1. Myocardial infarction biomarkers Lecture 5

2. Cases 1 Middle aged man referred by family doctor to a dermatologist because of extensive yellow papules with erythematous bases on his buttocks and elbow. He noticed yellow fatty streaks in palmar creases. What is your probable diagnosis?

4. Case 2 A recently retired lawyer was admitted to the hospital with chest pain that had been developed during the evening after a day spent digging in the garden. No specific signs on the ECG. Lab tests reports are: on admission 48h72h – Creatine kinase (total)-----300U/L----80U/L---40U/L ˂ 25-195U/L – Creatine kinase(CK-MB)----5U/L ˂25U/L (6% of CK) – Troponin T (after 12 hrs)--- ˂ 0.03µg/L---- (˂0.01µg/L)

5. Case 3 54 years old male having H/O hypertension comes to ED at 5.00 am with c/o crushing chest pain and difficulty in breathing. He complained of substernal pressure and described as someone is standing on my chest. He also described that pain was radiating to neck and jaw. What is the most probable diagnosis?

6. Definition – Obstruction to coronary circulation – Necrosis of heart tissue – Irreversible cardiac injury if obstruction lasts for more than 15-20 min. Pathophysiology  Atherosclerotic plaque  Rupture  Thrombus formation  Starts from endocardium spreads towards myocardium

7. Diagnosis Non-invasive – Ambulatory ECG and holter monitoring – Chest X-ray – Exercise stress test Invasive (Blood tests) – Cardiac enzyme – Troponins – CRP – Homocysteine – Fibrinogen – BNP – prothrombin

8. Cardiac enzyme CK – Creatine + ATP phosphocreatine+ ADP – Cytosolic and mitochondrial – Mytochondrial forms are CK CK-Mt – Cytosolic forms is dimer of M&B units – Three isoenzymes – Proportion of CK-2 varies from 5%-50% of the total CK activity. – Conc ranged from 15%-24% of the total CK in patients of CAD. CK Mg +

9. Normal skeletal muscles contain 1% CK-MB activity. Severe skeletal injury Cardiac proteins Myoglobin Low mol wt, oxygen binding protein and present in the cytoplasm Non specific as tissue of origin is not confirmed. Crushed injury, MI Immunoassay

10. Myocardial utility Early marker of myocardial injury Concentraion rises 1 hr after onset of chest pain Peak activity in 4-12 hr (sensitivity is 90-100%) Rapidly cleared of from the circulation Poor clinical specificity ˂ 80% as it is also released in skeletal muscle injury

11. Troponins Contractile protein of all myofibrils Complex of three subunits – Troponin C (calcium binding component) – Troponin T (tropomyosin binding component) – Troponin I (inhibitiry component) Localized primarily in the myofibrils (94-97%) with smaller fraction in cytoplasm (3-6%)

12. The early release kinetics of cTnI and cTnT are similar to those of CK-MB after AMI Increase above reference limit are seen in 4-8 hrs but remain elevated for 5-10 days. LD can be replaced by cTn in the detection of late presenting AMI individuals Clinical sensitivity of TnT is better than CK-MB cTnI rises 48-72 hrs after chest pain remain elevated for 3-5 days Highly specific for myocardial injury will not rise until and unless there is myocardial injury

15. Risk stratification Utility of cTnI, cTnT and CK-MB for identification of individuals at risk 1/3 -1/4 of the individuals with unstable angina have shown increased serum conc of cTnI or cTnT or both. Initial rise is of cytoplasmic release but continued rise is due to myofibril associated troponin.

16. Test Sensitivity and specificity Troponin test The most sensitive and specific test for myocardial damage. Because it has increased specificity compared with CK-MB, troponin is a superior marker for myocardial injury. Myoglobin (Mb) low specificity for myocardial infarction. Rises very early within 1-3 hours of pain. Pro-brain natriuretic peptide (pro-BNP) This is increased in patients with heart failure. It has been approved as a marker for acute congestive heart failure Glycogen phosphorylase isoenzyme BB high sensitivity and specificity early after chest pain. by ELISA Normal troponin levels 12 hours after chest pain has started mean a heart attack is unlikely

17. Myloperoxidase (MPO)  Elevated in chronic conditions CRP  Marker of atherosclerosis Pregnancy associated plasma protein A (PAPPA)  elevated in atherosclerosis when atheroma is about to rupture Oxidized LDL  A marker of atherosclerosis Choline  Test of prognosis  Rises in chest discomfort even without rise in troponin level.

18. MarkersTime of start rising (hr) Time until peak (hr) Time until returns normal (days) CK3-810-243-4 CK-MB3-810-242-3 LD8-1272-1448-14 Myoglobin1-36-91 Troponin I& T 3-824-48 72-100 3-5 I 5-19 T T only