Mid-Regional Pro-Adrenomedullin as a Novel Predictor of Mortality in Patients with Chronic Heart Failure

AIMS: Adrenomedullin (ADM) is a vasodilatory peptide. Its plasma levels or its precursors have not been evaluated in large populations of patients with chronic heart failure (CHF). We sought to explore mid-regional proADM (MR-proADM). METHODS AND RESULTS: We assessed MR-proADM in 501 CHF patients [age 63 +/- 11 years, New York Heart Association (NYHA) class I/II/III/IV 9/44/39/8%, median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 878 pg/mL (interquartile range-IQR 348-2480 pg/mL), median left ventricular ejection fraction (LVEF) 31% (IQR 25-37%)]. Mid-regional pro-adrenomedullin levels (median 0.64 nmol/L, IQR 0.49-0.87 nmol/L) increased with NYHA class (P < 0.0001). During 1-year follow-up, 70 patients (14%) died. Increasing MR-proADM was a predictor of poor survival at 12 months (hazard ratio 1.82, 95% confidence interval 1.24-2.66, P = 0.002) after multivariable adjustment. In receiver-operating characteristic curve analysis of 12-month survival, the area under the curve for MR-proADM and NT-proBNP was similar (P = 0.3). Comparison of Cox proportional hazard models using the likelihood ratio chi(2) statistic showed that both NT-proBNP and MR-proADM added prognostic value to a base model of LVEF, age, creatinine, and NYHA class. Adding MR-proADM to the base model had stronger prognostic power than adding NT-proBNP (both P < 0.01). CONCLUSION: Mid-regional pro-adrenomedullin is an independent predictor of mortality in CHF patients, which adds prognostic information to NT-proBNP.