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Cardiac Markers byN.X. Cardiac Markers 1. 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 Kinases 1. 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 Kinases 4. 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 Kinases A 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 Kinases Troponins 1. 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 Troponins Troponin I 1. 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 I NEJM 1996;335:1342-9 Troponin T 1. 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. Myoglobin 1. 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. Comparison NEJM 2002;Vol.346,No.26:2079-82 Comparison Comparison Cardiac markers in patients with CRF, n=159 (Circulation 1993;88:101-106) Comparison 1. 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 Surgery 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 CABG Chest 2002;121:103-111 Conclusion 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.