

significance row is 0.015 which less than 0.05, this

result consider that the predictor (osmolality) is very
significant

in

predicting

MACE

occurrence.

After

consider the predictor give a significant effect in

predicting MACE occurrence, there is one last test to
determine whether there is a significant difference if
the predictor is removed from the model. The test is
carried out using Model if Term Removed table and shows
the result 0.016 which is significant.
Table 1. Binary logistic analysis of Osmolality based
on MACE
Variable
Osmolality

Odd
Ratio

95% CI
Lower

Upper

2.69

1.21

5.99

p-value
0.015

From the logistic regression analysis it can be

summarize that the fitness between data and the model

33

is

good.

The

accepted,

final

which

result

means

that

concluded
with

that

the

the

H0

increase

of

osmolality value give impact to the increasing of MACE

occurrence.
The

baseline

characteristics

of

the

group

with

normoosmolal and hyperosmolal are depicted in Table 1.

This table showing how significant the influence of
each

variable

to

osmolality

in

predicting

MACE,

to

discover whether there is any other variable that may

confound

the

result

osmolality and MACE.

of

the

correlation

between

34

Table 2 . Characteristics of patients after grouping

based on the osmolality level
Characteristics
Demographic
Age, year (meanSD)
Onset, hour (meanSD)
Sex (n (%))
Male
Diabetes (n (%))
Hypertension (n (%))
IHD /stable angina (n
(%))
Systolic Pressure
(meanSD)
Diastolic Pressure
(meanSD)
Current smoking (n (%))
Dyslipidemia (n (%))
Family History (n (%))
Diagnosis (n (%))
STEMI
NSTEACS
STEMI (n (%))
Primary PCI (n (%))
Intervention and
Medication
Thrombolysis (n (%))
Heparin (n (%))
LMWH
UFH
Fondaparinux
No Heparin
Nitrate (n (%))
Aspilet (n (%))
Clopidogrel (n (%))
Statin (n (%))
ACE Inhibitor (n (%))
Beta Blocker (n (%))
Furosemide IV (n (%))
Vasopressor (n (%))
Inotropic (n (%))
Heart Rate (meanSD)
Routine Blood Test
Leucocyte (meanSD)
Thrombocyte (meanSD)
Creatinine (meanSD)
Haemoglobin (meanSD)
BUN ((meanSD)
Electrolyte
Sodium (meanSD)
Pottasium (meanSD)
Chloride (meanSD)
Glucose (meanSD)

Normoosmolal
N=137

Hyperosmolal
N=64

PValue

56.28.9
9.16.8

57.98.7
8.66.5

0.99
0.99

117(85.4)
12.4
61.3
10.2

47(73.4)
50.0
50.0
14.1

0.04
<0.001
0.13
0.43

130.623.5

129.123.6

0.99

80.814.6

78.513.4

0.99

54.7
7.3
2.2

40.6
17.2
0.0

0.06
0.03
0.23
0.06

77.4
22.6
37.1
25.5

82.8
17.2
13.2
29.7

34.3

34.4

7.3
78.1
10.9
3.6
99.3
100.0
100.0
100.0
83.9
53.3
0.0
0.0
0.0
75.514.6

7.8
84.8
4.7
3.1
100.0
100.0
100.0
100.0
76.6
50.0
1.6
1.6
1.6
77.319.1

0.49
N.A.
N.A.
N.A.
0.21
0.66
0.14
0.14
0.27
1.00

12.93.7
257.063.2
1.20.4
14.21.7
13.45.5

12.13.5
241.946.9
1.40.7
13.71.9
18.58.6

0.99
0.99
1.00
0.99
0.99

137.32.9
3.90.5
109.985.6
151.558.9

139.93.5
4.00.6
104.53.8
250.6132.1

0.99
0.99
0.99
0.99

0.06
0.54
0.99
0.56

35

Comparison through all groups was performed with the Chisquared test for the discrete data or the Kruskal-Wallis test for
the
continuous
characteristics.
ACE,
angiotensin-converting
enzyme;BUN;CABG,
coronary
artery
bypass grafting, ischemic heart disease;LMWH, low molecular weight
heparin; NSTEACS, non-segment T elevation acute coronary syndrome;
PCI,
percutaneous
coronary
intervention;
STEMI,
segment
T
elevation myocardial infarction;UFH, unfractionated heparin.

After got the result from logistic regression test with

significant result, the researcher continue analysis
using

multinominal

comparison

in

regression

table

1,

because

several

from

the

variables

data
show

significant difference between patients with MACE and

without MACE.
The incidence of MACE that happen in hospital is
declining over the past decade. This decrement can be
associate with many factors such as the improvement of
technology, pharmacology, and operator experience (Kern
et

al.,

2006).

Table

shows

the

comparison

of

characteristics between patients with MACE and patients

without MACE. Patients with age 60 years old (SD
8.2), onset of attack 8.5 hours (SD 5.9), haemoglobin
14.1 mg/dl (SD 1.8), and BUN 20.6 mmol/L (SD 10.4)
prone to have in hospital MACE.

36

Figure 1. Incidence of MACE in the research

Normoosmolal

Hyperosmolal
123

49

15

14

MACE

Non-MACE

37

Table 3 . Comparison of characteristics between

patients with MACE and patients without MACE
Characteristics
Age, year (meanSD)
Onset, hour (meanSD)
Sex (n (%))
Male
Diabetes (n (%))
Hypertension (n (%))
IHD /stable angina
(n
(%))
Current smoking (n (%))
Dyslipidemia (n (%))
Family History (n (%))
Diagnosis (n (%))
STEMI
NSTEACS
Primary PCI (n (%))
STEMI (n (%))
Thrombolysis (n (%))
Heparin (n (%))
LMWH
UFH
Fondaparinux
No Heparin
Nitrate (n (%))
Aspilet (n (%))
Clopidogrel (n (%))
Statin (n (%))
ACE Inhibitor (n (%))
Beta Blocker (n (%))
Furosemide IV (n (%))
Vasopressor (n (%))
Inotropic (n (%))
Haemoglobin (meanSD)
Systolic Pressure
(meanSD)
Diastolic Pressure
(meanSD)
Heart Rate (meanSD)
Leucocyte (meanSD)
Thrombocyte (meanSD)
Creatinine (meanSD)
BUN ((meanSD)
Sodium (meanSD)
Pottasium (meanSD)
Chloride (meanSD)
Glucose (meanSD)

With MACE
N= 29
60.88.2
8.55.9

Without MACE
N= 172
56.18.8
8.96.8

PValue
0.01
0.02
0.86

24(11.9)
5.0
9.0
1.0

140(69.7)
19.4
48.8
10.4

6.5
1.5
0.0

43.8
9.0
1.5

12.9
1.5
5.5
8.2

66.2
19.4
21.4
42.1

6.0

28.4

1.0
10.9
2.0
0.5
14.4
14.4
14.4
14.4
10.9
6.5
0.5
0.5
0.0
14.11.8
124.524.7

6.5
69.2
7.0
3.0
85.1
85.6
85.6
85.6
70.6
45.8
0.0
0.0
0.5
14.11.8
131.023.2

0.86
<0.001
<0.001
<0.001
0.39
0.39
0.15
0.14
0.27
0.04
0.52

78.215.0

80.414.2

0.98

82.121.4
13.43.9
238.152.5
1.61.0
20.610.4
137.64.0
4.20.8
103.24.2
238.5139.2

70.114.8
12.63.5
254.659.7
1.20.4
14.15.8
138.23.2
3.90.5
109.176.4
173.788.9

0.20
0.09
0.15
0.55
0.02
0.34
0.70
0.97
0.41

0.18
0.61
0.41
0.53
0.99
0.48
0.97
0.15
0.98
0.39
0.81

38

From

comparison

table

above

there

are

some

variables have significance under 0.05 such as age,

onset, haemoglobin, and BUN. The researcher continues
to

analyse

those

variables

since

they

may

have

influence in the occurrence of MACE.

Table 4. Binary logistic analysis of Age based on MACE
Variable
Age

Odd
Ratio

95% CI
Lower

Upper

1.06

1.02

1.11

p-value
0.009

Table 5. Binary logistic analysis of Onset based on

MACE
Variable
Onset

Odd
Ratio

95% CI
Lower

Upper

0.99

0.93

1.05

p-value
0.732

Table 6. Binary logistic analysis of Hemoglobin based

on MACE
Variable
Hemoglobin

Odd
Ratio

95% CI
Lower

Upper

1.01

0.81

1.26

p-value
0.91

Table 7. Binary logistic of BUN based on mACE

Variable
BUN

Odd
Ratio

95% CI
Lower

Upper

1.11

1.06

1.17

p-value
0.00

39

Table 8. Binary logistic analysis of variables with pvalue less than 0.05
Variable

Odd
Ratio

Lower

Upper

BUN

1.13

1.06

1.19

0.00

Age

1.07

1.01

1.13

0.01

Onset

0.95

0.88

1.03

0.19

Osmolality

2.69

1.21

5.99

0.01

Hemoglobin

1.25

0.98

1.61

0.07

The

main

95% CI

finding

of

this

p-value

logistic

regression

analysis is the strong association between increasing

value of on admission osmolality (hyperosmolality) and
the increasing of MACE occurrence. On admission was
independently and highly predictive of MACE occurrence
after

adjusting

inclusion

and

exclusion

criteria.

study about correlation between on admission osmolality

with all-cause of death in ACS patient has already been
done

with

the

result

of

strong

association

between

admission osmolality and all-cause death in ACS patient

undergoing PCI (Rohla et al., 2014).
But
influence

there

are

to

MACE,

dyslipidemia.
cardiovascular

There

also

some

such
is

outcomes

a
in

as

variables
sex

and

research
patients

that

show

history

analyzing
with

of

about

type

40

diabetes mellitus after having first acute myocardial

infarction attack, one of the independent risk factor
is dyslipidemia. Patient with dyslipidemia risk factor
having higher risk suffered at least one myocardial
infarction (Pastewka et al., 2003). Another research
discussing

about

the

relation

between

metabolic

syndrome; this syndrome consist of diabetes mellitus/

glucose

intolerance,

arterial

obesity,

dyslipidemia,

and

size

the

of

and

infarction

hypertension,

central

microalbuminuria;

gender,

stated

that

the

female

patient with metabolic syndrome tend to have larger

size of infarction that can lead to higher risk of
having

MACE

(Kranjcec

&

Altabas,

2012).

From

this

research all at once explaining that dyslipidemia and

sex also have influence to MACE occurrence.
There are also some variable that may influence in
determining MACE result as stated in table 4. Age,
onset,

haemoglobin,

and

BUN

have

significance

under

0.05. After analysed using binomial regression the only

variable having significance under 0.05 is BUN. There
are some studies discussing about MACE related with
variables above.

41

Age and onset are already established as clinical

factors that can increase the incidence of MACE. Beyond
being a risk factor for CAD and universal comorbidity
for

cardiac

related

disease,

age

is

an

important

predictor of outcome following PCI and CABG. Patient

with age more than 80 years old were 2 folds higher in
having 3-vessels CAD compared with younger patients (<
65 years)(38% versus 20%)(Kern et al., 2006). Since
inclusion criteria for this study is patients with age
range from 18-75 years old, age is not consider as
independent

predictor

based

on

analysis

result

from

Table 4 (p = 0.13). Onset as another risk factors of in

hospital

MACE,

the

average

time

from

onset

until

patients admitted to the emergency unit is 8.5 hours

(SD 5.9). This interval is way too long in this
study,

the

long

the

patient

delayed

will

increase

patients mortality and risk of MACE (Sadrnia et al.,

2013). From this research the onset of MI attack not
related with the occurrence of MACE (p = 0.18).
The

last

variable

that

may

influence

MACE

occurrence is blood urea nitrogen or BUN. BUN is one of

the components of osmolality. Osmolality itself already
proven become an independent predictor of MACE. There

42

is

also

study

predicting
patient.

discussing

survival
Patients

hypotension

that

rate
with

needs

about

in

BUN

chronic

high

serum

intervention

independently
heart

failure

BUN

develop

(Klein

et

al.,

2008). Another research in Japan also found that BUN of

>25

mg/dl

was

associated

with

long-term

mortality

predictor in ACS or stable CAD patients that undergoing

PCI (Kawabe et al., 2014).

43

CHAPTER V
CONCLUSION AND SUGGESTION

A.
There

is

strong

Conclusion
and

independent

association

between increasing value of on admission osmolality and

the increasing of MACE occurrence.
B.
1.

Further

test

with

Suggestion
adding

more

subjects

is

recommended to increase the accuracy in predicting

the outcome.
2.

Analysis

in

correlation

from

each

aspect

of

osmolality to MACE is needed to find if there is

independent predictor among blood glucose, sodium,
and BUN.
3.

multi

variation

analysis

for

predictor

is

recommended to know if there is any other factor

influencing the occurrence of MACE.

44

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APPENDIX
Table 9
MACE * Osmolable Cross tabulation
Osmolable
Hyper
MACE

No

Count

62

83

Expected Count

24,1

58,9

83,0

% within MACE

25,3%

74,7%

100,0%

% within Osmolable

72,4%

87,3%

83,0%

% of Total

21,0%

62,0%

83,0%

-,6

,4

17

Expected Count

4,9

12,1

17,0

% within MACE

47,1%

52,9%

100,0%

% within Osmolable

27,6%

12,7%

17,0%

8,0%

9,0%

17,0%

Std. Residual

1,4

-,9

Count

29

71

100

Expected Count

29,0

71,0

100,0

% within MACE

29,0%

71,0%

100,0%

100,0%

100,0%

100,0%

29,0%

71,0%

100,0%

Count

% of Total

Total

Total

21

Std. Residual
Yes

Normo

% within Osmolable
% of Total

Table 10
Tests of Normality
a

Kolmogorov-Smirnov
osmol
MACE

Shapiro-Wilk

Statistic

Df

Sig.

Statistic

df

Sig.

,529

137

,000

,346

137

,000

,474

64

,000

,525

64

,000

Case Processing Summary

Unweighted Cases
Selected Cases

N
Included in Analysis
Missing Cases
Total

Percent
201

100,0

,0

201

100,0

53

Unselected Cases
Total

,0

201

100,0

a. If weight is in effect, see classification table for the total number of

cases.

Table 11
Dependent Variable Encoding
Original Value

Internal Value

Not experiencing MACE

Experiencing MACE

Table 12
Categorical Variables Codings
Parameter
coding
Frequency
osmol

(1)

137

1,000

64

,000

Table 13
a,b,c

Iteration History

Coefficients
Iteration
Step 0

-2LL

Constant

169,332

-1,423

165,924

-1,742

165,887

-1,780

165,887

-1,780

a. Constant is included in the model.

b. Initial -2LL: 165,887
c. Estimation terminated at iteration number 4
because parameter estimates changed by less
than ,001.

Table 14

54

Classification Table

a,b

Predicted
MACE
Not
experiencing

Experiencing

Percentage

MACE

MACE

Correct

Observed
Step 0

MACE

Not experiencing MACE

Experiencing MACE

172

100,0

29

,0

Overall Percentage

85,6

a. Constant is included in the model.

b. The cut value is ,500

Table 15
Variables in the Equation
B
Step 0

Constant

-1,780

S.E.

Wald

,201

df

Sig.

78,644

,000

Exp(B)
,169

Table 16
Variables not in the Equation
Score
Step 0

Variables

osmol(1)

Overall Statistics

df

Sig.

6,174

,013

6,174

,013

55

Table 17
a,b,c,d

Iteration History

Coefficients
Iteration
Step 1

-2LL

Constant

osmol(1)

165,218

-1,063

-,529

160,224

-1,180

-,888

160,081

-1,184

-,985

160,081

-1,184

-,989

160,081

-1,184

-,989

a. Method: Forward Stepwise (Likelihood Ratio)

b. Constant is included in the model.
c. Initial -2LL: 165,887
d. Estimation terminated at iteration number 5 because
parameter estimates changed by less than ,001.

Table 18
Omnibus Tests of Model Coefficients
Chi-square
Step 1

df

Sig.

Step

5,806

,016

Block

5,806

,016

Model

5,806

,016

Table 19
Model Summary

Step
1

Cox & Snell R

Nagelkerke R

Square

Square

-2 Log likelihood
160,081

,028

,051

a. Estimation terminated at iteration number 5 because

parameter estimates changed by less than ,001.

Table 20
Hosmer and Lemeshow Test
Step
1

Chi-square
,000

df

Sig.
0

56

Table 21
Classification Table

Predicted
MACE
Not
experiencing

Experiencing

Percentage

MACE

MACE

Correct

Observed
Step 1

MACE

Not experiencing
MACE

172

100,0

29

,0

Experiencing MACE
Overall Percentage

85,6

a. The cut value is .500

Table 22
Variables in the Equation
95% C.I.for
EXP(B)
B
Step
1

osmolal
Constan
t

S.E.

Wald

df

Sig.

Exp(B)

,989

,408

5,874

,015

2,690

-2,173

,282

59,358

,000

,114

Lower
1,208

Upper
5,986

a. Variable(s) entered on step 1: osmolal.

57

Table 23
Variables in the Equation
95% C.I.for
EXP(B)
B
Step
1

S.E.

Wald

df

Sig.

Exp(B)

Lower

Upper

Umur

,002

,020

,008

,928

1,002

,963

1,042

Onset

-,036

,027

1,798

,180

,964

,915

1,017

HB

-,080

,098

,666

,415

,923

,762

1,119

,108

,030

13,272

,000

1,114

1,051

1,181

-,442

,466

,901

,343

,643

,258

1,601

-,720

2,218

,105

,745

,487

BUN
MACE(1
)
Constan
t

a. Variable(s) entered on step 1: Umur, Onset, HB, BUN, MACE.

Table 24
Variables in the Equation
95% C.I.for
EXP(B)
B
Step
1

BUN
Consta
nt

S.E.

Wald

df

Sig.

Exp(B)

,102

,026

15,464

,000

1,108

-3,478

,504

47,598

,000

,031

Lower
1,053

Upper
1,166

a. Variable(s) entered on step 1: BUN.

Table 25
Variables in the Equation
95% C.I.for
EXP(B)
B
Step
1

HB
Constan
t

S.E.

Wald

df

Sig.

Exp(B)

,013

,112

,014

,905

1,013

-1,968

1,589

1,533

,216

,140

Lower
,814

Upper
1,262

a. Variable(s) entered on step 1: HB.

58

Table 26
Variables in the Equation
95% C.I.for
EXP(B)
B
Step
1

Onset
Constan
t

S.E.

Wald

df

Sig.

Exp(B)

-,011

,031

,117

,732

,989

-1,687

,334

25,431

,000

,185

Lower

Upper

,931

1,052

a. Variable(s) entered on step 1: Onset.

Table 27
Variables in the Equation
95% C.I.for
EXP(B)
B
Step
1

Umur
Constan
t

S.E.

Wald

df

Sig.

Exp(B)

Lower

,062

,024

6,730

,009

1,064

-5,386

1,442

13,950

,000

,005

Upper

1,015

1,114

a. Variable(s) entered on step 1: Umur.

Table 28
Variables in the Equation
95% C.I.for
EXP(B)
B
Step
1

S.E.

Wald

df

Sig.

Exp(B)

Lower

Upper

BUN

,121

,030

16,127

,000

1,129

1,064

1,198

Umur

,068

,027

6,159

,013

1,070

1,014

1,128

Onset

-,051

,039

1,724

,189

,950

,881

1,025

,227

,128

3,133

,077

1,255

,976

1,613

-10,532

2,917

13,039

,000

,000

HB
Consta
nt

a. Variable(s) entered on step 1: BUN, Umur, Onset, HB.

59