aliases:
- BNP
- B-Type Natriuretic Peptide
- Natriuretic Peptide
- Brain Natriuretic Peptide
- Brain Natriuretic Peptide
- Brain Natriuretic Peptide
- B-Type Natriuretic Peptide
- B-Type Diuretic Peptide
- B Natriuretic Peptide
Introduction
Heart failure and cardiac injury markers are basic mandatory checks for admissions in various departments of our hospital, but it has not been very clear to what extent these indicate heart failure or cardiac injury. The following is a study summary, and this article is about the natriuretic peptide BNP.
Consider a few questions first
- What exactly is BNP?
- What are the sources of BNP and NT-proBNP? Among these two used for detecting heart failure, which is more ideal?
- What factors affect BNP?
- If BNP is normal, can heart failure be excluded?
- Does an elevated BNP mean heart failure?
- Does failure of BNP to decrease mean no remission of heart failure?
What is BNP
The natriuretic peptide family is a class of substances in animals that regulate circulatory system volume and osmotic pressure. There are many family members, including ANP, BNP (B-Type Natriuretic Peptide, of most concern to clinicians), CNP, DNP, etc.
Physiological functions of BNP
Mainly secreted by the ventricles, it acts through natriuresis and diuresis + inhibition of the RASS system + vasodilation, reducing ventricular pressure and lowering blood pressure.
- Proximal tubule — inhibits sodium reabsorption, promoting sodium and water excretion
- RASS system — inhibits aldosterone production, promoting kidneys to excrete more sodium and water
- Capillaries — dilates peripheral capillaries, reduces blood pressure, and lessens cardiac load
During heart failure, decreased ejection fraction, enlarged heart volume, and overstretched myocardial cells initiate a protective mechanism. The diaphragm cells (the thin membrane layer over myocardial cells) secrete BNP when stimulated. BNP promotes diuresis, natriuresis, and vasodilation, ultimately reducing cardiac load.
Note that BNP is expressed in ventricular muscle cells, atrial muscle cells, and brain tissue, so it is not specific to myocardial cells. Other factors besides heart failure can also cause changes in natriuretic peptide levels.
What’s the difference between BNP and NT-proBNP?
After myocardial cells are stretched, diaphragm cells secrete the proBNP precursor, which undergoes two modifications to form NT-proBNP (which has no physiological activity) and BNP (which executes various physiological functions).
flowchart TD
A[Under pressure on the ventricular wall, diaphragm cells secrete Pro-BNP precursor] --> B[Pro-BNP precursor]
B --> |Removal of 26 amino acid signal peptide| D[Pro-BNP]
D -->|Endopeptidase| E[NT-proBNP]
D -->|Endopeptidase| F[BNP]
E --> G[Renal clearance]
F --> H[Binding to NP receptor]
F --> I[Degradation by neutral endopeptidase]
F --> J[Action on adipocytes]
Metabolic pathway of NT-proBNP: cleared only through renal excretion
Metabolic pathways of BNP:
- Renal excretion
- Inactivation after binding with NP receptors
- Inactivation in large vessels by neutral endopeptidase (neprilysin)
Since BNP is consumed by these three pathways after production, direct measurement of its level is unstable. Meanwhile, NT-proBNP is produced in an equimolar amount, has no physiological effect, and is cleared solely by the kidneys, resulting in stable levels that better reflect BNP levels.
| BNP | NT-proBNP |
|---|---|
| Has physiological effects (natriuresis, diuresis, vasodilation, blood pressure reduction) | None |
| Cleared by three pathways, including renal clearance | Only one pathway, renal clearance only |
| Short half-life (20 min) | Long half-life (120 min) |
| Lower concentration | Higher concentration |
| Requires anticoagulants and non-siliconized glass tubes for collection | No special requirements |
In summary, NT-proBNP is more suitable for detection.
Factors Affecting BNP
Factors causing elevated natriuretic peptide
- Physiological: Age, obesity
- With increasing age, myocardial cell elasticity decreases and contractile function declines. Generally, NT-proBNP <300 excludes heart failure.
| Confirm acute heart failure | Age criteria |
|---|---|
| <50 years | >450 ng/L |
| 50-75 years | >900 ng/L |
| >75 years | >1800 ng/L |
-
Pathological:
- Cardiovascular factors:
- Atrial fibrillation (mainly): ~1/3 reduction in cardiac ejection function, enlargement of atria and ventricles
- Acute coronary syndrome, cardiomyopathy (e.g., left ventricular hypertrophy), myocarditis, pulmonary embolism, valvular heart disease, hypertrophic cardiomyopathy, congenital heart disease, atrial and ventricular arrhythmias;
- Cardiac contusion, infiltration or malignant tumors: electrical cardioversion, pericardial disease, invasive cardiac interventions or surgery, pulmonary hypertension (right heart failure), infiltrative cardiomyopathy, and use of cardiotoxic drugs;
- Endocrine factors:
- Hyperthyroidism (main): causes hyperthyroid heart disease, arrhythmia, and cardiac enlargement
- Metabolic factors:
- Renal failure patients cannot properly excrete BNP/NT-proBNP, especially NT-proBNP (kidneys are the sole excretion route)
- Respiratory factors:
- Pulmonary infection: lungs also secrete BNP; pulmonary infection elevates BNP due to hypoxemia and myocardial strain
- Pulmonary embolism: causes pulmonary hypertension and right ventricular enlargement
- Others: critical illnesses (sepsis syndrome and cytokine syndrome), stroke, pulmonary diseases (severe pneumonia, sleep apnea, chronic obstructive pulmonary disease), liver disease, severe anemia, severe metabolic and endocrine disorders (hyperthyroidism and diabetic ketoacidosis), and severe burns
- Cardiovascular factors:
-
Iatrogenic:
Because BNP has natriuretic, diuretic, vasodilator effects and antagonizes the renin-angiotensin-aldosterone system and sympathetic nervous system, hormones involved in this neuroendocrine axis influence BNP/NT-proBNP levels.- Hormones such as adrenaline, glucocorticoids, and thyroid hormones increase BNP/NT-proBNP levels.
- Antagonists of these hormones, like angiotensin-converting enzyme inhibitors, beta-blockers, adrenergic antagonists, and diuretics, can decrease BNP/NT-proBNP concentrations.
- Sartans and amiodarone also decrease BNP/NT-proBNP, while digitalis glycosides increase them.
- Direct supplementation of natriuretic peptides (e.g., nesiritide) and use of neprilysin inhibitors (e.g., sacubitril) raise BNP but do not affect NT-proBNP.
Factors causing decreased natriuretic peptide
-
Physiological:
- Obesity: insulin resistance inhibits BNP synthesis and secretion. Adipocytes express BNP receptors NPR-A and NPR-C, which promote BNP metabolism. In severe obesity (BMI ≥35), BNP and NT-proBNP less than half of normal values should be considered for heart failure.
-
Pathological:
- Acute pulmonary edema, constrictive pericarditis, and cardiac tamponade, etc.
Diagnostic Criteria
BNP/NT-proBNP for diagnosing heart failure:
Negative predictive value reaches 95%~98%, a negative BNP excludes heart failure.
Positive predictive value is 66%, about one-third of positive cases are not heart failure.
In short, a negative BNP basically excludes heart failure; positive BNP likely indicates heart failure.
BNP cutoff points:
- Chronic heart failure: <35 ng/L generally excludes; >150 ng/L diagnoses
- Acute heart failure: <100 ng/L generally excludes; >400 ng/L diagnoses
NT-proBNP cutoff points differ from BNP and are significantly influenced by age and renal function, requiring stratification:
- Chronic heart failure: <125 ng/L generally excludes; >600 ng/L diagnoses
- Acute heart failure: <300 ng/L generally excludes; >450 ng/L if under 50; >900 ng/L if 50–75; >1800 ng/L if over 75 diagnoses
- In renal insufficiency (glomerular filtration rate <60 ml·min-1·1.73 m-2), cutoff should be >1200 ng/L
- For atrial fibrillation patients, the NT-proBNP cutoff should be increased by 20%~30%.
References
Supplement: History of BNP Development (for understanding only)
- 1956: Henry Baleset proposed that atrial enlargement promotes sodium excretion.
- 1981: Bold proposed that the atrium has endocrine function and extracted ANP, which promotes natriuresis and diuresis, from the atrium.
- 1984: Japanese scientists extracted a substance from pig brain, published in Nature, and named it BNP (Brain Natriuretic Peptide).
- 2000: BNP approved by the US FDA as an auxiliary test method for heart failure.
- 2002: BNP testing named among the top ten international medical news and achievements. FDA approved Roche’s NT-proBNP.
- 2008: China issued related consensus and guidelines, including BNP as a test for heart failure.
- 2016: ESC and American College of Cardiology guidelines for diagnosis and treatment of acute and chronic heart failure recommend BNP/NT-proBNP as the only mandatory biomarker for all suspected heart failure patients.
- 2014 China Heart Failure Guidelines: BNP/NT-proBNP is routine testing for chronic heart failure patients, and used in diagnosis and differential diagnosis for patients suspected of heart failure due to dyspnea.