Cardiac Biomarker past, today and future by Dr. Anurag Yadav

A brief Note on Cardiac Biomarkers past, today and future persepctive

1. Cardiac Biomarker Dr Anurag Yadav PostGraduate

2. Classification of Cardiac Biomarkers according to various stages during cardiac disease process

3. Time of increase Peak Return to normal CK-MB 4-8 h 12-24h 72-96h (3-4D) LDH 2-5 D 10 D Myoglobin 2-4 h 8-10h 24 h cTnI 4-6 h 12 h 3-10 D cTnT 4-6 h 12-48 h 7-10 D

4. Comparison of cTn , CK-MB , Mb Time after onset of AMI (hours) Χ upper limit of reference interval

5. Stefan Blankenberg, MD; Renate Schnabel, MD; Edith Lubos, MD, et al., Myeloperoxidase Early Indicator of Acute Coronary Syndrome and Predictor of Future Cardiovascular Events 2005

6. Clinical usefulness of myoglobin : *if myoglobin concentration remains within the reference range 8 hours after the onset of chest pain, AMI can be ruled out essentially. *because of its rapid clearance by the kidney, a persistently normal Mb concentration will rule out reinfarction in patient with recurrent chest pain after AMI * Rapid monitor of success of thrombolytic therapy DRAWBACKS Due to poor specificity, myoglobin levels do not always predict myocardial injury

7. Comparison of cTn , CK-MB , Mb Time after onset of AMI (hours) Χ upper limit of reference interval

8. Drawbacks IMA levels raised in non- cardiac ischemia Modification to n- terminal end may also be induced by extracellular hypoxia, acidosis etc , Conclusion FDA in 2010 has approved a multimarker approach for using the combination of ECG, the cTnI , and the IMA levels achieving a sensitivity of 95% for ACS

9. H-FABP is 20 times more specific to cardiac muscle than myoglobin H-FABP is recommended to be measured with troponin to identify MI and ACS in patient presenting with chest pain. In addition to its diagnostic potential H-FABP also has prognostic value. The risk associated with ↑ H-FABP is dependent upon its concentration. Patients who were cTnI - but H-FABP+ have more risk of morbidity and mortality after 1 year follow up than those with cTnI+HFABP -.

10. Fig. Schematic representation of the ANP and BNP precursors with sequence numbering defining low-molecular-mass forms, N-terminal forms and high-molecular-mass precursors

11. Homocysteine

12. Homocysteine

13. miRNAs are appx . 20-25 nucleotide long non coding RNAs, that negatively regulate or inhibit gene expression by binding to sites in the untranslated regions of targeted messenger RNAs.

14. miRNA are found to be involved in almost every biological process, from cellular differentiation and proliferation to cell death and apoptosis Many different types of miRNA can be detected in circulating blood and these miRNA are present in remarkably stable form that even withstand repetitive freezing/thawing cycle and are protected against Rnases . Thousands of miRNAs have been described in human to date which ehibits tissue specific pattern of expression.

15. miRNAs that regulates cardiovascular system can be divided into 4 groups : 1 . miRNA regulating endothelium function and angiogenesis : miR126, miR17-92 cluster, miR130a, miR221, miR21 2 . cardiac myocyte specific mRNA : miR208a 3 . cardiac myocyte and skeletal muscle miRNA : miR1, miR133a, miR499 4. smooth muscle miRNAs :miR143, miR145 miRNAs hold promise as very specific and accurate marker of cardiac dysfunction.