What are the causes of raised troponin (cardiac biomarker) levels?

Causes of Elevated Cardiac Troponin Levels

Elevated cardiac troponin levels can be caused by numerous cardiac and non-cardiac conditions beyond acute myocardial infarction, with tachyarrhythmias, heart failure, hypertensive emergencies, critical illness, myocarditis, Takotsubo syndrome, and valvular heart disease being the most frequent causes. 1

Primary Cardiac Causes

Acute Coronary Syndromes

• Type 1 myocardial infarction (plaque rupture with thrombus formation)
  • Most common cause of significant troponin elevation (>5-fold upper reference limit has >90% PPV for acute type 1 MI) 1
  • Characterized by rising/falling pattern with symptoms of ischemia

Other Cardiac Conditions

• Heart failure (acute and chronic) 1
• Tachyarrhythmias and bradyarrhythmias 1
• Myocarditis (inflammatory cardiac disease) 1
• Takotsubo syndrome (stress cardiomyopathy) 1
• Valvular heart disease (particularly aortic stenosis) 1
• Hypertensive emergencies and hypertensive heart disease 1
• Cardiac procedures:
  • Cardiac contusion
  • Ablation
  • Pacing
  • Cardioversion
  • Endomyocardial biopsy
  • Percutaneous coronary intervention (PCI)
  • Coronary artery bypass grafting (CABG) 1

Vascular/Pulmonary Causes

• Pulmonary embolism and pulmonary hypertension 1
• Aortic dissection 1

Systemic Conditions

• Critical illness (shock, sepsis, burns) 1
• Renal dysfunction and associated cardiac disease 1
  • Troponin elevation in renal dysfunction should not be primarily attributed to impaired clearance but to underlying cardiac conditions 1
• Acute neurological events (stroke, subarachnoid hemorrhage) 1
• Extreme endurance efforts 1

Endocrine and Metabolic Causes

• Hypo- and hyperthyroidism 1

Infiltrative Diseases

• Amyloidosis
• Haemochromatosis
• Sarcoidosis
• Scleroderma 1

Toxic Causes

• Drug toxicity:
  • Cardiotoxic chemotherapy (doxorubicin)
  • 5-fluorouracil
  • Herceptin (trastuzumab)
• Poisoning (snake venoms) 1
• Rhabdomyolysis 1

Interpretation Considerations

Pattern of Elevation

• Rising and/or falling troponin levels suggest acute injury (as in MI)
• Stable elevations suggest chronic myocardial damage 1

Magnitude of Elevation

• Elevations beyond 5-fold the upper reference limit: high (>90%) PPV for acute type 1 MI
• Elevations up to 3-fold the upper reference limit: limited (50-60%) PPV for AMI and may be associated with many conditions 1

Clinical Context

• Troponin elevation reflects myocardial cell damage but doesn't define the cause
• Interpretation must consider clinical presentation, ECG changes, and imaging findings 1
• Even minor elevations indicate increased risk and warrant thorough evaluation 2

Clinical Pitfalls to Avoid

1. Don't assume all troponin elevations indicate ACS

   • Up to 40% of troponin elevations are due to non-ACS causes 2

2. Don't dismiss troponin elevations in renal dysfunction

   • These should not be primarily attributed to impaired clearance but to underlying cardiac conditions 1

3. Don't miss life-threatening non-coronary causes

   • Conditions like aortic dissection and pulmonary embolism can cause troponin elevation and require different urgent management 1

4. Don't rely on a single troponin measurement

   • Serial measurements showing a rise and fall pattern help distinguish acute from chronic injury 1, 3

5. Don't forget that even minor elevations have prognostic significance

   • Any elevation above the 99th percentile indicates increased risk 1, 4

Understanding the diverse causes of troponin elevation is essential for accurate diagnosis and appropriate management of patients presenting with elevated cardiac biomarkers.