Cardiovascular Disease Biomarkers

Cardiovascular Disease (CVD)

• CVD includes heart and blood vessel diseases that affect the circulatory system.
• Examples of CVD include:
  • Coronary heart disease (heart attack)
  • Cerebrovascular disease (stroke)
  • High blood pressure
  • Congestive heart failure
  • Congenital cardiovascular defects
  • Peripheral vascular disease

Cardiac Biomarkers

• A cardiac biomarker is a clinical laboratory test used to detect acute myocardial infarction (AMI) or minor myocardial injury.
• Cardiac biomarkers are most useful when patients have nondiagnostic ECG tracings.

Evolving Definitions of Myocardial Infarction (MI)

• The criteria for the definition of MI have evolved over the years, partly due to improvements in detection technologies, including biomarkers.
• The old diagnosis of AMI was based on 2 out of 3 of WHO criteria (1979), including:
  • Symptoms of ischemia (prolonged chest pain)
  • ECG changes
  • Cardiac biomarker concentrations (enzymes)
• The new definition of AMI is based on documenting an increase in cardiac troponin or CK-MB mass in the context of myocardial ischemia.

Ideal Marker to Detect AMI

• An ideal marker should have:
  • High concentration in myocardium
  • Absence from non-myocardial tissues
  • High sensitivity and specificity in circulation
  • Rapid release into blood following myocardial injury
  • Remain in blood for several days to allow detection
  • Blood levels correlate with extent of myocardial injury and prognosis
  • Rapid, simple, and automated commercial assays available

Troponins

• Troponins are regulatory proteins in striated muscle responsible for calcium-modulated interaction.
• There are cardiac-specific forms of troponin, including:
  • Troponin T (TpnT)
  • Troponin I (TpnI)
• Troponins T and I have different characteristics, including:
  • Molecular weight (37 kDa vs 22.5 kDa)
  • Nature of protein (structural vs catalytic)
  • Kinetics of release (biphasic vs single peak)
  • Duration of elevation (up to 14 days vs 5-7 days)

Troponin Release Kinetics

• Troponin release is biphasic, with:
  • Detectable in blood 3-12 hours after MI
  • Peak levels at 12-38 hours
  • Remain elevated for 5-10 days
• TnI remains elevated longer than CK-MB due to ongoing release of the myofibril-bound fraction.

Clinical Applications of Troponins

• Elevated TnI is found in 30-40% of patients with unstable angina and is a better risk indicator than CK-MB.
• Serial monitoring of TnI over 8-12 hours is becoming common practice in many well-developed institutions.
• To rule out an acute myocardial infarction, many centers are ordering CK-MB and TnI on admission and again at either 8 or 12 hours.
• An increase in plasma troponin concentration is indicative of myocardial injury, but not synonymous with MI.

Non-Ischemic Causes of Elevated Troponin

• Congestive heart failure
• Hypertension
• Circulatory shock
• Pulmonary embolism
• Covid-19
• Mechanical injury
• Cardiac contusion
• Cardiotrophic viral infections
• Chemotherapy
• Renal failure
• GI bleed