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. 2021 Mar;9(3):192-200.
doi: 10.1016/j.jchf.2020.10.008. Epub 2021 Jan 6.

Unexpectedly Low Natriuretic Peptide Levels in Patients With Heart Failure

Katherine N Bachmann  1 , Deepak K Gupta  2 , Meng Xu  3 , Evan Brittain  2 , Eric Farber-Eger  2 , Pankaj Arora  4 , Sheila Collins  5 , Quinn S Wells  2 , Thomas J Wang  6
Affiliations

Unexpectedly Low Natriuretic Peptide Levels in Patients With Heart Failure

Katherine N Bachmann et al. JACC Heart Fail. 2021 Mar.

Abstract

Objectives: The purpose of this study was to determine the frequency of unexpectedly low natriuretic peptide (NP) levels in a clinical population.

Background: Higher NP concentrations are typically observed as a compensatory response to elevated cardiac wall stress. Under these conditions, low NP levels may be indicative of a "NP deficiency."

Methods: We identified 3 clinical scenarios in which high B-type natriuretic peptide (BNP) levels would be expected: 1) hospitalization for heart failure (HF); 2) abnormal cardiac structure or function; or 3) abnormal hemodynamics. In Vanderbilt's electronic health record, 47,970 adult patients had BNP measurements. A total of 13,613 patients had at least 1 of the 3 conditions (hospitalized HF, n = 9,153; abnormal cardiac structure/function, n = 7,041; abnormal hemodynamics, n = 363). We quantified the frequency of low BNP levels. We performed whole exome sequencing of the NPPB gene in a subset of 9 patients.

Results: Very low BNP levels (<50 pg/ml) were observed in 4.9%, 14.0%, and 16.3% of patients with hospitalized HF, abnormal cardiac structure/function, or abnormal hemodynamics, respectively. A small proportion (0.1% to 1.1%) in each group had BNP levels below detection limits. Higher body mass index was the strongest predictor of unexpectedly low BNP. Exome sequencing did not reveal coding variation predicted to alter detection of BNP by clinical assays.

Conclusions: A subset of patients with confirmed HF or cardiac dysfunction have unexpectedly low BNP levels. Obesity is the strongest correlate of unexpectedly low BNP levels. Our findings support the possible existence of NP deficiency, which may render some individuals more susceptible to volume or pressure overload.

Keywords: B-type natriuretic peptide; BNP; electronic health record; natriuretic peptide; natriuretic peptide deficiency.

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Conflict of interest statement

Funding Support and Author Disclosures This research was supported by Career Development Award #IK2 CX001678 from the U.S. Department of Veterans Affairs Clinical Sciences Research and Development (CSR&D) Program, Vanderbilt University Medical Center Faculty Research Scholars award, and National Institute of Health Awards: National Heart, Lung, and Blood Institute grants K12 HL109019, 1K23HL128928-01A1, 1K23HL146887-01, R01 HL131532, 1 R01 HL146588, 3 R01 HL146588-01S1, 1 U01 HL125212-01, and R01HL140074; National Institute of Diabetes and Digestive and Kidney Diseases T32DK007061; and the National Center for Advancing Translational Sciences of the National Institutes of Health UL1TR000445 (Vanderbilt). The authors report they have no relationships relevant to the content of this paper to disclose.

Figures

Figure 1.
Figure 1.. Individuals who met criteria for groups of cardiac dysfunction.
Among 47,970 individuals with at least one BNP measurement, 9,153 patients had a BNP measured in the setting of a hospitalization for HF (“Hospitalized HF”), 7,041 individuals had a BNP measured in the setting of an echocardiogram showing abnormal cardiac structure or function (“Abnormal Echo”), and 363 individuals had a BNP measured in the setting of abnormal invasive hemodynamics (“Abnormal Hemo”). Sections A, B, C, and D represent individuals who met criteria for more than 1 group of cardiac dysfunction.
Figure 2.
Figure 2.. Prevalence of unexpectedly low BNP concentrations.
BNP levels below 50 pg/ml (represented by green shading) and BNP levels below 100 pg/ml (represented by combination of green and orange shading) are presented for patients with hospitalized HF, abnormal echocardiograms, and abnormal hemodynamics, respectively. BNP, B-type natriuretic peptide; HF, heart failure; Echo, echocardiogram.
Central Illustration.
Central Illustration.. Predictors of having BNP levels <50 pg/ml in patients hospitalized with heart failure.
In multivariable analyses, the strongest predictors of having BNP levels below 50 pg/ml in the setting of hospitalization with HF were higher BMI, followed by younger age, higher EF, and lower creatinine (p<0.001 for all).
See this image and copyright information in PMC

Comment in

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