CARDIAC ENZYMES

1. DR SAKINA ,MBBS,M.D
SENIOR LECTURER ,MSU

2. BIOMARKERS -
DEFINITION
• A biomarker is a clinical laboratory test
which is useful in detecting dysfunction
of an organ.
• Cardiac biomarkers are protein
molecules released into the blood
stream from damaged heart muscle
These biomarkers are used to detect
the heart diseases .
It has characteristic rise and fall
pattern

3. CARDIAC MARKERS
TESTED IN
• i. Any chest pain
• ii. Unstable angina
• iii. Suspicious ECG changes
• iv. History suggestive of
myocardial infarction
• v. Following surgical
coronary revascularization
• vi. Patients with hypotension
and dyspnea

6. HISTORY OF BIOMARKERS
1954 - SGOT (AST)
• 1955 - LDH
• 1960 - CPK
• 1972 - CPK isoforms by
Electrophoresis
• 1975 - CK - MB by immunoinhibition
• 1975 - Myoglobin
• 1985 - CK - MB Mass immunoassay
• 1989 - Troponin T
• 1992 - Troponin I

7. • Detecting myocardial damage whether
due to AMI or other cardiac process ??

8. • CK-MB
• Troponin-I/T
• LD (LDH)
• Myoglobin
• AST
• BNP
• Others

9. • Serial testing of the following cardiac
Markers is usually done to guide the
prognosis
• i. Creatine kinase (CKMB)
• ii. Cardiac troponin I (CTI) and
Cardiac troponinT (CTT).
• iii . Myoglobin
• iv. Brain Natriuretic Peptide (BNP).
It is a reliable marker of ventricular
function
• v. LDH and AST were previously
used as markers of myocardial
infarction, but no more used in
clinical practice.

10. CARDIAC MARKERS
• Enzymatic:
i. CK
ii. LDH
• AST
• Nonenzymatic :
i. Myoglobin
ii. Cardiac troponin T and I

11. Commonly used biomarkers for
early detection of acute
myocardial infarction are:
• 1. Cardiac troponins, TnI and TnT
• 2. Creatine kinase, CK-MB
• 3. Myoglobin.
• Of these, troponins and CK-MB are
the sensitive and specific markers,
whereas myoglobin though
sensitive, is non-specific

12. Aspartate
transaminase(AST)
• AST was the first used as a
marker of myocardial infarction in
olden days,The level is
significantly elevated in
myocardial infarction
• Normal Range-8-20U/L

13. MYOGLOBIN
• Small-size heme protein found in
all tissues mainly assists in
oxygen transport
It is released from all damaged
tissues
Increases often occur more rapidly
than TI and CK ,but it lacks
specificity
Released from damaged tissue
within 1 hour

14. CONDITIONS FOR
MYOGLOBIN INCREASE
• Acute myocardial infarction
Skeletal muscle damage,
muscular dystrophy,
inflammatory myopathies
Renal failure,
severe uremia
Shock and trauma

15. DRAWBACKS OF MYOGLOBIN
DRAWBACKS
Though sensitive ,Due to poor
specificity, myoglobin levels
do not always predict
myocardial injury

16. Brain Natriuretic
Peptide (BNP)
• The natriuretic peptide family consists of
three peptides:
• Atrial natriuretic peptide (ANP),
• Brain natriuretic peptide (BNP), and
• C-type natriuretic peptide (CNP). clinical
significance of CNPis not clear.
• ANP is produced primarily in the
cardiac atria.
• BNP is present in human brain, but
more in the cardiac ventricles

17. BRAIN NATRIURETIC
PEPTIDE (BNP)
Greatest proportion of
circulating BNP is thought to
come from the ventricles
(left) Therefore it is a reliable
marker of ventricular function
• Patients with congestive
heart failure have high
plasma concentrations of
ANP and BNP.

18. LACTATE
DEHYDROGENASE
Lactate dehydrogenase catalyses the
conversion of pyruvate to lactate.

19. LDH -ISOFORMS
• M4 form is seen in skeletal
muscles while
• H4 form is seen in heart.
• Normally LDH-2 (H3M1)
concentration in blood is greater
than LDH-1 (H4); but this pattern
is reversed in myocardial
infarction;

20. LACTATE
DEHYDROGENASE
• LDH levels are also high in
Tissue breakdown
• Hemolysis
• cancer,
• meningitis,
• encephalitis, or HIV.

21. LACTATE
DEHYDROGENASE
• LDH has only limited diagnostic
value because of its
non specific nature.
• Normal value of LDH in serum
is 100-200 U/L

22. Creatine kinase
(CK/CPK)
Creatine kinase (CK/CPK) is an enzyme
expressed in a number of tissues.
Function: it catalyses the
conversion of creatine to
phosphocreatine degrading ATP to
ADP
The CK enzyme consists of two subunits,
B (brain type) or M (muscle type),
Making three different isoenzymes:
CK-MM,
CK-BB and
CK-MB

23. Creatine kinase
(CK/MB)
• High specificity for cardiac
tissue
Begins to rise 4-6 hours after
onset of infarction
Peaks at about 12 hours
Returns to baseline at 24-48 hours
Can be used to indicate early re-
infarction if level normalizes and
then increases again
Normal serum value for CK is 15-
100 U/L for males and 10-80 U/L
for females

24. • Troponin is a complex of three regulatory
proteins that is integral to non-smooth
muscle contraction in skeletal as well as
cardiac muscle
• Troponin is attached to the tropomyosin
sitting in the groove between actin
filaments in muscle tissue
• three subunits, TnC, TnT, and TnI
– Troponin-C (calcium ions)
– Troponin-T (tropomyosin)
– Troponin-I (actin)

26. Troponins
• Troponin T and I are not detected in
healthy individuals
• Troponins are seen in skeletal and
cardiac muscles, but not in smooth
muscles.
• Significant increase in Troponins
reflects myocardial necrosis
They are quantitated by ELISA or immuno
turbidimetric) reactions.

27. Troponin I (TnI)
Troponin I (TnI) is encoded by 3
different genes, giving rise to 3
isoforms;
• the "slow" and "fast" moving forms
are skeletal variety.
• Cardiac isoform is specific for
cardiac muscle;
• the amino acid sequence is different
in skeletal muscle isoform.

28. Troponin I (cTnI)
• Troponin I is released into the blood
within 4 hours after the onset of
symptoms of myocardial ischemia;
peaks at 14-24 hours and remains
elevated for 3-5 days post-infarction

29. Cardiac Troponin T
(cTnT)
• Serum level of Troponin T (TnT)
increases within 6 hrs of
myocardial infarction, peaks at 72
hours and then remains elevated
up to 7-14 days.

31. • Therefore it has good utility for retrospectively
diagnosing AMI
• Remember, CK-MB returns to baseline by
•
Troponin Early
Rise(hrs)
Peak (Hrs) Duration
(Days)
Specficity Sensitivity
Tn T 4-6 10-24 10-24 80% >98%
Tn I 3-6 1-24 4-7 95% >98%

32. Timing Summary
TEST ONSET PEAK DURATION
CK/CK-MB 3-12 hours 18-24 hours 36-48 hours
Troponins 4-10 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

33. • Typical rise and gradual fall (troponin) or
more rapid rise and fall (CK-MB) of
biochemical markers of myocardial
necrosis with at least one of the
following:
• ischemic symptoms;
• development of pathologic Q waves on
the ECG;
• ECG changes indicative of ischemia (ST
segment elevation or depression);
• coronary artery intervention (e.g.,
coronary angioplasty)

34. Comparison

36. • SOS
• repeated at 2 and 72 hours later
• Assay times range from 5 to
30minutes
• TAT<60 min
• cTn T >0.1 ng/ml
• cTn I >1.0 ng/ml