Cardiac Biomarkers Cardiac Biomarkers 1. Advantages Disadvantages Highly sensitive to myocardial injury a. Minor injury can still give significant increase in level 2. Absolute myocardial specificity 3. Can detect late myocardiac infarction event up to 2 weeks 1. 2. 3. 1. Low sensitivity to very early stage myocardial infarction event below than 6 hours of time a. Should be repeated when produces negative reading 2. Limited ability to detect late minor infarction a. Superimposed by the long standing increased level of troponin during the 1st attack 3. Produces false positive in a. Rheumatoid arthritis b. Renal failure 1. 1. Starts to ↑ 1st 3-4 hours after onset of symptoms 2. Peak a. 12-24hours 3. Duration a. 10-14 days Pattern in release in MI is BIPHASIC 1. Troponin 1. Regulatory proteins in striated muscle 2. Responsible for Ca2+ modulated contraction 3. Exists in number of isoform 4. Cardiac specific frms immunologically separable a. Troponin T (Tpn T) b. Troponin I (Tpn I) 1. a. Timeline Description Creatine Kinase-MB (CKMB) Cardiac Troponin 4. Rapid Cost effective Accurate assays in detecting MI within 4-6 hours after onset of symptoms Able to detect early even of reinfarction Loss of specificity in the even of a. Severe skeletal muscle disease b. Skeletal muscle injury including surgery i. 5% of muscle are CK-MB isoform c. Marathon runners d. Chronic renal failure e. Hypothyroidism 2. Loss of sensitivity when MI happens early than 4 hours after onset of symptoms Total Creatine Kinase (Total CK) 1. 2. Not reccomended for routine diagnosis of MI Provides additional support for CK-MB test to confirm myocardial injury event through CK-MB/Total CK ratio 1. Poor sensitivity a. Present in the blood due to normal tissue turnover b. Normal reference interval indicates substantial interindividual variation 2. Poor specificity a. Lacks myocardial specificity b. Wide tissue distribution c. Loss specificity in the presence of skeletal muscle i. Disease ii. Injury Starts to ↑ 1st 4-6 hours after onset of symptoms 2. Peak a. 8-12 hours 3. Duration a. 2-3 days a. The best benchmark for biochemical marker to detect myocardial injury in the past 2. At the moment, the best alternative if cTn is not available CK Isoenzymes 1. CK-1 (CK-BB) a. Brain tissues 2. CK-2 (CK-MB) a. 10-20% in myocardium b. 5% in skeletal muscle 3. CK-3 (CK-MM) a. Skeletal muscle Macro Creatine Kinase 1. Type 1 a. CK-BB + Immunoglobulin 2. Type 2 a. Mitochondrial CK Myoglobin 1. 2. High diagnostic sensitivity Useful in the very early event of MI a. Early than 4 hours after the onset of symptoms 3. Most useful in ruling out MI a. ↑negative predictive value 1. Loss specificity in the presence of skeletal muscle a. Disease b. Injury 2. Rapid renal clearence a. Rapidly reduces to normal level for later presentation 3. Should not be used as the only diagnostic marker due to a. Lack of cardiac specificity b. Rapid renal clearence i. So that events after 6-12 hours can be detected confidently 1. Starts to ↑ a. 1st 2-3 hours after onset of symptoms 2. Peak a. 6 hours 3. Duration a. 12-24 hours 1. Relatively small protein located at the cytosol of a. Skeletal muscle cells b. Myocardium 2. Rapidly being release to circulation upon tissue damage 3. Oxygen binding protein