B-type natriuretic peptide (BNP) and N-terminal B-type natriuretic peptide precursor (NT-proBNP) are biomarkers of cardiac function, as well as the preferred biomarkers for the diagnosis and differential diagnosis of heart failure, disease severity and prognosis assessment, and have been recommended as Level I by several clinical practice guidelines.
BNP is mainly degraded in large blood vessels and other sites, while NT-proBNP is mainly excreted by the kidneys, and measurement of BNP or NT-proBNP levels in plasma can be used to diagnose and evaluate heart failure.
Although both BNP and NT-proBNP are cleaved from moles such as proBNP, they have different biological characteristics.
In summary, BNP has a short half-life of about 20 to 22 minutes, which is more valuable in understanding the immediate condition of the patient; NT-proBNP has a relatively longer half-life of 120 minutes, higher concentrations in peripheral blood, and is more stable in vitro, making it more suitable for clinical monitoring.
BNP is affected by neprilysin inhibitors (sacubitril, others), which reduces degradation and increases levels; NT-proBNP is not affected.
In addition to being metabolized by the kidney, BNP can also be removed by binding to receptors and enzyme degradation, and is relatively less affected by renal function. NT-proBNP is mainly metabolized by the kidneys and is more affected by renal function.
In addition, the NT-proBNP diagnostic threshold is more affected by age.
Immunoassay is the main method for the detection of BNP/NT-proBNP in clinical laboratories. There are three related peptides in peripheral blood: BNP, NT-proBNP and proBNP, which are further degraded into a variety of short peptides of different lengths under the action of various proteolytic enzymes, and the BNP/NT-proBNP detected by the laboratory is actually a variety of mixed peptides. The diversification of peptides is a challenge to achieve their standardization. There are currently no reference materials available to standardize BNP/NT-proBNP.
BNP/NT-proBNP and acute heart failure
The clinical value of BNP/NT-proBNP index in acute heart failure is greater than that of chronic heart failure, and the reliability of excluding cut-off points in acute heart failure is greater than that of diagnostic cut-offs.
1. Exclusion and diagnosis of acute heart failure:
Currently, BNP/NT-proBNP exclusion cut-offs are more reliable than diagnostic cut-offs in acute heart failure. The exclusion cut-off point is <100 pg/ml for BNP and <300 pg/ml for NT-proBNP.
2. Definitive diagnosis of acute heart failure:
The cut-off point for the diagnosis of BNP is ≥300 pg/ml, and the cut-off point for the diagnosis of NT-proBNP is ≥450 pg/ml (< 50 years old), ≥900 pg/ml (50~75 years old), and ≥1800 pg/ml (> 75 years old).
It is important to note that when NT-proBNP is used to rule out acute heart failure with a cut-off value of 300 ng/L, the negative predictive value is as high as 98~99%, therefore, NT-proBNP is a reliable marker of cardiac function.
BNP/NT-proBNP and chronic heart failure
1. Exclusion and diagnosis of chronic heart failure:
The exclusion cut-off point is <35 pg/ml for BNP and <125 pg/ml for NT-proBNP.
2. Definitive diagnosis of chronic heart failure:
Patients with chronic heart failure have been found to have lower levels of BNP/NT-proBNP than those with acute heart failure, and more differential diagnoses need to be made, such as non-heart failure disorders. The results of the history, clinical presentation, and other tests should be analyzed in conjunction with the results to further improve the accuracy of the diagnosis.
3. Prognostic assessment of chronic heart failure:
BNP/NT-proBNP is an independent risk factor for death and readmission in patients with heart failure, and its prognostic value is generally better than that of other biomarkers, such as endothelin, adrenomedullin, tumor necrosis factor α, C-reactive protein, etc. Testing for BNP/NT-proBNP upon patient admission can help assess long-term risk. A single measurement of BNP/NT-proBNP at any time contributes to risk stratification. Repeat assays provide more prognostic information.
In clinical application, most of the clinical diagnostic value of BNP and NT-proBNP can be substituted for each other, but there are certain differences between the two. It is mainly reflected in the fact that the diagnostic reference values of BNP are consistent among all age groups, and the results are more convenient to judge. NT-proBNP, on the other hand, has a long half-life and performs better in the early diagnosis of mild and chronic heart failure. Therefore, in clinical application, BNP and NT-proBNP can complement each other and play their respective roles.
