CARDIAC BIOMARKERS

Biomarkers: Biochemical substance which is useful in detecting

dysfunction of an organ.
Cardiac Biomarkers: Biochemical substance which is used to detect
cardiac diseases.
Myocardial ischemia: reduction of coronary blood flow 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
Diagnostic criteria of Myocardial Infarction
Clinical Manifestations
ECG
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
Types of Biochemical Markers for Myocardial Infarction
Cardiac Enzymes (isoenzymes):
Total CK
CK-MB
Lactate dehydrogenase (LD)
Aspartate aminotransferase (AST)
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+
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 OTHER CAUSES OF ELEVATION OF cTn
Trauma
Congestive heart failure
Acute pulmonary embolism

Postoperatively
Drug toxicity adriamycin , 5FU etc.
Inflammatory 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 )
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, malignant

Hyperpyrexia
CK MB
Cardiac specific isoenzyme
Cytosolic enzyme
After an AMI URL CK-2 mass < 5.0 ng /mL
CK MB activity is 5% of total CK activity
CK
Advantages:
Tissue specific
diagnosis of reinfarction
Limitations:
not useful in late presentors
MYOGLOBIN
Low Molecular Weight cytosolic protein of cardiac and skeletal
muscles
Early marker of MI
Advantages
Very sensitive marker (90-100%)
The most sensitive early marker for myocardial infarction
Limitation: lacks tissue specificity
Normal range 0 - 70 ng / mL
LACTATE DEHYDROGENASE
lactate + NAD pyruvate + NADH + H+
cytosolic enzyme ; tetramer of H and M

isoenzyme types:
LD I - ( HHHH )
LD 2 - ( HHHM )
LD 3 - ( HHMM )
LD 4 - ( HMMM )
LD 5 - ( MMMM )
Normally LD2 will be more in circulation. In acute myocardial infarction
LD1 (cardiac specific isoenzyme) level is increase.LD1 is more than
LDH2.normal ldh1:ld2 ratio is less than 1. When LD 1: LD 2 ratio 1 it is
called flipped pattern.
Causes of increased LD activity
artefactual invitro haemolysis
Marked rise AMI, circulatory failure, haemotological causes etc.
Moderate rise viral hepatitis, malignancy, and skeletal muscle disorders
etc.
Normal - 125 - 220 IU / L
AST:
L aspartate + 2 oxoglutarate oxaloacetate + L glutamate
In AMI,
causes of increased AST activity
hepatitis , AMI , renal infarction ,
progressive muscular dystrophy ,cirrhosis etc.
normal range - 40 IU / L
TIME COURSE OF CARDIAC BIOMARKERS IN AMI
GUIDELINES
Rule in/out AMI cannot be made from a single estimation

Use of two markers:

Early marker (rising 2-4 hr after pain onset)
Myoglobin
Definitive marker (rising 4-6 hr after pain onset)
High sensitivity and specificity
Remains abnormal several days
Preferred marker is a cardiacTroponin (I or T)
If Troponins are not available, best alternative is CK-Mb mass
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
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 (Heart type Fatty Acid Binding Protein)
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

Dehydrogenase
110 U/L

30 U/L

Serum Lactate

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