Heterogeneity of the prognostic significance of B-type natriuretic peptide levels on admission in patients hospitalized for acute heart failure syndromes

Highlights

• We evaluated heterogeneity of the prognostic significance of BNP levels in AHFS.

• Usefulness of BNP as a prognostic factor may be weakened in hyponatremic patients.

• Prognostic significance of BNP seems weaker in patients with renal dysfunction.

• High BNP levels may not be associated with higher mortality in hypertensive etiology.

• Overall, high BNP levels were an important prognostic indicator in AHFS patients.

Abstract

Background

We hypothesized that variation in baseline characteristics of patients with acute heart failure syndromes (AHFS) affects the prognostic significance of B-type natriuretic peptide (BNP) levels because of heterogeneity of this patient population. We evaluated the association of elevated BNP levels on admission with an increased risk of adverse clinical outcomes in subgroups of patients hospitalized for AHFS.

Methods

This study included patients from the acute decompensated heart failure syndromes (ATTEND) study, a multicenter prospective cohort of 4501 AHFS patients with BNP data on admission.

Results

The geometric mean BNP level was 654.9 pg/mL (95% confidence interval: 636.1–674.2), and the optimal cut-off value for all-cause death was 1157 pg/mL. All-cause mortality after admission was significantly higher in patients with high BNP levels (> 1157 pg/mL) than in those with low BNP levels (≤ 1157 pg/mL) (median follow-up: 508 days, log-rank P < 0.001). Subgroup analyses were performed to evaluate the heterogeneity of the prognostic significance of BNP levels. The effect of high BNP levels on the risk of all-cause mortality was significantly greater in the subgroup of patients with a non-hypertensive etiology, low creatinine levels (< 1.3 mg/dL), and high sodium levels (≥ 135 mEq/L) than in those without these factors (P = 0.024, P < 0.001, and P < 0.001 for the interaction, respectively).

Conclusions

The present analysis shows that underlying etiology of heart failure (i.e., hypertensive), renal function, and sodium levels should be considered for assessing the clinical significance of elevated BNP levels on admission in relation to the risk of adverse outcome after hospitalization for AHFS.

Introduction

Acute heart failure syndromes (AHFS) are a common clinical syndrome that greatly affects health-related quality of life, and its incidence, morbidity, and mortality are increasing worldwide [1], [2], [3], [4]. Reported variables in AHFS that are predictive of death include hypotension, renal dysfunction, and marked elevation of biomarkers such as B-type natriuretic peptide (BNP) [1], [2], [5], [6], [7]. BNP is a biologically active 32-amino acid peptide that is primarily produced by cardiac myocytes as a response to neuro-hormonal activation, myocardial stretch, and wall tension, and plays an important role in volume homeostasis and cardiovascular remodeling [8], [9]. Circulating plasma BNP levels are elevated in numerous cardiac pathologies in the presence of volume overload and increased cardiac fibrosis, and these levels correlate with the severity of symptoms and the prognosis [10], [11], [12], [13], [14], [15]. Therefore, the use of BNP is a well-established tool in the diagnosis, management, and risk stratification of patients with heart failure, and a report from a large registry showed that an elevated BNP level on admission is a significant predictor of in-hospital mortality in AHFS patients [5], [13], [14], [15], [16], [17]. Because of the heterogeneity of this patient population, however, we hypothesized that variation in baseline characteristics of patients with AHFS affects the prognostic significance of BNP levels. In addition, few AHFS registries have collected data on post-discharge, long-term outcomes [18]. Therefore, this study aimed to evaluate the heterogeneity of the association of an elevated BNP level with an increased risk of adverse outcomes in subgroups of patients who were hospitalized for AHFS. These patients were evaluated during hospitalization and post-discharge outpatient settings using data from a prospective AHFS cohort, the acute decompensated heart failure syndromes (ATTEND) study.