Differential prognostic utility of NTproBNP and Cystatin C in patients with acute exacerbation of chronic pulmonary disease

Abstract

Objectives: To determine whether serum Cystatin C (CysC) and NTproBNP have prognostic value among patients with long-standing chronic lung disease.

Design: Prospective, observational, non-interventional study.

Setting: CysC and NTproBNP are prognostic markers in several cardiac conditions. In addition, CysC acts as an antiprotease following Cathepsin activation, which has been involved in the pathogenesis of chronic obstructive pulmonary disease.

Participants: Patients with a basal functional status of II-IV (NYHA), admitted for an acute exacerbation of chronic pulmonary diseases and no previous history of symptoms related to pulmonary hypertension or heart failure.

Main outcome measures: NTproBNP and CysC were determined at admission in 107 patients with acute exacerbation of chronic lung disease. During 12-month follow-up, mortality, new hospital admissions and prescription of diuretics were recorded.

Results: During follow-up there were eight patient deaths (7.5%). Mean NTproBNP among the deceased was 1510.20 pg/mL (95% CI 498.44-4628.55) vs 502.70 pg/mL (95% CI 395.44-645.48) among survivors (p = 0.01). Twenty-seven patients (25%) were prescribed loop diuretics. Mean concentration of CysC was 1.45 mg/dL (95% CI 1.21-1.69 mg/dL) vs 1.17 mg/dL (95% IC 1.09-1.25 mg/dL) in those not prescribed (p = 0.004). NTproBNP concentration was 837.14 pg/mL (95% CI 555.57-1274.10 pg/mL) in patients prescribed diuretics vs 473.42 pg/mL (95% CI 357.80-632.70 pg/mL) in those not prescribed (p = 0.03). Kaplan-Meier analysis revealed a significant difference between death and diuretic prescription during follow-up when cut-off value for NTproBNP was 550 pg/mL (p = 0.03 and p = 0.02, respectively). For 1.16mg/dL of CsysC, a significant difference was only observed in diuretic prescription (p = 0.007).

Conclusions: In patients with chronic respiratory diseases NTproBNP has predictive value in terms of mortality whereas CysC does not. However, it is still possible that both can contribute to the early identification of patients at risk of developing clinical ventricular dysfunction.

Figure 1

Cumulative survival according to NTproBNP (top panel) and CysC (bottom panel) concentrations at admission. Solid line denotes a baseline concentration of NTproBNP above 550 pg/mL. Dotted line denotes a baseline concentration of NTproBNP below 550 pg/mL (top panel). Solid line denotes a baseline concentration of CysC above 1.16 mg/dL. Dotted line denotes a baseline concentration of CysC below 1.16 mg/dL (bottom panel)

Figure 2

Cumulative interval free from diuretics according to NTproBNP (top panel) and CysC (bottom panel) concentrations at admission. Solid line denotes a baseline concentration of NTproBNP above 550 pg/mL. Dotted line denotes a baseline concentration of NTproBNP below 550 pg/mL (top panel). Solid line denotes a baseline concentration of CysC above 1.16 mg/dL. Dotted line denotes a baseline concentration of CysC below 1.16 mg/dL (bottom panel)