Clinical InvestigationClinical Correlates and Prognostic Value of Proenkephalin in Acute and Chronic Heart Failure
Section snippets
Methods
This study was performed in 2 populations. First, a cardiorenal mechanistic cohort was used to investigate the association between pro-ENK and renal function, including hemodynamic parameters which were measured by means of radioactive tracers in patients with stable chronic heart failure.8, 9 Second, the PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload
Patient Characteristics
Baseline characteristics are presented in Table 1. The mean age was 60 ± 12 years, mean LVEF was 29 ± 10%, and 75 patients (79%) were male. The median value of pro-ENK was 62.2 (IQR 48.5 −92.5) pmol/L (Fig. 1), and 28 patients (29.5%) had pro-ENK levels above the 99th percentile upper reference limit of pro-ENK in healthy subjects. Higher pro-ENK tertiles were associated with higher age, female sex, lower blood pressure, higher New York Heart Association (NYHA) functional class, greater
Discussion
In acute and chronic heart failure, pro-ENK levels were higher in acute heart failure compared with chronic heart failure. Pro-ENK was clearly associated with RBF and GFR, but not with tubular function. In patients with heart failure, pro-ENK was associated with clinical outcome, but after adjustments for established prognostic predictors, including preexisting renal markers, the association was lost. Therefore, pro-ENK seems to be a renal marker but does not seem to have additive value on top
Conclusion
Pro-ENK levels were higher in acute heart failure compared with chronic heart failure. Pro-ENK levels were strongly associated with glomerular function and RBF, but not with tubular damage. Pro-ENK has limited additive prognostic predictive information on top of existing renal markers in this cohort of acute heart failure.
Disclosures
Y.M., J.M.t.M., and K.D., and have nothing to disclose. A.A.V. has received speaker/consultancy/research fees from Merck, Novacardia, Singulex, and Sphingotec. P.v.d.M. has received consulting fees from Novartis, Vifor Pharma, and ZS-Pharma. D.J.v.V. has received board membership fees from Amgen, BG Medicine, Biocontrol, Johnson and Johnson, Novartis, Sorbent, and Vifor. C.M.O'C. is a consultant to Merck. M.M. has received honoraria and reimbursements from Novacardia and Merck, that purchased
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Funding: The PROTECT trial was supported by Novacardia, a subsidiary of Merck. Alere, Singulex, and Sphingotec kindly provided assays and performed biomarker measurements.