Trace form in all muscle; 1-2% in skeletal, 15-20% in cardiac
Higher in skeletal in neonates, chronic muscle injury, respiratory muscles
Different assays; results not interchangeable
Dimer: M & B monomers
CK- 1: BB; neural & mesenchymal tissue
CK- 2: MB; muscle (<1%); heart (<40%)
CK- 3: MM; heart (60 - 80%); muscle (>99%)
CK MB isoforms
After relase, CK MB cleaved by removing single amino acid, changing charge
Half-life of tissue isoform = only 3 hours
Differentiates acute from chronic or remote muscle injury; not cardiac specific
New standard for detection of myocardial injury
Normally negligible levels in circulation
> 20 times in injury
Can detect even minor degrees of myocardial damage
Release from fibrils causes high levels for many days
For tni and tnt, differences between cardiac and skeletal muscle forms
Several studies suggest positive tn at presentation associated with poorer prognosis
Not clear if related to other variables
Troponins – ‘False positivity’
Non – ischemic cardiac injury
End stage heart failure
Skeletal muscle problems (1st generation assays)
Muscular dystrophy,Injury, Myositis,
Troponin T (TnT)
Cardiac-like form found in fetal skeletal muscle
About 6% cytosolic, detectable earlier than tni
Second generation assay detects less damage than tni
One assay manufacturer
Troponin I (TnI)
Found only in cardiac muscle
Only about 2% cytosolic, later detection than tnt
No standardization; different assays produce different results, detection limits
Tn in renal failure
Elevated TnT seen commonly in renal failure (up to 50%)
High TNI seen occasionally
Patients with tn have high likelihood of cardiac death in year after detection
? Higher likelihood for TNI
Problems with TnI
Different forms of troponin I found in serum (free, bound, and forms of bound)
Cannot confirm troponin results with any other assay since it is more “sensitive”
Different manufacturer’s assays variably measure these
No standardization, making comparison between labs difficult
In assays, fibrin may trap labeled antibody
Patients with ua / mi often on heparin, preventing full use of fibrinogen
Residual fibrinogen may form fibrin in instrument, causing false positive results
Rheumatoid factor, autoantibodies may cause false positive with some assays
Problems with TnI
Early rising markers provide potential for early diagnosis
Heart Fatty Acid Binding Protein(h FABP)
Combined with myoglobin, gives specificity
Useful for estimating infarct size after reperfusion
Longer window (MHC return normal = 14 days)
Glycogen Phosphorylase Isoenzyme BB (GPBB)
Early markers of cardiac injury
Since treatment of patients with thrombolytic therapy is more beneficial when started earlier after AMI, there is currently a lot of interest in defining those plasma marker proteins that permit an early and sensitive detection of AMI.
Non-enzymatic cardiac proteins are being used as early diagnostic markers of acute myocardial injury abundantly
What are these early markers?
Heart Fatty acid-binding protein (hFABP; 15 kDa) and Myoglobin (17 kDa) belong to the early biochemical cardiac markers and they represent the soluble cytoplasm of cardiomyocytes.
Due to their small size (15 and 17.8 kDa, respectively), they are released into plasma in significant amounts within 3 h of the onset of AMI, while plasma concentrations usually return to normal within 24 h [1–4].
These characteristics allow:
Early confirmation of AMI,
Monitoring of coronary recanalisation or reinfarction, and
What is significance of hFABP?
Cytosolic protein involved in intracellular transport of FAs
Aids metabolism of FA within myocyte
Related with muscle FA oxidation capacity
Is hFABP new?
Is it new?
No, usefulness of hFABP for detection of AMI has been known since 1988 but extensive clinical studies after that have proven its significance
FA metabolism depends on Transport Uptake Delivery to intracellular sites of β -oxidation The insoluble FA bound to special carriers to enhance their rate of transport and cellular uptake Plasma triglycerides serve to supplement FA transport Plasma albumin augments circulatory transport by increasing FA binding sites and binding of non-esterified FAs Fatty acid metabolism
Cardiac muscle [10-30%]
FABP levels in AMI and UAP at admission and one hour later
Comparison of FABP and CPK levels
Why is hFABP earlier?
In conclusion, plasma cardiac Troponin T concentration at 48 h after infarction can be used to distinguish MI, whereas H-FABP concentration at 3 h can be used for stratification of risk according to infarct size.
Pflügers Arch – Eur J Physiol (2000) 439:416–422
Why is hFABP earlier?
In contrast to hFABP and myoglobin, cardiac Troponin T is a protein that is structurally bound to the myofibrillar structure and hence it needs to dissociate before it can be detected in the blood
Besides, due to the small size, hFABP and Myoglobin can cross the endothelial cell barrier directly whereas Troponin must be transported through lymph drainage [like CK-MB]
Is hFABP earlier than myoglobin?
In contrast to myoglobin, hFABP has 4 times higher concentration gradient.
Thus, whilst both are released almost simultaneously, the percentage rise in hFABP is much sharper and higher.
Peak rise in hFABP = 30 fold vis-à-vis 15 fold with myoglobin
Why is hFABP more specific than myoglobin?
As compared to the amount of myoglobin present in the myocardium, double that amount is present in the skeletal muscle
In contrast to this myoglobin distribution, for hFABP only 10-50% of the myocardial amount is present in the skeletal muscle.
Does hFABP detect stable angina also?
As compared to the AMI and unstable angina, stable angina does not require acute intervention but bed rest principally
In contrast, episodes of unstable angina are like mini infarctions and hence more essential to establish faster.
Whether the test for hFABP is positive or not in unstable angina depends upon the amount of cell necrosis that occurs.
Is hFABP testing an ELISA test?
There are ELISA tests for the detection of hFABP but an immunochromatographic test to detect hFABP is faster.
At a predefined position, there are hFABP specific antibodies which react with hFABP if present in the blood sample to give visible proof.
What is sensitivity in hFABP testing?
This is a measure for the percentage of infarcts from the test detects.
The higher the number, the better it is.
A sensitivity of 100% would be ideal.
Sensitivity is calculated by setting the number of detected infarcts [TP = true positive] in relation to the number of infarcts not detected [FN= false negative]
Sensitivity % = TP/[TP+FN] x 100
Can false positives occur in hFABP testing?
Yes, there are 2 conditions where false positives can occur while testing for hFABP
Excessive physical activity – due to damage to skeletal muscle cells and release of hFABP with subsequent rise in the levels of hFABP;
Renal insufficiency – when deficient kidneys are not able to flush out the normal levels of hFABP presented for excretion by release from the skeletal muscles and subsequent increase in levels.
In case of false +ve with hFABP, what is done?
Retesting after half an hour or one hour
If the second test yields darker line, this is more likely then that an infarction has occurred.
What is specificity in hFABP testing?
This is a measure for how often a non-infarction is correctly recognized as such.
The higher the number, the better it is and a sensitivity of 100% would be ideal.
Specificity is calculated by setting the number of detected non-infarctions [TN=true Negative] in relation to the number of non-infarctions incorrectly detected as infarctions [FP=false positive]
Sensitivity % = TN/[TN+FP] x 100
Can false negatives occur in hFABP testing?
Yes, especially in the diagnostic early window period due to individual differences in the infarction process.
Hence, althought the test has a very high sensitivity [over 90%], it cannot be said to have absolute reliability.
For that matter, there are no medical tests with 100% reliability.
Any medications interfere with hFABP testing?
No interference is known to date with detection of hFABP.
Brain Natriuretic Peptide (BNP)
Predictor of mortality,progressive CHF & recurrent MI in ACS (STEMI,NSTEMI,UA)