Cardiac Biomarkers

Biomarkers
Biochemical substance which is
useful in
detecting dysfunction of an organ.

Cardiac Biomarkers
Used to detect cardiac diseases.

 Myocardial ischemia: reduction of

coronary blood flow to an extent that
leads to insufficiency of oxygen supply
to myocardial tissue

Myocardial Infarction: When this

ischemia is prolonged & irreversible,
myocardial cell death & necrosis.
Myocardial necrosis due to myocardial
ischemia.

Biochemical Changes

in Acute Myocardial

Infarction

(mechanism of release of myocardial markers)

ischemia to myocardial muscles (with low O2 supply)
anaerobic glycolysis
increased accumulation of Lactate
decrease in pH
activate lysosomal enzymes
disintegration of myocardial proteins
cell death & necrosis

clinical manifestations
(chest pain)

release of intracellular
contents to blood

BIOCHEMICAL
MARKERS

ECG
changes

Diagnosis of Myocardial
Infarction
1- Clinical Manifestations
2- ECG
3- Biochemical Markers

IDEAL CARDIAC MARKER

Cardiac specific
Rise soon after infarction
Procedure should be easy,
inexpensive
& rapid
Measurable at very low levels
Reflect the size of infarction
Help in determining the time of
infarction

Biochemical
Markers
for Diagnosis of

Myocardial
Infarction

Biochemical Markers
for Myocardial Infarction
Types of

1- Cardiac Enzymes (isoenzymes):

Total CK
CK-MB
Lactate dehydrogenase (LD)
Aspartate aminotransferase
(AST)
2- Cardiac proteins:

Myoglobin
Troponins

CARDIAC TROPONINS
Troponins are regulatory proteins found
in skeletal and cardiac muscle.
Three subunits have been identified:
Troponin I (TnI)- Inhibits contraction
Troponin T (TnT)-binds to Tropomyosin
Troponin C (TnC)-binds to Ca2+

CARDIAC

TROPONIN

Skeletal and cardiac isoforms of TnC

are identical
No structural difference
Skeletal and cardiac subforms for TnI
and TnT are distinct

cTnI & cTnT

After an AMI Rises

Peaks

Returns

cTn I

4 6 hrs

14 24 hrs 5 7 days

cTn T

3 - 6 hrs

10 24 hrs 6 10 days

OTHER CAUSES OF ELEVATION OF cTn

trauma
congestive heart failure
Acute pulmonary embolism
postoperatively
drug toxicity adriamycin , 5FU etc.
inflam. Diseases myocarditis
sepsis

cTn
Advantages

- sensitivity ~ 98%
- specificity ~ 95 98%

Limitations

- not useful in early diagnosis

- limitations in assay methods

CREATINE KINASE
Creatine + ATP ADP + creatine ~ P

dimer with B and M subunits

CK 1 ( CK BB )
CK 2 ( CK MB ) Cardiac specific
CK 3 ( CK MM )

Isoenzy Subu Tissu

me
nit
e

% in
ELEVAT
serum ED IN

CK-1

BB

BRAIN

BRAIN
TUMOUR

CK-2

MB

HEART

AMI

CK-3

MM

MUCSL
E

80

MUCLE
DISEASE

TOTAL CK
RI men - 46 171 U/L
women 34 145 U/L
CK activity is influenced by age , sex
, race , lean body mass , physical activity
etc.

INCREASED CK ACTIVITY
physiological - neonatal period
marked increase MI , rhabdomyolysis
, muscular dystrophies
moderate increase muscle injury ,
viral infections , exercise , malig.
Hyperpyrexia

CK MB
Cardiac specific isoenzyme
Cytosolic enzyme
After an AMI Rises

Peaks

Returns

4 - 6 hrs

10 24 hrs 48 72
hours

CK MB
Assay methods

1. Immunoassays CK MB mass conc.

2. Immunoinhibition techniques
3. Electrophoresis

URL CK-2 mass < 5.0 ng /mL

CK MB activity is 5% of total CK activity

CK MB
Advantages
- tissue specific
- diagnosis of reinfarction
limitations
- not useful in late presentors

MYOGLOBIN
LMW cytosolic heme protein of cardiac
and skeletal muscles
Early marker of MI
Rises

Peaks

Returns

1 - 2 hrs

2 12 hrs

24 36
hours

MYOGLOBIN
Advantages

- very sensitive marker (90-100%)

- useful to detect reinfarctions

The most sensitiveearly markerfor

myocardial infarction
limitation

- lacks tissue specificity (Nonspecific cardiac

markers)
muscle trauma,
myopathies
shock,
strenuous exercise
RI 0 - 70 ng / mL

LACTATE DEHYDROGENASE
lactate + NAD pyruvate + NADH + H+
cytosolic enzyme ; tetramer of H and M
LD I - ( HHHH )
LD 2 - ( HHHM )
LD 3 - ( HHMM )
LD 4 - ( HMMM )
LD 5 - ( MMMM )

Isoenzy Subu Tissu

me
nit
e

ELEVATE
D IN

LDH-1

% in
seru
m
HHHH HEART
30

AMI

LDH-2

HHHM RBC

35

HEMOLYS
IS

LDH-3

HHMM BRAIN

20

LDH-4
LDH-5

HMM LIVER
M
MMM MUCSL
M
E

10
5

LIVER
DISEASE
MUCLE
DISEASE

LACTATE DEHYDROGENASE

Rises

Peaks

12 - 18 hrs 72 144
hrs

Returns
6 10 days

LACTATE DEHYDROGENASE
flipped pattern - LD 1: LD 2 ratio 1
causes of increased LD activity
artefactual invitro haemolysis
marked rise MI , circulatory failure ,
haemotological causes etc.
moderate rise viral hepatitis ,
malignancy , skeletal muscle
disorders etc.
RI - 125 - 220 U / L

AST
L aspartate + 2 oxoglutarate
oxaloacetate + L glutamate
In AMI,
Rises

Peaks

Returns

3 - 8 hrs

24 hrs

3 6 days

AST
causes of increased AST activity
- hepatitis , MI , renal infarction ,
progressive muscular dystrophy ,
cirrhosis etc.
RI - males < 35 U / L
females < 31 U / L

TIME COURSE OF CARDIAC

BIOMARKERS IN AMI

GUIDELINES
Rule in/out AMI cannot be made from a
single estimation
Serial sampling is critical for accurate
diagnosis
Use of two markers:

Early marker (rising 2-4 hr after pain onset)

Mb
Definitive marker (rising 4-6 hr after pain onset)
High sensitivity and specificity
Remains abnormal several days

cTn

Preferred marker is a cardiacTroponin (I or T)

If Troponins are not available, best alternative
is CK-Mbmass
CK(total), AST & LDH - NOT recommended
An elevated Troponin level in the absence of
clinical evidence of ischaemia should prompt
search for other causes of cardiac damage

Diagnosis of Myocardial
Infarction
1- CHEST PAIN
2- ECG CHANGES 3- Biochemical Markers

CKCK
LDH
MYOGLOBIN
MB
CNT

BIOMARKER

CK
LDH
AST
MYOGLOBIN
CK- MB
CARDIAC TROPONINS (CNT&CNI)

ISCHEMIA MODIFIED ALBUMIN

Serum albumin is altered by free radicals released
from ischaemic tissue
IMA levels rise rapidly, remain elevated for 2-4 hrs
& return to baseline within 6h
marker of myocardial ischemia
highly sensitive and has high negative

predictive value
Not specific (elevated in stroke, some neoplasms,
hepatic cirrhosis, end-stage renal disease)
measured by albumin cobalt binding test

H FABP
Protein)

(Heart type Fatty Acid Binding

Small cytosolic glycoprotein of heart and

skeletal myocytes
Facilitates intracellular transport of LCFA
release kinetics similar to myoglobin
after AMI ,rises in 1 3 hrs ; comes
back to normal in 24 30 hrs
RI > 5ng / mL

A 48-year-old man came to the casualty with

complaints of chest pain and vomiting for the
past 6 hours. Gave history of consuming alcohol
the previous evening. He was anxious saying that
his father died of Myocardial Infarction at the
age of 65.
On examination, he was anxious. Pulse-86/min;
BP-140/90mmhg. ECG was normal. Blood was
drawn for biochemical analysis.Give your
comment on the following biochemical report.
Serum Creatine Kinase
125 U/L
Serum CK-MB (CK-2)
5 U/L
Serum Aspartate Aminotransferase
30 U/L
Serum Lactate Dehydrogenase
110
U/L

A 56-year-old businessman was admitted to

the emergency department of the Government
General Hospital with complaints of severe
retrosternal pain. He gave history of heavy
smoking and alcohol consumption for the past 25
years.
On examination, he was profusely sweating.
His blood pressure was 160/100mmHg. ECG
showed S-T segment elevation. Blood sample was
taken for biochemical analysis. What is your
diagnosis?
Serum CK
1160 U/L
Serum CK-MB
170 U/L
Serum AST
380 U/L
Serum LDH
470 U/L
Serum Uric acid
9 mg/dL

Thank
Thank
You

C-reactive protein
globulin ;disc-shaped
homopentamer
Acute phase reactant
Synthesised in the liver
enhances the inflammatory
and
prothrombotic
response

hs CRP
prospectively predicts risk of MI
useful prognostic indicator of MI
suggested in the multimarker
statergies for risk stratification

BRAIN NATRIURETIC PEPTIDE

counter regulatory hormone released in
response to ventricular stretch
diagnostic marker for congestive heart Failure
prepro BNP (134aa) pro BNP (108aa)
+ signal peptide (26aa)
proBNP (108aa) NT-proBNP (1-76)
+ BNP ( 32)

BRAIN NATRIURETIC PEPTIDE

URL

BNP < 100 ng / L

NT pro BNP < 400 ng / L
Advantages
- independent predictor of CHF
- linear relationship with severity of CHF
- screening of less symptomatic disease
- corelates with the amount of ventricular
dysfunction present after AMI

Lactate dehydrogenase (LD)

myocytes ,sktl musc, liver, kidney, platlts & RBCs

5 major LD isoenzymes, LD1LD5
LD1 & LD2 MI (LD1 > LD2)
LD4 & LD5 hepatic or Skl muscle injury
LD2, LD3 & LD4 platelets/Lymphatic
(Total activity)LD 2448 h, peak-36 d & N in 8
14 d
LD1 > LD2 pattern 1012 h, peak-2 to 3d & N in
710 d
LD1 & ratio sens & spec - 7590%

Aspartate aminotransferase
(AST,SGOT)
skltl muscle, liver, RBCs &
myocardium
T(mitochondrial)- 10 d,
(cytoplasmic)- 10 h.
Isoenzymes not fractionated for
clinical use
68 h ,peak 1824 h, N- 4 to 5 d

Myoglobin
cytoplasm of cardiac & sk muscle
cells
tissue/plasma ratio of myoglobin is
very
Earliest appearing marker routinely
available
same for both cardiac & sk muscle
cleared by kidneys (RF-)
rule out myocardial necrosis with a
negative predictive value approx

Timing Summary
TEST

ONSET

PEAK

DURATION

CK/CK-MB

4-8 hours

18-24 hours

36-48 hours

Troponins

3-12 hours

18-24 hours Up to 10 days

Myoglobin

1-4 hours

6-7 hours

24 hours

LDH

6-12 hours

24-48 hours

6-8 days

NECROSIS BIOMARKERS STILL

IN DEVELOPMENT
Heart-Type Fatty Acid-Binding
Protein(FABPs)
Carbonic anhydrase (III) (CAIII)

Heart-Type Fatty Acid-Binding Protein (H-FABP)

abundant in cytoplasm of striated musc

Specifically & reversibly bind long-chain f a
Myo & Sk muscle - same isoform of FABP, (HFABP)
Content in sk musc is only 1030% of that
found in cardiac musc
very good tissue/plasma ratio
Released soon after onset of MI- early marker
<3 h after MI & returns 1224 h
? myoglobin/H-FABP

Ischemia Modified Albumin

Albumins capacity to bind to cobalt is
reduced during myocardial ischemia (Nterminal)
Rises within minutes of ischemia, stays up for
6-12 hrs and normalises within 24 hrs
Elevated after enduring sports,but;aft 24 hrs
(?GI Ischemia)
Inhibited by endogenous lactate-limited use
in DKA,Sepsis,CKD
Less specific-cancers,CKD,sepsis,liver disease

A 48-year-old man came to the casualty with complaints of

chest pain and vomiting for the past 6 hours. Gave history of
consuming alcohol the previous evening. He was anxious saying that
his father died of Myocardial Infarction at the age of 65.
On examination, he was anxious. Pulse-86/min; BP-140/90mmhg.
ECG was normal. Blood was drawn for biochemical analysis.Give your
comment on the following biochemical report.
Serum Creatine Kinase
Serum CK-MB (CK-2)
Serum Aspartate Aminotransferase
Serum Lactate Dehydrogenase

125 U/L
5 U/L
30 U/L
110 U/L

A 56-year-old businessman was admitted to the emergency

department of the Government General Hospital with complaints of
severe retrosternal pain. He gave history of heavy smoking and
alcohol consumption for the past 25 years.
On examination, he was profusely sweating. His blood pressure
was 160/100mmHg. ECG showed S-T segment elevation. Blood
sample was taken for biochemical analysis. What is your diagnosis?
Serum
Serum
Serum
Serum
Serum

CK
CK-MB
AST
LDH
Uric acid

1160 U/L
170 U/L
380 U/L
470 U/L
9 mg/dL

thanks..