From the Guidelines
Elevated pro-brain natriuretic peptide (pro-BNP) levels are primarily caused by conditions that place increased stress on the heart, with heart failure being the most common cause, as stated in the 2016 ESC guidelines 1. When the heart's ventricles are stretched due to increased volume or pressure, cardiac myocytes release pro-BNP, which is then cleaved into BNP and NT-proBNP.
Cardiac Causes
Besides heart failure, other cardiac causes include:
- Acute coronary syndromes
- Valvular heart disease
- Atrial fibrillation
- Myocarditis
- Cardiac surgery
- Pulmonary embolism
- Myocarditis
- Left ventricular hypertrophy
- Hypertrophic or restrictive cardiomyopathy
- Valvular heart disease
- Congenital heart disease
- Atrial and ventricular tachyarrhythmias
- Heart contusion
- Cardioversion, ICD shock
- Surgical procedures involving the heart
- Pulmonary hypertension
Non-Cardiac Causes
Non-cardiac causes can also elevate pro-BNP levels, including:
- Pulmonary conditions like pulmonary embolism, pulmonary hypertension, and severe pneumonia
- Renal dysfunction significantly affects pro-BNP clearance, leading to elevated levels in chronic kidney disease
- Advanced age naturally increases baseline pro-BNP levels
- Certain medications like corticosteroids and thiazolidinediones can also cause elevations
- Severe infections, sepsis, burns, and critical illness may raise levels due to inflammatory cytokines and cardiac stress
- Endocrine disorders such as hyperthyroidism and Cushing's syndrome can increase pro-BNP through their effects on cardiac function
- Ischaemic stroke
- Subarachnoid haemorrhage
- Liver dysfunction (mainly liver cirrhosis with ascites)
- Paraneoplastic syndrome
- Chronic obstructive pulmonary disease
- Severe infections (including pneumonia and sepsis)
- Severe burns
- Anaemia
- Severe metabolic and hormone abnormalities
Understanding these various causes is essential for correctly interpreting pro-BNP results in clinical settings, as also discussed in the 2017 American Heart Association scientific statement 1 and the 2015 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials 1.
From the Research
Causes of Elevated Pro-BNP
Elevated pro-brain natriuretic peptide (pro-BNP) levels can be caused by various factors, including:
- Heart diseases such as heart muscle disease, valve disease, rhythm abnormalities, pulmonary hypertension, and cytotoxic injury to the heart 2
- Non-cardiac illnesses, including gram-negative sepsis 2
- Acute coronary syndrome, myocardial infarction, pulmonary embolism, and other cardiovascular diseases 3
- Heart failure (HF), with low levels of pro-BNP ruling out HF 4
- Acute congestive heart failure (CHF), with pro-BNP being a powerful tool in diagnostic assessment 5
- Other critical illnesses that mimic acute CHF, such as acute coronary syndromes, pulmonary embolism, chronic obstructive pulmonary disease, and pneumonia, which may result in elevated pro-BNP levels 5
Disease Processes Associated with Elevated Pro-BNP
Elevated pro-BNP levels have been associated with various disease processes, including:
- Cardiovascular diseases, such as heart failure, acute coronary syndrome, and pulmonary embolism 3, 6
- Non-cardiovascular diseases, such as gram-negative sepsis and pulmonary hypertension 2
- Renal dysfunction, which may affect pro-BNP levels 6
- Diabetes, which may interact with pro-BNP levels to predict HF readmission 6
Clinical Utility of Pro-BNP
Pro-BNP has been shown to be a useful marker for: