Midregional pro-adrenomedullin in addition to b-type natriuretic peptides in the risk stratification of patients with acute dyspnea: an observational study

Abstract

Introduction: The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of the newly described midregional fragment of the pro-Adrenomedullin molecule (MR-proADM) alone and combined to B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in patients with acute dyspnea.

Methods: We conducted a prospective, observational cohort study in the emergency department of a University Hospital and enrolled 287 unselected, consecutive patients (48% women, median age 77 (range 68 to 83) years) with acute dyspnea.

Results: MR-proADM levels were elevated in non-survivors (n = 77) compared to survivors (median 1.9 (1.2 to 3.2) nmol/L vs. 1.1 (0.8 to 1.6) nmol/L; P < 0.001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.81 (95% CI 0.73 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for MR-proADM, NT-proBNP and BNP, respectively (MRproADM vs. NTproBNP P = 0.38; MRproADM vs. BNP P = 0.009). For one-year mortality the AUC were 0.75 (95% CI 0.69 to 0.81), 0.75 (95% CI 0.68 to 0.81), 0.69 (95% CI 0.62 to 0.76) for MR-proADM, NT-proBNP and BNP, respectively without any significant difference. Using multivariate linear regression analysis, MR-proADM strongly predicted one-year all-cause mortality independently of NT-proBNP and BNP levels (OR = 10.46 (1.36 to 80.50), P = 0.02 and OR = 24.86 (3.87 to 159.80) P = 0.001, respectively). Using quartile approaches, Kaplan-Meier curve analyses demonstrated a stepwise increase in one-year all-cause mortality with increasing plasma levels (P < 0.0001). Combined levels of MR-proADM and NT-proBNP did risk stratify acute dyspneic patients into a low (90% one-year survival rate), intermediate (72 to 82% one-year survival rate) or high risk group (52% one-year survival rate).

Conclusions: MR-proADM alone or combined to NT-proBNP has a potential to assist clinicians in risk stratifying patients presenting with acute dyspnea regardless of the underlying disease.

Figure 1

Midregional pro-adrenomedullin concentrations at admission as a function of diagnosis. ADHF = acute decompensated heart failure; AECOPD = acute exacerbation of chronic obstructive pulmonary disease; MR-proADM = midregional pro-adrenomedullin.

Figure 2

Midregional pro-adrenomedullin, N-terminal pro B-type natriuretic peptide and B-type natriuretic peptide concentrations at admission as a function of survival at one year. BNP = B-type natriuretic peptide; MR-proADM = midregional pro-adrenomedullin; NT-proBNP = N-terminal pro-B-type natriuretic peptide.

Figure 3

Area under the receiver-operating characteristic curve for midregional pro-adrenomedullin, N-terminal pro B-type natriuretic peptide and B-type natriuretic peptide to predict 30-day and one-year mortality. AUC = area under the receiver-operating characteristic curve; BNP = B-type natriuretic peptide; MR-proADM = midregional pro-adrenomedullin; NT-proBNP = N-terminal pro-B-type natriuretic peptide.

Figure 4

Kaplan-Meier survival curves according to quartiles of (a) midregional pro-adrenomedullin, (b) N-terminal pro B-type natriuretic peptide and (c) B-type natriuretic peptide. BNP = B-type natriuretic peptide; MR-proADM = midregional pro-adrenomedullin; NT-proBNP = N-terminal pro-B-type natriuretic peptide.

Figure 5

Combined Kaplan-Meier survival curves. (a) Combined Kaplan-Meier survival curves according to midregional pro-adrenomedullin (MR-proADM) and N-terminal pro B-type natriuretic peptide (NT-proBNP) values below (low) and above (high) the median. (b) Combined Kaplan-Meier survival curves according to MR-proADM and B-type natriuretic peptide (BNP) values below (low) and above (high) the median.