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1. Cardiac markers

2. Biomarker
An indicator used for objective
measurement and evaluation of
Response to
therapeutic
intervention
Pathogenic
process
Normal
biological
process

3. Cardiac biomarkers
• Cardiac biomarkers were first developed for assisting
the cardiac events, especially acute myocardial
infarction.
• Better understanding of cardiac disease process and
advancement in detection technology has pushed the
application of cardiac biomarkers beyond the diagnosis
boundaries.
• Cardiac biomarkers are now used for staging of cardiac
disease, timing of cardiac events and prognostification.

4. CLASSIFICATION OF CARDIAC
BIOMARKERS
• Biomarkers of myocardial injury
▫ markers of myocardial necrosis
▫ markers of myocardial ischemia
• Inflammatory and prognostic Biomarkers

5. BIOMARKERS OF MYOCARDIAL
INJURY
• Markers of myocardial necrosis
▫ Creatine kinase – MB
▫ Myoglobin
▫ Cardiac troponins
• Markers of myocardial ischemia
Ischemia Modified Albumin (IMA)
Heart-type fatty acid binding protein (H-FABP)

6. Marker of Mocardial Ischemia
IMA
H-FABP

7. • Ischemia modified albumin is a marker formed
after damage in the N terminal region of the
albumin in ischemic conditions.
• Endothelial or extracellular hypoxia, acidosis and
free oxygen radicals causes increase in IMA.
• IMA rises within minutes from onset of ischemia
and remains elevated for several hours after
cessation of ischemia.
Ischemia Modified Albumin (IMA)

8. • Clinical uses of IMA :
it is used as diagnostic criteria for myocardial
necrosis .
It is a non specific marker, since it is also reported
to be elevated in pulmonary infarction, critical
limb ischemia and cerebrovascular disorders.

10. • Heart type fatty acid binding protein is a very stable
low molecular weight (14-15kDa) in the cytoplasm of
myocardial cells.
• FABPs are involved in active fatty acid metabolism
where it transports fatty acid from cell membrane to
mitochondria for oxidation.
• Small size of H-FABP facilitates rapid diffusion
through interstitial space, appearing as early as 1-3 hrs
after onset and peaking within 6hrs. It return to
normal levels with in 12-24hrs.
H-FABP

11. • H-FABP is 20 times more specific to cardiac
muscle than myoglobin
• H-FABP is recommended to be measured with
troponin to identify Miocardia Iinfarction in
patient presenting with chest pain.

12. Marker for cardiac necrosis
cTn
CK-MB
Myoglobins

13. Cardiac
Troponin

14. • Troponin is a complex of three regulatory proteins
(Troponin C, Troponin I and Troponin T) that is
associated with muscle contraction in skeletal and
cardiac muscle.
• Cardiac troponin is slightly different from skeletal
troponin structurally hence serve as a potent and
specific marker for cardiac disease.

17. Individual subunits serve different functions:
• Troponin C binds to calcium ions to produce a
conformational change in TnI
• Troponin T binds to tropomyosin, interlocking them to
form a troponin-tropomyosin complex
• Troponin I binds to actin in thin myofilaments to hold
the troponin-tropomyosin complex in place
Normal value : cTnT : ≤0.01ng/ml
cTnI : ≤0.04ng/ml
• Usually, Troponin is not detectable in healthy
individual.

18. • It is extremely useful in patients who do not seek
attention in the 2 to 3 days window when CK-MB is
elevated.
Rise : with in few hours after onset of chest
pain
Peak : 2 days
returns normal : 7-10 days
• TnT has cardiac as well as skeletal muscle source.
cTnT :

19. • It is cardiac specific because it has additional amino
acid residue on its N-terminal that are non existent
in skeletal muscle.
Rise : b/w 4-6 hr after onset of pain
Peaks : 12-18 hrs
Returns normal : 6 days
• Its measurement is advantageous over CK-MB as it
is not found in detectable amount in serum of
patients with multiple injuries, renal disease and in
those with acute and chronic skeletal muscle
disorders.
cTnI :

20. • Creatine kinase (CK) is a enzyme involved with
the transfer of energy in muscle metabolism.
• It catalyses the conversion of creatine to
phospho-creatine degrading ATP to ADP.
CK-MB

21. • CK is a dimer composed of two subunits B (brain
type) and M (muscle type), resulting in three
isoenzyme:
•
CK-BB (CK1) : is of brain origin, found in blood
only when BB is damaged.
CK-MB (CK2) : it is relatively specific for
myocardial origin
CK-MM (CK3) : it is found primarily in skeletal
muscle

22. • CK-MB :
it is a valuable tool for the diagnosis of
Miocardial Infarction because of its relative high
specificity for myocardial damage.
Rise : 4-6 hrs after onset of symptoms
Peak : 12 hrs
Return to normal : 24-36 hrs
• Can be used to indicate early re-infarction if
level normalizes and then increases again.

23. CK-MB
Relative Index = χ 100
Total CK

24. • Small-size heme protein found in all tissues mainly assists in
oxygen transport
• It is released from all damaged tissues
• Its level rises more rapidly than cTn and CK-MB.
• Released from damaged tissue within 1 hour
• Normal value: 17.4-105.7 ng/ml
• Timing:
▫ Earliest Rise: 1-4 hrs
▫ Peak 6-9 hrs
▫ Return to normal: 12 hrs
Myoglobin

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

26. Marker of Inflammation
hsCRP
homocystein

27. High-Sensitivity C-Reactive Protein

28. • CRP is Pentameric structure consisting of five identical
subunits of 23-kDa.
• Its plasma levels can increase rapidly to 10,000x levels.
• It is the most extensively studied marker of
inflammation. Despite some controversy regarding
its clinical use, it appears to be the most promising
to date.
• Although considered to be a general nonspecific
marker of inflammation, elevated baseline levels of
hsCRP are correlated with higher risk of future
Cardio vascular morbidity and mortality among
those with or without clinical evidence of Cardio
vascular diseases.

30. • Once ligand-bound, CRP can:
▫ Activate the classical compliment pathway
▫ Stimulate phagocytosis
▫ Bind to immunoglobulin receptors
▫ Endothelial dysfunction via ↑ NO synthesis
▫ ↑LDL deposition in plaque by CRP-stimulated macrophages
More recent data implicate CRP as an actual mediator
of atherogenesis

31. Clinical Uses
▫ Screening for cardiovascular risk in otherwise
“healthy” individuals
▫ Predictive value of CRP levels for disease severity in
pre-existing Coronary artery disease

32. Limitations of CRP
• Low specificity
• No evidence that lowering CRP levels decreases Cardio
Vascular risk

33. • Intermediary amino acid formed by the conversion of methionine to
cysteine
• Moderate hyperhomocysteinemia occurs in 5-7% of the population
• Recognized as an independent risk factor for the development of
atherosclerotic vascular disease and venous thrombosis
• Can result from genetic defects, drugs, vitamin deficiencies
Homocystein

34. • Homocysteine is implicated directly in vascular injury including:
▫ Disruption of elastic lamina
▫ Smooth muscle hypertrophy
▫ Platelet aggregation
• Proposed mechanisms by which it induces vascular injury are leukocyte
recruitment, foam cell formation, and inhibition of NO synthesis.
• Normal levels : < 6 mmol/l

35. • Elevated levels of homocystein appear to be an
independent risk factor, though less important than
the classic Cardio Vacular risk factors.
• Treatment includes supplementation with folate,
B6 and B12.