Cardiac MarkersCardiac MarkersbyN.X.

Cardiac MarkersCardiac Markers1. After the loss of integrity of cardiac myocyte

membranes,

intracellular macromolecules diffuse into the interstitium

lymphatics, and microvasculature.

2. CK, CK isoforms, troponins, and myoglobin

Creatine KinasesCreatine Kinases1. CK is formed by two subunits, B and M, and thus

including

isoforms CK-MB, CK-BB and CK-MM.

2. CK exists in various types of tissue.

3. CK-MB predominates in cardiac muscle.

- up to ~45% of total CK in cardiac muscle

- <1% of total CK in skeletal muscle

Creatine KinasesCreatine Kinases4. Serum CK-MB levels rise within 2~8 hours after AMI.

5. CK-MB values return to normal 2~3 days after the event.

6. Reference range in NTUH (Abbott assay)

CK 38~160 U/l

CK-MB <16 U/l

Creatine KinasesCreatine KinasesA ratio of CK-MB mass: CK activity 2.5

suggests MI.

CK-MB from skeletal muscle produces a plateau pattern.

CK-MB from MI peaks at approximately 12~24 hour.

Creatine KinasesCreatine Kinases

TroponinsTroponins1. Three subunits including troponin C, I, and T. The

complex

regulates the contraction of striated muscle.

2. TnC binds to calcium ions.

TnI binds to actin and inhibits actin-myosin interaction.

TnT binds to tropomyosin, attaching to thin filament.

3. Cardiac-specific isoforms

TroponinsTroponins

Troponin ITroponin I1. Cardiac Troponin I (cTnl) is a cardiac muscle protein

with a

molecular weight of 24 kilo-Daltons.

2. The human cTnl has a additional amino acid residues

on its N-terminal that are not exist on the skeletal form.

3. The half life of cTnI is estimated to be 2~4 hours.

4. Serum increase is found between 2-8 hours and returns to

normal 7~10 days after AMI.

5. Cardiac TnI levels provide useful prognostic information.

6. Reference range in NTUH (Abbott assay)

cTnI <2 ng/ml

Troponin ITroponin I

NEJM 1996;335:1342-9

Troponin TTroponin T1. Cardiac Troponin T (cTnT) is present in fetal skeletal

muscle.

2. In healthy adult skeletal muscle cTnT is absent.

3. The gene of cTnT may be re-expressed in skeletal muscle

disease. (Clin Chem. 1999;45:2129-2135)

4. Biological half life and early serum increases of cTnT are

similar to that of cTnI.

5. Peak between 12~96 hours and return to normal 14 days

after AMI.

MyoglobinMyoglobin1. The major protein responsible for O2 supply of

striated

muscle.

2. It is released into blood rapidly (as early as 1 hour) after

damage to muscle cell.

3. Early detectable, more sensitive but non-cardiospecific.

4. High negative predictive value.

ComparisonComparison

NEJM 2002;Vol.346,No.26:2079-82

ComparisonComparison

ComparisonComparison

Cardiac markers in patients with CRF, n=159

(Circulation 1993;88:101-106)

ComparisonComparison1. CK and CK-MB may be elevated in renal and

muscular

disorders.

2. Elevated cTnI level in uremic patients has been a source

of great controversy.

3. Elevated cTnT has been found in regenerating skeletal

muscle and in patients with ESRD. (cTnT is elevated in asymptomatic patients with CRF. Am J Clin

Pathol

1996;106:118-123)

4. Myoglobin is more suitable for the detection of reinfarction.

Utility After CABG or Vascular Utility After CABG or Vascular SurgerySurgery

1. Early ischemia or infarction after CABG is most likely to be

due to problems with the grafts.

2. Due to the surgical trauma, the usual indicators of MI

have uncertain diagnostic value.

3. It is important to establish new biochemical diagnostic

limits for perioperative MI after CABG.

4. Cardiac markers are released rapidly into blood (washout)

in cases of successful reperfusion after surgery.

5. Elevated cTnI (Dade assay) is associated increased risk of

6-month mortality and MI. (Circulation 2002;106:2366-2371)

Utility After CABGUtility After CABG

Chest 2002;121:103-111

ConclusionConclusion

1. Elevated serum cTnI in patients with renal disorders,

especially in lower ranges, should be interpreted with

caution.

2. Cardiac TnI is useful for predicting short-term mortality in

vascular surgery patients.

3. Normal values of cardiac markers after cardiac surgery

are still not defined.