What causes baseline elevated troponin levels?

Causes of Baseline Elevated Troponin Levels

Baseline elevated troponin levels can be caused by numerous cardiac and non-cardiac conditions, with chronic kidney disease, heart failure, and structural heart disease being among the most common causes. 1

Cardiac Causes

• Chronic Heart Failure: Both acute and chronic heart failure cause wall stress and myocyte damage, leading to persistent troponin elevation 1, 2
• Structural Heart Disease: Conditions such as aortic stenosis, hypertrophic cardiomyopathy, and other valvular diseases are associated with chronic troponin elevation 1, 2
• Left Ventricular Hypertrophy: Increased cardiac mass is associated with higher baseline troponin levels 1
• Stable Coronary Artery Disease: Chronic coronary syndrome can lead to persistent low-level troponin elevation through mechanisms including apoptosis, cardiomyocyte turnover, myocardial strain, and subclinical plaque rupture 1
• Infiltrative Cardiac Diseases: Conditions such as amyloidosis, hemochromatosis, sarcoidosis, and scleroderma can cause chronic troponin elevation 1, 2
• Chronic Inflammatory Cardiac Conditions: Ongoing myocarditis or pericarditis can result in persistent troponin release 2, 3

Non-Cardiac Causes

• Chronic Kidney Disease: Renal dysfunction is one of the most common causes of persistent troponin elevation, due to both reduced clearance and associated cardiac disease 1, 2
• Diabetes Mellitus: Often associated with chronic troponin elevation due to microvascular disease and subclinical myocardial injury 1
• Pulmonary Hypertension: Causes right ventricular strain leading to troponin release 1, 2
• Chronic Respiratory Failure: Ongoing hypoxemia can lead to persistent myocardial injury 1, 2
• Endocrine Disorders: Conditions such as hypothyroidism can cause chronic troponin elevation 2

Mechanisms of Chronic Troponin Elevation

• Apoptosis: In the absence of acute insults, ongoing programmed cell death can lead to chronic troponin release, particularly in heart failure 1
• Cardiomyocyte Turnover: Normal cell turnover in cardiac tissue may contribute to detectable troponin levels, especially with high-sensitivity assays 1
• Myocardial Cell Stretch: Integrin signaling in viable cardiomyocytes under stretch conditions can lead to troponin release without cell death 1
• Increased Membrane Permeability: Chronic inflammatory states may increase cell membrane permeability, allowing troponin leakage 1
• Subclinical Plaque Rupture: Ongoing minor plaque disruptions in coronary arteries can cause low-level troponin release 1

Clinical Approach to Baseline Elevated Troponin

• Distinguish from Acute Elevation: Acute myocardial injury typically shows a rising/falling pattern of troponin, while chronic elevation remains relatively stable 1, 2
• Serial Measurements: Multiple measurements over time help differentiate chronic elevation from acute injury 1, 2
• Consider Comorbidities: Evaluate for common causes such as CKD, diabetes, heart failure, and structural heart disease 1
• Avoid Dismissive Terminology: Terms like "troponin leak" or "troponinemia" should be avoided as they trivialize the prognostic significance of myocardial injury 1

Important Clinical Considerations

• Prognostic Significance: Chronic troponin elevation, even at low levels, is associated with increased cardiovascular risk and poor prognosis 1
• High-Sensitivity Assays: With high-sensitivity troponin assays, detectable levels may be present in many healthy individuals, making the pattern of change more important than absolute values 2
• False Positives: True false positives are rare with modern assays, though they have historically been reported with skeletal myopathies or heterophilic antibodies 1
• Not a Nuisance Finding: Chronic troponin elevation should not be dismissed as clinically irrelevant, as it indicates ongoing myocardial injury that carries prognostic significance 1

Common Pitfalls

• Misinterpreting as ACS: Not all troponin elevations indicate acute coronary syndrome; clinical context is essential 1, 4
• Overlooking Stable Elevation: Failing to recognize that a stable, minimally elevated troponin may represent chronic rather than acute injury 1, 5
• Excessive Testing: Ordering repeated troponin measurements in patients with known chronic elevation can lead to unnecessary testing and interventions 5, 6
• Ignoring Prognostic Value: Dismissing chronic troponin elevation as clinically unimportant overlooks its significant association with future adverse cardiovascular events 1