What are the causes of raised high-sensitivity troponin (hs troponin) levels in a patient?

Causes of Elevated High-Sensitivity Troponin

Elevated high-sensitivity troponin indicates myocardial injury but does not specify the underlying cause—the most common etiology is acute myocardial infarction, but numerous cardiac and non-cardiac conditions can produce troponin elevation, requiring clinical context and serial measurements to distinguish acute coronary syndrome from other causes. 1, 2, 3

Cardiac Causes

Acute Coronary Syndromes

• Myocardial infarction (Type 1) remains the most frequent cause of troponin elevation, reflecting myocardial cellular damage from coronary artery occlusion and distal embolization of platelet-rich thrombi. 2, 3
• Markedly elevated values (>5-fold the upper reference limit) have high positive predictive value (>90%) for acute type 1 MI. 1, 2, 3
• Type 2 MI occurs from supply-demand mismatch without coronary occlusion, commonly seen with tachyarrhythmias, hypotension, or severe anemia. 1, 4

Arrhythmias

• Tachyarrhythmias cause myocardial stress through demand ischemia, leading to troponin elevation without coronary occlusion. 1, 2, 3
• Bradyarrhythmias can similarly cause troponin elevation through supply-demand mismatch. 4

Heart Failure and Structural Disease

• Both acute and chronic heart failure cause wall stress and myocyte damage, resulting in troponin elevation. 1, 2, 3
• Hypertensive emergencies increase afterload, causing myocardial strain and troponin elevation. 1, 4
• Valvular heart disease, especially severe aortic stenosis, increases wall stress leading to troponin elevation. 1, 4

Inflammatory and Infiltrative Conditions

• Myocarditis causes inflammatory damage to cardiac myocytes, producing troponin elevation. 1, 3, 4
• Takotsubo cardiomyopathy produces catecholamine-mediated injury with troponin elevation. 1, 4
• Infiltrative diseases (amyloidosis, hemochromatosis, sarcoidosis, scleroderma) can cause troponin elevation. 4

Iatrogenic Causes

• Cardiac procedures including CABG, PCI, ablation, pacing, cardioversion, or endomyocardial biopsy cause troponin elevation. 1, 4
• Cardiac contusion from trauma produces troponin elevation. 1, 4

Non-Cardiac Causes

Pulmonary Conditions

• Pulmonary embolism causes right ventricular strain, leading to troponin elevation. 1, 2, 3
• Severe pulmonary hypertension causes chronic right heart strain. 3, 4
• Respiratory failure causes hypoxemia leading to myocardial injury. 3, 4

Vascular Emergencies

• Aortic dissection can involve coronary arteries or cause hemodynamic compromise, leading to troponin elevation. 1, 2, 4

Renal Dysfunction

• Both acute and chronic renal dysfunction reduce troponin clearance and associate with cardiac disease, causing troponin elevation. 1, 2, 3
• In end-stage renal disease, troponin elevations are common even without clinical evidence of ACS. 4

Critical Illness

• Sepsis causes troponin elevation through inflammatory mediators and demand ischemia. 1, 3, 4
• Critical illness including shock and burns can cause troponin elevation. 1, 4

Neurological Events

• Acute neurological events (stroke, subarachnoid hemorrhage) cause troponin elevation. 1, 4

Endocrine Disorders

• Both hypothyroidism and hyperthyroidism can cause troponin elevation. 1, 4

Interpretation of Troponin Elevations

Diagnostic Criteria

• The diagnostic cutoff for myocardial infarction requires cardiac troponin exceeding the 99th percentile of the upper reference level. 1, 3
• For diagnosis of acute myocardial necrosis, evidence of a rising and/or falling pattern with at least one value above the 99th percentile is required. 1, 3, 4
• If the initial value is elevated, a serial increase or decrease ≥20% is required to diagnose acute injury. 1, 3

Pattern Recognition

• Rising and/or falling troponin levels differentiate acute myocardial damage (as in MI) from chronic cardiomyocyte injury—the more pronounced the change, the higher the likelihood of acute MI. 2, 3, 4
• Stable elevations indicate chronic myocardial injury rather than acute events. 3, 4
• In MI, troponin rises within 3-4 hours of symptom onset and may remain elevated for up to 2 weeks. 4

Magnitude of Elevation

• Troponin should be interpreted as a quantitative marker: the higher the level, the higher the likelihood for myocardial infarction. 1, 2
• Mild elevations (<2-3 times upper limit of normal) in non-ACS conditions typically do not require workup for type 1 MI unless strongly suggested by clinical symptoms or ECG changes. 4
• Values in the thousands (>1000 ng/L) strongly suggest significant myocardial damage and correlate with increased mortality risk. 4

Prognostic Value

• Troponin elevations are useful for short- and long-term prognosis regardless of the underlying cause. 1, 2
• Even minor elevations carry prognostic significance, with elevated troponin associating with increased mortality risk independent of the underlying cause. 2, 4

Clinical Approach to Elevated Troponin

Serial Measurement Strategy

• Serial measurements at 3-6 hour intervals (or 0h/1h or 0h/2h with high-sensitivity assays) are essential to identify rising/falling patterns characteristic of acute myocardial injury—a single elevated value is insufficient for diagnosis. 1, 2, 3, 4
• In 10-15% of patients, troponin elevations may not be detected initially, making serial testing mandatory. 4

Clinical Context Integration

• Interpret troponin in clinical context, considering chest pain characteristics, ECG changes, or new wall motion abnormalities, which suggest MI. 2, 3, 4
• Without clinical evidence of acute coronary syndrome, consider non-coronary causes of troponin elevation. 4
• Assess for ischemic symptoms (chest pain, dyspnea, diaphoresis) and hemodynamic stability. 4

High-Sensitivity Assay Considerations

• High-sensitivity assays can detect troponin in most healthy individuals, making serial changes more important than absolute values. 1, 3, 4
• Compared with standard assays, high-sensitivity assays have higher negative predictive value for acute MI and reduce the "troponin-blind" interval leading to earlier detection. 1
• High-sensitivity assays result in approximately 4% absolute and 20% relative increase in detection of type 1 MI and a 2-fold increase in detection of type 2 MI. 1

Common Pitfalls and Caveats

• Troponin elevation indicates myocardial injury but does not specify the cause—clinical context is essential to distinguish MI from other etiologies. 1, 5, 6
• Point-of-care troponin tests have substantially lower sensitivity than central laboratory methods and may not accurately quantify extremely high values. 4
• Troponin may remain elevated for up to 14 days after myocardial injury, complicating detection of reinfarction. 4
• CK-MB and myoglobin are not useful for diagnosis of ACS with contemporary troponin assays. 1
• In patients with bundle branch block or paced rhythm, ECG is of no help for the diagnosis of NSTE-ACS, making troponin interpretation even more critical. 1