Cardiovascular Biomarkers: NT-proBNP

Optimal Takeaways

NT-proBNP is an inactive fragment cleaved from BNP, a compound produced by heart cells and released when the walls of the heart’s chambers are stretched due to increased volume or pressure.

Significantly elevated levels may be a marker for heart failure in those with related symptoms. Increased levels can be seen with congestive heart failure, cardiovascular disease, cardiac complications, hypertension, and diabetes. Levels increase with age and tend to be higher in women than men in general. A low NT-proBNP suggests the absence of heart failure.

Standard Range: 0.00 – 300.00 pg/mL

The ODX Range: 0.00 – 125.00 pg/mL

Low NT-proBNP suggests a low risk of heart failure and cardiovascular events. However, it may be lower in obese individuals even with an increased risk of heart failure (Palazzuoli 2010).

High NT-proBNP is associated with congestive heart failure, myocardial infarction, atherosclerosis (Pagana 2021), hypertension, diabetes mellitus (Hussain 2021), ischemic heart disease, cardiomyopathy, arrhythmias (Cao 2019), more severe COVID-19 pneumonia (Wang 2021), and all-cause mortality in elderly subjects (Rudolf 2020). Levels may increase in renal insufficiency and anemia without heart failure (Palazzuoli 2010).

Overview

NT-pro-BNP is the inactive N-terminal fragment of brain natriuretic peptide (BNP), a neuroendocrine peptide that opposes renin-angiotensin system activity. BNP is released when the heart’s chambers are stretched, reflecting increased pressure, which can be a sign of congestive heart failure. (Pagana 2021). BNP may also be involved in other pathologies, including hypertension, atherosclerosis, myocardial infarction, and COVID-19.

The test is beneficial for identifying heart failure as a cause of shortness of breath (SOB). If an elevated BNP or NT-pro-BNP accompanies SOB, it could be related to heart failure, which would be unlikely if BNP were low. Levels increase with age and tend to be higher in women than men. Laboratories may test BNP or NT-pro-BNP, and their recommended ranges differ. The conventional range for BNP is less than 100 pg/mL, while for NT-pro-BNP, it is below 300 pg/mL (Pagana 2021). BNP and NT-proBNP are considered “highly sensitive for the diagnosis or exclusion of acute or chronic decompensated heart failure” (Palazzuoli 2010).

An NT-pro-BNP level of 125 pg/mL or above may be associated with heart failure in high-risk individuals. Moderately elevated levels may also be clinically significant or predictive of future cardiac complications. Evaluation of data from 18,356 healthy participants with a mean age of 46.1 years revealed a median NT-pro-BNP level of 50 pg/mL. Levels rose as expected with age, likely partly due to a decreasing glomerular filtration rate. However, researchers did note that approximately 10% of healthy younger females had an elevated NT-pro-BNP of 125 pg/mL without apparent cardiac risk factors (Welsh 2022).

Ultimately, an elevated NT-pro-BNP above 125 pg/mL should be investigated further in a symptomatic or high-risk individual. Evaluation should include age, renal function, medical history, and cardiac risk factors. Females may have higher levels than males.

Although a level below 125 pg/mL is considered optimal, an NT-pro-BNP level alone is not considered diagnostic. According to the Cleveland, Clinic, a normal level of NT-proBNP is:

• Less than 125 pg/mL for patients aged 0-74 years
• Less than 450 pg/mL for patients aged 75-99 years

If you have heart failure, the following NT-proBNP levels could mean your heart function is unstable:

• Higher than 450 pg/mL for patients under age 50
• Higher than 900 pg/mL for patients aged 50 and older

An elevated NT-proBNP is recognized as a strong predictive marker for cardiovascular complications in diabetes mellitus, coronary heart disease, heart failure, and hypertension. An NT-proBNP of 100 pg/mL or above may be independently associated with a progressively greater risk of CVD mortality and events, including ischemic stroke, heart failure hospitalizations, and coronary heart disease incidents. The study was conducted on 9,309 subjects from the prospective Atherosclerosis Risk In Communities (ARIC) study who were free of CVD at baseline. An elevation in NT-proBNP appeared to compound the risk of adverse cardiovascular events even more than in systolic blood pressure (Hussain 2021).

An additional review of ARIC data suggests that compared to an NT-proBNP below 125 pg/mL, a level of 450 pg/mL or above can increase cardiovascular risk at least as much as a history of CVD does (Tcheugui 2022).

The diagnostic value of NT-proBNP is decreased in obesity, anemia, and renal insufficiency, and a more in-depth clinical assessment of CVD risk should be carried out in individuals with these disorders (Palazzuoli 2010).

References

Cao, Zhipeng et al. “BNP and NT-proBNP as Diagnostic Biomarkers for Cardiac Dysfunction in Both Clinical and Forensic Medicine.” International journal of molecular sciences vol. 20,8 1820. 12 Apr. 2019, doi:10.3390/ijms20081820

Hussain, Aliza et al. “Association of NT-ProBNP, Blood Pressure, and Cardiovascular Events: The ARIC Study.” Journal of the American College of Cardiology vol. 77,5 (2021): 559-571. doi:10.1016/j.jacc.2020.11.063

NT-proB-type Natriuretic Peptide. Cleveland Clinic. https://my.clevelandclinic.org/health/diagnostics/16814-nt-prob-type-natriuretic-peptide-bnp

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Palazzuoli, A et al. “Natriuretic peptides (BNP and NT-proBNP): measurement and relevance in heart failure.” Vascular health and risk management vol. 6 411-8. 1 Jun. 2010, doi:10.2147/vhrm.s5789  

Rudolf, Henrik et al. “NT-proBNP for risk prediction of cardiovascular events and all-cause mortality: The getABI-study.” International journal of cardiology. Heart & vasculature vol. 29 100553. 5 Jun. 2020, doi:10.1016/j.ijcha.2020.100553

Tcheugui, Justin Basile et al. “Elevated NT-ProBNP as a Cardiovascular Disease Risk Equivalent: Evidence from the Atherosclerosis Risk in Communities (ARIC) Study.” The American journal of medicine, S0002-9343(22)00572-1. 23 Aug. 2022, doi:10.1016/j.amjmed.2022.07.012    

Wang, Lan et al. “Association between NT-proBNP Level and the Severity of COVID-19 Pneumonia.” Cardiology research and practice vol. 2021 5537275. 8 Jul. 2021, doi:10.1155/2021/5537275

Welsh, Paul et al. “Reference Ranges for NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) and Risk Factors for Higher NT-proBNP Concentrations in a Large General Population Cohort.” Circulation. Heart failure vol. 15,10 (2022): e009427. doi:10.1161/CIRCHEARTFAILURE.121.009427