Expanding the role of serum BNP and serum NT-proBNP measurement

Central laboratory or point-of-care testing of blood to determine natriuretic peptide (either BNP or N-terminal proBNP) concentration has a clinically established role in the differential diagnosis of patients presenting with breathlessness; normal levels exclude a diagnosis of heart failure, a common cause of breathlessness. 

Over the last few years there has been an ever-increasing research interest in the notion that these tests might also have value in the early assessment of patients presenting with acute (ischemic) stroke. This interest was first sparked a decade ago with demonstration that in the hours and days following ischemic stroke, victims have increased blood concentration of natriuretic peptides, and the higher the level the greater is the risk of death.  

More recently, a number of studies have demonstrated that levels are highest in one form of ischemic stroke called cardioembolic stroke in which the offending blood clot that obstructs local blood flow within the brain is derived from the heart. 

Current interest is largely focused on establishing whether serum BNP or serum NT-proBNP measurement at the time of admission can reliably identify those approximately 25 % of stroke victims who are suffering cardioembolic stroke. 

This is important because early anticoagulant treatment prevents secondary recurrence, and significantly improves outcome for those with cardioembolic stroke. Since this treatment is not appropriate for other types of ischemic stroke, early diagnosis of cardioembolic stroke is vital and the indications thus far are that BNP/ NT-proBNP could prove helpful. 

Arguably, the most robust evidence to date in support of this use of natriuretic peptide testing is contained in the results of a recently published meta-analysis study. This international collaborative research effort involved pooling patient data from 23 previously published clinical studies. 

The pooled data allowed comparison of BNP or NT-proBNP values in the hours and days following onset of symptoms among 2834 stroke victims around the world; for each of these patients the cause (type) of stroke was clearly defined. Of the 2834 study patients, BNP was measured in 1570 and NT-proBNP in 1264. 

Statistical analysis confirmed that both peptides are significantly higher in patients who have suffered cardioembolic stroke compared with those who have suffered non-cardioembolic stroke. The study design precluded the possibility of defining cut-off values for diagnosis/exclusion of cardioembolic stroke. 

Instead the authors used highest and lowest quartile standardized BNP and NT-proBNP results to construct a predictive model. This predictive model was then applied to the second cohort of patients whose cause of stroke had not yet been clearly defined, but was subsequently clearly defined. 

This allowed the authors to demonstrate that diagnosis of cardioembolic was greatly improved by addition of natriuretic peptide measurement to currently used early clinical assessment. With the additional information provided by natriuretic peptide testing it proved possible to distinguish cardioembolic stroke for non-cardioembolic stroke with a sensitivity >90 % and specificity >80 %. 

This study also provides evidence to suggest that NT-proBNP measurement is superior to BNP measurement for diagnosis of cardioembolic stroke.