cardiac biomarkers that indicates any heart failure/disease in laboratories tests.

1. Cardiac Biomarkers Tests
-15701814-Saba Khanjani Moaf

2. Overview:
1. Cardiac biomarkers and Classification
2. Heart Disease Definition
3. Diagnostic Steps
4. Non-Laboratory test
5. Laboratory Test by Taking blood sample
6. Troponin Biomarkers
7. CK-MB Biomarkers
8. Myoglobin Biomarkers
9. Prognosis Biomarker
10. Novel Marker (IMA)

3. Cardiovascular diseases are
number 1 cause of death
around the world
Approximately 17.9 million
people died from CVDs in
2016.indicated 31% of global
HOW BIG IS THE
PROBLEM?
Most of CVDs are preventable by
monitoring risk such as: unhealthy
diet, no physical activity, consuming
alcohol/tobacco

4. What are cardiac biomarkers:
▪ Cardiac biomarkers are substances
that would released into blood when
the heart is damaged or stressed.
▪ Measurements are actually a helper to
diagnose acute coronary
syndrome(ACS) and cardiac ischemia
which is related with blood flow
insufficiency
▪ It is also used to help for monitoring
and prevention the risk of these
conditions for a person who is
suspected with ACS and ischemia.
High blood pressure, high blood lipid
drugs could have effect on protein
biomarkers for cardiovascular effecf
criteria for
Biomarkers
Should aid
treatment
with easy
diagnose
Rapid release
to blood while
MI occurs
Good
prognostic
value and
rapid release
High
sensitivity,
High
specificity
Must
provide
extra
information
Accurate
measurement
with
reasonable
cost

5. Antecedent biomarkers:
identify the risk of developing disease
Screening biomarkers:
Screening for subclinical disease
Diagnostic biomarkers:
Recognizing overt disease
Staging biomarkers: Categorizing disease severity
Cardiac biomarkers classifications:
(LABORATORY TESTS)

6. Old markersAST/LDH
• Aspartate transaminase (AST)
• Lactase dehydrogenase (LDH) and lactate
dehydrogenase iso enzymes (references range:
100-190 IU/L)
Current Markers
Troponin/CK-
MB/Mb
•Creatine kinase (CK) and muscle-brain creatine kinase (CK-
MB)
•Troponin T (TnT) and Troponin I (TnI)
•Myoglobin
Prognostic and under assessment with
potential for clinical use markersBNP/hs-CRP
•High sensitivity C-reactive protein (hs-CPR)
•B-type (formerly brain) natriuretic peptide (BNP)
Cardiac biomarkers classifications:

7. An acute occlusion of
coronary artery which
has done by
embolization and
thrombus which is lead
to myocardial
infarction
It is occurred
when blood
flow decreases
or stops in heart
(coronary
arteries
occlusion)
Most common
symptom is
CHEST Pain
Damage would be
permanent if blood
would not restored
after times! (heart
muscle would die
gradually)

8. Its crucial and growing
health problem, it is not only
from cardiac overload or
injury but also from complex
interplay among genetic
Heart Failure doesn’t happen
in a day it takes many
months if not years to
develop
It is come out from
inflammation, biological
changes and cardiac
interstitium

9. Endothelial
damage
inflammation
Plaque
formation
. Cytokines
.LP-PLA2
.PAPP-A
Plaque
Destabilization:
. IMA
.HSP
.H-FABP
Myocardial
ischemia
.H-FABP
.CK-MB
.MYOGLOBIN
Cardiac
necrosis
Cardiac
damage
Heart failureMyocardial
stretch/stress

10. Diagnostic steps:
H.Attack MI
suspected
Diognose
based on 3
major things:
1. Patient
History
2. screening the
most ECG
3. Take sample
of blood
1. Shortness of
breath
2. Dizziness
3. Chest pain
4. clammy skin, or paleness
symptoms
Ischemia
(checking
MA/FFA/H-
FABP)
Chronic heart
failure (BNP
Inflammation
by CRP

11. Non-laboratory Tests: they can be used for different purposes by looking for shape, size,
function of heart. test are applied By detecting heart rhythm and evaluating block arteries or
tissue damage
1. EKG
(ECG, electrocardiogram)
2. Nuclear scan
3. Coronary angiography
(arteriography)6.
Echocardiogram
5.
Stress test
4.
Chest X- ray

12. Cardiac test is carried
by blood test
(Serum/Plasma and
cardiac tissue)
draw blood will be done by
attaching needle to small
tube which is inserted in
vein and blood goes to tube
taking blood by
physician is safe
when appropriate
amount has been
collected needle would
be removed
In video above, you could see the
procedure of blood test analysis in
laboratory by physicians!
CARDIAC TEST SAMPLE
1.Red top tube
2.CK/MB
Radioimmunoassay
3.troponin:
immunoassay

13. Kinase/MB
just refer to
shape or pr on
molecular
level, they
will all spill
out of the
heart muscle
cells once
they start to
die and enter
to
blood(plasma
separator tube
yellow/green)
Myoglobin is
found
everywhere in
body as well
as the heart
muscle as a
result its not
very specific
to heart
muscle. It is
not vital to be
tasted
Troponin
specifically
could be
found in
cardiac
muscle so if
these
troponins end
up in blood
stream that
means there is
problem with
heart muscle
damage
When a cardio myocyte cell
dies, some protein will spill
out such as myoglobin, the
other protein such as
creatine kinase MB or
CKMB and they all go to
blood stream.
Troponin are the specified
cardiac marker for detecting MI.
as troponin assays have become
more sensitive they have
replaced both CK-MB and
myoglobin. More superior in
tissue ischemia.

14. TROPONIN Biomarkers:
* troponin is Regulatory protein complex
*Troponin level begins to increases
3-4 hours after myocardial injury.
*Elevation remains for up to two
weeks after MI (10 to 14 days)
*Normal values: between 0 and 0.4
ng/mL
*in healthy people, it is not
detectable
*High-sensitivity troponin
Troponin C
bind to
calcium ions
to produce a
change in
TnI.
Troponin C
Binds to
actin in thin
myofilament
to hold
trpomyosin
(protein
inhibitor)
Troponin I
Bind to
tropomyosin
to form a
troponin-
tropomyosin
Troponin T

15. cTnT
(binds to tropomycin)
Rise: chest pain in
few hours after on set
peak: 2 days
Returns to normal: 7-10 days
cTnI
(inhibitory protein)
Rise: 3-4 hours after
onset of pain (MI)
Peak: 12-18 hrs
Returns to normal: 6
daysAppears after 3-5hrs after MI
Not affected by muscle
injury or renal disease
unlike cTnT
*it is more specified
Immediately after signs
such as pain in your
chest, angina, heart
attack, pain neck, jaw,
and when angina
worsens, patient need to
be tasted for troponin
test
*Normal value: Less than
0.12 micrograms per litre
(mcg/L) (0.0 to 0.5 ng/mL)
*Normal value: Less than
0.01 mcg/L.

16. Troponin increases above 99th percentile
limit in hours and then decreases over
several days9(troponin I is an ideal marker
for MI since it could release in blood in 6-8
hours after MI
troponin concentrations slightly above
the decision limit for a very short time
troponin concentrations remain
constant for days to week
NORMA
L
RANGE:
0-0.4
ng/mL
Above 0.4
shows
positive
heart attack
Very high
level such as
10 shows
patient has
recently had
a heart
atttack

17. Muscle
cell(M)
Nerve
cells(B)
..
*CK is found in the heart,
muscles, and other
organs.(MOSTLY In heart)
* used to help detect a
second heart attack that
occurs shortly after the first,
now it replaced by troponin
test since troponin is more
specific for CK test
*elevated CK-MB/ck test
when the troponin test is not
available.
Timing is
important. If
you have the
test too soon
after a heart
attack, patient
may have a
false-negative
result
Peak in
blood: 12-
24 h
Returns to
normal in
2-3 days
CK-MB
Use for patient
with chest pain
or symptoms
like dizziness,
shortness of
breath
CK-MM ( in skeletal muscles/heart)
CK-MB (mostly in the heart, low amounts in skeletal muscles)
CK-BB (mostly in the brain/smooth muscle)

18. CK-MB is an enzyme which is present in
serum at low concentration. In case of
AST/ALT, ck is prefered
• Higher level of CK-MB = more heart damage
in the attack
It is rises after an acute MI and later
descends at normal level. It could also
increase in skeletal muscle damage
rarely!
• Appears in blood in 3-10 h of heart attack
• Disappear after a day
If rational of
ck-MB is more
than 2.5-3
(CPK level
reach to 5000
IU/L)
Heart damage
3 to 5% (5 to 25
IU/L)
Normal value
Skeletal
muscle
damage
High CK
Statin cause myalgia,
rhabdomyolysis, muscle
weakness and it could
rises CK level 2 to 10*
more than limit of normal

19. MYOGLOBIN
Thrombosis refer to blood clot which
has the ability to blocks blood flow to
organs and ended up to
RHABDOMYOLYSIS
•Antibiotics (amphotericin B, ampicillin)
•Anesthetics
•Antidepressants
•Antihistamines
•Aspirin (salicylates)
•Corticosteroids
Drugs which cause
RHABDOMYOLYSIS
muscle
weakness,
aches, dark
urine suspects
muscle damage
which need to
myoglobin to be
tasted
Its historic
use was as an
early-onset
marker since
it is elevated
first, before
CK-MB and
troponin
Myoglobin is a protein
found in skeletal muscle
and heart. Muscles
contract with the help of
myoglobin with trapping
oxygen in order to produce
energy

20. Myoglobin biomarker Peaks in
6-12
hours
Back to
normal in
24-36
hours
Reference
ranges:
Male: 17-
106
ng/mL
Female: 1-
66 ng/mL
Before CK-
MB and
troponin ,
myoglobin
is and
oxygen-
binding
protein in
cardiac and
skeletal
muscle
It is release earlier after muscle
injury than CK-MB and
troponin and return faster too!
*Since Myoglobin could be found in all
muscle types it is not a very specific marker
for cardiac damage and it rarely measured,
redness of muscle is because of myoglobin.
*Used less frequently, sometimes performed
with troponin to provide early diagnosis
*myoglobin release in blood few hours after
heart injury(Nearly in 1 hour)
*Myoglobin is usually determined as
an early, but not specific

21. evaluate risk of future cardiac
events (prognosis biomarkers)
Determine the risk of
heart attack in patient
who experienced HF
in the past.
Inflammation
stimulate this Protein
to rise
Hs-
CPR
Risk increases when
increasing level in
people with ACS
observe(marker for
congestive heart
failure)
BNP acts as heart
hormone
BNPLess than 100
pg/mL =Normal
100-300 pg/mL
= Mild Heart
Failure
300-700 pg/mL
= Moderate
Heart Failure
700+ pg/mL=
Severe Heart
Failure
Low risk:
less than
1.0 mg/L
Average
risk: 1.0 to
3.0 mg/L
High
risk:
above 3.0
mg/L
Use for:men 50
years old or younger
and women 60 years
old or younger have
intermediate risk

22. Novel Marker Of Ischemia
(IMA)
Ischemia-modified albumin may be utilized as a novel marker
of ischemia to diagnose acute coronary syndrome started with
immediate chest pain along with troponin and electrocardiogram
Increase level
in 6 hours
Remain in:
12h
Contain
short and
long-term
prognostic
significances
Measure by
(ACB)
albumin
cobalt
binding assay
highly sensitive
for the diagnosis
of myocardial
ischemia in
patients
presenting with
symptoms of
acute chest pain

23. UNSTABLE
ANGINA
STEMI
Non STEMI
Both CK and troponins are not
raise in unstable angina and
would not associated with
myocardial necrosis.It is a
components of acute coronary
syndrome due to occlusive
pathology
Troponin is in highest level
Both are increasing which
lead to mortality rise
Troponin and
creatinine kinase
change:
For both of these biomarkers, increase levels of them indicate myocardial necrosis, it actually shows
that some myocyte have died presumably as a result of infarction
Interestingly creatinine kinase is not commonly used these days since it has the ability to be
released from any damage muscle, so if physician needs to make sure he is responsible to do
specific ISO enzyme analysis. However, it will rise with myocardial damage
The more myocardial cell die the more the creatinine kinase will be rised.

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References: