High BNP levels linked to increased mortality regardless of heart failure status

High concentrations of B-type natriuretic peptide (BNP) are equally predictive of mortality in patients with and without heart failure, according to a study published May 7 in the Journal of the American College of Cardiology.

In fact, BNP was the most powerful predictor of any variable for the non-heart failure group, suggesting it should be taken seriously by clinicians even when heart failure isn’t identified.   

“For any given BNP level, the risk for death is similar whether heart failure is present, particularly in the acute care setting and even in the outpatient setting for modestly elevated or higher BNP values,” wrote lead author Michelle K. York, BS, and colleagues at Vanderbilt University School of Medicine. “This finding could have significant clinical implications, because a substantial proportion (15 percent) of the patients without heart failure had BNP levels of ≥400 pg/ml. Thus, our results suggest that clinicians should not disregard an elevated BNP value, even in patients in whom HF is excluded.”

York et al. used the Vanderbilt University Medical Center electronic health record to identify 30,487 black or white patients who had their BNP levels measured between 2002 and 2013. The patients were a median of 63 years old, 50 percent women and 17 percent black. Thirty-eight percent of them had heart failure.

In general, patients with heart failure had more circulating BNP. At low levels, the three-year death risk was greater for those with heart failure versus those without. But at higher levels, the mortality risks evened out between the groups.

For example, a BNP level of 400 pg/ml was linked to three-year mortality risks of 21 and 19 percent for those with heart failure and those without heart failure, respectively.

Also, jumping from the 25th to 75th percentile in BNP readings was associated with a doubling of death risk for all patients regardless of heart failure status. The association was actually slightly stronger for those without heart failure (2.08-fold) versus those with heart failure (1.91-fold).

“As natriuretic peptides are released from the heart as a counter-regulatory response to increased wall stress, sympathetic tone, and vasoconstriction, higher circulating natriuretic peptide levels among patients without heart failure and even within the ‘normal’ range may integrate cardiovascular and hemodynamic stress from multiple sources,” the authors wrote.

“In the non-heart failure group, higher heart rate, a marker of increased sympathetic activity, was also significantly associated with circulating BNP level and the third strongest predictor of death behind BNP and age, supporting that greater sympathetic activity may be an important contributor to mortality risk in our patient population.”

The authors acknowledged their study was limited by its single-center, observational design and added that randomized trials are needed to assess the best clinical approaches for patients with elevated BNP but no heart failure. In addition, they weren’t able to discern whether the patient deaths in the study were from cardiac causes.

In a related editorial, two French researchers pointed out elevated BNP concentrations could be a sign of asymptomatic heart disease or noncardiac conditions.

“Acute and transient increases in BNP levels could reflect poor cardiac reserve in such acute noncardiac events,” wrote Nicolas Vodovar, PhD, and Damien Logeart, MD, PhD. “Vascular aging as an integrator of diverse comorbidities and age is also associated with NP elevation and mortality. Plasma NP levels can therefore predict poor outcomes in numerous acute and chronic disorders.”

The editorialists said York et al.’s study should spur further research into how to treat patients with high BNP levels for whom heart failure is ruled out. For now, they noted higher levels “should lead to a more extensive cardiovascular evaluation with echocardiography and electrocardiography.”