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BNP also predicts mortality in patients without heart failure

Literature - York MK, Gupta DK, Reynolds CF et al. - J Am Coll Cardiol 2018;71:2079–88

Introduction and methods

B-type natriuretic peptide (BNP) concentration is a prognostic marker for recurrent heart failure (HF) hospitalizations and death in HF patients, but information is lacking about the prognostic significance of BNP levels in individuals without HF [1,2]. This retrospective analysis of electronic health record data therefore assessed the risk of all-cause death based on BNP levels and according to HF status.

The Vanderbilt University Medical Center Synthetic Derivative includes 2.5 million patient records spanning more than 20 years [3]. First, adult patients with plasma BNP concentration measurements were identified. Subsequently, the risk of death according to BNP levels was calculated in patients with and without HF. HF was identified using the International Classification of Diseases-9th Revision code before or at the time of BNP measurement. Death was confirmed through the Social Security Administration’s Death Master File linkage. The follow-up period was defined as the time elapsed from the date of BNP measurement to the date of death.

Main results

  • Of 30,487 patients with measured BNP levels, 62% did not have HF. BNP levels were lower in patients without HF (median 89 pg/ml; IQR: 34-238 pg/ml) compared with those with HF (median 388 pg/ml; IQR: 150-940 pg/ml; P <0.0001).
  • In patients without HF, higher BNP level was the strongest predictor of increased risk of death, followed by higher heart rate.
  • Among patients with HF, higher BNP was the second strongest predictor of mortality risk, after age, and followed by renal dysfunction as the third strongest predictor.
  • Diabetes mellitus and lower LVEF were associated with an increased risk of death in both groups.
  • An interquartile increase (from the 25th to the 75th percentile) in BNP was associated with an approximate doubling in the risk of death in patients without HF (HR: 2.08; 95%CI: 1.99-2.20) and in those with HF (HR: 1.91; 95%CI: 1.75-2.08).
  • At modestly and highly elevated BNP levels, the risk of death according to BNP levels was similar in patients with and without HF. For example, the 3-year risk for death at a BNP level of 403 pg/ml was 21% (95%CI: 20%-23%) among patients with HF and 19% (95%CI: 17%-20%) among those without HF, and at a BNP level of 55 pg/ml mortality risks were 9.9% in patients without HF (95%CI: 9.1-11%) vs. 13% in patients with HF (95%CI: 12-14%).


BNP is a strong predictor of death in patients with and without HF. The risk of death associated with elevated BNP levels is similar between patients with and those without HF. These data suggest that increased BNP values in patients without HF are important in clinical practice.

Editorial comment

In their editorial article, Vodovar and Logeart [4] note that in the study of York et al, HF was identified based on the International Classification of Diseases-9th Revision code before or at the time of BNP measurement, ‘a feature that limited the detection of patients with cardiac dysfunction but without HF.’ Moreover, they point out that BNP measurements were probably done when HF or other cardiovascular disease was suspected, and they discuss the probable reasons for BNP elevation in patients without HF, including asymptomatic cardiac disease, or poor cardiac reserve in non-cardiac diseases.

The authors end with: ‘In conclusion, the study by York et al. confirms that the BNP level is a powerful predictive tool and raises an important question about what to do for patients with an elevated BNP level in the absence of overt HF. York et al. should be commended for their work that will hopefully open the way for numerous studies on this topic to help define standard management for these patients.’


1. Rothenburger M, Wichter T, Schmid C, et al. Aminoterminal pro type B natriuretic peptide as a predictive and prognostic marker in patients with chronic heart failure. J Heart Lung Transplant 2004;23:1189–97.

2. Gustafsson F, Steensgaard-Hansen F, Badskjaer J, et al. Diagnostic and prognostic performance of N-terminal ProBNP in primary care patients with suspected heart failure. J Card Fail 2005;11:S15–20.

3. Roden DM, Pulley JM, Basford MA, et al. Development of a large-scale de-identified DNA biobank to enable personalized medicine. Clin Pharmacol Ther 2008;84:362–9.

4. Vodovar N and Logeart D. Similar BNP and Mortality Association in Patients With and Without Heart Failure: Any Increase Matters. J Am Coll Cardiol 2018;71:2089-2091.

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Schedule24 May 2024