BNP and Mortality in Patients With and Without Heart Failure

Study Questions:

What is the prognostic value of B-type natriuretic peptide (BNP) between patients with and those without heart failure (HF)?


The study investigators evaluated 30,487 patients (median age 63 years, 50% men, 17% black, 38% with HF) who had a first plasma BNP measurement between 2002 and 2013, with follow-up through 2015, from the Vanderbilt Medical Center electronic health record. They categorized a patient as having HF if either of the following criteria were met: 1) two or more mentions of an HF International Classification of Diseases-9th Revision (ICD-9) code 428.x, where at least one code was recorded on the day of or before the date of first BNP measurement; and/or 2) one or more mentions of code 428.x and treatment with an intravenous diuretic agent on the same day or within 90 days after the BNP measurement. These criteria were designed to capture chronic and new HF diagnoses, respectively. Patients of mixed phenotype (i.e., both HF and other comorbidities that may contribute to dyspnea, such as asthma or chronic obstructive pulmonary disease, pneumonia, and sepsis) were categorized as having HF. They quantified associations between clinical factors and BNP levels according to HF status. They then tested the hypothesis that the risk for mortality according to circulating BNP level is similar between patients with and those without HF using multivariate Cox proportional hazards models.


The study authors found that BNP levels were lower in patients without HF (median 89 pg/ml; interquartile range, 34-238 pg/ml) compared with those with HF (median 388 pg/ml; interquartile range, 150-940 pg/ml) (p < 0.0001). Over 90,898 person-years of follow-up, 5,903 patients without HF (31%) and 6,181 patients with HF (53%) died. In multivariate models including demographic and clinical characteristics, BNP and age were the strongest predictors of mortality in both patients with and those without HF. In acute care settings and even among outpatients with modestly elevated BNP, the risk for death according to BNP was similar between patients with and those without HF. For instance, a BNP level of 400 pg/ml was associated with a 3-year risk for death of 21% (95% confidence interval [CI], 20%-23%) and 19% (95% CI, 17%-20%) in patients with and those without HF, respectively. An interquartile increase (from the 25th to the 75th percentile) in BNP was associated with a doubling in the risk for death among patients without HF (hazard ratio [HR], 2.08; 95% CI, 1.99-2.20) and with HF (HR, 1.91; 95% CI, 1.75-2.08). A secondary analysis restricted to patients with neither HF nor prevalent coronary artery disease (n = 10,438) returned similar findings (HR, 1.89; 95% CI, 1.76-2.02). In an analysis of all patients regardless of HF status, the addition of BNP to the multivariate Cox model raised the C-statistic from 0.68 to 0.71 (p < 0.001, likelihood ratio test).


The study authors concluded that among patients without HF, plasma BNP level is a stronger predictor of death than traditional risk factors. The risk for death associated with any given BNP level is similar between patients with and those without HF, particularly in the acute care setting.


Although this was an observational study, the findings are important because it suggests that serum BNP levels as a risk marker are a continuum and therefore should trigger intensification of risk management when BNP is elevated even in the absence of HF. Prospective multicenter studies are needed to confirm these important findings.

Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Asthma, Biological Markers, Comorbidity, Coronary Artery Disease, Diuretics, Dyspnea, Electronic Health Records, Geriatrics, Heart Failure, Mortality, Natriuretic Peptide, Brain, Phenotype, Pneumonia, Pulmonary Disease, Chronic Obstructive, Risk Factors, Risk Management, Secondary Prevention, Sepsis

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