Cardiac Biomarkers : Troponins,Creatinine Kinase Myoglobin...

Cardiac biomarkers are substances released into the bloodstream in response to myocardial injury , making them essential tools for:

• Diagnosing acute coronary syndrome (ACS) including acute myocardial infarction (AMI) .
• Risk stratification and prognosis.
• Monitoring recurrence or response to treatment.

🧪 Obsolete Markers

Older enzymes like AST , LDH , and its isoenzymes are no longer preferred due to:

• Low specificity for cardiac tissue.
• Delayed elevation , limiting early diagnosis.

🔬 Creatine Kinase (CK) and CK-MB

Total CK

• Found in skeletal muscle, cardiac muscle, brain , and other tissues.
• Lacks specificity for cardiac injury.
• Elevated in trauma, seizures, hyperthyroidism, and renal insufficiency.

CK-MB (Creatine Kinase–Myocardial Band)

• More specific for cardiac muscle .
• Time course :
  • Rises: 4–6 hours post-infarct.
  • Peaks: 12–24 hours.
  • Normalizes: 2–3 days.
• Used for :
  • Early diagnosis of AMI.
  • Detection of reinfarction if troponin remains elevated.
  • Less commonly used today due to troponin superiority.

CK-MB Subforms

• CK-MB2 (tissue-specific) vs CK-MB1 (plasma).
• Ratio CK-MB2/CK-MB1 >1 suggests myocardial infarction.
• Not routinely used due to complex lab processing.

CK-MB/CK Relative Index

• Formula: (CK-MB / Total CK) × 100
• Interpretation:
  • <3 → Skeletal muscle source.
  • >5 → Cardiac source.
  • 3–5 → Indeterminate zone.
• Only useful if both CK and CK-MB are elevated .
• Do not use alone to diagnose MI.

🧬 Cardiac Troponins (cTnI, cTnT)

Overview

• Regulatory proteins in cardiac and skeletal muscle; only TnI and TnT are cardiac-specific.
• Central to universal definition of MI (4th Universal Definition of MI).
• Preferred biomarkers for diagnosis of myocardial injury.

Time Course

• Rises: 3–6 hours.
• Peaks: 12–24 hours.
• Persists: up to 7–14 days.

Troponin T vs I

• Both have high sensitivity and specificity .
• Troponin T may be elevated in renal failure , polymyositis , and dermatomyositis —not always due to MI.

Clinical Uses

• Elevated troponin only : Minor myocardial injury.
• Elevated CK-MB and troponin : Likely full-blown AMI.
• Late markers : Elevated for up to 2 weeks.

Reference Ranges

• Determined by:
  • 99th percentile of healthy population.
  • Coefficient of variation (CV) <10% at decision cutoff point.

🧫 Myoglobin

• Earliest marker : Rises in 2–4 hours, peaks at 6–12 hours, normal in 24–36 hours.
• High negative predictive value early on.
• Not specific for cardiac muscle → limited diagnostic utility.

📊 Cardiac Biomarker Testing Strategies

Recommended ACS Testing Approaches :

1. Single test (CK-MB or Troponin) 8–12 hours after symptom onset.
2. Serial testing :
   • Baseline and repeat at 90 minutes: Myoglobin + CK-MB or Troponin I.
   • 2-hour delta testing: Compare changes in CK-MB and Troponin I from baseline.
3. Repeat troponin at 6–12 hours post-admission for confirmation.

🧪 Other Emerging/Adjunct Cardiac Biomarkers

1. B-type Natriuretic Peptide (BNP)

• Released in response to ventricular wall stress .
• Useful in diagnosing heart failure , not MI.
• May aid in risk stratification in ACS.

2. C-Reactive Protein (CRP)

• Inflammatory marker .
• Elevated levels predict future cardiac events .
• Linked to atherosclerosis progression and plaque instability.

3. Myeloperoxidase (MPO)

• Released by activated neutrophils .
• Promotes oxidized lipid formation , vasoconstriction , and plaque rupture .
• Potential early marker for vulnerable plaques before ACS develops.

4. Ischemia-Modified Albumin (IMA)

• Produced when albumin interacts with ischemic cardiac tissue .
• Early but nonspecific marker .
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