Cardiac Biomarkers Flashcards
a substance used as an indicator of a biologic state. It is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.
A biomarker
substances released from heart muscle when it is damaged as a result of myocardial infarction
Cardiac markers
has been shown that cardiac markers can be released from cardiac tissue as a result of
damage from processes other than MI
TRIAD Diagnosis of Acute Myocardial Infarction
- Chest Pain: highly variable and subjective
- ECG: Objective ST or T-wave changes
- Biomarker elevations: Objective data defining ACS/AMI
Which Biomarkers?
CK (CPK) CK-MB Troponin-I/T LD (LDH) Myoglobin ALT/AST
1st Marker in response to AMI ?
0 - 1/2 day to be detected.
CK-MB isoforms
2nd Marker(s) in response to AMI ? 1 day to be detected
CK-MB
Cardiac Troponin
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
Skeletal muscle expresses
CK-MM (98%) &
CK-MB (1%)
The myocardium expresses
CK-MM (70%) &
CK-MB (30%)
CK therefore, lacks specificity for cardiac damage and needs to be augmented with ?
MB fraction and Relative Index (RI) to indicate true cardiac damage
(In cardiac as well as other tissues, phosphocreatine serves as
as an energy reservoir for the rapid regeneration of ATP)
Creatine kinase (CK/CPK) is an enzyme expressed in a number of tissues. How does it Function?
it catalyses the conversion of creatine to phosphocreatine degrading ATP to ADP
CK Needs _______ increase with simultaneous increase in CK-MB to be diagnostic for MI
> two-fold
CK fluctuation in levels in regards to time?
- Increases 4-6 hours after onset of MI
- Peak activity is at 18 to 24 hours
- Usually has returned to baseline levels by 36 hours
False positive (for MI) CK elevation can be seen in:
- Significant skeletal muscle injury
- Significant CNS damage (Stroke/Trauma)
- Occasionally from GI, renal, urologic disease
*elevations of CK secondary to non-cardiac causes have been noted to increase following a flatter curve
rising and disappearing at a slower pace that a cardiac source
CK-MB fluctuation in levels in regards to time?
Begins to rise 4-6 hours after onset of infarction
Peaks at about 12 hours
Returns to baseline at 24-36 hours
What enzyme has a High specificity for cardiac tissue damage?
CK-MB
CK-MB Can be used to indicate early re-infarction if ?
level normalizes and then increases again
False positive (for MI) CK-MB elevation can be seen in:
Significant skeletal muscle injury
- Cardiac injury for reason other than MI
- Cardioversion,
- Defibrillation (ACLS CPR/ICD firing)
- Blunt chest trauma (MVA/Sports injuries)
- Cardiac AND non-cardiac surgical procedures
- Cocaine abuse (vasospasm, tachycardia, - perfusion/demand mismatch)
- Non often elevated in myocarditis, unless severe
Cardiac specific forms of Troponins that are immunologically separable?
Troponin T (TpnT) Troponin I (TpnI)
- Regulatory proteins in striated muscle
- Responsible for calcium-modulated interaction
- Exist in a number of isoforms
Troponins
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
Troponin has three subunits,
TnC, TnT, & TnL
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
Thus far, studies have failed to find a source of Troponin-I outside the heart, but have found some Troponin-T in skeletal muscle
Because of it’s increased specificity, our lab uses
Troponin-I
heparin in blood sample can result in lowered values of what?
Troponin
Troponin-I levels begin to rise
2-3 hours after onset of MI
80% of patients with AMI will have positive values at
3 hrs
Elevations in Troponin-I and Troponin-T can persist for up to
10 days after MI
What is a good utility for retrospectively diagnosing an AMI ?
Troponin
Remember, CK-MB returns to baseline by
48 hrs
Troponin release can also be precipitated by
other conditions that cause myocardial damage
Degree of elevation of Troponin value can give
prognostic information
Some data suggest that the _______ peak TI value correlates with infarct size.
72-96 hour
Used in the past along with aminotransferases to diagnose AMI. It is non-specific for cardiac tissue, which contains LD-1. However, pancreas, kidney, stomach tissue and red cells also contain LD-1
LDH
In the setting of AMI, What is the LDH timing?
Onset: 6 - 12 hrs
Peaks: 24 - 48 hrs
Duration: 6 - 8 days
Ubiquitous small-size heme protein released from all damaged tissues. Increases often occur more rapidly than TI and CK. Not utilized often for AMI/cardiac damage assessment because of its very rapid metabolism (short plasma half-life) causing short burst increases that are difficult to assess clinically, as well as its lack of specificity for cardiac tissue.
Myoglobin
Used as surrogate markers of cellular damage in the past. Very non-specific so not used for assessment of myocardial damage any longer
ALT/AST
H-FABP
Heart-type fatty acid binding protein
The major protein responsible for O2 supply of striated
muscle.
Myoglobin
Early detectable, more sensitive but non-cardiospecific
