Katherine N Bachmann1, Deepak K Gupta2, Meng Xu3, Evan Brittain2, Eric Farber-Eger2, Pankaj Arora4, Sheila Collins5, Quinn S Wells2, Thomas J Wang6. 1. Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee, USA; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. Electronic address: Katherine.n.bachmann@vanderbilt.edu. 2. Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 3. Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 4. Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama, USA; Section of Cardiology, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA. 5. Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA. 6. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
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